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data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1004_en.txt

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+A 55-year-old man was found unconscious on the street and transferred to the emergency center of our hospital. At admission, the patient’s vital signs were stable, but he was unresponsive, the Glasgow Coma Scale (GCS) score was 4 (eye opening, 1; verbal response, 1; and motor response, 2), both pupils were maximally dilated (diameter, 6.5 mm), and pupillary light reflexes on both sides and vestibulo- ocular reflex (VOR) were absent. There were no visible local head injuries. Head CT revealed massive acute subdural hematoma above the right cerebral convexity causing prominent brain shift with subfalcine and transtentorial herniation, the obliteration of basal cisterns, as well as diffuse subarachnoid hemorrhage [-]. Immediately upon diagnosis, burr hole above the hematoma was made under local anesthesia, dura was opened, and subdural drainage tube was inserted. The patient was transferred to the OR, where large size right-sided decompressive craniotomy with removal of the bone flap was done and subdural hematoma was evacuated. However, prominent swelling of the brain and its protrusion through the bone defect remained, thus it was decided to perform internal decompression with extensive resection of the lateral and medial part of the right temporal lobe. Thereafter, frontal and parietal lobes still remained swollen, thus for the avoidance of brain compression after surgery the bulk of the temporal muscle down to the zygomatic arch was removed from the skull in one piece along with the periosteum. Extensive lax duraplasty with DuraGen® (Integra LifeSciences, Princeton, NJ) was done, probe for ICP monitoring was inserted, and skin was closed. No subdural or subcutaneous drainage was left.
+Immediately after surgery, CT demonstrated significant reduction of the brain shift, “reappearance” of the ambient cistern, large area of infarction within the right parietal and occipital lobes caused by compression of the posterior cerebral artery at the time of herniation, and subcutaneous hematoma [-]. The patient underwent standard treatment in ICU, including normothermia therapy. On the 1st postoperative day, his best motor response was characterized as withdrawal to pain, diameter of the left (contralateral) pupil reduced from 6.5 to 3.5 mm, and VOR has recovered, whereas on the 3rd day, the left pupil started to react to light . Gradual recovery of the patient continued thereafter. On the 45th day after primary surgery, cranioplasty and ventriculoperitoneal shunting were done, and on the 70th day, he was transferred for further treatment to the neurorehabilitation facility. At that time, his GCS score was 4T4 (eye opening, 4; verbal response, tracheostomy; and motor response, 4) and CT demonstrated asymmetric hydrocephalus, extensive infarction of the right parietal and occipital lobes, and small epidural CSF collection in the right temporoparietal area [-]. At 3 months after discharge, the condition of the patient corresponded to the Glasgow Outcome Scale (GOS) score 3 (severe disability).

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1017_en.txt

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+A 6-year-old boy, weighing 18.5 kg, white Kosova-Albanian ethnicity, presented with right groin pain, swelling and redness. Two days before admission the patient was injured during a football game in the right lower abdomen and the next day he complained of pain in the right inguinal area.
+Abdominal pain was permanent and increasing. The child was anorexic, but had no complaints of vomiting and diarrhea or disuria. On admission the patient was sub febrile (38°Celsius) with a painful non-reducible mass in the right inguinal region with signs of cellulitis in this area. There was a marked tenderness on palpation of the right lower abdomen and right hemiscrotum was moderately swollen and painful in palpation.
+Plain abdominal x-ray showed no fluid-air levels, but a metallic foreign body (pin) under right superior pubic bone was apparent [Fig ]. White blood cells were elevated. Surgical exploration was performed under general anesthesia. Inguinal canal is opened through transverse lower abdominal skin crease. Through swollen cremaster muscle and hernia sac we palpated a sharp metallic foreign body. Sharp side came from appendix lumen, two thirds of pin being in its apex. Dividing cremaster muscle we opened swollen hernia sac and we found the inflamed vermiform appendix perforated by a domestic pin [Fig. ]. The base of the appendix and coecum were in the internal ring closing it, thus blocking the fluid from the hernia sac returning to the abdominal cavity. Serous-purulent exudate in hernia sac was aspirated.
+Appendectomy and high ligation of hernia sac was performed. The wound was primary closed, without drainage. Antibiotics (ceftriaxon 500 mg and gentamicin 40 mg) twice a day for two days intravenously were administered. For postoperative analgesia paracetamol suppositories are given. Patient had uneventful postoperative course, and no complications in three years follow up.
+From parents we learned that the boy three weeks before the operation unintentionally ingested a few pins while drinking cola from the glass in a family ceremony.
+His mother has removed the pins from his mouth, and since he didn't have any complaints, he wasn't examined regarding foreign bodies in gastro-intestinal tract.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1019_en.txt

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+A 57-year-old female presented with vision loss in the left eye during the restoration of consciousness after endoscopic DCR surgery for the left eye. In this case, the DCR surgery was performed under general anesthesia. Notably, 2 ml of 1% lidocaine with 1:100,000 epinephrine was injected into the axilla of the middle turbinate and the frontal process of the maxilla using a dental syringe. In this case, the neurosurgical patties soaked in 2 ml of 1:1000 epinephrine were inserted between the inferior turbinate and the nasal septum and in the middle meatus to achieve topical decongestion. In the process of making mucosal flap and incision, the patient had a higher bleeding tendency than was noted with other patients, and a suction diathermy was used meticulously for the incidence of hemostasis. For this reason, it did not lead to a major bleeding in this case.
+The patient’s medical history was notable for thrombocytopenia and MHA. Upon review, the patient denied temporal headache, pain, or flashes. When tested, the patient’s best-corrected visual acuity (BCVA) was 20/20 in the right eye and light perception in the left eye. Her intraocular pressure (IOP) was 14 mmHg in the right eye and 16 mmHg in the left eye. Her visual field test result was normal for the right eye. However, the test could not be conducted for the left eye due to the incidence of poor vision. When tested with the swinging flashlight maneuver, a relative afferent pupillary defect was found in the left eye of the patient. Her extraocular movements were noted as being full and painless. However, mild periorbital bruising and swelling were detected in the left eye. Additionally, there was mild maxillary sinusitis noted as well. However, it was shown there was no underlying disease in the other sinuses. On the funduscopic examination, there were no obvious abnormal findings in the macula of either eye. The use of a fluorescent angiography did not reveal leakage or a filling defect at the disc. The baseline testing included blood tests to evaluate syphilis, systemic lupus erythematosus, and neuromyelitis optica. Her erythrocyte sedimentation rate and C-reactive protein results were noted as normal. Her pre-operative platelet count was 61 × 103/mm3. A chest x-ray was performed to evaluate sarcoidosis. She was transfused with six units of platelets preoperatively, which increased her platelet count to 123 × 103/mm3. No other cause of optic neuropathy was found in this evaluation.
+The pattern visual evoked potential revealed delayed P100 latency . Her electroretinogram showed normal electrical activity in the retina. The magnetic resonance imaging (MRI) of the orbit revealed a focal hyperintensity within the intra-orbital segment of the left optic nerve on the T2-weighted image (T2-WI) and flair image. At evaluation, the MRI showed an enhancement on the T1 post-contrast imaging . It did not show any demyelinating disease in the brain. The patient was diagnosed with left optic neuropathy and treated with 1 g/day of intravenous methylprednisolone for 3 days, followed by 1 mg/kg/day of oral prednisone with subsequent dose tapering. It is noted that the patient’s BCVA improved to 20/30 after the treatment. Although her vision improved, she was left with a visual field defect in the left eye.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1032_en.txt

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+A 54-year-old right-handed male patient known for RA treated with Methotrexate and anti-TNF-α was referred to a specialized shoulder and elbow clinic for right chronic elbow pain refractory to conservative management, consisting in intra-articular cortisone injection and physical therapy. He complained about posterior joint pain, swelling, and a deficit in extension, causing severe disability in his daily life and professional activities as a firefighter. Pain Visual Analogic Scale (pVAS) was 8/10,[ elbow Single Assessment Numeric Evaluation (SANE) score 25/100,[ Mayo Elbow Performance Score (MEPS) 35/100.[ Physical examination showed joint effusion with tenderness on palpation of the olecranon fossa, painful restricted range of motion (ROM) with 140–20–0° in flexion-extension compared to 150–0–0° on the contralateral side, pronosupination was unrestricted. There were no signs of ulnar nerve entrapment. Preoperative magnetic resonance imaging (MRI) showed a large intra-articular multilobulated pseudo-tumoral mass causing posterior humeroulnar impingement , with mixed components including lipomatous and synovial fringes , characteristic of LA. Due to the severity and duration of his disease with failed nonoperative measures, the patient underwent arthroscopic synovectomy and posterior humeroulnar decompression.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1037_en.txt

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+A 66-year-old female presented to our clinic with the mixed diagnosis of essential tremor and Parkinson’s disease, as she had both resting and action components of tremor in bilateral upper extremities with bradykinesia and rigidity that were somewhat improved on levodopa. The tremor was largely refractory to medication and interfered with her quality of life. She underwent bilateral DBS lead electrode implantation targeting the dentatorubrothalamic tract, specifically, the ventral intermediate nucleus (Vim), in the thalamus using the standard stereotactic protocol. A trajectory through the ventricle was avoided. Normally, we start by implanting the microelectrodes on the more symptomatic side and then proceed to the other side. In this case, three microelectrodes were simultaneously descended to target the left Vim (as her symptoms were worse in her right hand) first, followed by another three microelectrodes to target the right Vim. Their cannulas were used for macrostimulation to assess for improvement and to choose the best trajectory. Electrode placement (Medtronic 3387 model, Minneapolis, MN, USA) then occurred after confirmed improvement in tremor. The rostral ends of the electrodes were left in a subgaleal pocket to be accessed during a subsequent staged procedure for extension and pulse generator placement. The lead placement was verified in the operating room theater with computed tomography (CT) imaging before closure. Surgery was uncomplicated, and the patient remained interactive and conversant throughout. She was admitted to our neurosurgical ICU as per routine. Head CT performed on early postoperative day (POD) 1 was unremarkable . Physical examination revealed no deficit; the patient complained of headache with some nausea/vomiting. She desired to stay overnight. An examination later on the evening of POD 1 found her to be sleepy, and ultimately lethargic. Stat head CT performed revealed marked left-sided peri-lead edema extending into the centrum semiovale with cystic cavitation and trace right-sided edema . Physical examination on the morning of POD 2 revealed the patient to be alert but with global aphasia (not following commands and not speaking), right-sided neglect, and plegic right upper extremity. Corticosteroids (IV dexamethasone) were begun early on POD 2. She later became increasingly lethargic, and over concerns for airway protection was intubated. Repeat head CT revealed increased edema.
+The critical care team was concerned for fulminant gas- producing bacterial infection as suggested by neuroradiology interpretation of cavitation surrounding one lead and strongly pushed for lead removal, which was resisted. Vancomycin and meropenem were empirically begun. Systemic tests for infection, including C-reactive protein, erythrocyte sedimentation rate, and white blood cell counts, were normal, as well as blood cultures, which were ultimately negative at 24, 48, and 72 h. Such negative infectious workup and lack of change on serial repeat imaging disproved this idea. Magnetic resonance imaging could not be performed due to safety concerns at our institution with an incomplete DBS circuit. Acute venous infarction was also considered a possibility, but the radiological appearance of a cortical- subcortical typically wedge-shaped ischemic pattern was not present. This patient ultimately underwent tracheostomy and percutaneous endoscopic gastrostomy placement 6 days later. She was transferred to a rehabilitation facility on a steroid taper and subsequently discharged home on POD 40. She returned to the clinic 3 months after surgery fully recovered and ready for lead extension and pulse generator placement. Follow-up CT scans at the time showed significant resolution of the peri-lead edema and cystic cavitation .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1045_en.txt

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+A 25-year-old male, a worker in a garment factory, presented with complaints of band like feeling in the upper abdomen, not associated with any abdominal or back pain for 3 months duration. Simultaneously he had urinary hesitancy, a feeling of incomplete voiding of urine along with sense of inadequate evacuation of stool. Fifteen days later he developed descending paresthesia from the upper abdomen up to the both feet followed by weakness of trunk muscles, weakness and tightness of both lower limbs over a period of 2 months, which initially started in left lower limb and subsequently involved the right lower limb. There was no loss of perianal sensation. On examination, his higher mental functions and cranial nerves were normal. His upper limb power was 5 on both sides with normal tone and deep tendon reflexes. His lower limb power was 3 with hypertonia, exaggerated reflexes and ill-sustained clonus on the both side. He had sensory impairment below T5 corresponding to vertebral level D3. General physical examination and other system examinations were normal. A provisional diagnosis of thoracic myelopathy was made and patient was investigated. His complete blood count, renal profile, liver function tests, human immunodeficiency virus (HIV) and hepatitis B surface antigen were negative. His chest X-ray was normal. Erythrocyte sedimentation rate was moderately high and Mantoux was nonreactive. Magnetic resonance imaging (MRI) of whole cord revealed an iso- to hypointense lesion at D3 level on T1-weighted imaging (T1WI). The lesion was iso- to subtle hyperintense with central flow void onT2-weighted imaging (T2WI) , with cord edema rostral to the mass. Contrast-enhanced MRI showed a brilliantly enhancing lesion with hypointense centre at D3 with sharp margins . The oval-shaped lesion measured 16 × 10 mm. The diagnosis was intramedullary spinal cord tumor by MRI. Because of worsening of the patient's neurological examination, surgical removal of the lesion was undertaken. At D3-4, laminectomy was performed, posterior longidutinal myelotomy was executed, and a well-circumscribed pinkish fleshy mass was found to be located 2 mm anterior to posterior aspect of the cord. The lesion was dissected along a readily definable plane and was removed totally by use of the operating microscope. The histopathology showed multiple granulomas comprising of lymphocytes plasma cells, neutrophils, and large number of epitheloid cells in clusters with demonstration of acid fast bacilli (AFB) typical of Mycobacterium tuberculosis. Postoperatively the patient was given antituberculus treatment (ATT), started with isoniazid (INH) 300 mg/day, rifampicin (RF) 450 mg/day, pyrazinamide 1500 mg/day, and ethambutol 800 mg/day daily for 2 months, followed by INH and RF for 10 months. Pyridoxine at 40 mg/day was given for all 10 months. Postoperatively, the patient's neurological examination gradually improved and he could sit erect on the bed and able to walk over a period of 3 weeks without support. The follow-up time is 1 ½ year.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1050_en.txt

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+A medically and surgically free 6-year-old boy, with a weight of 22 kg and height of 122 cm, was brought to the ED of our hospital by his teacher with severe shortness of breath. The patient was witnessed ingesting popcorn when he suddenly started to develop cough and shortness of breath.
+In the ED, the patient was agitated, drowsy, and semi-conscious. There was no obvious upper airway obstruction, but auscultation revealed absent air entry in the left lung with subcutaneous emphysema in the right side of the neck. His oxygen saturation was acceptable on oxygen supplementation.
+Shortly after, patient became severely distressed and was intubated using midazolam, ketamine and succinylcholine. Chest x-ray was done after intubation and showed Endotracheal Tube (ETT) in good position, hyperlucent left hemithorax, flatting of ipsilateral hemidiaphragm, mediastinal shift to the right, and a radiopaque areain the left main bronchus . Auscultation after intubation showed minimal flow in the left lung (improved compared to initial presentation) with some episodes of desaturation.
+Otolaryngology – Head and Neck Surgery were contacted for urgent Direct Laryngoscopy and Bronchoscopy (DLB). After the patient was stabilized, he was taken to the operating room for DLB and foreign body removal with consent of the possible complications of bleeding, infection, inability to remove the foreign body, pneumothorax and/or teeth injury.
+In the operating room, patient was intubated on bag mask ventilation. Air entry was diminished bilaterally with scattered wheezing in both sides. There was difficulty in bag mask ventilation with obvious expansion in the left side of the chest. The patient was connected to standard monitors. Initial end tidal CO2 was 104 mm Hg, arterial blood gas showed pH of 6.87, PaCO2 181 mm Hg and PaO2 of 231 mm Hg.
+General anesthesia was maintained with propofol infusion of 250 mcg/kg/min, and dexmedetomidine 1 mcg/kg/hr. One dose of dexamethasone 0.5 mg/kg was given to help in relieving the possible airway edema.
+The patient was given succinylcholine during intubation in the ED followed by a dose of rocuronium, so the option of spontaneous ventilation was lost. The patient was maintaining his oxygen saturation (SaO2) on 100% O2 flow.
+The decision was made to proceed with flexible fiberoptic scope through the ETT to delineate the anatomy.
+First look was an unusual view of the foreign body which was seen saddling in the carina. The patient was extubated during flexible fiberoptic scope, so we proceeded with rigid bronchoscopy after irrigation with 2% lidocaine.
+While maintaining ventilation through the side port of the rigid bronchoscope, a foreign body was seen stuck in the trachea at the level of the carina, and a large right accessory tracheal bronchus was noted above the level of the foreign body . The foreign body was successfully retrieved as one piece under vision using fiberoptic forceps . A second look at the airway was done to exclude any other injuries and revealed a clear airway with no remaining foreign body and confirmed the presence of a right tracheal bronchus .
+After successful foreign body removal, another ETT was inserted and irrigation was done using normal saline. Airway entry improved, and arterial blood gas showed a pH of 6.95, PaCO2 of 141, and PaO2 of 40.3. Portable chest x-ray confirmed the ETT position and the absence of pneumothorax . The patient was shifted from the operating room to the pediatric intensive care unit (PICU) fully sedated and intubated. The patient was monitored in PICU and was extubated the same day.
+The patient was playful, tolerating orally, with no signs of respiratory distress and maintaining saturation on room air. He returned to his usual level of activity and was given dexamethasone 10 mg every 6 h (total of 4 doses). He was discharged home the following day in a good and stable condition with no need for further follow up.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1061_en.txt

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+A 33-year-old Chinese man was admitted to our department for sustainable foamy urine for more than one year. He also complained of intermittent hair loss and recurrence of oral ulcers.
+Approximately one year prior, the patient was hospitalized at a local hospital for the same reason, and routine urine tests indicated microscopic hematuria and proteinuria. He did not pay much attention, and there was no further diagnosis or treatment because of a lack of conscious symptoms. One month prior, his blood pressure rose to 145/91 mmHg for unknown reasons; microscopic hematuria and heavy proteinuria were again detected.
+The patient had no comorbidities.
+The patient's father had asymptomatic microscopic hematuria and proteinuria, as detected in a routine physical examination approximately 2 years prior. The patient had a daughter and a son; the daughter (7 years old) had asymptomatic microscopic hematuria, and the son had microscopic hematuria and proteinuria. His son had ever been diagnosed with chronic nephritis at a local hospital.
+The patient's appearance was normal, without edema. His systolic and diastolic blood pressures were 141 mmHg and 90 mmHg, respectively; his pulse rate was 81 beats per minute, and his respiratory rate was 19 breaths per minute. No obvious abnormality, including growth retardation, was detected during physical examination, and no specific nervous system symptoms were recognized. The patient was also subjected to audiologic assessments, but no hearing impairments were detected, even at high frequency. Furthermore, no symptoms were found in either eye by comprehensive ophthalmic examinations.
+Microscopic hematuria and proteinuria were confirmed by urine tests. The results of other tests, including routine blood tests and serum immunology, are listed in Table .
+No obvious abnormality was detected by abdominal ultrasound examination, X-ray diagnosis, or electrocardiographic examination. However, heart echocardiography showed a small amount of pericardial effusion.
+To further analyze the renal presentation, a histopathology study of renal biopsy was performed. By light microscopy, a total of 13 glomeruli were observed, with one glomerulus being enlarged and lobulated. Para-aminosailcylic acid staining and Masson staining were positive, showing mild mesangial matrix proliferation. The basement membrane was thickened. Three glomerular fibroblastic crescents and pericystic fibrosis of glomeruli were observed . In addition, deposition of erythrotropin under the endothelium of the capillary loop was detected . Electron microscopy revealed obvious basement membrane lesions including variable thickness and reticulation of the glomerular basement membrane, as well as irregular subepithelial protrusion of the lamina densa. Fine particles and electron-dense bodies were detected in the stratified basement membrane . Immunological staining for IgG, IgA, IgM, C3, C4 C1q, К, and λ was positive in four glomeruli, with the signals being deposited in the vascular lumen and mesangial area in a granular or linear form .
+A considerable investigation of family history was performed. The patient’s father had asymptomatic microscopic hematuria and proteinuria, as detected in a routine physical examination approximately 2 years previously. As mentioned above, the patient had a daughter and a son: The former had asymptomatic microscopic hematuria, and the latter had microscopic hematuria and proteinuria; his son had been diagnosed with chronic nephritis at a local hospital. Thus, three relatives had microscopic hematuria. Therefore, a diagnosis of ATS was highly suspected . For a precise conclusive diagnosis, the patient and his children were recommended to undergo genetic testing, and WES was performed. Genomic DNA was extracted from blood samples; WES was performed as previously described. After sequencing, the coverage of the target sequence was over 99.12%, and the mean sequencing depth was approximately 147. The sequencing analysis revealed a heterozygous substitution, NM_000091 c.2657-1G>A (p. V294fs) in intron 22 of the COL4A3 gene, which was confirmed by Sanger sequencing . The mutation was excluded from the single nucleotide polymorphism database but was included in the ClinVar database. As this mutation is located at an evolutionarily conserved splice site, this splicing mutation is thought to lead to the skipping of exon 23. In addition, this variant is classified as “likely pathogenic” according to the American College of Medical Genetics and Genomics standards and guidelines .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1074_en.txt

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+A 48-year-old Sudanese lady, coded as F83–581, presented with an abnormal gait as a manifestation of pure hereditary spastic paraplegia. Her condition started in early childhood with tip-toeing that progressed gradually in severity. At the age of 30 years, she could walk only using two sticks. She did not complain of any additional symptoms apart from occasional muscle cramps. Her parents were distantly related and had no family history of similar conditions. She was not on treatment. On examination, her lower limbs were spastic with severe weakness (power grade 3). There were bilateral deformities in the feet (pes equinovarus on the right and hammertoe on the left) and up-going plantar responses. Her upper limbs were normal except for mild spasticity and hyperreflexia on the right side. The patient (F83–581) had neither signs of cerebellar involvement nor evidence of sensory deficit. She was cooperative, oriented, and had no evidence of intellectual alteration. She could barely walk supported by two sticks, and her gait was spastic. Nerve conduction studies were normal. Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia with scattered ischemic foci in the white matter, cerebellum, and right side of the pons. The isthmus of the corpus callosum was thin, but it could be a normal variant. We noted neither cerebral, brain stem, nor cerebellar atrophy, nor acute ischemic changes on the brain MRI .
+We extracted DNA from the patient and four of her family members and investigated the patient and one of her healthy siblings, coded F83–582, using whole-exome sequencing . Whole-exome sequencing of the patient revealed a heterozygous variant, NM_001080414.4:c.1993G > A (p.E665K) (rs956104232), in the CCDC88C gene that results in substituting Glutamate at position 665 of the protein for Lysine. Sift , Polyphen2 HDIV , Mutation Taster , Provean and M-cap embedded in VarAFT software predicted this substitution as pathogenic with prediction scores of 0.002, 0.982, 1, − 3.21 and 0.069, respectively. Glutamate at position 665 of CCDC88C is highly conserved during evolution. The CADD score of 25 was also in favor of a pathogenic role of this change. We did not detect other convincing variants that could explain the phenotype in our patient. The variant NM_001080414.4:c.1993G > A (p.E665K) was reported once in the gnomAD v2.1.1 database in an individual of African ancestry and had a global allele frequency of 0.0000032 . Using Sanger sequencing, we validated that the variant NM_001080414.4:c.1993G > A (p.E665K) was heterozygous in the patient and absent in her healthy family members .
+To validate the pathogenicity of the NM_001080414.4:c.1993G > A (p.E665K) variant, we expressed the CCDC88C cDNA in human embryonic kidney (HEK) 293 cells and assessed its effect on c-Jun N-terminal kinase (JNK) / caspase-3 signaling pathway according to the presence or absence of the variant. Overexpressing CCDC88CE665K mutant protein caused a significant increase of JNK hyperphosphorylation and caspase-3 cleavage compared to the wild type protein, a pattern also seen when overexpressing the known SCA40 pathogenic proteins CCDC88CD43N and CCDC88CR464H . NM_001080414.4:c.1993G > A (p.E665K) was likely a de novo variant, though we did not have DNA samples from the parents. It had a low frequency in gnomAD database, predicted as pathogenic by multiple computational tools, and its pathogenicity was corroborated by functional studies, thus, fulfilling the criteria of likely pathogenic variants according to the American college of medical genetics and genomics guidelines for interpreting sequence variants published in 2015 . We have submitted the variant to the Clinvar database (accession VCV000978819.2).

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+A 41-year-old man with SIT since early childhood was referred to our hospital because of high serum carcinoembryonic antigen levels (6.0 µg/L). The patient had no surgical history. His body mass index was 24.3 kg/m2. Physical examination results were normal. All laboratory data were within the normal range, except for the tumor markers. Colonoscopy revealed a bulge at the orifice of the appendix, but pathological examination did not reveal any malignancy . Abdominal contrast-enhanced computed tomography (CT) showed complete “mirror-images” of the visceral organs . CT also showed appendiceal wall thickening, a cystic tumor with contrast effect, and an enlarged lymph node close to the tumor . CT and magnetic resonance imaging showed no solid component in the cystic tumor that would strongly suggest mucinous adenocarcinoma. The preoperative diagnosis was an appendiceal mucocele, which was considered a possible tumor such as low-grade appendiceal mucinous neoplasm (LAMN). We planned a laparoscopic-assisted ileocecal resection with D2 lymph-node dissection since the tumor was located at the root of the appendix with an enlarged lymph node. Preoperatively, we evaluated anatomical variations using 3D-CT, and no vascular anomalies except for completely inverted vessels were observed . In addition, we watched horizontally flipped videos of patients with normal anatomy undergoing similar operations to simulate mirror images and symmetrical procedures.
+Under general anesthesia, the patient was placed in lithotomy position. In contrast to normal surgery, the operator stood on the patient’s right side, the first assistant on the left side, and the scopist between the legs . A laparoscope was inserted through the umbilical trocar, and the other four trocars were placed opposite to their usual placement as shown in Fig. . Additionally, a 12 mm trocar was placed in the operator’s right hand, and two monitors were placed at the patient’s head. One monitor showed original images, and the other showed horizontally flipped images that looked the same as the normal anatomy . The central monitor 1 displayed the original images for the surgeons to see them easily, because it is dangerous and difficult to move the forceps while looking at flipped images due to paradoxical movement of the instruments. Moreover, the images displayed on the monitors were exchanged according to the surgical situation. As needed, the operation was momentarily paused to check for the range of mobilized regions and to visualize important anatomical structures by watching the monitor that showed flipped images .
+Laparoscopy and intraperitoneal observation revealed transposition of the visceral organs, such as the liver, gallbladder, stomach, and colon. The ileocecal resection procedure was performed using the retroperitoneal approach as usual. The small intestine was moved cranially to secure the surgical field, and we initiated ileocecal mobilization. We dissected the mesentery from the retroperitoneal tissue with a focus on the gonadal vessels and identified the transverse portion of the duodenum. Next, while dissecting along the descending portion of the duodenum , we dissected the lateral attachment of the colon to the left abdominal wall toward the cranial side and mobilized the hepatic flexure . Finally, we performed additional dissection around the duodenum and pancreatic head, completing the mobilization . Since D3 lymph-node dissection was not necessary, we divided the ileocolic vessels near its root without lymph node dissection around the superior mesenteric vein (SMV) and performed resection and reconstruction of the colon extracorporeally. In total, the operative time was 119 min, and the patient’s postoperative course was uneventful. Postoperative pathological examination revealed lymphoid follicles in the intestinal epithelium of the appendiceal orifice and inflamed appendiceal mucosa with neutrophils and eosinophils. No tumor cells suggestive of LAMN or malignancy were observed.
+Regarding laparoscopic surgical procedure for SIT, it was unclear how far the mobilization proceeded due to the mirror image; however, during the procedure, we periodically examined the mobilization progression by momentarily pausing the operation to watch the monitor showing flipped images. Additionally, we noted the following differences between surgery in SIT and surgery in patients with normal anatomy: (1) operability involving large movements such as moving the small intestine and securing the surgical field (2) recognition of anatomies such as orientation of the gonadal vessels and duodenum, positional relationship between the hepatic flexure and duodenum, and the hepatic flexure in the upper left abdomen being closer than expected as compared to the splenic flexure in normal anatomy. In such situations, we were able to appropriately address any confusion and misrecognition by checking the flipped monitor . Additionally, this procedural method allowed for safe operation on important organs, such as the pancreatic head . To enable the readers to understand the procedure, a video of the surgery with flipped images has been attached as a Additional file : Video S1.

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+A girl, now 20 years old, presented to our hospital for the first time at the age of 7 years and 8 months, with multiple-joint swelling and limited motion for more than 5 years and recurrent fever for 18 months. Her long-term history of arthritis could be traced back to when she started to suffer from symmetrical polyarthritis at the age of 2 years, and her arthritis was in both knees, both wrists, the metacarpophalangeal joints, the proximal and distal phalangeal joints. She presented to the pediatric doctors in the local hospital by her parents and was diagnosed with juvenile idiopathic arthritis (JIA). The doctor treated her mostly with nonsteroidal anti-inflammatory drugs (NSAIDs) and methotrexate (MTX). During the following 5 years, her symptoms were not well controlled. At the age of 6 years, she had repeated and unexplained fevers. Anti-infection and symptomatic treatment were given but were ineffective. She was taken to her local pediatrician many times and received steroid treatment for several months. When she was 7 years of age, she complained of attacks of redness in both eyes but denied any history of vision loss. She was diagnosed with anterior uveitis of both eyes and her ocular symptoms disappeared after receiving ophthalmic treatment (tobramycin dexamethasone eye drops). Regarding her complete past medical history, in addition to the above manifestations, she had a squamous rash once at 10 months of age, which was ignored by her parents at that time.
+In August 2009, when she was 8 years and 9 months old, the girl was referred to our hospital for the first time regarding recurrent arthritis in the absence of ocular complaints, rash and other symptoms. There was no other contributory past medical or history or family history. Physical examination revealed swan neck deformities of all fingers , limited joint mobility, swelling of the wrists, elbows, and knees, and a positive right 4-word test. No other remarkable findings were observed on physical examination. Blood tests showed a significant increase in the C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR). Her rheumatoid factor and human leukocyte antigen B27 (HLA-B27) were negative. No positive findings were found on her ophthalmic examination. MRI and other imaging examinations supported the manifestations of arthritis. With a diagnosis of JIA (polyarticular, RF negative), treatment was initiated and consisted of Etanercept, recombinant human tumor necrosis factor-Fc (rhTNFR:Fc), 0.8 mg/kg per week combined with MTX and NSAIDs. She showed improvement in her joint swelling and fever, but these symptoms still had recurred. In the following 10 years, the patient was followed up irregularly, and she had stopped etanercept on her own. Between 2015 and 2019, she was intermittently treated with prednisolone at doses ranging from 2.5 mg to 10 mg per day. Regrettably, the girl had vision loss in both eyes in 2018. An ocular examination showed obsolete iridocyclitis in both eyes and left eye cataracts. She underwent left eye cataract surgery in May 2018 in the Ophthalmology & Otorhinolaryngology Hospital, and her visual acuity recovered after the operation. In October 2019, she developed unexplained hypertension, which was found on a routine physical examination at school. She was referred to the local hospital and given nifedipine, but her blood pressure was not controlled.
+On October 24, 2019, the girl was transferred to our hospital. Physical examination revealed that her blood pressure (BP) was 140/70 mmHg in the left upper limb, 139/79 mmHg in the right upper limb, 167/76 mmHg in the left lower limb, and 165/67 mmHg in the right lower limb. Before this, her blood pressure was increased once in a visit in 2017 in the only few outpatient visits, and was normal at other times. Moreover, she had painless fixed flexion deformities of multiple joints on physical examination. Additionally, ophthalmologic checks showed bilateral band-shaped degeneration of the cornea, with a corrected visual acuity of 0.4 in the right eye (OD) and 0.3 in the left eye (OS). She was diagnosed with bilateral panuveitis by an ophthalmologist. Various laboratory tests were ordered, and the results were as follows: her 24-h urinary protein excretion was 0.19 g and her serum creatinine was 102 μmol/L. We collected data on the serum creatinine (Scr) and eGFR of the patient during the past 10 years . According to the results, her Scr began to increase (ranging from 75 to 92 μmol/L) in approximately 2017 and finally increased to 102 μmol/L in October 2019. Her renin–angiotensin–aldosterone, CRP, ESR and thyroid hormone were within the normal ranges. Her autoantibodies were negative. Ambulatory blood pressure monitoring (ABPM) showed that the 24-h average BP was 143/83 mmHg (> 130/80 mmHg), the daytime average BP was 144/86 mmHg (> 135/85 mmHg) the and nighttime mean BP was 140/76 mmHg (> 120/70 mmHg).
+B ultrasound demonstrated that the right kidney (8.85*3*3.42 cm) was smaller than the left kidney (10.2*3.86*4.05 cm). The difference in length between the two kidneys was 1.35 cm. We searched and summarized all the renal B ultrasound data of the patient in the past 10 years compared with kidney length normative values in children . The sizes of the kidneys did not increase with age, the right kidney gradually decreased in size, and the size difference of both kidneys gradually increased. 99mTc-DTPA renography demonstrated that the right kidney was smaller than the left kidney with poor renal perfusion and impaired renal function . The GFR [ml·min-1·(1.73 m2)-1] of the kidneys was 74.4 (right kidney 30.8, left kidney 43.6). A significant difference was observed in the two splits of renal function: the renal function was 41.4% in the right kidney and was 58.6% in the left kidney. Computed tomography angiography (CTA) of the renal artery illustrated that the branches of the renal artery in the right hilum had mild stenosis , and the right kidney was smaller than the left kidney . No significant abnormalities were observed in the thoracic aorta, abdominal aorta, or cerebrovascular system. No remarkable findings were revealed on echocardiography and during an electrocardiogram. To further clarify the situation of the patients’s renal vessels, we also suggested performing digital angiography. However, her parents refused this invasive examination. The patient was diagnosed with right renal vasculitis through CTA of the renal artery (mild stenosis in the branch of the renal artery of the right renal hilus) and 99mTc-DTPA renography (difference in bilateral renal function and GFR) based on her two unequally sized kidneys (the gradually shrinking right kidney and the normal left kidney).
+In view of the clinical manifestations mentioned above, including recurrent polyarthritis, fever, bilateral panuveitis and kidney involvement in medium-vessel vasculitis, it was obvious that this girl might in fact not have JIA. The diagnosis was likely an autoinflammatory disease. Thus, we performed whole genome sequencing (WGS) for the patient and her family. The results revealed that she had a de-novo heterozygous mutation in the NOD2 gene (c.1538 T > C, p.M513T) , with her parents presenting with the wild type. The M513T (1538 T/C) mutation was a heterozygous mutation and has been reported previously. According to the presentation and genetic test results, she was finally diagnosed with Blau syndrome and renovascular hypertension.
+Considering her ocular lesions and unsatisfactory therapeutic effect, we suggested treating her with an anti-TNF-α monoclonal antibody (adalimumab) based on the previous studies . However, the patient refused the treatment because of financial reasons. Finally, she temporarily accepted a low dose of oral prednisolone, MTX, metoprolol and plendil. Her BP was gradually decreased and was controlled at approximately 130/80 mmHg. The OD and OS corrected vision were gradually restored to 0.6 after approximately 3 months. Her serum creatinine level slightly decreased and remained between 80–90 μmol/L after nearly 3 months of follow-up. In February 2020, she was referred to an adult hospital after reaching the age of 18. In the latest telephone consultation with the patient in December 2022, she stated that she was receiving prednisolone (15 mg/day) and tofacitinib (5 mg bid), and MTX had been discontinued because of abnormal transaminase. There were no new symptoms in the joints or eyes. There were also no rashes. Hematology examinations indicated that the patient’s ESR (25 mm/h) and serum creatinine (138 μmol/L) had increased. Her blood pressure was maintained at approximately 140/90 mmHg without any antihypertensive therapy.

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+A 37-year-old Japanese woman had a history of gender identity disorder from childhood and had taken testosterone injections once every 2 weeks since she was 19 years old. She also had untreated high blood pressure. She had worked in the sex industry and had a tattoo on her right arm. In May 2017, she developed a headache and visual field deficits together with elevated blood pressure and was referred to our hospital. On admission, her blood pressure was 165/105 mmHg with regular heart rhythm. She was alert and well oriented. She had left homonymous hemianopia. Brain magnetic resonance imaging (MRI) showed a hyperintense lesion in the right parieto-occipital lobe on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, and fluid-attenuated inversion recovery (FLAIR) , which were not enhanced by contrast with gadolinium. MR angiography (MRA) showed steno-occlusive lesions in bilateral middle cerebral arteries (MCAs) . Three-dimensional contrast-enhanced angiography revealed occlusions of bilateral MCAs . She was initially suspected as having PRES related to reversible cerebral vasoconstriction syndrome (RCVS) and received treatment with an antihypertensive drug and 100 mg of aspirin. Routine blood testing showed the patient was HIV-1 antibody-positive. The CD4+ T-cell count was 140 cells/μl and the HIV viral load detected by PCR was 330,000 copies/ml. She underwent lumbar puncture, and no pleocytosis was found. Furthermore, PCR for herpes simplex virus (HSV), varicella-zoster virus (VZV), and JC virus in cerebrospinal fluid was negative. She had also developed pneumocystis pneumonia when she was diagnosed with AIDS. Antiretroviral therapy (ART) comprising dolutegravir sodium, emtricitabine, and tenofovir alafenamide fumarate was initiated, and she was discharged from the hospital. Two weeks later, she suffered a severe headache and worsening of visual disturbance in bilateral eyes. Her blood pressure was 153/93 mmHg and her visual acuities were finger counting. MRI showed the hyperintense lesion had expanded to bilateral posterior hemispheres . Stenotic lesions in bilateral MCAs remained on MRA and three-dimensional contrast-enhanced angiography . The CD4+ T-cell count at readmission was 189 cells/μl and HIV viral load was 94 copies/ml, indicating that AIDS activity was alleviated after ART. Although she was initially treated with edaravone, a free radical scavenger, and antihypertensive agents after readmission, her visual acuities fluctuated and contrast-enhanced MRI showed multiple punctate and linear gadolinium-enhanced lesions in the occipital and temporal lobes and the cerebellum . Brain biopsy was performed from the right occipital lobe. Histopathology showed severe tissue destruction, astrocytic gliosis, microglial activation, and vasculitis with marked lymphocytic infiltration in the cerebral white matter in the absence of multinucleated giant cells and lymphoma cells . Infiltrated lymphocytes were mostly CD8+ T-lymphocytes, while CD4+ T-lymphocytes were scarce . We finally diagnosed her as having CD8+ encephalitis, with an exacerbation caused by immune reconstitution inflammatory syndrome (IRIS) after ART. After brain biopsy, the patient was treated with 1000 mg of methylprednisolone intravenously for 3 consecutive days followed by 0.5 mg/kg/day of prednisolone. Her visual acuities and headache improved after corticosteroid treatment.

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+My patient was a 19-year-old man diagnosed in early childhood with ADHD and ASD. He was referred by his local doctor for ongoing treatment as an adult. He had experienced long-term difficulties in establishing and maintaining lasting relationships and reading social cues. His conversations were awkward and restricted to a narrow range of subjects and he was frequently impulsive and insensitive during these interactions. These impairments had contributed to his increasing social isolation and conflict within the family environment. He had a low threshold of irritation and intolerance of noise, light and crowds. There was also a long history of outbursts of anger, physical intimidation and frequent destruction to property at home. He was also disorganized, forgetful and had difficulty completing tasks. He has always been overactive, restless and impulsive. There was no history of pervasive mood disturbance.
+There were early concerns about a potential developmental delay and he was referred for a pediatric assessment at age two years. He received speech therapy prior to school and also repeated his pre-school year. Although he was of average intellect, his significant and specific learning, behavioral and communication difficulties warranted a placement in a special education unit to manage his needs. He experienced difficulties in both reading and writing and he performed below all national standards of literacy and numeracy. Reading remained effortful and unrewarding, with difficulties focusing on and reading along a line of text. At the age of seven he had an occupational therapy assessment, which reported difficulties with coordination, fine motor control, planning and sequencing. In the classroom he was reported to be distracted and restless, presented with extreme outbursts of anger and frequently ran away. He had poor interpersonal skills, established few friendships, had odd idiosyncratic language and repetitive hand flapping, and had a history of being bullied.
+He commenced stimulant medication during early childhood and had trials of immediate-release dexamphetamine and methylphenidate with improvement in classroom behavior. He had little interest or motivation in taking his medication, resulting in generally poor adherence. Without stimulant medication his behavior quickly deteriorated.
+Since leaving school he had obtained a number of part-time unskilled jobs for eight to ten hours per week. He was, however, unable to maintain them because of behavioral and communication difficulties. He did not smoke cigarettes or consume alcohol or illicit substances. There was no significant family psychiatric history.
+On presentation, he was taking methylphenidate extended-release 72mg daily via an osmotic-controlled release oral delivery system and melatonin 4mg every night. He had been prescribed this medication for the previous two years.
+During my clinical assessment, he was constantly restless, appeared disinterested and was easily distracted. He made little eye contact either when listening or speaking and his non-verbal interaction was limited. His answers to questions were minimal and his speech lacked normal prosody. His blood pressure and pulse were within the normal range although he was significantly overweight with a body mass index of 34kg/m2 (weight 102kg, height 1.72m).
+Following completion of his assessment an additional dose of methylphenidate was recommended in the late afternoon to try and reduce his frequent aggression at this time. However, he stated that this suggestion was of no interest to him and he did not care that others might be upset by his behavior.
+During the three months following his initial assessment there was no alteration to his pharmacotherapy and no improvement in his behavior. As a consequence of his persistent social difficulties the option of a trial of low-dose phenytoin was discussed. It was explained to my patient and his mother that improvements in social functioning had been observed by myself and been reported by other patients who also had taken low-dose phenytoin; although, these effects had not been demonstrated outside the clinic nor was this an approved indication for the medication. My patient and his mother signed a disclosure and informed consent document and a trial of medication was organized for the following consultation.
+Two weeks later a sublingual test dose of approximately 2mg phenytoin was administered. Prior to this dose my patient’s interaction reflected his usual behavior, with little interest and social engagement. He was reluctant to participate in conversation and his verbal responses were minimal and lacked elaboration; there was only minimal facial expression, which appeared to be unconnected to the content of his speech. Within 10 minutes of taking the sublingual phenytoin he reported a reduction in the effort required to contribute to conversation and was able to sustain eye contact both when listening and speaking. He was surprised about the effortless nature of his eye gaze and also commented that he had never done this before, and that previously he had always found it easier to avoid eye contact when speaking. He was now experiencing the reverse, finding it harder to break away from the mutual eye gaze. He stated he felt more relaxed and was less distracted by other environmental visual and sensory stimuli. His non-verbal interaction, demonstrated by the raising of his eyebrows, smiling and nodding of his head, appeared to be more spontaneous and natural. During this assessment he read aloud two standardized examples of a text, pre- and post-administration of the phenytoin. He reported a reduction in the effort required and improved comprehension and accuracy. He stated that he was no longer as distracted by the other lines of text on the page, which previously had resulted in becoming overwhelmed and lost on the page. His speech was also more fluid with more appropriate intonation. He denied any adverse effects of the test dose. The following day he started taking compounded 2mg phenytoin capsules in the morning in conjunction with his methylphenidate.
+After two weeks both he and his mother stated that his communication with the family had improved and there had been no aggressive outbursts. During the consultation he was noticeably more engaged and appeared to enjoy the interaction. His ability to maintain eye contact and his non-verbal communication - facial expression, head movements and posture -were more synchronized and spontaneous.
+Over the next four weeks he became inconsistent in taking the phenytoin, and then ceased altogether. His behavior reverted to the previous pattern of poor social interaction; he became oppositional with outbursts of anger and physical violence.
+Nine months later he resumed taking the phenytoin, this time as a single 4mg capsule in the morning. After his first dose there was an improvement of his social behavior similar to his previous response, although there was an apparent deterioration in the late afternoon. The dose was increased from 4mg to 5mg and a larger capsule formulated to try and prolong the release of the phenytoin. This appeared to achieve a more consistent improvement in behavior throughout the day, evident both at home and at work. Increases in the dose above 5mg were not associated with any additional benefit. He remained on the 5mg dose of phenytoin for over 18 months and reported that his work performance had consistently improved sufficient to increase his working hours and his level of responsibility. The violence and destruction at home abated. His confidence improved and for the first time he has established and sustained peer-appropriate friendships.
+His behavioral ratings prior to treatment with phenytoin and after seven months on the 5mg phenytoin are presented in Figure . The manner in which my patient endorsed the items on the AQ highlighted a reduction of symptoms, with the most robust improvements in his enjoyment of social occasions, ability to cope with chit chat, and his preference to be with people rather than be alone. His total AQ score dropped from 41 pre- to 27 post-treatment with phenytoin; a score of 32 or more is considered to indicate clinically significant levels of autistic traits . Before treatment with phenytoin, his DASS ratings recorded both depression and anxiety as severe and stress as very severe. Post-treatment, there was robust change in all domains, with an absence of depressive symptoms and with both anxiety and stress being recorded as moderate.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1119_en.txt

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+A 75-year-old man was diagnosed with gastric cancer through a medical check-up and was referred to our department. The patient had no subjective symptoms or remarkable past medical history. The tumor marker carbohydrate antigen 19-9 (CA19-9) was elevated, with a value of 231.5 U/ml . Upper endoscopy demonstrated a 5-cm circumferential ulcerated lesion at the cardia . Biopsy showed a poorly differentiated tubular adenocarcinoma. Computed tomography (CT) showed a wall thickening of the lesser curvature side of the upper gastric body . The patient underwent laparoscopic total gastrectomy with lymph node dissection, and the pathological diagnosis was consistent with a moderately differentiated tubular adenocarcinoma, pathological stage T4aN1M0, and IIIA according to the UICC classification . The postoperative course was unremarkable, and the patient was discharged. He refused adjuvant chemotherapy and was under close observation. The patient was regularly followed up with laboratory tests and imaging studies. Twenty-three months after the primary gastrectomy, a CT scan revealed an irregular mass near the port site wounds . The mass continued growing over time, and port site recurrence was suspected. The CA19-9 level increased to 142.2 U/ml . The patient underwent mass resection, and the pathological diagnosis was consistent with metastatic adenocarcinoma in the subcutaneous tissue at the port site . In the operative findings, there were no ascites and disseminated nodules in the abdominal cavity. Macroscopic findings of the resected specimen revealed that the center of the tumor was not in the peritoneum, but the abdominal wall. Therefore, it was considered to be a PSM rather than peritoneal dissemination. Thirteen months after the second surgery, CT revealed an enhanced mass in the abdominal wall. Furthermore, PET-CT showed an elevated uptake in the rectus abdominis muscle and a SUV of 3.1 . Fine-needle aspiration biopsy of the lesion detected malignant cells with suspected metastatic adenocarcinoma. The CA19-9 level was elevated to 53.6 U/ml again . The patient underwent mass resection again. The mass had macroscopically infiltrated into the rectus abdominis muscle . Similar to the first recurrence, there were no ascites or disseminated nodules in the abdominal cavity. The pathological diagnosis was identical to that of a gastric metastatic adenocarcinoma in the rectus abdominis muscle . After thirty-five months from the third surgery, CT revealed a mass in the left gluteal region. PET-CT revealed a 35-mm mass in the lateral subcutaneous area of the left iliocostalis lumborum muscle, which showed an elevated SUV of 9.6 . Percutaneous biopsy of the lesion revealed a metastatic adenocarcinoma, and the CA19-9 level was 111 U/ml . Another mass resection procedure was performed, and the pathological diagnosis was consistent with subcutaneous metastasis from the gastric adenocarcinoma . Since tumor cells were present at the resection margin, additional radiation therapy was performed. After each recurrence, the patient did not undergo adjuvant chemotherapy. The patient has survived 78 months after primary gastrectomy.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_112_en.txt

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+The patient was a 55-year-old woman with a history of smoking and prolonged opium inhalation, referred to Ghaem clinic in Mashhad with dysphonia, hoarseness, and occasional aspiration since last year. No sign of odynodysphagia, stridor, and dyspnea was observed in the case.
+The patient did not previously undergo any treatment. In laryngoscopy, prior to surgery, left arytenoid, aryepiglottic fold, left false vocal cord, true vocal cord, anterior commissure, and subglottic region were tumoral. In addition, other parts of the larynx and hypopharynx were normal. The left vocal cord was fixed. In the preoperative computed tomography scan, there was a transglottic involvement on the left side, and cervical lymphadenopathy was not detected. Laryngeal cartilage and hyoid bone were reported to be normal. The right paraglottic space was involved, and the epiglottis was normal. The tongue, esophagus, trachea, and thyroid were normal. The biopsy of the affected areas represented the well-differentiated squamous cell carcinoma. Furthermore, chest X-rays and liver function tests were normal. The patient was ultimately diagnosed with a transglottic squamous cell carcinoma of the T3N0M0 stage. Moreover, total laryngectomy with total thyroidectomy (due to subglottic involvement) and bilateral elective cervical lymph node dissection level I-IV were performed. The tumor was macroscopically removed, and the surgical margin was checked with a frozen section for the presence of the tumor. The neopharynx was closed with the suturing technique. The patient diagnosed with salivary fistula was initially treated with conservative management, including total parenteral nutrition, pressure dressing, and broad-spectrum antibiotic therapy .
+Despite the use of broad-spectrum antibiotics in the 12th day, due to swelling and cervical erythema on the right side, the case with a diagnosis of infectious colonization, followed by the salivary fistula, was transferred to the operating room.
+In addition, the drainage and diversion of salivary secretion away from the carotid sheath were performed under general anesthesia. Moreover, in order to sterilize the fistula and help the formation of fibrosis to close it, 10 cc of the acetic acid solution diluted to 0.25% was orally prescribed three times a day.
+To reduce the flow of saliva botulinum toxin injections in both submandibular glands were conducted under ultrasound guidance, and propantheline (i.e., an anticholinergic drug) was simultaneously prescribed for the patient.
+In spite of conservative treatment, the fistula was not recovered after 3 weeks.
+Due to the probable surgical procedures, such as gastric pull-up or free flap reconstruction, in the final stages of fistula treatment failure, the jejunostomy was inserted instead of gastrostomy, and intestinal gavage was initiated. There was no evidence of positive surgical margins on permanent specimen pathology.
+Regarding the completion of the medication, conservative treatment, lack of response to the closure of the fistula, and risk of carotid injury with the salivary flow, it was considered to repair fistula by a free flap or gastric pull-up. Therefore, a thoracic surgeon was consulted about gastric pull-up considering the fistula repair.
+It was decided to perform fibrin glue injection into fistula tract via the endoscopic approach after consultation with a gastroenterologist and thorax surgeon and according to the successful management of fistula with the use of plasma-rich compounds, such as fibrin glue, in addition to patient's desire for no major surgery. Furthermore, informed consent was obtained from the patient before the surgery.
+The case underwent an endoscopy to locate internal fistula orifice. In gastrointestinal endoscopy, a fistula was identified in the anterior wall of ​​the neopharynx .
+Fibrin glue was prepared from the patient’s blood sample under certain procedures. The PCF tract was endoscopically localized, and an endoscopic retrograde cholangio- pancreatography (ERCP) catheter passed through the fistula, pushed forward, and pulled backward gently to prevent injury to major vessels. The de-epithelialization of fistula orifice was performed, and the fibrin glue was endoscopically injected into the fistula tract via the catheter. Afterward, a nasogastric (NG) tube was inserted under the endoscopic view.
+Following the administration of fibrin glue, the patient with NPO (i.e., nothing through the mouth) underwent pressure dressing and continued conservative treatment. Two weeks later, the case was discharged with an NG tube and antibiotics (oral Clindamycine 300 mg TDS). One month after the fibrin glue injection, no evidence of contrast extravasation was observed on barium swallow test, and the fistula was completely closed . The normal saline serum was given to the patient with a methylene blue as a surgical marker, with no evidence of leakage. When oral feeding started, the patient tolerated the pain without difficulty. The NG tube was drawn 1 month after the fibrin administration, and the patient returned to normal oral feeding without any problems.
+Fibrin glue preparation
+Two components are required to prepare fibrin glue. The first component is fibrinogen, and the second one is thrombin. Fibrinogen is prepared after the extraction of blood from the patient's vein or blood bank and a series of other steps. The second part that is thrombin is produced as a ready-to-use commercial solution, as well as being extractable from the plasma of the patient. Thrombin is diluted in distilled water and combined with aminocaproic acid as an antifibrinolytic agent. The first component is prepared by three following methods:
+• The first method (plasma): Firstly, 36 ml of citrated blood from a blood bank is evenly divided into four tubes, and the tubes are centrifuged at 3000 rpm for 3 min. The plasma is then removed by pipet and combined with 1 ml of calcium chloride solution.
+• The second method (plasma cryoprecipitate): Firstly, 350 ml of frozen blood in a bag (frozen at -18°C) is placed in a refrigerator at 4°C until it melts slowly. Then, the melted blood is centrifuged at 5000 rpm for 5 min. Afterward, 1mm of calcium chloride solution is added. Finally, the substance sediment in the foam bag is used as fibrinogen.
+• The third method (plasma cryoprecipitate): Firstly, 36 ml of noncytarabine blood is collected in four tubes, each one containing 1 ml of 10% sodium citrated solution. Afterward, the tubes are centrifuged at 3000 rpm for 10 min. The obtained plasma is mixed with 1.3 ml of ammonium sulfate saturated solution in four silicon tubes in which fibrinogen is immediately precipitated and then centrifuged at 3000 rpm for 3 min. About 1.5 ml of white sediment is collected by siphoning and mixed with 1 ml calcium chloride.
+In this study, the second method was used for the preparation of fibrin glue.
+Fibrin glue injection
+In this case, fibrin glue was injected by endoscopy. Firstly, under the intravenous sedation and left lateral decubitus position under the cardiopulmonary monitoring, the endoscope entered into neopharynx through the mouth. The location of the fistula was observed in the anterior neopharyngeal wall and 12 cm from the incisive teeth. The probe of the endoscope was fixed at the fistula location. Then, the ERCP catheter passed through the endoscope into the fistula, pushed forward, and pulled backward gently to prevent injury to major vessels.
+The de-epithelialization of fistula orifice was performed, and 5 cc of the fibrin glue was endoscopically injected into the fistula tract via the catheter. In addition, some fibrin glue was percutaneously injected into the outer orifice of the fistula. The patient follow-up showed that the fistula was completely closed 3 months after the administration. The NG tube was removed, and oral nutrition was successfully started. The subsequent follow-up demonstrated that the patient tolerated a soft diet and fluids without any problems .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1137_en.txt

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+A 20-year-old young male presented to the emergency department following road traffic accident and on probing the patient, he had fallen with a flexed knee leading to axial impaction of tibial condyle over the posterior femoral condyle. Patient had an open lacerated transverse wound about 7 cm over the anterior aspect of the knee. The distal end of femur was protruding out along the avulsion of patellar tendon from the insertion site. Clinical examination was not possible because of open wound and intense pain. There was no distal neurovascular deficit and patient was hemodynamically stable.
+Radiological examination of the involved knee included the anterior-posterior and oblique views showing patella alta, suggesting the patellar tendon avulsion with fracture of anterior tibial spine and lateral-oblique view showing non-conjoint bicondylar Hoffa fracture. Initially, wound was debrided and an external fixator applied. The second procedure was taken after 2 days and both femoral condyles approached through the same open wound. The bicondylar Hoffa fracture was fixed with two 6.5 mm partially threaded cannulated cancellous screw. Screws were inserted from the non-articular portion of the femoral condyle on knee flexion. The anterior tibial spine fragment was fixed with 4.0 mm partially threaded cannulated cancellous screw and the patellar tendon avulsion was fixed to the tibia with ethibond trans-osseous suturing . The wound was primarily closed without the need of additional soft-tissue procedures. The patient was kept in external fixator for 6 weeks in view of healing of the patellar tendon and soft tissue. After 6 weeks, the external fixator was removed and patient was started on partial weight bearing and guarded knee flexion was started in fear of patellar tendon re-rupture. At the end of 3 months, full weight bearing was started and knee Rom was from 5° to 40°. At the end of 6 months, knee flexion further improved to 35° with the healing of the fracture .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1148_en.txt

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+A 53-year-old woman was admitted to The First Hospital of Jilin University in September 2019 because of right axillary metastatic carcinoma.
+The patient presented with an enlarged lymph node in her right axillary area 2 wk before she visited a local hospital for examination. A needle puncture biopsy of the lymph node indicated right axillary metastatic carcinoma, most likely originating from mammary tissue.
+She had no previous history of any illnesses.
+The patient had no relevant personal or family history.
+Physical examination indicated no lumps in the breasts. A hard, fused and fixed lump 6.0 cm × 3.0 cm in size was identified in her right axillary area.
+There was no abnormality.
+US revealed a hypoechoic mass 6.0 cm × 3.2 cm × 2.0 cm in size in the right axilla, which had internal vascularity. Breast lesions were not identified by US, mammography or magnetic resonance imaging . There was no evidence of a malignant primary lesion or distant metastasis on computed tomography scans of the thorax, abdomen and bone. Immunohistochemical staining results were positive for progesterone receptor (PR), cytokeratin (CK) 7 and specific breast markers GATA3 and gross cystic disease fluid protein-15. Tumor cells were negative for estrogen receptor (ER), human epidermal growth factor receptor-2 (HER-2), CK5/6, CK20 and villin.

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+A 74-year-old male was admitted to our hospital for the treatment of esophageal cancer. The patient had no symptoms with normal temperature at the time of admission. His past medical history included diabetes mellitus for 24 years. He underwent endoscopic submucosal dissection for early gastric cancer 4 years ago and video-assisted thoracic surgery for pulmonary adenocarcinoma in the right upper lobe 5 years ago. He occupation was making metal molds. He was ex-smoker: Brinkman index was 980. Laboratory studies showed white blood cells of 10.0 × 103/L, C-reactive protein of 6.07 mg/dL, hemoglobin A1c test of 8.8%, fasting blood sugar of 237 mg/dL on admission. Serum tumor markers, including CEA, CA19–9, SCC, CYFRA, were unremarkable. He underwent esophago-gastro-duodenoscopy for follow-up after endoscopic submucosal dissection for early gastric cancer. The upper endoscopy showed a 0-IIa lesion with relatively large granular nodules on the lower thoracic esophagus . The pathologic assessment of the biopsy revealed squamous cell carcinoma of the esophagus. The esophageal 0-IIa lesion with relatively large granular nodules let us consider the depth of esophageal cancer was deeper than M3/SM1. Chest X-Ray was normal, however, chest CT revealed a 1.3 cm × 0.9 cm pulmonary mass in the lower lobe of the right lung a month before admission . PET/CT showed the pulmonary mass had maximal standardized uptake value (SUVmax) of 3.88 (arrow) and part of the lower thoracic esophagus had SUVmax of 2.37 (arrowhead) 2 weeks before admission . Because the image of pulmonary mass had not changed between CT and PET/CT for 2 weeks and because he had no fever, even though he had inflammation reaction on laboratory studies, pulmonary mass was considered to be unlikely due to infection. Thus, he was initially diagnosed with esophageal cancer with a pulmonary metastasis or recurrence of a pulmonary adenocarcinoma. Considering the both possibilities, we started chemotherapy with cisplatin (CDDP) 70 mg/m2 day1 plus 5-fluorouracil (5-FU) 700 mg/m2 day1–4 on the day 4 after admission. On the day 8, CT revealed a slight pleural effusion in the right side . On the day 9, to rule out carcinomatous pleurisy, an ultrasound-guided aspiration of pleural effusion was performed. The effusion was serous and contained no malignant cells. After the aspiration, the patient got a high fever. Laboratory test showed white blood cells of 18.6 × 103/L (90.8% of Neutrophil), CRP of 25.87 mg/dL. Considering that fever was due to respiratory infection after the aspiration, intravenous Sulbactam/Ampicillin (6 g/day) was administered. On the day14, his fever was persistent and he also had a cough. Because CT revealed an increased amount of pleural effusion , we considered the mass was lung abscess. By the second ultrasound-guided aspiration of the pleural effusion, we got a 50 ml of white suppurative effusion. The effusion turned out to contain Actinomyces israelii , and proved pulmonary mass-like lesion was pulmonary actinomycosis. The patient received intravenous penicillin G (24 million units/day) for 4 weeks, followed by oral amoxicillin 2250 mg/day for 6 months. The patient received four courses of chemotherapy (CDDP/5-FU) and curative radiotherapy (1.8Gy/total 50.4Gy) as esophageal cancer deeper than M3/SM1. The pulmonary actinomycosis disappeared six months after the treatment with antibiotics . After the chemoradiation therapy without any complications, the esophageal cancer was in complete remission.

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+A 73-year old male with progressive impairment of gait, persisting neuropathic pain in his legs, dizziness due to postural changes, and unexplained weight loss of 20 kg (BMI 26.8 kg/m2) during the last 2–3 years presented to our outpatient clinic. Three years ago diagnosis of lumbar spinal stenosis was made and decompression surgery was performed to alleviate neuropathic pain. As symptoms progressed, 1 year before the first presentation a second surgical procedure was scheduled and it was only in the preoperative diagnostic workup that echocardiography revealed left ventricular hypertrophy suspected to represent cardiac amyloidosis (see Fig. ). Endomyocardial biopsy showed extensive amyloid deposition in Congo red stained tissue with a typcial apple green birefringence and fluorescence signal, which could be classified immunohistochemically as TTR derived amyloid (see Fig. ). Regarding the cardiac manifestation and the patient’s age and sex ATTRwt amyloidosis was suspected and treatment with tafamidis (61 mg daily) was initiated.
+At the time of referral, the patient was not able to walk unaided for almost 1 year due to weakness of his legs and impairment of balance. Neuropathic pain and dizziness due to orthostatic dysregulation had progressed and the patient reported no obvious improvement after approximately 1 year of treatment with tafamidis. The patient’s family history revealed frequent deaths due to cardiac events in his first-degree relatives (see Fig. ). His father died at the age of 67 from a cardiac event not further specified, as well as two of the patient’s brothers. One of them reportedly suffered cardiomyopathy and polyneuropathy. The only living brother, aged 68, was considerably impaired by a cardiomyopathy and peripheral neuropathy of unknown etiology.
+The clinical examination showed a severe impairment of gait due to sensory ataxia, bilateral distal paralyses of the lower extremities (ankle dorsiflexion MRC grade 2/5, plantar flexion MRC grade 2–3/5 on the right side, MRC grade 3–4/5 on the left side). A slight weakness of both hands (MRC grade 4/5) was evident, as well as moderate atrophy of distal limb muscles, distal symmetric hypesthesia, and lost tendon reflexes. Nerve conduction studies (NCS) confirmed a severe axonal sensorimotor neuropathy with bilaterally unobtainable sural and tibial nerve amplitudes. Corneal confocal microscopy (CCM) showed a highly reduced corneal nerve fiber density (7 fibers/mm2, reference: > 24 fibers/mm2) indicating prominent small fiber involvement. Extensive laboratory testing for potential causes of the neuropathy including HbA1c, vitamin B1, B6, B12, folic acid, TSH, ANA, ANCA, rheumatid factor, hepatitis serology, serum electrophoresis and immunofixation did not yield any relevant abnormalities. There was no history of alcohol abuse or any other exposure to neurotoxic agents. However, molecular genetic analysis (Sanger sequencing, bioinformatic analysis of collected data by means of Mutation Surveyor Version 3.10 and Alamut Visual Version 2.6.1) revealed a heterozygous sequence variant in exon 2 of the TTR gene (NM_000371.3 (TTR): c.194C > T, p.Ala65Val, s. Table and Fig. ), classified as likely pathogenic (class 4) according to the American College of Medical Genetics (ACMG) classification system, which had been reported in ClinVar twice (ClinVar Accession: VCV000448841.4, ClinVar Variation ID: 448841). In ClinVar, the variant is classified as a variant of uncertain significance (two submissions) and once with the condition amyloidogenic transthyretin amyloidosis, but there is no literature on individuals with TTR-related conditions with this genotype. ACMG criteria PM1 (variant located in a mutational hot spot), PM2 (variant absent from general population in databases gnomAD/ExAC), PM5 (novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before), and PP3 (multiple lines of computational evidence supported a deleterious effect on the gene product) were fulfilled . Presuming this genotype to be amyloidogenic, the patient’s brother underwent targeted genetic testing by Sanger sequencing that revealed the same heterozygous sequence variant.

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+Physical examination on admission: Obese 61-year-old woman (BMI 30.1 kg/m2), pulse 60/min, blood pressure 120/80 mmHg, temperature 36 °C, O2 saturation 94% under mechanical ventilation. Heart, lungs, and abdomen unremarkable. Laboratory studies: Complete blood count: unremarkable. Plasma coagulation study: normal, D-dimers within normal limits, Clinical chemistry: C-reactive protein 6 mg/L (normal 5 mg/L), all other values within normal limits. ECG: Sinus rhythm, HF 60, no AV-Block, no QT time prolongation, inverted T-waves in the inferior leads (III, aVF) . Fast echocardiography: Normal systolic right and left ventricular systolic function, severe mitral regurgitation, no pericardial effusion. Chest x-ray: Normal cardiac size with evidence of pulmonary venous congestion.
+Intensive care therapy achieved stabilization of the patient’s general condition. Controlled ventilation was stopped on the fourth day. Except for a hypoactive delirium, which was adequately controlled by administration of a neuroleptikum, no neurological deficits were manifested.
+Evaluation of the 12-lead ECG did not reveal any evidence of ECG changes, which are normally associated with canalopathies (Brugada, ARVC, long-, short QT syndromes etc.).
+However, we have registered recurrent ventricular salves during monitoring . In addition, we registered a short-lasting atrial fibrillation with spontaneous termination . Therefore, oral anticoagulation was initiated.
+Follow-up echocardiography showed a significant mitral valve insufficiency with preserved left ventricular pump function. The left ventricle demonstrated mild endsystolic and enddiastolic dilatation. A severe dilatation of the left atrium (LA area 45 cm2) was noticed . The lateral mitral annular velocities was quantified with Doppler tissue imaging. The peak systolic lateral mitral annulus velocity was 18 cm/s .
+Transesophageal echocardiography was performed to evaluate the mitral valve more precisely. A high-grade eccentric mitral valve insufficiency due to a pronounced PML and a mild AML prolapse could be demonstrated . Especially the PML showed thickening and myxomatous changes . The tendinous chordae appeared to be intact.
+For further clarification of the arrhythmogenic event, we ordered a CMR. This exploration has shown a discreet mid-wall LGE in the LV inferobasal region . Additionally, LGE of the PM was visible on mid short-axis view . The right ventricle showed no pathology by echocardiography and CMR. A significant mitral annulus disjunction (MAD) measuring 11,2 mm was identified. .
+Regarding the severe mitral valvular insufficiency due to the MVP, the case was discussed in the heart team. It was decided to provide the patient with an internal automatic cardioverter defibrillator (ICD) first and to repair the mitral valve by mini invasive surgery in 3 months.
+The patient showed regression of the delirium and an increasing mobility. After implantation of an ICD device , the patient was discharged in good general condition and without significant neurological deficits. A cardio-neurological rehabilitation was organized. The first ICD follow-up analysis after 3 Weeks did not show any arrhythmogenic events. At the 3 months ICD follow up, few days after the mitral valve reconstruction, we detected a VT, which has been successfully electrocardioverted .

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+A 52-year-old housewife referred after falling down on her right knee. Her initial symptom of discomfort on her knee had begun one year earlier when she attended the hospital. Although she complained of pain only on heavy activity for last year, she had not been aware of a swelling in her knee until falling. On physical examination, there was a hard mass on the posteromedial edge of the patellar tendon. Active range of movement of the knee was a little restricted and painful. Results of routine laboratory screening tests were unremarkable. There was no history of major or minor repetitive trauma in the past. Plain lateral radiographs of the knee revealed a well circumscribed mass in the infrapatellar area .
+The patient underwent total excision of the mass. The mass was found extra-capsular and it was adjacent to the patellar tendon. The gross appearance of the mass was lobular and irregular in shape. It approximately was 4.5 × 3.5 × 1 cm . Histologically, the lobules consisted of well differentiated bone tissue surrounded by cartilage with evidence of enchondral bone formation at the interface suggesting osteochondroma .
+Postoperative course was unremarkable. At the last follow-up visit in the tenth year, the patient had no clinical and radiographic evidence of recurrence with a full range of movement ( and ).

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+For this proof-of-concept study the 4D cardiac-gated CT scan from a 55 year-old male patient suffering from VT was used. The CT data of this VT patient has been previously used for other purposes in a work published by Gianni et al. . The treatment target for this patient had a size of 45 cm3 and it was located on the left ventricular free wall. This clinical target volume (CTV) was determined by electrophysiological mapping and contoured prior to the treatment by a medical doctor from the Texas Heart Arrhythmia Institute in Austin, USA. The left anterior descending coronary artery, the circumflex coronary arteries and the non-involved left ventricle were OARs near the target.
+First, the 4D CT scan of the VT patient was loaded into the Raysearch® Raystation treatment planning system (version 10B, Raysearch Laboratories AB, Stockholm, Sweden). Subsequently, a virtual representation of the prototype version of the proprietary US probe system of EBAMed (Geneva, Switzerland) was manually inserted as volume of interest (VOI) in two locations representing the estimated position of the apical and parasternal US viewing windows. A separate study has already verified that these US viewing windows provide US images of sufficient quality for VT patients in supine position . The US probe was simulated as a cube of 2 × 2 × 2 cm. It is equipped with infra-red markers such that the probe can be localized by an optical camera (see ) and it is attached to a holder such that it can be fixed on the chest of the patient allowing for hands-free imaging during the treatment. To account for uncertainties in repositioning of the US probe during the treatment, including probe position uncertainties due to respiration and breath-hold differences, an isotropic safety margin of 10 mm has been added to the union of the US probe, holder, and optical marker.
+The parasternal US probe position allowed entrance of the treatment beams from optimal directions with respect to dosimetry for this particular patient. After selection of this virtual US probe position, a pencil-beam scanned proton therapy treatment plan was generated with the treatment planning system using the CNAO (Pavia, Italy) synchrotron proton beam model adapted to the Hitachi PROBEAT gantry system with 360° range of beam angles . During planning, the solid angle was restricted to take into account the US probe, the probe holder and the localization marker. Two fields were applied both with a gantry angle of 25° and a couch rotation of 0° and 90° for beam 1 and 2, respectively. The treatment volume was planned with an internal target volume (ITV) approach in order to compensate for shape and position changes of the target due to the heartbeat. It was assumed that the motion of the heart due to respiration would be mitigated using a breath-hold technique or respiratory gating. The envisioned role of the US imaging during this treatment was real-time cardiac motion monitoring and sending an alert to the operator in case the measured motion was outside of predefined limits.
+For the generation of the ITV, the heartbeat motion envelope was extracted from the 4D CT scan by deformable registration of each phase of the 4D CT scan to the planning CT scan. The resulting ITV is the union of the CTVs at all phases of the 4D CT. Finally, the planning target volume (PTV) was generated by adding a 5 mm margin to the ITV based on typical patient set-up errors which are expected when no image guidance tool like US imaging is used.
+Dose constraints on dose-volume tolerances in agreement with prior investigators were set as planning objectives. All doses are reported in Cobalt Gray Equivalent Dose (CGyE). The plan required the ITV to be covered by the 25 CGyE isodose, which is a dose level used in prior clinical studies to achieve safe, efficacious radioablation. To achieve this, the plan was normalized so that PTV D92% = 25 CGyE. Also, in order to arrive at a satisfactory treatment plan (, ), robust optimization with 2 mm set-up error in all directions and 2% range uncertainty was used during planning.
+To verify the clinical acceptability of the generated plan, evaluation of standard target dose-volume metrics D98, D95 D50 and D2 was performed. In addition, the dose to OARs and the target dose conformity and homogeneity were evaluated.

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+A 27-year-old woman, gravida 2, para 0, with no history of previous disease and no family history of congenital anomalies, smoker and with a BMI of 18.3 received a diagnosis of spontaneous twin pregnancy at 12 weeks. The assessment of chorionicity in this gestational age was however hampered by the presence of an hematoma measuring 44 × 38 mm separating the two membranes, thus preventing the identification of the “lambda” or “T” sign.
+The anatomy scan at 20 weeks revealed two female fetuses, both presenting isolated levocardia (IL) with normal heart and situs inversus abdominalis with a left-sided liver and right-sided stomach and spleen . Noteworthy, in one fetus (A) the gallbladder was not visible.
+An amniocentesis was performed, with conventional cytogenetic evaluation indicating normal karyotype 46XX for both fetuses. No genetic anomaly was reported with the Chromosomal Microarray Analysis (CMA). Zygosity was assessed by microsatellite analysis; as shown in Table , twins share only a fraction of paternal and maternal alleles, indicating dizygosity.
+At 36 weeks one fetus was diagnosed to be growth restricted, having an abdominal circumference and an estimated fetal weight less than 3rd centile. At 37 weeks and 1 day, the pulsatility index (PI) of the umbilical artery of the growth restricted fetus, with an estimated fetal weight of 2171 g (below the 3rd centile, according to Hadlock growth chart), was 0.89 (corresponding to 46° centile), while the PI of the middle cerebral artery was 1.45 (26° centile). By contrast, the other twin had an estimated fetal weight of 2521 g with normal Doppler parameters. At 37 weeks and 3 days the mother underwent a scheduled cesarean delivery. The birthweight of the two female neonates were 2430 g and 2185 g.
+The histological analysis of the placenta confirmed the monochorionicity of the twin pregnancy, revealing the juxtaposition of an amnion on each surface of the dividing membrane . The chorion was not visible between the two amnion surfaces, thus excluding the rare occurrence of partially fused placentas [, ]. Postnatally, by using DNA extracted from blood samples, the molecular analysis confirmed the dizygosity of the twins, as already previously determined through amniocentesis.
+Moreover, the two babies turned out to have the same situs anomaly, with IL and situs inversus, thus confirming the prenatal diagnosis. In order to identify possible genetic causes of such a concordant abnormal phenotype, the twins were subjected to clinical exome analysis with evaluation of 17 genes known to be associated to situs inversus. However, according to the variant classification ACMG (The American College of Medical Genetics and Genomics), no pathogenic or probably pathogenetic variants have been identified. By opening the analysis to the whole clinical exome (4490 genes), the twins did not share pathogenic or probably pathogenetic variants. In addition, the twin whose gallbladder was not visualized prenatally, developed jaundice with acholic stool in her neonatal period.
+The complete abdominal scan performed at 20 days of extrauterine life showed a left sided, damage-free liver with regular size (lateral diameter of 6,3 cm), a reversed relation between superior mesenteric vein and artery and right-placed inferior vena cava in relation to the aorta. These findings perfectly fit with abdominalis situs inversus with isolated levocardia. The scan revealed for the first time a shriveled gallbladder, which led to the diagnosis of biliary atresia type IV associated with splenic malformations syndrome . The clinical exome analysis was unable to identify the genetic cause of these abdominal abnormalities.
+The twin with BASM at 38 days of extrauterine life underwent Kasai portoenterostomy, second-hand appendectomy and Ladd bridle dissection. Later, during the fifth month of extrauterine life, the baby was diagnosed to have a subclinical acute cholangitis, which was treated with continuous infusion of piperacillin tazobactam during hospitalization. Unfortunately, the baby had recurrent cholangitis during the whole first year of extrauterine life, and these are still occurring.

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+A 68-year-old Hispanic male with no significant past medical history was brought to the ED by emergency medical services (EMS) for confusion and altered mental status. EMS reported that they were called by the patient’s wife when she discovered him breathing erratically and could not rouse him. Upon arrival to the ED, the patient was obtunded and began to experience cardiac arrest with ventricular fibrillation. He was subsequently intubated and given Advanced Cardiac Life Support where cardiopulmonary resuscitation was administered and the patient was defibrillated. He went on to experience return of spontaneous circulation. An ECG obtained in the ED during this event demonstrated ST-segment elevations in V1–V3 and specific repolarization abnormalities in V1 and V2 .
+Additional ECG findings included the following: first-degree atrioventricular (AV) block, PR interval of 220 milliseconds (120–200 milliseconds), and QRS duration of 0.11 seconds (0.08–0.12 seconds).
+The patient was placed on an amiodarone infusion and transferred to a medical facility with a cardiac catheterization laboratory. Emergent cardiac catheterization was performed due to concerns for ST-elevation myocardial infarction (STEMI), but no acute findings were discovered. Laboratory values from the initial blood draw in the ED demonstrated the following: sodium 132 milliequivalent per liter (meq/L) (normal 136–145 meq/L); potassium 3.3meq/L (normal 3.5–5.0 meq/L); magnesium 3.3 milligram per deciliter (mg/dL) (normal 1.5–2.4 mg/dL); glucose 197mg/dL; troponin <0.02 nanograms per milliliter; brain natriuretic peptide (BNP) 65; prothrombin time (PT) 13.6 seconds (normal 11–13 seconds); international normalized ratio (INR) 1.3 seconds; and thyroid stimulating hormone (TSH) 59.4 milliunits per liter (mU/L) (normal 0.5–5.0 mU/L).
+Following cardiac catheterization, the patient was transferred to the intensive care unit where all vital signs remained stable and within normal limits. With members of the patient’s immediate family at bedside, information pertaining to his personal history was elicited for the first time. They reported that the patient had been in good health prior to the onset of his confusion and at no point did he complain of any discomfort or associated symptoms. Furthermore, they denied any significant past medical or surgical events in the patient’s history, including any personal or family history of heart disease or sudden cardiac death. They stated that the patient had no allergies, did not take any medications, never used tobacco or illicit drugs, and consumed alcohol occasionally during social events.
+The following day, the patient was extubated with excellent response and was found to have no focal deficits on physical exam. Thyroid replacement therapy was initiated for severe hypothyroidism discovered incidentally during the aforementioned care. Although no additional adverse cardiac events would occur for the duration of his hospital stay, the patient agreed to placement of an implantable-cardioverter defibrillator (ICD) as recommended for secondary prevention of Brugada syndrome.
+Further work-up of the patient during his hospital course included the following: magnetic resonance imaging of the brain, which demonstrated multiple small areas of infarct in the bilateral cerebral hemispheres and no other significant findings. Computed tomography angiography of the head and neck were found to be normal. After demonstrating an ability to ambulate 300 feet with front-wheel walker, the patient was discharged home on aspirin and statin medication.
+Left heart catheterization was performed 18 days later as recommended by the patient’s electrophysiologist. The right coronary artery was found without stenosis or blockage; the left anterior descending artery was patent; and overall coronary circulation and left ventricular function were normal. These findings, coupled with the patient’s presenting symptoms and findings found on ECG in the ED, ultimately corroborated a diagnosis of Brugada syndrome with a type 1 pattern.

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+A 13-year-old boy was admitted to Pediatric Intensive Care Unit (PICU) in a critical situation. After waking up in the morning, he complained of left-sided abdominal pain, nausea, and vomiting. Over the hours, the pain was intermittent and increasing in intensity.
+At admission, the patient looked pale, in a forced sitting position. On physical examination, his abdomen was tender in all quadrants with left upper quadrant pain rated as 10 out of 10 in intensity. The pain was described as very strong and increased if he laid down, thus requiring intravenous opioids. Upon examination, heart rate was 92 bpm along with low blood pressure 82/42 mmHg. Diminished breath sounds at the lung bases were noted, most likely due to limited excursions of the chest due to pain. There was no fever (temperature 36.5 C). There was no rash, nor lymphadenopathy. No hematomas or bruises were observed. After intravenous opioids and liquid administration, blood pressure was normalized.
+The patient and his father denied any history of trauma. They insisted the child had been totally healthy up until that morning. The child had no family history of coagulopathies, autoimmune diseases, or malignancies. According to his family, there were no bowel abnormalities; use of thrombolytic or anticoagulant drugs.
+Several laboratory and imaging examinations were performed immediately. Given the relatively large number of COVID-19 patients during this period, our main differential diagnoses were either a splenic rupture or a splenic artery thrombosis, due to COVID-19. Therefore, a nasopharyngeal swab specimen was collected for COVID-19 testing.
+The upright abdominal radiograph showed no abnormalities. Abdominal ultrasound revealed free fluid in the abdomen, but without any clear suspicion, so an emergent Computed tomography (CT) with contrast of the chest and abdomen was carried out. The thoracic CT scan was normal. Abdominal CT revealed hemoperitoneum with splenic laceration.
+Since the hemoglobin, hematocrit, and patient’s blood pressure were normal, with no active bleeding on CT, the splenic injury was initially managed conservatively. Twelve hours after presentation, a decrease in hemoglobin (Hb = 8.1 g/dL) and hematocrit (HCT = 25.6%) was noted and the patient’s blood pressure started dropping. He received 1 Unit of blood and the decision to proceed to surgery was made. During the operation, it was observed that the patient had plenty of blood in the abdominal cavity. Laceration of the splenic hilum and a large perisplenic hematoma was noted and splenectomy was performed. Two additional Units of blood were transfused intraoperatively.
+Human immunodeficiency virus (HIV) test, IgM and IgG antibodies for Epstein Barr virus (EBV) and cytomegalovirus (CMV) were negative. The polymerase chain reaction (PCR) was positive for COVID-19, making us think that the splenic rupture could be a consequence of COVID-19. The child’s clinical condition was stable after surgery. He was discharged, without further problems during the follow-up.

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+A 23 year old male patient presented to the orthopaedic clinic with complaints of an isolated scapular swelling (right) since 5 years . The swelling was also associated with crepitus and snapping of the right shoulder and slight restriction and pain on abduction. The patient reported no increase in size of the swelling over the years and demonstrated no increase in symptoms as well. There was no history of antecedent trauma, weight loss, loss of appetite or any other constitutional symptom. The patient wanted the swelling to be removed due to cosmetic reasons mainly as he was about to get married. Local examination of the swelling revealed increased prominence of superior angle of scapula. The skin overlying the same was normal. There were no signs of inflammation etc present. The swelling was non painful on touch. However, snapping and crepitus/grating could be demonstrated on scapulothoracic movements and restriction in abduction was evident. An antero posterior skiagram of the right shoulder revealed a pedunculated mass arising from the supero medial angle of the scapula .
+CT scan and MRI revealed a mushroom shaped exostosis over the superior angle of scapula .
+The swelling diagnosed as ventral osteochondroma was excised. A laparoscopic resection of the same has been described, however, we performed an open excision of the swelling.
+An incision was used along the medial border of scapula wherein it was most prominent .
+Extra periosteal resection of the swelling was performed and sent for biopsy. HPE analysis confirmed our diagnosis and ruled out any malignant transformation. Post operative course was uneventful and patient was able to perform full range of motion at his right shoulder after 1 month . Follow up was done till 1 year and no recurrence of the swelling was reported.

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+A 24-year-old male was admitted to the acute medical assessment unit through emergency department with presenting complaint of left sided chest pain. Chest pain was gradual in onset, started overnight with 6/10 in intensity, sharp in character, increased by deep breathing and lying down, and improved by leaning forward. Chest pain was associated with nausea and single episode of non-bloody vomiting. Patient also reported fever, generalized tiredness, lethargy, and insomnia. Patient also had pounding of heart but thought that it was result of his anxiety. There was no history of sore throat, rigours, chills, cough, or sputum. Patient also denied history of shortness of breath, paroxysmal nocturnal dyspnoea, and orthopnoea or ankle oedema. There was no history of chest trauma or skin rash. There was no prior history of chest pains. Patient had history of insomnia, had significant unintentional weight loss of 6–8 kg over last 3 weeks despite good appetite, heat intolerance, shakiness of hands, and nervousness. He adamantly denied any visual disturbance or change in appearance of his eyes. His vitals on arrival were temperature 38˚C, blood pressure 130/80 mmHg, heart rate 125 b.p.m., and respiratory rate 18.
+On clinical examination patient looked anxious and in agony, there were fine tremors on outstretched hands with sweaty palms. His pulse was fast, regular, and high in volume. There was no exophthalmos clinically. Neck examination shows diffuse enlargement of thyroid gland which was non-tender, there was no associated lymphadenopathy. No bruit was heard over thyroid gland. On cardiac examination, heart tones were normal and no rub was appreciated. Respiratory and rest of systemic examination was normal. His medical history was only significant for anxiety disorder. He was a non-smoker and teetotaller. He denied use of herbal medicines or recreational drugs. Family history was unremarkable for pericarditis or thyroidal problems.
+His electrocardiogram (ECG) showed sinus tachycardia, diffuse ST-elevation in both chest and limb leads, PR depression in most of limb leads. In addition, there was PR elevation and reciprocal ST-depression in lead aVR. All of these features were suggestive of acute pericarditis. Chest X-ray was normal. Ultrasound thyroid with Doppler was done which showed enlarged thyroid with heterogeneous echotexture and increased vascularity also known as thyroid inferno suggestive of Graves’ disease. In addition, there was neither focal nodule nor abnormality in thyroid, nor cervical lymphadenopathy. His thyroid function test demonstrated thyroid stimulating hormone (TSH) <0.02 mU/L (normal range 0.27–4.20) and freeT4 was >100 pmol/L (normal range 11–26). Anti-thyroglobulin antibodies were also significantly elevated 58.2 U/L (normal range 0–0.99). His first troponin was normal 14 ng/L (normal range 0–14), and repeat one was 19 ng/L (only minimally elevated). His C-reactive protein (CRP) was <5 mg/L (normal range 0–9) and erythrocyte sedimentation rate (ESR) was 5 (normal range 1–13). Antinuclear antibodies profile was negative , and rest of his blood investigations was unremarkable. Echocardiogram was performed which showed preserved left ventricular systolic function without any regional wall motion abnormalities. There was a small global pericardial effusion noted (1 cm around right atrial free wall, 0.6 cm around lateral wall, and 0.3 cm posteriorly) which was not causing any haemodynamic compromise or tamponade. Right ventricular systolic function was preserved with no evidence of right heart strain.
+His overall clinical picture, based on history and investigations, was consistent with a diagnosis of pericarditis associated with Graves’ disease. Given his clinical context, he was started on ibuprofen 400 mg thrice daily (TDS) to control pain and inflammation with Pericarditis along with Omeprazole 40 mg once daily (OD). Carbimazole 40 mg OD was commenced to control Graves’s systemic symptoms and Propranolol 40 mg TDS was prescribed to control anxiety, tremors, and tachycardia. Patient had remarkable improvement of his symptoms and was discharged a couple of days later with follow-up arranged in endocrine outpatients. He became clinically and biochemically euthyroid with subsequent thyroid functions after 12 weeks as: TSH 1.1 mU/L (normal range −0.27 to 4.20), free T4 20 pmol/L (normal range 11–26). Both his CRP and ESR on subsequent testing after 3 months remained normal. Both repeat ECG and echocardiography after 4 months revealed complete resolution of pericarditis.

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+A 47-year-old Chinese woman complained of blurred monocular vision in her left eye 1 month prior to her visit. She also reported that her vision deteriorated very quickly and that she became almost blind after 3 days since the onset of the disease. She denied headache, fever, or cough prior to the vision problem. The ophthalmologist at the local hospital found the visual acuity was 20/20 in the right eye with suspicious light perception in the left eye. The fundus examine and fundus fluorescein angiography were performed. She was diagnosed with CRVO in her left eye and was followed up for 1 month. The patient continued to lose vision, and the swelling of the optic disc and retina did not improve. She was referred to a neuro-ophthalmologist for further evaluation. She was a considerably healthy housewife living in a southeastern city of China. The chart review was only remarkable for mild hypertension. She neither smoked nor drank alcohol. There was no family history of neurological or hereditary diseases.
+The neuro-ophthalmological examination revealed the patient to be alert and oriented. Her visual acuity was 20/20 in the right eye with no light perception in the left eye. The left pupil showed no light reaction and an afferent pupillary defect. Slit lamp examination revealed no keratic precipitates or cells in the vitreous of either eye. The intraocular pressure was 13 mmHg in the right eye and 11 mmHg in the left eye. Funduscopic examination revealed a central retinal vein occlusion with optic oedema, dilated and tortuous veins, and extensive intraretinal haemorrhage. . The right fundus was unremarkable. There were no other abnormal focal neurological signs.
+Routine laboratory tests, including complete blood count and liver and renal function, were unremarkable. A rheumatology panel, including erythrocyte sedimentation ratio, C-reactive protein, anti-nuclear antibody, anti-extractable nuclear antibodies, and anti-neutrophil cytoplasmic antibody, were unremarkable. Angiotensin converting enzyme levels were within the normal limit. An infectious disease panel, including human immunodeficiency virus, herpes simplex virus, cytomegalovirus, Treponema pallidum antibody, and T-spot, were negative.
+The brain and orbital magnetic resonance imaging (MRI) with contrast showed enlargement of the left optic nerve in the orbit. The anterior part of the optic nerve showed heterogenous enhancement. There were no other brain lesions or masses . Chest computed tomography (CT) with contrast was unremarkable. The lumbar puncture showed normal intracranial pressure with normal cerebrospinal fluid components and biochemistry.
+She was diagnosed with optic neuropathy combined with CRVO/CRAO of unknown causes. She was given 500 mg/d intravenous methylprednisolone for 5 days and was then tapered off. Her visual acuity in the left eye maintained no light perception after treatment and the optic disc swelling resolved along with residual retinal haemorrhaging with the narrowing of the vessels. . The macular optical coherence tomography showed thinning of the inner layer of the right retina due to retinal artery occlusion. As she could not perceive light in her left eye, she was scheduled for an optic nerve biopsy. Histopathology showed that the optic nerve had lost its original structure and was infiltrated with numerous inflammatory non-caseating granulomas, which was consistent with sarcoidosis . The final diagnosis of neurosarcoidosis was made according to the clinical manifestation and pathology of the patient. She was only seen for follow-up with no further treatment due to no other systemic involvement of sarcoidosis. Her left eye maintained no light perception and the retina thinned afterwards.

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+A 41-year-old woman (weighing 68 kg, 157 cm tall) with a previous history of childhood asthma became pregnant during follow-up of breast cancer. She was scheduled to undergo total mastectomy with sentinel lymph node biopsy at 18 weeks of gestation. In order to minimize physiological stress on both mother and fetus during the perioperative period, we decided to administer general anesthesia combined with continuous ESP block.
+Her physical examination and preoperative laboratory tests indicated no abnormalities. After establishing standard monitoring, including bispectral index (BIS) and neuromuscular monitoring, general anesthesia was induced with intravenous propofol (target-controlled infusion [TCI] of 3.3 μg/mL) and remifentanil (0.25 μg/kg/min). Following calibration of the train-of-four (TOF) monitor, we administered rocuronium at fractional doses of 10 mg until the required degree of muscle relaxation was achieved. Tracheal intubation was uneventfully performed.
+After placing the patient in the right lateral position, a high-frequency linear ultrasound transducer (LOGIQe, GE Healthcare, Wauwatosa, Wisconsin) was aseptically placed on the patient’s back in a longitudinal parasagittal orientation approximately 3 cm from the midline. The erector spinae muscles were identified superficial to the tip of the T3 transverse process. An 18-gauge, 100-mm needle (Contiplex® S Ultra, B. Braun, Melsungen, Germany) was inserted using an in-plane approach and in a cranial-to-caudal direction to contact the tip of the T3 transverse process . The location of the needle tip was confirmed by visible fluid spread resulting in the lifting of the erector spinae muscles. A total of 20 mL of 0.25% levobupivacaine was injected through the needle, followed by insertion of a 19-gauge catheter 5 cm beyond the needle tip. Then, an infusion of 0.25% levobupivacaine into the erector spinae plane was started at the rate of 6 mL/h. General anesthesia was maintained with propofol (TCI of 3.0–3.3 μg/mL) to keep the BIS between 40 and 60, remifentanil (0.05–0.1 μg/kg/min) to maintain systolic blood pressure within 20% of preoperative values, and intermittent administration of 10 mg rocuronium to keep TOF counts below 2. The operative time was 111 min. The patient’s hemodynamics remained stable during the surgery. One thousand milligrams of acetaminophen was intravenously administered 15 min before the end of surgery. After full recovery from general anesthesia, the patient was extubated and transferred to the general ward of the department of surgical oncology.
+Postoperative pain was measured using a numerical rating scale (NRS; an 11-point scale, 0 was no pain and 10 was the worst pain imaginable) immediately after recovery from general anesthesia and at varied intervals postoperatively (at 2, 6, 24, and 36 h). NRS scores remained at 1 point throughout the postoperative period, indicating minimal pain. At 2 h after surgery, postoperative assessment of the fetus with Doppler ultrasound revealed no abnormalities. The catheter of the ESP block was removed at 24 h after surgery. Postoperative pain did not worsen after termination of the block. The patient did not need any additional analgesics during the postoperative period and was discharged home on the 15th day after surgery with no adverse effects on either mother or fetus.

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+A 4-year-old male was brought to the emergency department with a 2-week history of headache, lethargy and vomiting. CT and MRI brain revealed a 4.5-cm fourth ventricular lesion with associated obstructive hydrocephalus . Preoperative bloodwork showed no abnormalities, with normal liver function, platelet count and coagulation profile.
+A preoperative dose of 20 mg/kg of 5-ALA (Gliolan) was administered on the morning of surgery (weight 19 kg). The patient underwent insertion of a right frontal external ventricular drain, followed by suboccipital craniotomy, C1 laminectomy and complete resection of the lesion. The tumour fluoresced avidly intraoperatively. There was moderate intraoperative blood volume loss (400 mL); 2 units of red cells and a pool of Octaplex were transfused during the procedure. The patient was positioned prone for a total of 6 h. Immediate postoperative imaging revealed complete radiological resection with no new abnormalities seen. Histological examination of the resected specimen confirmed an anaplastic ependymoma (WHO grade III).
+The patient was successfully extubated after postoperative MRI on the day of surgery. He remained in the paediatric intensive care unit for monitoring.
+Laboratory results on postoperative day 1 revealed a platelet count of 5 × 103/mL with a significant transaminitis (AST 3027 iU/L; ALT 2367 iU/L). The patient was haemodynamically stable and neurologically intact with GCS 15/15.
+Despite the liver injury, there was no evidence of acute hepatic failure with PT only modestly elevated (16 s) and no evidence of encephalopathy. Despite treatment with platelets, plasma and red cell transfusions as well as tranexamic acid, vitamin K and fibrinogen, the acute thrombocytopaenia persisted and the patient’s haemoglobin level dropped progressively from 13.5 to 8 g/dL over 36 h. Liver biochemistry results had also worsened with AST peaking at 7198 iU/L and ALT at 4496 iU/L.
+On postoperative day 2, the patient’s external ventricular drain became blocked with blood clots, and he became drowsy. The right pupil became dilated and non-reactive. CT brain showed a new spontaneous right frontal intraparenchymal haemorrhage with intraventricular extension as well as acute subdural haematoma . The patient was brought to theatre for emergency craniectomy and evacuation of the haemorrhage. Intraoperative bleeding was difficult to control, and the massive transfusion protocol was enacted. Eventually, once haemostasis was achieved, the patient was brought back to PICU for ongoing management. The transaminitis improved over the following days and the thrombocytopaenia also resolved.
+Autologous cranioplasty was performed 1 month later. The patient then received adjuvant proton-beam therapy and chemotherapy. Three months later at outpatient follow-up, the patient was noted to be neurologically intact aside from a very subtle weakness of his left hand. Blood results were all within normal range. He was attending school full-time once again and had made an almost complete clinical recovery.

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+A 35-year-old male with no known past medical history presented to the hospital for progressively worsening rectal pain for the past three days. The patient stated that pain was worse with defecation and while sitting upright. He described the sensation of feeling an outgrowth or nodule present near his anus. He tried applying “lotion” at home without any relief of pain. He did endorse constipation for two to three weeks prior to presentation. He denied melena or hematochezia. The patient also complained of unintentional weight loss of 20 pounds over three months. He denied any constitutional symptoms.
+The patient reported he was seen by his family doctor four months earlier and underwent an annual physical examination, which was normal. A complete metabolic panel and complete blood count was done at this visit with no abnormality. He denied any history of unsafe sexual practices, intravenous drug use and had never chronically used probiotics.
+On admission, his vital signs showed a temperature of 36.2 °C, heart rate 111 beats/minute, blood pressure 138/42 mmHg, respiratory rate of 21 and saturating 100% on room air. On physical examination, tenderness was elicited to light touch and palpation at the perianal region. A hard, indurated region was palpated at the perianal region on the medial side, which was surrounded by erythema.
+Laboratory examination was negative for leukocytosis. His basic metabolic panel showed sodium of 132 mEq/l, potassium of 3.2 mEq/l, bicarbonate of 6 mEq/l and an anion gap of 23. His blood glucose was 280 mg/dL. Lactate was within normal limits. Urinalysis was positive for ketones and negative for infection. A contrast enhanced CT scan of the abdomen and pelvis showed a perianal abscess.
+Initial management included initiation of broad-spectrum intravenous antibiotics with vancomycin, cefepime, and metronidazole. General surgery was consulted, and the patient underwent incision and drainage of the perirectal abscess. Blood cultures came back positive for gram-positive rods and cocci, and later speciation showed Lactobacillus in both anaerobic bottles. Infectious disease was consulted, and oral amoxicillin and clavulanate potassium therapy was initiated at a dose of 500 mg-125 mg twice daily. Further laboratory testing revealed an HA1c of 15%, leading to an endocrinology consult, a new diagnosis of diabetes mellitus, and the initiation of insulin therapy. The patient continued to improve and repeat cultures were negative. There was low suspicion for endocarditis and echocardiogram was not pursued. He was discharged with a ten-day course of oral amoxicillin clavulanate 500 mg–125 mg and referred to endocrinology for outpatient follow up.

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+A 50-year-old female presented to the emergency department at the onset of acute severe chest and upper back pain. Her medical history consisted of controlled stage II hypertension, treated with losartan. No other comorbidities were present. Laboratory testing showed normal kidney functions. Blood pressure was 170/90 mmHg at presentation.
+Subsequent diagnostic contrast-enhanced computed tomography (CT) revealed a type B aortic dissection (TBAD) that extended from the left subclavian artery (LSA) to the right common iliac artery (RCIA) . Only the right renal artery (RRA) originated from the false lumen. The maximum compression was at T5 level, where the true lumen was compressed to less than 10% of the total diameter .
+Despite primary medical treatment with intravenous metoprolol and sodium nitroprusside and oral beta blockers controlling the blood pressure, the patient’s symptoms did not improve. Because of her persistent back pain over 4 days, invasive treatment was deemed necessary. Moreover, due to the involvement of the visceral aorta into the dissection, it was deemed necessary to treat the dissected aorta extensively. As the site was located in the Brazilian state of Tocatins, more than 2000 kilometers away from the closest vascular center, the decision was made to treat the patient locally.
+The procedure was performed on day 4 after symptoms onset, under local anesthetic and sedation. Unilateral ultrasound-guided right femoral access was obtained by a preclose technique with two Proglide devices (Abbot Vascular, Santa Clara, California). Proper guidewire introduction and advancement in the true lumen was ensured by angiographic guidance. Through a 20 Fr sheath, two overlapping multilayer stents were implanted. To ensure a sufficient healthy landing zone and obtain adequate proximal seal, decision was made to deliver the proximal stent over the aortic arch. The open mesh structure of the multilayer stent made this possible, ensuring preserved perfusion of the supra-aortic branches.
+No rapid pacing nor adjunctive procedure were necessary for the deployment of the stents. Angiogram at the end of the procedure showed approximation of the entry tear and total exclusion of the false lumen in front of the entry tear, with patent side branches, particularly the supra-aortic arteries, mesenteric arteries and both renal arteries. Total procedure time was 68 minutes. Less than 100 milliliters of contrast agent were administered.
+The patient was completely asymptomatic after the procedure. She remained in the ICU (Intensive Care Unit) for 12 hours postoperatively. There were no signs of stroke or spinal cord ischemia. Postoperative kidney function tests remained normal. The next day she was discharged from the hospital in good health. Dual antiplatelet therapy (DAPT), i.e., clopidogrel and acetylsalicylic acid, were started as per our site standard practice after endovascular procedures.
+At follow-up examinations after 6 and 12 months, the patient remained asymptomatic. Review of the CT scans confirmed that the stent had reopened the true lumen to the original aorta diameter, with stable true and false lumen diameters and volumes between 6 and 12 months. The 12-month follow-up CT scan revealed that the false lumen at the proximal end of dissection completely disappeared . Also, the maximum diameter of the false lumen significantly decreased whereas the true lumen diameter increased . All supra-aortic and visceral branches were patent .

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+A 39-year-old, gravida 7, para 2, woman came to the local hospital with a complaint of lower abdominal dull pain for 3 h at 34 weeks’ gestation. Her obstetrical history began with two preterm spontaneous vaginal delivery (one at 28 weeks’ gestation; one at 30 weeks’ gestation) at the age of 18 and 19, respectively. Her third, fourth, and fifth pregnancies ended in abortion at early gestation with dilation & curettage treatment. In her previous pregnancy at 36 years of age, she received laparoscopic left salpingectomy and methotrexate (MTX) treatment due to ectopic pregnancy. No other surgeries on the pelvis or abdomen has been performed.
+Her general condition was stable. Physical examination showed normal secretions, no vaginal bleeding or fluid, no cervical dilation, but irregular preterm contractions with a shortened cervical length. Ultrasonography revealed a decreased amniotic fluid index (AFI 4.0 cm) and a single intrauterine pregnancy with breech presentation and positive fetal heart activity. The placenta was located on the anterior wall of the uterus. Laboratory tests were performed at the time of admission and did not show any significant findings, and hemoglobin level was 120 g/L. Due to the risk of premature birth, dydrogesterone was used to relieve uterine contraction and dexamethasone was administered to accelerate fetal lung maturation. Over 2 days following admission, her symptoms gradually worsened. She presented with diffuse abdominal pain and distension. She also reported nausea and had problem in defecating. Ultrasonography of the abdomen represented intestinal dilatation and multiple intestinal contents and air-fluid levels in the colon. Therefore, an intestinal obstruction was suspected. Enema was used to help intestinal peristalsis.
+As there was no improvement in her condition, the patient requested a transfer to our hospital. Clinical examination revealed epigastric tenderness and mild abdominal distension, with no signs of guarding or peritonitis. Bowel sounds were weak. Consulting with the surgeon on duty, an abdominal computed tomography (CT) was performed after informed consent from the patient. CT represented dilatation of ascending colon and transverse colon . The symptoms were relieved after a nasogastric tube was inserted initially and enema was used. Since ultrasonography revealed oligohydramnios, a test for amniotic fluid crystal was performed, showing no signs of premature rupture of fetal membrane. On the fourth day following admission in our hospital, ultrasonography showed merely no fluid in the amniotic sac and the patient complained of no complete relief of bowel obstruction. Therefore, an emergency caesarean section (C-section) was performed. A healthy baby was delivered with no complications. Intra-operative assessment showed dense adhesion between the left wall of uterus and omentum, descending colon, and sigmoid colon. After adhesion dialysis and intestinal arrangement performed by a colon and rectal surgeon, uterine rupture with complete opening of the uterine wall at the site of left uterine cornua was found without active bleeding . The uterine scar was repaired using a double-layer closure.
+Re-evaluation of the former abdominal CT was taken, revealing discontinuity of the uterine muscle layer in the left uterine cornua , which was consistent with intraoperative findings. Considering that the hemoglobin level didn’t decrease, her blood pressure remained stable, and no fetal distress happened during her labor of the birth, we assumed that the uterine rupture may occurred very early. Since omentum and colon were attached to the site of perforation, no clinical signs of uterine rupture were presented. As uterus enlarged, changes in the transit of intestinal tract decreased the intestinal peristalsis and then caused obstruction.
+The patient recovered well without any complications and was discharged on the fifth postoperative day.

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+A 44-year-old Guatemalan woman presented to our outpatient clinic with a chief complaint of left knee pain for the last 6 months. One month prior our patient had consulted with an outside physician, who prescribed her with 300 mg of carbamazepine, 5 mg of prednisone every 24 hours, and ibuprofen every 8 hours as needed. The symptoms did not resolve and our patient increased the dose to 600 mg of carbamazepine and 20 mg of prednisone 7 days before consulting. She suddenly interrupted prednisone 3 days before consulting, because she felt this was making her pain worse. At the consultation, our patient complained of left knee pain, fatigue, and bilateral lower limb cramps. No pertinent medical, surgical, allergic, family, and psychosocial history was recorded and her vital signs were within normal limits (blood pressure of 118/64 mmHg; heart rate of 75/minute; respiratory rate of 14 beats/minute; temperature at 98.9 °Fahrenheit). Our patient was on day 12 of her menstrual cycle. A physical examination revealed mild facial edema, multiple port-wine stains on her upper and lower extremities associated with mild hypertrophy of the calves , more prominent on the right side with mild edema, the rest of the physical examination was non-contributory. Imaging and routine blood studies were requested. Our patient was seen the next day at the office with the laboratory results .
+Our patient presented with only a complaint of fatigue at this visit, however, no neurologic or physical disabilities were recorded, and her vital signs were within normal limits.
+Our patient was sent to the emergency department (ED) for electrolyte imbalance correction and for other diagnostic studies. In the ED, a 12-lead electrocardiogram did not show any electric abnormalities, her urinary Na+ (UNa+) was 164 mmol/L (normal 40–220 mmol/L), and osmolality 328 mmol/kg (50–1200 mmol/kg). No carbamazepine serum levels were recorded due to lack of reactive in the hospital. Our patient was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) secondary to carbamazepine use, hypokalemia secondary to corticosteroid therapy, and Klippel-Trénaunay-Weber (KTW) syndrome. Patient orders were to discontinue carbamazepine, fluid restriction to 1.5 L/day and intravenous potassium (K+) slow correction. She was discharged 3 days later with Na+ 128 mmol/L, K+ 4.6 mmol/L, and serum osmolality 265 mmol/kg. Our patient was seen in the office 1 week after discharge: she no longer felt fatigued, her cramps were not present and her left knee pain had mildly improved with acetaminophen use and local nonsteroidal anti-inflammatory drug (NSAID) cream. Her left knee pain was attributed to the KTW syndrome. She was not taking carbamazepine and prednisone at the time of the follow-up. Electrolyte studies revealed Na+ 138 mmol/L, K 4.6 mmol/L, and serum osmolality at 276 mmol/kg.

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+A 62-year-old previously healthy Sri Lankan native male from Gampaha, in the Western Province of Sri Lanka presented with high fever associated with chills and rigors for 17 days. He also complained of malaise, myalgia and arthralgia for the same duration but denied any urinary, respiratory or abdominal symptoms. Until he presented to us, he had obtained treatment froma local hospital for the illness with no clinical improvement. He had received co-amoxyclav, clarythromicin and paracetamol for 4 days. He had not been consuming any medication prior to the illness and had not received any drug that would result in extrapyramidal features. Around the 5th day of the clinical illness he had developed intermittent resting tremor in his right arm and leg. By the time he presented to us he had stiffness and very frequent intermittent resting tremor (Additional file : Video). This resulted in difficulty to carry out normal work with the right hand. He also found it difficult to walk due to unusual stiffness and heaviness of the right leg. Furthermore, he found it difficult to smile with others and felt very distressed. He denied similar previous episodes. There was no associated hearing impairment, seizures, or altered level of consciousness. There were no symptoms to suggest involvement of cerebellar system or autonomic nervous system. There was no family history of movement disorders. He had been working in his garden 7 days prior to the onset of fever and rest of the past medical history was unremarkable. Examination revealed intermittent high amplitude low frequency resting tremor in his right hand (Additional file : Video) and a mask like face where he found difficult to smile or show his teeth . He also had increased muscle tone limited to the right side with normal tendon reflexes.The rest of the central nervous system was unremarkable. His blood pressure was 140/90 mmHg in both supine and standing positions, pulse rate 88 beats per minute and there were no cardiac murmurs. The respiratory system revealed few basal crackles and the abdominal examination was unremarkable except for a superficial crater like lesion suggestive of an eschar. He did not have lymphadenopathy or a rash.
+His full blood count was 13.4 × 109/L (Neutrophils 43 %, Lymphocytes 56 %), Erythrocyte sedimentation rate was 80 mm/1st h and had a normal urine analysis, liver and renal function tests. The CT scan of the brain and the Electroencephalogram were normal. We did not perform a lumbar puncture or an Magnetic resonance image scan of the brain. He was positive for Immunofluoresence Assay (IFA)-IgM and IgG for O. tsutsugamushi on the 17th day of illness and the IFA-IgG titre using Orientia Karp antigen was 1:1024 which rose up to 1:16,384 after 2 weeks confirming scrub typhus. His fever settled with oral doxycycline and azithromycin within 48 h and demonstrated some improvement in his Parkinsonism features prior to discharge from hospital in 4 days. He vistied for review 2 weeks after discharge and by this time he showed complete improvement and was happy with a smiling face .

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+A 28-year-old Nigerian woman of Igbo ethnicity presented with a 6-week history of neck pain associated with paroxysmal tonic spasms of the left upper and lower limbs. She had no sphincter dysfunction or constipation. There was a positive Lhermitte's sign with neck flexion and severe burning sensation of the right lower limb. There was no prior neck trauma, cough, night sweats or weight loss and she did not complain of visual blurring. She was not hypertensive or diabetic but her father was hypertensive and her mother had diabetes. She was para 1 + 2 (1 alive) and had recurrent pregnancy losses twice in the mid-trimester period. She delivered a live male neonate 4 months before presentation and had a tetanus toxoid injection 3 days before presentation in addition to the three doses she had during antenatal care. She had a previous history of anterior neck swelling a month after delivery.
+General physical examination showed a young woman with frequent paroxysmal tonic flexor spasms lasting 2 minutes each and involving the left upper and lower limbs. Higher mental function was normal. The Lhermitte's sign was elicited by forward neck flexion. The pupils were 3 mm in size and she had a relative afferent pupillary defect in the right eye. Initial fundoscopy was normal. She had a spastic quadriparesis with a power of grade 4 [Medical Research Council (MRC) grading] and bilateral extensor plantar response and absent abdominal reflexes. Light touch, vibration and joint position sensations were impaired up to the C7/C8 dermatome. Romberg's sign was present. Her cerebellar system was normal and there was no spinal tenderness. Her pulse rate was 80 beats/minute and regular. Her blood pressure was 120/80 mmHg with normal heart sounds. Chest and abdominal examinations were normal.
+The cranial MRI showed normal T1 and T2 weighted images. The initial cervical T2 weighted MRI showed patchy ill-defined central linear hyperintense focus in the intramedullary portion of the spinal cord between C1 and C5 in keeping with transverse myelitis . Her erythrocyte sedimentation rate (ESR) on admission was 67 mm/hour and she had positive lupus erythematosus (LE) cells. Antinuclear and anti double-stranded antibodies were negative. Cardiolipin IgM was 15.0 MPL/ml (reference range 0.00–3.5 MPL/ml) while Cardiolipin IgG was within normal limits at 2.8 mGPL/ml (reference range 0.00–15.0 GPL/ml). Her prothrombin time (PT) was prolonged -PT 18.4s, control 12.9s, prothrombin time ratio (PTR) 1.4, international normalized ratio (INR) 1.6.
+Her thyroid, liver function test, blood glucose and electrolytes were normal. The results were: serum calcium 2.4 mmol/liter, potassium 3.9 mmol/liter, sodium 135 mmol/liter, bicarbonate 26 mml/liter, chloride 98 mmol/liter and urea 4.5 mmol/liter. She was retroviral negative.
+Her cerebrospinal fluid (CSF) test was normal: CSF protein 21 mg/dl, CSF glucose 2.8 mmol/liter, microscopy <5 WBC/mm3; CSF Immunoglobulin and serum NMO IgG assays could not be done.
+An initial assessment of transverse myelitis was made and she was placed on intravenous methylprednisolone 1 g daily for 5 days, thereafter oral prednisolone 70 mg daily which was gradually tailed off. Although her serum potassium level fell to 2.9 mmol/liter, she did not receive additional potassium supplement with the therapy. She was however advised to take foods high in potassium. Her drug therapy included diazepam 15 mg 6 hourly and Baclofen 10 mg at night given for relief of the spasms. Gabapentin 400 mg at night and carbamazepine 400 mg thrice daily were also administered for the neuropathic pain. She also had regular physiotherapy.
+The patient gradually improved with gradual resolution of the muscle spasms, weakness and rigidity. Muscle power increased to 5 globally and the repeat ESR reduced to 17 mm/hour.
+Ophthalmic examination done 4 weeks after admission revealed impaired visual acuity which was worse in the right eye (right eye – counting figure, left eye – 6/9). The corneal sensitivity was intact with a relative afferent pupillary defect. There was bilateral temporal pallor with slight blurring of the optic disc margins nasally. There were also nerve fiber defects along the superotemporal vascular arcade with moderate perivascular sheathing.
+A repeat MRI was done a month after the initial one and showed resolution of the earlier noticed signal intensity at the spinomedullary junction . A final diagnosis of Devic's NMO syndrome was made and she was discharged after 5 weeks to be followed up in the outpatient clinic. She has been seen many times at the clinic and there has been sustained clinical and neurological improvement. However, she did not receive additional immunosuppressive therapy after completing the intravenous methylprednisolone, neither was there a repeat confirmatory test done for her antiphospholipid status. She was followed up in the clinic for 8 months after her discharge.

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+In April 2017, a 72-year-old homeless male patient was admitted to the emergency department at the Ramos Mejia Hospital, Ciudad Autónoma de Buenos Aires, Argentina. The patient was in very poor hygienic condition, malnourished and dehydrated. He presented a deep necrotic ulcer in the anterior aspect of his left tibia of 9-months’ evolution, with exposure of both tibia and fibula, complete loss of muscle mass, severe ischaemia, foul discharge and heavy burden myiasis. Unfortunately, maggots had been rapidly discarded, allowing neither bacterial analysis nor entomological identification.
+The patient had a history of alcohol abuse and pulmonar tuberculosis in 1980 which resolved after complete treatment.
+On physical examination, his blood pressure was 100/60 mmHg, his heart rate 97 and his respiratory rate 20 breaths min−1. His body temperature was 36 °C. Haematological and biochemical exams on admission showed: leucocytes 24750 K µl−1, with 92.5 % neutrophils; glucose level of 237 mg dl−1, haematocrit 40 %, haemoglobin 13.3 g dl−1, uraemia 126 mg dl−1, creatinine 2017 mg dl−1; sodium 127 mmol l−1; potassium 5.5 mmol l−1; chloride 87 mmol l−1.
+Two blood culture sets were taken at the time of admission, at two different times. Gram-negative rods were obtained in pure culture. With this preliminary report, the case was described as sepsis caused by skin and soft tissue infection. Intravenous therapy with ciprofloxacin 400 mg/12 h and clindamicin 600 mg/12 h was initiated.
+Conventional phenotypic test and MALDI-TOF-MS (Bruker Daltonics) failed to identify the bacteria isolated.
+In order to confirm genus and species identification, PCR amplification of the 16S rRNA was performed. The nearly complete sequence of the 16S rRNA gene was amplified by PCR with the conserved primers 8F (5′-AGAGTTTGATYMTGGCTCAG-3′) and 1942R (5′-ACCTTGTTACGACTT-3′), as described previously . The sequence obtained showed a 100 % identity with the sequence corresponding to the 16S RNA ribosomal gene of I. indica, type strain FFA1 (GenBank accession number. EU008088.2). The 16S rRNA sequence obtained was deposited in GenBank under number MF062521.
+Due to the severity of the lesions, a supracondylar amputation had to be performed in order to allow for adequate and prompt infection source control, and antibiotic treatment for 14 days was completed, which led to resolution of sepsis and normalization of laboratory parameters. The patient had a favourable outcome, with no surgical complications.
+Members of the genus Ignatzschineria are difficult to identify using traditional methods, including classical biochemical tests and commercial bacterial identification systems. Even MALDI-TOF MS analysis has been unsuccessful. 16S ARNr gene sequencing has proved to be useful for identification, and is currently the most accurate method for clinical diagnostic laboratories.

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+A 34-year-old female patient was admitted to the hospital due to vaginal bleeding, fatigue and shortness of breath for 4 d without chest pain, hemoptysis, dyspnea or other symptoms.
+Computed tomography (CT) examination revealed a filling defect in the IVC before admission, which was initially thought to be a thrombus. Anticoagulant therapy was administered immediately. No other conditions were recorded when admitted to our hospital.
+Seven years ago, the patient had undergone a hystero-myomectomy (no medical records/pathological specimens were available). No other significant history of past illnesses was identified.
+The patient had no previous or family history of similar illnesses.
+Physical examination showed a surgical scar in the lower abdomen. A palpable hard mass was found in the lower abdomen, with poor mobility and mild tenderness. Vital signs were stable with a blood pressure of 135/80 mmHg, a heart rate 90 bpm, respiratory rate of 21 breaths/min and O2 saturation of 98%. The electrocardiogram showed sinus rhythm and incomplete right bundle branch block.
+The laboratory examinations showed elevated levels of cancer antigen 125 (47.73 U/mL), FDP (20.31 μg/mL) and D-Di (6.06 μg/mL), while the results of other laboratory examinations were in the normal range.
+Transvaginal ultrasonography showed that the uterus was 10.0 cm × 8.5 cm × 8.9 cm in size with multiple heterogeneously echogenic lesions. Transthoracic echocardiography revealed a strip-shaped mass extending to the right atrium and right ventricle, and protruding into the pulmonary artery . The diameter of the pulmonary artery was widened, and the pulmonary artery pressure was 66 mmHg. An enlarged uterus and multiple mixed-density masses in the myometrium were found on enhanced CT images . Filling defects were observed in the right iliac vein, ovarian vein, IVC, right atrium, right ventricle, pulmonary trunk and bilateral pulmonary artery branches . Magnetic resonance imaging (MRI) showed extensive myometrial thickening which was heterogeneously hyperintense on T2-weighted images . Diffuse infiltration of the cervix and vaginal vault was noted without rectal or pelvic wall involvement. Increased signal intensity of the lesions was observed on diffusion weighted imaging (DWI) . Following an intravenous injection of contrast medium, contrast enhancement of the lesions was heterogeneous and less intense than in the myometrium. The vessels around the uterus and cervix increased, and filling defects in the right iliac vein and left ovarian vein were noted . 18F-FDG positron emission tomography/computed tomography (PET/CT) demonstrated slightly high 18F-fluorodeoxyglucose uptake of the tumor in the IVC , and the maximum standard uptake value was approximately 2.8.

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+The proband, female of 1 year and 3 months old, was referred to the Research Centre for Medical Genetics because of severe failure to thrive. She was born from a first pregnancy. Parents were nonconsanguineous and had normal growth. The threat of miscarriage took place at 27 weeks. Delivery was emergent at 38 weeks and 5 days by cesarean section. The condition at birth was severe. Respiratory failure was increasing. The child was on a ventilator for five days. In total, respiratory support was required for five months. The patient was diagnosed with pulmonary hypertension.
+Body weight at birth was 1490 g (Z-score −4.50), 40 cm in length (Z-score −4.54). Head circumference was 32.5 cm (Z-score −2.59). Chest circumference was 24 cm. She had hydrocephalic head, short palpebral fissures, ocular and nipple hypertelorism, depressed nasal bridge, epicanthus, microstomy, high-arched palate, hypoplastic low-set ears, short neck, low hair line, and arachnodactyly. The baby had a pronounced progeroid appearance. The subcutaneous fat layer was not pronounced. An external examination of the genitals revealed hypoplasia of the labia majora, and the clitoris was hypertrophied. The liver protruded 3 cm below the edge of the right costal arch and 1 cm below the edge of the left costal arch. Motor activity was reduced.
+Upon screening at 9 months, the patient’s condition was severe, but her consciousness was clear, and her posture as active. The baby was responsive to communication. She had a body weight of 3.3 kg (Z-score −6.54), a height of 54 cm (Z-score −6.61), and a body mass index of 11.32 (Z-score −4.67). Her head circumference was 43.5 cm (Z-score −0.76), and her chest circumference was 30 cm. The patient’s physical development was extremely low, disharmonic. Pseudohydrocephalus, high forehead, triangular face, exophthalmos, narrow nasal dorsum, smooth philtrum, microgenia, microtia, and arachnodactyly were observed in the child during the examination. The skin was clean and dry. The girl had cyanosis of the face and upper half of the trunk when crying. The subcutaneous fat was underdeveloped. The patient’s chest was barrel-shaped. Hepatomegaly was observed. The child could not support her head but tried to turn her body from prone to supine. She had a pronounced interest in toys. Her speech consisted of babbling, with chains of syllables. X-ray showed delay in bone age – less than three months vs the patient’s actual age of 9 months. The bone structure was sparse. Valgus deformity of the knee joints was observed. Data on the condition of the patella were not provided because these bones are transparent on X-ray scans in young children, and ultrasonography was not performed. EEG recordings contained no epileptiform or focal pathological activity. Echocardiography showed no signs of heart defects. Patent foramen ovale and diagonal trabecula in the left ventricular cavity were observed.
+Another examination was performed at 1 year and 3 months was performed. The girl had a height of 58 cm (Z-score −7.06), a weight of 4 kg (Z-score −6.44) and a head circumference of 45 cm (Z-score −0.5). Hydrocephalic head, high forehead, triangular face, exophthalmos, narrow nasal dorsum, microgenia, microtia, severe hypotrophy, and areas of alopecia on the head were observed. Subcutaneous fat was not developed. The baby did not sit independently and could not steadily support herself on her feet, but she was able to stand with support. She played with toys, held objects in her hands, collected pyramids, and transferred small objects.
+The last time the patient was examined when she was 1 year 11 months old. Short stature (63 cm, Z-score −7.04) and growth retardation (5 kg, Z-score −6.16) were noted. Clinical examination revealed dysmorphic facial features, microtia. Absent patella was noted by palpation. .
+Initially, chromosomal abnormality was suspected in the child. Cytogenetic testing was performed. Karyotype 46, XX was detected. Hutchinson-Gilford progeria was assumed. A corresponding study of the LMNA gene was performed. No pathogenic changes were observed. Clinical exome sequencing was ordered, identifying two variants in the CDC6 gene. Parental examination revealed that they were heterozygous carriers of relevant changes in the nucleotide sequence.
+Neither variant had been registered in either the GnomAD database (v.2.1.1), the clinical databases (Clinvar, HGMD Professional (v.2021.1)), or the database of variants obtained by exome sequencing (WES, CES) in the Research Center for Medical Genetics – RuExac (1337 samples). The exon 3 nucleotide sequence variant of the CDC6 gene (chr17:38447363C>T) results in a premature translation termination site (p.(Gln78Ter), NM_001254.3). According to the pathogenicity criteria, ACMG is classified as pathogenic (PVS1, PS3, PM2). The criterium PS3 was used due to the previously functional study that demonstrated pathogenicity of LoF variants in the CDC6 gene. A variant in exon 3 of the CDC6 gene (chr17:38447361A>G), resulting in a missense replacement of (p.(Lys77Arg), NM_001254.3), is classified as a variant with uncertain clinical significance (ACMG: PM2, PM3).

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+A 64-year-old man presented with a dark red palpable mass in the bulbar conjunctiva (diameter: 0.5 cm) at the medial canthus of the right eye. The mass was reported to be present for at least three months . The past medical history was uneventful and in particular no B-symptoms were reported. CT scans of the right orbit showed a limited bulbar conjunctival mass not involving the lacrimal gland or orbital septum of the eyelids.
+Histologic examination of an incisional biopsy showed infiltration by a monomorphic cell population composed of small-to-medium-sized lymphocytes with irregular, indented, or cleaved nuclei, 3/10 HPF mitotic rate and partially nodular growth pattern, beneath the simple cuboidal cell layer of surface conjunctival epithelium .
+Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections, according to the manufacturers’ protocols. The primary antibodies used, the methods of antigen retrieval, and the dilution rates were as follows: CD20 (L26) (Novocastra, Newcastle, UK; microwave in 0.01 molar citrate buffer; 1:50), CD3 (PS1) (Novocastra, Newcastle, UK;microwave in 0.01 molar citrate buffer; 1:200), CD5 (4C7) (Novocastra, Newcastle, UK; microwave in RE7113 solution; 1:100), CD10 (56C6) (Novocastra, Newcastle, UK; microwave in citrate buffer; 1:100), CD23 (1B12) (Novocastra, Newcastle, UK; microwave in 0.01molar citrate buffer; 1:100), BCL-2 (3.1) (Novocastra, Newcastle, UK; microwave in citrate buffer; 1:100), cyclin D1 (P2D11F11) (Novocastra, Newcastle, UK; Trypsin digestion; 1:50), Ki-67 (MM1) (Novocastra, Newcastle, UK; microwave in citrate buffer; 1:100) and SOX11 (Atlas Antibodies, Stockholm, Sweden; heat-induced retrieval with ER2 BondMax buffer; 1:100) as previously described . The tumor cells were positive for CD20 , CD5, BCL-2, cyclin D1 , and SOX-11 and negative for CD3, CD10, and CD23. The Ki-67 proliferation index was 12%. By fluorescence in situ hybridization (FISH) analysis on formalin-fixed, paraffin-embedded tissue sections using commercially available LSI IGH/CCND1 XT dual color, dual fusion and LSI CCND1 BAP break apart probes (Abbott-Vysis), juxtaposition of IGH and CCND1 and a breakpoint in the CCND1 locus were detected in 85% and 97% of nuclei, respectively, indicating presence of the MCL hallmark translocation t(11;14)(q13;q32) . The histopathologic and genetic findings confirmed the diagnosis of conjunctival mantle cell lymphoma.
+The patient did not show up in his follow up Ophtholmology visit, however after two months was referred to an oncologist. Extensive clinical staging was performed and cervical lymph node and bone marrow involvements were discovered. Gastroscopy and laboratory workups such as liver function test, ESR, BUN, creatinine, β2 microglobulin, LDH, leukocyte count and serum protein electrophoresis were in normal ranges. The patient was allocated to the low-risk group with the MCL International Prognostic Index. Combined chemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) was administered. After five cycles (approximately 5 months) patient showed clinical response as a decrease in neck lymph-node sizes and shrinkage of the conjunctival lesion , however complete remission workup is pending after the sixth cycle.

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+A 42-year-old man was referred to our hospital due to an abnormal shadow on a chest X-ray, which was found during a physical examination. CT scan revealed numerous vascular structures in the left chest wall , anomalous arteries in the left lower lobe superior segment of lung (Lt. S6) , and a filling defect in the left apical segmental pulmonary artery of the left lower lobe (Lt. A6), which indicated a blood flow regurgitation from the dilated left 4th intercostal artery to the Lt. A6 . No other abnormalities were found by CT scan, laboratory tests and pulmonary function test, and a diagnosis of SPAS was established. The patients was asymptomatic, but based on the potential risk of future hemoptysis, we decided to treat him with TAE followed by S6 segmentectomy after a careful informed consent. On preoperative TAE, the 4th and 5th intercostal arteries and the left thyrocervical artery were identified as systemic arteries and all were embolized with microcoils . After the TAE, S6 segmentectomy was performed on the same day. First, interlobar fissure was dissected and A6 was ligated and transected to reduce blood flow of the pulmonary artery, followed by the dissection of the adhesions between S6 and parietal pleura, containing abundant blood vessels . Finally, Lt. S6 segmentectomy was performed using indocyanine green (ICG) . Intraoperative blood loss was 30 g. The patient had an uneventful postoperative course, and he was discharged on the 6th day after surgery. Histological examination of the resected left S6 showed a pleural thickening and large muscular arteries and adjacent dilated pulmonary arteries in the subpleural area, suggesting communications between them .

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+A 27-year-old woman visited our gynecology department because of abdominal pain and genital bleeding. Magnetic resonance imaging (MRI) revealed a cystic mass in the left retrorectal area, and she was referred to our department for detailed examinations and treatment. Her medical history was unremarkable. Her laboratory results, including serum tumor biomarkers, such as α-fetoprotein (AFP), carcinogenic embryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), were within normal limits. Computed tomography (CT) showed a 3-cm-sized multilocular cystic mass in the anterior sacrum on the left dorsal side of the rectum. The mass showed a gradual contrast effect on the margin and was suspected to have a solid component. No obvious calcification was observed . MRI showed no obvious fat in the area . Fluorodeoxyglucose-position emission tomography (FDG-PET) showed no abnormal uptake. Lower gastrointestinal endoscopy showed no abnormalities in the rectal mucosa. Endoscopic ultrasound (EUS) showed a 3-cm-sized extraintestinal cyst near the rectum. No obvious calcification was found inside .
+With the above tests, it was difficult to confirm the preoperative diagnosis of the presacral cystic mass. Teratoma, tailgut cyst, dermoid cyst, epidermoid cyst, etc., were considered in the differential diagnosis. Because there have been reports of malignant cases, we decided to perform surgical mass removal as a diagnostic treatment.
+The operation was conducted with the patient in the jack-knife position. A skin incision measuring approximately 3 cm was made from the coccyx to the anus. We made an incision in the mural fascia to reach the tumor and enable detachment without damaging the tumor. Since it was difficult to confirm the deep part of the tumor through direct visualization, we attached a GelPOINT® Path (Applied Medical, USA) placed two 10-mm trocars and a AirSEAL® (CONMED, USA) trocar in a triangular fashion to the incision and insufflated it at 12 mmHg with the AirSEAL® System to remove the tumor endoscopically while confirming the boundary between the tumor and the anterior coccyx/posterior rectal wall. The operative time was 171 min, with minimal blood loss .
+Histopathological examination revealed a benign mature teratoma . She did not have any complications and was discharged from our hospital 5 days after the surgery. Seven months later, she had no tumor recurrence or residual symptoms.

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+A 25-years-old male of Afghani origin with a history of recurrent acute pancreatitis was referred to the intensive care unit of the Jena University Hospital in November 2019.
+Abdominal pain debuted two years ago when the patient was 23 years old. The family history revealed that the patient’s brother and sister similarly suffer from abdominal pain and have been hospitalized several times. His niece died at the age of three due to acute pancreatitis. The patient’s whole family resides in Afghanistan, so neither clinical nor genetic investigation of relatives was possible in our clinic.
+On physical examination, the patient’s BMI was 23.4 kg/m2, blood pressure, and heart rate were 146/83 mm Hg and 95/min, respectively. He showed no xanthomas but did have lipemia retinalis on retinal examination. Examination of the abdomen revealed pain in the upper left area and an enlarged spleen. No other abnormalities were observed.
+TG levels were at 29 mmol/L, and low-density lipoprotein (LDL) and high-density lipoprotein cholesterol (HDL) cholesterol were within reference ranges. According to the previous records, TGs were as high as 82 mmol/L in the past. Inflammation markers (C-reactive protein and white blood cells) were remarkably elevated. There were no clinical symptoms or laboratory indicators of secondary (pancreoprivic) diabetes mellitus (HbA1c 5.1%, blood glucose 5.8 mmol/L). Other laboratory parameters are shown in Table .
+Abdominal computer tomography demonstrated edematous pancreatitis, most prominently within the corpus pancreaticus with surrounding fat tissue fibrosis and splenomegaly. There were no signs of choledocholithiasis.
+A panel screening for HTG-related genes (Additional file ) was performed. The sequencing was performed using the next-generation sequencing on Illumina-Sequencer (NextSeq500/NovaSeq6000) with a > 98% coverage of regions of interest. The analysis revealed homozygosity for a frameshift mutation of APOA5 (c427delC, p.Arg143Alafs*57) with a minor allele frequency of 0.006%. This mutation causes an alteration in the translational reading frame and results in a premature stop of protein synthesis due to the introduction of a stop codon at position 57. The patient was also a homozygous carrier of haplotype APOA5*2.
+Acute pancreatitis was treated with aggressive fluid resuscitation and therapeutic plasma exchange (Spectra Optia, Terumo BCT, Inc. Lakewood USA). The patient was then put on a low-fat diet and a combination of ezetimibe (10 mg daily) and fenofibrate (160 mg micronized daily). Shortly after the discharge, another episode of acute pancreatitis occurred. The patient was prescribed omega-3 fatty acids; however, the inability to obtain reimbursement for omega-3 fatty acids in Germany hindered their usage. The patient was regularly followed up at our outpatient clinic. A satisfactory range of TG, between 9.2 and 11.2 mmol/L , was maintained through a combination of stringent dietary measures and consistent intake of fibrates. After two years, another episode of pancreatitis occurred, with TG elevation up to 18.8 mmol/L. The patient was started on weekly injections of volanesorsen. On this regimen, TG levels were stably under 4 mmol/L . The platelet count decreased from 201,000 to 114,000/µL. Therefore, according to recommendations, we switched to biweekly administrations. As a result, the platelet count stabilized (at ~ 150,000/µL). The patient had no episodes of bleeding. Volanesorsen therapy was continued with regular assessment of platelet count.

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+A 67 year-old female patient presented with left chest wall sinus one year ago. Local redness, pain and persistent purulent discharge occurred around the sinus orifice. Reviewing the medical history, the patient had undergone left mastectomy 20 years ago due to the diagnosis of left breast cancer, followed by regular radiotherapy and chemotherapy for several times. At the same time, she suffered from coronary heart disease, hypertension and other cardiovascular diseases. She underwent coronary stent implantation in 2017, 2019 and 2020 respectively. Currently, she regularly takes anticoagulant drugs (Aspirin Enteric-coated Tablets 100 mg QD) and antihypertensive drugs (Nifedipine Sustained Release Tablets 30 mg QD). Due to repeated non-healing of chest wall wound and formation of chest wall defect, ulcer and fistula caused by debridement, the patient was admitted to our hospital for further treatment. Chest CT scan showed partial defect of left chest wall with sinus formation, high-density shadow of left clavicle and some ribs. According to the patient's symptoms and imaging examination, we diagnosed chest wall sinus with infection and chronic osteomyelitis.
+After admission, the patient continued to be given local cleaning and dressing changes on the wound surface. The purulent secretions at the sinus orifice were subjected to microbial culture and drug susceptibility tests. The results of the three secretion cultures were all suggestive of Pseudomonas aeruginosa. Her BMI was 18.4 kg/m2 and albumin was 24.5 g/L. We chose sensitive antibiotics for systemic anti-infective treatment. At the same time, nutritional support and correction of hypoalbuminemia were given. Enhanced chest CT and three-dimensional reconstruction were performed. Before chest CT examination, 50% meglumine solution was injected into sinus orifice through a thin drainage tube to fully understand the shape, scope and adjacent conditions of sinus. Due to the long course of disease and lack of confidence in treatment, the patients were given necessary psychological counseling and appropriate anti anxiety drug treatment.
+The operation was divided into two stages, both under general anesthesia. Before first-stage operation, we injected methylene blue solution from sinus orifice to make sinus wall fully stained to guide the scope of surgical curettage, which could not only ensure the complete removal of the diseased sinus wall tissue, but also avoided too much damage to the normal tissue and even the important organs behind the sternum. Taking the sinus orifice of chest wall as a center, a fusiform incision with a length of about 8 cm was made along the 1 cm around sinus orifice. The direction and length of the incision were determined according to the sinus shape (the sinus starts at the level of the left first rib and ends at the level of the left fourth rib, without communication with the thoracic cavity) shown on preoperative chest CT and the position of the myocutaneous flap to be filled. After incision of the skin, the sternum and infected area were fully exposed, sinus wall tissue was fully scraped with a curette, and then necrotic bone was completely removed with a rongeur (It starts from the junction of the left first rib and the manubrium cartilage. Part of the first rib, part of the lower edge of the left clavicle, and the adjacent medial end of the sternum are removed in sequence from near to far, from top to bottom, until the bone stump is fresh). When the chest wall wound tissue was fresh and there was no dye attached, we first rinse it with 1000 ml normal saline, then rinse it with diluted iodophor water (100 ml iodophor water and 400 ml normal saline) and 100 ml 3% hydrogen peroxide for one time, and then rinse it with 1000 ml normal saline again. Due to the huge wound defect after debridement, in order to ensure the cleanliness of the wound, improve local blood supply and prepare for the second-stage operation, vacuum sealing drainage (VSD) were performed after the operation . We adjusted the pressure scale of the VSD device to 0.04 Mpa, and the device was removed after 7 days.
+When the patient's general condition was good after first-stage operation, after the vacuum sealing drainage device was removed, the daily incision dressing change, anti-infection, nutritional support and other treatments were continued. When the granulation of sinus wound was fresh, the secretion was significantly reduced, the re-culturing of the wound secretion was negative, and the infection was preliminarily controlled, we were ready for the second-stage operation. Continue to appropriately expanded the wound along the original incision, thoroughly debrideed the necrotic tissue until the wound was fresh, and measured the size of the chest wall defect was about 15 × 8 cm. After hemostasis, rinsed the wound with a large amount of iodophor, hydrogen peroxide, and normal saline alternately. The patient's body position was changed to 90° lateral lying position. According to the preoperative planned flap incision, the pedicled latissimus dorsi myocutaneous flap was selected as the living tissue to fill the defect wound. The computed tomography angiography (CTA) examination of the subclavian artery showed that there were internal thoracic artery and thoracodorsal artery on the affected side without malformation. During the operation, first of all, an incision was made along the outer edge of latissimus dorsi muscle, starting from the proximal axillary apex, and the proximal and distal ends of latissimus dorsi muscle were dissociated and fully exposed in turn to protect the thoracodorsal artery and vein. Finally, a latissimus dorsi myocutaneous flap with thoracodorsal neurovascular bundle of sufficient length was formed. The size of the latissimus dorsi myocutaneous flap was about 30 × 8 cm, while the skin island of about 16cmx8cm was reserved. During harvesting of the myocutaneous flap, the blood supply should be preserved as much as possible, while avoiding excessive distortion of the pedicle of the myocutaneous flap. We first made a subcutaneous tunnel between the acquisition site of the myocutaneous flap and the sternal wound, transferred the myocutaneous flap to the chest wall defect wound, then sutured and fixed it with the soft tissue around the wound, closely combined the myocutaneous flap with the bottom of the chest wall wound to eliminate the dead space, and finally placed a drainage tube . The patient was treated with anti infection (Cefoperazone Sodium and Sulbactam Sodium + Levofloxacin and Sodium Chloride Injection), anti spasm (Raceanisodamine Hydrochloride Injection) and anticoagulation (Enoxaparin Sodium Injection) after operation. The color and temperature of the myocutaneous flap was closely observed and tested. The transplanted myocutaneous flap was kept warm, and the incision was avoided from compression to protect the smooth blood flow. The patient pulled out the chest tubes on the 4th postoperative day and was discharged from the hospital on the 7th day. At present, the patient was followed up for 6 months after the operation, the incision healed well and no malignant tumor tissue was found in the routine pathology after the two operations. Repeat chest CT showed that the chest wall sinus disappeared completely, and the pedicled myocutaneous flap fully survived.

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+A 34-year-old male patient presented to our hospital with multiple yellowish elevated masses in different locations of the body, including the dorsum of the hands, elbows, buttocks and feet. In addition, the patient also had bilateral arcus cornealis and Achille tendon masses . The total number of masses was 15, and the size of masses varied from 1 × 1 × 1 cm to 8 × 8 × 5 cm. The masses were initially asymptomatic; they appeared 10 years ago, and then they increased progressively in size. The patient complained of discomfort and difficulty dressing and sitting due to large masses in the buttocks. In addition, patients also reported difficulty wearing sandals due to the masses in the feet. The patient's hygiene was affected, and especially the masses made the patient feel inferior when in contact with others. Even the patient decided to divorce because of psychological influences related to abnormalities in the body. The results of the chest X-ray, abdominal ultrasound, electrocardiogram and echocardiogram of the patient were normal. The patient's family medical history was not taken because the patient did not wish to disclose it. The low-density lipoprotein cholesterol (LDL-C) level of the patient was 10.04 mmol/L (reference value, <2.6 mmol/L). Based on a high level of LDL-C, arcus cornealis and presence of xanthomas, the patient was diagnosed with Familial hypercholesterolemia (FH) based on the Simon Broome Criteria.
+After receiving the consultation, the patient agreed to be admitted to the hospital for surgery to remove the masses. Lipid-lowering therapy was immediately administered for the patient with Atorvastatin 40 mg/day. After 4 days of hospitalization, the patient then underwent surgery to remove the masses. The resected masses had a surface of normal skin. The core of the masses looked yellowish-colored uniform, relatively solid, without necrosis, and localized in the subcutaneous layer without invading the muscle or joint capsule . The skin incision was oval around the circumference of masses with the longitudinal axis parallel to the Langer's line. The excision margins were normal skin. After removing masses, all defects were sutured directly . A total of 13 masses were removed; the remaining 2 masses on the finger were not removed because the patient still had to use the fingers to take care of himself. The remaining 2 masses would be removed during the next surgery. Histopathology showed a typical xanthoma with infiltration of foam cells . The healing process was normal. All sutures were removed 14 days after surgery. The patient was discharged and continued treatment with atorvastatin 40 mg/day. Gene sequencing test (on the Nextseq, Illumina system) showed homozygous LDL-C receptor gene mutation on chromosome 19. Due to difficult economic conditions, the patient's family members did not undergo gene sequencing to find mutations causing FH. Follow-up at 1.5 months postoperatively, the LDL-C level of the patient was reduced to 8.8 mmol/L and the wounds healed well and no re-appearance of masses was observed .

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+A 7.6-year-old boy was referred for investigation of short stature. He was born after 39 weeks of gestation, with a birth weight of 3.38 kg (0.0 SD) and birth length of 47 cm (− 1.8 SD). Since the age of 1 year, height SD had gradually decreased from − 1.7 to − 3.3 SD, whereas the mid-parental height was − 0.8 SD. He did not have polydipsia or polyuria. The boy had previously been diagnosed with an autistic spectrum disorder, but his clinical examination was otherwise unremarkable; he had normal genitalia and there were no signs of puberty (Tanner stages A1 P1 G1, testes 1/1 ml). There was no familial history of constitutional delay. Endocrine results were suggestive of partial GH deficiency (circulating insulin-like growth factor-I 48 μg/L (− 2.5 SD) ; peak GH of 8.9 μg/L after glucagon). TSH was borderline elevated but free T4 was normal (TSH 5.3 mIU/L, free T4 14.6 pmol/L), and basal concentrations of circulating cortisol (8.8 μg/dL), dehydroepiandrosterone-sulphate (DHEAS 0.6785 μmol/L), luteinizing hormone (LH < 0.1 IU/L), follicle stimulating hormone (FSH 0.8 IU/L) and prolactin (4.7 μg/L) were unremarkable. MRI of the brain revealed a lipoma on the midline adjacent to the hypothalamus . The appearance of the anterior and posterior pituitary gland was normal. GH replacement treatment significantly increased height velocity from 5.2 cm/year to 9.4 cm/year in the first year of catch-up growth .

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+A 74-year-old Caucasian Greek man was referred to our surgical clinic for repair of a left inguinal hernia. The patient had noticed a gradually enlarging mass 10 years prior to presentation. His physical examination revealed an elastic, hard, slightly mobile mass that was initially confused with a scrotal hernia, although reduction maneuvers produced no result, even after the intramuscular administration of pethidine. No abnormal dermal findings were observed.
+Ultrasonography showed the presence of a large (9 cm × 4 cm), rigid, inhomogeneous structure starting from the left inguinal space under the skin but not penetrating the corresponding hemiscrotum. Doppler sonography demonstrated prominent, rich vasculature. On computed tomography (CT), the lesion was observed to be round, with a diameter of 13 cm, inhomogeneous to the surrounding fat tissue of the anterior abdominal wall at the level of the left spermatic cord, and pushing away the left testis . No intravenous contrast medium was used because of allergy of the patient.
+Intra-operatively, the mass was found to be oval-shaped with dimensions 8 cm × 7 cm × 3 cm, well encapsulated, resembling fat tissue with rich vasculature, and it seemed to arise from the scrotal part of the spermatic cord without adherence to the ipsilateral testis . The mass was excised, and, because of the parallel presence of an inguinal hernia, typical mesh repair was performed.
+Microscopically, the specimen consisted of loose fibrous tissue in which we found a large number of fibroblasts (vimentin- and CD34-positive and actin-, desmin-, and S100P-negative), inflammatory infiltration of lymphocytes, plasma cells, mast cells, and abundant capillaries, many of which with regenerating and degenerating forms . The walls of some tissues were thickened and those of others were hyalinized .

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+A 19-year-old woman noticed blurred vision with photopsia of the left eye. The patient had no notable medical or family history. Her best-corrected visual acuity (BCVA) was 1.0 OD and 0.9 OS with myopia of −9.0 diopters OU. Visual examination of the right eye showed no abnormality. Slit-lamp biomicroscopy revealed mild cells in the anterior vitreous OS. Funduscopic examination revealed multiple punctate yellow-white exudates at the level of the retinal pigment epithelium (RPE) in the posterior pole but not the midperiphery OS (Figure A). These exudates appeared as initial hyperfluorescence with late staining on fluorescein angiography (FA, Figure B) and hypofluorescence during the initial phase of ICGA (Figure C). SD-OCT images showed a loss of photoreceptor inner/outer segment junction (IS/OS) integrity corresponding to the nasal fovea (Figure D), accompanied by a moderately reflective, nodule-like lesion extending from the outer nuclear layer to the choroid, which corresponded to the exudates described above (Figure E). Humphrey threshold 30–2 perimetry showed an area of decreased sensitivity corresponding to the lesion area. Multifocal electroretinography (mfERG) showed decreased amplitudes at the posterior pole wider than the lesion area OS and normal amplitudes OD. The patient received a diagnosis of PIC OS. A regimen of oral prednisolone (30 mg/day) was initiated then gradually tapered for 4 months. Three months after treatment, BCVA increased to 1.2 OS. The areas of exudate scarred as IS/OS line integrity recovered. Twelve months after treatment, some of the scar lesions developed hyperpigmentation (Figure F), whereas BCVA and OCT findings remained stable.Twenty months after the initial visit, the patient complained again of central blurred vision in the left eye. Her BCVA was 1.2 OS. A punctate subretinal yellowish-white lesion nasal to the fovea OS (Figure A, F) appeared to have increased in size (Figure A, arrow), although the number of PIC lesions remained unchanged. The area of hyperfluorescence on late-phase FA (Figure B, arrow) or hypofluorescence on initial-phase ICGA (Figure C, arrow) corresponding to the lesion had expanded since the patient’s initial visit (Figure B, C). The patient was diagnosed with recurrent PIC. Treatment with oral prednisolone (30 mg/day) was restarted and continued for 3 months with tapering. Three months after this second round of treatment, BCVA remained unchanged, and the recurrent lesion had scarred with an associated improvement of the patient’s subjective symptoms.

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+A 68-year-old man with a history of hypertension, diabetes, and chronic kidney failure was undergoing treatment as an outpatient for angina pectoris and atrial fibrillation that was diagnosed 2 years prior to the carcinosarcoma. He reported a history of heavy smoking for approximately 40 years; moreover, his father had a history of lung cancer. The patient did not have any clinical symptoms of cancer, and no remarkable changes were noted on physical examination. However, a routine blood test done 3 months earlier indicated anemia (hemoglobin: 9.6 g/dL), and the patient’s stool sample tested positive for occult blood. We tested for tumor markers and found the squamous cell carcinoma (SCC) antigen was slightly elevated at 3.3 ng/mL, but the carcinoembryonic antigen (CEA) and CA 19–9 were within the reference range. An upper GI endoscopy showed a bleeding, irregular, protruding lesion located on the posterior wall of the lesser curvature within the body of the stomach ; the lesion was biopsied and identified as a poorly differentiated adenocarcinoma. Moreover, at the lower part of the esophagus, there was a slightly concave lesion that was entirely separate from the gastric tumor. Biopsy specimens from the esophageal lesion indicated SCC. The patient was scheduled for surgical tumor excision. First, en bloc resection via endoscopic submucosal dissection was performed for the esophageal cancer, and the pathological diagnosis was well-differentiated SCC with negative margins and slight infiltration of the mucosal lamina propria. At a later date, segmental gastrectomy was performed for the gastric tumor. The proximal gastric surgical margin was confirmed to be negative by rapid assessment. The resected gastric tumor was subjected to histopathological examination. Macroscopically, the gastrectomy specimen had a protruding lesion measuring 41 × 29 × 18 mm3 . The cross-section showed a grayish-white tumor with growth mainly on the mucous membranous surface as well as areas with a cystic appearance and a translucent cartilage-like matrix in parts . Histologically, the tumor was a carcinosarcoma with mixed adenocarcinomatous and sarcomatous components . Tumor invasion was limited to the submucosa. The adenocarcinomatous component exhibited tubular, papillary, and, in some parts, solid growth patterns. The adenocarcinoma cells were acidophilic and cylindrical; however, some regions comprised adenocarcinoma cells with clear cytoplasm. The adenocarcinomatous component resulted in diffuse lymphatic and venous invasion. The sarcomatous portion showed proliferation of atypical spindle cells and atypical round cells with a high nucleus-to-cytoplasm (N/C) ratio . In the sarcomatous portion, some parts showed chondrogenesis, and dyskaryosis was observed in chondrocyte-like cells . Immunohistochemically, the adenocarcinomatous component with clear cytoplasm comprised areas with alpha-fetoprotein (AFP)- and Sal-like protein 4 (SALL4)-positive AFP-producing gastric carcinoma . Moreover, there were synaptophysin- and chromogranin A-positive adenocarcinomatous regions that showed neuroendocrine differentiation . The sarcomatous portion was predominantly composed of undifferentiated areas as indicated by unstained regions, but included smooth muscle actin-positive leiomyosarcomatous areas composed of spindle cells with acidophilic cytoplasm as well as areas of desmin- and MyoD1-positive atypical round cells with rhabdomyosarcomatous differentiation . Furthermore, a proliferative focus with atypical “bare nucleus” cells that was partly composed of SALL4-positive germ cell-like cells did not indicate any specific differentiation in immunostaining . Histopathological analysis of the background stomach revealed chronic gastritis with intestinal metaplasia and negativity for Helicobacter pylori. There was no dysplasia around the gastric tumor.
+Approximately 1 month following the post-gastrectomy, a chest CT showed a ground glass opacity in the inferior lobe of the patient’s right lung; after 6 months, the lung lesion grew, and therefore the patient underwent a right lower lobectomy. Histopathology of the resected tumor indicated a lepidic growth pattern rather than a gastric tumor metastasis. Further examination revealed that the tumor was a primary lung adenosquamous carcinoma with a well-differentiated lung adenocarcinoma component, positive for thyroid transcription factor 1 (TTF-1) on immunohistochemical staining, that was admixed with an SCC component . Fourteen months after the segmental gastrectomy, a flat, protruding lesion appeared in the anastomotic region of the patient’s remaining stomach portion. This lesion was identified as a local recurrence, and a total gastrectomy was carried out . Examination of the resected specimen from the local recurrence showed the growth of only the adenocarcinomatous component, without a sarcomatous component . The recurrent tumor extended into the subserosa, and we observed 1 very small site of lymph node metastasis . The patient started adjuvant chemotherapy by TS-1, and at the time of writing this report, the patient had survived for 3 months after the total gastrectomy. Although he had been diagnosed with three independent cancers, he did not undergo further evaluations for inherited cancer syndrome.

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+A 78-year-old woman with an unremarkable past medical history presented to the clinic with symptoms of progressively worsening myelopathy including gait dysfunction and impairment of upper extremity fine motor skills. Noncontrast MRI of the cervical spine demonstrated multilevel degenerative disease and a dorsal intradural extramedullary lesion extending from C3-C6.
+The patient underwent an elective posterior C3-7 decompression, C3-T1 instrumented fusion, and resection of intradural tumor. Final pathology was psammomatous meningioma. The patient tolerated the procedure well and postoperatively was transferred to the neurological ICU for close monitoring.
+The patient was initially discharged from the hospital to an inpatient rehabilitation facility on POD 6. At the time of discharge, she was awake, oriented, and followed commands in all extremities with some mild weakness in the right deltoid and biceps, graded 4/5; the remaining muscle groups were 5/5. On POD 10, the patient developed progressive lethargy and was readmitted to the hospital for further evaluation. Upon readmission, she opened her eyes to verbal command, had incomprehensible speech, and would move all extremities spontaneously with strength 3/5 but did not follow commands. She was afebrile with WBC = 6.9 and no metabolic abnormalities. Given her recent intradural surgery, a lumbar puncture was performed. CSF cytology demonstrated 397 WBC, 20 RBC, 291 protein, and 40 glucose. CSF PCR was positive for HSV 1. Interestingly, intracranial imaging did not demonstrate the typical findings associated with herpes encephalitis . She was initially placed on broad spectrum antibiotics in addition to antiviral therapy. She was also connected to continuous EEG monitoring, found to be in status epilepticus, and required escalating therapy to the point of intubation with midazolam infusion. Seizure control was ultimately achieved, and she was maintained on levetiracetam 1500 mg q12H for 30 days and lacosamide 200 mg q12H for 7 days. The remainder of her infectious work-up was unremarkable, allowing her to be narrowed to only a 21-day course of IV acyclovir 500 mg q12H. Due to acute respiratory failure from encephalopathy, she underwent tracheostomy and PEG placement (POD 29); she underwent repeat MRI approximately 2 weeks after HSV diagnosis which still lacked typical findings of HSV . However, she continued to improve clinically; at the time of discharge, she would open her eyes spontaneously and followed simple commands in all extremities. Approximately 3 months out from being diagnosed with HSV encephalitis, she was oriented twice and followed commands in all 4 extremities with 5/5 strength in the bilateral upper and 3/5 in the bilateral lower extremities.
+At a three-month follow-up, the patient presented no new symptoms. The PEG was still in place and EEG revealed excessive theta waves during wakefulness and bilateral midtemporal delta slowing (left more prevalent than right). Though the patient had dysarthria and poor attention/processing, she followed commands in all 4 extremities consistent with her last evaluation. Vimpat 200 BID and 1500 mg of Keppra were prescribed for ongoing clonus spasticity. All other medications were continued as prescribed. In the following month, the patient had a normal LOC, very slight dysarthria, and improved situational awareness. No recent seizures had occurred. Lacosamide was reduced to 150 mg every 12 hours and Vimpat was reduced to 150 BID. Upon final examination, she followed commands in all 4 extremities with 5/5 strength in the bilateral upper and 4-/5 in the bilateral lower extremities.