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+A 38-year-old woman developed numbness in the right limb and weakness and limited movement in the left limb following a fall from hitting her head on a door beam. She was unconscious on the spot. After treatment, her whole body was numb and limb activity was limited. Half an hour later, she felt numb and weak in the right limb and weak in the left limb. She had no previous hypertension, diabetes, or coronary heart disease. 13 years ago, she developed numbness in her right hand after pregnancy and was diagnosed with congenital fusion of cervical C2-5, which was not treated at that time . Her symptoms had improved and had not interfered with her normal life. There was no diplopia, slurred speech, hiccups, nausea and vomiting, dysphagia, urinary incontinence, and no corresponding symptoms such as facial sensory abnormalities. Physical examination revealed a short neck, limited cervical mobility, and low occipital hairline. Below the C3 level of spinal cord, bounded by the anterior median line, there were different sensory and motor abnormalities from left to right. The patient had decreased pinprick and temperature sensation on the right side and normal pinprick sensation on the left side. Her sense of spatial position was normal. There was increased muscle tone in the right upper and lower limbs and decreased muscle tone in the left upper and lower limbs. The muscle strength of the left upper and lower limbs was 0 out of 5 and the strength of the right upper and lower limbs was 4 out of 5. After conservative treatment, her muscle strength gradually recovered. 10 days later, some of the muscle strength showed changes, and the muscle strength of the key muscle groups was as follows: shrugging shoulder muscle strength (left 2, right4), elbow flexion muscle strength (left 2, right 4), elbow extension muscle strength (left 2, right 4), wrist flexion muscle strength (left 1, right 4). finger flexion muscle strength (left 1, right 4), finger extension muscle strength (left 1, right 3), hip flexion (left 2, right 4), knee extension (left 2, right 4), dorsalis pedis (left 3, right 4), plantarflexion (left 3, right 4), and hyperreflexia of the biceps and triceps tendons bilaterally. Abdominal wall reflexes were present, knee and Achilles tendon reflexes were hyperactive, patellar clonus was positive on the right, patellar clonus was positive on the left, ankle clonus was positive on the right and ankle clonus was positive on the left. The dorsalis pedis artery was palpable bilaterally. The bilateral Hoffman's sign was positive. Babinski's sign was positive and Kernig's sign was positive. The findings of Magnetic resonance imaging (MRI) in the neck revealed that small C2-5 vertebral body with partial fusion of the vertebral body; increased anterior atlantoaxial space, posterior superior displacement of the cardinal vertebrae, the narrowing of the spinal canal at the corresponding level and marked compression and thinning of the spinal cord (C1-2 joint instability, discontinuity of the odontoid process, congenital fusion of cervical C2-5). posterior protrusion of the C7-T1 intervertebral disc, with compression of the corresponding dural sac. No significant abnormal signs were seen in the cervical medulla. We considered that the woman sustained BBS because she had previously suffered from KFS, which according to ASIA(American Spinal Injury Association) Impairment Scale was a grade B: incomplete injury. After admission, the woman was given methylcobalamin for neurotropism and tizanidine to reduce muscle tone and received acupuncture and hyperbaric oxygen therapy. After conservative treatment, her spinal cord oedema decreased and the numbness on the right side gradually subsided, but the results were still unsatisfactory so the doctor recommended surgery. She then underwent posterior decompression of the spinal canal, and lateral mass fixation between atlas and axis with screw-plate system . After surgery, her numbness subsided and she continued to receive adenosine cobalamin for neurotropic treatment. She came to our hospital for a check 5 months later after the operation. The numbness of the right limb significantly decreased and the dysfunction of the limbs was slightly better than before. She could sit independently and stand with assistance, but she was still unable to take care of himself. She then underwent regular rehabilitation treatment in our hospital. 18 months later, the numbness of her limbs had disappeared and she was able to take care of herself with assistance, and her condition improved from grade B to grade D according to the ASIA classification.

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+A 62-year-old Caucasian man presented with symptoms of cough, fever, myalgia and chills. Symptoms had begun 6 days prior to admission. He had tested positive for SARS-CoV-2 by Xpert Xpress SaRS-CoV-2 (Cepheid, Dx System Version 4.8) three days after symptom onset. His past medical history was unremarkable except for hyperlipidemia treated with atorvastatin 40 mg daily. No allergies were reported, the patient did not smoke, drink alcohol or use illicit substances. Kidney function was normal on admission.
+Computed tomography (CT) scan of the chest, abdomen and pelvis excluded pulmonary emboli and showed diffuse bilateral ground-glass infiltrates of the lungs with associated lymphadenopathy, moderate pleural effusions, normal-sized and -shaped kidneys with adequate perfusion and without cortical defects.
+Two days after admission the patient required intubation due to acute respiratory distress syndrome (ARDS). He was managed with prone positioning and was initiated on hydroxychloroquine after exclusion of glucose-6-phosphate dehydrogenase (G6PD) deficiency. Antibiotic therapy with amoxicillin-clavulanate was given empirically assuming bacterial superinfection of viral pneumonia. His clinical condition worsened with the development of atrial fibrillation, AKI, paralytic ileus, hemolytic anemia and a maculopapular rash on the trunk and lower extremities.
+The chronologic sequence of medications and clinical events are highlighted in Fig. . Laboratory results are shown in Table . Details of affected organ systems, diagnostics and therapies are listed in Table .
+A maculo-papular skin rash developed on day 7 after admission. Severe AKI with oliguria (AKIN 3), consecutive fluid overload and metabolic acidosis necessitated initiation of continuous veno-venous hemodiafiltration (CVVHDF) on day 9. Peak creatinine was 519 umol/L, urinalysis showed minimal proteinuria and microscopic hematuria. Proteinuria subsequently increased significantly and microscopic hematuria persisted, urine leucocytes were persistently within the normal range. .
+Several days after initiation of CVVHDF (on day 24) the patient developed severe microangiopathic hemolytic anemia, Coombs negative, which was transfusion dependent. Serologic screening was negative for HIV, hepatitis B and C virus infection; anti-nuclear antibodies, anti-DNA antibodies, anti-neutrophil cytoplasmic antibodies, anti-cardiolipin antibodies and complement levels were normal. Eosinophils were initially not significantly elevated. There was no evidence of urinary obstruction or rhabdomyolysis. Echocardiogram showed preserved cardiac function.
+Differential diagnosis of the AKI included acute tubular injury (ATI) due to hemodynamic instability; sepsis-associated AKI; ATI with pigmented tubular casts as a consequence of hemolysis; thrombotic microangiopathy - given the ongoing severe hemolysis with schistocytes on peripheral smear (despite lack of overt thrombocytopenia); collapsing glomerulopathy - given the large rise in proteinuria,; and acute interstitial nephritis associated with antibiotics - given concurrent skin rash, although peripheral eosinophilia and leucocyturia were not marked. In the absence of improvement of kidney function a transcutaneous renal biopsy was performed while the patient was proned in ICU, 32 days after admission.
+Light microscopy revealed 34 mostly normal glomeruli. Few glomeruli were mildly congested, without thrombi. There was diffuse interstitial edema and focal infiltrates with lymphocytes, histiocytes, rare plasma cells, neutrophils and eosinophils. Multiple non-caseating granulomas mostly consisting of lymphocytes and epithelioid histiocytes were present. There was very mild tubulitis with rare lymphocytes in the tubular epithelium. Many tubules had a dilated lumen, flattened epithelium and loss of brush border. Some had fine, isometric vacuolization of the cytoplasm. Rare lumina contained finely granular, mostly eosinophilic and very rare brownish casts only partially positive for hemoglobin in a few tubules. Some peritubular capillaries contained mononuclear cells, but no erythrocyte aggregation. There was mild arteriolar hyalinosis and arteriosclerosis, but no thrombi or vasculitis. Immunhistochemistry showed only trace IgM, Kappa and Lambda in the mesangium. IgG, IgA, C3 and C1q were negative in the glomeruli. Electron microscopy revealed myelin figures in the cytoplasm of a few parietal epithelia. No definite viral particles were detected.
+The biopsy was consistent with granulomatous tubulointerstitial nephritis, acute tubular injury and regeneration. There was no evidence of renal thrombotic microangiopathy, collapsing glomerulopathy or vasculitis.
+Mycobacterium tuberculosis infection as excluded and confirmed by negative cultures of urine and tracheal secretions. Serology for Sjogren’s Syndrome was negative. Sarcoidosis was considered clinically unlikely, despite thoracic lymphadenopathy which was interpreted as consistent with severe SARS Cov2 pneumonia. The ionized calcium levels were normal or low during the ICU stay. Angiotensin converting enzyme and Interleukin-2 levels were however not measured. The biopsy findings could not explain the proteinuria, which was interpreted as a consequence of kidney injury and profound inflammation associated with SARS Cov2 infection.
+Given that a medication reaction was a potential cause for kidney biopsy findings as well as for the rash and the hemolysis, a multidisciplinary decision was taken to stop ß-lactams, amiodarone and pantoprazole and to begin methylprednisolone 60 mg daily on day 37 . 47 days after admission urine output began to improve and CVVHDF was discontinued. The hemolysis resolved, the skin rash improved.
+On transfer to neurorehabilitation 48 days after admission, the patient was tetraparetic due to critical illness polyneuropathy but alert and able to follow simple commands, he had tracheostomy in place and was breathing spontaneously with little support. The course of rehabilitation showed progressive improvement of kidney function . The estimated GFR two months post-discharge was 43 ml/min/1,73 m2 suggesting a likely transition to chronic kidney disease.

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+A 73-year-old Caucasian woman with a medical history significant only for hypertension, presented to our emergency department complaining of intermittent subjective fever, anorexia, weakness, and fatigue for 2 weeks. Her subjective fevers were occurring almost nightly, and she had associated night sweats. Her weight was stable. She had a persistent non-productive cough. There was no sore throat or rashes. Her review of systems was negative for any other current symptoms. Her only medication was enalapril. Her family history was non-contributory.
+She had been previously assessed by her family doctor for the same symptoms 2 weeks prior to this presentation. Routine investigations were unrevealing. At that time, she had left knee pain that developed after a hike the previous month. X-rays of her knee and femur were unremarkable. Her pain resolved within a week. No therapeutic interventions were undertaken at that time.
+She had no sick contacts, no sexual partners, and no insect or tick bites. She had no known exposure to tuberculosis. She travelled to the Channel Islands 3 months before presentation. She had no animal exposures. She denied any history of injection drug use.
+On initial examination, she appeared non-toxic. Her vital signs included a temperature of 38.6 °C, a heart rate of 96 beats/minute, blood pressure of 130/65 mmHg, and oxygen saturation of 99% on room air. There were no rashes and no lymphadenopathy was present. There were no signs of hyperthyroidism and the thyroid itself was normal in size without any nodules. Her jugular venous pulse was 2 cm above the sternal angle. She had normal heart sounds with no extra sounds or murmurs. There were no stigmata of endocarditis. Her lungs were clear with equal breath sounds bilaterally. An abdominal examination revealed a soft and non-tender abdomen. There was no hepatosplenomegaly, jaundice, or asterixis. Examination of her knees did not reveal any redness, warmth, effusions, or pain. A screening neurologic examination demonstrated grossly normal cranial nerves, full strength bilaterally, and normal reflexes, tone, and coordination. She was admitted for further investigation for her fever of unclear cause. Empiric piperacillin-tazobactam and intravenously administered saline were started on admission as acute bacterial infection was in the differential diagnosis.
+Table displays the results of her laboratory investigations. A peripheral smear was unremarkable. Serum free light chains were normal. No monoclone was found on serum protein electrophoresis. Urine analysis was bland. Five sets of blood cultures, a urine culture, and Lyme serology were negative. A chest X-ray was normal. Computed tomography (CT) scans of her head, neck, chest, abdomen, and pelvis were all unremarkable. A transthoracic echocardiogram revealed a normal heart with no vegetations.
+She had one further temperature of 39.4 °C while in hospital, without any clear infectious source. Once the blood cultures were known to be negative, piperacillin-tazobactam was stopped. There was an impression that her workup could be continued on an out-patient basis as immediately life-threatening causes of fever had been ruled out. She was discharged home after an 8-day admission in hospital with plan for out-patient follow up.
+She was seen 1 month after discharge. She had no improvement in her symptoms and noted a recurrence of her left leg pain. Her C-reactive protein (CRP) was 207 mg/L. On examination, she had a large, warm, left thigh mass. An urgent ultrasound revealed a 4.5 × 6.8 × 11.6 cm spindle-shaped, well-defined soft tissue mass with internal vascularity . Magnetic resonance imaging (MRI) found that the mass met the femur but was not invading . An initial biopsy revealed a poorly differentiated malignant neoplasm.
+She underwent a distal femur excision with distal Global Modular Replacement System (GMRS) reconstruction. Final pathology revealed a grade 3, pT2bN0M0 undifferentiated sarcoma with epithelioid morphology. She had no nodal involvement or distant metastases at this time. Her CRP fell to 28.42 mg/L within 8 days of surgical excision. She recovered well from her surgery with resolution of her constitutional symptoms. She subsequently was planned to receive radiation therapy.
+Prior to receiving radiation therapy, a follow-up CT scan was done a couple months after her surgery. This revealed the presence of a new 4 mm pulmonary nodule in the lower lobe of her left lung that was not felt to be a metastasis. There was no other evidence of distant metastases. Given these results, adjuvant radiation treatment was begun. She received 6600 cGy given in 33 fractions to her leg.
+Roughly 1 month following the end of her radiation therapy course, she re-presented to our emergency room with painless hematuria and a month-long history of non-productive cough associated with decreased energy. CT scans of her chest revealed 16 pulmonary masses, measuring up to 6.2 cm. A CT scan of her abdomen and pelvis revealed a solitary nonobstructive renal calculus, as well as a new 3.2 × 6.5 cm pelvic mass.
+She was subsequently referred to radiation and medical oncology where a shared decision was made to pursue palliative management.
+Figure provides a timeline of the above described case.

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+The patient was a 37-year-old male from a non-consanguineous Chinese family. Since the age of 35, he had experienced progressive weakness of his hands and a reduction of grip strength, especially in his right hand. Six months later, muscle atrophy and muscle fibrillation were noticed in his hands, and he was unable to hold things or to write. One year later, he experienced weakness in his lower extremities with no sensory disturbance. He currently experiences difficulty in climbing the stairs and standing up from a squatting position, is unable to lift his foot upward, and trips over easily. Physical examination revealed that the cranial nerves were normal, and that orolingual fasciculations and atrophy were absent. The neck flexion strength was 5 (MRC muscle scale, grades 0–5). The muscle strength of both sides of the body was as follows: triceps and biceps 3/3, forearm flexors 2/2, intrinsic hand muscles 1/1, iliopsoas muscles 4/4, quadriceps muscles 3/3, tibialis anterior and gastrocnemius muscles 2/2. Deep tendon reflexes were absent. There was no sensory abnormality or coordination difficulty of any of the limbs. Atrophy was seen in most of the muscles, especially the interosseous muscles of the hands, bilateral gastrocnemius and anterior tibial muscles . Muscle fibrillation was observed in the biceps and quadriceps muscles.
+The patient’s serum level of creatine kinase was 668 U/L (normal range, 50–310 U/L). Extractable nuclear antigens were negative, and serum sex hormone levels were normal. Peripheral neuropathy antibodies such as GM1-antibody and GQ1b-antibody were also negative, and there was no albuminocytological dissociation of his cerebrospinal fluid. The nerve conduction velocity revealed severe reduction in compound muscle action potential (CMAP) amplitudes and motor conduction velocities in bilateral median nerves, ulnar nerves, and radial nerves, while the sensory conduction was normal (Additional file A and B). Right ulnar nerve F-waves were absent. Chronic denervation/reinnervation (e.g., motor unit action potentials of increased amplitude and duration, with reduced inference patterns) was observed in three regions on the electromyogram (EMG), including the bilateral extremities and sternocleidomastoid muscles (Additional file C, D and E). And spontaneous activity (positive sharp waves) was recorded from these muscles. Echocardiography and electrocardiogram evaluations did not detect any cardiac abnormalities. Lower limb muscle MRI showed marked involvement of the gastrocnemius muscle at the calf level. There was a strongly increased signal intensity in turbo inversion recovery magnitude (TIRM) sequences, indicating muscular edema. A mild increase in the signal intensity of soleus and tibialis anterior muscles was observed in the T2 sequence, indicating fat replacement . At the proximal leg level, slight fatty degeneration was detected in the posterior compartment, such as the semimembranosus and semitendinosus muscles .
+After providing written consent, a skeletal muscle biopsy was taken from the patient’s gastrocnemius muscle, precooled with isopentane, and frozen in liquid nitrogen. Frozen sections of 8 μm were then prepared and examined by light microscopy. A marked variation in fiber size was observed, with many angular atrophic fibers. Some fibers also showed structural changes with abnormal material deposits after staining with hematoxylin–eosin . On Gomori trichrome-stained sections, these abnormal deposits appeared as purple inclusions. They varied in size, shape, and thickness, and were either single or multiple . In the NADH-tetrazolium reductase reaction, oxidative activity was reduced in fibrous areas occupied by the inclusions, showing core-like lesions . Neurogenic changes, such as the grouping of angular atrophic fibers, were also present. Immunohistochemical analysis showed prominent FLNC immunoreactive deposits accumulating at subsarcolemmal and sarcoplasmic levels . Electron microscopy of the available transverse sections showed an inordinate myofibrillar structure and dissolved myofilaments. Subsarcolemmal accumulations of lipofuscin were also present .
+Next-generation sequencing identified a heterozygous missense mutation (c.7123G > A, p.V2375I) in the Ig-like domain 21 of FLNC . Confirmation of the variant was undertaken by Sanger sequencing using an ABI 3730XL DNA Sequencer (Applied Biosystems, Thermo Fisher Scientific, USA). The mutation was absent in the DNA of 100 healthy unrelated controls, and the allele frequency in the Asian population is zero according to the Exome Aggregation Consortium . The p.V2375I missense mutation affects valine at position 2375, which is highly conserved from mice to humans . To exclude other hereditary diseases similar to LMN disease, we also tested for mutations in the genes disrupted in SMAs and the androgen receptor gene, but none were found. Since the patient had no immediate family members and loses contact with other family members, further co-segregation analyses among the family cannot be conducted.

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+A 79-year-old woman presented with recurrent cough and hemoptysis. A computed tomography (CT) and laboratory studies indicated bronchiectasis in the lower lobe of the left lung associated with allergic bronchopulmonary mycosis. One month later, a sudden and massive hemoptysis prompted an emergency fiberoptic bronchoscopy (FOB), which exhibited substantial bleeding in the left lung and its aspiration into the right lung. A single-lumen endotracheal tube was immediately placed in the right main bronchus to isolate the right lung, followed by mechanical one lung ventilation (OLV). We had to choose a single-lumen tube in the endoscopy room unequipped for emergency airway management. An emergency computed-tomography angiography (CTA) revealed a bulged left bronchial artery, urging BAE. The common trunk of bronchial arteries arose from the thoracic aorta , complicating selective advancement of an embolization catheter. The BAE failed to achieve satisfactory hemostasis. During BAE, oxygenation worsened down to SpO2 40%. A shift to bilateral mechanical ventilation provided a slight amelioration in blood gas analysis at FiO2 0.35; pH 7.37, PaCO2, 35.5 mmHg, PaO2 104 mmHg, HCO3− 20.2 mmol/l, and BE − 4.5 mmol/l. However, we were afraid that severely decreased lung compliance produced by persistent blood afflux in both lungs would hamper sufficient and protective mechanical ventilation. We, thereby, decided to install VV-ECMO using a poly-2-methoxyethylacrylate (PMEA)-coated circuit (Capiox®, TERUMO, Japan) withholding the use of anticoagulants with the setting of pump speed 1500 rpm, pump flow 2 L/min, O2 flow, 2 L/min. The coagulation system examinations following the installation of ECMO were activated partial thromboplastin time (APTT) 40 s and serum fibrinogen 158 mg/dl.
+Following 2 days, no apparent active bleeding observed let us confine only to performing FOBs for bronchial cleaning, hoping for spontaneous hemostasis. The finding and lowering extracorporeal membrane oxygenation (ECMO) support (FiO2 1.0 to 0.5) suggested possible withdrawal from VV-ECMO despite chest X-rays manifesting atelectasis in the whole left lung . On day 3, however, an FOB found active rebleeding in the lateral and posterior basal bronchi, where thrombin solution was instilled. The single-lumen tube was replaced by a 35-Fr left-sided double-lumen endobronchial tube through which only the right lung was ventilated and the left lung was kept pressurized at a constant airway pressure 10 cmH2O with 100% O2, intending astriction. Notwithstanding the efforts, we thought such conservative means were only palliative and a radical surgical measure should be adopted. In the meantime, ECMO weaning trials were carried out in accordance with the Extracorporeal Life Support Organization guideline , indicating possible weaning. The ECMO was, however, kept operated at the minimal setting, pump speed 1250 rpm, pump flow 1.5 L/min, O2 flow 0.5 L/min, in preparation for surgery-associated worsening of gas exchange and unexpected hemorrhage. Preoperative total amounts of blood products transfused were fresh frozen plasma (FFP) 6 units, packed red cells (PRC) 6 units and platelets 10 units. The preoperative APTT was 42 s and serum fibrinogen 173 mg/dl.
+On day 4, resection of the left lower lung lobe was scheduled under inhalational anesthesia with sevoflurane while the patient was on ECMO. We were concerned about unstable depth of intravenous anesthesia produced by abrupt changes in hemodynamics and circulation volume. Depth of anesthesia was closely monitored with the bispectral index (BIS®, Medtronic, USA). The VV-ECMO remained well-controlled during the surgery without major cardiovascular or respiratory events. The surgery achieved considerable hemostasis, with the operation duration 3 h 51 min and intraoperative bleeding volume 863 ml. She was transfused with FFP 8 units, PRC 10 units, and platelets 20 units. Postoperative chest X-ray showed good aeration in the resting left upper lung . Bilateral mechanical ventilation presented a marked improvement in gas exchange. However, VV-ECMO still remained operated in the postoperative ICU at the minimal setting since unstable hemodynamics and slowly progressing anemia were sustained.
+On day 5, the patient developed a hematoma in the left thoracic wall. An exploratory thoracotomy was performed, achieving hemostasis. Intraoperative bleeding of 2500 ml was compensated by transfusions of FFP 18 units, PRC 12 units and platelets 20 units. Serum fibrinogen was below 100 mg/dl preoperatively but recovered to 132 mg/dl after surgery. For inspection of intravascular emboli formed possibly after prolonged anticoagulation-free ECMO, a postoperative CTA was performed and found, instead, extravasation of contrast medium from intercostal arteries. Transcatheter arterial embolization (TAE) provided a dramatic hemodynamic stability, enabling weaning from VV-ECMO on the same day. Eventually, VV-ECMO was kept operated without anticoagulation for as long as 5 days. On day 6, a CTA detected floating thrombi in the inferior vena cava and bilateral popliteal veins, which required a continuous heparin administration. She was extubated on day 8 and transferred to a general ward on day 9. She was discharge uneventfully from the hospital on day 53.

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+We report the case of a 37-year-old man with a 6-month history of headaches and blurred vision. Our patient had been followed by an otorhinolaryngologist for 2 years for cervical lymphadenopathy and a right submandibular swelling. The cervical lymphadenopathy biopsy was non-diagnostic twice, showing a non-specific inflammatory disease. He had no other medical background and no personal or familiar history of an autoimmune disease.
+On examination, he had significant swelling of the right hemi face and the neck with trismus and a decrease in the visual acuity of the right eye. The dilated fundus examination showed a right papillary paleness.
+Peripheral blood markers of inflammation were elevated. Screening for immunodeficiency and mycobacterial infections was negative.
+Cerebral MRI showed a pseudotumoral lesion developing in the right pterygoid-palatine fossa spreading to the orbital and the intracranial cavity through the superior orbital fissure. The intracranial portion forms a temporal extra-axial mass mimicking a meningioma that infiltrates the lateral wall of the cavernous sinus. The lesion was strongly enhanced after the injection of gadolinium . CT scans of the chest, abdomen, and pelvis were normal.
+The patient was operated through a pterional approach. Our first strategy was a gross total resection of the intracranial portion of the tumor. Regarding its very firm consistency, we opted for a large biopsy of the extra-axial lesion. The tumor was solid, well-delineated, and strongly adherent to the temporal lobe.
+Histological examination showed dense lymphoidplasmacytic infiltrate with storiform fibrosis [ and ]. Immunohistochemical staining revealed an increased number of IgG4-positive plasma cells . The inflammation is often focal, predominantly in a perivascular location.
+Our patient received high doses of corticosteroids (0.6 mg/kg/day) followed by progressive tapering. His neurological manifestations gradually improved and resolved after 2 months. A cerebral MRI was done 1 month after a well-conducted treatment and showed a reduction of the tumor’s size .

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+A 42-year-old female was seen in the emergency department with three days of severe abdominal pain and sepsis. Medical history included menometrorrhagia due to uterine fibroids and previous endometrial ablation in 2015. She used a contraceptive vaginal ring for three months prior and Provera for 2 days prior to presentation for persistent vaginal bleeding. Physical examination revealed the following vital signs: temperature 39.2°C; blood pressure 136/78 mmHg, pulse 132 beats/min, and respiratory rate 16 breaths/min. Oxygen saturation was 100% on room air. Physical exam revealed tenderness throughout the lower abdomen with voluntary guarding. Labarotory data revealed WBC of 12,000/µL, Hgb of 7.8 gm/dL and Hct of 25.7, sodium of 127 mmol/L, and chloride of 96 mmol/L. Lactate was normal at 1.5 mmol/L. Initial CT scan showed uterine masses, consistent with known fibroids, and minimal pelvic fluid .
+She was initially admitted to the medical service for sepsis. Given her lower abdominal pain, Gynecology was consulted for presumed pelvic inflammatory disease (PID). She was started on empiric antibiotics for PID (ceftriaxone IV 1 g every 24 hours, azithromycin IV 500 mg every 24 hours, and metronidazole IV 500 mg every 8 hours). Blood, urine, and stool cultures were sent upon admission, all of which were negative.
+Her pain continued to progress with rising leukocytosis to 20,000/µL. A repeat CT scan on hospital day four showed interval development of ascites . Surgical consultation was obtained, and she was found to have an acute abdomen. She was taken for a diagnostic laparoscopy, which revealed a dense fibrinous exudate and significant ascites in all four quadrants of the abdomen . Multiple peritoneal biopsies were taken, and peritoneal fluid was sent for gram stain, cultures, and cytology.
+Postoperatively, carcinoembryonic antigen (CEA) and CA-125 levels were obtained. CEA was within the normal range, and CA-125 was mildly elevated at 56.8 U/mL (normal 0–35.0 U/mL). Her WBC fluctuated between 15,000 and 25,000/µL. The peritoneal fluid gram stain did not reveal any bacteria. Cytology revealed rare mesothelial cells and abundant neutrophils but no malignant cells. Final pathology report stated the presence of benign fibromembranous tissue with severe acute inflammation and extensive necrosis, consistent with “severe necrotizing acute peritonitis.”
+Given the extensive inflammatory reaction, infectious disease was consulted. Group A Strep (GAS) peritonitis was suspected, and recommendations were made to continue ceftriaxone at 1 g IV every 24 hours in addition to one dose of clindamycin 600 mg IV. Azithromycin was added to ceftriaxone three days later (IV 500 mg every 24 hours). A streptolysin O antibody (ASO) titer was sent but came back normal at 61 I U/mL (normal range 0–330 IU/mL), arguing against GAS peritonitis. Ceftriaxone was stopped, and azithromycin was transitioned to oral 500 mg daily.
+She continued to have persistent abdominal pain and anorexia. A repeat CT scan obtained nine days after surgery showed peritoneal enhancement and several fluid collections. A diagnostic paracentesis was performed, and the peritoneal fluid was sent to an outside institution for 16S ribosome analysis, to isolate bacterial RNA.
+Her abdominal pain and leukocytosis slowly improved. She continued to have severe anorexia and food aversion, despite reassuring physical exam findings. On hospital day 23, she was discharged home on oral azithromycin. Several days after discharge, 16S ribosome testing revealed Mycoplasma hominis RNA within the peritoneal fluid. Her outpatient antibiotic was changed to oral doxycycline 100 mg twice daily for three months. She was closely followed as an outpatient and gradually demonstrated clinical improvement. She remains well ten months after hospitalization.

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+An 86-year-old male came to our attention seeking medical treatment for a growing lesion of the lower lip. The patient previously treated the lesion with topical antibiotics and steroids, with no improvement in the condition. The lesion was exophytic and with a warty appearance . Suspecting an SCC, the surgeon performed an excisional biopsy on the lesion. . A total body computerized tomography and an echography of neck and mandibular nodes were performed before surgery, showing no presence of suspect secondarisms.
+The histopathological examination confirmed the diagnosis of SCC, describing a histologically well-differentiated lesion. HPV typization of the lesion showed positivity for HPV 16 after a conventional polymerase chain reaction assay. The margins of the lesions were not microscopically clear. Considering the patient’s old age and the unwillingness to undergo another surgical procedure, the patient, one month after surgery, was sent to the Dermatological Unit of Magna Graecia University, Catanzaro, for examination . The patient was there treated with topical 5% imiquimod (Aldara, Meda Pharma S.p.A, Milan, Italy) application on the affected area once a day for two weeks, then once a week. The patient performed another total body computerized tomography one and a half years after surgery due to the follow-up of internal malignancy. No signs of SCC-related manifestations were assessed. Two years after the initial surgical procedure, the patient has not developed any sign of systemic or local relapse of the condition .

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+A 47-year-old Japanese woman, gravida 2, para 0, was referred to our institution for abnormal uterine bleeding. She had an extensive past medical history which included SLE, anti-phospholipid antibody syndrome (APS), idiopathic thrombocytopenic purpura (ITP), as well as previous dissecting right vertebral artery aneurysm and left cerebellar infarction. Her body mass index (BMI) was 18.1. Workup revealed severe anemia requiring an 8-unit red cell transfusion, and subsequent to gynecological examination, endometrial sampling cytology with conventional biopsy revealed Grade 1 endometrioid adenocarcinoma; serum tumor markers were obtained for evaluation and anticipated ongoing management of endometrial cancer; CA-125, CA19-9, and CEA levels were 176 U/mL, 27U/mL, and 1.8 ng/mL, respectively. Given her intravascular hypercoagulability due to ITP, we administered continuous heparin along with methylprednisolone (mPSL) pulse therapy to bring her hematology profile within an acceptable range of tolerability for surgery. The patient’s laboratory results and serologies are summarized in Table . Her medications included prednisolone 20 mg twice a day, candesartan 8 mg daily, amlodipine 5 mg daily, rabeprazole sodium 3 g daily, and 600 μg subcutaneous teriparatide daily.
+Magnetic resonance imaging (MRI) studies revealed cancer invasion into the uterine myometrium . On computed tomography (CT) imaging, abnormal masses involving a large segment of multiple encapsulated lymphadenopathies and measuring up to 6 cm were present both in pelvic and para-aortic lymph nodes , strongly suggesting retroperitoneal metastases from endometrial cancer. However, positron emission tomography-computed tomography (PET-CT) imaging showed only slightly abnormal FDG uptake in the lymph nodes (Standardized uptake value (SUV)-Max = 2.1) in comparison with high FDG uptake in the uterus (SUV-Max = 19.1). Eventually, total hysterectomy and bilateral salpingo-oophorectomy was performed for primary staging, avoiding lymph node dissection due to ongoing ITP-related thrombocytopenia.
+On the basis of preoperative findings, we initially diagnosed the patient as International Federation of Gynecology and Obstetrics stage IIIC2 uterine endometrial cancer, with 70 % myometrial invasion, lymphovascular invasion, and metastasis to the pelvic and para-aortic lymph nodes. The patient subsequently underwent adjuvant chemotherapy with paclitaxel (175 mg/m2) and carboplatin (area under the curve, 6). However, no change in size of lymphadenopathy was observed after 3 cycles of chemotherapy. As her overall condition improved, with platelets stabilizing at >80,000/μL, and the patient wishing to avoid radiation therapy due to the considerable complications, we then performed dissection of retroperitoneal (pelvic and para-aortic) lymph nodes. On gross exam, we found well-circumscribed lymph node masses growing along the lymph vessels , which were systematically dissected , and found to have no metastatic involvement or cured remnants of metastatic disease (0 out of 100 lymph nodes), although there was an option to perform intraoperative diagnosis using frozen sections if necessary. Final pathological diagnosis was consistent with LAM arising from the retroperitoneal lymph nodes.
+Microscopically, masses was composed of neoplastic smooth muscle leiomyoma-like tumor cells with clear to eosinophillic cytoplasm arranged in alveolar pattern without necrosis , and slit-like vascular channels lined by endothelial cells . Lymph node tumors were focally positive for smooth muscle actin (SMA), caldesmon, Melan A, HMB-45, and estrogen receptor (ER), characteristics suggestive of LAM . Interestingly, re-examination of uterine tissue from the primary operation revealed that regional LAM tissue was co-localized with endometrial cancer with similarly arranged alveolar structure . Unlike normal myometrium smooth muscle cells, immunostaining of smooth muscle cells for HMB-45 and Melan A was positive in the LAM lesions. Moreover, we found that LAM cells had locally invaded into the lymphatic vessels of the myometrium. Taken together, our findings presented herein suggest that LAM initially occurred in uterine smooth muscle, subsequently invading the retroperitoneal lymph nodes by ascending via a lymphogenous route. The patient is currently asymptomatic after the final diagnoses of LAM and endometrial cancer (stage IB), with no evidence of recurrence or metastasis to date. No recurrent enlargement of lymph nodes or pulmonary LAM has been observed on repeat CT imaging. However, she is currently maintained on low dose warfarin therapy for SLE-related intravascular hypercoagulability. Long-term follow-up by both internal medicine and gynecological healthcare providers will continue to be important to correctly diagnose LAM and/or cancer-related diseases.

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+A 9-year-old boy was admitted to the paediatric department because of an ongoing headache that had been getting worse in the weeks preceding the hospitalisation.
+The headache was the main symptom, it was ongoing and had been getting worse in the past weeks. The headache started eight months prior to the visit with a frequency of one per month, then escalated to one per week and has been present every day in the last week. He described it as a dull non-spreading pain above the right eyebrow, with an intensity of 5/10. The episodes lasted five to 15 min and usually disappeared after a short rest. He had no need for analgesics. Several times, he was also woken up during the night by the headaches and vomiting. He denied any history of nausea, flashing of light or scotoma.
+The boy had no history of other illness except middle ear inflammation at the age of 9 months and took no medications. He had no known allergies.
+At the admission, the physical examination was within normal limits, as was the neurological examination. The dilated fundus examination showed bilateral papilledema, indicating raised intracranial pressure.
+Laboratory examinations were within the normal range. The haemostasis was normal, as was the blood count and the biochemistry test. The routine laboratory results were normal.
+The MRI substantiated the diagnosis by showing hypointensive modality in the right part of the mesencephalic tectum, which was highly suspectful for a tectal low-grade astrocytoma. It was completely obstructing aqueduct of Sylvius, causing extensive supratentorial hydrocephalus with some reliable findings, such as enlarged third ventricle that was bulging into the sella turcica. Additionally, the periventricular hyperintensive area, effacement of cortical sulci, dilatation of lateral ventricles and intracranial hypertension with important narrowing of transverse sinuses were observed . There were no signs of a hyperdynamic CSF circulation on the MRI at the level of the aqueduct, suggesting a complete flow blockade by the tumour.

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+A 37-year-old woman with a history of chronic back pain and sciatica presented to our teaching hospital at 36.5 weeks' gestation in early labor. At the time of presentation, she was noted to have acute onset of mild-range elevated blood pressures (140s-150s/90s) with a urine protein-to-creatinine ratio of 0.37, consistent with a diagnosis of preeclampsia. Six hours after admission, her blood pressures progressed to severe-range, with a maximum of 195/105. Per protocol, she was given IV labetalol and MgSO4 for preeclampsia with severe features. Shortly thereafter, the patient retrospectively reported that she began to have mid-back pain along with numbness, tingling, and weakness in her right lower extremity, but she did not report these symptoms initially to her healthcare team, as she was more concerned about her pelvic pain with contractions. Approximately 3 hours after the onset of her neurological symptoms, a labor epidural was administered to help control her contraction pain and blood pressures. The epidural catheter was placed uneventfully at L3-L4 with the tip threaded to the maximum height of T11. As the epidural was being placed, the patient then reported to the anesthesiologist that she had been feeling weak. The patient was noted to appear lethargic on exam, but she was able to sit up with minimal assistance for her labor epidural. Therefore, her weakness was attributed to labor. She progressed to complete cervical dilation and had a vaginal delivery with vacuum assistance due to a 5-minute prolonged deceleration on FHT.
+The patient continued to complain of leg weakness after delivery. At 14 hours postpartum, the nurse encouraged the patient to attempt ambulation. However, even with her best efforts, the patient was unable to move her body from a distinct line below her breasts down to her toes. She also noticed numbness, burning, and electrical sensations to light touch from that line down to her toes. At this time the resident team was notified, and a Foley catheter was inserted. There was low suspicion for magnesium toxicity as she had intact reflexes with no complaints of shortness of breath, and her magnesium level was 5.9. She still had mild-range elevated blood pressures at the time, and she remained on IV magnesium for 24 hours postpartum.
+A stat CT scan of the head without contrast resulted in normal findings with no evidence of stroke. MRI of the spine showed a fluid sac suggestive of epidural blood, measuring 3.5 cm in the craniocaudal plane and 0.4 cm in the anteroposterior plane. There was also a mild-to-moderate degree of spinal stenosis at T5-T6 due to extrinsic mass effect of the epidural hemorrhage but no direct spinal cord compression . The patient was immediately started on IV dexamethasone 4 mg q6h. Upon evaluation by neurosurgery, the patient was not considered to be a surgical candidate because the MRI showed no clear evidence of spinal cord hemorrhage or spinal cord compression.
+On the morning of postpartum day #1, the patient remained with paresthesia in her lower extremities and flaccid paralysis from the waist down, but she was able to wiggle her toes. Her blood pressures were predominately normal (120-140/80-90) with a few mild-range elevated blood pressures. Per protocol, she was kept on IV magnesium for seizure prophylaxis until she was 24 hours postpartum. Diffusion-weighted imaging of the spine later that day showed an epidural lesion with a hemosiderin ring that had decreased in size to 2-3 mm in maximal depth, suggestive of a resolving epidural hematoma when compared to the most recent MRI .
+On postpartum day #2, the patient was started on PO nifedipine XL 30 mg daily to consistently maintain her blood pressures within normal range. Her mobility improved with demonstrated flexion and extension at the hips bilaterally, in addition to return of normal sensation in her lower extremities.
+The patient's movements and sensation continued to improve day by day while she was kept on IV dexamethasone and PO nifedipine. By postpartum day #4, the patient was ambulating with a walker and had good bladder and bowel control. On postpartum day #6, the patient was ambulating without assistance and reported complete resolution of her pain in the back and lower extremities. She was discharged home in stable condition.
+A follow-up MRI 6 weeks later showed complete resolution of the spinal epidural hematoma . At the time, she was still ambulating independently and had full control of her bladder and bowel function.

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+A 12-year-old boy complained headache for 6 months. MRI revealed a D-shaped mass adjacent to the superior sagittal sinus and falx in the right parietal lobe. The mass was well-circumscribed and dura-based, with a size of 15 × 27 × 22 mm. No necrosis, cysts or hemorrhage was found. MRI also showed isointense with cortex on the T1-weighted imaging and hyperintense on the T2WI sequence, lightly hyperintense on the T2-Flair weighted imaging, but MRI enhanced homogeneously and intensely after intravenous administration of the contrast with gadolinium . The gray matter next to the central gyrus was buckled. Dural tail sign was observed, suggesting a meningioma “en plaque”, but peritumoral edema was indistinct. Computerized tomography perfusion imaging further showed prolonged time to peak and mean transit time, as well as increased relative cerebral blood volume and flow.
+Simpson grade II gross total resection was performed in a right decubitus position. Through a craniotomy of 5.5 × 6.5 cm, we found his dural arteries and veins enlarged abnormally, while the bone flap had no signs of invasion . The tumor was close to the centerline, its anterior edge adhered to the right vein of Trolard, and the right wall of the superior sagittal sinus and falx was invaded. The central sulcus in close to the tumor was located by the somatosensory evoked potential with cortical electrode on the cortex surface, and the epilepsy wave detected by the electroencephalogram was not found during the operation. The lobulated tumor with the size of 3 × 2.5 cm had a clear boundary with many nodules on the surface and adhered to the normal brain tissue, without full arachnoid membrane between the tumor and the brain. The strata externum of the sagittal sinus and falx was removed, and the inner of the sinus was kept intact. The bone flap was returned to the patient. No neurological adverse events occurred during the follow-up.
+KF-PRO serial scanner was used, and pathological assessment was performed using K-Viewer software. Pathologically, the tumor cells manifested nested, sheet-like or whorled aggregates of spindle to epithelioid cells prominently with indistinct cell borders. Mitotic count was less than 1 per 10 high-power fields. Focally, rhabdoid cells were identified, accounting for 10% of the tumor . Rhabdoid morphology was characterized by incomplete differentiation and intercellular adhesion, not accompanied by paranuclear inclusion body. Atypical features including brain invasion, hypercellularity, small cell formation, macronucleoli, sheeting architecture and spontaneous necrosis, were not identified in this tumor. Therefore, the patient was diagnosed as WHO grade I meningioma with focal rhabdoid features. The tumor cells showed diffuse and strong EMA and SSTR2 immunoreactivity. Immunohistochemistry for CD34, S100, STAT6, CK and SOX10 were negative in all tumor cells. Most tumor cells showed diffuse expression for SMARCB1/INI-1. The Ki-67 index was less than 1%.
+To determine molecular features and seek potential treatments, a next-generation sequencing-based gene panel (Simceredx, Nanjing, China) was used for genomic profiling in primary tumor tissue and matched blood. Except for a novel MAML2-YAP1 fusion break point (5’ MAML2 exon 1 fused to 3’ YAP1 exons 7–9) identified , no other mutations like single nucleotide polymorphism, InDel and copy number variations were detected.

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+A 52-year-old, right-handed, previously healthy woman presented to our hospital for unprovoked numbness and worsening impairment of sensibility at the level of her right thumb, index, middle finger, and radial half of her ring finger. She also complained of impairment in everyday activities due to worsening weakness of her opponens pollicis muscle. Only slight improvement in her symptoms was reported during the past 12 months despite splinting the hand using a wrist brace, undergoing physiotherapy, and taking high doses of non-steroidal anti-inflammatory drugs (NSAIDs) and Gabapentin. The patient reported a chronic history of repetitive movements of the fingers and wrists with chronic pressure points on the right wrist.
+On examination, the affected hand revealed no swelling or local heat. Atrophy of the thenar muscle and hypoesthesia in the distribution of the median nerve were noted. Both Phalen’s test and Tinel’s sign were positive on the right side with no restriction in the range of motion of wrist and fingers. Nerve electrodiagnostic testing suggested right median nerve compression at the level of the right carpal tunnel. An initial plain radiograph of the right wrist showed an oval radio-opacity on the volar side of the wrist joint facing the carpal bones .
+A confirmatory magnetic resonance imaging (MRI) of the right hand and wrist showed a solitary oval calcification (low-intensity lesion both in T1WI and T2WI) measuring 2 × 0.8 × 0.6 cm (cm), located in the carpal tunnel centrally between the flexor tendons of the wrist, at the lunatum-capitatum junction, without surrounding adherence (the boundary between the lesion and the surrounding tissues was clear) . The lesion is also surrounded by a reactive fluid collection . The MRI also showed subtle tenosynovitis of the flexor’s tendon sheaths, with mild compression of the median nerve . The patient’s full blood count, vitamin D, calcium, phosphate, electrolytes, uric acid, urea, creatinine, and alkaline phosphatase were within normal range. Other laboratory data including an endocrine and rheumatology panel were also normal. Subsequently, the patient was diagnosed with CTS secondary to a localized calcareous mass.
+Given that conservative treatment was ineffective, the patient’s condition was managed by open incisional carpal tunnel release. An incision of approximately 4 cm was performed on the volar side of the right wrist facing the third metacarpal bone . The palmar aponeurosis was then dissected, and the flexor retinaculum was located and transected. The white calcareous tumor was lying over the carpal bones of the osteofibrous canal, and it was only visualized after retracting the median nerve. A 2.1 by 1.0 cm mass was easily removed with no adhesion to surrounding tissues. Histological sections showed calcified deposits encased in a fibrocartilaginous tissue with inflammatory infiltrates composed of giant cell granulomas. These findings supported the diagnosis of tumoral calcinosis [, ].
+During her follow up, three months following the surgery, no clinical or radio-graphical signs of recurrence were noted and the patient reported complete resolution of her symptoms.

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+A 43-year-old Caucasian woman presented to our clinic with a mild itching sensation in her arms and legs. She was referred by her physician for contact eczema. A physical examination revealed erythematous papular lesions over her metacarpophalangeal and proximal interphalangeal joints together with a periungual involvement with redness, hyperkeratosis, and capillary telangiectasia along the distal nailfolds on both her hands . No other skin findings such as heliotrope rash or erythema on the extensor surface of her extremity joints were present.
+She complained about pain and weakness in the muscles of her proximal extremities and neck flexor muscles with difficulty raising her arms and climbing stairs. At the same time she experienced swallowing difficulties and reported an uncharacteristic weight loss of 10 kg in the last 3 months. She had a 30 pack-year history of cigarette smoking with persistent nicotine use at the time of presentation in our clinic. A neurological examination showed symmetrical mild proximal muscle weakness. The rest of her physical examination including auscultation of her lungs, body temperature and lymph nodes status was normal.
+The laboratory findings revealed elevated serum levels of myoglobin 397 μg/l (normal range 25 to 58), creatine phosphokinase (CK) 881 IU/L (normal range 0 to 145 IU/L) and aldolase 11.8 U/l (normal range up to 7.6 U/l). Her liver enzymes were slightly elevated as were aspartate transaminase (AST) 69 U/l (normal range up to 31 U/l) and alanine transaminase (ALT) 50 U/l (normal range up to 34 U/l). Antinuclear antibody (ANA 1/160) was weakly positive while extractable nuclear antigens (ENAs) including anti-Jo-1 antibody were negative. Other laboratory parameters such as C-reactive protein (CRP) and lactate dehydrogenase (LDH) were normal. A histopathologic examination of the skin/muscle biopsy showed vacuolar degeneration of the basal membrane with perivascular inflammatory infiltration together with a lymphohistiocytic infiltration. In addition, an extensive mucin deposition in her dermis and linear atrophy of her muscle layer were detected. The morphologic features were compatible with dermatomyositis. An electromyogram and magnetic resonance imaging (MRI) of the muscles of her extremities showed a symmetric moderate myopathy mainly of proximal muscles which confirmed the diagnosis of dermatomyositis. A chest X-ray showed an unspecific pulmonary nodule in the upper field of her right lung. Computed tomography (CT) of her chest revealed a nodule of 20×22 mm in her right upper pulmonary field without mediastinal or axillar lymphadenopathy . A CT-guided biopsy of the lung nodule revealed a lung adenocarcinoma of moderate differentiation. After diagnosis of the lung tumor was made, she underwent a thorough screening including CT of her abdomen and MRI of her head/neck in order to exclude other tumors, lymph metastases or organ metastases. Furthermore we performed an endoscopy of her upper digestive tract and a gynecological control to exclude any other types of cancer. All of them were negative. Her pulmonary function tests and echocardiography were normal as well.
+She was given a presumed diagnosis of a lung adenocarcinoma with clinical manifestations of paraneoplastic dermatomyositis. No metastatic lesions were found, and there were no abdominal or cerebral abnormalities. A corticosteroid treatment with prednisolone 1 mg/kg/day was administered. In the absence of cardiologic or anesthesiologic contraindications she was assessed to be eligible for surgery. She underwent a right upper lobectomy. The histopathology showed a moderately differentiated adenocarcinoma that was pathologically staged as T1b N0 M0. In the postoperative period, she presented partial improvement of her skin lesions, muscle weakness and dysphagia.

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+A 14-year-old iTaukei (indigenous Fijian) girl presented to our hospital with a 1-month history of abdominal pain. Two days prior to her admission, her abdominal pain became worse, especially after movement, and was relieved by lying down. She also developed a high-grade fever and nausea and had one episode of vomiting. She gave no history of cough, diarrhea, vomiting, or dysuria. Her last menstrual period was on 28/9/2017. She denied any history of sexual intercourse.
+She was referred to a nearby hospital, where ultrasonography showed a cystic structure measuring 4.9 cm × 4.4 cm at the right adnexal region. Minimal free fluid was seen in the pouch of Douglas. No obvious appendix abnormality was seen, and other structures, including the uterus, were normal. She was then transferred to one of the main hospitals in Fiji for further investigation and management.
+The patient’s past medical history was unremarkable. She had no record of previous admission. She had not been receiving any regular medication and had no known allergies.
+The patient resides in a village that is approximately a 45-minute drive from the nearest town. She lives in a two-bedroom corrugated house with her parents and three younger siblings. Her usual diet consists of boiled root crops (such as cassava and taro), local vegetables, and fish. The water source is a spring that supplies the whole village. The family uses a water seal toilet. She gave no history of travel outside her village in 2017.
+On examination at the main hospital, the patient looked unwell. Her pulse was 116 beats per minute, blood pressure 114/60 mmHg, respiratory rate 21 breaths per minute, and temperature 38.8 °C. The results of her chest and cardiovascular examinations were normal. Abdominal examination revealed generalized tenderness on light palpation. However, there was no guarding or rebound tenderness, and no mass was palpable. The result of the per rectal examination was normal, as was the remaining examination.
+Blood tests revealed a hemoglobin of 9.8 g/dl (normal range [NR] 11.5–18.5 g/dl) and white blood cell count of 14,100 cells/mm3 (NR 4000–11,000 cells/mm3). Two blood cultures revealed no growth after 48 hours. The patient’s full blood count, liver and renal function, and serum electrolyte test results are shown in Table . The results of her chest and abdominal x-ray were normal.
+Exploratory laparotomy revealed serosal appendicitis with erythema and abundant fibrinous peritoneal fluid; hence, an appendicectomy was performed. It was noted that the right ovary was enlarged and had ruptured because of pus collection. The right ovary was incised, and pus was drained. This pus was cultured and yielded a pure growth of Salmonella Typhi , which was identified by using Microbact™ 12A/12B identification kits (Oxoid Microbiology Products, Altrincham, UK). This identification was later confirmed by Salmonella-specific antiserum testing (Difco™; Becton, Dickinson and Company, Franklin Lakes, NJ, USA). The antimicrobial sensitivity test was performed using a disk diffusion method on Mueller-Hinton agar. The organism was susceptible to all tested antibiotics (ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, gentamicin, cephalothin, ceftriaxone, ciprofloxacin, and nalidixic acid). Histopathology of the resected appendix revealed reactive lymphoid follicle in mucosa and acute inflammation on the serosal layer, compatible with periappendicitis.
+The patient was treated with intravenous ceftriaxone 1 g twice daily, cloxacillin 1 g four times daily, and metronidazole 500 mg three times daily for 5 days. She made an uneventful recovery and was discharged to home on the sixth postoperative day to complete a further 8 days of oral cotrimoxazole. Patient was reviewed 1 week after her discharge from the hospital. She did not have any complaint; her surgical wound was clean; and there were no remarkable physical findings. The result of her stool culture after completion of treatment was negative for Salmonella.

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+A 24-year-old gentleman with no past medical history had been experiencing debilitating chest pains for 2 years. He described these as varying in intensity, worsened by exercise, and relieved partially by analgesia. They were not associated with palpitations or syncope.
+Unfortunately, due to his symptoms he had to give up his studies and minimize his physical activity. He had trialled multiple analgesics (daily paracetamol and tramadol) with partial relief of symptoms.
+He underwent serial investigations at his local cardiology unit, including a cardiac CT which identified an absence of pericardium on the left side of the heart. He was referred to the Adult Congenital Heart Disease (ACHD) team at The Royal Brompton Hospital.
+When first reviewed in the ACHD clinic he was not cyanosed, in sinus rhythm with no evidence of cardiovascular decompensation. His apex beat however was grossly displaced to the left and more so on lying supine. His first heart sound was normal, second split, there was also a soft one-sixth systolic heart murmur. The rest of his examination was unremarkable.
+His electrocardiogram showed him to be in sinus rhythm at 78 b.p.m., with normal conduction times but a poor R wave progression and an intermittently changing axis.
+A chest radiography which showed situs solitus, levocardia, with a left aortic arch, no displacement of the heart to the left, and a protrusion at the level of the left atrial appendage at the left upper quadrant of the heart.
+His echocardiogram showed a structurally normal heart with maintained ventricular function. Stress echocardiography showed mild right ventricular dilatation at rest with increase in right ventricular volume directly after exercise. A cardiac CT revealed a partial absence of pericardium on the left side with a small layer of pericardium on the upper right heart border. The heart was grossly shifted leftwards and posteriorly, highly suggestive of enhanced heart mobility. Similarly, no pericardium could be seen on cardiac magnetic resonance imaging (CMR). There was lung tissue in between the base of the heart and diaphragm , the heart was displaced to the left of the chest and the RV appeared dilated .
+The patient’s symptoms were thought to be due to his absent pericardium and related to cardiac mobility. We were struck by the discrepancy of the erect Chest X-ray (CXR) and supine CMR with regards to cardiac position, mobility, and the severity of disabling symptoms. We thus discussed the patient at our ACHD Multidisciplinary Team meeting and offered him surgery, in an attempt to immobilize his heart, hoping to improve his symptoms and quality of life.
+The heart was exposed via a left postero-lateral thoracotomy. There was complete pericardial agenesis on the left side and on the diaphragmatic surface. Several 0.4 mm thickness Gore-tex® patches were sutured together to create a large sheet and this was sutured down with widely spaced interrupted 3-0 Prolene® sutures to the posterior mediastinum, starting at the level of the left pulmonary artery, posterior to the left atrial appendage and along the left hilum and inferior pulmonary ligament, to the diaphragm and down. This was then brought forward to the anterior chest wall and then fixed anteriorly along the anterior chest wall with the superior end free (see Figure ). A left pleural drain was inserted and a paravertebral catheter for analgesia, followed by routine multilayered chest closure.
+The post-operative course was uneventful apart from a small left apical pneumothorax with a small pleural effusion. Both resolved spontaneously within days.
+Echocardiography on Day 5 showed that the RV was of normal size with no evidence of pericardial effusion nor compression of cardiac chambers. The patient was discharged 8 days after his procedure on simple analgesia, mobilizing well with improved symptoms.
+Three months from surgery the patient had come off analgesia completely, with resolution of his debilitating chest pains. He was resuming his University studies and restoring normality in his life.

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+A 44-year-old Caucasian man presented to an outpatient clinic with a 2-month history of fatigue, night sweats, weight loss, loss of appetite, and mild abdominal discomfort. The patient did not have fever, chills, cough, nausea, vomiting, itching, urinary, or bowel symptoms. The patient had a past medical history significant for biopsy-proven sarcoidosis of the mediastinal lymph nodes, which was diagnosed 9 years prior. At that time, the patient had hilar lymphadenopathy seen on a routine chest radiography. The disease seemed inactive, as the patient never had symptoms related to sarcoidosis nor received treatment throughout the years. He also had a history of hypertension, hyperlipidemia, bipolar disorder, coronary artery disease with percutaneous coronary intervention performed a month prior to the current presentation, as well as a recently diagnosed type 2 diabetes mellitus. His regular home medications included amlodipine, metoprolol tartrate, lisinopril, lamotrigine, clopidogrel, metformin, rosuvastatin, and sildenafil. The patient denied any history of alcohol or tobacco use and stated that he used to work as a secretary.
+On physical examination, the vital signs were normal. Body mass index was 37.2 kg/m2, and weight was 263 pounds. The general, lung, heart, and abdominal examinations were unremarkable, and no palpable lymphadenopathy was identified. A battery of laboratory tests were performed and revealed the following: alanine aminotransferase and aspartate aminotransferase levels were within normal limits; however, the alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) levels were elevated (ALP = 258 U/L, reference = 38-126 U/L; GGT = 274 U/L, reference = 12-73 U/L). He was also found to have hyperbilirubinemia (total bilirubin was 1.7 mg/dL, reference = 0.0-1.3 mg/dL, and direct bilirubin was 0.7 mg/dL, reference = 0.0-0.3 mg/dL). The total protein, albumin, serum creatinine, and calcium levels were within normal limits. Further workup including ceruloplasmin, serum iron saturation, lactate dehydrogenase, serum angiotensin converting enzyme level, and erythrocyte sedimentation rate were normal. Alpha-1 antitrypsin antigen, a viral hepatitis panel, and anti-mitochondrial and anti-smooth muscle antibodies were negative. A slight elevation in β2-microglobulin levels were noted (3.2 mg/L, reference = 0.8-2.34 mg/L).
+Ultrasound examination of the abdomen was negative for common bile duct dilatation but showed a 3.5 × 4.1 cm abdominal mass at the head of pancreas. Computed tomography (CT) scan of the abdomen and pelvis with intravenous contrast demonstrated cirrhotic appearance of the liver with steatosis, with enhancing hepatic masses, splenomegaly, and multiple enlarged lymph nodes in the periaortic and portocaval areas. The largest lymph node was measured at 7.2 × 4.3 cm in diameter in the precaval area. There was, however, no visible pancreatic lesions, biliary duct dilatation, or gallbladder stones .
+Histopathological examination of a transjugular liver biopsy showed expanded portal areas containing occasional granulomas with the majority of the granulomas appear non-necrotizing, with a few demonstrating central necrosis. Mild macrovascular steatosis and chronic inflammation is noted . Auramine-rhodamine and GMS stains was negative for acid-fast bacilli and fungal organisms. Staining for iron and immunoglobulin G4 was negative.
+Evaluation for other etiologies of abdominal lymphadenopathy was performed to exclude malignancies and infectious granulomatous diseases. Infectious workup for granulomatous hepatitis was negative for Histoplasma, Bartonella, tuberculosis, and Coxiella burnetii (Q fever). An autoimmune workup including ANA, ANCA, immunoglobulin G4, complement C3, and complement C4 levels was performed and was unremarkable.
+A provisional diagnosis of hepatic sarcoidosis and nonalcoholic steatohepatitis was procured based on the biopsy results. Unfortunately, at that time the patient refused steroid treatment as well as immunosuppressive therapy; however, he agreed to ursodeoxycholic acid 1500 mg daily to help with itching.
+Two months later, the patient started to complain of excruciating pain in his lower back with radiation to his thighs and legs, in addition to diffuse joint pain. His loss of appetite and fatigue did not improve significantly, and he continued to lose weight. A whole body positron emission tomography-CT scan showed extensive hepatic uptake, hypermetabolic lymphadenopathy involving the chest, cervical, supraclavicular regions, upper abdominal, retroperitoneal, iliac chain, and inguinal lymph nodes, as well as numerous fluorodeoxyglucose-avid osseous lesions involving the thoracic and lumbar spine, left proximal humerus, left scapula, pelvis, and proximal right femur. There was a concern of metastatic bone disease given the widespread distribution of the lesions . Evaluation with spine, pelvis, and upper extremity, magnetic resonance imaging (MRI) showed multiple small marrow lesions involving the vertebral bodies in the thoracic and lumbar spine, with small spotty lesions noted in the sacrum, pelvis, hips, ribs, and humerus on the left. MRI of the brain showed no evidence of neurosarcoidosis. An ophthalmologist evaluated the patient, and ocular involvement was ruled out. The patient underwent a bone biopsy of the T12 vertebra, which revealed benign trabecular bone with replacement of the marrow space with numerous non-necrotizing granulomas and fibrosis consistent with diagnosis of vertebral sarcoidosis .
+Of note, while this extensive workup was taking place, the patient developed a sudden onset of left flank pain and hematuria. There was a small left ureteric stone on abdominal imaging identified. He underwent laser lithotripsy and left ureteral stent placement.
+The patient agreed to immunosuppression and was started on methotrexate 20 mg subcutaneously once weekly, folic acid 1 mg daily, and prednisone 5 mg daily as treatment for systemic sarcoidosis. However, 2 months later, he developed actinomycosis skin infection of the groin. Methotrexate was held, and he was treated with amoxicillin until the infection resolved. The patient was restarted on methotrexate. Two months after restarting methotrexate, the patient reported significant clinical improvement of his pain, loss of appetite, and has gained 40 pounds since the start of methotrexate. His liver enzymes improved significantly. A repeat positron emission tomography-CT scan demonstrated a decrease in the lymph nodes, bone, and hepatic lesions size.

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+A 4-year-old boy (height, 100 cm; weight, 16 kg) was hit in the chest by a car. He was conscious and complained of chest tightness. Upon arrival to the local hospital at 18 min after the injury, he was semiconscious and cyanotic. Breath sounds were not heard in the right hemithorax, and his vital signs were unstable: heart rate( HR) of 162 beats per minute (bpm), blood pressure (Bp) of 102/56 mmHg, respiratory rate (RR) of 32 times per minute, and oxygen saturation (SPO2) of 70%. For sedation, 30 mg of propofol was administered intravenously, and emergency endotracheal tube above the carina was performed. Chest computed tomography (CT) showed right pneumothorax with lung compression of 90%, and the left clavicle was fractured . A chest tube was positioned in the right thoracic cavity, and a breathing balloon was used for ventilation. His vital signs were as follows: HR of 155 bpm, Bp of 97/50 mmHg, RR of 22 times per minute, and SPO2 of 98%. Twenty-four minutes later, he was admitted to the Emergency Department of our hospital for further treatment. The results of blood gas analysis were as follows: pH, 7.12; carbon dioxide partial pressure (PaCO2), 76 mmHg; oxygen partial pressure (PaO2), 68 mmHg. Bronchoscopy indicated that the right middle lobe bronchus was ruptured. Transthoracic echocardiography ruled out associated blunt cardiac injury. Emergency exploratory thoracotomy and right middle or right middle and lower lobectomy were planned. The patient went into sudden cardiac arrest after being sent to the operating room (SPO2, 76%; end-tidal carbon dioxide partial pressure (PetCO2), 46 mmHg). Return of spontaneous circulation after twelve minutes of external chest compression. He did not regain consciousness. Mainstem intubation of the left bronchus was performed under direct fibreoptic guidance to ventilate the left lung. With pressure control ventilation, the fraction of inspiration O2 was 100%, peak pressure was 32 cmH2O, and tidal volume was 45 mL; HR was 145 bpm, Bp was 92/48 mmHg (0.05 µg/kg/min norepinephrine), RR was 20 times per minute, and SPO2 was 70%. Blood gas analysis results at this time were as follows: pH, 6.87; PaCO2, 114 mmHg; PaO2, 46 mmHg; plasma lactic acid (Lac), 6.7 mmol/L; K + , 3.2 mmol/L; haemoglobin 7.3 g/dl; and Ca + + 1.21 mmol/L. As sudden cardiac arrest occurred due to severe respiratory acidosis, we decided to initiate V-V ECMO. Our hospital has an adult ECMO centre, and it is 300 km away from our nearest paediatric ECMO centre, approximately a 3.5-h drive. To prevent death, we decided to use small adult ECMO tubes. ECMO was initiated percutaneously in the left femoral vein, and an incision was made in the right internal jugular vein (MAQUET 2050, Cardiopulmonary GmbH BE-PLS, Germany; left femoral vein: 15 Fr/5 mm single-stage drainage cannula, MAQUET, Germany; right internal jugular vein: 14 Fr/ZX 4.7 return cannula, Changzhou Kangxin Medical Equipment Co., Ltd., China). The blood flow was 1.7 L/min, sweep gas was 1.5 L/min, and FiO2 was 100%. Cardiac arrest occurred again after ECMO, and we immediately administered cardiopulmonary resuscitation. Blood gas analysis results at this time were as follows: pH, 6.84; PaCO2, 72 mmHg; PaO2, 61 mmHg; Lac, 9.7 mmol/L; K + , 9.8 mmol/L; haemoglobin 7.3 g/dl; and Ca + + 1.21 mmol/L. Insulin (2 U) were added to the glucose injection (10%, 100 ml), and sodium bicarbonate (5%, 32 ml) and calcium chloride injection (3%, 0.1 g) were administered immediately. Spontaneous sinus rhythm was restored after 18 min. An exploratory thoracotomy was performed successfully; the root of the right middle lobe bronchus was found to be ruptured , as was a branch of the right middle lobe artery. Right middle lobectomy and right middle bronchoplasty were performed. The patient was admitted to the intensive care unit (ICU) after the operation. Mechanical ventilation and ECMO were continued, and we adjusted the ventilator parameters as follows: FiO2 at 30%; positive end expiratory pressure (PEEP) at 10 cmH2O; respiratory rate at 12 times/minute, and tidal volume at 6 mL/kg. Oxygen saturation was between 98 and 100%. Along with mild hypothermia for brain protection (34-36 °C for 30 h), piperacillin sodium and tazobactam injection for the prevention of infection, methylprednisolone injection (16 mg q12 h) to reduce pulmonary exudation, and norepinephrine 0.15 µg/kg/min to maintain blood pressure were applied. On postoperative day 2, he became conscious and was responsive. Due to the traumatic wet lung on the left and secondary pulmonary infection, ECMO was withdrawn on the 6th day after the operation, with a total ECMO time of 137 h. Mechanical ventilation was withdrawn on postoperative day 11. On postoperative day 12, chest CT showed a mass of a high-density shadow in the upper lobe of the left lung with cavitation, which was considered a large traumatic pseudocyst . The patient left the ICU on postoperative day 16 and was discharged from the hospital on postoperative day 31 without neurological deficit. He is able to communicate and play normally. The timeline of the treatment process is shown in Fig. .

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+A 19-year-old female had a subcutaneous implant placed one year prior to a visit to her physician. During the implantation of the device, abnormal cutaneous bleeding was noted. After the physician was unable to locate the implant, an ultrasound was performed. The ultrasound was unable to locate the contraceptive device. A thoracic CT scan revealed that the implant had migrated into the lower left lobular segmental pulmonary artery. The patient reported no symptoms related to the migration of the implant. After a multidisciplinary consultation involving a cardiac surgeon, anaesthesiologists, a gynaecologist, a cardiologist, and an interventional radiologist, an endovascular approach was considered. The patient underwent a preoperative consultation with a gynaecologist, an anaesthesiologist, and an interventional radiologist to explain the removal procedure and the known risks of pulmonary arterial catheterization. The procedure planning included the de-sterilization of a Nexplanon® to assess its flexibility. The team decided to perform the removal under bi-planar fluoroscopic guidance, as routinely done in our department for foreign body retrieval. Both right and left anterior obliquities were chosen to ideally expose the contraceptive implant . The procedure was conducted under general anaesthesia. Following a right femoral venous puncture under ultrasound guidance, a long 8F NeuronMax® introducer (Penumbra, Inc., Alameda, CA, USA) was placed under fluoroscopic guidance into the right inferior vena cava. The left pulmonary artery was catheterized using a 5F 145° angled Pigtail catheter (Merit Medical, UT, USA). An angiogram confirmed the position of the contraceptive implant, without thrombosis. After guide exchange with a stiff guide wire (Terumo, Tokyo, Japan), the NeuronMax® catheter was subsequently advanced to the left pulmonary artery, just upstream of the foreign body. A 25-mm diameter loop snare (One Snare®, Merit Medical, UT, USA) was deployed. Once captured, the contraceptive implant was removed under fluoroscopic guidance without removing it into the NeuronMax® catheter. The procedure lasted 60 min. The fluoroscopic dose was 261 mGy, and fluoroscopy time was 10 min. The following day, a thoracic CT scan showed no procedure-related complications, and the patient was discharged. The patient did not receive any medical treatment before, during, or after the procedure.

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+We report the case of a 36-year-old Sri Lankan Sinhalese man from Kandy, Sri Lanka, who presented to a tertiary care hospital with a 3-day history of an acute febrile illness. He had been in apparently good health and working as farmer involved in paddy cultivation. Three days prior to admission he developed high spiking fever with chills and rigors associated with severe arthralgia and myalgia. He could not mobilize due to severe muscle cramps in lower limbs. He developed shortness of breath at rest with a non-productive cough 1 day prior to admission and was anuric for 12 hours prior to hospital admission. His past medical history was unremarkable and there was no significant medical illness in his family. He was an occasional ethanol consumer and did not smoke tobacco.
+On admission to our emergency unit, we found an averagely built man with a body mass index of 24 who was in severe distress and pain. He was severely dehydrated. He had mild icterus with injected and suffused conjunctiva. He had a temperature of 39.5 ºC with warm peripheries. His pulse rate was 140/minute with a blood pressure of 80/40 mmHg and he had marked postural symptoms on attempting a standing blood pressure. He was dyspneic with a respiratory rate of 32 cycles per minute on air saturation of 90%; it improved with 10 L oxygen via a face mask. On examination of his lung fields he had bilateral coarse crepitations. He had 3 cm hepatomegaly which was tender without palpable spleen or flank dullness. Although he was agitated and in distress, he was oriented in time, place, and person with normal neurology.
+His laboratory results showed a leukocyte count of 24.6 × 109/l (90% neutrophils) with a platelet count of 86 × 109/l and hemoglobin of 14.5 g/dL. A peripheral smear showed neutrophil leukocytosis with toxic neutrophils, few myelocytes, and abnormal lymphocytes with thrombocytopenia. His aspartate aminotransferase (AST) level was 924 U/l (normal up to 31 U/l) and alanine aminotransferase (ALT) was 331 U/L (normal up to 31 U/L). His serum bilirubin level was 55 mmol/L (normal 1–21 mmol/L) with direct fraction of 55%. His alkaline phosphatase level was 459 U/L (normal 64–306 U/L). His serum creatinine was 217 micromoles/L on admission with a potassium of 2.9 mmol/L and sodium of 136 mmol/L. His blood urea nitrogen level was 40 mg/dl (normal 8–20 mg/dl). His coagulation profile was normal. His C-reactive protein (CRP) was 379 mg/dl on admission. Arterial blood gas revealed a partially compensated metabolic acidosis (pH 7.26) with an arterial bicarbonate of 14.5 mmol/L and carbon dioxide partial pressure of 20 mmHg. His creatinine kinase level was 440 mcg/l (10–120 mcg/l). His arterial lactate was 5 mmol/L. A chest X ray on admission showed bilateral air space opacifications. An electrocardiogram (ECG) showed T inversions in the anterior leads (V1–V6) with a troponin I of 0.16 ng/mL (0.04 ng/mL). Bedside two-dimensional echocardiography revealed global hypokinesia with a left ventricular ejection fraction of 40% which was suggestive of myocarditis.
+A working diagnosis of severe leptospirosis with multiorgan dysfunction was made based on the above findings in the background of significant mud exposure and epidemiology of the locality. He was immediately moved to a high dependency unit and oxygen was given via a face mask. He had 50 ml of concentrated urine after catheterization. After fluid resuscitation of 1.5 L of crystalloids, he was started on intravenously administered noradrenalin as his blood pressure remained low. Intravenously administered cefotaxime with orally administered doxycycline was prescribed after taking blood cultures. Acidosis was corrected with 8.4% sodium bicarbonate. An N-acetyl cysteine (NAC) infusion was started considering his elevated transaminases. Hypokalemia was corrected with intravenously administered potassium chloride. He was given 1 g of intravenously administered methylprednisolone.
+On day 2 of illness, our patient was clinically improved with less myalgia. Inotrope requirement was reduced from 0.8 mcg/kg per minute to 0.2 mcg/kg per minute. His oxygen requirement improved from 10 L/minute via face mask to 2 L/minute oxygen via nasal prongs. His urine output was 525 ml/last 24 hours.
+On day 3 of illness his blood pressure was normalized without inotropes and on day 4 of illness his saturation on air was 99%.
+Over the subsequent 5 days his clinical condition gradually improved with gradual normalization of biochemistry.
+Methylprednisolone 1 g continued for 3 days and intravenously administered cefotaxime and orally administered doxycycline for a total of 7 days. He was discharged after an uneventful recovery on day 7 of hospital admission.
+His dengue NS1 antigen test was negative on day 3 of fever. Throat and nasal swabs taken on admission were negative for influenza A (H1N1) viral RNA. A microscopic agglutination test (MAT) for IgM and IgG against Leptospira was done on day 7 and was negative. It was done in the Medical Research Institute of Sri Lanka, which is the reference center which tests for all the common serovars of leptospirosis in Sri Lanka. Blood taken on day 7 was positive for IgM against hantavirus on 1:100 dilutions. Unfortunately, our patient did not turn up for subsequent testing at 4 weeks to demonstrate the rising antibody titers in convalescence.

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+A 73-year-old man visited our emergency room (ER) in October 2004 with right upper abdominal pain and fever for the previous two days. Vital signs on arrival at the ER were blood pressure (BP): 161/107 mmHg, pulse rate (PR): 90/minute, respiratory rate (RR): 20/minute, and body temperature (BT): 38.9ºC. His consciousness was unaffected but he had an acutely ill appearance. Tracing back his medical history, he had hepatitis B virus (HBV)-related liver cirrhosis (Child-Pugh Classification Grade A), and in August 1999, a small HCC (Segment 5 of the liver, diameter less than 2 cm) was diagnosed. He received transcatheter arterial chemoembolization (TACE) at a medical center and a second TACE again in May 2001 for recurrent HCC. He declined further TACE for residual recurrent lesions. Therefore oral chemotherapy with the regimen tegafur/uracil (100 mg/224 mg) had been prescribed to him from December 2001 to November 2003, and was ceased due to loss at follow-up.
+Physical examination in the ER found no yellowish skin, no icteric sclera but moderate right upper quadrant (RUQ) abdominal pain. Murphy's sign was positive. Bowel sounds were normal and his abdomen was soft, with no rebounding pain. There was no shifting dullness. Lab data included: white blood cell count (WBC): 14,520/mm3 (Neu/Lym: 83.5/6.4%), platelets: 169 k/mm3, total and direct (T/D) bilirubin: 1.4/0.6 mg/dL, serum glutamic-oxaloacetic transaminase/serum glutamic-pyruvic transaminase (sGOT/sGPT): 38/32 U/L, albumin (Alb): 3.9 gm/dL, C-reactive protein: 11.9 mg/dL, NH3: 98 mcg/dL, and α-FP level: 231.1 ng/mL. Abdominal echogram revealed a thickened gall bladder wall, gall stones and a suspected tumor mass in the distended gall bladder. An abdominal computed tomography (CT) scan showed liver cirrhosis, gall stones, diffusely thickened gall bladder wall with increased contrast enhancement compatible with acute cholecystitis, and a hypodense mass lesion without contrast enhancement in the gall bladder . There was no roentgenographic evidence of a suspected recurrent lesion in the liver parenchyma at that time.
+An open cholecystectomy via a right subcostal incision was performed on the next day. A distended gall bladder with multiple pigmented gall stones and a tumor mass, 6.0 × 4.0 × 2.0 cm in size, were found in the gall bladder lumen. When seen, the mass had already detached from the mucosa at the opening of the sac and no stalk could be identified . The mucosal surface of the gall bladder wall was smooth without evident tumorous or ulcerative lesions .
+Microscopic pathologic examination of the gall bladder revealed heavy neutrophil and lymphocyte infiltration as in ordinary acute and chronic inflammation. The mucosa was congested and showed no evidence of tumor invasion. The vessels in the gall bladder wall were free from tumor emboli .
+The sections of the tumor showed extensive infarction necrosis. The viable tumor cells were seen as uniform polygonal cells with eosinophilic granular cytoplasm arranged in tiled array or microtrabecular pattern mostly surrounding the blood vessels . Immunohistochemistry staining with α-FP antibody demonstrated varied positive staining intensity in the cytoplasm of the tumor cells . Other antibodies including CK7, chromogranin, and synaptophysin were all negative, excluding the possibility of carcinoid tumor or adenocarcinoma.
+The patient recovered from the surgery well without major or minor complications and was discharged one week after the surgery. He received regular follow-up in our gastrointestinal (GI) outpatient department and his α-FP levels went down to 3.1 ng/mL in March 2005, and to 3.08 ng/mL in August 2005, five and 10 months after cholecystectomy, respectively. He died in July 2006 in another hospital due to upper gastrointestinal bleeding from a hemorrhagic duodenal ulcer complicated by hepatorenal syndrome.

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+A 28-year-old man complained of an abdominal mass and continuously increasing pain over the previous 2 months. Physical examination revealed a midabdominal mass on abdominal palpation, atrophy and minimal induration in the right testis on scrotal palpation. The left testis was found to be normal. No abnormal finding was noted on digital rectal examination. Examination of the other systems, including the endocrine system, was normal.
+His white blood cell count and urine microscopy were normal. Aspartate aminotransferase (AST): 56 mg/dl (normally 1 to 40), alanine aminotransferase (ALT): 42 mg/dl (normally 1 to 38), alkaline phosphatase (ALP): 768 mg/dl (normally 80 to 306), gamma glutamyl transferase (GGT): 160 mg/dl (normally 6 to 50) and lactate dehydrogenase (LDH): 6302 mg/dl (normally 266 to 501) were found in the blood biochemistry. His erythrocyte sedimentation rate was high (110 mm/hour). Values for alpha-fetoprotein (AFP) (5.9 ng/ml (normally 0 to 10.0)) and beta human chorionic gonadotrophin hormone (β-hCG) (0.773 mIU/ml (normally <4)) were within normal limits. Chest X-ray was normal. Scrotal ultrasonogram revealed minimal hypoechogeneity and non-homogeneity in the right testis. Abdominal computed tomography (CT) revealed a very large retroperitoneal mass (13×8 cm), extending across the midline . Thorax CT was normal.
+Needle aspiration biopsy was performed for the retroperitoneal mass and malignant tumour infiltration was reported. After the immunohistochemical studies, cytokeratin (CK) (-), vimentin (-), leukocyte common antigen (LCA) (-), β-hCG (-) and placental alkaline phosphatase (PLAP) (+) immunoreactivity were noted, indicating a germ cell tumour.
+Scrotal ultrasonogram revealed hypoechogeneity and non-homogeneity in the right testicle. Evidence of a tumour was not found. The left testicle and epididymis were normal. After pre-operative evaluation, right inguinal orchiectomy was performed to determine the primary site of the tumour. Histological examination of the biopsy specimen revealed a large area of hyalinization, tubular hyalinization, interstitial fibrosis and focal Leydig cell hyperplasia. There were no pathological findings in the epididymis and spermatic cord. The final pathological diagnosis was 'burned-out' testicular tumour .
+Because of the large retroperitoneal lymph node metastasis, primary chemotherapeutic treatment was performed. Combination chemotherapy, consisting of bleomycin, etoposide and cisplatin, was given in three weekly cycles of four courses. After the four courses of chemotherapy treatment, the abdominal mass had regressed from 13×8 cm to 3×2 cm .
+After the chemotherapy, a control CT scan was obtained revealing regression in the para-aortic and para-caval lymph nodes (3×2 cm and multiple lymph nodes). After 6 months, tumour markers had increased (AFP: 3.59 ng/ml (normally 0 to 10.0) and β-hCG: 20.95 mIU/ml (normally <4)). Because only the β-hCG level had increased, the histology of the primary tumour seemed to indicate a seminoma. For this reason, retroperitoneal lymph node dissection was planned. Exploratory laparotomy revealed a retroperitoneal mass which extended both sides of the midline and involved the major vessels and extended to the eosophogastric junction, indicating an unresectable mass. A biopsy was performed from the unresectable mass and histological examination of the biopsy specimen showed only necrotic tissue and no tumour cells.
+Salvage chemotherapy consisting of paclitaxel, ifosfamide and cisplatin (TIP) was given in monthly cycles of four courses. After this chemotherapy, an abdominal CT scan revealed regression in the para-aortic and para-caval lymph nodes (milimetrical). AFP and β-hCG levels were normal (AFP: 1 ng/ml (normally 0 to 10.0) and β-HCG: 0.180 mIU/ml (normally <4)).
+The patient has been disease and recurrence free for 5 years since the primary surgical and medical treatment.

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+A 55-year-old male patient was presented to a general hospital with fever, myalgia, and persistent cough. Polymerase chain reaction testing for COVID-19 was positive and he was admitted to the hospital due to severe respiratory symptoms. The patient is a known diabetic and hypertensive with a history of a nonfunctioning pituitary macroadenoma for which he underwent an endoscopic endonasal transsphenoidal resection 11 years ago in another hospital. Pituitary tumor recurrence was documented in the available two postoperative magnetic resonance imaging (MRI) studies . After surgery, the patient was kept on maintenance levothyroxine and hydrocortisone for panhypopituitarism.
+Six days after admission, the patient complained of severe headache and acute onset of ptosis and diminution of vision in the left eye. Ophthalmological evaluation revealed complete visual loss in the left eye, a visual acuity of 20/60 in the right eye, left oculomotor nerve palsy with ptosis, and dilated nonreactive pupil. Fundus examination revealed a pale left optic nerve head. Neurological examination was otherwise normal. Computed tomography revealed hyperdensity of the sellar and suprasellar areas. MRI was consistent with PA in a recurrent large pituitary adenoma [ and ].
+The patient was transferred to our center and underwent an urgent endoscopic endonasal transsphenoidal surgery through which a near total excision of the tumor was achieved [ and ].
+The procedure was performed under strict COVID-19 precautions including use of powered air purifying respirators and limited OR personnel. Intraoperative findings were similar to those usually seen in cases of PA and included dark blood mixed with purple-red adenoma tissues of variable consistencies . It was our observation that the nasal mucosa was pale and separated easily from the underlying bone. We have previously observed such features in two patients who previously tested positive for COVID-19. Histopathological examination demonstrated classic features of PA.
+Within the first 3 postoperative days, the patient had some improvement of vision of the left eye so that he was able to perceive hand movement. Ptosis also improved partially. However, his chest condition progressed and he had to be transferred to COVID-19 intensive care unit in the referring hospital where he was intubated and put on mechanical ventilation. One week later, the patient unfortunately passed away due to complications of severe COVID-19 pneumonia.

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+The patient was a 67-year-old man, who had been admitted to the hospital due to melena and a hematocrit level of 20.1 %. Nasogastric intubation revealed a fresh blood clot in the stomach. Urinalysis, chest and abdominal films, and liver function tests were within normal limits, and serum creatinine was 1.2 mg/dl. Five units of packed blood cells were transfused promptly.
+Abdominal CT scan showed a well-defined, heterogeneous mass (3 × 4 m) which was located in the lower part of the stomach body . Gastric endoscopy showed the ulcerated tumor with bleeding along the lesser curvature of the proximal stomach and a submucosal nodule that measured about 3 cm in diameter in the lower part of the stomach body . No other metastatic lesions in other organs were found on abdominal ultrasonography or the CT scan. High-grade gastrointestinal bleeding persisted, necessitating the additional transfusion of ten units of packed red blood cells. Subsequently, the patient underwent a total gastrectomy. During the operation, there was no other evidence of metastatic disease in the intra-abdominal cavity. Macroscopic examination of the total gastrectomy specimen showed Borrman type-2 tumor measuring 5 × 6 cm and submucosal nodule measuring 3 × 4 cm in the stomach . On histopathological examination, the Borrman type-2 tumor gastric tumor showed transmural infiltration by a poorly differentiated diffuse adenocarcinoma . There was no vascular invasion and no lymph node metastasis. Further histopathological examination of the submucosal nodule revealed GIST of the low-risk category , which was composed of cytologically bland spindle cells and showed a low mitotic index (< 5/50HPF).
+The immunohistochemistry indicated strong staining for CD34 and C-kit, while expressions of SMA and S-100 were negative . These findings confirmed the simultaneous development of gastric cancer and GIST. The patient was subsequently discharged without any complications.

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+Preceding availability of COVID-19 vaccination, a 58-year-old Caucasian male presented to his primary care provider with one-week of cough, low-grade fever, and general malaise. He was diagnosed with follicular lymphoma 10 months prior and received 6 cycles of chemo-immunotherapy (bendamustine and rituximab), achieving clinical remission, and received an additional dose of maintenance rituximab one month prior. An oropharyngeal swab was positive for SARS-CoV-2, but he did not require hospitalization at that time.
+Twenty-seven days after the initial positive swab, he developed hypoxemia prompting hospital admission. Initial NP swab was negative and computed tomography (CT) imaging demonstrated recurrent ground glass opacities with bilateral interstitial pneumonia, compatible with COVID-19. Blood tests revealed lymphopenia (0.1 × 109/L, normal: 0.7–3.5 × 109/L) with increased C-reactive protein (57.0 mg/L, normal: 0.0–8.0 mg/L) and ferritin (2047 μg/L, normal: 30–500ug/L). He improved with dexamethasone 6 mg daily for 10 days. However due to relapsing hypoxemia and radiographic progression, a diagnosis of organizing pneumonia as sequelae of COVID-19 was considered. Bronchoscopy was declined, and oral prednisone 50 mg daily was initiated with a planned dose taper.
+On day 90, 73 days post admission, following ongoing reduction of prednisone (10 mg), the patient presented with new onset of pyrexia and recurrence of hypoxemia. RT-PCR testing was again positive by NP swab . The patient was re-initiated on dexamethasone with bronchoscopy performed. Bronchoalveolar lavage was both SARS-CoV-2 RT-PCR (Ct 18.7) and culture positive (1.17 × 104 pfu/mL, wild-type G clade) and negative for bacterial, mycobacterial, other viral and fungal growth. Transbronchial biopsies demonstrated active pneumonitis with occasional foci of organizing pneumonia, and patchy interstitial fibrosis. Symptoms were consistent with COVID-19 relapse and remdesivir was given (200 mg intravenous loading dose then 100 mg daily) for 5 days concurrently with dexamethasone . On day 107, there was clinical improvement with reduction in oxygen requirements to room air and RT-PCR Ct of 24.4 Subsequent investigations revealed hypogammaglobinemia (IgA 0.48 g/L, IgG 3.29 g/L, IgM 0.05 g/L (normal: 0.6–4.2 g/L, 6.8–18.0 g/L, 0.4–3.00 g/L, respectively), likely secondary to prior rituximab administration. He was initiated on monthly intravenous immunoglobulin. He clinically improved and was discharged home on day 107 with an oral dexamethasone (4 mg) taper. Viral culture load at time of discharge was not detectable.
+On day 118 the patient re-presented to hospital with respiratory failure. A repeat SARS-CoV-2 RT-PCR swab was positive with Ct of 23.7and a viral culture load of 1.25 × 101 pfu/mL, suggestive of ongoing viral persistence and a third COVID-19 relapse . SARS-CoV-2 testing failed to demonstrate remdesivir resistance (supplementary material). He was re-treated with another course of remdesivir for 5 days with modest clinical improvement. Repeat CT scans demonstrated persistent, migratory bilateral ground glass opacities . Subsequent medical therapy included bamlanivimab 700 mg (day 133; one dose), IVIG 75 mg (days 137, 165 and 193; one dose each) and a third course of remdesivir (day 146; ten-day course). The patient demonstrated a gradual clinical recovery with progressive reduction in oxygen therapy and eventual negative swab by RT-PCR on day 189. On days 174 and 202, the mRNA-1273 COVID-19 vaccine was administered. On day 202 after initial presentation, he was ultimately discharged home with repeat COVID-19 swabs (days 209 and 224) negative. He has continued to improve with gradually increasing exercise tolerance.
+Notably, whole genome sequencing of the patient’s viral samples over the duration of the time-period demonstrated an identical sequence belonging to SARS-CoV-2 clade D614G equivalent to the PANGO B.1 lineage viral strain with a specific sublineage of B.1.160. A review of the local epidemiology during this period noted B.1.160 as the 12th highest lineage, accounting for only 1.4% of the those sequenced from the general population. Based on the sequencing results, relapse of infection by an identical virus strain was demonstrated rather than re-infection with different strains. Finally, serology testing completed was negative to the nucleocapsid antibody, however positive for the spike antibody (value of 1515.3AU/mL; positive threshold of > 50AU/mL).

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+A 55-year-old man was admitted to The Second Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China) in October 2021 with rapidly worsening heart failure.
+The patient had been experiencing heart failure for 3 mo, but had begun to experience chest tightness, dyspnea, edema, and fatigue after activity.
+The patient had undergone a pulmonary resection 20 years prior to address carcinoma in situ; his current disease state was considered stable.
+The patient’s personal and family histories were unremarkable.
+The patient’s blood pressure was 87/49 mmHg, pulse rate was 101 beats per minute with a regular rhythm, and O2 saturation was 97% at room air. Physical examination revealed that he had clear lungs and normal heart sounds with no murmurs or gallops on auscultation. His lower extremities showed mild bilateral pitting edema. No enlargement of lymph nodes, liver, or spleen was found.
+Laboratory tests showed normal findings in a complete blood count and comprehensive metabolic panel. The levels of serum lactate dehydrogenase and β2-microglobulin were within normal limits. However, the levels of brain natriuretic peptide (385.7 pg/mL; normal: < 100) and troponin T (0.058 ng/mL; normal: < 0.014) were over the normal upper limits. Creatinine was within the normal range (at 51.9 μmol/L), while urine analysis was negative for protein. Quantitation of 24-h urinary lambda light chain showed a level of 365.2 mg. Quantitative serum immunoglobulin analyses demonstrated normal levels of IgG (at 10.5 g/L), IgA (at 2.01 g/L), and IgM (at 0.28 g/L). Serum immunofixation was used to evaluate an underlying gammopathy and showed lambda light chain proteinemia. The level of serum-free lambda light chain (FLC) was normal (at 15.56 mg/L), with the difference between the involved and uninvolved serum FLC levels being 6.75 mg/L. A bone marrow aspirate smear showed 5% infiltration of plasma cells, while flow cytometry analysis showed an abnormal population of plasma cells that accounted for 5.8% of normal cells, most of which were positive for surface CD38, CD56, CD138, and cytoplasmic λ light-chain. The fluorescence in situ hybridization test was negative, which included a 1q21 amplification, 13q14 deletion, p53 deletion, and translocation of t (4; 14), t (11; 14), t (14; 16).
+Positron emission tomography/computerized tomography (PET/CT) was performed and showed no abnormal metabolic lesions. An electrocardiogram showed low voltages in the limb leads. Echocardiogram revealed severe left ventricular hypertrophy, a reduced left ventricle ejection fraction of 38.1%, and an elevated left ventricular filling pressure E/A of more than 2.04. Cardiovascular magnetic resonance imaging (MRI) showed the morphologic phenotype of increased left ventricle wall thickness, while 99technetium pyrophosphate (99mTc-PYP) planar scintigraphy showed a heart-to-contralateral ratio of 1.31.
+Cardiac amyloidosis was considered as a possible etiology of the cardiomyopathy due to the left ventricle thickness on echocardiogram and the heart-to-contralateral ratio of 1.31 on 99mTc-PYP. An endomyocardial biopsy was performed with electron microscopy, revealing fibroid deposits in the myocardium and after Congo-red staining, fibrous tissue with apple green birefringence visualized by polarized light microscopy . Immunohistochemistry analysis showed dominant positivity for monoclonal lambda light chains.

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+A 56-year-old male patient presented with a pancreatic cyst identified by abdominal ultrasonography on a comprehensive medical examination and was admitted to our hospital. He had a past medical history of type 2 diabetes, hyperlipidemia, and chronic hepatitis C for which he received interferon therapy for chronic hepatitis C more than 20 years previously. He had no family history of cancer. Laboratory tests revealed normal levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9, and alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) were absent. Endoscopic ultrasound (EUS) showed a cystic mass measuring 13 mm in size in the pancreatic head and a low-density mass measuring 16 mm in size in the pancreatic tail , which was partially enhanced on the contrast-enhanced ultrasound image . Contrast-enhanced computed tomography (CT) revealed branch duct type intraductal papillary mucinous neoplasms in the pancreatic head and an early enhanced nodule measuring approximately 10 mm in size in the pancreatic tail . An enhancement of the nodule lasted until the late phase, although its density was gradually attenuated. Magnetic resonance imaging (MRI) did not detect the corresponding nodule in the pancreatic tail.
+Based on the above features, our initial differential was that of a neuroendocrine tumor or a solid pseudopapillary neoplasm (SPN). Endoscopic ultrasound-guided fine-needle aspiration (FNA) was performed to make a definitive diagnosis. FNA cytology showed that the tumor cells exhibited an acidophilic cytoplasm with small, round nuclei. Immunohistochemistry was performed to differentiate between a neuroendocrine tumor, SPN, and acinar cell carcinoma. The tumor cells were positive for cytokeratin, nuclear/membranous β-catenin, CD10, and CD56 and were negative for chromogranin A, synaptophysin, progesterone receptor, vimentin, and Bcl-10. Therefore, we suspected that the hypervascular tumor in the pancreatic tail was suspected to be SPN, but the results were not convincing. Laparoscopic spleen-preserving distal pancreatectomy was performed. Macroscopically, a well-circumscribed whitish-yellow solid mass, measuring 7 mm in the greatest dimension, was found in the pancreatic tail . Histologically, polygonal tumor cells with round nuclei and abundant eosinophilic cytoplasm formed thick trabeculae. The differentiation was moderate . Immunohistochemically, the tumor cells were positive for hepatocyte paraffin 1, AE1/AE3, and CD10 and negative for AFP, progesterone receptor, vimentin, chromogranin A, and synaptophysin . A canalicular pattern was confirmed on the polyclonal CEA staining . HC is characteristically hepatocyte paraffin 1 (HepPar1)-positive and has a canalicular pattern on polyclonal CEA staining. Finally, a diagnosis of moderately differentiated pancreatic HC was made. The patient’s postoperative course was uneventful, and he was discharged in good health 10 days after the operation. The patient did not receive adjuvant chemotherapy and remained recurrence-free at 6 months after the surgery. The serum levels of AFP (3 ng/mL) and PIVKA-II (28 mAU/mL) were normal at 1 month after the surgery. The latest serum levels of AFP (2 ng/mL) and PIVKA-II (25 mAU/mL) were normal at 6 months after the surgery.

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+The patient was a 59-year-old woman with complaints of intermittant abdominal pain, distention, and dyspepsia over 6 months. There were no specific diseases in her history except chronic atrial fibrillation. The laboratory results were in normal range except Gamma-glutamyl transpeptidase (358 IU/L) and alkaline phosphatase (288 IU/L) levels. Tumor and hepatitis markers were negative. Ultrasound examination had revealed a 49-mm mass, creating a dense acoustic shadow on the posterior area of the neck of the gallbladder. Magnetic resonance cholangiopancreatography (MRCP) had showed a hidropic gallbladder with an excessively dilated CBD, and a 110 mm × 41 mm stone emerging from CBD, showing finger-like projections into the biliary ducts. Intrahepatic biliary ducts were dilated, especially in the left lobe, having milimetric calculus inside; there was a 39 mm × 20 mm stone in the proximal segment of the left lobe, coalescing with the stone in CBD [Figures and ]. CBD was 5 cm in width, filled with a stone, emerging into the intrahepatic biliary ducts. Following a partial sphincterotomy, a stent of 12 cm length and 10 F diameter was inserted in CBD.
+In the operation, following cholecystectomy, an excessively dilated CBD was seen and after choledochotomy, a very large calculus that filled CBD completely was observed . Choledochotomy incision was carried forward and the calculus was extracted . After the extraction, it was observed to be a giant calculus, nearly 15 cm in length and 4.5 cm in width, that had taken the shape of CBD . After exploring CBD for any other masses, a T-tube choledochostomy with choledochoduodenostomy (CD) was performed . The bile duct was not biopsied to rule out a possible pre-existing choledochal cyst preoperatively. The patient was discharged without any complications on postoperative 8th day.

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+A 55-year-old female was admitted to the hospital’s emergency department with the chief complaint of a painful mass located in the right thigh and perineal area and with progressed pain and paresthesia to the right thigh and right shin. The patient seemed ill but not toxic. No history of fever, abdominal pain, digestive dysfunctions, chest pain, cough, hemoptysis, urticarial were found. The vital signs were in a normal range, and there was no family history.
+Physical examination showed that the skin over the mass had no discoloration, and the size of the mass was around 5.7 cm long. The blood tests were normal, and the lab results showed no eosinophilia. The result of the ultrasonography examination was a cystic mass with suspicion toward femoral hernia. After a CT scan, the result of secondary workups was a multi-lobular cystic mass with no connection to the abdominal region , which suggested a hydatid cyst.
+The patient underwent surgery under spinal anesthesia in the next step, and the right thigh was opened up. A cystic mass with ecto- and endocyst with clinical similarity to a hydatid cyst was removed with wide margins and without penetration of the cyst wall. The removed specimen was sent for histological examination with the first impression of cystic hydatidosis.
+Received specimen in formalin consist of a creamy-whitish colored cyst M = 7 * 5 * 3 cm filled by multiple variable-sized creamy cysts . The cyst consists of three layers; the outermost fibrous pericyst layer, the middle laminated ectocyst layer, and the inner hyaline and acellular endocyst as the germinative layer, which encompasses daughter cysts and brood capsules with scolices. There may be granulomatous palisading reaction and pseudocyst formation as seen in cutaneous lesions .
+Following the surgical removal of the cyst, the patient underwent recovery. Besides, Post-surgical Abdominal and thoracic Ultrasonography screening were used to exclude recurrence. Albendazole 400 mg PO BID was prescribed for 3–6 months. An 18-months follow-up demonstrated no reoccurrence or any other site of cystic hydatidosis.
+After a year of routine follow-up, the patient did not demonstrate any signs of recurrence of the adverse effect of surgery, and she was entirely well.

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+A 47-year-old male who complained of upper abdominal pain and vomiting was referred to our hospital. He was a heavy drinker and had a past history of hospitalization for alcoholic chronic pancreatitis. Laboratory data revealed elevated levels of amylase (245 IU/L), CRP (14.99 mg/dl), and white blood cell count (14900/μL). Plain abdominal computed tomography (CT) showed a cystic lesion of 7 cm in size in the lumen near the second part of the duodenum. The cystic lesion showed high density inside. The pancreas was slightly enlarged, and the main pancreatic duct was dilated. Calcifications were seen in the uncus of the pancreas . Gastrointestinal endoscopy revealed that the lumen of the duodenum was deformed by a submucosal tumor-like mass and the endoscope could not pass through it . However, active bleeding was not seen in the lumen of the duodenum. A submucosal tumor or hematoma of the duodenum or a pancreatic pseudocyst associated with chronic pancreatitis was suspected. On the fourth day of hospitalization, his hemoglobin level had decreased from 14.0 to 11.1 g/dl. Contrast-enhanced CT demonstrated a high-density spot on the wall of the cystic lesion . A pancreatic pseudocyst complicated with intracystic hemorrhage was preliminary considered. Angiography was immediately performed, and a pseudoaneurysm was identified in the branch of the anterior superior pancreaticoduodenal artery (ASPDA) . The pseudoaneurysm was successfully treated with transcatheter arterial embolization (TAE). Anemia did not progress after that. Upper gastrointestinal series demonstrated a filling defect in the duodenum, while the inside of the cystic lesion was not contrasted . Magnetic resonance cholangiopancreatography (MRCP) was performed but did not show a communication between the cyst and the pancreatic and biliary ducts. Follow-up CT on the 27th day after TAE showed that the cyst had decreased in size to 2 cm and obstruction of the duodenum was gradually improved . Surgical treatment was considered for the pancreatic pseudocyst with intracystic hemorrhage. However, he refused an operation and was discharged on the 34th day after TAE.
+Two years later, abdominal pain and vomiting recurred. The cyst was enlarged again, and CT showed that it contained high-density fluid. Recurrence of a pancreatic pseudocyst with intracystic hemorrhage was suspected because of anemia progression. TAE was performed in the branches of the ASPDA and posterior superior pancreaticoduodenal artery (PSPDA). After TAE, the size of the cyst decreased and symptoms were relieved. However, the same symptoms recurred 2 months later. We obtained informed consent for surgical treatment, and we performed subtotal stomach-preserving pancreatoduodenectomy (SSPPD). Intraoperatively, severe inflammatory adhesion was noted around the pancreas head and the border between the pancreas and the cystic lesion was unclear. Macroscopically, a cystic mass of 5 cm in size was adjacent to the second part of the duodenum on the pancreas side and was close to the ampulla . A pinhole-sized communication was identified between the cyst and the duodenum lumen. Microscopically, the cyst was filled with mucus and the wall of the cyst was composed of gastric mucosa and shared a common proper muscle layer with the duodenum. Chronic ulcers and erosions were seen in the cyst . Ectopic gastric mucosa was observed in non-ulcerative region . Based on these findings, a diagnosis of duodenal duplication cyst was made. The patient’s postoperative course was uneventful, and he was discharged on the 30th day after the operation.

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+A 77-year-old woman presented to the hospital with progressive swelling in the right hemiabdomen, a loss of appetite, and a weight loss of 8 kg in a period of 5 months. She was a former agricultural worker (including undocumented pesticide handling) and had no significant medical history, eight natural births, no alcohol or tobacco abuse, and no history of signs and symptoms of cholelithiasis. At the clinical examination, skin pallor and a firm, tender, slightly mobile lump in the right hypochondrium and the right iliac fossa, without signs of ascites, were detected.
+The abdominal ultrasound revealed a solid mass occupying the entire right hemi-abdomen, though it could not provide details about the origin or the relationships with neighboring structures, due to the large size and the inhomogeneous character of the tumor.
+MRI highlighted an abdominal tumor located in the right hypochondrium and right abdominal flank with liver invasion (segment V). At the lower pole, the tumor wall was discontinuous. Intraperitoneal tumor extension was detected over a length of approximately 25 mm, with the invasion of the small bowel and omentum at this level. The tumor had a mixed appearance: solid-wall, gadolinophilic, with a maximum thickness of 35 mm and an inhomogeneous central liquid portion. Multiple stones, some of them with a diameter of 18 mm, were visible in the lower part of the tumor, but most agglutinated in the upper part, with dimensions varying between 5 and 30 mm. There were no lymph nodes and no metastasis. The common bile duct appeared with a normal caliber, alithiasic, and pushed antero-superior by the tumor mass, with no sign of invasion. This imaging result is characteristic of primitive gallbladder cancer . A cT3N0M0 stage was established under the limitations of the imaging evaluation difficulties regarding the large volume of the tumor, which made it hard to evaluate its relationships with the neighboring structures. CEA and CA 19.9 levels were within normal ranges.
+After the median laparotomy, a giant tumor (25/17 cm) occupying the entire right abdominal flank from the subhepatic region to the right iliac fossa was identified, which included the gallbladder, segment V of the liver, mesocolon, omentum, and a jejunal loop invasion, with numerous inflammatory adhesions with the neighboring structures . A cholecystectomy was performed with liver wedge resection, enterectomy, the partial resection of the mesocolon and omentum, and loco-regional lymphadenectomy. The complete resection of the tumor was performed en bloc with the abovementioned structures.
+The postoperative evolution progressed without incident, with discharge on the 7th postoperative day.
+The microscopic description was suggestive of biliary-type intracholecystic papillary–tubular neoplasm, with high-grade dysplasia/carcinoma in situ and without neoplastic invasion in neighboring structures, pT2aN0Mo.
+The oncological (multidisciplinary) re-evaluation established an R0-type excision. Adjuvant treatment remained as a reserve (such as FOLFOX or FOLFIRI) in the case of loco-regional relapse or the appearance of metastases. Only clinical and paraclinical monitoring was decided.
+The patient is still alive two and a half years later, with no signs of local recurrence or metastases.
+The case depicted in exhibited a poorly differentiated adenocarcinoma with a poorly cohesive cell pattern (B), associated with a pancreatobiliary-type ICPN with high-grade dysplasia (C), being diffusely positive for specific lineage markers such as CK7 and MUC1 and expressing focal MUC5AC and MUC6.

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+A 52-year-old female patient with OI had recently injured her left knee, rupturing her anterior cruciate ligament (ACL). She had pre-existing degenerative changes in her right knee with a deficient medical collateral ligament (MCL) of clinical grade 3, which had been symptomatic for 2 years prior to her fall . We opted to perform a right total knee replacement before addressing the left knee injury. This would provide her with an immediate stable right limb prior to addressing her left knee.
+A Nextgen Rotating Hinge Knee (ZimmerBiomet®) hinged prosthesis was used because of her incompetent MCL . The smallest components available were used because of her small anatomical bony dimensions. The OI population tend to experience growth retardation and standard implant sizes are generally over-sized for these patients. This necessitates pre-operative planning in the form of templating to ensure the specific implant sizes are available for the patient. In the absence of such implants, patient-specific implants and cutting guides should be considered for outlier cases . The initial postoperative course was uneventful. The patient mobilised slowly though. She had poor flexion at 6 weeks and a gentle manipulation was performed cognizant of the inherent dangers. She is currently at 2-year post-op with full extension and flexion to 110 degrees. The patient-reported outcome measures improved as follows: her visual analogue score (VAS) was 7/10, 3/10 and 2/10 before, 6 and 24 months after surgery respectively. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee score was 36.4, 59.4 and 86.4 before, 6 and 24 months after surgery respectively. She continued to wear a brace on left knee as she was reluctant to undergo an ACL reconstruction.

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+A 79-year-old male complained of persistent diffuse abdominal pain for 4 d.
+Initially, the abdominal pain occurred abruptly after eating a big meal, 4 d prior to admission. The initial abdominal pain was mainly located in the right upper quarter abdominal area and then migrated to the whole abdomen. Additionally, the patient experienced nausea, vomiting, constipation, and fever. Recurrent abdominal pain was noted for the 4 d as well. Sonography-guided percutaneous catheter drainage of the left subphrenic abscess, as shown by contrast computed tomography (CT) of the abdomen, was performed. The bilirubin level was 76.0 mg/dL and volume of abscess drainage was around 600 mL. The abscess culture yielded Enterococcus faecalis and Enterobacter cloacae complex. The blood culture yielded no pathogen isolates. Biloma was confirmed. However, the patient still complained of epigastric pain after drainage.
+The patient had a medical history of hypertension and had taken an antihypertensive drug regularly.
+The patient’s personal and family histories were unremarkable.
+Initial vital signs were a temperature of 37.8 °C, heart rate of 126 beats/min, blood pressure of 163/93 mmHg, and respiratory rate of 32 breaths/min. There was no apparent loss of consciousness. Physical examination showed icteric sclera, abdominal fullness, diffuse tenderness, and muscle guarding. Follow-up vital signs before repeat abdominal CT for persistent abdominal pain were a temperature of 37.5 °C, heart rate of 116 beats/min, blood pressure of 162/84 mmHg, and respiratory rate of 20 breaths/min. Severe muscle guarding and diffuse tenderness were observed.
+Abnormal laboratory findings included hyperbilirubinemia (total bilirubin: 3.0 mg/dL; reference range: ≤ 1.2 mg/dL), mildly elevated alkaline phosphatase (138 U/L; reference range: 40-129 U/L), hyponatremia (sodium: 127 mmol/L; reference range: 136-145 mmol/L), impaired renal function (creatinine: 1.59 mg/dL; reference range: 0.70-1.20 mg/dL), white blood cell count of 3200/μL (reference range: 3400-9500/μL), and 8% band form of white blood cells (reference range: 0.0%-4.2%).
+Plain abdominal radiography showed ileus and contrast abdominal CT showed a dilated common bile duct (CBD) and left subphrenic abscess . Repeat contrast CT of the abdomen was performed for persistent abdominal pain after biloma drainage and showed bile leakage and gastric wall thickening . Esophagogastroduodenoscopy (EGD) showed an edematous, hyperemic gastric mucosa with poor distensibility . Endoscopic retrograde cholangiopancreatography after EGD showed a dilated CBD with one filling defect of about 10 mm in size .
+The gastric mucosal culture yielded Enterococcus faecalis and the biopsy showed that the gastric submucosa and mucosa were infiltrated by clusters of lymphocytes, neutrophils, and plasma cells . According to initial CT and endoscopic retrograde cholangiopancreatography, the etiology of the initial abdominal pain with fever was a CBD stone with cholangitis and spontaneous biloma. However, according to serial CT images and gastric mucosal culture, the persistent pain after biloma drainage was caused by PG. The etiology of PG was bile leakage after biloma drainage.

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+A 47-year-old man was found to have optic disc swelling by his optometrist. MRI revealed a 7.1 cm sellar mass (Additional file : Figure S1), shown to be an ACTH-positive pituitary adenoma on transsphenoidal biopsy. He had a history of obesity, hypertension, gout and renal calculi but no cyclical symptoms or blood pressure fluctuations. Body mass index was 52.1 kg/m2 but he had no supraclavicular fat pads, Cushingoid striae, facial plethora, ecchymoses or proximal weakness. He had a right-sided oculomotor nerve palsy and right-sided proptosis and conjunctival injection suggesting ophthalmic vein compression. He was eupituitary apart from fluctuating ACTH-dependent cortisol production ranging from normal to 35-fold ULN (Additional file : Figure S1). He was diagnosed with CCD due to a giant corticotrophinoma with intermittent biochemical hypercortisolism, although the precise temporal cyclicity could not be defined prior to transcranial partial tumour resection 1 week later. Histopathology confirmed a corticotrophinoma with no significant mitotic activity and a Ki67 count of < 1%. He was eucortisolaemic immediately pre- and postoperatively with ACTH lowering from 376 ng/L (ULN 60) to 169 ng/L (Additional file : Figure S1). Postoperative complications included acute kidney injury, transient hyperglycaemia, pneumonia, deep vein thrombosis and central hypothyroidism. He later noticed improved BP control, reduced appetite and improved satiety with early but transient weight loss. Serial MRI showed a stable 4.2 cm tumour remnant (Additional file : Figure S1). Despite having typical CS comorbidities and postoperative complications, he has had no cyclical symptoms to guide the timing of investigations and no further episodes of overt hypercortisolism have been detected during intermittent testing. His family history is negative for endocrine tumours.
+We performed WES of germline and tumour DNA and single nucleotide polymorphism (SNP) array of tumour DNA to identify sequencing variants and copy number variation in circadian/pituitary-associated genes. Tumour immunohistochemistry was performed to further evaluate the leading genetic variant of interest. Further details are provided in Additional file : Supplementary Methods.

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+A 26-year-old man complained of foamy urine for 3 years without hospital examination. Proteinuria was found in routine physical examinations 1 month prior, and he attended our clinic on the basis of these results. Laboratory data were as follows: urine analysis showed proteinuria (dipstick 2 +) and hematuria (3 +), 24-h uric protein quantification was 0.75 g/day (normal range, 0–0.15 g/day), and serum creatinine (Scr) was 151 μmol/L (normal range, 88–104 μmol/L). Based on abnormalities in the examination indicators, the patient was admitted to the nephrology department with an initial diagnosis of glomerulonephritis and renal insufficiency.
+Further detailed consultations and examinations were carried out. The patient felt no other discomfort. His routine physical examinations showed no obvious abnormalities. He had no edema or hypertension, and his urine output was normal. During neurological examination, the patient was found to have an imperceptible tremor in his hands. A review of medical history revealed that the patient had allergic purpura 22 years prior and pneumothorax 7 years prior. The patient denied having consumed alcohol or abused drugs and denied having a history of hepatitis or family history of chronic or genetic diseases. His parents had a nonconsanguineous marriage. Laboratory examinations indicated normal white blood cell counts and hemoglobin levels. Urinalysis showed 2 + proteinuria with microhematuria (approximately 100 erythrocytes per high-power field), and his 24-h uric protein quantity fluctuated from 0.75 to 1.1 g/day. Abnormal renal function with an Scr of 150–170 μmol/L was detected. Liver function was normal, and other laboratory examinations, including serum electrolytes, thyroid function, C-reactive protein, and serum complement (C3 and C4), were also within the normal range. Additionally, immunoglobulin levels (IgG and IgM) were normal, except for mild elevation of IgA (3.73 g/L, normal range: 0.97–3.2 g/L). Serological tests were negative for anti-nuclear, anti-neutrophil cytoplasmic, anti-glomerular basement membrane, anti-hepatitis B virus, and anti-hepatitis C virus antibodies. Routine physical examination results indicated normal electrocardiogram and color Doppler ultrasound with normal kidney size and shape. Color ultrasound of the liver, gallbladder, spleen, and pancreas indicated rough echo in the liver.
+Renal biopsy was performed to identify kidney disease. Analysis of renal biopsy specimens using light microscopy showed mesangial cells and matrix proliferation with glomeruli focal segmental hyperplasia and sclerosis (1/10 glomerulus; Fig. a). Epithelial cells were vacuolated and showed granular degeneration. Additionally, brush margins disappeared, the lumen dilated, and focal atrophy (atrophy area of approximately 15%) was observed in some renal tubules. Interstitial focal inflammatory cell infiltration was accompanied by fibrosis, and the walls of arterioles showed no obvious pathological changes . Immunofluorescence staining showed granular deposition of IgA+++ in the mesangium . No glomeruli were observed by electron microscopy. Silver staining showed shedding of tubule bristles and enhancement of interstitial edema . The pathologic diagnosis was focal hyperplastic IgA nephropathy accompanied by acute tubular interstitial injury (Lee grade III, Oxford grade M1E0S0T1).
+Diagnosis of IgA nephropathy is relatively simple based on hematuria, proteinuria, and renal biopsy results; however, renal pathology may not yield a clear diagnosis. In our study, the observed pathological changes associated with IgA nephropathy did not explain the renal dysfunction in our patient. Additionally, the degree of tubular injury was not consistent with glomerular lesions. Thus, reasons other than IgA nephropathy may contribute to tubular injury. More importantly, the young patient in our study showed rough echo of the liver in our ultrasound findings. Although we repeatedly questioned the patient about his medical history, no common causes of liver damage, such as hepatitis or a history of drugs and alcohol, were reported by the patient. Furthermore, magnetic resonance imaging of the liver revealed liver atrophy and splenomegaly. The unexplained symptoms were confusing; however, the chief physician of our institution observed the mild involuntary fingertip tremors of the patient, and WD was then considered as a potential diagnosis based on this nonspecific neurological abnormality combined with the observed liver damage.
+Renal biopsy was re-examined, and some subtle changes that had been overlooked on the first analysis were detected. For example, granular deposition in the cytoplasm of renal tubule epithelial cells was observed using light microscopy . Under electron microscopy, some renal tubular epithelial cells showed degeneration of mitochondria in the cytoplasm. The size of mitochondria varied, the inner and outer membranes were separated, and the cristae became shorter and disappeared . Moreover, lysosome size increased, and some round granules were deposited in the lysosome . Timm’s copper staining revealed some brown to black deposits in some renal tubular epithelial cells . Measurement of copper metabolism further confirmed the diagnosis of WD; lower levels of serum ceruloplasmin (0.02 g/L, normal range: 0.27–0.47 g/L) and increased urinary excretion of copper (260.4 μg/day, normal range: 10–60 g/day) were detected, although normal copper serum levels (12.52 μmol/L, normal range: 7.12–21.29 μmol/L) were also observed. The presence of K–F rings in the patient’s eyes, as observed by slit lamp examination, also supported the diagnosis of WD. To confirm this diagnosis, we also performed DNA sequence analysis and identified two mutations in the ATP7B gene; one was a known pathogenic mutation, whereas the other was a suspected pathogenic mutation .
+Finally, the patient was diagnosed with WD. The observed kidney damage was identified as WD-associated renal injury, including renal tubulointerstitial injury and focal proliferative IgA nephropathy. The patient agreed to targeted treatment, including penicillamine 250 mg twice daily and oral zinc sulfate daily. Additionally, he was prescribed losartan to control proteinuria while monitoring renal function and blood pressure. During the 3-year follow-up, the tremor in his hands disappeared, and his 24-h uric protein level fluctuated from 0.3 to 0.5 g/day. Renal dysfunction was reversed, and Scr was maintained at approximately 110–130 μmol/L. Moreover, 24-h uric cooper dropped from 260.4 to 69 μg. The patient retained normal liver function and maintained a good quality of daily life.

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+A 20-years-old, British, male sustained cervical spinal cord injury (ASIA impairment scale B) at C-5 level in 1970 while teaching gymnastics. He was a physical training instructor in army and he landed on the wrong side of a trampoline. This gentleman had been managing his bladder by penile sheath drainage until 2013 when he underwent surgery for upper gastrointestinal bleeding. Since then, he had been draining urine by urethral Foley catheter.
+Following a routine change of urethral catheter by a health professional, this patient started sweating profusely. The Foley catheter was draining urine; there was no bypassing, no bleeding per urethra, and no haematuria. Patient’s wife, who had been looking after her tetraplegic husband for more than forty years, told the health professionals that the catheter might have been placed incorrectly but her concerns were ignored by health professionals. Therefore, this patient came to spinal unit for advice. On clinical examination, this patient was sweating profusely over his head and face. Blood pressure was 140/70 mm Hg. The patient did not have symptoms of urine infection nor did he feel unwell. Ultrasound scan of urinary tract revealed no urinary calculi, no hydronephrosis. The balloon of Foley catheter was not seen in urinary bladder but this finding was not recognised by radiologist and spinal cord physician. Patient continued to sweat profusely; therefore, Computed Tomography (CT) of pelvis was performed, but there was a delay of ten days. Special attention was taken to include the entire urethra in addition to urinary bladder for scanning, as misplacement of urethral catheter was suspected by the spinal cord physician. CT revealed the balloon of Foley catheter in the over-stretched prostato-membranous urethra . The tip of Foley catheter was not located within the urinary bladder but was lying distal to bladder neck . Flexible cystoscopy was performed and Foley catheter was inserted into the bladder over a guide wire. The intensity of sweating decreased; noxious stimuli arising from traumatised urethra might take a long while to settle.
+24-hours ECG monitoring revealed bradycardia: slowest being 39 beats per minute , 214 episodes, and 36 beats at 00:09:04. There was a pause of 2.08 seconds at 22:14:51 . X-ray of pelvis revealed marked osteoarthritic changes in both hips; X-ray of lumbar spine revealed slight scoliosis concave to the right; anterior hyperostosis, most marked at L4/5; disc spacing was well maintained.
+Ultrasound scan revealed normal size right kidney measuring 12.5 cm with no hydronephrosis or calculi. The left kidney was atrophic measuring 8.4 cm, cortical depth of 14.1 mm. No calculus was seen. Blood tests: Urea: 5.9 mmol/L; Creatinine: 69 micromol/L; HbA1c: 36 mmol/mol; PSA: 0.15 ug/L. Urine culture yielded growth of >108/L of Staphylococcus aureus. Cytology of urine revealed abundant neutrophils and red cells. Groups of urothelial cells were seen with slightly enlarged nuclei. Some of the groups have a vaguely papillary appearance, which could be seen in low-grade urothelial neoplasms, infection, instrumentation or stones. A follow-up urine cytology revealed a few inflammatory cells and urothelial cells. No malignant cells were seen.

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+A 37-year-old Caucasian female nonsmoker with no known past medical history presented to our emergency department with 4 months of dyspnea and back pain. At her initial presentation 4 months prior to an outside facility, she underwent a chest C-ray and chest computed tomography (CT) scan, which showed a right upper lobe consolidation. She had been treated for and discharged with a diagnosis of pneumonia. Two months after her initial presentation, she underwent an outpatient bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial right upper lobe biopsy owing to persistent symptoms and a concern for malignancy. Fungal studies and acid-fast bacilli fluorochrome smears were negative, and biopsy results were negative for malignant cells; the pathology results were consistent with chronic inflammation. Upon arrival to our emergency room, she again reported similar symptoms. Physical examination was notable for neck pain on palpation and tachypnea. A chest CT with intravenous (IV) contrast was performed, revealing near-complete right upper lobe collapse, right upper lobe consolidation, enlarged subcarinal lymph node, and enlarged station 6 lymph node . Magnetic resonance imaging (MRI) of the spine was performed, demonstrating a C7 50% compression fracture and lytic lesions throughout the spinal vertebrae, concerning for metastatic disease. A CT of the abdomen and pelvis was also performed, revealing a single 15-mm hypodense nodule on the liver .
+The patient subsequently underwent a transthoracic right upper lobe biopsy, which showed dense fibrous pleural bits, samples of alveolar parenchyma showing interstitial fibrosis, and a patchy dense lymphocytic infiltrate; no malignant cells were seen on histopathological examination. Next, the patient underwent bronchoscopy and endobronchial ultrasound with transbronchial lymph node sampling, as well as brushing and BAL of the right upper lobe. Most studies were unremarkable except the BAL cytology exhibit, which was positive for poorly differentiated neoplastic cells, raising the possibility of a poorly differentiated carcinoma; however, the material on the cell block was insufficient to run immunostains. As the concern for metastatic disease remained high on our differential diagnosis, we pursued a liver biopsy to better characterize the malignancy. The patient underwent a fluoroscopy-guided liver biopsy of the aforementioned liver nodule, which demonstrated a malignant undifferentiated neoplasm with epithelioid morphology and weak neuroendocrine differentiation.
+The cells formed nests/cords in a background of hyalinized sclerotic stroma, frequently demonstrating eosinophilic cytoplasm and round-to-ovoid nuclei . These ancillary studies were insufficient to rule out epithelioid synovial sarcoma, breast malignancy, renal malignancy, thyroid malignancy, gynecologic primary tumors, and epithelioid osteosarcoma. The neoplastic cells were weakly reactive for synaptophysin, and CD99 staining showed a membranous pattern . In a subset, GATA-3 was positive and PAX-8 was weakly positive . However, the neoplastic cells were nonreactive to ER (breast marker) and SATB2 (lower gastrointestinal and osteosarcoma marker). Moreover, the tumor cells were negative for Oscar pankeratin, CK7, CK20, Moc-31, TTF-1, WT-1, HMB45, Melan-A, SOX-10, S100, Inhibin, SMA, MyoD1, CD117, CD45, CD30, and CD34. Thus, the liver tissue was sent for a second opinion for evaluation by a pathologist with expertise in gastrointestinal, liver, soft tissue, and cardiothoracic pathology in a state-of-the-art center at the national and international levels. They found that a specialized panel of immunohistochemical stains revealed that the tumor cells were reactive to MUC4 expression. BRG1 and INI1 immunostains revealed preserved nuclear staining; however, claudin-4, ERG, CD31, CAMTA1, P40, ETV-4, and NUT stains were negative. Subsequently, a diagnosis of sclerosing epithelioid fibrosarcoma was concluded.
+Based on our diagnostic workup, the patient was promptly started on doxorubicin therapy. The patient ultimately joined a genetic research protocol at a major cancer research center. Next-generation sequencing (Tempus genetic testing) was completed to evaluate for any variant known to increase her risk for cancer. There were no genes identified that would increase her risk for cancer. However, there was an identified variant of unknown significance of the WRN gene, an autosomal recessive gene associated with Werner syndrome (WS). She has not had any clear manifestations of WS other than malignancy and has yet to be assessed for osteoporosis. At 3-month follow-up, she is in the early stages of her treatment course and has tolerated her regimen without issues.

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+An 83-year-old man was brought to our emergency room with 10-day history of fever, severe headache, and difficulty in moving. MRI revealed a brain abscess, which was treated by abscess drainage and systemic antibiotic treatment. Although the patient had no symptoms, a CT performed to determine the cause of the brain abscess revealed thickening of the wall of the esophagus , and the patient was referred to our department.
+Barium swallow revealed a tumor measuring 6 cm in length with an abnormal ulcer mound in the middle thoracic esophagus; endoscopy revealed a Type 2 tumor . Histopathological examination of biopsy specimens revealed the squamous cell carcinoma. Abdominal and chest CT revealed wall thickening in the middle thoracic esophagus without invasion of the adjacent mediastinal organs or mediastinal lymph node metastasis. In addition, CT revealed an azygos lobe in the right thoracic cavity . We planned the esophagectomy for the esophageal cancer after control of the brain abscess. Although intrathoracic adhesions were anticipated on account of a previous history of bacterial pyothorax 14 years ago, we decided to perform esophagectomy via a thoracoscopic approach without any preoperative treatment because of his advanced age. After consulting with the respiratory surgeons, we planned to resect the abnormal azygos vein during esophagectomy.
+The patient was placed in the prone position. Due to the adhesions in the thoracic cavity as expected, insertion of the trocars required some ingenuity. We performed dissection of adhesions using a 10-mm flexible scope and obtained an adequate field of view. Trocars were inserted as needed while performing dissection of adhesion, and we finally inserted the four trocars into the right thoracic cavity: three 12-mm trocars into the fifth intercostal space on the posterior axillary line, seventh intercostal space at the midpoint between the inferior scapular angle line and the posterior axillary line, and ninth intercostal space on the level of the inferior scapular angle, and a 5-mm trocar into the sixth intercostal space on the mid-axillary line. Although we usually insert a trocar into the third intercostal space on the mid-axillary line, we could not insert it due to adhesion of upper lobe of the of right lung. Therefore, we performed all surgical procedures via the four trocars. Then, we continued the dissection of remaining adhesion in the thoracic cavity. The middle and lower mediastinum was manipulated first because of the strong adhesions around the esophagus in the middle and lower mediastinum and the tumor's extensive contact with the left main bronchus on preoperative CT . Fortunately, the adhesions were detached without any damage, and the esophagus could be dissected from surrounding organs. Adhesions around the upper esophagus were not severe and fortunately found the azygos lobe easier than expected, and the azygos vein was supported by the mesentery draining into the superior vena cava . It might interfere with forceps operation and the surgical field or pose a risk of injury during esophagectomy, after dividing the mesentery, we clipped and cut the vessel with a vessel-sealing system, and both ends were ligated using the endloop™ . After that, we performed McKeown esophagectomy with dissection for three field lymph nodes including around bilateral recurrent laryngeal nerve, as previously described . The operation time for the thoracic part was 325 min, and the blood loss during the thoracic part of the surgery amounted to 29 ml. The postoperative course was uneventful and physical functions that were impaired by the brain abscess recovered well. The patient was discharged on the 21st postoperative day. Histopathological examination of the resected specimen confirmed the diagnosis of esophageal squamous cell carcinoma, and the lesion was classified as pT3, pN0, M0, pStageIIB (UICC 8th).

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+A 78-year-old male with chronic kidney disease, dementia and sequelae of cerebral hemorrhage presented to his family doctor complaining of back pain; however, there were no abnormal findings on physical examination. Three days later, the back pain worsened and an ambulance was called. When the ambulance crew (including an emergency doctor) arrived at his home, his systolic blood pressure was 50 mm Hg, and the doctor performed portable echocardiography on site. Cardiac tamponade was diagnosed, and pericardiocentesis was performed using a puncture needle via the subxiphoidal approach. After draining ~ 500 ml of bloody pericardial fluid, the patient’s blood pressure immediately increased to 124/98 mm Hg. The patient was transferred to our hospital by helicopter with the outer cannula of the puncture needle placed in the pericardial cavity, and his hemodynamic status was stable at the time of arrival. We immediately started intravenous administration of saline (200 mL/h) to prevent the decrease in blood pressure due to blood loss. Electrocardiogram revealed negative T waves with slight ST elevation in II, III, and aVF leads, and echocardiography revealed severe hypokinesis at the left ventricular inferior wall and a small pericardial effusion. Laboratory tests showed the abnormal values in white blood cell (12.5 × 109/L, reference range, 3.3 to 8.6 × 109/L), C-reactive protein levels (68.5 mg/L, reference range < 1.4 mg/L), creatinine (1.24 mg/dL, reference range, 0.46–0.79 mg/dL), and highly sensitive troponin I (6559 ng/L, reference range < 34.2 ng/L). Creatinine phosphokinase levels (101 IU/L, reference range, 41 to 153 IU/L), hemoglobin (12.3 g/L, reference range, 11.6 to 14.8 g/L), and platelets (254 × 109/L, reference range, 158 to 348 × 109/L) were within reference range. We quickly performed contrast-enhanced computed tomography of the chest. A small protrusion of contrast media was observed on the inferior wall of the left ventricle, suggesting cardiac rupture due to acute myocardial infarction (AMI) . The tip of the outer cannula was confirmed in the pericardial cavity and appeared to reach epicardial adipose tissue around the right ventricle . Emergency coronary angiography was then performed, which confirmed occlusion of the posterior descending branch of the left circumflex coronary artery . Stenotic or occluded lesions were not found in other coronary arteries, and the patient's coronary tree was left side dominant. In addition, extravasation of contrast medium due to Ellis type III coronary artery perforation was observed in the acute marginal branch of the right coronary artery . We considered that coronary artery perforation had occurred as a complication of the pericardial puncture, and we performed transcatheter coil embolization of the perforated branch. A hydrophilic microcatheter (internal diameter, 0.018-in.; MIZUKI standard, KANEKA, Japan) was advanced selectively immediately proximal to the site of leakage in the acute marginal branch. One 0.018-in. and 20-mm-long tapered microcoil (diameter, 2 mm; Hilal, Cook, USA) was quickly released using the microcatheter, and angiography confirmed immediate vessel sealing and hemostasis 170 min after the emergency pericardiocentesis . After the coil embolization, there was no new bloody pericardial effluent and the patient was hemodynamically stable. Therefore, we reduced the rate of intravenous saline administration to 1 mL/kg/h. The total amount of drained bloody pericardial fluid was 610 ml including the first 500 ml. Hemoglobin level decreased to 8.9 g/L, and we performed blood transfusion. The total amount of contrast medium used in contrast-enhanced computed tomography and coronary angiography was 165 ml. Creatinine increased to 1.89 mg/dL 48 h after the use of contrast medium, and the urine volume decreased. Therefore, intravenous administration of saline continued, and then the urine volume gradually increased. Consequently, Intravenous administration of saline had been performed for 7 days. Timeline of clinical presentation and treatment was presented in Table .
+Oozing-type cardiac rupture due to AMI was considered as a cause of the cardiac tamponade, but the time of onset of AMI could not be identified, and subsequent blood tests had shown no increase in cardiac enzyme levels. Considering the general condition of the patient, who had dementia and comorbid chronic kidney disease, and the requests of the patient and his family, the patient underwent conservative treatment without cardiac surgery for oozing-type cardiac rupture and any procedure for occlusion of the posterior descending branch of the left circumflex coronary artery. Although the patient made steady progress without a further increase in pericardial effusion after the procedure, the patient needed treatment for a concomitant aspiration pneumonia (from day 3 to day 24 of admission) and rehabilitation for muscle weakness due to protracted bed rest. Finally, the patient was discharged on the 50th day after admission. Creatinine level was 1.28 mg/dL at the time of discharge.

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+In October 2009, a four-year-old girl was referred to the Rare Disease Unit of Bambino Gesù Children Hospital, presenting with phthisis bulbi (atrophy of the ocular bulb) of the left eye. She was the second child of Caucasian, non-consanguineous parents. Since the age of two-year-old, she developed recurrent episodes of conjunctivitis with pseudomembranes on the eyelids. After the failure of medical treatments, topical antibiotics and steroids, the lesions were surgically excised, but after a few weeks, they recurred, and conjunctivitis persisted. The surgical procedure was repeated twice.
+After the third recurrence, she was referred to our unit with a suspected diagnosis of LC.
+At first examination, the left eye presented a red, woody-like pseudomembrane (9 mm thick) that involved the edge of the upper lid and the upper tarsal conjunctiva, causing ectropion of the lid . Slit lamp examination revealed a yellow-white membrane affecting the bulbar conjunctiva, fornix, and cornea, hampering the evaluation of both anterior and posterior segments. Brain MRI with Optic Nerves study, showed severe involvement of the left eye .
+The right eye examination showed a small area of corneal de-epithelialization with a paracentral stromal opacity, and a whitish-yellow soft pseudomembrane involving the upper tarsal conjunctiva. The bulbar conjunctiva was not involved, and the rest of the ocular examination was normal. .
+After approval of the local Ethical Committee, treatment was started with topical plasminogen drops prepared from fresh frozen plasma (Kedrion Industrie Farmaceutiche, Lucca, Italy) in sodium hyaluronate, according to the Watts formulation [, ]. An intensive treatment schedule was chosen, with two drops instilled every two hours in both eyes.
+A rapid and complete response was observed in the right eye after one week. . In the left eye, we observed a reduction of the pseudomembranes after one week of treatment . The therapy was further intensified three days before surgery to two drops every hour. After that the red woody-like membrane was surgically removed. The thickened subconjunctival tissue was debulked via a conjunctival approach but the ectropion and lid retraction was not corrected until the upper lid retractors were recessed. The debulked posterior surface of the tarsus was left bare to granulate and the debulked flaps of conjunctiva were approximated to the upper border of the tarsus. The eyelid margin was left intact. A prosthetic shell was inserted behind the eyelids to maintain the conjunctival sac. The plasminogen was restarted every two hours.
+The eye drop schedule was prolonged from every two hours to every four hours, and there was no evidence of membrane reformation at the twelve-month follow-up evaluation up to the present twelve-year follow-up and the eye prosthesis is well tolerated .
+After three years of follow-up a nodular asymptomatic gingival hypertrophy with ulceration around the eruption site of tooth 36, was found. Non-surgical management of the lesion and strict follow-up was performed. The first molar erupted completely, with no signs of bone and periodontal pathology.
+Genomic DNA was extracted from peripheral blood by using NucleoSpin tissue, according to the manufacturer's protocol (Macherey–Nagel, Germany). Whole exome sequencing (WES) was conducted on the proband and his parents by using kit Twist Custom Panel (clinical exome—Twist Bioscience) on platform NovaSeq6000 (Illumina). The bioinformatics analysis was performed trough BWA Aligner or DRAGEN Germline Pipeline systems and the sequences were aligned to reference human genome GRCh37. The DNA sequence analysis showed the variants c.112A > G (p.Lys38Glu) and c.217 T > C (p.Cys73Arg) in compound heterozygosity of PLG gene. The first variant was inherited by the father and the second by the mother.

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+A 49-year-old male Chinese HCC patient with chronic hepatitis B virus (HBV) infection (having lasted more than 20 years) and cirrhosis. The laboratory results showed the following: alanine aminotransferase (ALT) 43.4 U/L, aspartate aminotransferase (AST) 35.7 U/L, alkaline phosphatase (ALP) 200.5 U/L, gamma-glutamyl transpeptidase (GGT) 188.1 U/L, bilirubin (TBil) 15.5 μmol/L, and a-fetoprotein (AFP) > 2000 μg/L. Liver function of the patient was Child-Pugh A grade and preoperative indocyanine green retention rate (ICG) was 10.5%.
+Computed tomography (CT) showed a large mass about 11.3 × 9.9 cm2 in size in the right hepatic lobe, and a tumor thrombus (TT) in the right hepatic vein (RHV) extending into the IVC .
+Using both his medical history and imaging findings, he was diagnosed with HCC associated with IVCTT. The clinical stage was BCLC stage C. The patient had no symptoms of right heart failure or pulmonary embolization at admission. Considering that the patient had normal hepatic function without distant metastasis, anterior approach right hepatectomy combined with IVC thrombectomy using trans-diaphragmatic intrapericardial IVC occlusion was planned for this patient .
+Surgery was performed via a subcostal inverse-L-shaped incision. At laparotomy, a tumor located in the right lobe of cirrhotic liver and no detectable ascites or peritoneal metastasis was observed. After the right hepatic artery and the right portal vein branch were ligated, hepatic parenchymal resection was performed using the clamp-crushing technique with inflow occlusion (Pringle’s maneuver) following the demarcation . Then the suprarenal IVC and portal vein were dissected and taped from the caudate lobe . The retrohepatic IVC below the confluence of the common channel of the left and middle hepatic veins was encircled by a vascular clamp. The diaphragm was transected via a vertical incision exposing the right atrial appendage. Then intraoperative ultrasonography was used to show that a TT in the RHV, involving the IVC, but it had not entered in the right atrium. The supradiaphragmatic IVC was encircled though trans-diaphragmatic intrapericardial IVC . The sequence of total hepatic vascular exclusion is shown in Fig. d and the IVTT was then removed en bloc successfully with Babcock forceps, the whole removal of IVCTT with IVC exclusion cost 20 min. The total operation required 481 min and the intraoperative hemorrhage was 900 ml.
+The macroscopic findings of tumor measured 10 × 11 × 13 cm3 and the TT measured 3.0 × 2.0 cm2 . Postoperative histological diagnosis showed moderately differentiated HCC (grade II-III Edmondson) had invaded the right hepatic vein with hepatic fibrosis and intravascular tumor thrombus. No positive resection margins or local lymph node metastasis were observed microscopically . The TNM stage was T3bN0M0.
+Postoperative recovery was uneventful. The patient was discharged with few adverse events after the operation. The patient was disease-free at 32 months after the initial treatment .

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+The patient, a 5-month-old boy, was delivered full-term and vaginally without complications. The neonatal course was uneventful. At discharge, he was exclusively breastfed and his weight and length were in the 50th percentile.
+A family history revealed consanguineous parents coming from Northern Africa; the mother had a history of two miscarriages before the birth of his older siblings. His elder brother had asthma and presented with abnormalities of the rib cage, while his sister underwent surgical treatment for transposition of the great vessels.
+At age 3 months, after a chickenpox infection, he experienced his first respiratory exacerbation followed by recurrent wheezing associated with airway infections, that required frequent admissions to the emergency room and treatment with inhaled beta2-adrenergic drugs, antibiotics and oral steroids. The child had received all of the mandatory and recommended vaccines for his age; he had no allergies and no history of apparent prior failure to thrive. At the age of 5 months, he was admitted to our Pediatric Unit for acute respiratory distress in a framework of suspected viral bronchiolitis. He presented with tachypnea (103/min), retractions, and hypoxemia (oxygen saturation on room air at 88 % at rest), requiring oxygen supplementation. Expiratory wheezing and crackling were the main respiratory auscultation findings. A clinical examination also revealed a significant reduction in growth velocity (both weight and length from the 50th to 10th percentile). Blood gas analysis revealed a respiratory acidosis (pH: 7,30; PaCO2: 48 mmHg; HCO3: 19 mmol/l). A chest radiograph revealed over-inflation of the lungs with some interstitial markings in the pulmonary hilum and right upper lobe. Nasal secretions were analyzed for respiratory syncytial virus, rhinovirus, influenza virus, parainfluenza virus and adenovirus; all resulted negative. After a first therapeutic trial with nebulized β2-adrenergic agonists without improvement of symptoms, he was treated with respiratory support in combination with appropriate fluid and nutrition management.
+Considering the persistent hypoxemia, despite supplemental oxygen support together with the associated pronounced respiratory distress and the clinical and radiological findings, the bronchiolitis diagnosis was determined to be misleading and an extensive diagnostic workup was performed. Complete blood count and measurement of serum immunoglobulin levels were normal; sweat test, serological tests for bacterial infections (Chlamydia and Mycoplasma pneumoniae, Bordetella pertussis), echocardiography and intraluminal impedance pH monitoring were negative. Assessment of the ciliary ultrastructure, beat frequency and pattern from a brush biopsy of the nasal epithelium excluded the diagnosis of primary ciliary dyskinesia. Subsequently, genetic testing for all exons encoding the ABCA3 surfactant gene (ATP-binding cassette 3) and the SFTPC gene (surfactant protein C) was carried out for suspected genetic surfactant disorders, with negative results. A diagnostic bronchoscopy excluded airway malacia and a bronchoalveolar lavage (BAL) revealed the high prevalence of neutrophils and the presence of slightly enlarged lymphocyte aggregates and macrophages with intracellular lipids. Microbiological examination of the BAL fluid showed an important colonization by Streptococcus pneumnoniae, Moraxella catarrhalis, Rhinovirus and Adenovirus. Meanwhile, high-resolution chest computed tomography (HRCT) showed air trapping in the left upper lobe and both lower lobes, and ground-glass opacities of the middle-upper lobes and of the lingula . This typical radiological pattern raised the possibility of neuroendocrine cell hyperplasia of infancy (NEHI). In order to complete the diagnostic workup, an open lung biopsy performed at 9 months of age showed the presence of areas characterized by macrophage alveolitis associated with neuroendocrine cell hyperplasia of the small airways. Immunohistochemistry demonstrated a significant number of bombesin-positive cells in the small airways walls . Finally, NEHI was diagnosed on the basis of radiological and histopathological findings typical of NEHI, while pulmonary interstitial glycogenosis was excluded with the biopsy findings. The infant was initially treated with oral prednisolone (1 mg/kg daily); afterwards, he required long-term oxygen and nutritional supplementation.
+At follow up visits he exhibited gradual clinical improvement. At 12 months of age, oxygen support was administered only at night. At the age of 18 months, his respiratory rate improved and his growth values were back within the normal range (50th percentile). At this time, the daily dose of steroids was stopped. Currently, at age 2 years, he only requires symptomatic treatment of any respiratory infection.

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+A 37-year-old white man, suffering from hepatitis B, presented to the emergency department with cough, low grade fever and night sweats. He was heterosexual with no history of intravenous drug use and worked as a bartender. Radiological examination of the abdomen and chest revealed no pathologies. Biochemical and hematological profiling showed: SGOT: 71 U/liter, SGPT: 61 U/liter, LDH: 931 U/liter, CRP: 28.33 mg/dl, leucocytosis (12,900/μL) associated with polymorphonucleosis (88.2%), Ht 35% and Hb 11.8 g/dl. The serologic examinations for HIV and hepatitis C were negative, as well as the Mantoux reaction.
+The next day, the patient presented with dyspnea and auscultation revealed diminished breath sounds with diminished vocal resonance in the right hemithorax. A chest X-ray revealed a pleural effusion in the right hemithorax. Computed tomography (CT) scanning of the chest and abdomen revealed a pleural effusion and a liver abscess . The abscess measured 14 × 9 × 7 cm, occupying a great percentage of the right lobe. An echogram of the liver showed septae within the abscess and for this reason echo- or CT-guided drainage was avoided. An operation was scheduled for the following day, but a rapid deterioration of the patient's clinical condition was observed that evening. The patient was febrile (oral temperature 39.2°C) with hypotension, tachypnea (32 breaths/minute) and tachycardia (110 beats/minute) and signs of an acute abdomen. Therefore, emergency surgery was deemed necessary. During exploratory laparotomy, a large volume of free fluid (~2200 ml) together with debris was found on entry into the peritoneal cavity. A rupture of the hepatic abscess at the position of segment VIII was found <Authors: and surgical drainage of the hepatic abscess (that contained many septae) was performed and two wide drains (32G) were placed in the remaining hepatic cavity. Finally, a thoracic drain tube (Büllau) was placed and gave only yellowish reactive fluid. The patient was hospitalized in the ICU for 14 days and for another 14 days in our department. The cultures of the pus were negative for any microorganisms. The diagnosis of an amebic abscess was made by the pathologists who identified E. histolytica in the debris . The patient was discharged receiving metronidazole (Flagyl, Rhone Poulenc Rorer) 500 mg three times a day.

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+A 15-year-old averagely built male, having no significant medical history, presented to the casualty with a history of closed trauma of the right knee following self-fall while playing. The mechanism of injury was hyperextension of the knee joint with a valgus stress. On physical examination, the patient had difficulty to move and was unable to stand on his right lower limb. There was visible swelling over his right knee and distal third of thigh with no skin defect. The attitude of the affected limb was that of abduction and external rotation with visible deformity around the right knee. There was a limb shortening of about 3 cm of the right lower limb as compared to the normal limb. The pulsations of the popliteal, tibialis posterior, and dorsalis pedis arteries were positionally palpable.
+An urgent color Doppler of the right lower limb was done which revealed positional variability in the pulsatality of the popliteal artery with compromised lumen and showing triphasic waveform in certain positions only. The anterior and posterior tibial arteries and dorsalis pedis artery also showed positional variability in the pulsatality with biphasic waveform in certain positions. Thus, the limb was maintained in the position where pulsations of the major arteries were felt . The capillary refill and toe movements were present. No motor or sensory defect was found. Plain AP and lateral X-ray of the right knee revealed a distal femur physeal fracture (Salter and Harris type I) with complete metaphyseal fragment displacement .
+The patient was operated within 12 h after the injury. Under spinal anesthesia, patient was positioned supine. Closed reduction was attempted using a proximal tibial Steinman pin for skeletal traction and manipulation of the right lower limb. After a gentle continuous traction, manipulation was done in the form of downward pressure on the distal epiphysis and an upward pressure on the proximal metaphyseal fragment of the femur. The reduction was not achieved and hence the fracture site was opened up using a Lateral approach. After the fracture site was visualized, the proximal fragment was held using bone holding forceps and the distal fragment fixed using a clamp , and traction and manipulation was done to achieve anatomic reduction of the fracture site. Reduction was confirmed under fluoroscopy and fixed using three 2.5 mm K-wires in a crossing manner , 2 from lateral to medial side and 1 from medial to lateral side. For additional stability, a long leg splint was given anteriorly in 20–30 degrees flexion of the knee.
+Post-operative radiographs revealed anatomic reduction of the physis of the distal femur with restoration of the normal axis of femur . Post-operative surgical outcome was satisfactory. Close monitoring of the patient was done for the first 24 h postoperatively and no signs of secondary vascular thrombosis were found. Patient was started with hamstring and quadriceps strengthening exercises postoperatively. The slab was kept for 6 weeks, following which the K wires were removed. A review X-ray done showed healing of the fracture , and partial weight bearing was initiated with the help of walker. On subsequent follow-up, after 4 and 8 months, correct limb axis alignment and no significant post-operative complications were found. After 6 months, the patient had become free of pain and had a complete range of movement in the right knee joint . There was no significant angular deformity or shortening in the right lower extremity.

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+A 19-year-old man developed blurry vision with new headaches in November 2014. He had bilateral papilledema. A MRI brain showed a large right-sided lesion involving the parieto-temporal lobes, hyperintense on T1 and T2-weighted sequences, with significant surrounding vasogenic edema on T2-weighted fluid-attenuated inversion recovery (FLAIR), contrast enhancement post-gadolinium, and a right-to-left midline shift . The overall appearance of this lesion looked a bit unusual for a classical GBM. He had a subtotal resection on January 30th, 2015, and was diagnosed by a local pathologist with a “GBM”. He completed 6 weeks of radiation therapy (RT) and temozolomide (TMZ). Four months later, a follow-up MRI showed an increase in the size of the enhancing tumor and, despite the possibility of pseudoprogression, a second surgical resection was performed on June 2nd, 2015 and showed “GBM”. Maintenance TMZ was started and follow-up imaging showed stable disease .
+The patient was referred to the Neuro-Oncology clinic at MCC in June 2015. Histology review showed that he had a malignant PXA grade III–IV, rather than a GBM. It had multinucleated giant cells, prominent nucleoli, and eosinophilic granular bodies on 600 × HPF, and a high mitotic index with dysplastic neurons on 200 × HPF . Histological samples were GFAP positive, with necrosis, ATRX retained, had a proliferation rate of 2% by Ki-67, and was positive for BRAF V600E on IHC . Foundation one testing confirmed the BRAF V600E mutation, IDH1 wild-type, and no EGFRviii. Other testing showed that the tumor was negative for 1p/19q co-deletion and was O6-methylguanine-DNA methyltransferase (MGMT) promoter unmethylated.
+After an initial 17 months of stable disease, on his MRI, there was a small increase in the size of his tumor . Accordingly, combination therapy with BRAF kinase and MEK inhibitors, Dabrafenib 150 mg PO BID and Trametinib 2 mg PO OD, was started on November 2016. As soon as 2 months after starting treatment, there was radiographic evidence of disease regression, though it did not meet the criteria for a Partial Response because of its small size. The patient was continued on this treatment regimen for 10 months and further serial imaging showed stable disease.
+After 8 months of treatment, in July 2017, treatment was held to give the patient a “drug holiday,” but, 2 months later, his MRI showed disease progression. Dabrafenib and Trametinib were re-started, and he remained stable until January 2018 when he had disease progression with BRAF MEKi. Since resistance to BRAF inhibition can be overcome by autophagy inhibition [–], we added the autophagy inhibitor chloroquine (500 mg PO daily) to his BRAF MEKi therapy. Each tablet of chloroquine contains 500 mg of chloroquine phosphate USP and the equivalent to 300 mg chloroquine base, which is the standard, maximal safe dose that is FDA-approved for adults .
+Based on the Response Assessment in Neuro-Oncology (RANO) criteria, the lesion size was measured, the sum of the perpendicular diameters (SPD) calculated and plotted . The tumor decreased by more than 25% after BRAF MEKi was started but unfortunately increased after a drug holiday , and continued to grow despite re-starting therapy with BRAF MEKi , at which point the autophagy inhibitor chloroquine was added halting the rate of tumor progression and even causing a slight decrease in the lesion size .
+There are no reported potential interactions between chloroquine and Dabrafenib and/or Trametinib. Chloroquine’s adverse effects can be multisystemic affecting the eyes (e.g., retinopathy, visual disturbances), hearing, liver, gastrointestinal system (e.g., nausea, vomiting, diarrhea, abdominal cramps), muscles (e.g., myopathy), skin (e.g., erythema multiforme, Stevens–Johnson syndrome), cardiac (e.g., prolonged QT interval), hematologic system (e.g., pancytopenia), and nervous system (e.g., seizures, extrapyramidal signs) . Given these side effects, we had taken precautionary measures with close monitoring every 1–2 months since started triple therapy, checking complete blood cells counts, complete metabolic panels, electrocardiogram, and echocardiograms. Overall, our patient tolerated the triple therapy well for 17 months until recently, when he complained of mild nausea, diarrhea, and a skin rash. The decision was made to hold chloroquine, while continuing Dabrafenib and Trametinib, with plans to re-assess him in 2 months.
+In summary, radiographically, he has had Stable Disease with BRAF MEKi for 14 months, and later with the addition of chloroquine for a total of > 2.5 years of treatment (triple therapy for 17 months), without major side effects from the treatment, until recently for which he is receiving a drug holiday from chloroquine.

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+In April 2023, a 39-year-old Chinese woman presented to our hospital complaining of a black shadow in front of her right eye for 5 days. This patient had been diagnosed with acute lymphoblastic leukaemia in 2017 and received an autologous HSCT in 2018. Unfortunately, she suffered a relapse of leukaemia and underwent an allogeneic HSCT in October 2022. The patient developed ocular symptoms at 6 months after receiving the transplant. After the consultation, the patient received a series of tests including visual acuity, slit lamp, noncontact tonometer, ocular ultrasound, macular optical coherence tomography, and Optos fundus photography. The patient’s best corrected visual acuity was 20/20 in both eyes using the Snellen visual acuity chart. The intraocular pressure was within the normal range. Slit lamp examination revealed that the anterior segmental structures of both eyes were normal. Ultrasound of the eye suggested flocculent vitreous clouding in the lower part of the right eye . Partial signal enhancement in the retina of the left eye was found, and part of the photoreceptor cell layer was missing on optical coherence tomography(OCT) . Fundus photography revealed a yellowish-white exudate with haemorrhage in the peripheral retina of the right eye and a faint haemorrhage in the lower retina of the left eye . Combining the medical history and relevant ophthalmic examination, we highly suspected that the patient had developed cytomegalovirus retinitis.
+Therefore, we performed anterior atrial puncture and extracted aqueous humour from the patient for viral testing on 23, April. We further refined FFA + ICGA on April 25. Surprisingly, utilizing broad-spectrum high-throughput sequencing, it was found that the aqueous humour of her right eye tested positive for three viral DNAs-CMV, EBV, and HSV . Internal markings and no template control were added to rule out a false detection of both herpes viruses during the high-throughput sequencing. The left eye was positive for CMV only. The FFA + ICGA findings indicated a small amount of retinal exudate in the patient’s right eye, and a large area of obscured fluorescence in the subnasal and inferior choroid . The patient was then treated with bilateral vitreous cavity ganciclovir injections. Viral DNA was retested one week later and no virus was detected in the aqueous humour of either eye by quantitative polymerase chain reaction(QPCR). The test was negative for viral DNA. OCT and fundus photography indicated no significant changes in the fundus. The patients underwent weekly serum cytomegalovirus and EBV testing after the second stem cell transplant. She was cytomegalovirus positive only between November 15, 2022 and January 14, 2023, with viral copy numbers ranging from 1.02 × 102 to 2.37 × 104 during this period. Each test was negative for EBV. The patient was treated with systemic antiviral therapy in the hematology department since February, 2023. As of May 22, 2023, her fundal lesions all remained stable.

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+A 50-year-old female with a history of well-controlled focal epilepsy presented to her neurologist with new symptoms of recurrent ‘sudden collapse’. At the age of 30, the patient had been diagnosed with non-lesional temporal lobe epilepsy characterized primarily by episodes of tonic–clonic seizures preceded by a sensation of déjà vu. She had been started on carbamazepine at that time with excellent seizure control. Her medical history was positive for hypertension and dyslipidaemia. She also maintained a family history of cardiac disease, unspecified. The patient had not suffered from any seizures or syncopal events until 5 months before her presentation. She complained of ‘unusual’ episodes, witnessed by her husband, of sudden drop attacks with brief loss of consciousness and postural tone associated with urinary incontinence. The syncopal episodes occurred without warning and without an associated trigger. She sustained no significant injuries from her syncopal events. Her clinical examination and biochemical profile on blood work were unremarkable. Magnetic resonance imaging of the head did not reveal evidence of acute changes to explain her presentation. Her carbamazepine dose was escalated in an attempt to control these episodes but failed to result in any improvement. Her antiepileptic medication was then changed from carbamazepine 200 mg p.o. t.i.d. to brivaracetam 75 mg p.o. b.i.d., again with no improvement. The patient underwent a continuous video-electroencephalographic study to characterize these events further.
+During observation in the epilepsy unit, the patient was observed to have an episode of sudden of loss of consciousness and urinary incontinence without any tonic–clonic activity or a prominent post-ictal state. Continuous electrocardiogram (ECG) monitoring revealed a concurrent episode of asystole lasting ∼20 s, followed by sinus bradycardia at a rate of 20–30 beats/min . There was no evidence of seizure activity on the electroencephalogram (EEG) preceding, during or following this event. The patient recovered and was subsequently admitted to the coronary care unit. On examination, her heart rate was 82 per minute, blood pressure was 128/74 mmHg, 86 kg, body mass index 32.1, and the systems examination was normal. She was recorded to have two episodes of symptomatic Mobitz type I atrioventricular (AV) block. Overall, her findings were consistent with isolated symptomatic bradyarrhythmia rather than ictal bradyarrhythmia or seizures. An echocardiogram was completed, which did not reveal any abnormalities. She underwent the successful implantation of a dual-chamber pacemaker. Her device was programmed to AAI-DDD with lower and upper rates of 50–130. Paced AV delay was set to 220 ms, and sensed AV delay 200 ms. Rate drop response was programmed ‘on’ to both low rate and rate drop. At 13-month follow-up, the patient was symptom free with no recurrence of her presenting events. Interrogation of her pacemaker revealed atrial pacing at 15.2% and ventricular pacing at 11%, suggesting a bradyarrhythmia of atrial aetiology.
+The patient was maintained on brivaracetam as her antiepileptic and was well tolerated. A decision was made not to switch back to her original anticonvulsant, carbamazepine, despite the non-ictal aetiology of her event. Carbamazepine exerts its therapeutic function through sodium channel blockade and can therefore theoretically affect depolarization currents within cardiomyocytes. Its use has been reported by the Food and Drug Administration (FDA) to be associated with AV block. As such, given the patients bradyarrhythmia, she was maintained on the alternative agent.

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+A 75-year-old man with a history of persisting abdominal pain and mild diarrhoea for three months was referred by a general practitioner to the hospital. During this period the patient observed a weight loss of 2 kg, but did not show any B symptoms. A colonoscopy was performed without pathological findings. A subsequent CT examination of the abdomen showed two separate fat-containing retroperitoneal masses one in the adrenal gland and the second lateral of the psoas muscle inferior to the right kidney, outside the peri-renal adipose tissue. The lesions were separate and had no connecting tissue in between them . To further confirm the obtained CT scan results an MR imaging was performed and showed again a fat-containing lesion in the adrenal gland and a 7 × 5 × 7 cm soft tissue-tumour inferior to the right kidney without invasion of the right kidney, urethra or renal vasculature. Both lesions appeared similar in the CT and MR imaging and were consistent with a well-differentiated liposarcoma . Aware of the fact that a liposarcoma of the adrenal gland is extremely rare, a primary benign and fat containing tumour derived from the adrenal gland itself, such as a lipoma or myelolipoma was considered. Regarding tumour markers, only increased levels of CA 19-9 were detected (81.86 U/ml reference < 37 U/ml, CEA 2.2 μg/l, reference < 5 μg/l). To exclude a neuroendocrinological pathology additional tests were performed but did not reveal any noticeable conspicuities.
+Consequently, we assumed a combination of a retroperitoneal liposarcoma and a primary benign, lipomatous tumour of the adrenal gland. Alternatively, the very rare case of the combination of a retroperitoneal liposarcoma and an adrenal liposarcoma was taken into consideration. Therefore, two therapeutic options were considered on these accounts. In the unlikely case of simultaneous liposarcomas an enbloc resection including both masses would be required after pre-treatment. But, in the probable situation of a benign lipomatous primary lesion of the adrenal gland in combination with a retroperitoneal liposarcoma an adrenalectomy with an additive biopsy of the infrarenal mass was decided as the strategy of choice in this individual case.
+Concerning this strategy a neoadjuvant radiotherapy followed by radical surgery, preventing the kidney, could have been performed as it has been approved as follows. To perform a neoadjuvant therapy a positive biopsy for sarcoma would be a compulsory prerequisite. Prognostic survival markers for retroperitoneal liposarcomas are the histologic subtype and margin of resection . Response rates to neoadjuvant chemotherapy alone are less than 10% . Preoperative radiation therapy or combined radio-chemotherapy with consecutive radical resection improves survival [,]. Concerning surgery complete resection of the lesion is to be achieved. Extended resection including contiguous organs without pre-treatment is associated with an increased risk without influence on disease specific survival and is therefore considered to be inappropriate .
+According to our described strategy, the patient received a laparotomy. As expected, the adrenal tumour appeared well-encapsulated in accordance with a benign lipomatous tumour. Following the above mentioned second option first an adrenalectomy was performed. The rapid section of the adrenal lesion revealed the result of a myelolipoma. Having in mind that both lesions presented morphologically identical in CT and MR imaging and the assessed intraoperatively analogousness of the masses, we resigned a biopsy of the infrarenal tumour and removed it in toto without the kidney. Once more the rapid section revealed a myelolipoma. The final histology described a 4 cm sized and in weight 46 g well-encapsulated myelolipoma of the adrenal gland. Further a 14 cm sized and in weight 250 g well-encapsulated retroperitoneal myelolipoma was determined, without capsule involvement. Both tumours were composed of predominantly mature adipose tissue with mature myeloid elements, allowing the diagnosis of an extra-adrenal and adrenal myelolipoma. Consequently no other treatment than surgery was indicated and has not been performed in this case.
+Postoperatively, the patient's recovery was uneventful and he was subsequently discharged.

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+A 14-year-old female came to our facility with concerns about difficulty in walking owing to weakness in both lower limbs, an erythematous, pruritic rash that covered her face, neck, axilla, elbows, and knees, and photosensitivity that had been present for eight months. It was unknown if she had any allergies. Patient underwent surgery 1.5 years after being diagnosed with retinoblastoma two years prior. After the enucleation, the patient underwent 40 cycles of radiation therapy and 13 cycles of chemotherapy with the drugs cyclophosphamide, etoposide, carboplatin, vincristine, and dactinomycin. In addition to developing proximal muscular weakness in both the upper and lower body after undergoing chemotherapy for 10 months, the patient also got a rash over their face that progressed.
+The patient was brought with these issues to our facility. Indicators of the patient's weakness in the proximal muscles of the upper and lower limbs were difficulty in rising from a sitting position and lifting the arms over the head. Her lower limbs had grade II muscle power and her upper limbs grade III, according to the examination. The CMAS score for childhood myositis was 36. Her vital signs were normal, and she had no underlying systemic issues. On inspection of the joints, there were no indications of active synovitis. At presentation, her neck flexor strength was higher than grade IV. Findings of skin examination showed hallmark manifestations consistent with DM, well defined to ill defined hyperpigmented scaly lichenified plaques over the neck, face, axilla , elbows, knees, including the V neck sign/Shawl sign, heliotrope eruption over the face especially on the forehead and periorbital region , Gottron papules over the digits of upper limb on both sides , calcinosis cutis involving the extensor aspect of elbows .
+The initial blood tests, such as complete blood counts, liver and renal functions, were all normal. Both lactate dehydrogenase (578 U/L) and creatine phosphokinase (171.61 U/L) levels were high. Positive antinuclear antibodies were found. Features of Dermatomyositis with interface dermatitis and mucin deposition in the dermis was consistent in the skin punch biopsy. Electromyography was done which showed small polyphasic motor unit potentials with fibrillations, positive sharp waves suggestive of Dermatomyositis. A muscle biopsy revealed fibres of the muscle that were necrosed and fragemted [Fig. ].
+According to the online calculator of EULAR/ACR classification for Juvenile Idiopathic Inflammatory Myopathies(IIM), the criterion score was 15.7, which was suggestive of Definite IIM . According to the Bohan and Peter criteria , JDM was determined to be the cause of the symptoms, which included the characteristic heliotrope rash with Gottron papules, symmetrical proximal weakness, raised muscle enzyme levels, electromyographic alterations, and even JDM-related changes in the muscle biopsy.
+Prednisolone oral 2 mg/kg/day and methotrexate oral 15 mg/m2 once weekly were started on the patient. After beginning the therapy for a week, the youngster displayed a slight improvement in symptoms as shown by lessened joint discomfort, stiffness, and erythema. Exercises for muscle strengthening and physiotherapy were started. During the patient's future hospital visits, it was seen that the patient's muscle strength had significantly improved.

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+We presented a 20-year-old male patient, who fell from a height of about 30 feet. He was initially managed at a nearby community hospital where he was diagnosed to have multiple rib fractures on both sides, with bilateral hemopneumothorax. The primary management of patient was performed with bilateral intercostal chest drains and positive pressure ventilation for lung contusion. The patient had no neurological deficit at initial presentation. He was then referred to our center after four weeks for further management.
+On examination, there was tenderness over the tenth thoracic vertebrae with mild knuckle deformity. There was no motor or sensory deficit at any level. Superficial and deep tendon reflexes were normal. Radiographs and computerized tomography showed a fracture dislocation with spondyloptosis of the ninth thoracic vertebra (T9) over the tenth thoracic vertebra (T10) with vertebral body fracture of the eight vertebral body ( - ). The pedicles of both T9 and T10 vertebrae were fractured bilaterally, thus separating the posterior elements from their respective vertebral bodies. There was complete spondyloptosis of T9 over T10 vertebral body and both T9 and T10 vertebral bodies could be seen in a single transverse section of computerized tomography . The patient was scheduled for surgery after improvement in general and lung condition. The spine was approached through standard posterior midline incision. There was no significant kyphosis seen and the posterior elements of the eighth and ninth thoracic vertebrae were lying almost in place with undisplaced fractures in the lamina of respective vertebra. The pedicle screws were inserted in the fifth, sixth and seventh thoracic vertebrae proximally and the tenth, eleventh and twelfth vertebrae distally ( - ). An in-situ posterior instrumentation with laminectomy of T8 and T9 vertebrae and posterolateral fusion from the fifth to twelfth thoracic vertebrae was performed. No attempt was made to reduce spondyloptosis of T9 over the T10 vertebrae. The patient tolerated the operation well and there was no postoperative neurological deterioration. He was mobilized with the help of customized dorsolumbar rigid orthosis on fifth postoperative day. He was followed up at monthly intervals and radiographs along with computerized tomography showed satisfactory in situ fusion between T9 and T10 vertebral bodies . The patient returned to his previous occupation.