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data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1009_en.txt

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+We report the case of a 29-year-old male patient (smoker) not known to have any medical illnesses. He presented to our outpatient clinic at King Abdullah University Hospital, Jordan, complaining of a painless mass in the right breast of 2 weeks duration. The patient denied any history of trauma. The systemic review and family history were unremarkable. The examination revealed a retroareolar painless lump in the right breast at 2 o'clock, about 1 × 1 cm in diameter, not associated with skin changes or regional lymphadenopathy. Contralateral breast and axillary lymph nodes were unremarkable.
+Breast ultrasound showed a hypoechoic soft tissue lesion measuring about 5 × 2 mm with increased vascularity. Laboratory tests including complete blood count and blood chemistry were within normal ranges.
+An excisional biopsy with margin through a periareolar skin incision was performed. Histopathology revealed a 1.3 × 1 × 0.4-cm mass, with clusters of inflammatory cells including lymphocytes, neutrophils, epithelioid histiocytes and giant cells surrounding a cyst-like lesion lined by squamous cells, consistent with GM .
+The tissue was cultured, and special stains were used. No microorganisms were identified. There was no evidence of malignancy. Patient follow-up at 3 months did not show any evidence of recurrence.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1069_en.txt

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+A 9-year-old boy (14 kg) was admitted with feeding difficulties after birth caused by spastic CP.
+After birth, the patient had persistent feeding difficulties, accompanied by repeated coughing and vomiting after eating. He was diagnosed with spastic CP along with severe malnutrition, thoracic scoliosis, laryngomalacia, pneumonia, and multiple site deformities, including those of the airway, thorax, hip joint, and both hands and feet. In addition to epilepsy and taking clonazepam 1 mg, phenobarbital 25 mg, levetiracetam 150 mg, and sodium valproate oral liquid 5 mL twice daily, he had a history of aspiration pneumonia and copious purulent sputum, for which he was prescribed antibiotics for 9 d. He was scheduled to undergo implantation of an implantable venous access port and gastrostomy to improve feeding and nutrition. This was not a typical elective operation and was difficult to adjust to a conventionally safe state, because the pneumonia was protracted and nursing conditions were limited.
+The patient was diagnosed with spastic CP along with severe malnutrition, thoracic scoliosis, laryngomalacia, pneumonia, and multiple site deformities, including those of the airway, thorax, hip joint, and both hands and feet.
+The patient had been abandoned as a toddler, and his birth and family histories were uncertain.
+The patient’s general physical examination revealed typical facial dysmorphism, thoracic deformities, scoliosis, oxycephaly, and hip dislocation. He showed a Mallampati class IV airway with severely limited neck movement, thyromental distance of fewer than three fingers, and 20-mm-inter-incisor distance. Auscultation indicated an obvious UAO with distinct sputum sounds, and oxygen saturation (SpO2) was 85%-90% on 3 L/min of supplemental oxygen using a nasal oxygen cannula. Preoperative evaluation exhibited a class III physical status of American Society of Anesthesiologists with a difficult airway.
+Routine blood tests showed a hemoglobin (Hb) level of 9.7 g/dL, hematocrit of 33.3%, mean corpuscular volume of 73.9 fL, mean corpuscular Hb of 21.6 pg, and mean corpuscular Hb concentration of 29.2 g/dL. Other blood test results showed no significant abnormalities.
+Chest radiography demonstrated pneumonia, scoliosis, and right deviation of the trachea . Computed tomography (CT) scans revealed scoliosis, osteoporosis of the spine, significant atrophy of the muscles of the back in the bilateral thoracolumbar region with fat infiltration, and thoracic and tracheal malformation . Lateral cervical spine CT scans displayed laryngomalacia and malformations of the pharynx and cervical spine .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1081_en.txt

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+A 39-year-old female patient presented to our facility with a 2-day history of fevers, malaise, and central dull chest pain that was neither pleuritic nor altered by position. She had a past history of relapsing Philadelphia-positive ALL for which she had received two consecutive allogeneic stem cell transplants (SCT) from a sibling donor, as well as an infusion of donor lymphocytes. She had no previous history of cardiovascular disease and at the time of presentation had been in remission from her ALL for 6 months. Her post-remission course had been uneventful prior to her emergency presentation.
+On assessment she was dehydrated, tachycardic (up to 130 b.p.m.) and hypotensive (90/65 mmHg) with a temperature of 38.5°C. The remainder of the cardiovascular examination was unremarkable. Blood tests demonstrated an elevated C-reactive protein of 72.7 mg/L (<10) and a Troponin T of 2490 ng/L (0–14). Her white cell count was normal (10.4 × 109/L), and peripheral blood film examination did not identify precursor cells. The remainder of her biochemistry was within normal parameters including her haemoglobin, electrolytes, creatinine, and liver function tests. Multiple blood cultures were taken and remained negative. Chest radiography was normal. Electrocardiogram (ECG) demonstrated a sinus tachycardia with new deep T-wave inversion (TWI) in leads V3–V6, not seen on a previous ECG . A transthoracic echocardiogram demonstrated mild–moderate left ventricular hypertrophy with anterior and anteroapical hypokinesis and a small circumferential pericardial effusion. The left ventricular size was normal, but systolic function was impaired with a left ventricular ejection fraction of 45%. There was no significant valvular pathology . Coronary angiography did not reveal significant obstructive disease.
+The patient was resuscitated with IV fluids, given tazocin 4.5 g 6 hourly and commenced on therapy for presumed severe myopericarditis, receiving pulsed 1 g intravenous methylprednisolone daily for 3 days; however, failed to respond with ongoing fevers, tachycardia, and hypotension. Differential diagnoses including infiltrative, tachycardic, and catecholaminergic cardiomyopathies were considered. In the absence of a clear aetiology and given her failure to respond to initial therapy, an urgent cardiac magnetic resonance imaging (CMR) was sought. Cardiac magnetic resonance imaging identified severe, patchy increased signal intensity involving the myocardium and pericardium in the basal antero-septum, anterior wall, mid-lateral wall, and the distal interventricular septum on oedema-weighted, and late gadolinium sequences with associated regional wall motion abnormalities consistent with severe myocarditis .
+She subsequently underwent transjugular endomyocardial biopsy (EMBx). Endomyocardial biopsy revealed a heavy infiltrate of malignant lymphocytes percolating between myocytes , with resultant atrophy of the intervening myocardial fibres as well as an accumulation of the malignant cells in a prominent perivascular and pericardial distribution , confirming a leukaemic infiltrate in the myocardium. The lymphocytes exhibited mild to moderate nuclear pleomorphism with scattered mitoses and hyperchromatic nuclei with increased N:C ratio and stained strongly positively for CD20, CD10, TdT, and PAX5 immunoperoxidase stains , confirming the presence of immature lymphoid lineage blood cells. Interphase FISH Probes for BCR/ABL1 [t(9; 22)(q34; q11.2)] revealed a signal pattern consistent with BCR-ABL1 rearrangement in the infiltrating cells and DXZ1 (X centromere), DYZ1(Yq12) loci-specific probe set confirmed that the majority of the cells contained recipient (XX) origin, with only occasional donor (XY) cells noted . These findings were in keeping with recurrence of the patient’s ALL.
+Her clinical course was complicated by runs of non-sustained ventricular tachycardia (treated with amiodarone 300 mg orally thrice daily in a weaning regimen and coupled with low-dose bisoprolol 2.5 mg daily, titrated to blood pressure), persistent fevers, and intermittent chest pain with associated changes in serum troponin. Within 2 weeks of confirmation of diagnosis by EMBx the patient had evidence of lymphoblasts (50%) in her peripheral blood. She was commenced on a second-line compassionate-access tyrosine kinase inhibitor, Ponatinib (45 mg orally once daily), as a palliative measure, though she failed to respond and by 4 weeks her blast count was 23.71 × 109/L with a doubling time of under 24 h. She soon thereafter died from fulminant multi-organ failure.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1111_en.txt

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+The patient presented here is a 4 year-old girl of healthy consanguineous parents. Her younger sister was also healthy. Prenatal echography revealed short limbs. The PPS was evoked at birth and the patient was addressed for facial dimorphisms. Clinical investigations including karyotype, pediatric and ophthalmologic exams were performed after informed consent. At birth, she was underweight 2660 g (-1.6 SD), her length was 46 cm (-1.4 SD), and occipitofrontal circumference (OFC) 34 cm (±0 SD). Apgar score was 8/10. Neonatal exams revealed complete bilateral cleft lip and palate, large anterior fontanel, hypertelorism and a coccygeal dimple suggesting vertebral schisis. She also had disproportionate short stature and facial dysmorphism including dolichocephaly, round face, small nose with reverted nostrils and erased and long philtrum. Short limbs in the proximal segment and brachydactyly with bilateral clinodactyly of the fifth finger were also seen. Transfontanel ultrasound imaging showed quadri ventricular hydrocephaly and microcephaly caused by agenesis and atrophy of corpus callosum. Ophthalmologic exam revealed bilateral central corneal opacity without buphthalmos or congenital glaucoma.
+In addition to these typical features for PPS, the patient showed sexual ambiguity without urogenital anomalies. In fact, she had hyper pigmented labia majora with pseudo scrotal aspect without clitoris hypertrophy, but she had two distinct (urethral and vaginal) orifices. Abdomen ultrasound showed a morphologically normal uterus with normal size, but renal pyelo-calicial dilation on left side was appreciated. Chromosome analysis on lymphocytes revealed a normal 46, XX karyotype. At the age of 4 years, the patient's weight was 11 kg (-2SD), length 78 cm (-3SD) and OFC 47 cm; without delayed psychomotor development.
+B3GALTL is the only gene known to be associated with Peters Plus syndrome, and most affected individuals tested to date are homozygous for a hot spot splice mutation in the acceptor splice site of intron 8 (c.660 + 1G > A). Sequencing of the 15 coding exons and flanking introns boundaries of the B3GALTL gene showed that the patient is B3GALTL mutation-negative. But we cannot exclude the presence of splice site mutation distant from the coding sequence, or mutation in the regulatory sequences of the gene. In addition, screening of the three intragenic SNP(s) which are described to be associated with B3GALTL gene mutations showed that the patient is heterozygous for two SNP (rs9315120, rs877103) and homozygous for the rs877104 one . These results suggest but not confirm the exclusion of the B3GALTL gene in this case .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1132_en.txt

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+A 24-year-old southeast Asian woman was admitted with a history of a white spot on the right cornea and increasing discomfort. On examination, her vision was 6/36 on the right and 6/9 on the left. She had a corneal ulcer measuring 5.5 × 2 mm on her right cornea. A small localized area of scarring was present lateral to where the defect was present . There was a +1 cell reaction in her right anterior chamber. She had a history of bilateral anterior uveitis. Corneal sensation was normal in both eyes. There were early bilateral posterior subcapsular cataracts.
+In view of the findings, corneal scrapes were taken for microscopy, culture, and sensitivity. Virology assays inclusive of herpes simplex virus and varicella-zoster virus polymerase chain reaction were performed. Our patient had normal C-reactive protein, rheumatoid factor, anti-nuclear antibody, extractable nuclear antigen, syphilis, and hepatitis B and C serology. She was started on topical g. cephalothin 5% and g. gentamicin 0.9% hourly for 48 hours. She made a mild initial improvement and was changed to topical g. chloramphenicol 1% four times each day and g. prednisolone 0.5% four times each day once her microbiology and virology results were negative. A bandage contact lens was inserted to facilitate healing .
+In the third week of admission, she complained of a headache and was found to be mildly tachycardic. She was apyrexial with no reported malaise. A urinary dipstick analysis was performed, and her urinary glucose level was 21 mmol/L. Blood glucose was urgently requested and was found to be 23 mmol/L. A blood gas analysis showed a pH of 7.38, a partial pressure of carbon dioxide (pCO2) of 44.7 mmHg, and a partial pressure of oxygen (pO2) of 89.5 mmHg.
+She was transferred to the care of the medical team and a diagnosis of type 1 diabetes was made. She was started on treatment with insulin. Her corneal ulcer persisted and punctal plugs were inserted to increase the tear film and facilitate healing. Autologous serum drops were started every two hours during waking hours. There was a rapid reduction of the epithelial defect as her blood glucose levels normalized .
+Four days after insulin treatment was started, her ulcer had healed and she was discharged from the hospital and follow-up was conducted at her local diabetes clinic. At a one-month review in the eye clinic, her ulcer remained healed, leaving a localized area of subepithelial scarring .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1152_en.txt

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+A 31-year-old woman, gravida-1 (23 weeks' gestation), para-0, presented with acute severe pain in her left buttock region radiating to the leg and increasing with ambulation. No underlying pathologies or drug abuse were present and no systemic symptoms were encountered. Backache was initially attributed to nerve compression. Nonsteroidal anti-inflammatory drugs and rest were prescribed.
+After 4 days, the pain became worse. Physical examination revealed a temperature of 39.2 ºC, pulse rate of 111 beats/minute, respiratory rate of 43 breaths/minute and blood pressure of 100/50mmHg. The laboratory test results were significant for leukocytes of 5400/mm3 with left shift (92%), haematocrit of 24%, D-Dimer of 946.8μg/L and platelet count of 85,000/mm3. Chest X-ray showed images of bilateral pulmonary condensation.
+The patient was admitted to the intensive care unit with a diagnosis of septic shock and acute respiratory distress. Doppler ultrasound examination of both legs and pulmonary arteriography disproved the diagnosis of pulmonary embolism. An echocardiogram did not find any evidence of endocarditis.
+Treatment with broad-spectrum antibiotics (gentamicin and ceftriaxone), inotropic drugs and ventilatory support was prescribed. Her general status improved throughout the following days. Nevertheless, her back pain became worse. A magnetic resonance imaging (MRI) scan revealed left-sided sacroiliitis with a small abscess at the lower joint margin extending into the iliac notch. A computed tomography-guided aspiration of the abscess was performed and the patient reported partial relief of her symptoms.
+Sacroiliac aspiration yielded a small amount of fluid. Although blood cultures were positive for Staphylococcus aureus, culture of the material from the sacroiliac aspiration failed to yield positive results. Intravenous cloxacillin was added to the antibiotic therapy and a rehabilitation programme was initiated so that the patient might recover her strength and mobility.
+A new MRI performed 6 weeks later showed progression of sacroiliac joint destruction and focal osteomyelitis . A cesarean section was performed under general anaesthesia at 34 weeks' gestation and a 2570g male neonate was delivered.
+The total length of intravenous antibiotic treatment was 8 weeks. She continued with oral rifampicin and ofloxacin for 4 months. After cesarean section, the patient noticed progressive decreased pain and increased ambulatory ability. One year after the onset of symptoms, Technetium-99 conjugated with methylene diphosphonate (Tc-99m MDP) bone scintigraphy still demonstrated increased uptake in the left sacroiliac region. Figure shows single-photon emission computed tomography/computed tomography (SPECT/CT) results. The patient is doing well with normal ambulation, although she continues to experience mild discomfort in her left buttock.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1190_en.txt

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+The proband is a 6.5- year-old Saudi boy born by emergency cesarean section as preterm (gestational age 33 weeks) to first cousin parents. He had respiratory distress and required oxygen via nasal canula, but settled quickly. He had no dysmorphic features and neurologic and other systems examination revealed normal findings. Following discharge from the neonatal intensive care unit (NICU) and during follow up in clinic, he was found to have delayed developmental milestones. He sat unsupported at 1 year, walked at 30 months and showed unsteadiness since starting to walk. Speech acquisition was delayed till 5 years.
+Examination at the age of 6.5 years showed no craniofacial abnormalities, normal head size (47.5 cm) and normal systemic examination. There was no muscle wasting, fasciculation, ocular apraxia, nystagmus or saccadic pursuit. Muscle tone, power, sensation and deep tendon reflexes were normal. Plantar response was flexor. There were no signs of ataxia in either the upper or lower limbs. IQ testing revealed mildly impaired cognitive abilities (IQ = 67). Laboratory investigations showed normal complete blood count (CBC), electrolytes, creatine kinase (CK), hepatic and renal function tests. Screen for metabolic disorders revealed no abnormalities. Visual evoked potential (VEP) was normal in both eyes, and brain auditory evoked response.
+(BAER) showed normal results. Nerve conduction study was essentially normal in the upper and lower limbs. Magnetic resonance imaging (MRI) at the age of 2.5 years showed normal cerebellar volume and folia with no signs of atrophy. The vermis had normal size and the cerebellar gray and white matter were also normal.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1196_en.txt

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+A 9-year-old girl presented to our hospital emergency department with a 3-wk history of ineffective right limb movement.
+The treatment timeline is shown in Figure . A head computed tomography (CT) scan revealed a quasi-circular mass in the left frontal-parietal region with high-density and associated hemorrhage . Brain magnetic resonance imaging (MRI) revealed low signals on T1 weighted imaging with high surrounding signals. High signals on T2 weighted imaging with low surrounding signals were observed, with marked enhancement on contrast measuring 4.8 cm × 5.0 cm × 4.5 cm in the left motor area of the frontal-parietal lobes . The imaging characteristics were similar to meningioma. An unenhanced chest CT scan revealed no nodules in the chest.
+Laboratory tests including complete blood cell counts, bleeding time, activated partial thromboplastin time, prothrombin time, liver and renal function and blood glucose level were within normal ranges.
+Her temperature was 36.6 ℃, resting respiratory rate was 16 breaths/min, heart rate was 90 bpm and blood pressure was 120/75 mmHg. Neurological examination showed that her Glasgow Coma Scale score was 15 (E4V5M6), and muscle strength was grade 2 in the right limbs. She did not have any other neurological deficits.
+She had no personal or family history of benign or malignant tumors.
+The patient had no history of prior illness.
+The patient had ineffective right limb movement for 3 wk. She also had headaches, accompanied by nausea and vomiting and excess sleep. A head CT scan revealed a quasi-circular mass in the left frontal-parietal region with high-density and associated hemorrhage.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1226_en.txt

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+A 60-year-old man was referred to our hospital with suspected pancreatic tail cancer based on a high carbohydrate antigen 19-9 (CA19-9) concentration found during a medical checkup. He was a past smoker (Brinkman Index, 800) and drinker (20 g/day of ethanol for 20 years). He had no remarkable past illnesses, including diabetes, and no familial history of pancreatic cancer. His body mass index was 20.8 kg/m2. The patient had no weight loss events. Dynamic contrast-enhanced computed tomography (dCECT) at our hospital revealed a hypovascular lesion in the pancreatic tail . Adenocarcinoma was confirmed using endoscopic ultrasonographic fine-needle aspiration. His CA19-9 concentration at our hospital was 286.8 U/mL, and his HbA1c concentration was 5.6%. dCECT revealed that the tumor was anatomically resectable. No synchronous liver metastasis was identified by gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI). Positron emission tomography revealed a high standardized uptake value (maximum 6.6; Fig. b). Thus, the patient underwent distal pancreatectomy and regional lymph node dissection in accordance with radical antegrade modular pancreatosplenectomy . In this surgery, the pancreatic parenchyma was cut just above the superior mesenteric vein using tri-stapler technology. The operative time was 251 min, and extra blood loss was 720 mL. Although he developed a clinically relevant postoperative pancreatic fistula, it improved without any invasive intervention, and he was discharged on postoperative day 40. Pathological examination revealed a 36 × 18 × 17-mm moderately differentiated tubular adenocarcinoma. No lymph node metastasis was identified (0/27). No microscopic lymphatic invasion was observed, but microscopic venous invasion was observed. The cancer slightly invaded the extrapancreatic connective tissue. The pancreatic cut and dissected margins were negative. Postoperative staging was stage IB (T2N0M0) according to the Union for International Cancer Control 8th edition. Adjuvant S-1 chemotherapy (120 mg/body/day) was administered for 6 months after surgery.
+Two years after the initial pancreatectomy, a solitary hypovascular lesion was identified in liver segment 4 on follow-up dCECT . This was considered liver metastasis from pancreatic cancer in conjunction with the MRI results. The CA19-9 concentration was slightly elevated at 44.5 U/mL. However, the tumor did not show a significant standardized uptake value on positron emission tomography . Gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2 was administered on day 1, 8, and 15 every 4 weeks for the liver metastasis. Dexamethasone (6.6 mg) was administered as a premedication. After 14 cycles of gemcitabine/nab-paclitaxel, the CA19-9 level, which had fallen to the normal range, became elevated again (660.7 U/mL) and the tumor had increased in size (from 10 to 15 mm in diameter); therefore, the chemotherapy was converted to a modified FOLFIRINOX regimen (5-fluorouracil 2400 mg/m2, levoleucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and irinotecan 150 mg/m2) as second-line therapy, which was administered triweekly. Steroid use as a premedication remained unchanged (6.6 mg dexamethasone). However, the CA19-9 concentration further increased to 3130.0 U/mL after nine cycles of FOLFIRINOX chemotherapy. The tumor diameter increased to 25 mm; however, no further metastases developed. The MRI findings before and after chemotherapy are summarized in Fig. e, f. The number of tumors did not change (i.e., the patient did not develop more than one tumor), the tumor was resectable, chemotherapy was minimally effective, and the patient’s general status was well maintained; therefore, we decided to perform surgical resection at this time after a multidisciplinary team conference. Left hepatectomy and cholecystectomy were also performed. Preoperative three-dimensional simulation and intraoperative photographs are shown in Fig. . The operation time was 239 min and the blood loss was 480 mL. Pathological examination revealed that the tumor was a moderately differentiated adenocarcinoma compatible with metastasis from pancreatic cancer . On hematoxylin and eosin staining, there was little heterogeneity between the primary and metastatic lesions. No microscopic vessel invasion (portal, venous, arterial, or bile) was found. The surgical margins were negative. Adjuvant therapy was not administered after the second surgery. The patient was alive with no recurrence 2 years after hepatectomy.
+At the time of diagnosis of liver metastasis, the HbA1c level was elevated to 7.2%. Thereafter, this value increased rapidly; 6 months later, it increased to 10.0%, and insulin therapy was initiated. The serum C-peptide concentration was 3.65 ng/mL at that time. Although the HbA1c concentration decreased after insulin induction, it increased again in parallel with the increase in CA19-9 concentration. Finally, 15 units of regular insulin and 18 units of long-acting insulin were administered for preoperative glycemic control. After curative hepatectomy, the patient’s glycemic control improved immediately. The patient started oral intake and insulin injection at the same amount as before on postoperative day 2. Blood glucose levels fluctuated between 100 and 150 mg/dL. Therefore, the dose of insulin was reduced. At discharge, regular insulin was terminated. Furthermore, insulin therapy was completely terminated 2 months after the surgery. The clinical course of the patient is summarized in Fig. .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1311_en.txt

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+A 4-year-old female Caucasian child was admitted to the emergency department with fever and acute respiratory failure. The personal and familial anamnestic recall brought no elements of suspicion for a past SARS-CoV-2 infection. The chest X-ray and subsequent computed tomography (CT) showed multiple and bilateral ground glass areas and patchy consolidations in the inferior lobes, pneumomediastinum with supraclavicular and cervical bilateral subcutaneous emphysema . The microbiological assessment on broncho-alveolar lavage (BAL) was positive for Pneumocystis jiroveci (PJ) and galactomannan, SARS-CoV-2 proved negative. As her respiratory dynamics progressively deteriorated, she was intubated and assisted through mechanical ventilation.
+At the anamnestic recall the parents reported a history of recurrent respiratory infections since she was 3 years old, a previous episode of ocular HSV infection and recurrent oral thrush. Due to the patient’s medical history and the evidence of PJI and pulmonary aspergillosis, an immunological assessment was performed, and a severe CD4-penia emerged: CD4+ was 1.06% (6 cell/µl, normal value 500–1000). Soon after the diagnosis of HIV-positivity was finalised with a viral load of 83.429 copies/ml. She was classified as a stage 3, according to Centres for Disease Control (CDC) classification system for HIV infection . Combined ART was initiated at the diagnosis of HIV infection, with a lamivudine, zidovudine and lopinavir/ritonavir; alongside treatment for PJ and aspergillosis was started with Trimethoprim/Sulfamethoxazole, Caspofungin and Ambisome.
+The microbiological assessment run to investigate possible coinfections proved positivity for CMV (31,446 copies/ml) and EBV (8542 copies/mL). Also, at the oral cavity inspection, the patient presented some vesicles positive for HSV. Acyclovir and Gancyclovir were then added to her therapeutic regimen. On the 51st day after she had started ART, she started presenting fever with a progressive worsening of clinical conditions: no other microbiological agents were isolated at the analysed samples (blood, stools and urine) and there was no improvement with broad-spectrum antibiotic therapy.
+Her laboratory assessment showed progressive trilinear cytopenia (lowest values: haemoglobin 7,7 g/dl, absolute neutrophil count 690 cells/mcl, platelet count 14.000 cells/mcl), progressive increase of C-reactive protein (up to 4,28 mg/dl), hyponatremia (serum sodium 129 mEq/l), hypoalbuminemia (3,1 g/dl) and hypofibrinogenemia (76 mg/dl ). Triglycerides were slightly increased (160 mg/dl) and ferritin levels were increased (up to > 12.000 ng/ml). Cardiac enzymes showed progressive elevation (high sensitivity troponin up to 40,9 pg/ml and proBNP 1548 pg/ml). At that time her HIV viral load was undetectable and CD4+ cell count was 35 cells/mcl (normal value 630–2110). We have always studied the expansion trend of expansion of CD4+ cell in relation to CD8+ cell, we also evaluating the expression of CD45 RA+RO− (naïve) and CD45RA−RO+ (memory) on the T cells: these analyses were compatible with the success of ART .
+In order to assess the differential diagnosis between HLH and IRIS, T-cell activation was investigated through the HLA-DR+ and CD38+ evaluation on CD4+ lymphocytes, which resulted always less than 1/microliter . In the suspicion of HLH and in order to assess other causes of cytopenia, a bone marrow aspirate and biopsy were performed: evidence of bone marrow cytopenia with prevalence of T-cells and macrophages with signs of phagocytosis was found. The immune activation markers, HLA-DR + and CD38+, were present on the CD8+ lymphocytes , making the diagnosis of HLH even more suggestive . We could not assess soluble IL2-R at that time in our hospital.
+Due to the presence of six diagnostic criteria the diagnosis of HLH was made: persistent fever > 38,5 °C, cytopenia involving more than two lineages, hypertriglyceridemia and hypofibrinogenemia, splenomegaly, hyperferritinemia and hemophagocytosis in bone marrow. Furthermore, Patient’s NK showed a lower degranulation after stimulation with K562 cells than healthy donor . However due to an ongoing treatment with systemic corticosteroids such assay can only be partially considered reliable for degranulation.
+Then a glucocorticoid therapy with three pulses of methylprednisolone (30 mg/kg/day) was started. The patient returned upyretic after the first pulse of methylprednisolone. After the three pulses, she was started on dexamethasone (10 mg/m2/day) as maintenance therapy. The laboratory assessment showed a progressive improve of the inflammatory parameters with worsening cytopenia and coagulopathy.
+In consideration of the insufficient response to glucocorticoid therapy, the treatment was implemented with intravenous interleukin-1 receptor antagonist (Anakinra, 100 mg twice a day = 14 mg/kg/day).
+After the treatment with anakinra was started, the patient’s clinical conditions and laboratory parameters showed a progressive improvement. Glucocorticoid therapy was progressively reduced and the interleukin-1 receptor antagonist was initially reduced to 7 mg/kg/dose (100 mg once per day) after 21 days of treatment. Anakinra was reduced by 25% after 5 days; after 3 days, the dose was reduced by 30% and eventually stopped after an additional 24 h of treatment. After the immunosuppressive therapy was stopped, the patient maintained good clinical condition and normalization of inflammatory markers.

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+A 57-year-old Caucasian woman was originally diagnosed with invasive ductal carcinoma in her right breast in February 2011 (ER-positive, PR-positive and HER2-negative). She was also diagnosed as carrying a mutation of BRCA 2. The patient underwent bilateral mastectomy and right-sided sentinel lymph node biopsy with 1 of 6 lymph nodes being found to be positive for metastasis. Unfortunately, she declined adjuvant chemotherapy and radiation recommended by her treating physicians, but only received adjuvant hormonal therapy with letrozole. In February 2012, she presented with renal failure and severe bony pain, and was found to have hypercalcemia with extensive osseous metastasis. CT-guided biopsy of one of the pelvic lesions revealed metastatic adenocarcinoma, consistent with her ER-positive primary breast cancer. The patient received aggressive hydration and denosumab for hypercalcemia. She also received radiation to her sacrum and bilateral sacroiliac joints to palliate her pain. The patient was enrolled in a clinical trial, receiving hormonal therapy with the combination of tamoxifen and metformin. Her monthly denosumab injection for bone metastasis was also continued. Unfortunately, her disease continued to progress, and she was found to have extensive lymphadenopathy involving the cervical, mediastinal and pelvic area. In January 2013, the patient was transferred to our center.
+As breast cancer in BRCA mutation carriers has been previously shown to respond to platinum-based chemotherapy , treatment with single-agent carboplatin (AUC 5) was initiated. Three days after starting carboplatin, the patient developed a severe headache and projectile vomiting. An MRI of her brain revealed a large, dura-based, contrast-enhancing extra-axial mass, approximately 3.3 × 4.3 cm in size, causing severe vasogenic edema in the right frontotemporal region, resulting in a significant midline shift. She was seen by a neurosurgeon, and an emergent decompressive craniotomy was performed. The pathology of the resected mass was consistent with metastatic breast cancer. Postoperative brain MRI showed marked improvement, but unfortunately it also demonstrated some small dura-based masses over the left cerebral hemispheres. The patient recovered quickly and subsequently received whole-brain radiation therapy to treat dural metastases. Despite the delay of systemic therapy for almost 2 months due to craniotomy and radiation, her extra-cranial disease responded well radiographically to the first dose of carboplatin, and thus this agent was continued until June 2013.
+At this time, PET-CT showed a progression of the disease in the cervical, mediastinal and retroperitoneal lymph nodes. Carboplatin was discontinued and PLD was initiated as a second-line chemotherapy. For the first cycle, a total of 85 mg (40 mg/m2) of liposomal doxorubicin in 250 ml of D5W (5% glucose solution) was prescribed with the same premedications used for the prior carboplatin. PLD was infused at a rate of 1 mg/min for the first 20 min. As no infusion-related adverse effects were observed, the rate was increased to 1.6 mg/min in order to complete the infusion over 1 hour according to our standard protocol. Twenty minutes later (approximately 50 mg PLD in total was given), the patient was noted to develop confusion. She had some tangential thoughts, started to make nonsensical comments to the people around her and began to tell stories from the past. The infusion was held and she was observed for 30 min, but her symptoms did not improve. An on-call physician was contacted to assess her. She was found to be alert and oriented and also able to answer questions appropriately. There were no neurological deficits. As the patient had an MRI earlier that day, no further imaging studies were performed. The infusion was discontinued due to the mental status change, and the patient was observed closely. Her symptoms persisted for 18 h and then resolved spontaneously. The patient's acute transient encephalopathy was deemed secondary to PLD. When she returned for the second cycle of chemotherapy, she was not rechallenged with PLD; instead, she was being administered conventional doxorubicin. This agent was tolerated well without any mental status change for another 5 months. Unfortunately, the patient developed a disease progression, requiring further palliative therapy with an eventual transfer to a hospice service, where she died 2 months later.

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+A 14-year-10-month-old Han Taiwanese boy was presented to the pediatric out-patient clinic with a 3-month history of swelling of the left clavicle. His family history included his father’s ankylosing spondylitis and his mother’s uveitis. Physical examination revealed mild tenderness. An erythematous immobile firm mass measuring approximately 2 × 2.5 cm was found overlying the left proximal clavicle, immediately lateral to the SCJ. Furthermore, he expressed pain when the clinician pressed down on his right hip and bilateral ankles. We did not perform modified Schober test in our patient because LBP was not obvious and he was a suspicious case of JIA.
+The patient had right hip arthritis and bilateral Achilles enthesitis. White blood cells count was 7.8 × 103 /μl, with 57% neutrophils and 32% lymphocytes (normal 3.9–10.6 × 103 /μl; neutrophils 42–74%; lymphocytes 20–56%). Biological inflammatory syndrome was observed with elevated erythrocyte sedimentation rate (33 mm/hr.; normal < 17 mm/hr) and C-reactive protein (22.6 mg/l; normal < 5 mg/L). Human leucocyte antigen (HLA) typing was positive for B27. Meanwhile, uric acid, rheumatoid factor, complements C3 and C4, anti-nuclear antibody, and anti-double-strand DNA were all normal. Furthermore, his renal and liver function, urine analysis, and muscle enzyme tests results were all normal.
+The patient was initially treated empirically with oral augmentin (amoxicillin trihydrate + clavulanate potassium) and cefixime for 1 week, but did not respond favorably to the antibacterial treatment. We then treated the patient with naproxen (500 mg/day), a non-steroidal anti-inflammatory agent, and followed up. He claimed to have no history of trauma, fever, weight loss, loss of appetite, or intravenous drug abuse. We observed no skin lesions, such as acne or pustulosis palmaris et plantaris. Ultrasonography examination revealed a heterogeneous hypoechoic mass in the left SCJ (2 × 2.5 cm; Fig. ), and he was hospitalized to our pediatric ward. A computed tomography (CT) scan of the chest further indicated a turbid collection at the left SCJ . Bone window testing demonstrated irregular bone surfaces on the SCJ due to erosion, thus suggesting arthritis. Bone scintigraphy (MDP Tc-99 m) showed a focal area of increased uptake in the trochanteric region of the right proximal femur .
+We performed a left SCJ arthrotomy on the patient, in which the clavicular head was excised and the left SCJ was debrided. Due to suspicion of malignant infiltration, we performed a histopathological examination, but no malignant cells were observed. A histologic examination of the tissue exposed acute and chronic inflammatory cell infiltration. Aspirated joint fluid cultures were negative; therefore, diagnosis of infection could be excluded.
+In view of the historical facts and clinico-radiological correlation, including CT findings, we made a working diagnosis of JIA of the medial end of the left clavicle and initiated JIA therapy. The onset of arthritis and enthesitis after 6 years of age in a boy with HLA-B27 and a family history allowed him to meet the strict diagnostic criteria of the JIA subtype enthesitis-related arthritis. Given that SCJ disorders are rare, there is a probability that many clinicians do not have substantial training or experience injecting the SCJ with corticosteroids . This lack of experience, combined with a complex and frequently distorted SCJ anatomy, may result in poor injection accuracy. After surgical debridement, we prescribed a naproxen, sulfasalazine 1000 mg/day (4 months before prednisolone), and prednisolone 0.6 mg/kg/day combination for 4 weeks, followed by naproxen + oral methotrexate (MTX) 10 mg/m2/week + prednisolone for the next 3.5 months. Due to persistent high disease activity under salfasalazine, an alternate immunomodulator therapy MTX was selected. Etanercept has been indicated in the treatment of refractory JIA . He achieved full remission from the JIA with etanercept 25 mg twice a week within 4 weeks , and tolerated etanercept with good adherence. The patient reported complete cessation of pain and no longer needed analgesics, MTX, or prednisolone after 3 months. The aim of our treatment was to achieve maximum effectiveness and reduce the dosage of concomitant therapy because concomitant therapy substantially elevates the risk of side effects. A prospective study also revealed the effectiveness of etanercept therapy . Furthermore, 38.3% of patients with JIA treated with etanercept in combination with any medication could completely discontinue these concomitant drugs. Our patient continued the etanercept treatment 25 mg twice a week for at least 2 years to maintain a stable condition without any relapse during the outpatient follow-up. We repeated the ultrasound of the left clavicle, which revealed complete healing of the initial findings after 13 months of etanercept treatment.

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+A female aged two years and 11 months was brought to the ED by ambulance for a generalized tonic-clonic first-time seizure. The patient had otherwise been in her usual state of health with no recent febrile illnesses. Her mother noted that the patient had an acute episode of unresponsiveness with a blank stare and called 9–1–1. Upon emergency medical services arrival, the child developed generalized tonic-clonic seizure activity. She received a weight-based dose of 1.7 milligrams (mg) of midazolam en route to the hospital, which resolved the movements. Upon arrival to the hospital, the child was no longer actively seizing and appeared to be sleepy, consistent with a postictal state. The estimated total seizure length was approximately two minutes. The patient had no notable past medical history. Family history was notable for Graves disease in the patient’s mother.
+Vital signs on arrival were as follows: temperature 37.9° Celsius measured rectally; heart rate 188 beats per minute; respiratory rate 27 breaths per minute; and blood pressure 125/62 millimeters of mercury. Her height was 103 centimeters, 99th percentile, and her weight was 16 kilograms, 87th percentile. Her physical exam was notable for exophthalmos and small goiter but was otherwise unremarkable, including a non-focal neurological examination. Of note, her tachycardia and widened pulse pressure persisted after resolution of her seizure and postictal period.
+Her electrocardiogram was notable for left ventricular hypertrophy and sinus tachycardia but had no evidence of ischemia or abnormal intervals. Her laboratory evaluation was notable for a normal fingerstick blood glucose, elevated alkaline phosphatase with mild transaminitis, mild microcytic anemia, undetectably low thyroid-stimulating hormone (TSH) and unmeasurably high free thyroxine.
+The pediatric endocrinologist was consulted who, based on the patient’s weight, recommended starting atenolol 12.5 mg, methimazole 7.5 mg, and 1 milliliter (mL) potassium iodide-iodine (Lugol’s saturated solution of potassium iodide {SSKI}) solution (to be given one hour after atenolol and methimazole). After treatment was initiated, the patient’s heart rate improved to the 160s, and she was admitted to the pediatric intensive care unit (PICU). While in the PICU, further levels were obtained and were notable for unmeasurably high free triiodothyronine (T3), unmeasurably high total T3, and elevated thyroid-stimulating immunoglobulins (328% baseline). While in the PICU, the patient was continued on atenolol, methimazole, Lugol’s solution, and hydrocortisone 50 mg every eight hours. She was in the PICU for approximately 24 hours and then transferred to the medical ward.
+The patient remained in the hospital for one week and was discharged home with methimazole, propranolol, and SSKI. She was followed in endocrinology clinic multiple times over the next few months. The SSKI was eventually stopped, and propranolol was changed to atenolol. She had trouble with compliance with medications as the formulations available for atenolol are not child friendly. She was referred to another hospital system for a total thyroidectomy given inability to tolerate swallowing pills. She has not had recurrent seizure activity since initiating thyroid treatment.

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+A 58-year-old male smoker with known heart failure with preserved ejection fraction, renal insufficiency, hypertension, and obesity presented with a two-to-three month history of dyspnea, lower extremity edema, and intermittent angina. He was admitted to a referring hospital with a three-to-four-day history of persistent back pain, worsening exertional dyspnea, and orthopnea. He had mild troponinemia and an elevated B-type natriuretic peptide. Chest plain-film radiography demonstrated cardiomegaly, vascular congestion, and pleural effusion. Electrocardiogram showed new-onset atrial fibrillation with rapid ventricular response, and he was started on apixaban. He was worked up for an acute-on-chronic heart failure exacerbation and underwent a myocardial perfusion imaging showing a large anterior septal and apical region scar without reversibility. This was consistent with a former myocardial infarction in the left anterior descending (LAD) artery territory, and the patient corroborated that years ago he had an episode of severe chest pain radiating to the right shoulder which left him bedridden. A transesophageal echocardiogram for cardioversion was performed, which diagnosed an acute TAAD and demonstrated an ejection fraction of 30%. He was initiated on anti-impulse control and promptly transferred to our facility.
+Given that the patient was approximately six days post-dissection, without malperfusion, contained rupture, pericardial or pleural effusions, with a well-controlled blood pressure on anti-impulse therapy, and had received five days of anticoagulation, the decision to delay definitive repair was made in order to let the apixaban metabolize and decrease the bleeding risk. While plausible that his heart failure and scar were related to coronary malperfusion secondary to his TAAD, emergent revascularization would have had limited benefit to the infarcted tissue considering the time from infarct. Given preserved GFR and no clinical renal malperfusion, CCTA was performed to assess the need for concomitant revascularization with a moderately obstructive proximal LAD lesion and complete occlusion of the mid-LAD after take-off of a large diagonal branch consistent with known prior infarction , occlusive disease of the left circumflex artery as well as diagonal and obtuse marginal branches, and nonobstructive disease in the right coronary artery. Additionally, the CCTA demonstrated the dissection flap extending proximally to the sinotubular junction (STJ) . Left heart catheterization was not performed, given concern for wire and catheter manipulation within a fresh dissection including navigating a multi-fenestrated flap.
+Four days after his last apixaban dose, the patient was taken to the operating room for an ascending aorta hemiarch replacement with aortic valve resuspension, two-vessel CABG, and left atrial appendage clipping. Following sternotomy and pericardiotomy, the left internal mammary artery and saphenous vein graft conduits were harvested, and the patient was heparinized. Cardiopulmonary bypass (CPB) was instituted with central arterial and dual venous cannulation and left ventricular vent. The heart was arrested, and the patient was cooled to 18 °C. The aorta was transected at the STJ, where a circumferential tear was noted at the level of the STJ. The aortic valve was resuspended, and the intimomedial tear was plicated circumferentially to the true lumen.
+After deep hypothermic circulatory arrest and the initiation of retrograde cerebral perfusion, as is routinely performed by the aortic surgeon at our institution, the diseased segment of the aorta was resected from the base of the innominate artery to the inner curvature of the proximal descending thoracic aorta. A 28-mm Gelweave graft was beveled and anastomosed to the native aorta to complete the distal anastomosis. An aortic cannula was placed into the side-arm for resumption of CPB. The proximal ascending aorta was resected to the level of the STJ, and the graft was sewn end-to-end to the STJ. The left atrial appendage was clipped with a 45 mm AtriClip (Atricure, West Chester, OH). The saphenous vein graft was anastomosed to the first obtuse marginal, and the left internal mammary artery was anastomosed to the LAD. The proximal vein graft was then anastomosed to the aortic graft. The patient was rewarmed, weaned off CPB, and chest closure was performed. There were no complications, and the patient was transported to the cardiovascular intensive care unit in stable condition.
+Postoperatively, the patient was quickly extubated and weaned from vasopressors. The post-operative course was complicated by delirium and atrial fibrillation requiring direct current cardioversion. The patient was discharged home on post-op day 8; however, required readmission for volume overload which rapidly improved with diuresis and blood pressure control. Follow-up appointment ten days after readmission showed resolution of symptoms and normalization of blood pressure.

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+A 20-year-old healthy Japanese woman had a 2-day history of high fever and consulted the emergency room in Kawasaki Medical School. There was no significant past medical history except for mycoplasma pneumonia at the ages of 1 and 18. She had sex for the first time 6 months earlier. She had erythema in the pharynx and lymph node enlargement at the posterior cervical and left axillary region, but there were no findings on physical and neurological examination. Her chest sounds were clear, and she had no cough. The tips of the liver and spleen were not palpable. Her vital signs were as follows: heart rate 108 beats/minute, blood pressure 101/58 mmHg, and temperature 38.9°C. Table shows the laboratory data on admission. Leukocytopenia and increased C-reactive protein (CRP) were observed: white blood cell (WBC) count, 1710 /μL (neutrophils 76.0%; monocytes 5.0%; lymphocytes 18.0%; atypical lymphocytes 1.0%); CRP, 3.92 mg/dl. She had mild liver dysfunction: γ-GTP, 78 U/L; alkaline phosphatase (ALP), 276 U/L; aspartate aminotransferase (AST), 30 U/L; alanine aminotransferase (ALT), 28 U/L. Her chest X-ray and computed tomography (CT) on admission revealed no remarkable change including pneumonia, and her abdominal CT revealed slight hepatomegaly and splenomegaly. Neither influenza A nor B antigens were detected, and Mycoplasma pneumonia antigen was not detected. Her hepatitis B surface antigen and hepatitis C antibody tests were negative. Human immunodeficiency virus (HIV) antigen/antibody test was negative (cutoff index <0.3). Her Treponema pallidum hemagglutination (TPHA) was negative. Pathogenic bacteria were not detected, although small amounts of Corynebacterium sp. and Gram-positive cocci were detected in urine culture. We started antibiotic therapy (500 mg/day of levofloxacin), because we failed to rule out a bacterial infection due to an elevated CRP level. She was suspected of having a bladder infection by her previous doctor, and in fact she had bacteriuria. Her virus antibodies were as follows: EBV (EBV) anti-viral capsid antigen (VCA) immunoglobulin M (IgM) antibody, 0.2 (−) (fluorescent antibody method [FA], SRL Inc., Tokyo); EBV anti-VCA immunoglobulin G (IgG) antibody, 0.2 (−) (FA, SRL Inc., Tokyo); EBV anti-EBV nuclear antigen (EBNA) Immunoglobulin (Ig) G antibody, 0.1 (−) (FA, SRL Inc., Tokyo); CMV IgM antibody, 3.89 (+) (enzyme immunoassay (EIA), SRL Inc., Tokyo); CMV IgG antibody, 24.0 (+) (EIA, SRL Inc., Tokyo). Based on these findings, we finally arrived at a diagnosis of primary CMV infection. Four days later, her temperature was reduced to under 37°C, and about 1 week later, her clinical symptoms disappeared and laboratory data including leukocytopenia and liver dysfunction were improved . She was discharged 10 days after admission. She did not experience another abnormal physical condition after discharge, but we continued to observe her condition on an outpatient basis. Therefore, we checked her virus antibodies. Her CMV IgM antibody became negative about 3 months later, and we confirmed that her CMV infection was a prior infection pattern.
+About 5 months later, she again experienced fever and lymph node enlargement at the posterior cervical region and visited our emergency room. She had no symptoms other than high fever and lymph node enlargement, and there were no findings on physical or neurological examination. Her vital signs were as follows: heart rate 85 beats/minute, blood pressure 98/56 mmHg, and temperature 38.9°C. Table shows the laboratory data at that time. Atypical lymphocytes were detected and the CRP level was slightly increased: WBC count, 6860/μL (neutrophils 19.0%; monocytes 6.0%; lymphocytes 73.0%; atypical lymphocytes 2.0%); CRP, 0.57 mg/dl. Furthermore, she had severe liver dysfunction: γ-GTP, 291 U/L; ALP, 1060 U/L; AST, 379 U/L; ALT 381 U/L. We thought that it would be better to hospitalize her and start drip infusion of monoammonium glycyrrhizinate glycine for severe liver dysfunction, but she did not agree to the hospitalization. Therefore, instead we started 60 mL/day of monoammonium glycyrrhizinate glycine on an outpatient basis. At that time, we suspected viral infection and thus we did not administer antibiotics. She visited our office for drip infusion of monoammonium glycyrrhizinate glycine every day, and about 5 days later the high fever disappeared. About 1 week later, her clinical symptoms and laboratory data were improved and we stopped the therapy with monoammonium glycyrrhizinate glycine. At that time, her EBV antibodies were as follows: EBV anti-VCA IgM antibody, 1.7 (+); EBV anti-VCA IgG antibody, 5.7 (+); EBV anti-EBNA IgG antibody, 0.1 (−). Therefore, we finally diagnosed her condition as primary EBV infection.
+In addition, we checked the antibodies for both CMV and EBV infection several times in this patient, and Table shows the time course for these antibodies. Such time course clearly shows that this patient had primary EBV infection shortly after primary CMV infection.

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+A 54-year-old woman applied to an out medical center with the complaints of weight loss, jaundice, and pain in the epigastric and right upper quadrant of the abdomen. Computer tomography (CT) scan revealed a mass with a size of 13 mm in the ampullary region consistent with periampullary tumor .
+The patient underwent an endoscopic retrograde cholangiopancreatography (ERCP) procedure which revealed significant dilatation in the middle and distal segments of the common bile duct together with an abrupt ending in the distal segment of the common bile duct. A plastic stent was inserted to the common bile duct via ERCP, and multiple biopsies were taken from the periampullary region. The histopathological result was squamous cell carcinoma. The patient was referred to our hospital for further investigations.
+The physical examination of the patient was unremarkable. Laboratory tests revealed elevated ALP (200 U/l; normal range, 30–120 U/l) and GGT (181 U/l; normal range, 0–38 U/l) levels. Billirubin level was within the normal limits. The serum level of the tumor markers of CEA and CA-125 were 2.41 and 14.23 ng/ml (normal range, 0–35 U/ml), respectively. CA-19-9 was 47.47 U/ml (normal range, 0–27 U/ml).
+Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) examinations demonstrated a T1 hypointense lesion with a size of 43 × 43 mm in the periampullary region occluding the distal segment of the common bile duct .
+Because of the low incidence of squamous cell carcinoma in the periampullary region, primary malignancies of other organs were also explored. Positron emission tomography (PET CT) revealed FDG (fluorodeoxy-glucose) uptake only in the periampullary region of the pancreas .
+The patient underwent an explorative laparotomy. Upon confirmation of neither lymphovascular invasion nor solid organ metastases, we decided to proceed with Whipple’s procedure. The postoperative course of the patient was uneventful. The patient was discharged, and adjuvant chemotherapy was recommended.
+The histopathological examination demonstrated a moderately differentiated squamous cell carcinoma of periampullary tumor with a size of 3.7 × 3.1 × 2.1 cm, invading the duodenum and pancreas .
+Multiple serial sections of the tumor specimen failed to detect any adenomatous component. Although there were no signs of lymphovascular invasion, perineural invasion was present in the samples. Upon these findings, the tumor was staged as pT3N0M0.
+Immunohistochemical analysis showed that tumor cells were positive for p63 and high molecular-weight cytokeratin (HMWCK). To exclude other possible origins of primary squamous cell carcinoma, additional immunohistochemical staining analyses were performed. Tumor cells were negative for synaptophysin and chromogranin, ruling out neuroendocrine origin. Similarly, thyroid transcription factor-1 (TTF1) and CK19 were negative, excluding primary squamous cell cancer of the lung and cholangiocarcinoma. Photomicrographs of the resected specimen are shown in Figs. , , , and .
+Distal common bile duct, ampullary, and duodenal cancers are less common than pancreatic cancer . The most common histopathological type of tumor in the ampulla of Vater is adenocarcinoma. Other primary tumors that have been reported in the ampulla of Vater are squamous cell carcinoma, neuroendocrine carcinoma [, ], and signet cell carcinoma [, ]. There are only four case reports with primary squamous cell carcinoma [–] and one case report with co-existent primary squamous cell carcinoma and adenocarcinoma in the ampulla of Vater .
+Because of the rarity of primary squamous cell carcinoma in the ampulla of Vater, other primary squamous cell malignancies must be excluded in all the patients. Buyukcelık et al. reported a case of squamous cell carcinoma of the larynx , and Sreenarasimhaiah and Hoang reported a case of esophageal squamous cell carcinoma metastasized to the ampulla of Vater . Therefore, in the present case, extensive imaging studies with CT, MRI, and PET CT were performed to rule out other possible origins.
+There are also few case reports of neuroendocrine carcinoma of the ampulla of Vater with squamous cell components [, ]. Sugawara et al. reported a case of small cell neuroendocrine carcinoma of the ampulla of Vater with foci of squamous differentiation. In their case, immunohistochemical analyses including synaptophysin, chromogranin, neuron-specific enolase (NSE), and Leu-7 were performed to identify neuroendocrine cells, and squamous cell carcinoma components were weakly positive for NSE . In our case, after revealing squamous cell carcinoma by HMWCK and p63, additional staining analyses with synaptophysin and chromogranin were performed to exclude a neuroendocrine component.
+The ampulla of Vater is normally devoid of squamous cells. Although the malignant transformation of ectopic squamous epithelium, the differentiation of the duodenal pluripotent stem cells , and squamous metaplasia secondary to chronic inflammation are all among the proposed mechanisms, the exact pathogenesis of primary squamous cell carcinoma in the ampulla of Vater is still unknown.
+Treatment options for periampullary tumors are surgical resection, operative or nonoperative palliation, and neoadjuvant or adjuvant therapies regardless of histopathology of tumor. Surgical resection which was also the choice of treatment in our case is the major treatment method for periampullary tumors. In another case of primary squamous cell carcinoma of the ampulla of Vater, the patient underwent curative resection without any further treatment and overall survival was 5 months after surgery was reported .
+With limited experience of primary squamous cell carcinoma in the ampulla of Vater, long-term survival rates are not well known. On the other hand, pure squamous cell carcinomas of the biliary tract are associated with decreased survival rates compared to adenocarcinomas and adenosquamous carcinomas [, ]. Therefore, we suggest that primary squamous cell carcinomas of the ampulla of Vater should be considered as more aggressive than adenocarcinomas, and adjuvant chemotherapy should be recommended as another treatment option.
+Different adjuvant chemotherapy regimens have been investigated for metastatic and advanced ampullary adenocarcinomas in recent years. Shoji et al. reported a retrospective study comparing 5-fluorouracil-based regimens with gemcitabine-based regimens for median progression-free survival and median overall survival time in patients with advanced ampullary adenocarcinomas . Median overall survival time was found to be longer with gemcitabine-based regimens. A phase II study evaluated the efficacy of a combination regimen of capecitabine with oxaliplatin in advanced ampullary and small bowel adenocarcinomas . The response rate for this regimen was lower in the ampullary adenocarcinomas compared to small bowel adenocarcinomas. This difference was suggested to be related with the heterogenous epithelium of origin and the molecular heterogeneity for ampullary tumors. In many centers, the general approach to periampullary cancers has been to use gemcitabine-based regimens for pancreatic and biliary carcinomas and fluorouracil-based regimens for duodenal and ampullary carcinomas which is also the choice of treatment in our center.

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+An 83-year-old man with psoriatic arthritis presented with persistent and progressive gait instability, impaired motor dexterity, and hand numbness for 2 months. He underwent C3-C5 laminoplasty for myelopathy with multilevel cervical stenosis and a L2-L4 laminectomy for radiculopathy with lumbar stenosis 4 and 3 years prior, respectively.
+The patient spent 5 months in a wheelchair prior to consultation due to multiple falls. Examination revealed 4/5 bilateral strength in his deltoids, shoulder external/internal rotators, wrist flexors/extensors, abductor/flexor pollicis brevis, finger extensors, and opponens. He had full biceps/triceps strength bilaterally with intrinsic wasting in his dominant left-hand; left forearm and upper arm showed atrophy. Hand and finger numbness noted bilaterally with positive Hoffmann’s signs. His brachioradialis reflex was inverted bilaterally and biceps/triceps reflexes were brisk (3+). Meniscal and Achilles reflexes could not be elicited and clonus was absent. Babinski signs were equivocal. Light touch sensation was present bilaterally from L1-S1. Lower extremity strength was recorded bilaterally for his gastrocnemius (5/5), quadriceps (5/5), iliopsoas (4/5), tibialis anterior (4/5), and extensor hallucis longus (3/5). The patient’s pre-operative modified Japanese Orthopedic Association (mJOA) scale score was a 9. Cervical spine magnetic resonance imaging revealed an eccentric right pannus posterior to his C1 arch causing cord compression to a 6–7 mm space. A ponticulus posticus was absent and the C1 lateral mass had sufficient height for fusion. Vertebral arteries entered at C6 with normal codominant courses. The subaxial spine was open from prior laminoplasty .
+Given the presentation, surgical intervention was indicated. A microsurgical C1 laminoplasty and decompression with posterior C1–C2 atlantoaxial fusion (AAF) was performed (Pre-operative Planning-). The patient was placed in the prone position with his head elevated. A midline incision was made from the skull base down to the C2 spinous process with dissection at the midline raphae sparing the extensor muscles. The C1 lamina was exposed and dissected using curettes and Cobb elevators protecting the vertebral arteries superior to the C1 lamina. Next, a translaminar C1 lateral mass screw was drilled to 28 mm (2 mm increments) and a ball-tip probe was used to ensure the lateral mass walls and floors were not violated; a 3.5 mm screw was placed. This process was repeated contralaterally to obtain lateral mass fixation and placement was confirmed . The C2 pars were then dissected to the C1–C2 joint. The joint was decorticated bilaterally and demineralized bone matrix was placed into the space to promote facet fusion. The pedicles were then cannulated bilaterally and two 3.5 mm screws (26 mm) were placed into the C2 pedicles. Proper screw placement was confirmed intraoperatively and postoperatively (-).
+Attention was, then, turned to decompressing the spinal cord through laminoplasty at the C1 arch; to visualize this portion of the procedure see additional file 1: Movie 1. Bilateral hinges were made on either side of the C1 lamina while protecting the vertebral arteries. A midline defect was made in the lamina and both sides of the lamina were hinged open. A custom allograft bone block was placed to hold the hinges open which was secured with suturing; both sutures were tied down on either side through a small bone tunnel made on both sides of the hinge. A 3.5 mm titanium rod was then placed across the lateral mass with a pedicle screw between C1 and C2 bilaterally. Set screws were placed, completing the C1–C2 fixation. The remaining marginal C1 lamina and the C2 spinous process, lamina, and pars were decorticated. A combination of autograft, BMP, and demineralized bone matrix were placed across the decorticated bone.

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+The patient is a 57 years old never smoker female who initially received a clinical diagnosis of pneumonia. As symptoms failed to resolve with antimicrobials, a subsequent CT scan of the chest revealed a partially cavitary mass in the right lower lung lobe. This imaging finding was followed with CT scans for two years at an outside facility showing slow growth. Eventually, a CT guided biopsy revealed mucinous adenocarcinoma of the lung with predominant lepidic pattern. A PET CT and MRI of the brain at the time did not show any other disease sites and she received a right lower lobectomy which confirmed the diagnosis and the stage as pT2bpN0M0 (IIA). Following surgery, the patient received adjuvant chemotherapy with carboplatin and paclitaxel for four cycles.
+She carried a diagnosis of idiopathic autoimmune hearing loss, that had been successfully treated with mycophenolate mofetil. Her family history included lung cancer in both of her parents and her sister, all smoking related, as well as breast cancer in her maternal aunt.
+A year after her surgery, disease recurrence was documented on imaging in the right pleura. The same neoplasm was identified upon pathology review of a right pleural biopsy and she received local radiation therapy as salvage treatment. Follow up imaging in 3 months identified new lung nodules and the patient was referred to our institution. Figure shows the metabolically avid right pleural thickening that was radiated and one of the lung nodules at the time of disease recurrence following radiation. Molecular analysis of the original lobectomy material with next generation sequencing revealed a BRAF V600E mutation. Subsequently, she was initiated on combination of dabrafenib and trametinib treatment in the context of a clinical trial.
+While on the experimental drugs for two weeks, she experienced significant fatigue, persistent fevers up to 38 °C and generalized myalgias necessitating holding dabrafenib and trametinib. Nevertheless, symptoms persisted and infectious and rheumatology workups were initiated at the time. In addition, three weeks after stopping dabrafenib and trametinib, she was admitted for left eye vision loss and acute kidney injury. An ophthalmology exam with eye dilation indicated left central artery occlusion. Additional data from her history, exam and laboratory evaluation revealed the following: a history of recurrent sinusitis, acute onset visual loss and renal insufficiency during the current admission, and evidence of a saddle-nose deformity on exam which the patient believed was present for several years prior. She subsequently received a unifying diagnosis of granulomatosis with polyangiitis (GPA) on the basis of these findings as well as high-titer characteristic antibodies (p-ANCA titer 1:640, myeloperoxidase antibody > 30). Other lab results including rheumatology workup are shown in Table . Due to acute vision loss, giant cell arteritis was considered and a temporal artery biopsy was obtained and found negative. Her acute vision loss and creatinine elevation were thought secondary to retinal and renal vascular involvement by GPA. Nevertheless, review of the pleural biopsy and the resection specimen by pathology in retrospect, did not reveal any granulomatous change or vasculitis. She was initiated on rituximab, corticosteroids were successfully tapered, and further anti-neoplastic drugs were held. Lung cancer was followed clinically with scans.
+A year after diagnosis of GPA, a growing lung nodule was proven with biopsy to be malignant and was treated with SBRT. To-date, three years following GPA diagnosis and lung cancer recurrence, both conditions remain controlled without any further systemic therapy for lung cancer and while she continues on rituximab for GPA.

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+A 58-year-old woman from Grenada presented with a chief complaint of nausea, vomiting, and jaundice after her primary care physician (PCP) discovered elevated LFTs on routine labs.
+The patient had a 10-day history of fatigue, nausea, and intermittent non-bilious, non-bloody emesis. Four to five days before admission, she noticed that her eyes began to turn yellow, prompting her to visit her PCP. These symptoms were also associated with decreased appetite, weight loss of 10 lbs, and dark urine. She stated that she did not take her statin medication regularly, but she reported drinking a “green juice” for the past 3 d before admission. It consisted of watercress, garlic, and ginger. The patient denied abdominal pain, diarrhea, constipation, other changes in diet, or other use of supplements.
+The patient’s past medical history was significant for chronic hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. There was no history of excessive alcohol use.
+The patient denied any family history of liver disease or autoimmune disorders.
+On admission, the patient was hypertensive (blood pressure 168/98 mmHg), tachycardic (heart rate 77 beats per min), and afebrile (37.1 C F). She was alert and oriented. No asterixis was noted in her upper extremities. She had mild bilateral scleral icterus. An abdominal exam revealed an overweight, non-distended, non-tender abdomen with no masses, no hepatomegaly, no flank tenderness, and no fluid wave.
+The laboratory work-up showed: Serum alanine aminotransferase (ALT) 2500 U/L (reference range 10-49 U/L), serum aspartate aminotransferase (AST) 3159 U/L (reference range 8-34 U/L), alkaline phosphatase 714 U/L (reference range 46-116 U/L), serum lipase 61 U/L (reference range 12-53 U/L), total bilirubin 6.4 mg/dL (reference range 0.3-1.2 mg/dL), direct bilirubin 4.4 mg/dL (reference range 0.1-0.3 mg/dL), prothrombin time 12.7 s, and INR 1.07. Table portrays a trend from admission to discharge of pertinent values. Serological markers for hepatotropic viruses such as A, B, C, and E were all negative. She had no clinical signs of infection. Further infective work-up revealed negative serology for cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 & 2, and human immunodeficiency virus. All tested autoantibodies, including antinuclear antibody (ANA), smooth muscle antibody, anti-mitochondrial antibody, liver soluble antibody, and anti-liver kidney microsome 1 antibody, were negative . The patient was tested for Wilson’s disease, for which her ceruloplasmin levels came back as slightly elevated at 62 mg/dL. We attributed this to her current inflammatory state.
+An abdominal ultrasound with Doppler showed no significant parenchymal abnormalities with normal arterial and venous Doppler of the liver and spleen. The gallbladder was contracted with no definite evidence of cholecystitis . A follow-up magnetic resonance cholangiopancreatography (MRCP) with and without contrast was then conducted to rule out biliary causes of acute hepatitis . The MRCP showed a biliary system with no filling defects, stones, or ductal dilation. All other organs were within normal limits.
+The patient underwent a liver biopsy, which showed moderate to severe active hepatitis with focal confluent necrosis, consisting mostly of lymphocytes with few eosinophils, plasma cells, and neutrophils with scattered acidophil bodies. Her biopsy was negative for cholestasis, granulomas, or malignancy . Differentials from the pathology report include drug/toxin/herbal/supplement-induced injury and infection (including viral hepatitis E), and less likely immune-mediated injury given negative autoimmune workup (negative ANA, anti-smooth muscle antibody, anti-mitochondrial antibody, anti-liver kidney microsome-1 antibody, and anti-soluble liver antigen antibody).

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+A 63-year-old female patient with a medical history of type 2 diabetes, hypertension, and hyperlipidemia visited our hospital complaining of chest, waist, and back pain radiating to both groin for 15 days. It aggravated on bending over, but there was on obvious cause. No nausea, vomiting, diarrhea, or discomfort, such as numbness or fatigue of the lower limbs, was reported. The initial treatment administered was for back pain. After admission, the patient developed a fever and abdominal pain. Peripheral leukocyte count was 12.92×109/L(normal range, 3.5–9.5×109/L) with 11.51×109/L neutrophils (normal range, 1.8–6.3×109/L) and an elevated C-reactive protein of 101.59 mg/L, and Erythrocyte sedimentation rate was 120mm/hour. The computed tomography angiography (CTA) examination revealed a thoracic aortic pseudoaneurysm. Abdominal CTA confirmed the formation of a pseudoaneurysm in the aorta, approximately in the T10-T11 vertebral body plane .
+Blood was drawn during fever, gram-negative bacilli were Gram-stained, and Salmonella paratyphi A was cultured. Susceptibility testing by the minimum inhibitory concentration (MIC) gradient method revealed that the isolate was susceptible to piperacillin/Tazobactam, Imipenem, ampicillin, and gentamicin based on the Antimicrobial Susceptibility Testing criteria (piperacillin/Tazobactam MIC≤8ug/mL; Imipenem MIC≤1ug/mL; Ampicillin MIC≤2ug/mL). Furthermore, susceptibility testing by Kirby-Bauer drug-sensitivity test showed that the isolate was susceptible to Cefotaxime, Ceftriaxone, Ciprofloxacin, and Levofloxacin based on the Antimicrobial Susceptibility Testing criteria (Cefotaxime inhibition zone diameter = 28mm; Ceftriaxone inhibition zone diameter = 30mm; Ciprofloxacin inhibition zone diameter = 26mm; Levofloxacin inhibition zone diameter = 28mm).
+The endovascular stent-graft treatment was performed immediately. After inducing local anesthesia, the left femoral artery was punctured using the Seldinger’s method. 5F arterial sheath was implanted, and a pigtail catheter was inserted in descending aorta for aortography, which showed signs of a thoracic aortic pseudoaneurysm. An oval-shaped soft tissue-density mass measuring 2.5×2.1 cm was detected in the descending thoracic aorta at the level of the T10-T11 vertebral body. The right femoral artery was then exposed, and Ultra Stiff Wire (ASAHI, Japan) was put in. After that Hercules™ Sterile Thoracic Stent-Graft System (Microport, Shanghai) was put in along Wire and then released to cover pseudoaneurysm. The procedure lasted 45 min. Aortography was conducted again, which revealed that the pseudoaneurysm had almost disappeared without leakage.
+Moreover, piperacillin sulbactam sodium 5 g was administered once every 8 h intravenously for 14 days in combination with levofloxacin 0.4 g once a day intravenously for 7 days. Abdominal pain was relieved, and the body temperature returned to normal. The treatment was well tolerated by the patient, and she was discharged on postoperative Day 10.
+At the 2-month follow-up, the patient was asymptomatic, and CTA confirmed the total exclusion of the pseudoaneurysm with no signs of endoleaks . After discussion with the institutional research office, formal ethical approval was deemed unnecessary if written informed consent was obtained from the patient. Verbal and written informed consent were obtained from the patient for publishing the report.

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+A 70-year-old Japanese man with melena that began five days before admission was admitted to our hospital. He complained of abdominal discomfort and epigastralgia. Five years before, he had undergone a right upper lobectomy for lung cancer (T1b N0 M0 Stage IA). Physical examination revealed no abnormal findings associated with the abdomen except a surgical scar on the right side of his chest. Evaluation of laboratory data on admission revealed that his hemoglobin level was 7.0 g/dL and hematocrit value was 23.1%. Upper gastrointestinal endoscopy revealed a distinctly protruding lesion (diameter: 5 cm) at the lesser curvature of the middle third of the gastric body . The surface of the tumor bled easily on contact with the endoscope. Microscopic examination of hematoxylin and eosin (H&E)-stained biopsy specimens of the lesion revealed sheets of spindle cells. Immunohistochemical studies showed that the tumor cells were positive for S-100 and negative for c-kit, CD34, and smooth muscle actin. The MIB-1 index was 48.5%. Based on these findings, the tumor was diagnosed as a gastric malignant schwannoma. Abdominal computed tomography (CT) revealed a thickened posterior wall of the gastric body . There was no evidence of lymph node swelling surrounding the stomach or metastatic liver tumors.
+He underwent a distal gastrectomy with regional lymph node dissection. Macroscopically, the elevated lesion was approximately 6 × 5 cm in diameter and located at the lesser curvature of the gastric body . The covering mucosa was ulcerated. The tumor was located mainly in the proper muscle layer. There was no lymph node involvement and the surgical margin was negative for tumor cells. Microscopic examination of the resected and H&E-stained specimens showed a spindle cell neoplasm arranged in a palisade manner that was consistent with a schwannoma . Mitosis was scattered with 10 mitoses per 50 high-power fields. Immunohistochemistry revealed that the tumor cells were positive for S-100 protein and negative for c-kit and smooth muscle actin . These histopathological and immunohistochemical findings are consistent with a gastric malignant schwannoma.
+His postoperative course was uneventful and he was discharged from our hospital on day 12 after surgery. However, abdominal CT performed three months after surgery revealed multiple liver metastases and ascites .. He died five months after surgery without undergoing any additional treatment.

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+A 61-year-old lady with a history of rheumatoid arthritis since 1986 was referred to the orthopaedic surgical clinic by her treating rheumatologist. She had a total shoulder replacement implanted 11 years previously at a different hospital trust and did not have any delayed healing or episodes of infection post-operatively. On attendance at the orthopaedic clinic, she reported a 1 month history of pain and swelling in the shoulder, which had progressed to an intermittently discharging sinus over the posterior aspect of her shoulder. She had not recently undergone any dental intervention or other surgical procedures, and had otherwise been systemically well throughout this period. X-rays revealed elevation of the humeral head consistent with rotator cuff failure. The replacement head had also migrated medially due to failure of the supporting glenoid bone and there was osteolysis around the humeral implant (.).
+The patient had been on immunosuppressive medications, which included anti-TNF medication and methotrexate for rheumatoid arthritis for the previous 5 years, and was not taking antibiotics at the time of presentation to the clinic. Initial superficial wound swabs were taken for culture at this clinic attendance, all of which revealed no growth at this stage.
+Initially, the patient did not wish to undergo revision surgery and instead wished to consider management with suppressant antibiotic therapy, but after further consideration, she decided to proceed with a revision procedure. A two-stage procedure was planned that initially comprised implant removal, debridement, temporary spacer insertion and empirical intravenous antibiotic therapy post-operatively, followed by reimplantation of a custom-made prosthesis at a later second stage. At the first-stage operation, the implant was removed, the sinus was excised, and an extensive debridement and washout was performed. A large loculated collection and copious infected tissue were noted. Seven deep tissue samples were obtained with sterile instruments and sent to the microbiology laboratory for culture and sensitivity testing in a sterile container. An antibiotic-loaded cement spacer (model H48G, Synicem Shoulder Spacer, Lima Orthopaedics UK Ltd, Letchworth Garden City, UK) loaded with 1.50 g of gentamicin was inserted to maintain tissue tension and joint alignment. The patient was started empirically on IV flucloxacillin 2 g QDS following surgery since Gram-positive organisms are the commonest pathogens in prosthetic joint infections, while awaiting results from the intra-operative samples.
+Tissue samples were homogenized using a vortex machine with the addition of saline broth and were plated on the blood, cystine–lactose–electrolyte-deficient (CLED) and chocolate agar. Further, fastidious anaerobe broth (FAB) was also inoculated for each sample and was read each day for a total of 5 days of incubation. was isolated from two out of seven tissue samples at 48 h from the blood plate and subsequently identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) technology. One out of the two positive tissue samples, with further FAB, isolated a similar pathogen. Ciprofloxacin, amoxicillin and ceftriaxone etests were set up, and the organism was detected to be sensitive to all as per European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Antibiotics at this stage were rationalized as per microbiology advice and the patient was commenced on intravenous ceftriaxone 2 g once a day for 14 days, followed by a further 28 days of oral ciprofloxacin 500 mg BD (equivalent to twice a day) to complete a total 6-week course. A transthoracic echocardiogram was performed in view of the risk of endocarditis, and this was negative.
+The second-stage procedure for implantation of the definitive prosthesis (custom-made Lima shoulder, Lima Orthopaedics UK Ltd, Letchworth Garden City, UK) was performed 10 months following the first stage (with two delays due to anaesthetic concerns and the presence of pressure ulcers). At the second-stage procedure, there was no evidence of an active infective process and implantation of the new custom-made prosthesis was undertaken. Three deep tissue samples were obtained using sterile instruments and sent to the microbiology laboratory for culture and sensitivity testing. Samples were processed in a similar manner as previously stated with additional broth incubation for 5 days. The patient was commenced empirically on intravenous vancomycin, dosed as per the local vancomycin calculator, and co-amoxiclav 1.2 g TDS (three times a day), as per the local hospital guidelines for revision surgery post-operatively. No pathogens were isolated from any deep tissue specimens following a final read at 5 days. The patient was subsequently discussed in the Bone Infection MDT (Multi-Disciplinary Team) meeting and it was advised that the antibiotics be rationalized to oral ciprofloxacin 500 mg BD to complete the 6-week post-operative period because the patient was immune suppressed and had a high risk of relapse.
+The patient completed the course of antibiotics and recovered post-operatively with no further complications from the shoulder perspective. She continued to make progress, and her range of motion at the shoulder joint improved slowly. However, her post-operative physiotherapy was limited to over-the-phone sessions during the coronavirus disease 2019 (COVID-19) crisis and 7 months post-surgery the patient fell, sustaining a closed, right tibial shaft fracture that was successfully managed non-operatively in serial casts, although this further limited her shoulder rehabilitation. Twelve months post-operatively, her radiographs were satisfactory and she had regained function to a level beyond her pre-operative range. Her inflammatory markers were CRP 36.6, ESR 59 (consistent with her rheumatoid clinical picture), and WCC 6.8; and her clinical shoulder scores were 36 for the Oxford shoulder score, with a Constant score of 43.
+At 14 months post-second stage surgery, the patient was admitted with sepsis, with the likely focus originating from a right foot ulcer that had led to osteomyelitis. Superficial ulcer swabs from the right foot isolated (MSSA). The patient declined any further ongoing treatment and elected to return home with her family for palliative care.

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+A 20-year-old Japanese man presented with his father to our periodontic clinic at Osaka University Dental Hospital, Japan, because of his poor oral condition. His chief complaint was severely painful gums, which led to crying. He was unable to provide detailed information about when and how this problem had started. His father told us that our patient had thought there was a gingival problem since childhood, had complained of gingival pain for the previous six months, and had been unable to brush his teeth for the last two weeks. Our patient's height was 153 cm and his weight was 62 kg. His medical history included a three-month hospital stay caused by low birth weight and cyanosis just after birth. A clinical diagnosis of PWS had been made on the basis of symptoms such as hypotonia, genital hypoplasia, acromicria (short hands and feet) and genetic testing.
+An intra-oral examination revealed poor oral hygiene with heavy generalized plaque throughout the permanent dentition. His gingival tissues showed marginal redness, swelling, and food impaction . An apparent anterior open bite, increasing overjet, an anterior crowded arch and malpositioning of the teeth were noted. In addition, circular caries and attrition of the mandibular first molars were present. Pocket depths ranged from 4 mm to 8 mm. Mobility grade 2 was present in the mandibular left second premolar. We tried to measure the pocket depth and clinical attachment level at his first visit. Unfortunately, however, our patient did not allow the pocket measurement because of pain. Thus, we could not perform the conventional pocket measurement and examined only the mesial and buccal/labial pockets. Periapical radiographs disclosed localized vertical bone resorption (mesiolateral of maxillary right first molar and mesiolateral of mandibular left first molar) . Of particular note, the mesiopalatal pocket depth of the maxillary right first molar was 8 mm.
+Based on pocket measurements and an X-ray examination, our patient was diagnosed with localized periodontitis. In addition, our patient exhibited several caries lesions from the mandibular right anterior teeth to the left molars. An orthopantomogram showed full permanent teeth with unerupted lower third molars. There was no family history of periodontitis.
+Advice on periodontal treatment was provided in the presence of one of our patient's parents. This included oral hygiene instructions on how to control plaque using a manual toothbrush (Sam Friend Supersoft #300; Sun Dental, Osaka, Japan), 0.2% w/w chlorhexidine mouth rinse (ConCool F; Weltech, Osaka, Japan) and 1% v/w chlorhexidine gel (ConCool Gelcoat F; Weltech). Professional scaling was also performed to remove supragingival plaque. Our patient kept his treatment appointments with his father every three weeks, but his plaque control was poor. His father told us that our patient was motivated to brush his teeth and did so happily, but sometimes he fell asleep without brushing because of daytime somnolence; a common occurrence in PWS . He refused to allow his parents to help him brush his teeth. Furthermore, malpositioning of the teeth and difficulties with hand and wrist movements inhibited adequate plaque control. After three visits to the clinic our patient had become accustomed to the dental treatment, and subgingival scaling was performed using an ultrasonic scaler. However, active treatments such as root planing and periodontal surgery were not employed because of poor plaque control. Both tooth-brushing instruction (TBI) and subgingival scaling were performed every three weeks. Although some gingival inflammation remained, his gingival swelling and redness were reduced by six months after his first visit .

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+A 9-week-old male infant presented multiple diffuse red skin lesions. These swellings gradually increased in number and size and were associated with subcutaneous harder blue lesions . Neurological examination revealed progressive macrocrania associated with irritability and vomiting. A total body angio-MR study showed multiple diffuse vascular lesions in the brain, spinal cord, bones, muscles, and viscera. Brain lesions were disseminated, involving both supra- and infratentorial regions, with intense and homogeneous contrast enhancement. The largest lesions were deep within the cerebral and cerebellar hemispheres, particularly the one located in the right lenticular nucleus, which showed acute hemorrhage with vasogenic edema, leading to compression of the mesencephalic aqueduct and resulting in triventricular hydrocephalus . An endoscopic ventriculocisternostomy (ETV) was performed on the same day. Surgical approach had included a transfontanellar access on the right, with navigation references to select the entry point and define the route for the 0° Gaab rigid endoscope. Fenestration was achieved between the mammillary bodies and the infundibulum of the pituitary gland using only a Fogarty balloon. During the procedure, we noted that the ventricular ependyma had a petechial appearance, but no significant hemorrhage occurred, and only minor bleeding was controlled with continuous irrigation. A post-operative MRI showed adequate flow signal through the stoma . A biopsy was performed during hospitalization to study some ulcerated and bleeding lesions, which revealed papillary endothelial hyperplasia with no pathognomonic features of a specific entity. Genetic mutations (EIF2AK4, ACVRL1, BMPR1B, BMPR2, CAV1, ENG, KCNK3, SMAD9, NOTCH3, and WES sequences) were investigated with no evidence found. Therapy was initiated with Prednisone (2 mg/kg/day) and Propranolol (1 mg/kg/day). However, due to further massive epistaxis requiring a blood transfusion and no improvement, the therapeutic scheme was modified to combine Prednisone and Vincristine. After 3 weeks of therapy with no improvement, Vincristine was replaced by Rapamycin (0.8 ml/day) with ethical committee consent. The therapy was effective, with no more bleeding observed, and the lesions gradually became smaller and clearer with some desquamative features. The patient was discharged, and therapy continued at home, with Rapamycin doses adjusted based on blood levels, while corticosteroids were gradually decreased. Follow-up over 5 years confirmed the absence of new lesions .

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+A 5-year-old girl was presented to our institution because of failure to thrive. She was the fifth child of unrelated parents originating from the same village in the south of Lebanon. She was born vaginally at term to a 33-year-old mother; her birth weight was 2,200 grams. The course of pregnancy was normal and the mother denied any medication use, smoking, or alcohol intake. The girl’s perinatal history was significant for neonatal jaundice requiring phototherapy. The family history was unremarkable except for mental retardation in a maternal uncle and a congenital heart defect in an older brother.
+In early infancy, the girl had feeding difficulties and failed to thrive. She also had a history of recurrent respiratory infections and eczematous skin changes. In addition, since birth she had had a musty urine odor that had never been reported in her family. Urine analyses were repeatedly normal.
+At consultation, developmental evaluation revealed a hyperactive child with significant speech delay. Her vocabulary consisted of 10–15 words. She used few two-word sentences. Otherwise, the gross and fine motor abilities were adequate for her age. She made good eye contact and could understand and carry out simple verbal instructions, but she had a short attention span and impulsive behavior.
+Upon examination, her height was reported at 84 cm, her weight was 10 kg, and her head circumference was 44 cm, all below the third percentile according to US Centers for Disease Control growth charts.
+She had fair, dry skin and sparse, fine blond hair. Her face was elongated with a high sloping forehead. She had sparse lateral eyebrows, long eyelashes, wide-set eyes (telecanthus) with hypertelorism, low-set ears, a broad nasal bridge with a prominent tip, micrognathia, a thin upper lip, a high-arched palate, dental caries, a sacral dimple, and eczematous skin changes on the extremities, mainly on the flexural areas ( and ).
+When she smiled, her facial skin wrinkled and she looked like a prematurely aged girl . The remainder of the physical examination was normal.
+Laboratory workup yielded normal results for the following tests: complete blood count, serum blood urea nitrogen, creatinine, sodium, potassium, chloride, total serum protein, liver function, lipid profile, thyroid hormone, urine organic acids, plasma acylcarnitine profile and free carnitine level, plasma amino acids, serum lactate and pyruvate levels, plasma zinc, plasma immunoglobulins including normal immunoglobulin E levels, urinalysis, urine cultures, stool studies, insulin-like growth factor 1, antiendomyseal antibodies, sweat chloride, and 46, XX karyotype.
+Other tests included MRI examination of the brain, X-rays of the spine, a voiding cystourethrogram, and an upper gastrointestinal series; all were normal. An echocardiography revealed a trace mitral regurgitation. Bone age was 2-years delayed compared with the chronological age.

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+A 37-year-old G9P0171 (seven spontaneous abortions reported) with a history of chronic hypertension, type 2 diabetes mellitus, chronic kidney disease, neuropathy with Charcot foot, class III obesity with a BMI 52, and prior preterm delivery for superimposed preeclampsia transferred her care to our high-risk practice at 24w2d. During her initial prenatal visit, she also disclosed a history of multiple MRSA containing skin abscesses on her chest that she reported had originated from spider bites.
+Prior to transferring her care, she first presented to the Emergency Department with shooting left upper back and flank pain at 18 weeks. At that time at the outside institution, a CT scan without contrast was ordered to evaluate for nephrolithiasis, but the abdomen visualized inferiorly from the diaphragm was largely unremarkable. She presented to the Emergency Department six more times from 18 through 34 weeks gestation with complaints of ongoing pain, occasionally describing the pain shooting down her legs and causing lower extremity numbness. Throughout her visits no motor or sensory deficits were elicited on exam, and she was repeatedly afebrile with no pain on spine palpation. She was treated with acetaminophen and cyclobenzaprine for possible paraspinal muscle spasm. During one of these visits at 33 weeks a urine drug screen was obtained by the triage provider due to their concerns about the patient’s poor compliance with prenatal care appointments, as she had not presented to scheduled visits for over eight weeks. This screen resulted positive for fentanyl and was negative for all other substances included in the basic toxicology screen. She adamantly denied any opioid use, presenting a diagnostic challenge, and requested repeat testing the following day as well as five days later. Both subsequent tests were positive. The patient continued to deny any opioid use, however the placement and number of infected skin lesions on her chest raised suspicion for injection drug use. At a much later date, she disclosed she had been a restrained passenger in a motor vehicle collision during the first trimester of her pregnancy and stated this was the first time she noticed the back pain.
+At 36w1d, she was directed to the Obstetrics Emergency Department for evaluation after a biophysical profile score of 2/8 and amniotic fluid index of 0.7 was noted during routine antenatal testing. At this time, she also reported that her back pain had been significantly exacerbated by a fall en route to the hospital. Due to reactive non-stress test upon arrival, decision was made for observation until delivery via repeat cesarean section at the next available scheduled OR slot. Anesthesia attempted to place a combined spinal and epidural block at L2-L3, as was the standard of care for obese patients. Following the initial spinal dose, placement of the epidural catheter was abandoned after the patient experienced pressure and pain with local anesthetic infusion. The procedure continued under single-shot spinal anesthesia. Her mean arterial pressure (MAP) dropped to 75 mmHg for a few minutes following the spinal, and then corrected to her baseline MAP of 115–125 mmHg with fluid resuscitation prior to the procedure. The repeat cesarean section was then completed and was overall uncomplicated. Final quantitative blood loss was 910 mL. Her neonate had 1 and 5 min APGAR scores of 3 and 7, respectively, initially requiring some positive pressure ventilation but with an overall uncomplicated neonatal course.
+While in the post anesthesia care unit, she developed severe range blood pressures (systolic pressures persisting in the 170 s over fifteen minutes apart) requiring acute treatment with labetalol and hydralazine. Complete blood count, complete metabolic panel, lactate dehydrogenase, urine protein to creatine ratio (U P:C) were obtained which were unremarkable aside from a significant increase from baseline in her U P:C. Superimposed pre-eclampsia with severe features was diagnosed and intravenous magnesium sulfate was initiated for seizure prophylaxis and continued over the next 24 h. Her MAP nadired at 68 mmHg during this 24 h period, and she did not require further acute treatment of severe range blood pressures. Throughout treatment she continued to complain of back pain at a similar severity to the antepartum period. Since reflexes in the bilateral lower extremities were poorly elicited and this was thought to be her baseline, reflexes in her upper extremities were used for her serial examinations while receiving magnesium. She was noted to have full voluntary motor function in all four extremities during this time.
+On post-operative day one, after completion of magnesium treatment, the patient complained of inability to move her legs. Physical examination demonstrated impaired pain and light touch sensation below the umbilicus, no voluntary strength in bilateral lower extremities, no Babinski or ankle jerk reflex, and the patient was unable to void after Foley catheter removal. MRI of the spine showed discitis osteomyelitis at T9-T10 with phlegmonous change in the soft tissues anterior to the vertebral column. This phlegmonous area extended into the ventral and dorsal epidural space resulting in severe spinal cord narrowing at T9-T10. There was also focal kyphosis in this region, indicating chronicity of some of these changes. MRI images are displayed in Figs. and . Orthopedic surgery was consulted and the patient was taken for emergent T9-T10 laminectomy, wound debridement, and T7-T12 fusion for suspected spinal cord infarction secondary to arterial disruption in the setting of infection. Intra-operatively, a “thick phlegmon” was noted overlying the dura which was dissected away to decompress the cord. She received 4 units of packed red blood cells and 2 units of fresh frozen plasma intraoperatively due to neurogenic shock. Cultures collected during surgery grew Methicillin-sensitive Staphylococcus aureus. Postoperatively, she had persistent bilateral lower extremity motor and sensory deficit and was admitted to inpatient rehabilitation. Her lower extremity function and sensation improved over months of physical therapy. As of four months following the initial injury, the patient had been discharged from the hospital and was undergoing home physical therapy. She was not ambulatory but could stand with support equipment. Please refer to Fig. for a visual of the clinical timeline.

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+A 54-year-old man with a body mass index of 43.7 kg/m2 (weight, 124.8 kg; height, 169.0 cm) had a medical history of high blood pressure, bronchial asthma, sleep apnea syndrome, and surgery for a right bronchial gangliocytic paraganglioma. He had previously undergone esophagogastroduodenoscopy (EGD) at another hospital for screening examination, without any symptoms and abdominal findings. EGD revealed a tumor in the duodenal bulb; therefore, he was admitted to our hospital for close examination.
+EGD revealed two smooth elevated lesions with a diameter of 10 mm in the anterior wall of the duodenal bulb . A biopsy of the tumors in the anterior wall indicated the presence of neuroendocrine cells. The tumors were diagnosed as duodenal neuroendocrine tumors (NET). Abdominal plain computed tomography (CT) revealed no lesions, apparent enlarged lymph nodes, or distant metastasis. Endoscopic ultrasonography showed that the lesions were hypoechoic masses primarily comprising the third layer having an unclear border with the fourth layer. Because this finding suggested that the tumors had invaded the muscle layer, we decided that surgical resection was necessary. Therefore, laparoscopic distal gastrectomy with lymph node dissection and Roux en-Y reconstruction was performed. The extent of lymph node dissection was D1+ with No.12a lymph node because the tumors were located in the duodenum bulb. Intraoperative findings revealed that the tumors were not exposed to the serosal surface. The surgery was performed in the same way as usual for gastric cancer. The duodenum was transected using linear stapling device, and the stump was reinforced with serosal muscle suturing. A curative resection was performed without intraoperative complications. On the basis of pathological findings and immunostaining, the diagnosis was NET, which was classified as NET G1 according to World Health Organization (WHO) classification 2010 .
+From the physical findings and laboratory test results, the postoperative course up to postoperative day (POD) 3 was uneventful. The drain amylase level at POD1 was as low as 157 U/L; he started eating on POD3. He had a fever on POD5; hence, the meal was stopped, and a course of antibiotics was started. However, the fever was not improved, so CT was performed on POD8. Abdominal plain CT showed fluid collection in the anterior cavity of the pancreatic head . Consequently, CT-guided drainage of the collected fluid was performed. The contrast radiography through the drainage tube showed that there was no fistula between the fluid and gastrointestinal tract and no obvious anastomotic leakage. The amylase level of the drainage fluid was high at 4667 U/L, which suggested that the peripancreatic fluid collection was caused by pancreatic fistula and poor drainage. The drainage was continued, and the fluid cavity tended to shrink.
+On POD28, he passed a large amount of blood stool. His vital signs were stable. Abdominal contrast-enhanced CT showed a small amount of fluid collection on the anterior side of the pancreatic head but no apparent extravasation findings. Although the CT imaging showed no evidence of abdominal bleeding or pseudoaneurysm, bleeding from a pseudoaneurysm was suspected because of the clinical findings; therefore, an emergency angiography was performed. We performed angiography of the celiac artery, splenic artery, and gastroduodenal artery as well as their branches that perfused the pancreas and the inferior pancreaticoduodenal artery branching from the superior mesenteric artery; however, no apparent pseudoaneurysm or extravasation was found. Therefore, no action other than observation was performed .
+EGD showed no bleeding from the gastrojejunal anastomosis site, jejunojejunostomy, and duodenal blind end. Colonoscopy also revealed no bleeding foci. We could not detect the source of bleeding, and there was no blood stool subsequently. The meal was restarted on POD34. Abdominal contrast-enhanced CT on POD36 showed no hemorrhage or pseudoaneurysm, and the abscess had disappeared. Therefore, on the same day, we removed the drainage tube. He was discharged on POD50.
+A plain CT 6 months after the surgery showed no abnormal findings and no pseudoaneurysm. Approximately 1 year after the initial surgery (POD350), he passed a bloody stool and was admitted to a local hospital after experiencing hemorrhagic shock. Laboratory tests revealed severe anemia with a hemoglobin level of 4.5 g/dL; therefore, blood transfusion was performed. Because colorectal bleeding was suspected, a colonoscopy was also performed; however, the bleeding source was not detected. A few days later, he again experienced a bloody stool and subsequently underwent EGD. An ulcer with pulsating exposed blood vessels near the duodenal blind end was observed. He was diagnosed as having a hemorrhage from a delayed pseudoaneurysm associated with surgery and was transferred to our hospital.
+Although his vital signs were stable, laboratory tests showed a hemoglobin level of 7.1 g/dL. Abdominal contrast-enhanced CT revealed a pseudoaneurysm arising from the proximal gastroduodenal artery (GDA), extending into the duodenal wall . Emergency angiography was performed, which revealed a pseudoaneurysm that had developed from the proximal GDA, as demonstrated in the CT findings . Transcatheter arterial embolization (TAE) was successfully performed with the isolation and packing technique. First, the proper hepatic artery distal to the pseudoaneurysm was embolized by using coils. Second, the pseudoaneurysm and posterior superior pancreaticoduodenal artery branching from the pseudoaneurysm were embolized with N-butyl-2-cyanoacrylate. Finally, the common hepatic artery proximal to the pseudoaneurysm was also embolized by using coils . Laboratory tests performed 1 day after TAE showed no evidence of liver failure. No clinical signs of rebleeding were observed during the course, and he was discharged on the seventh day after TAE. Subsequently, abdominal contrast-enhanced CT was performed twice approximately 3 and 9 months after TAE, and there were no findings, such as pseudoaneurysm recurrence, and no symptoms suggesting rebleeding.

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+A 77-year-old woman presented to our hospital with a history of hypertension, hyperlipidemia, and diabetic mellitus. She also had occlusion of the left central retinal artery due to ipsilateral carotid stenosis 3 years prior, after which no further ischemic events had occurred. Neck MRA demonstrated severe stenosis of the proximal left internal carotid artery (ICA), and the external carotid artery was not detected . Intracranial MRA showed weak flow signal intensity of the left ICA and left middle cerebral artery [ and ], and neck computed tomography revealed severe circular calcification . 123I-iodoamphetamine single-photon emission computed tomography (123I-IMP SPECT), additionally, showed reduced CBF and cerebral vascular reserve [ and ] in response to acetazolamide in the left hemisphere.
+Staged therapy was subsequently performed, as this patient had a high risk of HPS following conventional CAS or CEA. Dual antiplatelet therapy (DAPT) (aspirin 100 mg and clopidogrel 75 mg) was administrated 2 weeks before PTA. The procedure was performed under local anesthesia. After intravenous administration of 5000 U heparin, the lesion was crossed with a 0.014 inch guide wire, and submaximal angioplasty was performed using a 2.5 mm × 12 mm noncompliant Gateway® balloon (Stryker Neurovascular, Kalamazoo, Michigan). The stenotic lesion was sufficiently expanded immediately; however, elastic recoil was observed ten minutes later. PTA was then performed using a 3.0 mm × 12 mm Gateway® balloon. After expanding the stenotic lesion, we observed that flow delay was improved [-]. Two days after first stage PTA, 123I-IMP SPECT revealed improvements in CBF . In addition, no neurological morbidity was observed during the interval between the first and second stages.
+In the second stage, CEA was conducted under general anesthesia 7 days after the first stage, using real-time near-infrared spectroscopy (NIRS) monitoring. The carotid sheath was dissected, and the arteriotomy was completed. Furui’s double balloon shunt system was used to maintain blood flow from the common carotid artery to the ICA. When the ICA was clamped, left cerebral hemisphere NIRS dropped by 10%. However, once reperfusion to ICA was delivered through the shunt system, NIRS returned to baseline. Further, we found a calcified plaque with a large thrombus at its proximal end . The plaque was, then, extracted, and the ICA was closed. The skin incision was then closed. Intracranial and neck MRA showed normal flow signals [ and ]. CBF was improved, and hyperperfusion was not detected in postoperative 123I-IMP SPECT immediately and 2 days after CEA . The postoperative course was uneventful, and the patient was, then, discharged with no neurological deficits. She continued to receive DAPT until 6 months after completing CEA.
+The extracted thrombus was found to consist of calcified plaque. A hematoxylin-eosin stain of the thrombus showed mostly intact and partially lytic blood cells, without necrotic tissue . Therefore, the thrombus was assumed to be between 1 and 5 days old, as per previous reports.[,] We, therefore, found that the thrombus was formed after the first therapeutic stage.

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+A 32 weeks pregnant, 23-year-old known asthmatic woman presented to a peripheral hospital with acute respiratory failure during winter. Cold air was a known precipitant for her asthma. She was intubated and ventilated for presumed severe acute asthma with refractory bronchospasm. Following intubation she was found to be extremely difficult to ventilate and was retrieved to our intensive care unit for further management.
+She had widespread, faint, prolonged monophonic wheeze on auscultation with no evidence of pneumothorax. Mechanical ventilation in volume control mode was commenced with an inspired oxygen fraction of 1.0, external Positive End Expiratory Pressure (PEEP) 0 cmH2O, respiratory rate six breaths per minute, a tidal volume of 300 ml, and inspiratory flow rate of 30 L/min. However, high peak airway pressures truncated each breath. Intrinsic PEEP was measured as 30 cmH2O, with evidence of dynamic hyperinflation and accompanying hemodynamic instability despite inspiratory to expiratory ratio of close to 1:16. An arterial blood gas sample revealed severe respiratory acidosis (pH of 6.92, PaO2 116 mmHg, and PaCO2 143 mmHg). There was evidence of foetal distress on Cardiotocograph (CTG). Bronchoscopy demonstrated a pedunculated tumour arising from the posterior tracheal wall, extending from the tip of the Endotracheal Tube (ET) and measuring approximately 4 cm by 2 cm. The tumour acted as a ball valve to cause severe expiratory airflow obstruction . The bronchoscope was advanced beyond the lesion and the ET advanced over the bronchoscope to bridge the lesion, resulting in dramatic improvements in lung mechanics and haemodynamics. Urgent Caesarean section was performed due to persistent decelerations on CTG, with birth of a healthy baby. Access to her previous records revealed that she previously presented with haemoptysis at 16 weeks of the current gestation. At this time she had a small polyp (~0.5 cm) in the same tracheal location, which had been excised and diagnosed as LCH.
+The following day, tumour debulking was attempted. In view of the high risk of major haemorrhage and hypoxemia, precautionary cannulation for veno-venous Extra-Corporeal Membrane Oxygenation (ECMO) was established via a bi-femoral approach. Surgical debulking was complicated by significant haemorrhage causing desaturation (SpO2 < 80%). She was promptly commenced on ECMO with recovery of arterial oxygen saturation and minimal disruption to surgery. A small bolus of heparin (2000 units) was given intravenously just prior to connection of the ECMO circuit, but no further heparin was administered until after surgery. On return to the ICU, a low dose heparin infusion (10 units/kg/hour) was used to maintain ECMO circuit patency. The histopathology revealed recurrent LCH , with intact overlying epithelium (Arrow) and lobular arrangements (*) of proliferating capillaries (horizontal arrow) in an edematous fibro-myxoid stroma, containing extravasated red blood cells (vertical arrow). There was intense staining with CD31 Immunohistochemical staining highlighting proliferating endothelial cells and vascular origin of tumor. Her trachea was subsequently stented and ECMO was discontinued. She made a full recovery.

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+An 84-year old white male, presented at the Department of Dermatology (6th IKA Oncological Hospital of Athens) with a pale, ulcerated lesion (1.3 cm in diameter), on the middle of his lower lip. There was no associated lymphadenopathy and an excisional biopsy was performed. Histopathological and immunoistochemical features revealed a Merkel cell carcinoma (MCC) but as the excision was incomplete the patient was sheduled for a wider excision in the following 2 months. In the meantime, the lesion recurred and the patient returned with a protruding white lesion of 1.1 cm in diameter. There was no associated lynphadenopathy and a wider excision, with an 8 mm margin, was performed. Histopathology confirmed the nature of MCC and the second excision was within healthy margins.
+Two months later, the patient was referred to the Depatment of Plastic Surgery, for another protruding ulcerated lesion, 3 cm in diameter, on his lower lip . On examination, multiple palpable lymph nodes in the submandibular and cervical area (superficial and deep cervical lymphadenopathy) were present.
+Past medical history revealed that 8 years earlier, the patient had been diagnosed as having chronic lymphocytic leukemia (CLL), (nodular and intermediate type), but he didn't receive any treatment. CT scan of the head and neck area, showed a soft tissue lobular mass, 3 cm in diameter, on the lower lip, with a possible extension to the mandible. The past medical history of CLL with the recent occurence of MCC posed a problem in the differential diagnosis of the patient's lymphadenopathy. A W-excision (4 × 3.5 × 1 cm) of the lip lesion was performed, with an open biopsy of one submandibular lymph node.
+Histopathology, confirmed recurrence of MCC. An undifferentiated small cell carcinoma with hyaluronated stroma was identified. The cells arranged in nodules or rosettes, had dense nuclear chromatin, with mitoses and nuclear debris which are regular features of MCC .
+Immunoistochemical procedures showed Neuron Specific Enolase (NSE) positivity, while antibodies for Epithelial Membrane Antigen (EMA) and Chromogranin were negative. The excision was described as complete. The submandibular lymph node was positive for malignacy but was associated with the CLL (non Hodgkin's, B cell small lymhocytic lymphoma). There was no evidence of metastatic infiltration by MCC and this was confirmed immunoistochemically with the positive expression of CD5 and CD20 antibody and negative expression of CD10 antibody and NSE. Due to the age of the patient, chemotherapy was not considered.
+A month later, a new CT scan of the head and neck, depicted a soft tissue mass, consistent with recurrence of MCC, between the left angle of the mandible and the hyoid bone. Multiple enlarged superficial and deep cervical lymph nodes were present. Fine needle aspiration (FNA) of the submandibular swelling was performed and confirmed MCC (small atypical cells were found, isolated or forming rosettes and exhibited dense core granules of chromatin and scanty cytoplasm). The patient underwent one month of neck radiotherapy with Cobalt 60, a total dose of 4600cGy in 23 days. A further boost of 600cGy in 2 days, on the left submandibular area was administered.
+The treatment was successfully completed with full remission of the cervical lymphadenopathy. Two months following the radiotherapy, a new CT scan of the head and neck showed reduction and obscurrence of the pre-existing mass on the left mandibular area, while the lymph nodes were smaller too. The patient is on regular follow up and CLL status is stable with no evidence of progression or further recurrence of MCC 9 months post- radiotherapy.

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+A 33-year-old man developed diarrhoea 1 day after eating fried pork with chili and fever the next day, with a body temperature of 40 °C. The results of blood and faecal cultures were positive for Salmonella Dublin. Influenza A virus, influenza B virus, Mycoplasma pneumoniae, Chlamydia pneumoniae, respiratory syncytial virus, Haemophilus influenzae, varicella-zoster virus, Legionella, Campylobacter and SARS-CoV-2 tests were all negative. The patient developed drowsiness after 3 days, with gradual weakening of the limbs, dysarthria, binocular abduction paralysis, and ataxia. His brain MRI scan was normal. After 5 days, the patient could not raise his limbs. These symptoms were accompanied by liver function damage and myocardial damage. After 7 days, the patient still had weakness of the limbs and dysarthria. However, as other indicators improved, he was transferred from the Intensive Care Unit ward to the Neurology ward. Physical examination of the nervous system mainly showed flaccid paralysis of the limbs, disappearance of the bilateral tendon reflex, inability to speak, ataxia (bilateral limb paralysis limited the ability to assess gait), and positive bilateral Babinski signs. At that time, lumbar puncture results for intracranial pressure, CSF protein, and CSF cell number were normal, and the CSF was cultured for 3 days with no bacterial growth. On re-examination, the brain MRI and cervical MRI were normal. As BBE was suspected clinically, IVIg therapy (0.4 g/kg) was given for 5 days, but the patient’s symptoms did not improve significantly. Twenty days after admission, lumbar puncture examination showed that the protein content had increased by 0.86 g/L (the normal range is 0.08–0.43 g/L); the cell number was normal (the number of nucleated cells was 6, normal range 0–8; the red blood cell count was 0), CSF and serum anti-GQ1b antibody was negative, and CSF anti-MOG, anti-AQP4, and anti-MBP antibodies were all negative. The results of electrophysiological examination were normal (14 days and 60 days after onset). Considering no obvious improvement, at 21 days, he was given IVIg again at the same dose for 5 days. The patient’s symptoms gradually improved, and he was able to start walking on his own. His limb collateral movement was significantly better than before, his eye movement was normal, and his voice was low. The patient’s speech could be heard clearly, and he was given speech rehabilitation training. After 3 months, the patient could walk 10 m without assistance but was unable to run (the grade of the GBS disability scale was 2) . His speech also returned to normal.

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+A 32 year old Korean woman presented with a one week history of right ocular surface discomfort, and the sudden appearance of a firm cystic lesion fixed to the palpebral conjunctiva of her right lower eyelid by a central trunk . The lesion was non-tender, had never ulcerated or haemorrhaged, and was increasing in size daily. At presentation, its dimensions were 5 mm × 7 mm × 3 mm. A history of bilateral epiblepharon correction performed in Korea three months prior was given. The patient was systemically well, and had no other significant ocular or medical history. Her uncorrected visual acuity was 6/5 bilaterally. Extraocular movements were full and painless. Bilateral anterior segment and dilated fundus examinations were unremarkable. The lesion was completely excised at the trunk under local anaesthesia with minimal bleeding. Chloramphenicol ointment QID OD was commenced post-operatively for one week. There were no signs of recurrence one week post-excision. Histopathology demonstrated a central zone of myxoid change (containing spindle-cells, stellate-cells, sparse blood vessels, and patchy inflammation), surrounded by a zone of fibrous connective tissue . Alcian blue staining was positive for connective tissue mucin . Digested Periodic-acid-Schiff (PAS) staining was negative for epithelial mucin. Complete systemic evaluation excluded any further myxomas (including cardiac), unusual areas of pigmentation, and endocrine abnormalities.
+Conjunctival myxomas are rare. Grossniklaus et al. (1987) noted four cases of conjunctival myxoma in a review of 2455 conjunctival specimens [, ]. Similarly, Shields et al. (2004) reported one case of conjunctival myxoma in a clinical review of 1643 conjunctival lesions [, ]. Including this case, the mean age at presentation is 45 years [–]. A review of 58 patients with myxomas in other soft tissues found the mean age to be 55 years . No significant trends in gender or racial predisposition have been noted to date, however the number of reported cases remains small [, ].
+Conjunctival myxomas typically present as slow-growing, painless, well circumscribed, yellow-pink, cyst-like masses, with fibrous, vascular, soft tissue trunks [–]. Not including this case, the mean timeframe before patients presented for ophthalmic review of their conjunctival myxoma was 34 months . This patient’s conjunctival myxoma developed rapidly over one week to a 5 mm × 7 mm × 3mm lesion. Lesions have been reported to range between 4 mm and 20 mm in diameter . This lesion reached almost half the recorded maximum size within one week. The majority of cases are painless –although there have been two reported cases of conjunctival myxoma with ocular pain . Ninety percent of reported conjunctival myxomas occurred in the bulbar conjunctiva - with the majority being temporal . This is the second case to be documented as arising from the inferior palpebral conjunctiva . There have been no previous reports of conjunctival myxoma developing within close proximity to trauma or ophthalmic surgery [, , , ]. This patient presented with her myxoma within 3 months of having bilateral uncomplicated surgical correction of her congenital epiblepharon - a common occurrence in Asians . We could not determine any connection between her bilateral congenital epiblepharon and conjunctival myxoma. The conjunctival myxoma in this case had a typical clinical appearance. It was atypical because of its rapid growth rate, its unusual location on the inferior palpebral conjunctiva, and its occurrence in association with recent eyelid surgery.
+Histologically, myxomas resemble Wharton’s jelly, the loose mucoid tissue found within the umbilical cord [, ]. The characteristic histopathological features of conjunctival myxoma are, sparsely scattered stellate- and spindle-shaped cells distributed throughout a mucinous matrix, with delicate reticulin fibres, minimal blood vessels, and mature collagen fibres [, , , , ]. The mucinous matrix is predominantly composed of hyaluronic acid, with a lesser amount of chondroitin sulphate, and has been reported to react to vimentin, Alcian blue, and alpha-smooth-muscle actin staining, suggesting a fibroblastic cell phenotype [, , ]. It is non-reactive to S-100 protein, desmin, myoglobulin, and digested Periodic-acid-Schiff (PAS) staining [, ]. The differential diagnosis of conjunctival myxomas includes, amelanotic naevus, amelanotic melanoma, fibrous histiocytoma, conjunctival cyst, lymphangioma, myxoid neurofibroma, spindle-cell lipoma, rhabdomyosarcoma, and liposarcoma [–]. Histologically, an absence of pigmentation, the presence of sparse vascular structures, characteristic cellular morphology, and mucin staining, help differentiate conjunctival myxomas from these lesions .
+To date all cases of conjunctival myxoma have been treated with excisional biopsy [, ]. There have been no previous reports of malignant transformation in a mean follow-up time of 30 months (range 5–132 months) [, , ]. There has only been one reported case of recurrence, which occurred 12 months after the original excision in a patient with the Carney Complex . In general, the recurrence rate of all myxomas is documented as being relatively low. A review of 58 patients with soft tissue myxomas found a 3 % incidence of recurrence 8–10 months post-excision .
+Conjunctival myxoma has been associated with both the Carney Complex and Zollinger-Ellison syndrome [, , ]. The Carney Complex is an autosomal dominant syndrome that requires at least two of the following criteria for diagnosis: the presence of myxomas; spotty mucocutaneous pigmentation (face, trunk, lips, eyelid, conjunctiva); endocrine overactivity (Cushing’s syndrome, pituitary adenoma, and/or sexual precocity); or psammomatous melanotic schwannomas [, , ]. Ophthalmic manifestations of the Carney Complex include eyelid lentigines, conjunctival or caruncle spotty pigmentation, and eyelid or conjunctival myxomas [, ]. The one case of conjunctival myxoma associated with the Carney Complex exhibited palpebral conjunctival, eyelid, coetaneous, and left ventricular myxomas . Carney reported that greater than 50 % of patients with the Carney Complex suffered a significant embolic event in their lifetime related to cardiac myxomas . Ophthalmic manifestations of the Carney Complex, not limited to myxoma, have been shown to precede embolic events [, ]. Early identification of ocular myxomas and subsequent screening and monitoring for cardiac myxoma is recommended.
+Conjunctival myxoma has been associated with a case of pancreatic gastrinoma in Zollinger-Ellison syndrome . Zollinger-Ellison syndrome may be a manifestation of the Carney Complex, given the neural crest origins of myxomas, schwannomas (seen in the Carney Complex), and gastrinomas . Conjunctival myxomas have not been reported with other systemic diseases associated with myxomas, such as Mazabraud syndrome (intramuscular myxoma) and McCune-Albright syndrome (intramuscular and coetaneous) [, ].

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+A 30-year-old Han Chinese man was riding his motorcycle at 80.5km/hour when he collided with an oncoming car. He complained of back pain and right shoulder pain and was admitted to a local hospital. He sustained double inferior lung contusion with a few hemothoraces, fractures of right clavicle and vertebrae T6 to T7 inclusive. After 6 hours, he was transferred to our hospital. On clinical examination, there was no neurological deficit. A three-dimensional reconstruction of computed tomography showed spinal fracture-dislocation of T6 to T7 , a fracture of right clavicle whereas fracture of ribs was not found , magnetic resonance imaging showed spinal fracture-dislocation of T6 to T7 , horizontal computed tomography scans showed a large bilateral hemothorax , fractures of bilateral pedicles of vertebral arch , three vertebral levels in one cut , and anteroposterior thoracic spine plain X-ray showed spinal fracture-dislocation of T6 to T7 and realignment of his fractured-dislocated spine .
+Despite the normal neurological systems below T7, the spine was considered unstable and an operation was planned. Chest drains were inserted bilaterally. A day later, the patient was put in the prone position under general anesthesia, the fascia was opened and his paravertebral muscles were dissected following a midline vertical incision of T4 to T11; the right pedicle of the T8 vertebra and the right lamina of the T6 vertebra were found to be fractured. Laminectomy of the T6 to T7 vertebra was done. The dura and spinal cord were found to be normal. Then the spinal canal was examined with a rubber catheter and found to be good. Transpedicular screws were put in the T5, T6, T9 and T10 vertebrae. Realignment of the thoracic spine was achieved with rods. Bony fusion of the transverse processes of the T5, T6, T7 and T8 vertebrae was done. The fracture of his right clavicle was also reduced and autologous bone graft was performed too. His nervous system was intact postoperatively. He was discharged on the 10th day after his operation. He was very well at the follow-up examination 3 months later.

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+A 76-year-old woman who had a past medical history of hypertension, atrial fibrillation, and right thalamic hemorrhage was admitted to the hospital because of fever and impaired balance. She suffered neck pain and dysarthria two days after admission and became somnolent. CSF examination showed pleocytosis (130 cells/mm3 [mononuclear cell: 130 cells/mm3], normal < 5 cells/mm3) and increased protein levels (113 mg/dL, normal < 50 mg/dL). She was treated with intravenous acyclovir on suspicion of viral meningoencephalitis. Her symptoms did not improve, and she was referred to our hospital for further investigation and treatment 22 days after onset. On admission, she was afebrile, and her consciousness level was E3V3M5 on the Glasgow Coma Scale. Her speech was slurred and barely comprehensible. She had left hemiparesis because of a past thalamic hemorrhage and flaccid muscle weakness in her right lower extremity. Tendon reflexes were hyperreflexia in both upper limbs and areflexia in both lower limbs. She had nuchal rigidity, but Kernig’s sign and Brudzinski’s sign were not observed.
+Peripheral blood cell counts showed mild thrombocytopenia (141 × 103 /µL, normal range: 158–348 × 103/µL). Biochemical examinations showed hypoalbuminemia (2.8 g/dL, normal range: 4.1–5.1 g/dL) and an elevated urea-nitrogen creatinine ratio suggestive of dehydration. C-reactive protein was within the normal limit. Serum thyroid stimulating hormone and free thyroxine levels were within normal limits. A mild elevated carbohydrate antigen 19 − 9 level was observed (39.2 U/mL, normal ≤ 37.0 U/mL). Serum anti-nuclear antibody and anti-aquaporin 4 antibody were negative. Anti-neuronal antibodies including anti-amphiphysin, CV2, Ma2, Ri, Yo, Hu, recoverin, SRY-related HMG-box gene 1, titin, zinc-finger protein of the cerebellum 4, Tr, and glutamic acid decarboxylase 65 antibodies were all negative results (Euroimmun, Lübeck, Germany). Mycobacterium tuberculosis specific interferon-gamma release assay and serum Candida, Aspergillus, and Cryptococcus antigens were negative.
+CSF examination showed normal opening pressure (105 mmH2O), pleocytosis (42 cells/mm3 [mononuclear cell: 41 cells/mm3]), increased protein levels (95 mg/dL), and mildly decreased glucose levels (40 mg/dL). Bacterial culture had a negative result. Herpes simplex virus and Mycobacterium tuberculosis polymerase chain reaction tests also gave negative results. CSF cytology showed no malignant cells. Later, CSF GFAP-IgG was detected by transfected cell-based assay and tissue-based immunofluorescence assay according to previous reports [, ] .
+Brain MRI scans showed abnormal signal changes caused by a past right thalamic hemorrhage and extended white matter hyperintensity lesions in the deep and periventricular white matter in the right frontal and parietal lobes on T2-weighted and FLAIR images . Gadolinium contrast-enhanced brain MRI scans showed heterogeneous thickening of the dura mater . Spinal MRI showed no abnormal signal changes in the spinal cord. Whole body computed tomography (CT) showed no findings of neoplasia. However, early-stage breast cancer was found in the left breast on mammography.
+Based on these results, the patient was diagnosed with GFAP-A. She was treated with an intravenous infusion of 1 gram per day methylprednisolone for 3 days starting on day 8 after admission. Her nuchal rigidity disappeared on day 10. Her consciousness level gradually improved starting on day 11 and became completely clear on day 32. She was also treated with intravenous immunoglobulin (0.4 gram per kilogram body weight for 5 days) on day 36 and again on day 60. She was temporarily transferred to the local hospital on day 91 for rehabilitation.
+A month later, the patient was re-admitted to our hospital and underwent a simple mastectomy for breast cancer. The pathological findings were invasive ductal carcinoma, tubule forming type . Immunohistochemical analysis showed that the restricted tumor expressed GFAP . The infiltration of CD3 + T cells were observed in the peritumoral and intratumoral areas . The most common infiltrating lymphocytes were CD8 + T cells . CD4 + T cells and CD20 + B cells were also observed in the predominant peritumoral area . Her condition did not deteriorate, and no relapse occurred thereafter.

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+The patient was a 67-year-old woman who was admitted to the clinic in September 2019.
+The patient was suffering lumbar pain for 7 years and aggravation with interspace claudication since the preceding February.
+Twenty years previously, the patient had undergone partial thyroidectomy for thyroid nodules at a primary hospital. Post-operative examination of the resected specimen suggested a benign thyroid lesion.
+The patient had no history of food or drug allergies, and genetic diseases.
+Physical examination revealed mild limitation of lumbar flexion and extension activity, L4 paravertebral tenderness, no obvious abnormalities in sensation/movement, and normal blood circulation in both lower limbs. The results of the straight leg raising test, strength test, and bilateral Patrick's sign were negative. No abnormal nodules were touch in the bilateral thyroid glands, and cervical lymph nodes showed no enlargement bilaterally.
+Color ultrasonography indicated solid nodules in the middle of the right lobe of the thyroid, thyroid imaging reporting and data system (TI-RADS) category 4A, and hypoechoic nodules in the bilateral lobes of the thyroid gland, TI-RADS category 3. Therefore, a nodular goiter was considered. No abnormal enlargement of the bilateral cervical lymph nodes was observed. Lumbar computed tomography (CT) and magnetic resonance imaging (MRI) results suggested metastatic or malignant tumors . Thyroid fine-needle aspiration demonstrated a large number of red blood cells (RBCs) with benign proliferative follicular epithelial cells. Thyroid needle biopsy results indicated a small number of thyroid follicles with nodular hyperplasia. Pathological examination of the L4 vertebral puncture biopsy indicated fibrinoid necrosis, broken bone, and thyroid tissue, which suggested metastatic thyroid cancer. Therefore, we sent the sample for pathological consultation at the Shantou University Medical College. Their examination indicated that bone marrow tissue, bone trabecula, and thyroid follicular tissue were observed in the puncture tissue of the L4 vertebral body. Considering the potential for ectopic thyroid tissue, we wanted to exclude FTC. Thyroid function was normal. However, MRI of the lumbar spine indicated malignancy, and whole-body positron emission tomography (PET)-CT was consistent with spinal tumors. No other metastases were found .

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+A 62 year old Caucasian female was hospitalized for six days for treatment of a chronic obstructive pulmonary disease (COPD) exacerbation. Management included steroids and antibiotics. Home medications included clopidogrel for coronary artery disease. Her weight was 46.58 kilograms with a BMI of 17.7 and an estimated glomerular filtration rate (eGFR) of 60.65 ml/min. During the hospitalization she was treated for DVT prophylaxis with enoxaparin 40 mg by subcutaneous injection daily.Seven days after discharge, the patient returned to the emergency department complaining of diffuse abdominal pain, increasing abdominal girth, and anterior wall bruising. An abdominal CT scan confirmed a large RSH . Both general surgery and interventional radiology were consulted. She was managed conservatively. Her hematocrit dropped from 34.8 to 25.3%; however, she declined transfusion of blood products. During the course of her stay, the patient experienced acute hypoxic respiratory failure and did not wish to be intubated. Her medical status deteriorated and, with support from her family, the patient chose to be made comfortable with minimal supportive care. She expired due to sepsis and respiratory failure two days after re-admission.
+A 79 year old male Caucasian was admitted for worsening dyspnea and management of atrial fibrillation with rapid ventricular rate and COPD exacerbation. His clinical course was further complicated by resistant gram negative and gram positive pneumonia and hypoxic respiratory failure. His weight was 59 kilograms with a BMI of 18 and initially his eGFR was 41.98 ml/min. He received subcutaneous abdominal injections of both prophylactic enoxaparin 30 mg and insulin sliding scale therapy. On day 2, his eGFR was calculated at 53.94 and his enoxaparin dose was increased to 40 mg daily.On day 5, he was noted to have abdominal pain and a noncontrast CT scan confirmed a left RSH that expanded considerably over 12 hours on follow up CT. Interventional radiology was consulted but ultimately the patient was managed conservatively with fluid resuscitation and close observation. His hematocrit dropped from 46 to 25.8%. The patient was discharged after 15 days to a long term acute care facility for further management of his respiratory failure and healthcare associated pneumonia.
+An obese 44 year old Caucasian female with multiple chronic medical problems was readmitted to our facility from a ventilator capable extended care facility for sepsis and acute on chronic hypoxic respiratory failure. Comorbidities included spina bifida and central obesity with a BMI of 27. She was admitted on warfarin therapy for a history of recent deep vein thrombosis; however, she was subtherapeutic, with an International Normalized Ratio (INR) of 1.59. She was, therefore, treated with full dose enoxaparin 80 mg by subcutaneous injection twice daily. Her eGFR was 148.65 ml/min. Coumadin was held as the patient was treated with anitfungal and antimicrobial therapy that could prolong her INR.On day 8, she complained of abdominal pain and a CT scan confirmed a large right RSH . Repeat CT scan one day later showed extension of the hematoma and concern for possible active arterial extravasation. Both general surgery and interventional radiology were consulted. The patient underwent a failed attempt at embolization due to access complications. Due to hemorrhagic shock she required transfusion with 10 units of RBCs and pressure support ventilation in the intensive care unit. Her hematocrit dropped from 34.9 to 20.6%. Anticoagulation was reversed with fresh frozen plasma, vitamin K, and one dose of recombinant factor VIIa. The patient subsequently underwent successful embolization with thrombin and coiling of the right inferior epigastric artery by vascular surgery two days after the initial hematoma. Serial CT scans confirmed no further bleeding. After two weeks, anticoagulation therapy was reinstituted without further evidence of bleeding. The patient was ultimately discharged to a long term acute care facility for continued management of her chronic respiratory failure.

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+A 41-year-old, previously healthy Sri Lankan female presented with sudden onset severe headache for one day. The headache started in the occipital region and spread towards the vertex. It worsened with standing and was accompanied with nausea and vomiting. The patient described it as her ‘worst-ever’ headache. She denied a past history of migraine. Remarkably, the headache resolved with lying supine and recurred on sitting up or standing. It would commence as a sensation of ‘heaviness’ of her head that would gradually progress to a severe, disabling headache. The maximum duration that she could tolerate an upright posture was approximately one hour. She did not have any other co-morbidities and denied use of any medicinal or recreational drugs. There was no history of surgery or trauma involving the head, neck or spine.
+On examination, she was comfortable in the supine position and detested sitting up or standing. The cardiovascular, respiratory, abdominal and nervous system examinations were normal.
+Haematological and biochemical blood investigations including full blood count, electrolytes, random blood glucose, liver and renal function tests, erythrocyte sedimentation rate and C-reactive protein were normal. Electrocardiogram was normal. Computerised tomography (CT) scan of the head did not reveal any abnormality. However, gadolinium-enhanced magnetic resonance imaging (MRI) showed generalized meningeal enhancement . The MR angiogram was normal.
+Lumbar puncture done in the lateral decubitus position revealed a CSF opening pressure of less than 30 mm of H2O. The biochemical, cytological and microbiological analysis of CSF was normal and there was no xanthochromia. MR myelography failed to identify the site of CSF leak.
+The patient was managed with bed-rest and hydration with infusions of normal saline. She was prescribed analgesics and encouraged to drink excess amounts of coffee ad libitum. Over the ensuing 3 months, her headaches became less intense and she could progressively tolerate longer durations in the upright posture. At three months’ review she was able to maintain her upright posture for up to 6 hours without headache. Since she showed small but definite improvement each day, the plan for epidural blood patching (EBP) was perpetually deferred. However, in retrospect, given the protracted time to recovery it would have been appropriate to have instituted EBP earlier.

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+A 56-year-old female patient was initially admitted to a secondary care centre. Her medical history included arterial hypertension, type 2 diabetes mellitus and breast cancer undergone full remission following treatment more than 15 years ago. The patient had just returned from a pilgrimage when she noticed a subacute sensorimotor deficit in her left hand. Initially physicians suspected a stroke, but the brain magnetic resonance imaging (MRI) showed no signs of acute or subacute ischemia or inflammation. She was admitted for further diagnostic evaluation. The next day she complained of blurred vision with no reported loss of visual acuity at that time. Over the next 3 days there was a marked clinical deterioration: The patient developed a vesiculopapular rash with secondary clustered crustation on her neck, ear and décolletage and became increasingly agitated and confused. Cerebrospinal fluid (CSF) examination revealed a mild pleocytosis of 10 [0–4] /μl. Empirical antiviral treatment with aciclovir was started on suspicion of herpes zoster encephalitis. However, subsequent polymerase chain reaction testing of the CSF was negative for varicella-zoster, herpes simplex and other neurotropic viruses. A follow-up cerebral MRI revealed a right parahippocampal T2 lesion that was not evident on the initial MRI . In addition, there were T2 hyperintense lesions in both optic nerves, which were consistent with optic neuritis . At this point the patient was referred to our tertiary care facility.
+Here the patient was diagnosed with blindness in the right eye, severe reduction of visual acuity in the left eye (<0.1) and a marked ataxic tetraparesis. The rash, misdiagnosed as herpes zoster, turned out to be self-induced excoriation caused by the patient’s own fingers in an attempt to relieve a perceived severe burning and itching over the skin, which we attributed to a central pain syndrome, probably the cause of the agitation.
+MRI of the spinal cord revealed spinal cord T2 hyperintense lesion locations and extension compatible with transverse myelitis (,). A follow-up spinal tap was negative for oligoclonal bands. Chest/lung computed tomography scan revealed no evidence of pulmonary sarcoidosis. Initial testing for anti-AQP4 and anti-MOG antibodies was performed 12 days after clinical onset and prior to immunotherapy. Sera were analysed by cell-based indirect immunofluorescence at EUROIMMUN (Lübeck, Germany); staining at serum dilutions ≥1:10 was considered positive. Assays were negative at that time and at follow-up . In contrast to AQP4-Ab-positive NMOSD, the diagnostic criteria for seronegative NMOSD are far more complex and require the presence of ≥2 core criteria, at least one of which must be ON, LETM or area postrema syndrome. Additional MR criteria must also be met. In our case, the patient had two core clinical features (bilateral ON and LETM) with brain MRI showing extensive (>1/2 optic nerve length) T2 hyperintense lesions of both optic nerves, a white matter lesion not suggestive of MS and acute myelitis involving more than 3 contiguous segments. In addition, differential diagnoses were ruled out as far as possible by repeated serological and CSF analysis. Thus, we diagnosed seronegative NMOSD according to the 2015 revised criteria of the International Panel for NMO Diagnosis . We started treatment with high-dose intravenous methylprednisolone at 1 g per day for 5 consecutive days. Due to lack of improvement, 7 sessions of plasma exchange were performed every other day with concomitant oral prednisolone therapy (60 mg/d) and prolonged tapering. The concomitant medications at that time were pantoprazole, L-thyroxine, liraglutide, basal insulin, naloxegol, pregabalin and mirtazapine.
+Given the recently approved therapies for AQP4-positive NMOSD and the fulminant onset of the disease, we decided to start INE as an off-label use. Administration of 300 mg on days 1 and 15 was well tolerated with no immediate or subacute adverse events. Prior to discharge to a rehabilitation clinic, the patient could recognise the basic shapes of most everyday objects with her left eye and was able to stand with much assistance.
+At a follow-up visit 3 months later, the patient reported being able to walk up to 500 m with a walker. The right eye remained blind, colour vision had returned to the left eye, but she was still unable to read a newspaper. A brain MRI showed a new inflammatory T2 lesion in the left frontal white matter, possibly representing paraclinical disease activity before the immunotherapy could take full effect. Prednisolone was reduced from 20 mg to 5 mg/d. When we administered the second cycle of INE at the six-month follow-up, there were no new cerebral lesions and the inflammatory cervical myelopathy decreased in volume . Walking was unrestricted; unfortunately, the visual impairment remained unchanged. Clinical stability was maintained after 12 months of treatment. A synopsis of the clinical course is shown in .

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+On the 2nd of March 2013, a 26-year-old man resident of Rafsanjan (Kerman province, south-eastern, Iran) was admitted to Shahid Sadoughi Hospital of Yazd, Iran with symptoms of severe abdominal pain. The patient reported extensive biting on his left leg by a dog showing marked aggressiveness, on the 22nd of September 2012, eight months before symptomatic disease onset. The dog had bitten four people who had received rabies immune globulin (RIG) and vaccine while our study patient had not received this treatment. The dog died three days after the biting incident. On admission, our study patient stayed at the surgery unit for one day because of his severe abdominal pain followed by two days at the neurology unit because of behavioral changes. After consultation, he was transferred to the infectious diseases ward.
+On the first day of hospital admission, the patient had malaise, diplopia, headache, depression, vomiting and severe abdominal pain in the hypogastria. He also had a five-year history of consumption of narcotic substances (opium) but had quit use since six months ago. Complete blood count revealed a normal count of leucocytes (9200/μL). Blood had a slight increase of glucose (111 mg/dL). Wright and Widal tests were negative. Cerebrospinal fluid (CSF) was analyzed and showed 100% lymphocytes, two white blood cells (WBC), 159 red blood cells (RBC) and protein 40 mg/dL.
+On the 3rd and 4th of March 2013, the patient had a slight fever (38.1°C), malaise, headache, abdominal pain and abnormal behavior. Finally, the patient died on the 4th of March 2013. Cerebrospinal fluid sample was submitted to the Pasteur Institute of Tehran, Iran. The polymerase chain reaction (PCR) test was performed. This test was positive and proved rabies disease.

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+A 24-year-old virgin Persian woman presented with a labial mass that had emerged 12 years earlier and grown gradually in size, but caused no pain or discomfort until recently. Her medical history revealed no evidence of any underlying disease or mental disorder. She had a Bachelor’s degree and was unemployed. Menarche occurred at the age of 11 years, and the patient’s menstrual cycle was regular. She had no family history of breast or gynecological cancer. A pedunculated mass measuring 75 × 44 mm was observed in the upper left labium and looked exactly like a penis. Its texture was relatively soft, the skin temperature normal, and the lesion had clear boundaries with no ulceration . There was no connection between progressive growth of the lesion and the patient’s menstrual cycle. The lesion was asymptomatic during menstruation. The patient sought no medical advice until she experienced discomfort in the genital area and had difficulty standing up and sitting down. At admission, her vital signs were blood pressure 115/75 mmHg, pulse rate 73 beats per minute, temperature 36.8 °C, and O2 at 99%. Chest examination was normal and she was well oriented. Breast and abdominal examinations were normal. Axillary and supraclavicular lymph nodes could not be palpated. The patient reported no pain on palpation and had no enlarged lymph nodes in the groin.
+Ultrasonography of the lesion revealed a hyperechoic mass with clearly defined margins, internal echoes, and fibroglandular tissue measuring 70 × 40 mm in size. On pelvic ultrasound, there was no abnormality in the uterus and the ovaries. Blood, urine, and serology tests were normal.
+We decided to perform a resection of the mass, which was then completely removed under local anesthesia and sedation . The tissue was sent for pathological examination. No postoperative complications were encountered. The patient was discharged from the hospital after a few days.
+The pathological investigation revealed a benign lesion. It was an accessory breast composed of female breast tissue, with a proliferative and dilated ductus lined with two layers of endothelial and myoepithelial cells in fibrotic stroma, and invaded by mononuclear inflammatory cells . She was reviewed in the gynecology outpatient clinic at 2 weeks, 6 weeks, and 10 months post-surgery. Examinations confirmed full recovery with no evidence of recurrence.

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+A 67-year-old Caucasian female, former smoker with hypercholesterolaemia, depression, fibromyalgia, and migraine (using propranolol 10 mg t.i.d.), was referred to the outpatient clinic for evaluation of periodic drop attacks since 8 years. The attacks, which presented with and without transient loss of consciousness (TLOC), typically occurred once a month and usually in the first minutes of walking. In general, the duration of TLOC was only seconds and episodes were accompanied by symptoms of headaches, light-headedness, dyspnoea, and chest pain. Aside from the syncopal episodes, she had these symptoms on a regular basis, sometimes every day.
+Because of the drop attacks, she fractured her radial head, wrist, and humerus (twice) on separate occasions. Physical examination was unremarkable upon presentation as was blood examination (including normal thyroid/adrenal function). Neurological analysis (including electroencephalogram, computed tomography, and cerebral magnetic resonance imaging) was normal, as were electrocardiogram, echocardiography, and 72 h ambulatory rhythm monitoring.
+Exercise testing (max 80 W) provoked symptoms of dyspnoea, chest pain, and light-headedness with a slightly hypertensive blood pressure (BP) course (max 197/67 mmHg) but no signs of ischaemia. An implanted loop recorder registered only normal sinus rhythm during eight consecutive syncope episodes. Unrelated to the drop attacks, regular supraventricular tachycardias of 180 b.p.m. were observed for which propranolol was switched to metoprolol 100 mg q.d., reducing both her tachycardias and some of her symptoms. However, because of progressive dyspnoea, the beta-blocker was halved, unfortunately causing her original complaints to return. Echocardiography, ambulatory rhythm monitoring, and exercise testing were negative again for significant abnormalities. Subsequent coronary computed tomography angiography did not show significant coronary artery disease. Hereafter, supine and upright measurements of BP and a passive head-up tilt test were performed. Both of which interestingly provoked her symptoms. Within 30 s after standing her BP rose from 130/85 to 180/90 mmHg while she developed her familiar complaints of dyspnoea, chest pain, headaches, and light-headedness. After lying down, SBP quickly returned to stable values of 135 mmHg and symptoms declined. The same occurred with 70° tilt testing. After 90 s, her BP had risen to 200/105 mmHg, it remained high for more than 15 min and her symptoms returned. Nitroglycerine also provoked a hypertensive response. Her heart rate remained stable following standing and tilting and she did not faint.
+As we suspected autonomic dysfunction with excessive catecholamine release, we started the alpha-blocker doxazosin 4 mg q.d. Two months later, she reported that she was free of symptoms besides minor dizziness after standing up and we repeated the tilt test (. Following standing and 70° tilt testing, SBP decreased from 140 to 120 mmHg and remained stable throughout the next 30 min without any complaints. After nitroglycerine, a typical hypotensive response occurred.
+Two years later, she is still free of symptoms.

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+79-year-old female with presented to emergency department with one day of abdominal pain.
+She described the pain in the right upper quadrant of abdomen as sudden onset, moderate to severe in intensity, non-radiating aching associated with chest discomfort. Patient also reported more about 8 pounds weight loss over the past 5 months and poor appetite.
+Her medical comorbidities include Hypertension, hyperlipidemia, Gastroesophageal reflux disease, Osteoarthritis, Rheumatoid arthritis, paraesophageal hernia. Patient denied any toxic habits.
+Over the last two years’ patient had the hospitalization for the abdominal pain and dizziness. She is noted to have large HH and managed for the same. She did not report the dysphagia.
+Her surgical history included right breast lumpectomy for breast cancer and status post chemotherapy and radiotherapy, left eye surgery for macular degeneration and lumbar laminectomy. She denied any thoracic surgery. Family history was negative for any gastrointestinal cancers.
+On presentation her vitals were temperature: 97.1 degrees °F, pulse of 66 bpm, respiratory rate of 19/min and blood pressure of 154/77 mmHg.
+On general physical examination she looked cachectic and dehydrated. Abdominal examination revealed non-distended, soft, non-tender abdomen with no rebound tenderness and normal bowel sounds. The bowel sounds could be perceived on the right chest. Exam of the cardiovascular, pulmonary and Neurological was unremarkable. Retrospectively we were not able to corroborate the radiological finding on the physical exam.
+The hemoglobin of 13 gm/dL with interval decrease due to intravenous hydration. There is no significant leukocytosis and had thrombocytopenia. The renal function was well preserved. Patient was noted to have the elevated lipase at the time of the presentation. She had transaminitis and elevated alkaline phosphatase with the interval improvement during the hospitalization . Her lipase was normal at the normal at the prior hospitalization before 3 mo.
+During the index hospitalization she had computed tomography (CT) of the chest and abdomen with oral and intravenous contrast were for the further evaluation of persistent chest discomfort. CT chest revealed interval enlargement of a massive HH, containing stomach and much of the bowel as well as pancreas and distal extrahepatic biliary duct, probably responsible for obstructive effect upon same. Increased prominence of the pancreas consistent with pancreatitis. Compressive atelectasis in portions of lung adjacent to the hernia, and mass effect upon mediastinum. CT of the abdomen and pelvis with IV contrast reported as large HH causing obstructive effect with dilated biliary system along gall bladder wall edema and pancreatitis.
+Ultrasound of the abdomen showed distended gallbladder, with layering sludge, and continued visibility of intrahepatic biliary ductal dilatation; extrahepatic ducts which were seen to be dilated and massive HH.
+The CT of the chest performed during the prior hospitalization revealed the large HH with herniation in to chest with the stomach and colon in the its content. The pancreas was not present in the hernia content.
+The final diagnosis of the presented case is Pancreatitis and hepatitis as a complication of HH.
+For the management of the acute pancreatitis patient was treated with Intravenous hydration with Lactated Ringer's Solution, analgesics along and intensive care monitoring during resuscitation. We acquired surgery consultation for large HH. In view of no signs of bowel obstruction and acute pancreatitis, no emergent or urgent intervention was recommended. The hydration therapy, monitoring the tolerance of the oral dietary intake and the incentive spirometry were the mainstay of the conservative management. The spirometry induced positive pressure is expected to reduce the HH. In view of the advanced age and the high risk from surgical complications, patient and the family perused palliative care. The interval CAT scan to review the reduction hernia content was planned but could not be done.

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+On January 28, 2020, a 49-year-old female patient was transferred to our hospital for further treatment after being diagnosed with COVID-19. At admission, She presented with fever, cough, sputum, and mild dyspnea. Her body temperature was 38 °C, blood oxygen saturation (SPO2) was 93% under ambient air, oxygen inhalation was immediately given by nasal catheter. After admission, levofloxacin and human immunoglobulin were injected into the veins, recombinant with human interferon a2b atomized inhalation. On the 5th day of admission, the disease deteriorated and her mental state was poor, body temperature was 38.8 °C, blood gas analysis: PO2 49 mmHg, PCO2 38 mmHg. She suffered from type I respiratory failure, which conformed to the diagnostic criteria of severe COVID-19 according to the COVID-19 health guidelines of China national health commission. On the 8th day, oxygen inhalation was given by oxygen storage mask (8 L/min), SPO2 was 93%, blood gas analysis: PO2 49 mmHg, PCO2 38 mmHg, Chest CT indicated multifocal ground glass opacities in both lungs with consolidation in partial lungs, which involving more than 75% of the lungs . On the 12th day of admission, the patient was anxious, agitated, Alprazolam was administered for sedation. Under high-flow oxygen inhalation (FiO2 90%, 50 L/min), SPO2 was 83 to 90%, blood gas analysis: PO2 55 mmHg, PCO2 44 mmHg, the oxygenation index<70 mmHg, which indicating poor oxygenation status, and non-invasive positive airway pressure ventilation was immediately performed. On the 14th day of admission, SPO2 was 90%, blood gas analysis: PO2 48 mmHg, pCO2 37 mmHg, under the condition of non-invasive positive airway pressure ventilation, FiO2 70%, which revealed poor and difficult to ameliorate hypoxemia, mechanical ventilation became imperative. The patient progressed to critical cases and was transferred to intensive care unit (ICU), mechanical ventilation was performed by orotracheal intubation, ventilator conditions: Volume Control ventilation, VT 240 ml, VF 15 times/min, FiO2 100%, PEEP 10 cm H2O, prone position ventilation was performed at the same time. After intubation, maintaining the use of propofol and midazolam for sedation, SPO2 rose to 95% and hypoxemia improved. On the 16th day of admission, the patient’s SPO2 was difficult to maintain with poor oxygenation index and high airway platform pressure, salvage VV-ECMO therapy was performed. Under the guidance of B-ultrasound, the right femoral vein was inserted into the inflow cannula, the right jugular vein was inserted into the outflow cannula, the venous cannula was 20F, the arterial cannula was 17F, the depth of venous cannula was 43 cm, and the depth of arterial cannula was 14 cm. Initial ECMO parameters: speed 3200 rpm, flow 5 L/min, Sweep gas 3 L/min, FiO2 70%. Coordinated ventilator parameters: Assist-Control ventilation, VT 210 ml, VF 18 times/min, FiO2 40%, PEEP 12 cm H2O. Reviewed blood gas analysis: PO2 84 mmHg, PCO2 46 mmHg, oxygenation index improved significantly after ECMO. During the treatment of ECMO, deep sedation was performed and heparin was continuously pumped to maintain activated partial thromboplastin time (APTT) being 40–60s. On the 19th day of admission, support condition of ECMO for the patient was still high, ECMO could not be removed in a short time, and the lung compliance was poor. Chest radiograph showed increased multiple patchy density shadows in both lungs . We decided to coordinating prone position ventilation to improve pulmonary ventilation-to-perfusion ratio. On the 22th day of admission, bronchoscopy showed: a little white sputum could be seen in the main bronchus, and slightly swelling, hyperemia could be seen in the grade 1–4 bronchial mucosa of both lungs. On the 27th day of admission, the patient was tested negative for SARS-CoV-2 nucleic acid by the fluorescence quantitative RT-PCR for two consecutive times. After the withdrawal of sedative drugs, the patient was conscious, had a firm handshake, we stopped the ventilator, ECMO parameters was adjusted: speed 3600 rpm, flow 4 L/min, Sweep gas 3 L/min, FiO2 70%, oxygen was inhaled through the endotracheal tube whit high-flow oxygen therapy (FiO2 45%, 40 L/min). After observated for 30 min, blood gas analysis: PO2 71 mmHg, pCO2 45 mmHg, heart rate was 83 beats per minute, breathing rate was 25 times per minute, and blood pressure was 136/63 mmHg, the endotracheal tube was removed, awake ECMO was performed. Treatment strategies during awake ECMO stage: 1. Strengthen the monitoring and management of bleeding and thrombosis, monitoring the levels of hemoglobin, platelets, APTT and fibrinogen, and set the corresponding target values to be 90 g/L, 100*10^9/L, 40S, 2.0 g/L respectively, supplement the substrate by transfuse some components of blood if failed to meet target values. 2. Pulmonary rehabilitation: prone position or high lateral lying position was adopted for drainage to promote lung recruitment, and a large dose of ambroxol and acetylcysteine were used to dispersing phlegm. 3. During the awake ECMO period, patients had intermittent anxiety and delirium, enhanced psychological counseling, quetiapine and haloperidol were given to fight anxiety and delirium. 4. Combined Piperacillin tazobactam, Datomycin and Voriconazole to fight infection. 5. Strengthen liquid management and nutritional support therapy. On the 35th day of admission, the patient’s oxygen saturation could be maintained at 98%. After re-examination of chest radiograph , the patient was evacuated from ECMO. Reexamination chest CT on March 6, 2020 indicated the ground glass opacities absorbed, and leave some fibrotic stripes . After further treatments of anti-infection, pulmonary rehabilitation, nutritional support, psychological counseling and physical rehabilitation, the patient recovered and was discharged on March 15, 2020.

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+A 44-year-old woman with bipolar disorder was referred to our outpatient clinic 2 months after her first manic episode. She developed bipolar disorder with depressive episodes when she was 42 years old. Her first depressive episode was ameliorated with 3 months’ treatment with sertraline. She had no previous episodes of hypomania or mixed states, and no history of thyroid disease. When she presented at our clinic, she had been treated with quetiapine for 1 month, but still had elevated mood, irritability, and mood-congruent delusions. According to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, we diagnosed her as having bipolar I disorder, and added 200 mg of valproate on 100 mg of quetiapine. Valproate was later increased to 400 mg, after which, her manic symptoms ameliorated.
+Despite her mood being well controlled, she developed severe fatigue 30 days after starting valproate. She had no depression-related symptoms other than fatigue, and no findings suggesting sedation with valproate such as somnolence or impaired attention. Her blood concentration of valproate was 24.2 μg/mL, which was not at the toxic level (normal range 50–100 μg/mL). She had never had a similar reaction to previously used psychotropics. A physical examination and laboratory test found no abnormalities except for low values of free thyroxine 0.50 ng/dL (F-T4; normal range 0.8–1.5 ng/dL) and free triiodothyronine 1.85 pg/mL (F-T3; normal range 2.0–3.8 pg/mL). Although F-T4 was decreased, thyroid-stimulating hormone 2.97 μU/mL (TSH; normal range 0.34–3.8 μU/mL) was within the normal range, suggesting central hypothyroidism. Since other fatigue-causing medical conditions and medications were ruled out by systematic evaluations, we considered that the severe fatigue was associated with hypothyroidism. Thyroid autoantibodies were negative, and gadolinium-enhanced magnetic resonance imaging of the pituitary gland showed no evidence of a pituitary lesion. Considering that her F-T4 levels progressively decreased with increasing doses of valproate (F-T4 0.70 ng/dL under 200 mg and F-T4 0.50 ng/dL under 400 mg), we suspected that her hypothyroidism was caused by valproate. Therefore, we stopped valproate 33 days after its introduction. Her severe fatigue then improved, completely disappearing in about 20 days. A laboratory test 35 days after stopping valproate confirmed that her thyroid function had normalized (TSH 2.17 μU/mL, F-T3 2.99 pg/mL, F-T4 1.10 ng/dL). For the next 12 months, she had no recurrence of mood episodes, hypothyroidism, or fatigue under maintenance treatment with risperidone and carbamazepine.

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+A 50-year-old female patient with the main complaint of “irregular vaginal bleeding and fatigue for 6 months” visited our hospital on 12 February 2019. A mass was presented in the endometrium of the patient detected by ultrasonic examination. On pelvic MRI, a mass in the uterus involved deep muscular layer was confirmed as a 5*6 cm mass that appeared to be pelvic lymph node metastasis . Blood test showed a serous hyponatremia with Na+ level of 123∼131 mmol/L.
+The patient received diagnostic curettage, and the pathological result showed high-grade malignant endometrial carcinoma. Tumor markers including carbohydrate antigens 125 (CA125) and human epididymis protein 4 were detected in normal ranges, and no intraepithelial or malignant lesions were found in cervical exfoliative cytology examination.
+The uterus with enlargement in smooth and hard nature was found in the posterior position according to the gynecological examination. Hard nodules with poor activity and no tenderness can be touched in the anterior uterine wall. Based on the pathological result, endometrial carcinoma invading the serosa was diagnosed in the patient. For the huge mass in the endometrium and the poor state of patient, she received two circles of neoadjuvant chemotherapy with taxol and carboplatin, while improving the persistent hyponatremia, then staging operation of endometrial cancer was conducted under general anesthesia on 21 May 2019.
+During the operation, it was found that the enlarged uterus was located in the middle of the pelvis, the size was about 60 days of pregnancy, and the surface was smooth. The appearance of the main ligament and bilateral fallopian tubes and ovaries was normal, and no tumor was found on the surface of the appendix, omenta, and peritonea. The lymph nodes in the pelvis and surrounding the abdominal aorta were enlarged. First, we get the cytology of peritoneal fluid which resulted negative. And then laparotomy radical hysterectomy with bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy was performed. Incision of the uterus showed that the solid tumor of the posterior wall of the uterus with diameter of 2 cm, slightly brittle texture and pale in color protruded from the muscle wall to the uterine cavity. No lesion was found in the vaginal fornix and cervix. The normal appearance of the bilateral attachments was found, and the lymph nodes in the pelvis and surrounding the abdominal aorta were evidently enlarged.
+Pathological gross examination of the tumor showed that there was no obvious tumor in the serous surface membrane of the uterus. Incision of the uterus showed that the solid tumor of the posterior wall of the uterus with diameter of 2 cm, slightly brittle texture and pale in color protruded from the muscle wall to the uterine cavity. Microscopically, the endometrium was presented with mixed carcinoma. Histologically, two kinds of carcinoma were distributed separately. And the carcinoid was distributed in the muscles of myometrium with invasive pattern, accounting for about 70% of the tumor. Diffused infiltrating carcinoma of myometrium of the uterus is neuroendocrine tumor, with no obvious cellular atypia, abundant cytoplasm, rare mitograms of 0–1/10 HPF, Ki67 index of about 2%, consistent with carcinoid, multifocal vascular and lymphatic invasion, nerve invasion. Squamous cell carcinoma is arranged in the uterine body cavity, accounting for about 30% of the tumor . There is no glandular (or tubular) structure or keratinization of the tumor cell components. The tumor has penetrated the uterine serous membrane. Multi-lesions of lymphatic vessel space infiltration were found. Of the 23 harvested lymph nodes from the pelvic, 5 metastasized lymph nodes were identified in the abdominal aortic and left pelvic lymph nodes with mixed carcinoma. Negative reaction was displayed in the cervix, bilateral ovary, and oviduct. Immunohistochemically, in carcinoid carcinoma, the tumor cells were partly positive for synaptophysin (Syn), S-100, NSE, chromogranin A (CgA), CD56, cytokeratin (CK), H-CK, P63, and P40. The progesterone receptor and the estrogen receptor were negative. CA125, P16, Napsin A, WT-1, CD99, and vimentin were negative. The Ki67 proliferation index was 10%. Elastic fibers show vascular invasion. D2–40 showed lymph node metastasis. In squamous cell carcinoma, the tumor cells were partly positive for CK, CK7, CEA, P63, P40, PAx-8, and CEA. Additionally, results of villin, CDX-2, and CK20 were all negative. The histologic features of the tumor and its immunohistochemical profile support the diagnosis of carcinoid of the endometrium with squamous cell carcinoma .
+Based on the revision of FIGO 2009 staging for endometrial carcinoma, the patient was classified as stage IIIC2. Postoperatively, the patient was given adjuvant chemotherapy with cisplatin and etoposide under interval of 3 weeks and received “sandwich” therapy of chemotherapy-radiotherapy-chemotherapy. In the first circle of chemotherapy, grade 1 nausea and vomiting and grade 3 myelosuppression were developed in the patient. The patient received radiotherapy followed by 3 circles of chemotherapy with no sign of further deterioration. A complete response was achieved in the patient on the basis of the RECIST1.1 criteria. She is currently under close follow-up with no recurrence for 4 years and 4 months after surgery.

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+A 53-year-old man with a history of hepatitis B virus infection was admitted to our hospital owing to sudden vision loss in his left eye. On ocular examination, the best-corrected visual acuity was 20/30 in the right eye and hand motion at 60 cm in the left eye. Fundoscopic examination demonstrated near-total rhegmatogenous retinal detachment with breaks at the 4 and 7 o’clock positions in the left eye. The patient underwent placement of an encircling scleral silicone sponge (#506G; MIRA Inc.) and pars plana vitrectomy with silicone oil tamponade An incidental lens contact with posterior capsular damage was noted intraoperatively. Cataract gradually matured and obscured the fundal view; thus, phacoemulsification was performed two weeks later. During the operation, a fragmatome was used through the sclerotomy to remove the dropped lens with suction pressure of 400 mm Hg, flow limit 20 ml/min and an ultrasonic power output of 70% with pulse rate 5 pulse/second. The followability of the lens was poor in silicone oil and lens material was also difficult to be grasped and pulled out. Lens materials were usually pushed into the peripheral vitreous cavity by the fragmatome tip. Because the room lighting and illumination of the microscope were turned off and both the surgeon and the assistant concentrated on the fundal view under the microscope, so change of the eyelid or sclera were ignored. After the dropped nuclear materials were removed and illumination of the microscope and room lighting were turned on, a whitish wound with scorch and tissue defect on the nasal aspect of the left upper eyelid were noted . Examination of the superonasal sclerotomy site, which was created for the passage of fragmatome, also revealed a focal avascular area that resemble the scleral tissue following electro-cauterization. . An area of focal greyish necrosis was noted surrounding the whitish avascular area. Afterwards, the sclerotomy was closed with 7–0 vicryl sutures, and there was no postoperative leakage. We prescribed tobramycin and dexamethasone ointment (Tobradex®, Alcon, Rijksweg, Belgium) twice a day for the suspected thermal wounds on the eyelid and sclera. Because of the posterior capsular tear, the Sensar® 3-piece Intraocular Lens (AR40E, Johnson & Johnson, CA, US) was inserted and placed into the ciliary sulcus. The retina was attached under silicone oil tamponade. After following-up for one month, both eyelid and scleral wounds healed gradually with scar formation . The patient was then lost to follow-up.

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+A 47-year-old man (height of 175.8 cm and weight of 74.8 kg) complained of a tingling sensation in his leg. He had a history of hypertension and asthma in the previous two years, and history of sinus surgery for sinusitis in the previous one year. Ten days before admission, the patient had a tingling sensation in his left leg, from the posterior thigh to the foot. His spinal radiography findings were unspecified. Therefore, the patient was suspected as having a disc herniation, and observation was decided while continuing the medical treatment. Four days before admission, the patient had a tingling sensation that progressed in both legs. The symptoms did not improve, and motor weakness progressed below the ankle. In the physical examination at admission, motor power was grade 5 in the hip flexor and knee extensor in both lower extremities. However, it was grade 0 in the ankle dorsiflexor, and first toe extensor and flexor, and grades 4 and 0 in the ankle plantar flexor on the right and left sides, respectively. Sensory loss was not found in the L1 - L4 dermatomes, yet was 50% on the right side and 0% on the left side for the L5 and S1 dermatomes. He also had a heating sensation in his left foot and no knee-jerk reaction. He showed a weight loss of 6 kg during the last month, and the signal intensity of the bone marrow on L-spine magnetic resonance imaging (MRI) was diffusively reduced to be less than or equal to the disc. These findings indicated a hematologic disease and the possibility of malignancy with little preserved fat marrow. Abdominal and pelvic computed tomography (CT) revealed diffuse wall thickening of the gallbladder with some irregularity. However, the bone marrow biopsy slides showed a generally hyper-cellular (50% to 60%) marrow for the patient’s age, with small hypo-cellular regions (0% to 20%). On aspirate smears, the eosinophil counts were markedly increased, with expanded eosinophil myelocytes and metamyelocytes. The results of the pulmonary function tests showed an obstructive pattern, such as a forced vital capacity of 54%, a forced expiratory volume in one second of 46%, and forced expiratory flow between 25% and 70% of 33% of the predicted values. The findings from a nerve conduction study suggested multiple mono-neuropathies. In addition, his laboratory findings showed peripheral eosinophilia and positivity for myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA; ). Therefore, CSS was strongly suspected, and steroid and cyclophosphamide therapies were started after nerve biopsy under spinal anesthesia. At that time, the symptoms were progressing to the left wrist drop and both legs. However, nerve biopsy results were consistent with demyelinating peripheral neuropathy. The patient underwent cholecystectomy under general anesthesia to exclude gallbladder cancer, suspected on the basis of CT findings, and pathological confirmation was possible with a gallbladder specimen .

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+A 50-year-old Asian female presented to the hospital with dysphagia, diarrhea, retractable nausea and vomiting, and persistent orthostatic hypotension. She was admitted for further workup due to debilitating orthostatic hypotension and dehydration.
+Her medical history was notable for gastrointestinal amyloidosis (diagnosed via stomach biopsy; unknown mutation due to lack of records), persistent nausea, peripheral neuropathy, and carpal tunnel syndrome. However, due to the patient recently immigrating to the United States from Vietnam, it was difficult to ascertain complete medical history without any available documentation from her doctors in her home country.
+Prior to the diagnosis of cardiac amyloidosis, the patient was taking 40 mg pantoprazole twice daily for acid reflux symptoms and metoclopramide as needed for nausea.
+On initial physical examination, she was afebrile with a blood pressure of 86/73, heart rate of 88 beats/min, respiratory rate of 18 breaths/min, and pulse oximetry saturation of 97% on room air. Her chest was clear to auscultation; she had a regular rhythm and no audible murmurs; her jugular venous pressure was not elevated; her abdomen was non-tender to palpation. She had good pulses bilaterally in both the upper and lower extremities. She did not complain of fever, headaches, vision changes, myalgias, fatigue, chest pain, palpitations, skipped beats, shortness of breath, or edema. She later did endorse bilateral upper and lower extremity paresthesia, syncopal episodes, and dizziness in addition to her presenting complaints.
+On initial presentation at the hospital, she was volume resuscitated with intravenous fluids without improvement in orthostasis. Midodrine and fludrocortisone were started, as well as antiemetics and proton pump inhibitors for symptom relief. With improvement in her hemodynamic status, she was able to be discharged and followed up in our cardiomyopathy clinic for further management.
+Routine blood tests and cardiac biomarkers were obtained . To first rule out gammopathy, serum and urine electrophoresis, serum-free light chains were obtained and were negative for Amyloidosis light chain (AL).
+The chest radiograph did not show any acute findings. Electrocardiogram (ECG) showed normal sinus rhythm with first-degree atrioventricular block, left axis deviation, and low voltage in limb leads. No prior echocardiogram (ECHO) was available, so an initial ECHO was obtained showing preserved ventricular ejection fraction (EF), moderate left ventricular hypertrophy (LVH), stage II diastolic dysfunction, and small pericardial effusion ( and ).
+Owing to the complexity and the multisystem involvement, along with the patient’s symptoms and history of GI amyloidosis, the main differential diagnosis was cardiac amyloidosis. Other differentials, such as high-output heart failure and restrictive cardiomyopathy, were considered but were less consistent with the patient’s presentation.
+Next, we performed a 99Technetium pyrophosphate (99mTc-PYP) planar scintigraphy . A quantitative analysis of the heart retention pattern showed a heart-to-contralateral lung (H/Cl) ratio of 1.66 , strongly suggestive of amyloid deposition. To differentiate the type of cardiac amyloidosis, genetic testing was obtained and revealed a heterozygous pathogenic mutation in the TTR gene, diagnostic for TTR amyloidosis.
+Of note, the patient does have a strong family history of amyloidosis. She has stated that four out of her seven siblings have passed away from amyloidosis in Vietnam (three brothers and one sister). It is unknown if the patient’s parents also suffered from this disease. Unfortunately, family history cannot be verified, and therefore, a pedigree chart cannot be completed. Cascade screening performed for her two sons living in the United States was found to be negative.
+Hereditary transthyretin cardiac amyloidosis secondary to Gly67Ala mutation.
+The main goal of her treatment was to optimize her cardiac function and symptom management. Our patient had numerous manifestations of both cardiac and GI amyloidosis that affected her daily life. She underwent multiple esophagogastroduodenoscopies (EGD) for her ongoing dysphagia, complaint of food being stuck in her throat, as well as persistent nausea and vomiting. Initially, she was diagnosed with reflux esophagitis, but with repeat imaging studies, she was eventually also diagnosed with gastroparesis, for which she was continued on metoclopramide and pantoprazole. Her orthostatic hypotension was treated with 2.5 mg midodrine three times daily and 0.1 mg fludrocortisone daily. She was sent to a neurologist for further evaluation of her peripheral neuropathy. She underwent nerve conduction and EMG studies and was found to have moderate axonal sensorimotor polyneuropathy with superimposed bilateral median nerve neuropathy. She was initially prescribed gabapentin with mild relief of her symptoms, but it was discontinued due to the patient’s persistent syncopal episodes. She was then started on TTR-specific medication 284 mcg/1.5 mL Inotersen subcutaneously weekly for her neuropathic symptoms related to TTR amyloidosis. Although Inotersen somewhat reduced her symptom of neuropathy, it was eventually discontinued due to persistent thrombocytopenia, and unfortunately, Tafamidis was not approved at that time. She was later started on Patisiran infusion, at which point she was finally able to stand up with minimal dizziness. However, approximately six months after the initiation of Patisiran, it too had to be stopped due to the patient’s intolerance to this medication, with the main complaints of debilitating fatigue and persistent nausea and vomiting. At that time, the patient did agree to start Tafamadis, and ongoing efforts are being made to make this drug available to this patient.
+Her overall condition and response to treatment were closely monitored in our clinic with monthly follow-up visits. The patient initially tolerated medications as stated above. However, despite medical management, her overall condition has been deteriorating. She continued to have a poor appetite and lost a significant amount of weight which further contributed to her weakness and fatigue. She has been hospitalized a multitude of times throughout the last two years with ongoing dysphagia, hypotension, orthostasis, syncope, nausea, and vomiting, ultimately being admitted for dehydration and malnutrition. The patient eventually underwent further evaluation by her gastroenterologist, and a percutaneous endoscopic gastrostomy tube was placed for nutrition purposes. She continues to follow up with cardiology and gastroenterology clinics. She was also hospitalized on several occasions with obstructive urinary tract infections and urinary retention, which ultimately resulted in the placement of a chronic foley catheter. She is now being closely monitored by urology services as well. The patient had several repeat ECHOs without major changes from imaging obtained on the initial clinic presentation. The most recent ECHO is without any significant changes. Her EF continues to be normal, and she continues to have moderate LVH and stage II diastolic dysfunction with persistent, small pericardial effusion. Fortunately, she was never hospitalized with symptoms of heart failure. Her current medication regimen includes pantoprazole, amitriptyline, gabapentin, fludrocortisone, midodrine, droxidopa, and metoclopramide. Her main complaints remain to be orthostatic hypotension, syncope, dizziness, weakness, and peripheral neuropathy with resultant insomnia.

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+In December 2022, a 26-year-old Iranian woman was referred to the otolaryngology clinic of our institution, complaining of a growing neck mass, hoarseness, dysphagia, and nocturnal sweating over four months. Her family history and past medical history were unremarkable.
+On examination, a palpable mass (approximately 4 × 4 cm) was located at the left thyroid lobe. The mass was mobile, non-tender, and hard in consistency. The rest of the physical examination findings were unremarkable.
+The laboratory tests revealed no abnormalities, and her thyroid function test results were all in the normal range.
+Neck ultrasonography showed the increased size of the thyroid gland (right lobe 50×19×17 mm and the left lobe 72×31×27 mm). Parenchymal echo of the isthmus and left thyroid lobe was decreased and heterogeneous, suggesting replacing the entire left lobe and the isthmus with a hypoechoic mass. Moreover, it revealed two hypoechoic nodules (sizes of 6 and 10 mm) with distinct boundaries in the right thyroid lobe. No calcification and lymphadenopathy were reported in the neck ultrasound.
+Fine needle aspiration (FNA) cytology of the left lobe of the thyroid gland revealed colloid goiter without evidence of malignancy.
+The patient underwent a total thyroidectomy. Intraoperatively, due to the firm consistency of the mass and suspicion of malignancy, the frozen section was performed. The frozen section analysis of the left lobe and isthmus was positive for malignancy. According to the lack of evidence regarding the lymph nodes’ involvement in ultrasound and benign FNA cytology results, only paratracheal lymph node dissection was performed for the patient, instead of complete neck dissection.
+The postsurgical course was uneventful, and the patient was discharged on the third day following the operation.
+Postoperative histopathological examinations of the surgical specimens obtained from surgery were performed. Gross examination showed the replacement of most of the left thyroid lobe and isthmus with a white multinodular mass, as well as a part of the right lobe with different tumors, including a white multinodular mass and two distinct white nodules. On microscopic examination of the same tumors in the left and right lobe by H and E staining, tumor cells had ill-defined cell borders with vesicular nuclei and distinct nucleoli arranged in well-demarcated lobular growth with fibrous bands separating variably sized solid islands and some lymphocytes between tumoral cells with focal necrosis. The immunohistochemical analyses of this tumor were positive for CD5, P63, CD117, CK 5/6, CKAE1/AE3, and Ki-67 labeling index (15-20%, hot spot) but negative for thyroglobulin, calcitonin, TTF 1, and TdT. Hence, based on the immunohistochemical results, this tumor was definitely diagnosed as ITTC.
+The gross examination of two other smaller tumors, which were near the first tumor in the right lobe, showed two white cream nodules with sizes of 0.2 and 0.7 cm attached to the thyroid capsule. Microscopic examination of both nodules showed small to medium-sized follicular structures with nuclear grooves, intranuclear inclusions, and ground glass appearance. These tumors were diagnosed as follicular variant of papillary thyroid carcinoma according to the immunohistochemical analyses: negative for CD5, P63, CK 5/6, while positive for TTF 1, thyroglobulin, and CKAE1/AE3.
+The excised paratracheal lymph nodes were tumor-free based on histopathological studies.
+ITTC invaded the cervical muscles and fibrofatty tissue with no lymphovascular or perineural invasion, but the PTC tumor was localized into the thyroid gland and did not spread outside the thyroid capsule.
+The pathological and immunohistochemical analysis results of our case are shown in and , respectively.
+The patient underwent postoperative radiotherapy with 60 Gy in 30 fractions over one month. She remained well during the one month of the follow-up period, with no tumor recurrence or metastasis on imaging studies.

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+A 75-year-old man with a history of stage 4 prostate carcinoma that was first diagnosed in 2008 developed an idiopathic limbal stem cell deficiency and underwent bilateral keratoepithelioplasty by a previous doctor in 2011. He was prescribed the therapeutic contact lenses postoperatively. He was referred to our clinic for further ophthalmic therapy in November 2012.
+Our initial examination found that he had bilateral end-stage primary open-angle glaucoma, prior bilateral keratoepithelioplasty, and phacoemulsification with posterior chamber intraocular lens implantation in the left eye. His decimal visual acuity with Landolt broken ring chart was 0.07 in the right eye and 0.2 in the left eye, and his intraocular pressures were 13 mmHg in the right eye and 13 mmHg in the left eye. He had been treated with 0.3% topical gatifloxacin and 0.1% topical fluorometholone twice a day, topical travoprost and timolol maleate once a day, and 1% topical dorzolamide hydrochloride three times a day for glaucoma. He was also prescribed therapeutic contact lenses for both eyes to protect the corneal epithelium. Systemically, he had stage 4 prostate carcinoma and had had a cerebral infarction. He had been treated with oral anti-androgen drug and 0.1mg/day of dexamethasone. His general condition was very poor. He was examined monthly, and his ocular condition had stabilized by September 2015. His decimal visual acuity with Landolt broken ring chart was 0.2 in the right and left eyes, and his intraocular pressures were 6 mmHg in the right and left eyes in September 2015.
+He visited our clinic in October 2015 with blurred vision in his left eye of two weeks duration. Our slit-lamp examination showed a greyish-white epithelial opacity in the central cornea of his left eye . His decimal visual acuity with Landolt broken ring chart was 0.2 in the right eye and 0.07 in the left eye, and his intraocular pressures were 14 mmHg in the right eye and 15 mmHg in the left eye. The patient was advised to stop using the therapeutic contact lens and 0.1% topical fluorometholone. Fungiflora Y staining of cultures of corneal smears and therapeutic contact lens swabs were negative for fungus but Gram-positive organisms were detected. The organisms were unicellular, spherical, and contained multiple endospores . We identified the organisms as Prototheca spp. based on the morphology. He was started on topical 0.3% tobramycin four times a day, but he could not continue because of irritation. So, 0.5% AMPH-B ointment was prescribed three times a day along with 0.2% topical FLCZ six times a day, and corneal surface debridement was performed four times. The keratitis improved and 4 months later a culture of the ocular surface was negative for Prototheca spp..
+We planned to continue the AMPH-B and FLCZ treatments but had to stop the eye treatments because of a worsening of his general condition. Two months later, a greyish-white epithelial opacity in the cornea of his left eye was detected again . We considered either continuing with the medical treatments or performing therapeutic penetrating keratoplasty (PKP) even though there was a risk of disseminating Prototheca into the intraocular space. We presented the risks of both treatment plans, and the patient declined undergoing therapeutic PKP. So, he was retreated with 0.5% AMPH-B ointment three times a day and 0.2% topical FLCZ six times a day without debridement, and the lesion did not recur. From November 2016 to April 2018, the grayish-white lesion continued to recur during periods of radiation for the recurrence of the prostate carcinoma and invasion of the urinary bladder. We continued the AMPH-B and FLCZ treatments, and the lesions were improved whenever his general condition recovered. The recurrent lesions were intermittent and remained only in the epithelial layer and did not spread into deeper layers. In April 2018, 300 mg/day of oral VRCZ was added to the treatment regimen because new grayish-white epithelial infiltrations were noted. Two months later he stopped the oral medication because he was diagnosed by his oncologist to be at the terminal stage, and he was switched topical 1% VRCZ six times a day. The infiltration was slowly resolved but he died in September 2018.