MultiCaRe
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MultiCaRe: Open-Source Clinical Case Dataset
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[
{
"age": 53,
"case_id": "PMC3738355_01",
"case_text": "A 53-year-old woman presented with a 10-year history of intermittent abdominal pain, swelling and continuous vomiting. The patient denied presence of fever, nausea, and weight loss. There were no significant findings at physical examination. An abdominal ultrasound exam revealed a 10.4 x 10.0 cm mass of heterogeneous echogenicity in the left upper abdomen. Axial unenhanced CT scan (Fig. 1a) confirmed an ill-defined heterogeneous mass 9.1 cm in diameter that filled the left abdominal quadrant, located between the left lobe of the liver and the spleen. The CT attenuation of the mass was around 26-53 HU on non-enhanced scan. After intravenous contrast medium injection the mass enhanced gradually and heterogeneously (Fig. 1b-e), but was still hypodense relative to the spleen. There was no accompanying lymphadenopathy or evidence of malignant process elsewhere in the abdomen. Because the origin of the mass was unknown and a primary malignancy could not be excluded, the patient underwent an explorative laparotomy. During the operation, a well-encapsulated mass was found under the left hepatic lobe and the pedicle arising from the spleen. Resection of the mass and the spleen was performed. \nGross examination of the spleen showed splenomegaly (580 g, 15 x 10 x 9 cm) with an ill-defined brownish nodule (5 x 8 x 8 cm). Histologic examination (Fig. 2) revealed that the lesion was composed of variably sized vascular channels lined with flat and tall endothelial cells, with papillary fronds extending into the vascular channels. No atypical cells or mitosis were present. The endothelial lining cells of the vascular channels were positive for CD31 and CD68, factor VIII and negative for CD34, CD21, and CD8. These findings were considered diagnostic of benign splenic littoral cell angioma.",
"gender": "Female"
}
] |
PMC3738355
|
[
{
"age": 69,
"case_id": "PMC5015624_01",
"case_text": "A 69-year-old Caucasian female with coronary artery disease, hyperlipidemia, bilateral cataract extraction three years prior, and a fifty pack-year smoking history presented to the clinic with chronic, progressive vision loss greater in the right eye, bilateral photophobia and flashes, and right eye and temple pain. Best corrected visual acuity was 20/50 in both eyes. Pupils were equal and without afferent pupillary defect (APD). Intraocular pressure was 12 mmHg and 10 mmHg in the right and left eyes, respectively. Confrontation visual fields revealed an inferonasal depression in the right eye. Slit lamp biomicroscopy showed iris neovascularization of both eyes (Figure 1 (Fig. 1)). Dilated fundus examination showed unremarkable optic nerves, attenuated arteries, and dilated, non-tortuous veins in both eyes with few drusen in the right macula and very few hemorrhages. Optical coherence tomography showed no evidence of macular edema (Figure 2 (Fig. 2)). \nFluorescein angiography exhibited delayed arterial filling and poor peripheral perfusion (Figure 3 (Fig. 3)). Right temporal artery biopsy was negative for giant cell arteritis. We ruled out hyperviscosity syndromes, blood dyscrasia, diabetes, Takayasu, collagen vascular disease, thyroid orbitopathy and various infectious causes of retinal ischemia and aortitis. CBC, SPEP, HbA1c, ESR, CRP, FTA-ABS, and hypercoagulation panel were unremarkable. Carotid duplex ultrasound indicated only mild carotid stenosis (1-39%) bilaterally. At the time of initial presentation, the patient was taking Lipitor, Aspirin 81 mg, Relafen, Klonopin, Zoloft, and Nexium. \nThe patient received pan-retinal photocoagulation (PRP) in the right eye. Due to low tolerance, a retrobulbar block without epinephrine was administered to the right eye prior to the second PRP ten days later at which time 3,625 spots with a duration of 20 milliseconds of 500 mW were delivered using the indirect laser ophthalmoscope. Eighteen days after this laser session visual acuity had dropped significantly in the right eye to count fingers at 3' with APD and attenuated posterior vasculature consistent with central retinal artery occlusion. MRA Extracranial showed proximal occlusion of aortic arch branches (Figure 4 (Fig. 4)). Due to concern for diminished blood supply from the aortic arch, the patient received a left subclavian artery to right common carotid artery bypass graft. One month after surgery, neovascular glaucoma developed in the right eye with intraocular pressure of 34 mmHg and 22 mmHg in the left eye. Pressures remained stable on Combigan twice daily. We treated the left eye with short sessions of laser for a total of 2,200 burns (0.05-0.07 sec, 300 micron) using the Laser indirect system for one session and the Varia multicolor slit-lamp system for the remaining 5 sessions. Six months after the bypass surgery, she maintained a visual acuity of 20/50 in the left eye and intraocular pressure was 18 mmHg.",
"gender": "Female"
}
] |
PMC5015624
|
[
{
"age": 60,
"case_id": "PMC6381877_01",
"case_text": "A 60-year-old male smoker presented with persistent cough and severe right-back pain. His performance status (PS) was 2 by the pain despite opioid use in palliative care. In the imaging test of full body, chest X-ray and chest CT revealed a large lung mass, extending to posterior chest wall and vertebral body, surrounded by lymphangitic carcinomatosis in the right lower lung as well as multiple lymphadenopathy and right pleural effusion (Fig. 1a, b). Bronchoscopic biopsy of the tumor lead to a diagnosis of primary lung adenocarcinoma (cT4N2M1a, stage IV) harboring the EGFR exon 19 deletion mutation. No other molecular analysis was performed. The patient was started on gefitinib at 250 mg/day for the treatment of lung adenocarcinoma. However, by 28 days after the start of gefitinib therapy, his symptoms further deteriorated along with the increased tumor size, resulting in PS 3 (Fig. 2a, b).\nThen, repeat biopsy was performed from the lung tumor. First, in addition to the preserved EGFR exon 19 deletion mutation, EGFR T790M mutation was analyzed, resulting in negative status. Second, as a possible molecular alteration next to EGFR T790M mutation, fluorescence in situ hybridization (FISH) analysis for MET amplification was analyzed, resulting in positive status (mean MET per cell = 6.7, MET/CEP7 [centromeric enumeration probe for chromosome 7] ratio = 2.5). At this point, cytotoxic chemotherapy was not a candidate for treatment due to his poor PS. Furthermore, although crizotinib was known as potential MET inhibitor as well as anaplastic lymphoma kinase (ALK) inhibitor, combination therapy with crizotinib and EGFR-TKI was considered to lack the evidences about safety. Therefore, combination therapy with bevacizumab and erlotinib was selected on the basis of the potential efficacy for activated MET signaling pathway as well as the confirmed safety by the JO25567 phase II clinical trial.\nThe patient was started on erlotinib at 150 mg/day plus bevacizumab at 15 mg/kg every 3 weeks. By 21 days after the start of this combination therapy, his symptoms gradually improved along with the decreased tumor size, resulting in better PS with no severe toxicities (Fig. 3a, b). However, after 2 cycles of bevacizumab administration, he unfortunately fractured his face from falling down during the rehabilitation to improve the deteriorated activity of daily life (ADL). Then, he underwent open reduction and fixation of his face fracture under general anesthesia. Eventually, he was forced to quit this promising combination therapy.",
"gender": "Male"
}
] |
PMC6381877
|
[
{
"age": 41,
"case_id": "PMC5912312_01",
"case_text": "A 41-year-old female with a past medical history of hypothyroidism and Prinzmetal's angina presented with worsening typical chest pain for 1 day. She was 10 weeks postpartum. Her pain was unresponsive to nitroglycerin and aspirin. Electrocardiogram showed T-wave inversions in anterolateral leads. She was taken to the cardiac catheterization laboratory and was found to have SCAD of the left main (LM), left anterior descending (LAD), and left circumflex arteries (LCx; Figure 1). She was managed with emergent coronary artery bypass graft (CABG) of 2 vessels, including, left internal mammary artery to the LAD and saphenous vein graft (SVG) to the ramus intermedius artery. Her subsequent recovery was uneventful and she was asymptomatic with normal echocardiogram at the 6-month follow-up.",
"gender": "Female"
},
{
"age": 51,
"case_id": "PMC5912312_02",
"case_text": "A 51-year-old male with a history of SCAD presented to our medical Center with refractory angina and decreased exercise tolerance for 2 days. Electrocardiogram showed nonspecific ST-T wave changes with initial troponin level of 0.8 ng/mL (normal <0.01 ng/mL). He was taken to the cardiac catheterization laboratory where coronary angiography showed dissection of both the LAD and the right coronary artery (RCA; Figure 2). He was managed with the deployment of 2 overlapping drug-eluting stents with good angiographic results in the RCA. In his LAD, he had a residual dissection with an angiographically determined good flow. At the 3-month follow-up, he showed recovery of his exercise tolerance and no further episodes of angina.",
"gender": "Male"
},
{
"age": 34,
"case_id": "PMC5912312_03",
"case_text": "A 34-year-old African American female with a recent Cesarean section presented with sudden-onset chest pain for 15 minutes. On admission, electrocardiogram showed ST-segment elevations in V4, V5, and V6. Cardiac catheterization was performed. It revealed a long dissection of the LAD, originating just distal to the ostium and extending up to the mid portion. Thrombolysis in myocardial infarction (TIMI) grade 3 flow (normal flow) was noted. She was initially managed with medical therapy. Two days later, she had recurrent chest pain. Electrocardiogram changes were consistent with ischemia. Repeat catheterization showed stable LAD dissection with new RCA dissection with TIMI grade 1 flow (incomplete filling of distal coronary artery; Figure 3). She underwent an emergent 2-vessel CABG (SVG to LAD and SVG to RCA). Her postoperative period was uneventful. She developed peripartum cardiomyopathy after 3 months but had recovered left ventricular systolic function at the 6-month follow-up.",
"gender": "Female"
},
{
"age": 45,
"case_id": "PMC5912312_04",
"case_text": "A 45-year-old female, professional marathon runner, with a history of Raynaud's phenomenon, migraines, gastroesophageal reflux disease, and serum-positive HLA-B27, developed a sudden-onset chest pain while riding her bicycle. The pain lasted 2 hours, throughout the duration of exercise, and was noted to radiate to her back and jaw. In the emergency room, the electrocardiogram showed anterior wall myocardial infarction (MI) with positive serum troponin of 0.15 ng/mL (normal <0.01 ng/mL). Cardiac catheterization ruled out coronary atherosclerotic disease. However, the LM had a long SCAD that was extending to the mid LAD. The blood supply distal to the lesion was compromised. It was successfully stented with 2 bare metal stents. At the 3-month follow-up, she had an uneventful recovery with partial recommencement of her strenuous physical activity.",
"gender": "Female"
},
{
"age": 49,
"case_id": "PMC5912312_05",
"case_text": "A 49-year-old female with stage IV sarcoidosis presented to our hospital with chest pain and shortness of breath. Electrocardiogram showed STEMI in the anterolateral leads. Emergent catheterization revealed SCAD in the mid LAD with an unsuccessful wiring (Figure 4). The patient was managed conservatively. Later, her hospital course was complicated by a left ventricular thrombus and an embolic stroke requiring anticoagulation. She was discharged to rehabilitation center where she stayed for a period of 6 weeks. At the follow-up in the outpatient clinic, the patient had no residual deficits of recent stroke and had no angina. Over the next year, she had worsening pulmonary hypertension secondary to her sarcoidosis and was deemed a suitable candidate for a heart and lung transplantation.",
"gender": "Female"
},
{
"age": 56,
"case_id": "PMC5912312_06",
"case_text": "A 56-year-old female developed sudden-onset, sharp chest pain that led to syncope. On admission, electrocardiogram showed NSTEMI with a troponin level of 4.5 ng/mL (normal <0.01 ng/mL). Left heart catheterization showed a SCAD involving the LCx with TIMI grade 3 distal flow (Figure 5). While receiving cardiac catheterization, she developed an acute stroke with left-sided visual field deficit and received intravenous tissue plasminogen activator with complete resolution. She was managed conservatively with medical therapy for NSTEMI. She remained compliant with her medications. Follow-up catheterization due to persistent chest pains showed healed LCx dissection with no atherosclerotic disease in the rest of her coronary arteries. She was started on nifedipine for possible diagnosis of Prinzmetal's angina (variant angina). Her symptoms improved drastically on subsequent follow-up visits.",
"gender": "Female"
},
{
"age": 60,
"case_id": "PMC5912312_07",
"case_text": "A 60-year-old female presented to our medical institution with chest pain lasting 15 minutes. Electrocardiogram showed a new-onset right bundle branch block and she was found to have a troponin of 0.24 ng/mL (normal <0.01 ng/mL). Coronary angiogram showed an abnormality in the diagonal branch of the LAD (mid D1 radiolucency) concerning for thrombus versus dissection (Figure 6). Optical coherence tomography was performed to distinguish the lesion. Therein, a SCAD was noted, which was managed with drug-eluting stent placement. Final angiography displayed no evidence of thrombosis, distal embolization, or further dissection. She remained compliant with her dual antiplatelet therapy for 8 months. Subsequently, she experienced a major gastrointestinal bleeding after which clopidogrel (Plavix) was discontinued. She remained symptom-free on follow-up visits.",
"gender": "Female"
},
{
"age": 34,
"case_id": "PMC5912312_08",
"case_text": "A 34-year-old female who was 38 weeks pregnant presented with atypical chest pain for 1 day. Electrocardiogram showed ST-segment elevations in the anterolateral leads with a negative first troponin level. Coronary angiogram showed SCAD of the mid portion of the LAD with large intramural hematoma compromising the blood flow to the first and second diagonal branches of the LAD with TIMI grade 3 flow into distal vessel (Figure 7). No intervention was done and she was admitted to the cardiac care unit where a conservative approach was adopted. After undergoing Cesarean section, repeat coronary catheterization was performed. It showed no evidence of intramural hematoma and a healed LAD dissection.",
"gender": "Female"
},
{
"age": 36,
"case_id": "PMC5912312_09",
"case_text": "A 36-year-old female who was 6-days postpartum presented with typical chest pain radiating to her left arm for 1 hour. Electrocardiogram showed ST-segment elevations in leads V2 and V3 and ST depressions in the inferior leads. Emergent catheterization showed a dissection of the proximal LAD after the first 2 septal perforators with evidence of luminal compromise by a hematoma (Figure 8). Conservative management was planned and she was started on dual antiplatelet therapy. Follow-up catheterization after 6 weeks showed no progression of the LAD dissection with resolution of the hematoma. She remained asymptomatic on follow-up visits.",
"gender": "Female"
}
] |
PMC5912312
|
[
{
"age": 30,
"case_id": "PMC5287946_01",
"case_text": "A 30-year-old man came to Peking Union Medical College Hospital (PUMCH) with headaches, fatigue, diplopia, and impaired visual field and acuity for 6 months which had worsened since the previous 2 weeks. He denied polydipsia, polyuria, sexual hypoactivity, or any symptoms of unconsciousness, epilepsy, convulsion, and cognitive disorders. Physical examinations revealed that his right visual acuity was 0.5 and the left was 0.4. Goldmann perimetry revealed a bitemporal hemianopia. He was found to have ptosis of the right eyelid. The right pupillary reaction to light was absent. Other neurological examination results were normal. His past history was negative for head trauma. His social and family history and his system review were negative.\nThe magnetic resonance imaging (MRI) demonstrated an abnormal mixed signal mass with suprasellar, parasellar, and suprasellar invasiveness in the sellar area (Fig. 1A-C). The lesion was about 2.8 x 1.9 x 1.9 cm, inside which was some spotty necrosis. A dynamic contrast-enhanced scan showed heterogeneous enhancement. Relatively normal pituitary tissue with normal enhancement could be seen near the inferior lesion margin, but was squashed. The optic chiasma was mildly compressed but the basic shape was generally normal. The bilateral internal carotid arteries were also partly wrapped. Laboratory tests used to explore pituitary disorders showed normal levels of pituitary hormones, including prolactin (N < 20 mug/L), luteinizing hormone (LH) (N > 10 IU/L), follicle-stimulating hormone (FSH) (N > 20 IU/L), thyrotropin, and corticotropin. The diagnosis of nonfunctioning pituitary macroadenoma was suspected.\nVia a trans-nasal-sphenoidal approach, a surgical exploration was performed. After drilling the sellar floor and opening the dura, a firm, tough, wheaten mass was found. As its consistency was too elastic and hypervascular to be easily cut by a surgical blade, and it adhered so tightly to the cavernous sinus and internal carotid artery, only subtotal resection was ultimately achieved. Repair of the sellar defect was done with autologous fat and fascia lata. The immediate postoperative sellar MRI was not performed. In a surprise twist, postsurgical hematoxylin and eosin (H & E) stained sections showed that the lesion contains epithelioid and spindled cells with eosinophilic cytoplasm arranged in sheets and nests. Mild-to-moderate nuclear atypia could also be observed. On immunohistochemical evaluation, the tumor cells were positive for Vimentin, CD68, CD34, Nestin, GFAP, Desmin, SMA, AE1/AE3, and S-100 protein, but were negative for NSE, Synuclein, NeuN, EMA, pituitary hormones (LH, FSH, ACTH, TSH, growth hormone, and prolactin), synaptophysin and chromogranin. Ki-67 proliferation index was 6% (Fig. 2A-K). The pathological test supported the diagnosis of adenohypophysis spindle-cell oncocytoma. The postsurgical course was uneventful and his clinical symptoms of headache and diplopia were markedly improved.\nHowever, 1 month after the surgery, the patient's vision declined sharply and meanwhile he complained of severe ophthalmodynia of the right eye. The sellar MRI revealed that the tumor recurred (Fig. 1D and E) and the patient underwent a gamma-knife treatment. But the symptoms were not relieved significantly. Three months later, the sellar MRI showed the lesion was approximately 2.8 x 2.2 x 3.1 cm with equal T1 signal and inhomogeneous long T2 signal, which were enhanced with mass or nodosity after contrast administration. The suprasellar region, bilateral cavernous sinuses, and optic chiasma were further invaded. Necrosis, cyst degeneration, and hemorrhage within the tumor could be detected (Fig. 1F-H). A secondary surgery was performed through the left pterional approach. The tumor's texture was firm to elastic and the bleeding was heavy; therefore, we just performed a partial resection, decompressed the optic nerves and chiasm. The sellar MRI after 1 week of the secondary surgery was shown as Fig. 1I to K. Postsurgically, transient central diabetes-insipidus persisted for 2 weeks. Visual field and acuity remained unimproved. Histological evaluation revealed similar morphology and immunohistochemical profiles to the previous specimen. The Ki-67 index for this time increased to 19%. From the perspectives of pathologists, the pathological grade was considered WHO III.\nOne month after the secondary surgery, the patient came to PUMCH again complaining almost blindness and severe headache. A sellar MRI was arranged, demonstrating that the tumor recurred again to approximately 4.9 x 3.6 x 3.1 cm with necrosis, cyst degeneration, and hemorrhage. The enhancement was inhomogeneous and the surrounding structures and tissues were further invaded (Fig. 1L-P). The third surgery via a transsphenoidal approach was conducted for decompressing. Partial resection was achieved and the visual disturbance and headache were alleviated a lot. Pathological evaluation results were similar to previous, confirming the diagnosis of ASCO. And the Ki-67 proliferation index increased to 45% (WHO III-IV grade, Fig. 2L), highly suggesting its malignancy. The patient has already been followed up for nearly half a year and reported no recurrence of headache and visual deterioration. His right visual acuity was 0.4 and the left was 0.3, evaluated recently.",
"gender": "Male"
}
] |
PMC5287946
|
[
{
"age": 40,
"case_id": "PMC9106225_01",
"case_text": "A 40-year-old female patient was referred for evaluation of an asymptomatic swelling on the lower lip of 6 months duration with a history of local trauma. Clinical examination revealed a well-defined, nontender, smooth-surfaced, roughly oval, fluctuant swelling [Figure 1]. No relevant medical history was elicited. Oral hygiene was fair. A provisional diagnosis of mucocele was made; the lesion was excised under local anesthesia. Histopathological examination of the excised tissue revealed cystic lumen devoid of lining epithelium and surrounded by compressed granulation tissue and peripherally located mixed salivary glands. The lumen was filled with numerous mucinous globular structures which were oval or round in shape and of varying sizes [Figure 2]. Most of the globules present in the cystic lumen were attached to the surrounding cystic capsule and seemed dissociated from one another because of their globular organization. Some of the globules were suspended freely within the lumen [Figure 3]. Individual globules exhibited a mildly cellular core with peripheral laminations of dystrophic calcifications [Figure 4]. The granulation tissue forming the cystic wall was highly cellular, consisting of chronic inflammatory cells. The mucinous globules showed positive results for PAS and Alcian blue [Figures 3 and 4].",
"gender": "Female"
}
] |
PMC9106225
|
[
{
"age": 29,
"case_id": "PMC7276389_01",
"case_text": "A 29 years old female, physician by profession presented to the emergency department with a history of aggressive vomiting five weeks back followed by left upper abdominal, a single episode of loose motion, subcostal pain radiating to left shoulder associated with shortness of breath (SOB) and was unable to take full inspiration. The patient has a history of heartburn, early satiety, indigestion, and food regurgitation six years ago and diagnosed and managed as gastroesophageal reflux disease in her native country.\nThe primary evaluation shows a toxic looking afebrile patient with vitals as; respiratory rate-27/min, pulse 87/min. Along with first-level management, abdominal ultrasonography (US) and initial laboratory workup were done in ED with no abnormal findings and the patient discharged home after the primary management independently and not asking surgeon on-call help. Upon no improvement, the patient revisited the ED where chest x-ray (CXR) as primary imaging modality was requested by surgeon on-call that showed raised right hemidiaphragm with no well discernible outlines, air-filled bowel loops above the hepatic shadow, a chilaiditi's sign, with no mediastinal shift (Fig. 1a), thus a provisional diagnosis of the right-sided diagrammatic hernia was made.\nFollowing CXR, a non-contrast CT requested showing stomach and parts of the colon in the right thoracic cavity (Fig. 2a) along with spleen located posterior to the heart - the retrocardiac spleen (Fig. 2b), thus a final diagnosis of Bochdalek hernia was made.\nSevere vomiting, a few weeks earlier was the triggering event in the patient that led to the initiation of the clinical picture. After initial stabilization, the patient was transferred to a regional tertiary care facility for cardiothoracic surgeon evaluation and management where via open thoracotomy, contents reduced and fortunately there was no vascular compromise. Repair done. Post-operative chest x-ray shows normal findings (Fig. 1b). The patient had uneventful recovery and discharged home on 10th post-operative day. The patient did well in her follow-up period. To the best of our knowledge, it is the first reported case of Bochdalek hernia associated with the retrocardiac spleen in an adult female in the published literature.",
"gender": "Female"
}
] |
PMC7276389
|
[
{
"age": 63,
"case_id": "PMC3134036_01",
"case_text": "A 63-year-old multiparous woman, gravida 4, para 3, complained of abnormal vaginal bleeding of 2 months' duration. She went into menopause at age 54. The patient had no remarkable medical or family histories. On vaginal examination, the uterus was enlarged, non-tender, smooth and movable. Vaginal ultrasonogram and magnetic resonance imaging showed a polypoid mass of 14 x 10 cm in size in the uterus, possibly representing a carcinosarcoma or leiomyosarcoma. No free pelvic fluid was identified. Computed tomography (CT) showed the liver and bile ducts to be normal. The endometrial Pap smear was evaluated as positive. Biopsies of the endometrium were carried out and the histological diagnosis revealed carcinosarcoma. The serum AFP level was 10,131 ng/ml (normal <20). Other tumor markers and liver function test results were within normal limits. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy.\nThe resected enlarged uterus, weighing 560 g and measuring 14 x 12 x 7 cm, had a smooth glistening surface. The polypoid tumor originated from the uterine cavity when the anterior wall of the uterus was opened. The uterine adnexae were normal in shape and size. There was no evidence of a tumorous lesion. Microscopic examination showed that the polypoid tumor was a mixture of carcinomatous and sarcomatous components (fig. 1a). The tumor had invaded the uterine cervix, but no metastases were found in the dissected lymph nodes. The carcinomatous component showed adenocarcinoma arranged in sheets and cords with a hepatoid appearance. Reactivity for AFP was cytoplasmic in the hepatoid carcinoma lesion (fig. 1b). The sarcomatous component showed no reactivity for AFP. The large pleomorphic cells were positive for desmin, actin, CD10, MyoD1, and myoglobin and could be regarded as being rhabdomyosarcoma. There was no staining with S-100. In summary, the tumor was histopathologically diagnosed as heterologous uterine corpus carcinosarcoma associated with AFP-producing hepatoid adenocarcinoma.\nPostoperatively, the patient received six courses of chemotherapy with paclitaxel (175 mg/m2) and carboplatin (AUC 5). This regimen was repeated every 3 weeks. After the third course of chemotherapy, the patient's serum AFP level decreased to 4.5 ng/ml. The patient is alive with no evidence of recurrence or increase in the serum AFP level in the 2 years since treatment.",
"gender": "Female"
},
{
"age": 82,
"case_id": "PMC3134036_02",
"case_text": "An 82-year-old woman, gravida 0, para 0, was referred to our hospital with vaginal bleeding of 2 months' duration. She had undergone surgery due to breast cancer at the age of 68. On pelvic examination, enlarged uterus without a palpable adnexal mass was detected. The vaginal wall showed no abnormalities. Portio vaginalis could not be detected, so the endometrial Pap smear could not be done. Magnetic resonance imaging revealed an enhanced mass, 8 cm in size, in the uterine corpus cavity, possibly representing malignant tumor. CT scan demonstrated ascites and no lymph nodes were detected. CT and ultrasonography revealed no abnormalities in the liver or bile duct. The serum AFP level was elevated (401 ng/ml), but no elevation of other markers, such as carcinoembryonic antigen or carbohydrate antigen 125, was observed. The blood count and serum biochemical data were unremarkable. From these results, malignant uterine tumor was highly suspected. A total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic washings was carried out. The resected uterus was enlarged and filled with a spongy material. There was no apparent extrauterine extension of the tumor. A partially necrotic polyp, 8 cm in size, was present within the endometrial cavity, which infiltrated into the myometrium for about two-thirds of its thickness but did not invade the cervix. Cytology of the pelvic washings was negative. Histologically, the tumor was composed of carcinomatous and sarcomatous components (fig. 2a). The carcinomatous component was an endometrioid adenocarcinoma with trabecular hepatoid cells, mostly showing hepatocellular carcinoma-like proliferation. Immunohistochemistry also revealed AFP-positivity in many tumor cells (fig. 2b).\nThe sarcomatous component showed rhabdoid features including spindle-shaped tumor cells. Occasional cells with eosinophilic cytoplasm and cytoplasmic cross-striations were identified. Immunohistochemistry showed focal positivity of tumor cells with desmin, MyoD1, and CD10. On pathologic examination, the tumor was interpreted as being a heterologous uterine corpus carcinosarcoma associated with AFP-producing hepatoid adenocarcinoma.\nWe did not carry out any adjuvant chemotherapy or irradiation because of the patient's advanced age, in addition, she and her family refused these therapies. Two months after the surgery, the patient's serum AFP level decreased to a normal level. However, multiple lung metastases with a high-serum AFP level reappeared and the patient died 1 year after the operation.",
"gender": "Female"
}
] |
PMC3134036
|
[
{
"age": null,
"case_id": "PMC9184873_01",
"case_text": "The characteristics of patients are outlined in Table 1. Twenty of the 34 MM patients were females and 14 were males, the median age was 73,2 years (range 64.6-80.3) and the median time from diagnosis of MM to the first treatment with daratumumab was 37 months (range 235-3). Cytogenetic characteristics were obtained from only 7 patients, of these only one was unfavorable. Each patient received one line of therapy and 6 (14,7%) patients received two lines or more. All 34 RRMM patients received a previous bortezomib-based therapy in which bortezomib was given with dexamethasone alone (3 cases) or combined with melphalan (16 cases) or with thalidomide (15 cases). In addition, 4 patients received lenalidomide, 3 patients received pomalidomide and 1 patient received Carfilzomib. Before DRd, seven patients (20,6%) underwent to a prior autologous stem cell transplantation (ASCT), that it is consisted in a single ASCT in 5 patients and in a double ASCT in the other 2 cases.\nSixteen patients (47%) presented one or more comorbidities: cardiovascular diseases (11), solid tumors (4), metabolic disorders (3), other hematological disorders (2), rheumatological diseases (1), pulmonary diseases (1), neurological diseases (1) and gastrointestinal diseases (1).\nTwelve patients (36%) were refractory to the previous therapy. Eight patients (23,5%) presented with anemia (Hb < 10 g/dl), 3 (8,8%) with chronic kidney disease (creatinine > 2 mg/dl), 19 (55,9%) with bone lesions, while none of the patients presented with hypercalcemia (Ca2+ > 11 mg/dl). Among the 34 patients, 18 (53%) had a monoclonal component (CM) > 2 g/dl and 18 patients (53%) had a Bence-Jones proteinuria.\nAll RRMM patients received daratumumab IV at the standard dose of 16 mg/kg whereas in 30 (88,3%) patients it was combined with lenalidomide and dexamethasone (DRd) and in the remaining 4 cases (11,7%) with bortezomib and dexamethasone (DVd). A median number of 8 cycles (range 1-32) was administered within a median follow-up of 16 months (range 1-35). Among DRd treated patients, the lenalidomide starting dose was reduced in 12 patients (35%) according to the renal function or due to neutropenia or thrombocytopenia. At the time of analysis, 25 (73,5%) patients were currently receiving treatment. Nine patients (26,5%) discontinued treatment for progressive disease (8 patients) and intolerance (1 case).\nPatients who received at least two doses of daratumumab-based triplets were included in the statistical analysis. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier product-limit estimator.\nThe overall response rate (ORR) was 88%. A Complete Response (CR) occurred in 12% of cases, a Very Good Partial Response (VGPR) in 44%, and a Partial Response (PR) in 32%. The Median time to achieve at least a PR was 40 days (range 30-110 days). Progressive disease was observed in 8 patients (23,5%), in which 5 cases (14,7%) led to death. Twenty-six patients (76,4%) were responding to treatment at the time of analysis.\nMoreover, 4 transplant-eligible patients, however refractory to the VTD scheme after a median of 6 cycles of daratumumab, deepened their response, allowed themselves to receive an ASCT, and then continued DRD therapy. One of these four patients progressed and died within 100 days after the transplant.\nAdverse events are summarized in Table 2. The most common hematological toxicities of any grade were neutropenia (15 patients; 44%), managed with lenalidomide dose reduction, and thrombocytopenia (10 patients; 29%). Other common non-hematological toxicities of grade 1 involved 10 patients (29%), including asthenia, light-headedness and breathlessness, edema of lower extremities, intestinal intolerance with diarrheal episodes, and epigastralgia. Two patients (5,4%) presented pulmonary AEs, one case with pneumonia and the other case with a chronic obstructive pulmonary diseases (COPD) exacerbation. The only grade 4 AE case was observed at the beginning of the third cycle and consisted of intolerance with persistent gastrointestinal disorders that required patient hospitalization leading to a discontinuation of the therapy.\nAfter an extensive oral premedication of our patients consisting of cetirizine dihydrochloride 10 mg, montelukast 10 mg, paracetamol 1000 mg and dexamethasone 20 mg that was administered once/daily from the day before to the day after the infusion, we observed a DARA infusion-related reactions (IRRs) in only 3 patients (8,8%). All IRRs were a grade 1 - 2 and occurred during the first infusion, with urticaria, tachycardia, and respiratory symptoms, such as bronchospasm and dyspnea.\nAt a median follow-up of 16 months (range 35 - 1), the median PFS and OS have not been reached (NR); the 12-month PFS and OS rates were 78% and 86,5%, respectively (Fig. 1. A and B). In the univariate analysis, the achievement of at least a VGPR, receiving just one line of previous therapy and the male gender resulted in a statistically significant better PFS (Fig. 1. C, D, and E), whereas the absence of anemia at the start of the daratumumab-based triplets and the achievement of at least a VGPR predicted a better OS (Fig. 1. F and G).\nIn the multivariate analysis, only the achievement of at least a VGPR resulted as an independent predictor of prolonged PFS, showing an HR of 0.037 (95% CI of 0.0001-0.988; p= .049). Interestingly, other potential predictors of unfavorable prognoses, such as the condition of early or late relapse, did not impact patients' clinical outcomes after DRd.\nIn the present series, 4 patients received DVd because they were previously exposed to lenalidomide. Compared to the DRd treated patients, they showed a worse PFS and a similar OS. Once again, the small number of cases did not allow conclusions to be drawn concerning this issue. Apart from the daratumumab triplet used, many other factors may have contributed to the worse outcome of these four patients, as for example, the fact that they all had received more than one line of previous therapies.",
"gender": "Female"
}
] |
PMC9184873
|
[
{
"age": 71,
"case_id": "PMC6186336_01",
"case_text": "A 71-year-old female with a history significant for hypertension, hepatitis B, and hypothyroidism, underwent bone marrow biopsy which showed a hypercellular bone marrow with >90% cellularity and 81% myeloblasts expressing CD 34 and CD 117 markers, confirming a diagnosis of acute myeloid leukemia (AML). Molecular testing showed no evidence for FMS-like tyrosine kinase 3 internal tandem duplication, absence of nucleophosmin1 and KIT exon 8, and 17 mutations, suggesting a lower risk of relapse after chemotherapy. Based on cytogenetic studies, secondary AML was diagnosed. Given her advanced age, decitabine therapy was commenced. A baseline 2-D transthoracic echocardiogram (TTE) showed normal function with an ejection fraction (EF) of 55-60%. After completing 10 cycles of decitabine, she was noted to have a tachycardia and dyspnea by self-report. She was therefore referred to cardiology with these symptoms in preparation for allogeneic stem cell transplant.\nThe heart rate was 110/min, and a 2/6 ejection systolic murmur and a loud P2 with an S3 and S4 gallop were heard. Lungs were clear. No jugular venous distension or pedal edema was noted.\nLaboratory data is significant for a serum creatinine level of 0.8 mg/dl, estimated glomerular filtration rate of 80 ml/min per 1.73 m2, and N-terminal pro-b-type natriuretic peptide level of 517 pg/ml. Her complete blood count showed a white blood cell count of 12.6 x 109/l with greater than 50% blasts, low hemoglobin at 7.8 g/dl, hematocrit value of 25%, large platelet count of 212 x 109/l, and lactate dehydrogenase level of 588 U/l. Serum troponin or creatinine phosphokinase levels were not performed due to a lack of discernibility in patients undergoing chemotherapy for cancer. Echocardiogram showed severe left ventricular systolic dysfunction (EF 28%), mildly abnormal end systolic dimension (Figure 1), and a mild reduction in right ventricular systolic function. Global averaged left ventricular longitudinal peak systolic strain was abnormal at -12% (normal more negative than -18%) (Figure 2). Nuclear stress test showed no evidence of coronary disease. Patient was euthyroid at the time of diagnosis.\nThe patient was diagnosed with New York Heart Association class II and American Heart Association stage B heart failure with reduced ejection fraction. In the absence of any viral illness, toxins, or coronary disease, or concomitant cardiotoxic medication use and known recent normal ejection fraction, the etiology was attributed to decitabine use. The patient was subsequently started on metoprolol succinate 50 mg twice a day and furosemide 20 mg daily. Follow-up echocardiogram 4 weeks later showed no change in the ejection fraction of 28%, but there was mild improvement in the global left ventricular longitudinal peak systolic strain at -15% (improved from -12%).",
"gender": "Female"
}
] |
PMC6186336
|
[
{
"age": 24,
"case_id": "PMC9937515_01",
"case_text": "A 24-year-old female was brought to the emergency department with complaints of altered mental status and recurrent seizures associated with low-grade fever, headache, and altered sensorium for the last three days. The seizure was acute in onset, generalized tonic-clonic in nature, and associated with tongue biting, blood-tinged frothing, and urinary incontinence. It was her second episode of abnormal body movement and altered sensorium after being admitted to the hospital. Each episode lasted for 20-30 minutes. She returned from a hill station a few days ago, and her family and social history were insignificant.\nOn admission, the patient was afebrile, with a blood pressure of 110/70 mmHg, a Spo2 of 97%, and a heart rate of 86/min. Her physical examination revealed a Glasgow coma scale (GCS) score of 11 (eye: 4, verbal: 2, motor: 5). Her rest systemic examination was unremarkable. Her initial laboratory investigations were within normal range except for mild elevation of transaminases (Table 1). Further evaluation with a non-contrast computed tomography (CT) head shows a ring-enhancing lesion in the left temporal region with perifocal edema, an eccentric, and an inflammatory granuloma (Figure 1). In addition, magnetic resonance imaging (MRI) brain showed a well-defined rounded discrete hyperintense lesion in the left parietal region with mild to moderate vasogenic edema, leading to partial effacement of the adjoining sub-arachnoid space and moderate peripheral rim enhancement (Figure 2). On follow-up after two weeks, an MR venogram revealed that the left transverse sinus was hypoplastic, as shown in Figure 3.\nFollowing confirmation of diagnosis, the patient was started on albendazole 400mg twice daily and carbamazepine. However, on follow-up after two weeks, the patient developed skin rashes, remarkably elevated liver enzymes, and total bilirubin (Figure 4).\nAfter proper evaluation, immediately anti-epileptic drugs were discontinued, and for skin rashes, the patient was given oral fexofenadine and methylprednisolone, levetiracetam beside topical steroids. On subsequent follow-up, her rashes and deranged aminases resolved, and the patient was doing well.",
"gender": "Female"
}
] |
PMC9937515
|
[
{
"age": 0,
"case_id": "PMC10196249_01",
"case_text": "A 27-day-old boy presented to the emergency room with a 7-hour history of fever. After giving superficial skin cooling at home, the baby remained febrile. The peak temperature was 38.5 C. The baby had a poor appetite and symptoms of sneezing and a stuffy nose without vomiting and coughing. He was a term baby without extraordinary perinatal history. His parents had a history of sore throat and cough for several days during the Omicron epidemic, but they didn't test for SARS-CoV-2. After admission to our NICU, he was febrile at 38.3 C with a respiratory rate of 52 breaths/min and oxygen saturation of 95%-99% while breathing ambient air. His examination was remarkable for congested nares, clear rhinorrhea, and mild subcostal retractions. There were coarse breath sounds in all lung fields. No murmur of the heart could be heard. The liver was palpated at 1 cm-2 cm under the costal margin (consistent with age), and the spleen was not palpated. Laboratory data revealed that the total WBC count and the proportions of the major leukocyte subsets in peripheral blood were normal. Blood gas, C reactive protein (CRP), and transaminase levels were in the normal range. RNA test for SARS-CoV-2 from a throat swab was positive. Then, the baby was given physical cooling and nasal secretion removal to keep the airway clear (see Table 1).\nThe baby presented febrile once daily in the following four days, and the peak temperature decreased from 38.4 to 38 C. Meanwhile, he developed a cough and sputum, along with a dropping of SpO2 to 80% when feeding. His lung demonstrated scattered crackles (see Figure 1). Because of continuous fever and pneumonia, more investigations were performed. The total WBC count and the proportions of the major leukocyte subsets were still in the normal range. CRP was 4.3 mg/L (0-10 mg/L). Anemia was noticed: RBC was 2.73 x 1,012/L, hemoglobin was 91.0 g/L, and hematocrit was 27.4%. Alanine transaminase (ALT) was 88 U/L(<=41 U/L), aspartate transaminase (AST) was 180 IU/L(<=40 U/L), and glutamyltranspeptidase (gamma-GT) was 109 U/L(6-42 U/L). Further, pathogens tests identified that parainfluenza virus RNA was positive, but there was no evidence of infection for other pathogens such as RSV, EBV, TORCH, ECHO virus, Coxsackie virus (CA16/CVB), influenza A/B/H1N1/H3N2, adenovirus, mycoplasma, chlamydia, HIV, Human metapneumovirus, rhinovirus, and hepatitis B/C virus. Ultrasonography for the heart and abdomen was normal. Therefore, the baby was given the nebulization treatment of budesonide and ipratropium bromide solution and given Glutathione for hepatoprotection. In addition, he inhaled oxygen intermittently to avoid hypoxia when feeding.\nOn the 7th day after admission, the patient was no longer febrile but was still coughing and had nasal congestion. On the 10th day, respiratory symptoms improved greatly, and we re-tested the liver function after 5 days of hepatoprotective treatment. The transaminase level elevated markedly. ALT was up to 645 U/L(<=41 U/L), AST increased to 480 IU/L(<=40 U/L), and gamma-GT was 491 U/L(6-42 U/L). However, bilirubin, blood ammonia, blood glucose, lipids, lactate, coagulation function, and albumin levels were within the normal range. The patient's perinatal medical history and family history were tracked carefully, and the possibility of inherited metabolic liver disease was ruled out. Furthermore, the patient's history of drug exposure before/after admission was also reviewed, and there was no evidence of drug-induced liver injury. So, virus infection may contribute to liver injury and the elevation of transaminase levels. When the immune system clears the virus, the injury should be alleviated. Thus, we only administered glycyrrhizin and bicyclol to promote recovery.\nOn the 14th day, the baby looked well with the normal physical examination. Laboratory tests demonstrated that ALT decreased to 125 U/L(<=41 U/L), AST was 44 IU/L(<=40 U/L), and gamma-GT was 283 U/L(6-42 U/L). He continued to take glycyrrhizin and bicyclol after being discharged home. The liver transaminase level returned to normal on 8 and 15 days after discharge (see Table 2 and Figure 2).",
"gender": "Male"
},
{
"age": 0,
"case_id": "PMC10196249_02",
"case_text": "A 7-day-old girl was admitted to our NICU because of a 30-hour intermittent fever with a peak temperature of 38.5 C. Her parents noted that she had a stuffy nose with clear rhinorrhea and choked when feeding over the past two days. She coughed occasionally but had sputum in her throat. Her appetite was unchanged without increasing work of breathing, vomiting, and diarrhea. Her caregivers had confirmed infection of SARS-CoV-2 several days ago. Her mother was healthy during pregnancy but detected fetal hydronephrosis with the right duplex kidney in the third trimester. The baby was born through an uneventful C-section delivery at a gestational age of 40w+6. The baby looked well after birth, and there was no evidence of early-onset sepsis. On physical examination, she had a temperature of 38.6 C and mild tachypnea of a respiratory rate of 50 breaths/min without retraction. Her lungs demonstrated coarse breath sounds without crackles and wheezes. The lab investigations showed that CRP was increased to 19.8 mg/L(0-10 mg/L) (see Table 1).\nWBC, blood gas analysis, transaminase level, and bilirubin levels were all in the normal range. The blood culture for bacteria was negative. Chest x-rays suggested increased and blurred bilateral lung markings in both lung fields (see Figure 1). Cardiac ultrasound demonstrated a left-to-right shunt of 2.6 mm through a patent foramen ovale (PFO). Abdominal ultrasound showed mild bilateral hydronephrosis and calculus in the right kidney (3.1 mm x 2.7 mm), and there were no abnormalities in the liver, gallbladder, and spleen structures. PCR and quick antigen tests for SARS-CoV-2 from the throat swab were positive. There was no evidence of infection from other viruses [RSV, EBV, TORCH, ECHO virus, Coxsackie virus (CA16/CVB), influenza A/B, adenovirus, mycoplasma, chlamydia, HIV, Human metapneumovirus, rhinovirus, and hepatitis B/C virus]. Normal saline helped to clean the airway, and nasal drops were used to relieve nasal congestion. Moreover, superficial skin cooling was given when the baby was febrile, and piperacillin/tazobactam was administered for pneumonia.\nThe baby's body temperature declined to normal on the 2nd day after admission. The respiratory symptom alleviated over the following days. On the 6th day, the laboratory tests showed that the transaminase level increased significantly without abnormality of bilirubin and albumin (see Table 2 and Figure 2). Then, the hepatoprotective treatment of glycyrrhizin and bicyclol was administered.\nALT decreased by half on the 11th day. Given that the baby had recovered from fever and respiratory symptoms, she was discharged home with oral drugs of glycyrrhizin and bicyclol and was continued to be followed up in the outpatient department. Two weeks later, lab tests suggested that ALT and AST decreased to the normal range.",
"gender": "Female"
},
{
"age": 0,
"case_id": "PMC10196249_03",
"case_text": "A 15-day-old girl was brought to the emergency center with a 2-day recurrent fever after contracting confirmed cases of COVID-19. The peak temperature was 38.1 C. Besides fever, she had a stuffy nose and a mild cough. She did not develop diarrhea and vomiting during the course. She had no complicated perinatal history. Her examination was febrile at 38.1 C with a respiratory rate of 48 breaths/min and oxygen saturation of 98%-100%. She had normal respiratory effort, and coarse breath sounds could be heard in all lung fields. Lab data of the WBC, CRP, blood gas, transaminase levels, and bilirubin levels were all in the normal range. The PCR test was positive for SARS-CoV-2 without other positive findings of other pathogens [RSV, EBV, TORCH, ECHO virus, Coxsackie virus (CA16/CVB), influenza A/B, adenovirus, mycoplasma, chlamydia, HIV, Human metapneumovirus, rhinovirus, and hepatitis B/C virus]. After admission, the baby was given the nebulization treatment of budesonide and ipratropium bromide, using normal saline and nasal drops to relieve nasal congestion and keep the nasal cavity clean (see Table 1).\nThe baby returned to normal temperature and developed frequent coughs over the days. Her lung examination demonstrated scattered crackles on the back side, and then, phlegm and wheezing sounds could be heard in the following days. Chest x-rays showed that bilateral lung markings increased and blurred, with patchy shadows on the right upper lung field (see Figure 1). The piperacillin/tazobactam for pneumonia was administered on the fourth day after admission. Since then, her symptoms and signs of respiratory improved gradually.\nThe baby got better on the 6th day after admission with wild nasal congestion. Laboratory tests showed that ALT and AST increased significantly (see Table 2 and Figure 2). She was also administered hepatoprotective treatment of glycyrrhizin and bicyclol. After a 2-week treatment, the liver function recovered totally.",
"gender": "Female"
},
{
"age": 0,
"case_id": "PMC10196249_04",
"case_text": "A 24-day-old boy was admitted to the NICU for an 8-hour history of fever with a peak temperature of 38 C. The parents complained that the baby had a mild cough with sputum, and they noticed he seemed to have facial and lip cyanosis when feeding. The baby was lethargic and had a poor appetite, accompanied by watery diarrhea without emesis. He was born at a gestational age of 36w+4 via cesarean delivery. He had no remarkable perinatal history. His mother confirmed COVID-19 with fever and cough before he had symptoms. On physical examination, his temperature was 38 C with a respiratory rate of 46 breaths/min; blood pressure was in the normal range, and his SpO2 was 97% while feeding and breathing ambient air. Coarse breath without crackling sounds in all lung fields could be heard. No heart murmur was detected. Prominent reticulated mottling of the skin could be seen on the lower extremities, especially when he was febrile. Capillary refill time in the lower extremity was 2 s. The liver was palpated at 1 cm under the costal margin, and the spleen was not palpated. Laboratory data revealed that WBC, subsets proportion, CRP, procalcitonin (PCT), blood gas, electrolytes, transaminase, and bilirubin levels were all in the normal range. Blood culture was negative. No other apparent abnormalities were reported on the routine stool test. PCR test for the SARS-CoV-2 virus was positive. The common respiratory pathogens such as influenza A/B, RSV, parainfluenza, adenovirus, mycoplasma, and chlamydia were negative. Chest x-rays showed that bilateral lung markings increased and blurred (see Figure 1). The cardiac ultrasound was normal. The CRP tests were repeated, and sepsis was ruled out in the next few days. So, the baby was administered piperacillin/tazobactam for 36 h and nebulization treatment was given (see Table 1).\nThe fever lasted for 2 days, and the peak temperature was 38.6 C. The baby recovered with occasional cough and mild nasal congestion on the 5th day after admission. On the 6th day, the ALT and AST were significantly increased (see Table 2 and Figure 2). There was no evidence of infection for other pathogens related to liver injuries such as EBV, TORCH, ECHO virus, Coxsackie virus (CA16/CVB), and hepatitis B/C virus. He was also administered hepatoprotective treatment of glycyrrhizin and bicyclol.\nThe baby received hepatoprotective treatment for 5 days. On the 11th day after admission, repeated lab tests demonstrated that ALT and AST decreased to 97 U/L and 40 IU/L, respectively. Then he was discharged with hepatoprotective drugs. 4 days after discharge, the liver function went back to the normal range.",
"gender": "Male"
}
] |
PMC10196249
|
[
{
"age": 5,
"case_id": "PMC4122203_01",
"case_text": "Gloria lived in an intact family with her parents and three younger siblings until her parents divorced at age 5, but she provided no details about her childhood before this time and would not speak at all about her biological father. Gloria and her siblings lived predominantly with their mother after the divorce. Her mother remarried 5 years later when Gloria was 10 years old and she viewed her stepfather as her \"actual\" father. She described him as being humorous, loved, and trusted, but she also described him impulsive, irascible, and argumentative. Gloria seemed insecure about her stepfather's acceptance, wondering how far she could push him before he would break. Would he accept her even if she acted like a wild child? Gloria stated that \"once a week I pushed him until he burst,\" and she told how she tested him with \"mischievousness\" so as to push her stepfather into beating her. Gloria's deliberate misbehavior and her stepfather's beatings were central to their relationship.\nGloria's first major traumatic experience as a sadistic rape in late adolescence. The only details that she provided about her rape was that it occurred during daytime and that she did not know the rapist. After the rape, she began around 3 weeks later to have sudden headache and fainting attacks, fainting as much as three times a day. She also developed chronic dissociation experiences. Gloria's symptoms appeared to be associated with feeling of being exposed and to school or performance-related pressure. Although these problems persisted, she did not seek psychological treatment. Her symptoms, especially fainting, diminished when she studied abroad. Her symptoms reoccurred after returning home 2 years later, however, and she decided to go back abroad.",
"gender": "Female"
},
{
"age": 30,
"case_id": "PMC4122203_02",
"case_text": "Gloria's second major traumatic experience was at 30 years old when her boyfriend of 2 years died in an accident. Gloria had separated from him shortly before his death, the reason being that she was no longer able to tolerate physical closeness. She felt severely guilty about his death and her guilt had masochistic qualities. As a result, she did not have another intimate relationship for many years.\nGloria had recently experienced a third trauma prior to her decision to seek treatment. She had been in a serious accident in which she had been thrown out of her car and into the air rendering her unconscious. She was thought at first to be dead. Her physical injuries included three spinal discs and a strain on the cervical spine and her fainting episodes increased to many episodes a day. Although Gloria reported in her initial interview, almost proudly, saying \"I survived this,\" and she had since was unable to work.\nGloria felt that her symptoms had become debilitating, and she noticed that her fainting spells seemed related to stress. Her headaches had become so severe that she risked becoming unconscious. She was not able to recall what preceded the headaches and she could not remember any indicators associated with their onset, such as less debilitating headaches or other physical warning signs. Gloria described herself as being on autopilot. This \"defensive mechanism\" had saved her life more than 20 years ago, but now this automatic mechanism was out of her control.\nGloria had not allowed herself to think about this until she entered treatment and her treatment goal was \"to get rid of it.\" She had a stiff commitment to being strong and carrying on. \"I want to function. I will get through this. I want to be able to work. I have worked for many years to wipe out the traumatic event, to get rid of it, to repress it.\" This perspective had dominated her life and kept her moving forward. She was frightened of not being able to be in control of her symptoms and the prospect of becoming dependent on the pain medication prescribed to combat her severe headaches.\n was a prominent psychoanalyst to use ethological concepts to describe the infant's biologically predisposed attachment to a primary caregiver. He viewed relatedness in early childhood as a primary and independent developmental goal that is not subservient to a physiological needs (e.g., hunger) or psychoanalytically defined primary processes. The infant is perceived from an interactional perspective, with a focus on the relationships with primary attachment figures. Attachment theory maintained some foundations of psychoanalytic theory (e.g., the developmental point of view) and there is a strong literature that discusses the divergences and convergences of psychoanalysis and attachment theory (e.g.,) and also developed some aspects further, particularly the delineation of the internal world.) overview of the intersection of these two approaches demonstrated that the relationship between attachment theory and psychoanalysis is more complex than adherents of either community have generally recognized. This paper addresses some of these complexities by integrating attachment assessment using the Adult Attachment Projective Picture System (AAP) in psychodynamic psychotherapy in an adult traumatized patient.\n proposed that one major difference between psychoanalysis and attachment theory falls in the description of forms of defensive processes. Traditional psychoanalytic models provide a complex constellation of defenses to interpret a broad range of intrapsychic phenomenon, including phantasy, dream, wish, and impulse (e.g.,). Attachment theory delineates two basic processes that manifest in three forms. According to), Bowlby defined defense as forms exclusion directed to modulating difficult and anxious experiences with attachment figures, and the child's experiences with incomplete or failed bids for parental protection, care, and comfort. He defined defenses in terms of two qualitatively distinct processes: deactivation (retaining elements of intellectualization and denial) and cognitive disconnection (retaining elements of splitting).) pointed out that under normal circumstances these two exclusion processes are associated with goals to maintain physical and psychological proximity in the attachment-caregiving relationship under conditions when the child's experiences with the attachment figure are less than satisfying. George and Solomon refined model suggesting that deactivation and cognitive disconnection organized and supported at least minimal forms of representational, behavioral, and emotional regulation. proposed that these forms defensive exclusion functioned to segregate (akin to repression) memory, affect, and experience when the attachment figure was not available, conceiving of an extreme process he termed \"segregated systems.\" Segregated systems were thought as associated with the painful and chronic distress experiences, such as those that accompany loss. Bowlby posited that segregated systems were the intrapsychic root of symptoms related pathological mourning and severe psychopathology. Attachment theorists have since demonstrated that segregated systems are associated with experiences of failed protection, attachment trauma, and disorganized/dysregulated attachment behavior and representation.\nConsistent with a psychoanalytic approach, some attachment theorists have suggested that utilization of defensive process models is needed to provide a complete picture of the emotional and behavioral regulation processes individuals develop from their childhood relationships with attachment figures. Further, concluded, \"In order to understand the relationship between adult attachment and mental health risk we need to examine the attachment concepts of defense and segregated systems, the mental processes that define disorganization\" (p. 295). These theorists operationally defined basic defense scheme as a central element for evaluating representational patterns of attachment using the Adult Attachment Projective Picture System. Suggesting that these representational structures have developed under conditions of attachment trauma (abuse, loss, failed protection), the concept of segregated systems is fruitful to explain some forms of relationship-based psychopathology in adults.\nThe discussion that follows provides some ideas about using attachment concepts in clinical work by showing how the perspectives of a psychoanalyst and attachment assessment may improve the understanding of an individual case of a traumatized patient with the diagnosis of a PTSD with dissociative states (e.g., fainting in response to stressful situations).\nThe lifetime prevalence of PTSD in Germany has been found to be 1.3% with a female-to-male ratio of 3.25-1. Traumatized patients are frequently misdiagnosed and mistreated in the mental health system. The number and complexity of the symptoms lead to fragmented and incomplete treatment. PTSD patients are vulnerable to become re-victimized by caregivers because of their difficulties with close relationships. Severely traumatized PTSD patients (complex trauma) develop difficulties in modulating arousal and show signs of severe affect dysregulation (e.g., aggression against self and other, and problems with social attachment and dissociative states).\nDissociation, defined as a deficit of the integrative functions of memory, consciousness and identity, is often related to traumatic experiences and traumatic memories. During clinical interviews, dissociation is suggested either by such a degree of unwitting absorption in mental states that ordinary attention to the outside environment is seriously hampered. Dissociation can be accompanied by a sudden lack of continuity in discourse, thought or behavior of which the person is unaware (supposedly due to intrusion of dissociated mental contents in the flow of consciousness). Thus, for instance, a dissociative patient may suddenly interrupt her speech during a therapeutic session, stare into the void for minutes, and become unresponsive to the therapist's queries as to what is happening to her. Or a patient suffering from PTSD may suddenly utter fragmented and incoherent comments on intrusive mental images (usually related to traumatic memories) that surface in consciousness and hamper the continuity of the preceding dialog with the therapist. In the most extreme variety of dissociation (Dissociative Identity Disorder), an alternate ego state may appear during the clinical dialog, reporting (sometimes with an unusual tone of voice, e.g., like a child) memories of childhood abuse of which the patient has previously been totally unaware, or expressing attitudes and beliefs quite extraneous to the patients' personality.\nFurthermore, shattered meaning propositions predominate. Trust, hope and sense of agency is accompanied by social avoidance, with loss of meaningful attachment and therefore lack of participation in preparing for future.\nThe founding premise of attachment theory is that stress, especially traumatic stress, produces a strong desire for proximity to and comfort by attachment figures; this desire is built into human biology as a survival safety mechanism and the mechanism is functions unchanged throughout the life span. Attachment experience shapes the ways in which individuals manage stress and are especially important when individuals experience a traumatic event. When attachment is secure, individuals know how and when to seek attachment figures and develop internal representations of self as deserving of care. Attachment security fosters confidence and trust that figures are available, empathic, and sensitive to their needs; security is a buffer or resilience factor that supports recovery from trauma. When attachment is insecure, emotional and behavioral reactions when distressed may be made even more painful by unconscious evaluations that wishes for comfort are illegitimate. Insecurity may result in additional painful interactions with the attachment figures rather than the functional comfort and protection for which attachment was intended. Insecurity fosters anxiety, anger, and fear, and increases the risk of developing trauma-related emotional disorders. Extreme forms of insecurity are associated with the breakdown of attachment and caregiving regulatory mechanisms risk emotional and homeostatic dysregulation, often termed disorganized attachment. The risk of dysregulation is heightened when attachment relationships are threatened or threatening, such as parental loss or psychiatric debilitation or maltreatment. defined events such as these as attachment traumas, events that involve terrifying threats to the integrity of self or attachment relationships. Attachment disorganization, conceived in terms of mechanisms of dysregulation and attachment trauma, has been shown to predict vulnerability to severe psychiatric symptomology, including dissociative symptoms.\n found the metaphor of a \"drama triangle\" useful in thinking about the intersection between dissociation and disorganized attachment. The dissociation triangle addresses how disorganized attachment fosters dissociative mechanisms that create incompatible and separate representations of self as victim, rescuer, and persecutor. The child's representation of the attachment figure is represented in a conflicting manifold way. On the one side, the attachment figure is represented as source of the child's fear, the self as a victim of attachment figure as persecutor. On the other side, the attachment figure by virtue of being the child's biological protector is viewed as the child's source of safety and protection (rescuer). In the child's mind, representation of self and attachment figure shift among these three incompatible models that are too complex to be synthesized into an integrated model of self. Liotti's model provides us with an integrated psychodynamic and attachment approach to our first questions concerning Gloria's illness, questions regarding the childhood origins of her episodes of near unconsciousness and her inability to ask for help following traumatic assault.\n examined cognitive perspectives on unresolved attachment in patients diagnosed with PTSD. They proposed that unresolved loss, as defined in attachment assessment during interview, involves intrusion avoidance phenomena similar to those of PTSD. Specifically, they develop a model based on unresolved loss that involves the failure to integrate representations of self and the world following a loss. The features of unresolved loss can be understood as emerging as a result of the activation of unintegrated representations of the loss experience and cognitive and behavioral avoidance processes. In this model, the sudden intrusion of memories, cognitions, and emotions associated with the loss automatically captures attention and initiates behavioral dispositions that are incompatible. With regard to attachment, the authors suggested that this was the mechanism that interfered with caregiving behavior. Lack of attentional resources and incompatible response tendencies can also result from safety behaviors directed at avoiding the perceived negative consequences of activating trauma memory. The authors proposed that these processes offer a novel way of understanding the disturbances in behavior and speech that are evident in mothers who are designated as unresolved with respect to loss.\nThis suggests that representational attachment measures, like the AAP, can provide a good understanding of the movement that the client might be making toward empowerment, integration, or understanding. Thus, even if a patient's overall attachment is unresolved (i.e., dysregulated), there may be indications in their responses to the AAP stimuli that suggest they are moving toward mental organization. Given the negative outcomes that are associated with abuse, focusing on resources and defensive strategies is arguably important for therapeutic recommendations.",
"gender": "Female"
}
] |
PMC4122203
|
[
{
"age": 20,
"case_id": "PMC7174775_01",
"case_text": "The DMD participants had different levels of hand function. Participant one (DP1, 20 years old) was able to use his hands functionally, and no contractures relevant to hand/wrist movement were observed. Participant two (DP2, 22 years old) was able to functionally use his hand but experienced a decrease in strength and minimal contractures relevant to hand/wrist movement. Participant three (DP3, 25 years old) was not able to use his hands at all and was affected by immediate onset of fatigue during its use. Extensive contractures relevant to finger movement were observed, and only minimal movement of the fingers was possible (see Supplementary Video). All participants were able to perform the experimental protocol.\nThe Medical Ethics Committee of Twente approved the study design, the experimental protocol, and the procedures (Protocol number: NL59061.044.16). The study was conducted according to the ethical standards given in the Declaration of Helsinki in 1975, as revised in 2008.\nThe experimental setup (Figure 1) included several components, and it was designed to record HD-sEMG signals from the forearm in a repeatable and systematic way. Muscular activity was measured with a 128-channel amplification system (REFA 128 model, TMS International, Oldenzaal, The Netherlands). We used 64 monopolar electrodes around the forearm to acquire the raw sEMG signals. The signals were recorded with a decimal gain of 26.55 before the analog-to-digital converter (ADC); however, this gain factor is compensated by the acquisition software (Polybench, TMS International, Oldenzaal, The Netherlands), after the ADC. Additionally, REFA includes a first-order analog low-pass filter placed before the ADC with a -3 db point at 6.8 kHz. The 6.8-kHz low pass helps to make the REFA immune to high-frequency electromagnetic interference such as mobile phone networks. The analog signals were sampled with a frequency of 2,048 Hz and digitally converted with a 24-bit conversion (a resolution of 0.018 muV per bit, 300 mV dynamic range). The ADC of the device has an anti-aliasing digital low-pass filter with a cutoff frequency of 0.2 * sample frequency. This filter inside the ADC is used to convert the 1-bit signal with a high frequency into a 24-bit signal with a lower frequency. The acquisition software was executed in a host laptop (Lenovo Thinkpad T490, Lenovo, Beijing, China) with a Windows 10 operating system (Microsoft Corporation, Washington, USA). A computer screen was used to provide visual feedback of the task to the participants.\nElectrode placement and configuration were based on previous work that normalized the electrode locations to each participant's arm circumference in order to account for different forearm thicknesses (Table 1). The inter-electrode distance in the longitudinal direction of the forearm was kept constant at 2 cm for covering the entire forearm.\nFirst, we cleaned the skin of the dominant forearm of the participant with alcohol. Then, we measured the forearm length from the lateral epicondyle until the styloid process of the ulna and the forearm circumference at 20% of the forearm length from the elbow (Figure 1). The participant had to wear a perforated sleeve (Figure 1) with equally placed holes and elastic only along the circumferal direction to ensure that the electrode placement was standardized for all participants. We used a non-permanent marker to mark the skin of the participant (Figure 1) and then visually inspect the markings before applying the electrodes.\nConductive gel was applied to each of the 64 electrodes with a syringe, and they were subsequently attached to the forearm. The first row of electrodes was placed above the imaginary line between the lateral epicondyle and the styloid process of the ulna and the last row below in such a way that the line lay in the middle between the two rows of electrodes (Figure 1). The first electrode was attached proximally starting at the 20% of the forearm length from the elbow. Electrodes were placed from proximal to distal and in counterclockwise direction (from the perspective of a right-handed participant). This way, electrodes 1-32 were placed over the dorsal side (mostly extensor muscles) and 33-64 over the ventral side (mostly flexor muscles) of the forearm. The reference electrode was placed at the distal end of the forearm, over the head of the ulna.\nParticipants performed seven different gestures involving hand and wrist motions (Figure 2). The chosen gestures included: hand open/close, thumb flexion/extension, wrist flexion/extension, and index extension. These were chosen as they are involved in the most frequent ADL. First, each participant was instructed to perform all gestures without constraints (dynamic) with maximal voluntary effort in a single recording. This way, we recorded the maximum voluntary contraction (MVC) for every electrode across all gestures. For every gesture, 10 repetitions of 3 s contractions were performed, together with 10 repetitions of 3-s resting periods between the contractions (Figure 2). The participants were instructed to perform all movements in a comfortable fashion in order to avoid forceful contractions that may elicit co-contractions of agonist-antagonist muscle groups.\nThe timing of the gestures was dictated with the use of visual feedback. The visual feedback illustrated via photographs of human hands which gesture had to be performed. The sequence of images served to instruct the participant as a metronome when to perform the gesture (image of gesture appearing for 3 s) and when to relax (image of relaxed hand appearing for 3 s). Additionally, the measurements were performed in the morning in order to avoid effects of the end-of-the-day fatigue, especially for the participants with DMD. Furthermore, the participants had short breaks between gestures in order to rest.\nAll signal processing and data analyses were performed in Matlab 2018b software (The MathWorks Inc., USA). The raw sEMG signals were processed offline in order to compute the envelopes for each of the 64 electrodes per gesture and per participant. First, the raw data were filtered with a band-pass filter (fourth-order Butterworth, 20-450 Hz). Additionally, a second-order digital infinite impulse response notch filter (cutoff frequency of 50 Hz, Q factor of 50) was used to remove the power line noise (50 Hz for the EU). Despite its main limitation (signal distortion around the attenuated frequency), notch filtering is the mainstream technique for powerline signal removal, and a narrow bandwidth with a high Q factor can already address this. For highly powerline-contaminated signals, spectral interpolation may be more appropriate. The signals were subsequently rectified and filtered with a low-pass filter (third-order Butterworth, 2 Hz). Our choice for the cutoff frequency was motivated by the low-frequency dynamic tasks involved in this study and our previous study on real-time sEMG control of a hand exoskeleton. The resulting envelopes were visually inspected segmented, according to the acquisition protocol, to 10 contractions and periods (each lasting approximately 3 s) and normalized. A threshold was selected to define the onset of the activity, and the next 3 s after the onset were chosen as a contraction period. The threshold was defined as the time that the signal exceeded 10 standard deviations of the baseline (non-contraction) activity similar to Di Fabio, and the final segmentation was additionally assessed visually. The maximum value of the envelope of each electrode across the complete dataset was used as a normalization value for each electrode. This value was acquired using a moving average window of 1 s in order to account for signal artifacts. Signal quality was visually assessed both in the time and frequency domains, and faulty channels were replaced by linear interpolation of their surrounding neighboring channels (8-neighborhood). Different local conditions were applied to faulty electrodes placed in the longitudinal extremes (<8 neighboring channels).\nEvery 3-s contraction was further segmented in 1-s segments by keeping only the middle second of the contraction (steady-state phase) and discarding the transient phase. For every electrode, the average of this 1-s contraction was calculated and used to construct 10 heatmaps per gesture (Figure 2). For the visual inspection of the forearm activity per gesture, we constructed activity heatmaps by averaging the 10 repetition heatmaps (Figure 3).\nWe analyzed the data to assess HD-sEMG pattern repeatability, peaks, and dimensionality, as well as individuals' potential to generate activation patterns suitable for myocontrol applications for both healthy and DMD participants. The raw data used for this analysis are available online. All signal processing and data analyses were performed in Matlab 2018b software (The Mathworks Inc., USA). In the remainder of this section, we describe a set of analyses aimed at investigating differences between DMD and healthy participants at the level of motor control properties (Motor Control Properties section) and myocontrol performance (Myocontrol Performance section).\nThe degree of repeatability across repetitions per participant was calculated using squared Pearson correlation. Each heatmap (8 x 8) was reshaped into a vector (1 x 64) before the calculation of the squared Pearson correlation. The coefficient was extracted among the 10 repetitions per gesture and per participant. For every gesture, this resulted in 45 unique comparisons between the 10 repetitions and thus 45 coefficients per gesture (Figure 4).\nThe temporal distribution of activations between healthy and DMD was calculated via normalized and absolute activations per repetition of each gesture (Figure 5A). A normalization factor was calculated across all gestures and repetitions. For each gesture, the maximum absolute and normalized value of the 64-electrode heatmap were calculated for every participant and each repetition and plotted.\nFigure 5B shows the average spatial distribution of the healthy and DMD participants. The spatial distribution of the sEMG potentials over the 8 x 8 normalized heatmap was calculated using the center of gravity (COG) by calculating the dorsal-ventral and the proximal-distal position of it as proposed by Elswijk et al.. The COG was calculated over electrodes presenting activations equal or larger than 80% of the maximal value of the heatmap (Figure 3). This way, only clusters of electrodes with a high peak amplitude were considered for the calculation of the COG in order to focus on the most relevant area of activation for each gesture.\nThe 10 heatmaps, one per gesture repetition, were used to construct one single average heatmap per gesture per participant (Figure 3) that was used for the motor control analysis. We quantified differences in dimensionality of orthogonal and uncorrelated sEMG patterns between the healthy and DMD participants via a PCA to the gesture-specific heatmaps per participant. For every participant, we performed a PCA to the concatenation (64 x 70) of the sEMG heatmaps of all gestures and repetitions per participant [64 electrodes x (7 gestures x 10 repetitions)]. The number of PCs needed to reconstruct the original seven gesture heatmaps was identified per participant by means of the variance explained (VE), and it was taken as the number of PCs that summed together explained more than 90% of the total variance. This number was used to explore the repertoire of orthogonal and uncorrelated sEMG patterns produced by the two groups of participants (Figure 6A).\nAdditionally, we calculated the squared Pearson correlation between all the gestures per participant (the same way as we did for the repeatability, Activation Pattern Repeatability Tests section). The coefficient was extracted from the average normalized heatmap of the 10 repetitions per gesture and per participant. For every participant, this resulted in 21 unique comparisons between the seven gestures and thus 21 coefficients per participant. We averaged the correlation values of the healthy participants and the participants with DMD separately to identify which gestures are mostly correlated per population, and we presented this in the form of a similarity matrix (Figure 6B).\nWe explored participants' gesture recognition performance via an offline pattern recognition algorithm applied to the band-pass filtered data (fourth-order Butterworth, 20-450 Hz) of each participant. We used a linear discriminant analysis (LDA) to recognize each of the gestures performed. LDA is a commonly used pattern recognition algorithm for prosthetic control and already commercialized by COAPT LLC (Chicago, USA). We chose it for the ease of implementation, classification speed, and high accuracy compared to other similar approaches. The 10 steady-state segments for every gesture were concatenated and created a 10-s vector. We trained the classifier by extracting four time-domain features from the raw segmented data including mean absolute value, zero crossing, slope sign change, and waveform length. We chose for a feature extraction window of 200 ms (with an overlap of 100 ms), which would be within acceptable range for real-time myoelectric applications. The classifier was validated with a three-split Monte Carlo cross-validation approach. Each time, a different part of the segmented data was used for training (always 70%) and testing (always 30%). The average off-line classification accuracy of these three trainings was used as performance metric per participant. Additionally, we tested how the offline classification accuracy per participant was affected by the number of gestures that had to be classified.",
"gender": "Male"
}
] |
PMC7174775
|
[
{
"age": 58,
"case_id": "PMC7969344_01",
"case_text": "A 58-year-old female presented with complaints of progressive loss of vision and flashes of light in both eyes (OU). Her past ocular history was significant for progressive nyctalopia which was gradually worsening since her childhood. Her past medical history was significant for asthma, depression, musculoskeletal pain, well-controlled hypertension, and hyperlipidemia. Her systemic medications included hydrochlorothiazide, lisinopril, aspirin, albuterol, buspirone, duloxetine, lorazepam, gabapentin, hydrocodone-acetaminophen, tizanidine, and trazodone.\nThe patient's family history of adRP was further explored. Her paternal grandmother and the grandmother's two daughters were affected by RP. She has one son who is also affected with nyctalopia.\nHer best-corrected visual acuity (BCVA) was 20/40 OD and 20/30 OS. Her intraocular pressure (IOP) was 20 OD and 19 OS. Anterior segment examination was unremarkable.\nFundoscopy of the right eye revealed normal optic nerve with a cup-to-disc ratio of 0.1 bilaterally. Examination of the posterior pole revealed perimacular pigmentary changes in a bull's-eye pattern. Large area of retinal atrophy in a doughnut shape was noted around vascular arcades. Attenuated vasculature was noted in the area of the dystrophic retina. Peripheral retinal examination revealed bone spicule pigmentation along the inferonasal quadrant.\nFundoscopy of OS showed similar findings. Bone spicules were noted in the inferotemporal quadrant.",
"gender": "Female"
},
{
"age": 38,
"case_id": "PMC7969344_02",
"case_text": "The patient's 38- year-old son had similar symptoms of nyctalopia since he was a child. His past medical history was unremarkable. He denied distortions, floaters, and flashing lights OU. His past ophthalmic history was unremarkable.\nHis BCVA was 20/40-2 OD and 20/60-2 OS. Her intraocular pressure (IOP) was 20 OD and 19 OS. Anterior segment examination was unremarkable.\nFundoscopy of OD revealed normal optic nerve with a cup-to-disc ratio of 0.1 bilaterally. The fovea was normal. Large area of retinal atrophy was noted along the inferior arcade. An attenuated vasculature was noted in the area of the dystrophic retina. Peripheral retinal examination revealed bone spicule pigmentation along the inferonasal quadrant.\nFundoscopy of OS showed similar findings. Bone spicules were noted in the inferotemporal quadrant.",
"gender": "Male"
}
] |
PMC7969344
|
[
{
"age": 8,
"case_id": "PMC5769854_01",
"case_text": "An 8-year-old boy presented at our hospital complaining of recurrent headache and vomiting for 3 months. The patient saw a doctor in a clinic before admission to our hospital and took some medicine for cold. The symptoms got relief temporarily but became severe 1 week ago.\nNeurological examination showed impaired vision and mild paresis (IV-grade of muscle strength) of the left extremities. CT (Fig. 1A, B) revealed an iso- to hyperdense lesion in the right basal ganglion extending to superasellar cistern, 4.0x4.4 cm in size with peripheral calcification. No hyperostosis of sellaturcica was noticed (Fig. 1C). Magnetic resonance imaging (MRI) demonstrated most of the mass lesion was iso-intense on T1-weighted, T2-weighted and fluid-attenuated inversion recovery images with inhomogeneous enhancement (Fig. 2A-E). No duraltail sign was noted. Diffusion tensor image revealed the right pyramidal tract was partially disrupted.\nUnder the guide of navigation, a transcortical (through the right middle frontal gyrus) approach was adopted to explore the lesion. There was no dural attachment, but the tumor was tightly adhered with the anterior cerebral artery (ACA). Small vessels supplied the anterior aspect of the tumor, subtotal resection (STR) was achieved.\nHistopathological examination revealed features of atypical meningioma with Ki-67 labeling index been approximately 10% (Fig. 3A-C). Immunohistochemistry showed the tumor positive for epithelial membrane antigen and negative for glial fibrillary acidic protein and S-100 protein (Fig. 3D-F).\nThe patient suffered transient exacerbation of impaired vision and weakness of contralateral limbs after operation, which resolved significantly after 3 months follow-up. Postoperative MRI revealed that most of the tumor had been resected and the residual part has been detached from dorsumsellae (Fig. 2F).",
"gender": "Male"
}
] |
PMC5769854
|
[
{
"age": 58,
"case_id": "PMC7265352_01",
"case_text": "A 58-year-old female presented with the left lower radiculopathy. Seven years ago, she had a prior L5-S1 ALIF. On examination she had decreased the left lower-extremity 1/5 motor function in the tibialis anterior and extensor hallucis longus distributions, plus a 3/5 in the gastrocnemius. The MRI showed what appeared to be an L4-L5 left-sided disk herniation above the level of her prior fusion (i.e., adjacent L4-L5 segment disk disease) [Figure 1].\nShe subsequently underwent an L4-L5 left-sided minimally invasive microdiscectomy. After the laminotomy was completed and nerve root identified, there was a large venous plexus in the nerve root axilla extending ventrally and laterally. This was successfully coagulated with bipolar cautery. Due to the fragility of the plexus and recurrent venous bleeding, multiple hemostatic agents were repeatedly employed to control the bleeding [Figure 2]. After successful cauterization, a thorough examination of the nerve root and disk showed no free fragments or accompanying disk herniations.\nPostoperatively, she reported immediate improvement of her foot strength and resolution of her left lower extremity and buttock pain. She was discharged on postoperative day 1 after a follow-up MRI confirmed an EVP as the ultimate etiology of her radiculopathy [Figure 3]. Six months later, an examination showed improvement to 4-/5 motor strength in the left tibialis anterior and extensor hallucis longus distributions, plus 4+/5 in the gastrocnemius.",
"gender": "Female"
}
] |
PMC7265352
|
[
{
"age": 80,
"case_id": "PMC6159178_01",
"case_text": "An 80-year-old male was being investigated at a tertiary hospital for iron deficiency anaemia. His medical history, symptomology and physical examination did not indicate a cause. After gastroscopy and colonoscopy were also unremarkable he was referred for capsule endoscopy. The delivery of the capsule in the morning was routine; however, review of the images 8 hlater showed a static picture and no evidence the capsule had entered the stomach. The patient was clinically stable and contacted to present to the emergency department with a suspicion of capsule impaction.\nA chest radiograph demonstrated a metallic object at the level of the second thoracic vertebra to the left of the trachea (Figure 1). The patient had no known oesophageal or tracheal diverticulum and expressed no symptoms of dysphagia. To pinpoint the exact anatomical location of the foreign body a non-contrast CT scan of the neck (Figure 2) was performed. The effective dose of CT was 0.81 mSv. This confirmed the object was the capsule endoscope lying to the left of the hypopharynx. The adjacent soft tissue was obscured by aliasing metal artefacts arising from the capsule. A single photon metal artefact reduction (MAR) software technique (O-MAR; Philips Healthcare, Cleveland, OH) was applied which successfully removed most of the metallic artefacts. It revealed the capsule was impacted in an oesophageal diverticulum.\nThe capsule was successfully endoscopically removed under a general anaesthetic and the patient's recovery was uncomplicated. A follow-up barium swallow study confirmed the presence of a Zenker's diverticulum which the patient opted not to surgically repair as he was asymptomatic. He was also offered endoscopic insertion of the capsule endoscope to bypass the diverticulum; however, the patient refused. His anaemia resolved with iron transfusions but no definitive cause was found. He was discharged from the clinic.",
"gender": "Male"
}
] |
PMC6159178
|
[
{
"age": 15,
"case_id": "PMC3678730_01",
"case_text": "For each death, the DSS has systematically recorded the age at death and the date of death (including day and month of death). A detailed VA questionnaire has been collected for deaths of children aged < 15 years old since 1985, and for all deaths since 2003. VA questionnaires are usually completed by close relatives of the deceased. For adults, they include an assessment of whether the deceased was pregnant at the time of death. After review of VA data by physicians, a likely cause of death is assigned to each recorded death using ICD-9 codes. According to this database, maternal mortality is high ( 915 per 100,000 live births for 2003-06,).\nIn August 2010, we conducted a pilot study aimed at determining the feasibility of linking retrospective survey data collected during SSH to DSS data, at the individual level. Prior studies comparing SSH and DSS data had been conducted at the aggregate level, and thus did not permit examining misclassification biases. In total, we interviewed 268 women aged 15-59 years who had at least one female sibling known to have died at reproductive ages according to the DSS datasets since the 1980s. Respondents were asked to complete the standard SSH questionnaire used during the 2005 DHS in Senegal. Interviewers were recruited among those who had participated in that DHS. Some survey respondents were members of the same sibship, and some deaths were thus potentially reported multiple times during the SSH survey.\nWe focus here on the subset of deaths having occurred in 2003-2009 because detailed VA questionnaires for adult deaths were systematically introduced in the Bandafassi DSS in 2003, and because this period matches the \"reference period\" usually used in producing estimates of adult and maternal mortality using SSH data (Timaeus and Jasseh 2004). We identify PR deaths in the DSS data as follows: 1) we use demographic surveillance data on dates of births and deaths to identify deaths having occurred at the time of delivery or within 2 months of a delivery regardless of the actual cause; 2) we use data from the VA questionnaires (i.e., a yes/no question asking VA respondent whether the deceased was pregnant at the time of the survey) to identify deaths having occurred during pregnancy. It is important to note that, in order to classify a death as PR or non-PR according to the DSS data, we do not use the ICD-9 codes assigned by physicians to each death. In SSH data, we define PR deaths as deaths reported to have occurred either during pregnancy, delivery or within 2 months of delivery according to the respondent.\nWe could not compare PR classifications obtained from SSH and DSS data for all deaths observed between 2003 and 2009 because, for some of the deceased, there were no eligible sisters in the DSS population or eligible sisters could not be located. In other cases, we could not ascertain whether the recorded death was PR because of missing data in the DSS dataset and/or the VA questionnaire. We thus begin by comparing the age at death, date of death, and PR classification obtained from the DSS of included vs. excluded deaths. We do so using chi2 tests of association. Among included deaths, we then examine the cross-classification of deaths as PR or non-PR, according to the SSH and DSS data. We calculate the proportion of deaths identified as PR (non-PR) in the DSS dataset, which were also classified as PR (non-PR) deaths in the SSH data. We do so for all reports collected during the SSH survey, and for a restricted sample in which we select at random one report of death per sibship (to avoid double-counting). In the case of discrepant classifications of PR deaths between SSH and DSS data, we report a) the cause of death as ascertained by physicians (using VA data), b) the time since the last recorded birth of the deceased, and c) the relationship between the deceased and the person who completed the VA questionnaire (e.g., sister-in-law). Finally, we use SSH data to investigate agreement between sisters about the reported timing of death in sibships where multiple sisters were interviewed.",
"gender": "Female"
}
] |
PMC3678730
|
[
{
"age": null,
"case_id": "PMC7201103_01",
"case_text": "The demographic and clinical characteristics are shown in Table 1. The median age was 62 years (IQR, 51 to 70). Fever (95.3%) and cough (65.1%) were the most common symptoms, while diarrhea (16.3) was not common. 37.2% of patients had at least one underlying disorder (i.e., hypertension, diabetes, cardiovascular diseases, and chronic lung diseases). There is no significant difference in median age between male and female groups, but the maximum of the range of IQR is lower in male (66 years in men vs. 73 years in women). Symptoms and comorbidities were comparable between men and women. As expected, men had a higher level of hemoglobin. However, male patients also had elevated serum creatinine, white blood cells, and neutrophils. Among the 43-case series, 13 (30.2%) were diagnosed with Mild or Moderate pneumonia, while 14 (32.6%) and 16 (37.2%) were diagnosed with Severe and Critical pneumonia, respectively. Chi-square (chi2) test for trend indicated that men's cases of COVID-19 tended to be more serious than women's (P = 0.035), according to the clinical classification of severity (Figure 1).\nBetween March 25 and May 22, 2003, a total of 524 SARS patients, including 139 deaths, in the Beijing area were reported from 29 hospitals enrolled in our analysis. Fever (98.4%) and cough (76.9%) were the most common symptoms, while diarrhea (6.7%) was not common. 57.0% of the patients had at least one of the concomitant diseases including hypertension, diabetes, cardiovascular diseases, and chronic lung diseases. The mean duration from self-reported symptoms to death was 15 (IQR: 10-19) days. Table 2 summarizes the clinical and biochemical characteristics of all SARS patients. The median age of the deceased patients was much higher than that of the patients who survived (57 vs. 32, P < 0.001). The rate of the concomitant diseases in the deceased patients was also higher than that of the patients who survived (57.0% vs. 17.9%, P < 0.001). While the deceased patients were significantly older than the patients who survived (Figure 3A), ages were comparable between men and women in both patients who deceased and survived with SARS (Figure 3B). The proportion of men was higher in the deceased group (53.2%) than in the group who survived (42.3%) (chi2 test, P = 0.027) (Figure 3C). Survival analysis showed that men had a significantly higher mortality rate than women (31.2 vs. 22.6%) in this hospital-based cohort (hazard ratio [95% CI] 1.47 [1.05-2.06], P = 0.026) (Figure 3D).",
"gender": "Female"
}
] |
PMC7201103
|
[
{
"age": 54,
"case_id": "PMC7373792_01",
"case_text": "The proband (II-2), a 54-year-old lady, came to the hospital due to recurrent chest pain in last 2 years. Coronary angiography indicated approximately 60-80% stenosis of the anterior descending coronary artery (Figure 1B), ECG testing also suggested the patient suffered from CHD (Figure 1C). However, the lipid testing described the level of LDL-c (3.94 mmol/L; control: <3.12 mmol/L) and a distinctly reduced levels of HDL-c (0.41 mmol/L; control: 0.9-2.19 mmol/L) of the proband (Table 1). This discovery attracted our interest because most patients with ASCVD commonly presented high levels of LDL-c, TC, and TG. We then investigated the family history of the proband (II-2), which indicated that her young sister (II-4) has been diagnosed as the occlusion of left iliac artery and her father (I-1) was died from myocardial infarction at 60-year-old. Lipid testing further described that both her son (III-1) and her young sister (II-4) showed an overt reduced levels of HDL-c and normal levels of LDL-c, TC, and TG (Table 1). And his young sister (II-4) also suffered from arterial plaque in the left lower limb. The blood pressure of the proband was 80-120 mmHg and the fasting blood-glucose was 5.2 mmol/L. The proband (II-2) accepted the treatment of percutaneous coronary intervention, the proband did not complain any uncomfortable after treatment. And breathing sound of the lungs was clearly, the heart rate was normal (Figure 1D), and the insertion site recovered well. The II-4 is accepting recovery treatment by exercise and diet control.\nWe supposed that the low levels of HDL-c may be the leading cause of AS and ASCVD in this family. However, what's the genetic lesion underling the reduced levels of HDL-c in this family? We then isolated the genomic DNA of the proband and other family members (I-2, II-1, II-2, II-4, III-1, and III-2). Whole exome sequencing of the proband (II-2) was performed to detect the candidate gene of reduced levels of HDL-c.\nIn short, Exome capture and next-generation sequencing were conducted by Novogene Bioinformatics Institute (Beijing, China). One microgram of qualified genomic DNA from each person was captured by the Agilent's SureSelect Human All Exon kit V5 (Agilent Technologies, Inc., Santa Clara, CA, United States) and sequenced by Illumina Hiseq4000 (Illumina Inc., San Diego, CA, United States). Shortly, genomic DNA were randomly carved by Covaris S220 sonicator (Covaris, Inc., Woburn, MA, United States). Then the fragmented DNAs underwent three enzymatic steps: end repair, A-tailing and adapters ligation. The adapter-ligated DNA fragments were amplified with Herculase II fusion DNA polymerase (Agilent). Later, the exomes in the pre-capture libraries were captured by SureSelect capture library kit (Agilent). After DNA quality estimation, the captured DNA library was used for next-generation sequencing on Illumina Hiseq4000 platform. Downstream processing was carried out by Genome Analysis Toolkit (GATK), Varscan2 and Picard, and variant calls were performed by the GATK Haplotype Caller. Variant annotation referred to Ensemble release 82, and filtering was conducted by ANNOVAR Documentation.\nThe filtered non-synonymous SNPs or INDELs with an alternative allele frequency more than 1% in public databases were kicked before further analysis. The public databases contains the NHLBI Exome Sequencing Project Exome Variant Server (ESP6500), dbSNP1441, the 1000 Genomes project2, the ExAC database3 and in-house exome databases of Novogene (2500 exomes). Then the filtered SNVs and INDELs, predicted by SIFT4, Polyphen25, and MutationTaster6 to be damaging, were remained.\nAfter data filtering, a novel nonsense mutation (NM_007168: c.3460C>T; p.R1154X) of ABCA8 was identified and validated by Sanger sequencing in the proband (Figure 1E). Previous studies have revealed that deleterious heterozygous ABCA8 mutations may disrupt cholesterol efflux and reduce HDL-c levels in humans and mice. No other meaningful mutations related to lipid metabolism has been identified. Sanger sequencing further confirmed that only the affected individuals (II-2, II-4, and III-1) carried the novel nonsense mutation (NM_007168: c.3460C>T; p.R1154X) of ABCA8 (Figure 1F). The novel mutation, resulting a truncated protein, was absent in the healthy members (I-2, II-1, and III-2) and 200 local people who were used as an internal control to exclude the SNP in local people. Bioinformatics predicted that the newly identified mutation was deleterious and may disrupt the structure and function of ABCA8. On the basis of ACMG guidelines, the novel variant meetings the following criteria from the ACMG guidelines: PVS1, PS3, and PM2.",
"gender": "Female"
}
] |
PMC7373792
|
[
{
"age": 68,
"case_id": "PMC8138243_01",
"case_text": "A Caucasian 68-year-old male, without systemic diseases, was admitted in March 2020 to a tertiary care center (Hospital Vera Cruz, Campinas, Sao Paulo, Brazil) with history of right upper eyelid swelling and redness for 10 days, which became progressively worse. He denied fever, worsening of visual acuity, or pain due to eye movements.\nAt presentation, the patient's right eye was closed by erythematous and swelling of the right upper lid (Fig. 1). Vital signs at the time of hospital admission were as follows: systemic blood pressure = 130 x 70 mm Hg, cardiac frequency = 71 bpm, and body temperature = 37.1 C. The full blood count presented a white blood count of leukocytes = 6,478 mm3 (neutrophils = 4,060 mm3, eosinophils 30 mm3, basophils = 20 mm3, lymphocytes = 1,790 mm3, and monocytes = 580 mm3). All of them were within the normal range.\nOphthalmologic exam at the time of admission showed visual acuity of 0.4 logMAR in both eyes (OU) with spectacles, clear conjunctiva, clear cornea, and nuclear cataract 2+ in OU. Ocular motility and pupillary reflex were normal in OU. The intraocular pressure was 12 mm Hg in OU (with Icare tonometer, which is a rebound tonometer). Fundoscopy showed pink optic disc with sharp margins and a cup to disc ratio of 0.5 in OU.\nComputerized tomography revealed preseptal and soft tissue edema with an abscess in the anterior right upper eyelid but no signs of orbital involvement or orbital fractures. Figure 2 presents the aspect of both eyelids in the tomography. A presumptive diagnosis of hordeolum with preseptal cellulitis and abscess was made, and intravenous amoxicillin and clavulanate potassium 500/125 mg were administrated twice a day.\nThe development of purulent discharge from the upper eyelid with an abscess and necrosis was evident. Therefore, the patient underwent abscess drainage and wound debridement. During the procedure, necrosis was observed involving almost the full thickness of the right upper eyelid, measuring 30 x 30 mm in the central area. The tissue surrounding the abscess was friable and necrotic and did not bleed. The necrotic tissue was debrided until healthy viable tissue appeared throughout the wound and no evidence of infection was present in the reminiscent tissue. The wound was left open to heal by secondary intension. Figure 3 presents the eyelid aspect immediately after the surgery.\nGiven the clinical improvement in his local and systemic condition, the patient was continued on intravenous amoxicillin and clavulanate twice a day for 48 h and was discharged with the same oral antibiotics. He also started using topical medication with retinol acetate (10,000 IU/g), amino acids (25 mg/g), methionine (5 mg/g), and chloramphenicol (5 mg/g) in the affected eyelid for 7 days, 3 times a day.\nSeven days after debridement, he presented satisfactory cicatrization without any symptoms (Fig. 4). After 2 months, the eyelid was completely healed with no retraction (Fig. 5a, b).",
"gender": "Male"
}
] |
PMC8138243
|
[
{
"age": 35,
"case_id": "PMC3546213_01",
"case_text": "A 35-year-old woman developed MVD due to a left HFS 6 years ago, which was refractory to medical treatment. Results of preoperative brain magnetic resonance image and electromyography were normal. Surgery was successfully performed, and the postoperative findings revealed that the branch of the left anterior inferior cerebellar artery had been compressing the VII-VIII cranial nerve complex. The pateint did not show any specific symptoms for about 3 and a half years after MVD. But, the symptoms began to recur 1 year ago and she was medicated with 0.5 mg clonazepam for 3 months, and received two local botulinum toxin injections. No treatment effect occurred, so she visited our pain clinic. The patient was experiencing a twitch on the infraorbital area and chin when the HFS was severe, and spasm frequency was 3-4 Hz. Discomfort on the visual analogue scale (VAS) was 10/10. We initially attempted a left stellate ganglion block twice, but no effect was observed, Then, we performed a fluoroscope-guided left facial nerve block twice using 4 ml of 2% lidocaine, and 20 mg triamcinolone. No complications occurred, and the HFS symptoms were relieved for 4 days. Thus, we decided to perform PRF on the facial nerve. In the right lateral decubitus position, the patient's chin was slightly lifted, which exposed the mastoid process. Both sides of the mastoid process and mandible were superimposed on a lateral fluoroscope imaging view (Fig. 1). The skin was prepared with betadine and aseptic draping. We used a 10 cm, 22-G Sluijter-Mehta cannula needle with a 0.5 mm active tip and verified accurate needle position by fluoroscopy. A 5 mm skinwheal appeared from the mastoid process to the nose beginning at the needle entry point of the local anesthetic. We explored facial nerves with 50 Hz, 0.5 V sensory stimulation to the tongue and 2 Hz, 1.0 V motor stimulation to the left hemi face when the tip of the needle was positioned around the stylomastoid for amen. We administered three PRF pulses at 42C for 120 seconds after confirming that the needle tip was near the facial nerve. After the procedure, we injected 3 ml of 4% lidocaine mixed with 20 mg triamcinolone. The patient was symptom free for only 4 days, so we applied additional PRF treatments twice using the same method to obtain a longer effect. When the patient returned as an outpatient 1 week after the second PRF treatment, HFS frequency was improved to < 0.25 Hz, and subjective complaints improved on the VAS (2-3/10). The modified MacNab criteria at 1 week after the procedure were good. The patient was followed up at 3, 6, 9, and 12 months via telephone, and symptom relief was maintained continuously.",
"gender": "Female"
}
] |
PMC3546213
|
[
{
"age": 20,
"case_id": "PMC9852490_01",
"case_text": "A 20-year-old male presented with pain and limited motion in the right knee for 15 years. The patient presented to our clinic with HA, restricted flexion and extension of the right knee and a sagittal deformity of the right femur 8 months prior to the surgery. He was diagnosed with severe haemophilia A (coagulation factor VIII was 1.52%) and haemophilic arthritis of right knee. At the age of 13, the patient was fixed with plaster for a fracture of the femoral shaft, which resulted in a malunion.\nBecause he was positive for inhibitors, the patient was re-examined regularly by the Haematology Clinic after discharge. The patient did not take any interventions during the first 4 months while being positive for inhibitors. During this period, the patient suffered from knee joint bleeding and recovered after ice compression and lying in bed. In the 5th month after the discovery of the inhibitors, the patient received irregular injections of factor VIII intravenously (1,000 IU, BIW or TIW, Kovaltry, Bayer), which did not follow the haematologist's recommendation. After 66 days of injections, he was still positive for inhibitors. Since then, the patient started to receive regular injections of factor VIII (1,500 IU, BID) intravenously. Forty-nine days after the first injection, he became negative for inhibitors (Table 1). The patient came to the hospital again 3 days prior to the surgery.\nPreoperative examinations showed the patient had pain in his right knee. His right foot could not touch the ground. The range of joint motion (ROM) was 20 -90 , the visual analogue scale (VAS) was 7 and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was 106 (Figure 1, Table 2). Other systemic examinations were normal. X-ray and CT showed that the patient's right knee joint space was narrow, with a right femoral flexion deformity (30 , sagittal, anterior) (Figure 2).",
"gender": "Male"
}
] |
PMC9852490
|
[
{
"age": 42,
"case_id": "PMC4108191_01",
"case_text": "A 42-year-old, non-smoking, virgin woman presented to our institution with complaints of dyspnea and pleuritic chest pain since 2 days ago along with 2-month transient spotting. She had a history of leiomyoma since 5 months ago, and was hospitalized due to vaginal bleeding, and had been undergone therapy by a gonadotropin-releasing hormone (GnRH) agonist and medroxyprogesterone acetate, intramuscularly. To control her anemia, she was given oral ferrous sulfate. There was no relevant familial history of the same condition. On physical examination, she was anxious and tachypneic on admission, with body mass index of 24.7 kg/m2, body temperature 37 C, blood pressure 100/70 mmHg, heart rate 120 beats per min, respiratory rate of 24 breaths per min, and 96% oxygen saturation while breathing room air. Other findings included regular heart beat with a 2/6 systolic murmur in the left sternal border, clear lung sound, and a non-tender abdomen with a 20-week size uterus. There was no swelling in her lower limbs.\nAn electrocardiogram revealed a sinus tachycardia and inverted T waves in v1 to v3 and inferior leads. Hematologic testing revealed hemoglobin of 11.3 g/dL and other results were within normal limits. Coagulation factors were also unremarkable. A chest radiograph showed Westermark sign without pleural effusion. An ultrasound investigation revealed an acute DVT in the popliteal and superficial femoral veins of her left leg and an enlarged leiomyoma of the uterus. Thereafter, transesophageal echocardiography (TEE) demonstrated normal left ventricle systolic function, severe right ventricle enlargement, McConnell sign, moderate tricuspid regurgitation, severe pulmonary hypertension of 110 mmHg, and dilatation of the main pulmonary artery. In addition, a 2.6 1.6 cm echogenic mass was detected in the left pulmonary artery, consistent with thrombosis (Figure 1). Given her leiomyoma history, she underwent magnetic resonance imaging (MRI), which revealed a huge uterine-derived mass compressing both common iliac veins (Figure 2).\nDue to massive PE, the patient was administered loading dose of 250 000 units of streptokinase and the infusion of 100 000 units per hour during 24 h. After undergoing thrombolysis, her general condition significantly improved, and then she underwent anticoagulation therapy. One unit of packed red blood cells was also transfused. Examination by TEE on the fourth day revealed the disappearance of the pulmonary artery thrombosis. After achieving a therapeutic range of international normalized ratio (range 2.0-3.0), she was discharged on warfarin 5 mg daily.\nThe patient was followed for 3 months and then evaluated again and examined using TEE and ultrasonography, which demonstrated normal findings. After withholding warfarin preoperatively, she underwent myomectomy instead of hysterectomy due to her uterus preservation. Warfarin therapy commenced again following surgery, and she was discharged in stable condition on warfarin therapy. Nine months after myomectomy, she was well, without evidence of thromboembolism.",
"gender": "Female"
}
] |
PMC4108191
|
[
{
"age": 67,
"case_id": "PMC8200619_01",
"case_text": "A totally bimaxillary edentulous male patient, aged 67 years, diagnosed with prostate cancer who underwent intravenous bisphosphonates treatment (zoledronic acid) for about one year presented himself in March 2018 to Maxillofacial Surgery Department of County Clinical Hospital of Craiova.",
"gender": "Male"
},
{
"age": null,
"case_id": "PMC8200619_02",
"case_text": "The patient had pain in the anterior mandibular arch, with exposed necrotic bone. Diagnostic was stage 2 MRONJ.\nBisphosphonate treatment was discontinued about 6 months in advance.\nFollowing clinical examination corroborated with the imaging investigations, it was decided to adopt a conservative treatment which consisted in removing the necrotic bone tissue by marginal resection of the mandible down to the clinically healthy bone, associated with lavages with antiseptic solutions and antibiotic therapy.\nPatient gave the written informed consent for the treatment, and also for publication of his case.\nAlthough initially the evolution was favorable, after about 2 weeks there were numerous infectious episodes that required repeated antibiotic treatment.",
"gender": "Male"
},
{
"age": null,
"case_id": "PMC8200619_03",
"case_text": "The patient developed a dehiscence in the operated area (Figures 1 a, b).\nDue to the progressive nature of MRONJ, it was decided to perform a radical surgery, with the written informed consent of the patient.\nUnder general anesthesia, a submandibular incision was made from the left mandibular angle to the right mandibular angle with the exposure of the entire mandibular body (Figure 2a).\nIt was revealed a large area of bone necrosis in the anterior mandibular arch level (Figure 2b).\nThe contour of the mandibular arch was recorded with a guide plate.\nSegmental anterior mandibular resection was performed with large bone bur drills under saline irrigation down to healthy bone with normal bone specific bleeding (Figures 2 c, d).\nThe surgical specimen was sent for histopathological examination to exclude malignancy.\nAs the resulting defect was large, it was decided to restore the contour of the mandibular arch with titanium primary reconstruction plate covered with a pectoralis major flap to close the resulting defect (Figures 2 e, f).\nThe thoraco-acromial artery was included in the pectoralis major flap (Figure 2f).\nIt was rotated in the oral cavity with the tegument part closing the endo-oral mucosa defect (Figure 2g).\nThe donor site was closed primarily after flap harvest.\nSurgical treatment was associated with postoperative antibiotic therapy for a period of 7 days.\nBoth the endo-oral wound and the donor site wound healed without complications.",
"gender": "Unknown"
},
{
"age": null,
"case_id": "PMC8200619_04",
"case_text": "There were no more inflammatory areas and the patient did not complain of local pain.",
"gender": "Unknown"
},
{
"age": null,
"case_id": "PMC8200619_05",
"case_text": "The patient was monitored weekly for the first month after discharge and then monthly for up to one year after surgery (April 2019).\nAt 6 months and 1 year after the intervention, there were no recurrences of MRONJ (Figures 3 a,b).",
"gender": "Unknown"
}
] |
PMC8200619
|
[
{
"age": 32,
"case_id": "PMC5420015_01",
"case_text": "A 32-year-old woman in the 28th week of her fifth pregnancy was referred to our institution with a 3-week history of fetal bradycardia (fetal heart rate 60 beats per minute [bpm]). She had no personal or family histories of cardiac arrest, seizures, or syncope. Of her 4 pregnancies, only 1 had ended in a miscarriage. The initial fetal echocardiogram at our institution revealed a structurally normal heart with normal size, normal function, and second-degree AVB (V rate 60 bpm, atrial rate 120 bpm). Her antibody screen was negative for anti-SSA and anti-SSB antibodies. One week later, a follow-up fetal echocardiogram showed a ventricular rate of 220 bpm (atrial rate was 130 bpm) (Figure 1A). An fMCG was then performed which revealed nonsustained VT alternating with sinus rhythm (rate 130 bpm) (Figure 1B). The VT was present about 75% of the time. The QTc was 591 ms (Figure 1C).\nOver the ensuing days, the TdP continued and the fetus developed severe hydrops. We therefore decided to administer an intravenous loading dose of magnesium (4 g) followed by a continuous infusion (1-1.4 g/h) to maintain a maternal serum level of 1.2-1.4 (normal = 0.65-1.05 mmol/L). The mother's baseline magnesium level was 0.72 mmol/L. Within 3 days of magnesium infusion the frequency of TdP decreased (by fMCG the fetus was in sinus rhythm 80% of the time). Because of the concern for an SCN5A R1623Q mutation, we began treatment with mexiletine (600 mg orally per day). The fetus remained in sinus rhythm (rate 100 bpm) with continuous magnesium infusion and oral mexiletine given to the mother. At 35 weeks the fetus became bradycardic and was found to be in second-degree AVB.\nThe mother underwent an elective cesarean section at 35 weeks' gestation and a 2334-g male infant was delivered. The heart rate at birth was 56 bpm owing to functional second-degree AVB with 2:1 conduction (Figure 2A). Immediately after delivery, temporary transvenous pacing wires were placed. On the second day of life, a permanent pacemaker was implanted. We also administered oral mexiletine (4 mg/kg/d) and intravenous propranolol (0.02 mg/kg/h); no VT was observed. On the 14th day of life, the infant's electrocardiography showed sinus rhythm with a left bundle branch block pattern (Figure 2B). On the 40th day of life, the mexiletine blood levels declined, and TdP occurred despite ventricular pacing (VVI 80 bpm). The TdP spontaneously terminated.\nThe VVI pacing rate was increased to 110 bpm. When the infant was at the age of 5 months, weighing 6.6 kg, we placed an implantable cardioverter-defibrillator (ICD). The shock lead was implanted subcutaneously through the left thoracodorsal region, and the generator was placed under the right abdominal rectus muscle (Figure 2C). Following implantation of the ICD, the child did not experience any appropriate or inappropriate shocks during 4 years of follow-up. He received oral mexiletine (12 mg/kg/d) and propranolol (2 mg/kg/d).\nGenetic testing of this case revealed a KCNH2 missense mutation (S624R). To date, there has been no functional analysis of this mutation. His mother's QTc was 440 ms, and his father's was 390 ms. Neither of the parents had any mutation in this locus. However, we did not exclude parental germinal mosaicism.",
"gender": "Female"
},
{
"age": 35,
"case_id": "PMC5420015_02",
"case_text": "A 35-year-old woman was referred to our institution at 24 weeks' gestation because of a fetal pericardial effusion and fetal tachycardia. The family history was positive for a paternal KCNH2 missense mutation (T613M) diagnosed after a syncopal episode. The fetal echocardiogram revealed a peristent tachycardia with atrioventricular dissociation (Figure 3A). The fMCG confirmed the clinical diagnosis of VT with a rate of 220 bpm (Figure 3B) with a prolonged (511 ms) QTc during brief (<20% of the recording time) episodes of sinus rhythm (rate 110-120 bpm) (Figure 3C). The mother was admitted to the hospital for continuous intravenous magnesium treatment to terminate the fetal VT. However, despite maternal serum magnesium levels of 1.28 mmol/L (normal range 0.65-1.05 mmol/L), the VT persisted and the fetus became hydropic (Figure 3D). Ten days after the mother was on magnesium, we initiated propranolol (initial dose 60-120 mg orally per day), following which the VT resolved. We continued magnesium by a continuous infusion (1.4 g/h) after we started propranolol. fMCG revealed a decreased fetal sinus rate from 120 to 110 bpm. The hydrops then improved gradually. The mother's daily total heart beats decreased from 129,108 to 103,206 (average heart rate decreased from 90 to 71 bpm) after propranolol administration, indicating beta-adrenergic blocking effect. Subsequently, the fetal sinus rhythm (rate 110 bpm) was maintained. A 2010-g female infant was delivered by elective cesarean delivery at 37 weeks' gestation. After birth, the infant's electrocardiography showed an intermittent left bundle branch block pattern. On the fifth day of life, she developed second-degree AVB with a ventricular rate of 60-80 bpm and metabolic acidemia owing to poor cardiac output. She urgently underwent temporary epicardial ventricular pacing lead implantation. At the age of 3 months, sustained VT occurred immediately after permanent pacemaker implantation and was successfully terminated by cardioversion. Hypokalemia (serum potassium level was 2.9 mmol/L) during intensive care likely contributed to the VT. VT did not recur after the potassium was corrected. Her genetic testing identified the KCNH2 missense mutation (T613M), identical to that of her father. She received oral mexiletine (7 mg/kg/d) and propranolol (3 mg/kg/d) with pacing (VVI 110 bpm) for 23 months.",
"gender": "Female"
}
] |
PMC5420015
|
[
{
"age": 53,
"case_id": "PMC6288572_01",
"case_text": "A 53-year-old male, smoker (20 pack-years), occasional alcoholic, presented with complaints of blood expectoration of 400 ml in one episode followed by 100-150 ml for 2-3 days. He had 3 episodes of similar history which required hospitalizations and emergency care since 9 months. He denied history of fever, chest pain, and loss of appetite. He underwent cholecystectomy 3 years ago. There was no history of systemic immune suppression like diabetes. He had undergone bronchial artery embolization for massive haemoptysis; however, his haemoptysis persisted and diagnosis remained elusive after evaluation with sputum studies and CT-guided aspiration cytology, biopsy, and bronchoscopic lavage. He was treated for LRTI with multiple courses of antibiotics for more than 9 months.\nOn examination, vitals were normal with no respiratory distress. Oral hygiene was poor with dental caries. Respiratory examination revealed scattered crackles in the left lower lobe area. Chest X-ray showed an inhomogeneous opacity in the left lower zone with raised left diaphragm (Figure 1), and CECT (contrast-enhanced computer tomogram) chest showed a hypodense lesion with irregular margins in the anterior segment of the left lower lobe adjacent to the descending aorta and associated subcarinal lymphadenopathy (Figures 2 and 3). Image-guided transthoracic biopsy showed type 2 alveolar cell hyperplasia with negative immunohistochemistry. Bronchoscopy confirmed left lower lobe bleed with any endoluminal lesion. Bronchial wash was negative for microbiological and cytological studies including AFB stain, geneXpert for MTB complex, and pyogenic culture. Patient's symptoms of haemoptysis persisted; hence, CT angiogram was performed, which showed dilated vascular channels within the lesion without any obvious extravasations of contrast and no aortic abnormality.\nProbable diagnosis of the left intrapulmonary vascular lesion was made and hence the patient underwent left lower lobe lobectomy. Intraoperatively, the left lower lobe was adherent posterolaterally to the aorta and diaphragm. Multiple prominent blood vessels in areas of adhesion were seen. Histopathology was suggestive of chronic inflammatory cells with focal aggregates of lymphocytes with positive GMS staining for actinomycosis (Figure 4). Postoperatively, the patient received parenteral benzylpenicillin 20 lakh units 6th hourly for 3 months. The patient was in regular follow-up, and no further episodes of haemoptysis and no recent respiratory complaints are reported.",
"gender": "Male"
}
] |
PMC6288572
|
[
{
"age": 33,
"case_id": "PMC6921157_01",
"case_text": "A 33-year-old woman with intractable epilepsy was referred to our epilepsy center for clinical evaluation. At age 31, she experienced status epilepticus subsequent to a febrile episode and following prolonged coma that continued several weeks. She had no prior history of epilepsy or seizure-related disorders. Initial diagnosis was limbic encephalitis, based on inflammatory findings of cerebrospinal fluid. She was treated with intravenous steroid administration and plasma exchange at another hospital. Although she gradually recovered from comatose state and discharged home in two months without any disability for daily living, symptomatic epilepsy with frequent seizures with impaired awareness persisted. She described that her seizure started with strange odor or deja vu sensation, and then she felt dizziness or lightheadedness. It sometimes accompanied jerky movements of the right side of her face and arm, and eventually led to impaired awareness. Although she was taking levetiracetam 1000 mg and lamotrigine 400 mg, she usually had 1-2 seizures a day. She had previously taken carbamazepine, lacosamide, perampanel and topiramate which did not lead to improvement.\nHer latest brain magnetic resonance imaging (MRI) revealed a cluster of variably sized multiple nodular high intensity lesions on T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) in white matter of the left temporal lobe along with the border of inner cortex (Fig. 1A). The lesions did not show any mass effect or enhancement with gadolinium. Similar findings were also observed in the past MRI when the patient had encephalitis two years before, and the size of the lesions were not different from the latest one. The characteristics of MRI findings were consistent with those of MVNT. 18 fluoro-2-deoxyglucose positron emission tomography (FDG-PET) of brain demonstrated moderate decrease of uptake in the lesion area (Fig. 1B). Laboratory findings of her blood and cerebrospinal fluid did not reveal any other causes of epilepsy.\nLong-term video electroencephalogram (vEEG) was performed for 72 h and three habitual seizures were recorded: Two of them started with deja vu and strange odor sensation followed by nodding movement of the head and subsequent fluttering of right hand and foot. Her consciousness was partially impaired during the seizure. vEEG showed rhythmic wave that started from the left middle temporal area and spread to the ipsilateral frontal region, and then to the contralateral hemisphere (Fig. 2A); The other started with lightheadedness and vEEG showed similar rhythmic waves that started from the right anterior temporal area (Fig. 2B). Interictal EEG showed frequent multifocal spikes and sharp waves in the bilateral anterior to middle temporal area.\nBased on the EEG findings that demonstrated the multiple independent seizure onsets in both hemispheres, the patient was considered to have bilateral multifocal epileptic foci, whereas the lesions with MVNT appearance on MRI were localized in the left temporal lobe. Although MVNT had been described as an epilepsy-related brain tumor, we refrained from resection surgery because it was not certain that the lesions were epileptogenic in this patient. She has been followed up with multiple antiepileptic drugs.",
"gender": "Female"
}
] |
PMC6921157
|
[
{
"age": 4,
"case_id": "PMC4550780_01",
"case_text": "Considerable variations in recursive abilities have also been observed developmentally. Dickinson showed that recursive language production abilities emerge gradually, in a piecemeal fashion. On the comprehension side, training improves comprehension of singly embedded relative clause constructions both in 3-4-year old children (Roth,) and adults (Wells et al.,), independent of other cognitive factors. Level of education further correlates with the ability to comprehend complex recursive sentences (Dabrowska,). More generally, these developmental differences are likely to reflect individual variations in experience with language (see Christiansen and Chater, Forthcoming), differences that may further be amplified by variations in the structural and distributional characteristics of the language being spoken.\nTogether, these individual, developmental and cross-linguistic differences in dealing with recursive linguistic structure cannot easily be explained in terms of a fundamental recursive competence, constrained by fixed biological constraints on performance. That is, the variation in recursive abilities across individuals, development, and languages are hard to explain in terms of performance factors, such as language-independent constraints on memory, processing or attention, imposing limitations on an otherwise infinite recursive grammar. Invoking such limitations would require different biological constraints on working memory, processing, or attention for speakers of different languages, which seems highly unlikely. To resolve these issues, we need to separate claims about recursive mechanisms from claims about recursive structure: the ability to deal with a limited amount of recursive structure in language does not necessitate the postulation of recursive mechanisms to process them. Thus, instead of treating recursion as an a priori property of the language faculty, we need to provide a mechanistic account able to accommodate the actual degree of recursive structure found across both natural languages and natural language users: no more and no less.\nWe favor an account of the processing of recursive structure that builds on construction grammar and usage-based approaches to language. The essential idea is that the ability to process recursive structure does not depend on a built-in property of a competence grammar but, rather, is an acquired skill, learned through experience with specific instances of recursive constructions and limited generalizations over these (Christiansen and MacDonald,). Performance limitations emerge naturally through interactions between linguistic experience and cognitive constraints on learning and processing, ensuring that recursive abilities degrade in line with human performance across languages and individuals. We show how our usage-based account of recursion can accommodate human data on the most complex recursive structures that have been found in naturally occurring language: center-embeddings and cross-dependencies. Moreover, we suggest that the human ability to process recursive structures may have evolved on top of our broader abilities for complex sequence learning. Hence, we argue that language processing, implemented by domain-general mechanisms:not recursive grammars:is what endows language with its hallmark productivity, allowing it to \"...make infinite employment of finite means,\" as the celebrated German linguist, Wilhelm von Humboldt (: p. 91), noted more than a century and a half ago.\nLanguage processing involves extracting regularities from highly complex sequentially organized input, suggesting a connection between general sequence learning (e.g., planning, motor control, etc., Lashley,) and language: both involve the extraction and further processing of discrete elements occurring in temporal sequences (see also e.g., Greenfield,; Conway and Christiansen,; Bybee,; de Vries et al.,, for similar perspectives). Indeed, there is comparative, genetic, and neural evidence suggesting that humans may have evolved specific abilities for dealing with complex sequences. Experiments with non-human primates have shown that they can learn both fixed sequences, akin to a phone number (e.g., Heimbauer et al.,), and probabilistic sequences, similar to \"statistical learning\" in human studies (e.g., Heimbauer et al.,, under review; Wilson et al.,). However, regarding complex recursive non-linguistic sequences, non-human primates appear to have significant limitations relative to human children (e.g., in recursively sequencing actions to nest cups within one another; Greenfield et al.,; Johnson-Pynn et al.,). Although more carefully controlled comparisons between the sequence learning abilities of human and non-primates are needed (see Conway and Christiansen,, for a review), the currently available data suggest that humans may have evolved a superior ability to deal with sequences involving complex recursive structures.\nThe current knowledge regarding the FOXP2 gene is consistent with the suggestion of a human adaptation for sequence learning (for a review, see Fisher and Scharff,). FOXP2 is highly conserved across species but two amino acid changes have occurred after the split between humans and chimps, and these became fixed in the human population about 200,000 years ago (Enard et al.,). In humans, mutations to FOXP2 result in severe speech and orofacial motor impairments (Lai et al.,; MacDermot et al.,). Studies of FOXP2 expression in mice and imaging studies of an extended family pedigree with FOXP2 mutations have provided evidence that this gene is important to neural development and function, including of the cortico-striatal system (Lai et al.,). When a humanized version of Foxp2 was inserted into mice, it was found to specifically affect cortico-basal ganglia circuits (including the striatum), increasing dendrite length and synaptic plasticity (Reimers-Kipping et al.,). Indeed, synaptic plasticity in these circuits appears to be key to learning action sequences (Jin and Costa,); and, importantly, the cortico-basal ganglia system has been shown to be important for sequence (and other types of procedural) learning (Packard and Knowlton,). Crucially, preliminary findings from a mother and daughter pair with a translocation involving FOXP2 indicate that they have problems with both language and sequence learning (Tomblin et al.,). Finally, we note that sequencing deficits also appear to be associated with specific language impairment (SLI) more generally (e.g., Tomblin et al.,; Lum et al.,; Hsu et al.,; see Lum et al.,, for a review).\nHence, both comparative and genetic evidence suggests that humans have evolved complex sequence learning abilities, which, in turn, appear to have been pressed into service to support the emergence of our linguistic skills. This evolutionary scenario would predict that language and sequence learning should have considerable overlap in terms of their neural bases. This prediction is substantiated by a growing bulk of research in the cognitive neurosciences, highlighting the close relationship between sequence learning and language (see Ullman,; Conway and Pisoni,, for reviews). For example, violations of learned sequences elicit the same characteristic event-related potential (ERP) brainwave response as ungrammatical sentences, and with the same topographical scalp distribution (Christiansen et al.,). Similar ERP results have been observed for musical sequences (Patel et al.,). Additional evidence for a common domain-general neural substrate for sequence learning and language comes from functional imaging (fMRI) studies showing that sequence violations activate Broca's area (Lieberman et al.,; Petersson et al.,; Forkstam et al.,), a region in the left inferior frontal gyrus forming a key part of the cortico-basal ganglia network involved in language. Results from a magnetoencephalography (MEG) experiment further suggest that Broca's area plays a crucial role in the processing of musical sequences (Maess et al.,).\nIf language is subserved by the same neural mechanisms as used for sequence processing, then we would expect a breakdown of syntactic processing to be associated with impaired sequencing abilities. Christiansen et al. tested this prediction in a population of agrammatic aphasics, who have severe problems with natural language syntax in both comprehension and production due to lesions involving Broca's area (e.g., Goodglass and Kaplan,; Goodglass, :see Novick et al.,; Martin,, for reviews). They confirmed that agrammatism was associated with a deficit in sequence learning in the absence of other cognitive impairments. Similar impairments to the processing of musical sequences by the same population were observed in a study by Patel et al.. Moreover, success in sequence learning is predicted by white matter density in Broca's area, as revealed by diffusion tensor magnetic resonance imaging (Floel et al.,). Importantly, applying transcranial direct current stimulation (de Vries et al.,) or repetitive transcranial magnetic stimulation (Udden et al.,) to Broca's area during sequence learning or testing improves performance. Together, these cognitive neuroscience studies point to considerable overlap in the neural mechanisms involved in language and sequence learning2, as predicted by our evolutionary account (see also Wilkins and Wakefield,; Christiansen et al.,; Hoen et al.,; Ullman,; Conway and Pisoni,, for similar perspectives).\nComparative and genetic evidence is consistent with the hypothesis that humans have evolved more complex sequence learning mechanisms, whose neural substrates subsequently were recruited for language. But how might recursive structure recruit such complex sequence learning abilities? Reali and Christiansen explored this question using simple recurrent networks (SRNs; Elman,). The SRN is a type of connectionist model that implements a domain-general learner with sensitivity to complex sequential structure in the input. This model is trained to predict the next element in a sequence and learns in a self-supervised manner to correct any violations of its own expectations regarding what should come next. The SRN model has been successfully applied to the modeling of both sequence learning (e.g., Servan-Schreiber et al.,; Botvinick and Plaut,) and language processing (e.g., Elman,), including multiple-cue integration in speech segmentation (Christiansen et al.,) and syntax acquisition (Christiansen et al.,). To model the difference in sequence learning skills between humans and non-human primates, Reali and Christiansen first \"evolved\" a group of networks to improve their performance on a sequence-learning task in which they had to predict the next digit in a five-digit sequence generated by randomizing the order of the digits, 1-5 (based on a human task developed by Lee,). At each generation, the best performing network was selected, and its initial weights (prior to any training):i.e., their \"genome\":was slightly altered to produce a new generation of networks. After 500 generations of this simulated \"biological\" evolution, the resulting networks performed significantly better than the first generation SRNs.\nReali and Christiansen then introduced language into the simulations. Each miniature language was generated by a context-free grammar derived from the grammar skeleton in Table 1. This grammar skeleton incorporated substantial flexibility in word order insofar as the material on the right-hand side of each rule could be ordered as it is (right-branching), in the reverse order (left-branching), or have a flexible order (i.e., the constituent order is as is half of time, and the reverse the other half of the time). Using this grammar skeleton, it is possible to instantiate 36 (= 729) distinct grammars, with differing degrees of consistency in the ordering of sentence constituents. Reali and Christiansen implemented both biological and cultural evolution in their simulations: As with the evolution of better sequence learners, the initial weights of the network that best acquired a language in a given generation were slightly altered to produce the next generation of language learners:with the additional constraint that performance on the sequence learning task had to be maintained at the level reached at the end of the first part of the simulation (to capture the fact that humans are still superior sequence learners today). Cultural evolution of language was simulated by having the networks learn several different languages at each generation and then selecting the best learnt language as the basis for the next generation. The best learnt language was then varied slightly by changing the directions of a rule to produce a set of related \"offspring\" languages for each generation.\nAlthough the simulations started with language being completely flexible, and thus without any reliable word order constraints, after <100 generations of cultural evolution, the resulting language had adopted consistent word order constraints in all but one of the six rules. When comparing the networks from the first generation at which language was introduced and the final generation, Reali and Christiansen found no difference in linguistic performance. In contrast, when comparing network performance on the initial (all-flexible) language vs. the final language, a very large difference in learnability was observed. Together, these two analyses suggest that it was the cultural evolution of language, rather than biological evolution of better learners, that allowed language to become more easily learned and more structurally consistent across these simulations. More generally, the simulation results provide an existence proof that recursive structure can emerge in natural language by way of cultural evolution in the absence of language-specific constraints.\nNP {N (PP)}\nPP {adp NP}\nAn important remaining question is whether human learners are sensitive to the kind of sequence learning constraints revealed by Reali and Christiansen's simulated process of cultural evolution. A key result of these simulations was that the sequence learning constraints embedded in the SRNs tend to favor what we will refer to as recursive consistency (Christiansen and Devlin,). Consider rewrite rules (2) and (3) from Table 1: \n(3) [NP buildings [PP from [NP cities [PP with [NP smog]]]]]\n(4) [NP [PP [NP [PP [NP smog] with] cities] from] buildings]\n(5) [NP buildings [PP [NP cities [PP [NP smog] with]] from]]\n(6) [NP [PP from [NP [PP with [NP smog]] cities]] buildings]\nTogether, these two skeleton rules form a recursive rule set because each calls the other. Ignoring the flexible version of these two rules, we get the four possible recursive rule sets shown in Table 2. Using these rules sets we can generate the complex noun phrases seen in (3)-(6): \nThe first two rules sets from Table 2 generate recursively consistent structures that are either right-branching (as in 3) or left-branching (as in 4). The prepositions and postpositions, respectively, are always in close proximity to their noun complements, making it easier for a sequence learner to discover their relationship. In contrast, the final two rule sets generate recursively inconsistent structures, involving center-embeddings: all nouns are either stacked up before all the postpositions (5) or after all the prepositions (6). In both cases, the learner has to work out that from and cities together form a prepositional phrase, despite being separated from each other by another prepositional phrase involving with and smog. This process is further complicated by an increase in memory load caused by the intervening prepositional phrase. From a sequence learning perspective, it should therefore be easier to acquire the recursively consistent structure found in (3) and (4) compared with the recursively inconsistent structure in (5) and (6). Indeed, all the simulation runs in Reali and Christiansen resulted in languages in which both recursive rule sets were consistent.\nChristiansen and Devlin had previously shown that SRNs perform better on recursively consistent structure (such as those in 3 and 4). However, if human language has adapted by way of cultural evolution to avoid recursive inconsistencies (such as 5 and 6), then we should expect people to be better at learning recursively consistent artificial languages than recursively inconsistent ones. Reeder, following initial work by Christiansen, tested this prediction by exposing participants to one of two artificial languages, generated by the artificial grammars shown in Table 3. Notice that the consistent grammar instantiates a left-branching grammar from the grammar skeleton used by Reali and Christiansen, involving two recursively consistent rule sets (rules 2-3 and 5-6). The inconsistent grammar differs only in the direction of two rules (3 and 5), which are right-branching, whereas the other three rules are left-branching. The languages were instantiated using 10 spoken non-words to generate the sentences to which the participants were exposed. Participants in the two language conditions would see sequences of the exact same lexical items, only differing in their order of occurrence as dictated by the respective grammar (e.g., consistent: jux vot hep vot meep nib vs. inconsistent: jux meep hep vot vot nib). After training, the participants were presented with a new set of sequences, one by one, for which they were asked to judge whether or not these new items were generated by the same rules as the ones they saw previously. Half of the new items incorporated subtle violations of the sequence ordering (e.g., grammatical: cav hep vot lum meep nib vs. ungrammatical: cav hep vot rud meep nib, where rud is ungrammatical in this position).\nThe results of this artificial language learning experiment showed that the consistent language was learned significantly better (61.0% correct classification) than the inconsistent one (52.7%). It is important to note that because the consistent grammar was left-branching (and thus more like languages such as Japanese and Hindi), knowledge of English cannot explain the results. Indeed, if anything, the two right-branching rules in the inconsistent grammar bring that language closer to English3. To further demonstrate that the preferences for consistently recursive sequences is a domain-general bias, Reeder conducted a second experiment, in which the sequences were instantiated using black abstract shapes that cannot easily be verbalized. The results of the second study closely replicated those of the first, suggesting that there may be general sequence learning biases that favor recursively consistent structures, as predicted by Reali and Christiansen's evolutionary simulations.\nThe question remains, though, whether such sequence learning biases can drive cultural evolution of language in humans. That is, can sequence-learning constraints promote the emergence of language-like structure when amplified by processes of cultural evolution? To answer this question, Cornish et al. (under review) conducted an iterated sequence learning experiment, modeled on previous human iterated learning studies involving miniature language input (Kirby et al.,). Participants were asked to participate in a memory experiment, in which they were presented with 15 consonant strings. Each string was presented briefly on a computer screen after which the participants typed it in. After multiple repetitions of the 15 strings, the participants were asked to recall all of them. They were requested to continue recalling items until they had provided 15 unique strings. The recalled 15 strings were then recoded in terms of their specific letters to avoid trivial biases such as the location of letters on the computer keyboard and the presence of potential acronyms (e.g., X might be replaced throughout by T, T by M, etc.). The resulting set of 15 strings (which kept the same underlying structure as before recoding) was then provided as training strings for the next participant. A total of 10 participants were run within each \"evolutionary\" chain.\nThe initial set of strings used for the first participant in each chain was created so as to have minimal distributional structure (all consonant pairs, or bigrams, had a frequency of 1 or 2). Because recalling 15 arbitrary strings is close to impossible given normal memory constraints, it was expected that many of the recalled items would be strongly affected by sequence learning biases. The results showed that as these sequence biases became amplified across generations of learners, the sequences gained more and more distributional structure (as measured by the relative frequency of repeated two- and three-letter units). Importantly, the emerging system of sequences became more learnable. Initially, participants could only recall about 4 of the 15 strings correctly but by the final generation this had doubled, allowing participants to recall more than half the strings. Importantly, this increase in learnability did not evolve at the cost of string length: there was no decrease across generations. Instead, the sequences became easy to learn and recall because they formed a system, allowing subsequences to be reused productively. Using network analyses (see Baronchelli et al.,, for a review), Cornish et al. demonstrated that the way in which this productivity was implemented strongly mirrored that observed for child-directed speech.\nThe results from Cornish et al. (under review) suggest that sequence learning constraints, as those explored in the simulations by Reali and Christiansen and demonstrated by Reeder, can give rise to language-like distributional regularities that facilitate learning. This supports our hypothesis that sequential learning constraints, amplified by cultural transmission, could have shaped language into what we see today, including its limited use of embedded recursive structure. Next, we shall extend this approach to show how the same sequence learning constraints that we hypothesized to have shaped important aspects of the cultural evolution of recursive structures also can help explain specific patterns in the processing of complex recursive constructions.\nSo far, we have discussed converging evidence supporting the theory that language in important ways relies on evolutionarily prior neural mechanisms for sequence learning. But can a domain-general sequence learning device capture the ability of humans to process the kind of complex recursive structures that has been argued to require powerful grammar formalisms (e.g., Chomsky,; Shieber,; Stabler,; Jager and Rogers,)? From our usage-based perspective, the answer does not necessarily require the postulation of recursive mechanisms as long as the proposed mechanisms can deal with the level of complex recursive structure that humans can actually process. In other words, what needs to be accounted for is the empirical evidence regarding human processing of complex recursive structures, and not theoretical presuppositions about recursion as a stipulated property of our language system.\nChristiansen and MacDonald conducted a set of computational simulations to determine whether a sequence-learning device such as the SRN would be able to capture human processing performance on complex recursive structures. Building on prior work by Christiansen and Chater, they focused on the processing of sentences with center-embedded and cross-dependency structures. These two types of recursive constructions produce multiple overlapping non-adjacent dependencies, as illustrated in Figure 1, resulting in rapidly increasing processing difficulty as the number of embeddings grows. We have already discussed earlier how performance on center-embedded constructions breaks down at two levels of embedding (e.g., Wang,; Hamilton and Deese,; Blaubergs and Braine,; Hakes et al.,). The processing of cross-dependencies, which exist in Swiss-German and Dutch, has received less attention, but the available data also point to a decline in performance with increased levels of embedding (Bach et al.,; Dickey and Vonk,). Christiansen and MacDonald trained networks on sentences derived from one of the two grammars shown in Table 4. Both grammars contained a common set of recursive structures: right-branching recursive structure in the form of prepositional modifications of noun phrases, noun phrase conjunctions, subject relative clauses, and sentential complements; left-branching recursive structure in the form of prenominal possessives. The grammars furthermore had three additional verb argument structures (transitive, optionally transitive, and intransitive) and incorporated agreement between subject nouns and verbs. As illustrated by Table 4, the only difference between the two grammars was in the type of complex recursive structure they contained: center-embedding vs. cross-dependency.\nThe grammars could generate a variety of sentences, with varying degree of syntactic complexity, from simple transitive sentences (such as 7) to more complex sentences involving different kinds of recursive structure (such as 8 and 9).\n(7) John kisses Mary.\n(8) Mary knows that John's boys' cats see mice.\n(9) Mary who loves John thinks that men say that girls chase boys.\nThe generation of sentences was further restricted by probabilistic constraints on the complexity and depth of recursion. Following training on either grammar, the networks performed well on a variety of recursive sentence structures, demonstrating that the SRNs were able to acquire complex grammatical regularities (see also Christiansen,)4. The networks acquired sophisticated abilities for generalizing across constituents in line with usage-based approaches to constituent structure (e.g., Beckner and Bybee,; see also Christiansen and Chater,). Differences between networks were observed, though, on their processing of the complex recursive structure permitted by the two grammars.\nTo model human data on the processing of center-embedding and cross-dependency structures, Christiansen and MacDonald relied on a study conducted by Bach et al. in which sentences with two center-embeddings in German were found to be significantly harder to process than comparable sentences with two cross-dependencies in Dutch. Bach et al. asked native Dutch speakers to rate the comprehensibility of Dutch sentences involving varying depths of recursive structure in the form of cross-dependency constructions and corresponding right-branching paraphrase sentences with similar meaning. Native speakers of German were tested using similar materials in German, where center-embedded constructions replaced the cross-dependency constructions. To remove potential effects of processing difficulty due to length, the ratings from the right-branching paraphrase sentences were subtracted from the complex recursive sentences. Figure 2 shows the results of the Bach et al. study on the left-hand side.\nSRN performance was scored in terms of Grammatical Prediction Error (GPE; Christiansen and Chater,), which measures the network's ability to make grammatically correct predictions for each upcoming word in a sentence, given prior context. The right-hand side of Figure 2 shows the mean sentence GPE scores, averaged across 10 novel sentences. Both humans and SRNs show similar qualitative patterns of processing difficulty (see also Christiansen and Chater,). At a single level of embedding, there is no difference in processing difficulty. However, at two levels of embedding, cross-dependency structures (in Dutch) are processed more easily than comparable center-embedded structures (in German).\nChristiansen and MacDonald demonstrated that a sequence learner such as the SRN is able to mirror the differential human performance on center-embedded and cross-dependency recursive structures. Notably, the networks were able to capture human performance without the complex external memory devices (such as a stack of stacks; Joshi,) or external memory constraints (Gibson,) required by previous accounts. The SRNs ability to mimic human performance likely derives from a combination of intrinsic architectural constraints (Christiansen and Chater,) and the distributional properties of the input to which it has been exposed (MacDonald and Christiansen,; see also Christiansen and Chater, Forthcoming). Christiansen and Chater analyzed the hidden unit representations of the SRN:its internal state:before and after training on recursive constructions and found that these networks have an architectural bias toward local dependencies, corresponding to those found in right-branching recursion. To process multiple instances of such recursive constructions, however, the SRN needs exposure to the relevant types of recursive structures. This exposure is particularly important when the network has to process center-embedded constructions because the network must overcome its architectural bias toward local dependencies. Thus, recursion is not a built-in property of the SRN; instead, the networks develop their human-like abilities for processing recursive constructions through repeated exposure to the relevant structures in the input.\nAs noted earlier, this usage-based approach to recursion differs from many previous processing accounts, in which unbounded recursion is implemented as part of the representation of linguistic knowledge (typically in the form of a rule-based grammar). Of course, this means that systems of the latter kind can process complex recursive constructions, such as center-embeddings, beyond human capabilities. Since Miller and Chomsky, the solution to this mismatch has been to impose extrinsic memory limitations exclusively aimed at capturing human performance limitations on doubly center-embedded constructions (e.g., Kimball,; Marcus,; Church,; Just and Carpenter,; Stabler,; Gibson and Thomas,; Gibson,; see Lewis et al.,, for a review).\nTo further investigate the nature of the SRN's intrinsic constraints on the processing of multiple center-embedded constructions, Christiansen and MacDonald explored a previous result from Christiansen and Chater showing that SRNs found ungrammatical versions of doubly center-embedded sentences with a missing verb more acceptable than their grammatical counterparts5 (for similar SRN results, see Engelmann and Vasishth,). A previous offline rating study by Gibson and Thomas found that when the middle verb phrase (was cleaning every week) was removed from (10), the resulting ungrammatical sentence in (11) was rated no worse than the grammatical version in (10).\n(10) The apartment that the maid who the service had sent over was cleaning every week was well decorated.\n(11) *The apartment that the maid who the service had sent over was well decorated.\nHowever, when Christiansen and MacDonald tested the SRN on similar doubly center-embedded constructions, they obtained predictions for (11) to be rated better than (10). To test these predictions, they elicited on-line human ratings for the stimuli from the Gibson and Thomas study using a variation of the \"stop making sense\" sentence-judgment paradigm (Boland et al.,; Boland,). Participants read a sentence, word-by-word, while at each step they decided whether the sentence was grammatical or not. Following the presentation of each sentence, participants rated it on a 7-point scale according to how good it seemed to them as a grammatical sentence of English (with 1 indicating that the sentence was \"perfectly good English\" and 7 indicating that it was \"really bad English\"). As predicted by the SRN, participants rated ungrammatical sentences such as (11) as better than their grammatical counterpart exemplified in (10).\nThe original stimuli from the Gibson and Thomas study had certain shortcomings that could have affected the outcome of the online rating experiment. Firstly, there were substantial length differences between the ungrammatical and grammatical versions of a given sentence. Secondly, the sentences incorporated semantic biases making it easier to line up a subject noun with its respective verb (e.g., apartment-decorated, service-sent over in 10). To control for these potential confounds, Christiansen and MacDonald replicated the experiment using semantically-neutral stimuli controlled for length (adapted from Stolz,), as illustrated by (12) and (13).\n(12) The chef who the waiter who the busboy offended appreciated admired the musicians.\n(13) *The chef who the waiter who the busboy offended frequently admired the musicians.\nThe second online rating experiment yielded the same results as the first, thus replicating the \"missing verb\" effect. These results have subsequently been confirmed by online ratings in French (Gimenes et al.,) and a combination of self-paced reading and eye-tracking experiments in English (Vasishth et al.,). However, evidence from German (Vasishth et al.,) and Dutch (Frank et al.,) indicates that speakers of these languages do not show the missing verb effect but instead find the grammatical versions easier to process. Because verb-final constructions are common in German and Dutch, requiring the listener to track dependency relations over a relatively long distance, substantial prior experience with these constructions likely has resulted in language-specific processing improvements (see also Engelmann and Vasishth,; Frank et al.,, for similar perspectives). Nonetheless, in some cases the missing verb effect may appear even in German, under conditions of high processing load (Trotzke et al.,). Together, the results from the SRN simulations and human experimentation support our hypothesis that the processing of center-embedded structures are best explained from a usage-based perspective that emphasizes processing experience with the specific statistical properties of individual languages. Importantly, as we shall see next, such linguistic experience interacts with sequence learning constraints.\nPrevious studies have suggested that the processing of singly embedded relative clauses are determined by linguistic experience, mediated by sequence learning skills (e.g., Wells et al.,; Misyak et al.,; see Christiansen and Chater, Forthcoming, for discussion). Can our limited ability to process multiple complex recursive embeddings similarly be shown to reflect constraints on sequence learning? The embedding of multiple complex recursive structures:whether in the form of center-embeddings or cross-dependencies:results in several pairs of overlapping non-adjacent dependencies (as illustrated by Figure 1). Importantly, the SRN simulation results reported above suggest that a sequence learner might also be able to deal with the increased difficulty associated with multiple, overlapping non-adjacent dependencies.\nDealing appropriately with multiple non-adjacent dependencies may be one of the key defining characteristics of human language. Indeed, when a group of generativists and cognitive linguists recently met to determine what is special about human language (Tallerman et al.,), one of the few things they could agree about was that long-distance dependencies constitute one of the hallmarks of human language, and not recursion (contra Hauser et al.,). de Vries et al. used a variation of the AGL-SRT task (Misyak et al.,) to determine whether the limitations on processing of multiple non-adjacent dependencies might depend on general constraints on human sequence learning, instead of being unique to language. This task incorporates the structured, probabilistic input of artificial grammar learning (AGL; e.g., Reber,) within a modified two-choice serial reaction-time (SRT; Nissen and Bullemer,) layout. In the de Vries et al. study, participants used the computer mouse to select one of two written words (a target and a foil) presented on the screen as quickly as possible, given auditory input. Stimuli consisted of sequences with two or three non-adjacent dependencies, ordered either using center-embeddings or cross-dependencies. The dependencies were instantiated using a set of dependency pairs that were matched for vowel sounds: ba-la, yo-no, mi-di, and wu-tu. Examples of each of the four types of stimuli are presented in (14-17), where the subscript numbering indicates dependency relationships.\n(14) ba1 wu2 tu2 la1\n(15) ba1 wu2 la1 tu2\n(16) ba1 wu2 yo3 no3 tu2 la1\n(17) ba1 wu2 yo3 la1 tu2 no3\nThus, (14) and (16) implement center-embedded recursive structure and (15) and (17) involve cross-dependencies. Participants would only be exposed to one of the four types of stimuli. To determine the potential effect of linguistic experience on the processing of complex recursive sequence structure, study participants were either native speakers of German (which has center-embedding but not cross-dependencies) or Dutch (which has cross-dependencies). Participants were only exposed to one kind of stimulus, e.g., doubly center-embedded sequences as in (16) in a fully crossed design (length x embedding x native language).\nde Vries et al. first evaluated learning by administering a block of ungrammatical sequences in which the learned dependencies were violated. As expected, the ungrammatical block produced a similar pattern of response slow-down for both for both center-embedded and cross-dependency items involving two non-adjacent dependencies (similar to what Bach et al.,, Bach et al., found in the natural language case). However, an analog of the missing verb effect was observed for the center-embedded sequences with three non-adjacencies but not for the comparable cross-dependency items. Indeed, an incorrect middle element in the center-embedded sequences (e.g., where tu is replaced by la in 16) did not elicit any slow-down at all, indicating that participants were not sensitive to violations at this position.\nSequence learning was further assessed using a prediction task at the end of the experiment (after a recovery block of grammatical sequences). In this task, participants would hear a beep replacing one of the elements in the second half of the sequence and were asked to simply click on the written word that they thought had been replaced. Participants exposed to the sequences incorporating two dependencies, performed reasonably well on this task, with no difference between center-embedded and cross-dependency stimuli. However, as for the response times, a missing verb effect was observed for the center-embedded sequences with three non-adjacencies. When the middle dependent element was replaced by a beep in center-embedded sequences (e.g., ba1 wu2 yo3 no3<beep> la1), participants were more likely to click on the foil (e.g., la) than the target (tu). This was not observed for the corresponding cross-dependency stimuli, once more mirroring the Bach et al. psycholinguistic results that multiple cross-dependencies are easier to process than multiple center-embeddings.\nContrary to psycholinguistic studies of German (Vasishth et al.,) and Dutch (Frank et al.,), de Vries et al. found an analog of the missing verb effect in speakers of both languages. Because the sequence-learning task involved non-sense syllables, rather than real words, it may not have tapped into the statistical regularities that play a key role in real-life language processing6. Instead, the results reveal fundamental limitations on the learning and processing of complex recursively structured sequences. However, these limitations may be mitigated to some degree, given sufficient exposure to the \"right\" patterns of linguistic structure:including statistical regularities involving morphological and semantic cues:and thus lessening sequence processing constraints that would otherwise result in the missing verb effect for doubly center-embedded constructions. Whereas the statistics of German and Dutch appear to support such amelioration of language processing, the statistical make-up of linguistic patterning in English and French apparently does not. This is consistent with the findings of Frank et al., demonstrating that native Dutch and German speakers show a missing verb effect when processing English (as a second language), even though they do not show this effect in their native language (except under extreme processing load, Trotzke et al.,). Together, this pattern of results suggests that the constraints on human processing of multiple long-distance dependencies in recursive constructions stem from limitations on sequence learning interacting with linguistic experience.\nIn this extended case study, we argued that our ability to process of recursive structure does not rely on recursion as a property of the grammar, but instead emerges gradually by piggybacking on top of domain-general sequence learning abilities. Evidence from genetics, comparative work on non-human primates, and cognitive neuroscience suggests that humans have evolved complex sequence learning skills, which were subsequently pressed into service to accommodate language. Constraints on sequence learning therefore have played an important role in shaping the cultural evolution of linguistic structure, including our limited abilities for processing recursive structure. We have shown how this perspective can account for the degree to which humans are able to process complex recursive structure in the form of center-embeddings and cross-dependencies. Processing limitations on recursive structure derive from constraints on sequence learning, modulated by our individual native language experience.\nWe have taken the first steps toward an evolutionarily-informed usage-based account of recursion, where our recursive abilities are acquired piecemeal, construction by construction, in line with developmental evidence. This perspective highlights the key role of language experience in explaining cross-linguistic similarities and dissimilarities in the ability to process different types of recursive structure. And although, we have focused on the important role of sequence learning in explaining the limitations of human recursive abilities, we want to stress that language processing, of course, includes other domain-general factors. Whereas distributional information clearly provides important input to language acquisition and processing, it is not sufficient, but must be complemented by numerous other sources of information, from phonological and prosodic cues to semantic and discourse information (e.g., Christiansen and Chater,, Forthcoming). Thus, our account is far from complete but it does offer the promise of a usage-based perspective of recursion based on evolutionary considerations.\nIn this paper, we have argued that there are theoretical reasons to suppose that special-purpose biological machinery for language can be ruled out on evolutionary grounds. A possible counter-move adopted by the minimalist approach to language is to suggest that the faculty of language is very minimal and only consists of recursion (e.g., Hauser et al.,; Chomsky,). However, we have shown that capturing human performance on recursive constructions does not require an innate mechanism for recursion. Instead, we have suggested that the variation in processing of recursive structures as can be observed across individuals, development and languages is best explained by domain-general abilities for sequence learning and processing interacting with linguistic experience. But, if this is right, it becomes crucial to provide explanations for the puzzling aspects of language that were previously used to support the case for a rich innate language faculty: (1) the poverty of the stimulus, (2) the eccentricity of language, (3) language universals, (4) the source of linguistic regularities, and (5) the uniqueness of human language. In the remainder of the paper, we therefore address each of these five challenges, in turn, suggesting how they may be accounted for without recourse to anything more than domain-general constraints.\nOne traditional motivation for postulating an innate language faculty is the assertion that there is insufficient information in the child's linguistic environment for reliable language acquisition to be possible (Chomsky,). If the language faculty has been pared back to consist only of a putative mechanism for recursion, then this motivation no longer applies:the complex patterns in language which have been thought to pose challenges of learnability concern highly specific properties of language (e.g., concerning binding constraints), which are not resolved merely by supplying the learner with a mechanism for recursion.\nBut recent work provides a positive account of how the child can acquire language, in the absence of an innate language faculty, whether minimal or not. One line of research has shown, using computational results from language corpora and mathematical analysis, that learning methods are much more powerful than had previously been assumed (e.g., Manning and Schutze,; Klein and Manning,; Chater and Vitanyi,; Hsu et al.,; Chater et al.,). But more importantly, viewing language as a culturally evolving system, shaped by the selectional pressures from language learners, explains why language and languages learners fit together so closely. In short, the remarkable phenomenon of language acquisition from a noisy and partial linguistic input arises from a close fit between the structure of language and the structure of the language learner. However, the origin of this fit is not that the learner has somehow acquired a special-purpose language faculty embodying universal properties of human languages, but, instead, because language has been subject to powerful pressures of cultural evolution to match, as well as possible, the learning and processing mechanism of its speakers (e.g., as suggested by Reali and Christiansen's,, simulations). In short, the brain is not shaped for language; language is shaped by the brain (Christiansen and Chater,).\nLanguage acquisition can overcome the challenges of the poverty of the stimulus without recourse to an innate language faculty, in light both of new results on learnability, and the insight that language has been shaped through processes of cultural evolution to be as learnable as possible.\nFodor argue that the generalizations found in language are so different from those evident in other cognitive domains, that they can only be subserved by highly specialized cognitive mechanisms. But the cultural evolutionary perspective that we have outlined here suggests, instead, that the generalizations observed in language are not so eccentric after all: they arise, instead, from a wide variety of cognitive, cultural, and communicative constraints (e.g., as exemplified by our extended case study of recursion). The interplay of these constraints, and the contingencies of many thousands of years of cultural evolution, is likely to have resulted in the apparently baffling complexity of natural languages.\nAnother popular motivation for proposing an innate language faculty is to explain putatively universal properties across all human languages. Such universals can be explained as consequences of the innate language faculty:and variation between languages has often been viewed as relatively superficial, and perhaps as being determined by the flipping of a rather small number of discrete \"switches,\" which differentiate English, Hopi and Japanese (e.g., Lightfoot,; Baker,; Yang,).\nBy contrast, we see \"universals\" as products of the interaction between constraints deriving from the way our thought processes work, from perceptuo-motor factors, from cognitive limitations on learning and processing, and from pragmatic sources. This view implies that most universals are unlikely to be found across all languages; rather, \"universals\" are more akin to statistical trends tied to patterns of language use. Consequently, specific universals fall on a continuum, ranging from being attested to only in some languages to being found across most languages. An example of the former is the class of implicational universals, such as that verb-final languages tend to have postpositions (Dryer,), whereas the presence of nouns and verbs (minimally as typological prototypes; Croft,) in most, though perhaps not all (Evans and Levinson,), languages is an example of the latter.\nIndividual languages, on our account, are seen as evolving under the pressures from multiple constraints deriving from the brain, as well as cultural-historical factors (including language contact and sociolinguistic influences), resulting over time in the breathtaking linguistic diversity that characterize the about 6-8000 currently existing languages (see also Dediu et al.,). Languages variously employ tones, clicks, or manual signs to signal differences in meaning; some languages appear to lack the noun-verb distinction (e.g., Straits Salish), whereas others have a proliferation of fine-grained syntactic categories (e.g., Tzeltal); and some languages do without morphology (e.g., Mandarin), while others pack a whole sentence into a single word (e.g., Cayuga). Cross-linguistically recurring patterns do emerge due to similarity in constraints and culture/history, but such patterns should be expected to be probabilistic tendencies, not the rigid properties of a universal grammar (Christiansen and Chater,). From this perspective it seems unlikely that the world's languages will fit within a single parameterized framework (e.g., Baker,), and more likely that languages will provide a diverse, and somewhat unruly, set of solutions to a hugely complex problem of multiple constraint satisfaction, as appears consistent with research on language typology (Comrie,; Evans and Levinson,; Evans,). Thus, we construe recurring patterns of language along the lines of Wittgenstein's notion of \"family resemblance\": although there may be similarities between pairs of individual languages, there is no single set of features common to all.\nEven if the traditional conception of language universals is too strict, the challenge remains: in the absence of a language faculty, how can we explain why language is orderly at all? How is it that the processing of myriads of different constructions have not created a chaotic mass of conflicting conventions, but a highly, if partially, structured system linking form and meaning?\nThe spontaneous creation of tracks in a forest provides an interesting analogy (Christiansen and Chater,). Each time an animal navigates through the forest, it is concerned only with reaching its immediate destination as easily as possible. But the cumulative effect of such navigating episodes, in breaking down vegetation and gradually creating a network of paths, is by no means chaotic. Indeed, over time, we may expect the pattern of tracks to become increasingly ordered: kinks will be become straightened; paths between ecological salient locations (e.g., sources of food, shelter or water) will become more strongly established; and so on. We might similarly suspect that language will become increasingly ordered over long periods of cultural evolution.\nWe should anticipate that such order should emerge because the cognitive system does not merely learn lists of lexical items and constructions by rote; it generalizes from past cases to new cases. To the extent that the language is a disordered morass of competing and inconsistent regularities, it will be difficult to process and difficult to learn. Thus, the cultural evolution of language, both within individuals and across generations of learners, will impose a strong selection pressure on individual lexical items and constructions to align with each other. Just as stable and orderly forest tracks emerge from the initially arbitrary wanderings of the forest fauna, so an orderly language may emerge from what may, perhaps, have been the rather limited, arbitrary and inconsistent communicative system of early \"proto-language.\" In particular, for example, the need to convey an unlimited number of messages will lead to a drive to recombine linguistic elements is systematic ways, yielding increasingly \"compositional\" semantics, in which the meaning of a message is associated with the meaning of its parts, and the way in which they are composed together (e.g., Kirby,).\nThere appears to be a qualitative difference between communicative systems employed by non-human animals, and human natural language: one possible explanation is that humans, alone, possess an innate faculty for language. But human \"exceptionalism\" is evident in many domains, not just in language; and, we suggest, there is good reason to suppose that what makes humans special concerns aspect of our cognitive and social behavior, which evolved prior to the emergence of language, but made possible the collective construction of natural languages through long processes of cultural evolution.\nA wide range of possible cognitive precursors for language have been proposed. For example, human sequence processing abilities for complex patterns, described above, appear significantly to outstrip processing abilities of non-human animals (e.g., Conway and Christiansen,). Human articulatory machinery may be better suited to spoken language than that of other apes (e.g., Lieberman,). And the human abilities to understand the minds of others (e.g., Call and Tomasello,) and to share attention (e.g., Knoblich et al.,) and to engage in joint actions (e.g., Bratman,), may all be important precursors for language.\nNote, though, that from the present perspective, language is continuous with other aspects of culture:and almost all aspects of human culture, from music and art to religious ritual and belief, moral norms, ideologies, financial institutions, organizations, and political structures are uniquely human. It seems likely that such complex cultural forms arise through long periods of cultural innovation and diffusion, and that the nature of such propagation depends will depend on a multitude of historical, sociological, and, most likely, a host of cognitive factors (e.g., Tomasello,; Richerson and Christiansen,). Moreover, we should expect that different aspects of cultural evolution, including the evolution of language, will be highly interdependent. In the light of these considerations, once the presupposition that language is sui generis and rooted in a genetically-specified language faculty is abandoned, there seems little reason to suppose that there will be a clear-cut answer concerning the key cognitive precursors for human language, any more than we should expect to be able to enumerate the precursors of cookery, dancing, or agriculture.\nPrior to the seismic upheavals created by the inception of generative grammar, language was generally viewed as a paradigmatic, and indeed especially central, element of human culture. But the meta-theory of the generative approach was taken to suggest a very different viewpoint: that language is primarily a biological, rather than a cultural, phenomenon: the knowledge of the language was seen not as embedded in a culture of speakers and hearers, but primarily in a genetically-specified language faculty.\nWe suggest that, in light of the lack of a plausible evolutionary origin for the language faculty, and a re-evaluation of the evidence for even the most minimal element of such a faculty, the mechanism of recursion, it is time to return to viewing language as a cultural, and not a biological, phenomenon. Nonetheless, we stress that, like other aspects of culture, language will have been shaped by human processing and learning biases. Thus, understanding the structure, acquisition, processing, and cultural evolution of natural language requires unpicking how language has been shaped by the biological and cognitive properties of the human brain.\nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.",
"gender": "Female"
}
] |
PMC4550780
|
[
{
"age": 72,
"case_id": "PMC5987309_01",
"case_text": "A 72-year-old male with a past medical history of quadriplegia, hypertension, hyperlipidemia, neurogenic bladder, type 2 diabetes mellitus, chronic obstructive pulmonary disease, and chronic hepatitis presented to the emergency department with an acute change in mental status. He was a full-time resident at an assisted living nursing home, and his baseline mental status was awake, alert, and oriented to person, place, and time (AAOx3). Upon arrival in the emergency department, he was oriented only to self. Prior to this admission, the patient was being treated for a urinary tract infection and was on day seven of nitrofurantoin and cefepime. On examination, he was hypotensive at a blood pressure of 81/59 mmHg, pulse rate of 115 beats per minute, respiratory rate of 21 breaths per minute, and oxygen saturation of 78% while breathing ambient air. He was in visible respiratory distress and was lethargic, but arousable. He received a nebulizer treatment and was placed on a non-rebreather mask at 6 liters, after which his oxygen saturation rose to 99%. A chest X-ray was taken and revealed left lower lobe pneumonia. His urinalysis was positive for an infection despite current antibiotic compliance. He began vancomycin and piperacillin/tazobactam for health care-associated pneumonia and was admitted to the ICU. Respiratory status worsened, and he required intubation.\nDespite these interventions, on his second day of admission, he continued to have copious clear secretions. Pulmonology diagnosed him with aspiration pneumonia and sputum cultures were obtained, which demonstrated moderate white blood cells, rare epithelial cells, few Gram-positive cocci in clusters, and rare yeast. His antibiotics were adjusted for sensitivities to vancomycin and meropenem. To further evaluate his ongoing pulmonary issues, a chest CT scan was obtained, revealing increasing bilateral pleural effusions and patchy sclerotic foci concerning for possible bone metastases, enlarged mediastinal lymph nodes, and nodular infiltrate in the right mid- and upper lung fields. Gastroenterology was consulted for colonoscopy to identify a primary tumor, but the patient was deemed too unstable for a nonemergent procedure. Thoracocentesis revealed exudative pleural effusions negative for malignancy. Abdominal and pelvic CT demonstrated hydronephrosis and a right-sided staghorn renal calculus but no masses.\nWith these interventions, our patient began to improve, yet daily sedation interruptions and spontaneous breathing trials failed. Initial blood culture results showed Gram-positive bacilli, and further speciation of the organism was requested. On day 13, blood cultures were finalized and grew Clostridium subterminale. Sputum and stool testing showed Pseudomonas aeruginosa and Clostridium difficile, so metronidazole was started. Gastroenterology again stated that the patient was too unstable for colonoscopy and suggested a bone biopsy, which he underwent the following day. The preliminary pathology report stated that the bone biopsy was likely malignant adenocarcinoma, which was confirmed on hospital day 21. Biopsy indicated that the tumor was positive for markers CK7 and CA19-9; primary sites with this immunophenotypic profile include the upper GI tract and pancreaticobiliary system. Carcinoembryonic antigen (CEA) was elevated at 73.8 (normal CEA nonsmokers < 5.1; smokers < 6.6) and CA19-9 was 3,146 (normal < 45). Per oncology, he was not a candidate for any interventions due to his comorbidities.\nOn day 23, he had increasing secretions and was agitated despite completion of his antibiotic course. The patient's three daughters decided on terminal extubation, and comfort measures were initiated. At 21 : 12 on hospital day 23, the patient was pronounced dead.",
"gender": "Male"
}
] |
PMC5987309
|
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in Data Studio
MultiCaRe: Open-Source Clinical Case Dataset
MultiCaRe is an open-source, multimodal clinical case dataset derived from PubMed Central’s Open Access (OA) Case Report articles. It links de-identified case narratives to figure images/captions and article-level metadata, enabling cross-modal supervision and retrieval.
- Source and process: OA case reports from PMC; parsed metadata and abstracts; extracted case narratives; downloaded and processed figures; aligned captions; curated image taxonomy (>140 classes).
- Scale: 85k+ articles with 110k+ patient mentions and 160k+ images (v2.0).
- Tasks enabled: narrative classification, retrieval, summarization; multimodal modeling with image joins; VQA/doc-QA with figure references.
- Citation: Paper — https://www.mdpi.com/2306-5729/10/8/123; Zenodo — https://zenodo.org/records/13936721.
This repository: per-case dataset Per-case clinical narratives and demographics extracted from case reports.
Schema
- case_id: case identifier (joins to images.patient_id)
- article_id: PMCID (joins to articles.article_id)
- case_text: clinical case narrative
- age: age in years (0 if <1 y.o.)
- gender: Female, Male, Transgender, Unknown
Quick start
from datasets import load_dataset
cases = load_dataset("openmed-community/multicare-cases", split="train")
print(cases[0]["case_text"][:600])
Join with images
from datasets import load_dataset
cases = load_dataset("openmed-community/multicare-cases", split="train")
imgs = load_dataset("openmed-community/multicare-images", split="train")
cid = cases[0]["case_id"]
imgs_for_case = imgs.filter(lambda e: e["patient_id"] == cid)
imgs_for_case[0]["image"].show()
Notes
- No official splits; recommend patient/article-level splitting to avoid leakage.
- Per-item OA licenses are provided at the image level and via articles.
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