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data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1002_en.txt

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+In July 2006, a 41-year-old female presented with a swelling in the right preauricular region, which had persisted for the past two years, and was having difficulty opening her mouth for the past four months. The swelling was insidious in onset and progressive. In the first six months, the patient indicated the swelling was painless, only later becoming painful as the size increased.
+Local examination found a diffuse 5 × 4 cm firm to cystic mass with restricted mobility in the right preauricular region. Examination of the oral cavity, ear, cranial nerves, and other systems was unremarkable. MRI analysis indicated a large mass in the right infratemporal fossa with significant infiltration into the adjoining muscles. This mass was hypo-isointense on T1 and heterogeneously hyperintense on T2 weighted images . The mass had significant enhancement in post-contrast MRI . Hematological and biochemistry analyses were normal. Fine needle aspiration cytology (FNAC) revealed a monotonous population of small, round lymphoid cells with regular nuclei, compact chromatin, inconspicuous nucleoli, and scant basophilic cytoplasm. These findings were consistent with NHL. Diagnostic biopsy of the tissue confirmed small lymphocytic non-Hodgkin's lymphoma. The patient was investigated further to determine the staging of the NHL, but no lymph node or other organ was found to be involved. The patient was scheduled for chemo-radiation treatment and given nine cycles of the CHOP regime (cyclophosphamide, doxarubicine, vicristine, and prednisolone) and a total of 55G radiation in 25 fractions over five weeks. The patient remained asymptomatic for seven months.
+In Nov 2007, the patient again presented with similar symptoms. A computed axial tomography (CT) scan revealed a hypodense mass of 37 Hounsefield unit (HU) density and measuring 4.25 cm × 4.0 cm in the right temporal and infratemporal region. Post-contrast, this mass showed heterogeneous enhancement (66 HU density) and normal contents (muscles) were not identifiable from the mass. The tumor was excised and histopathology again confirmed the diagnosis of NHL. The patient was given six cycles of ifosfamide, metoxantron, and etoposide, with the last cycle on June 3rd, 2008. The patient was on regular follow up, and in Aug 2008 presented with increasing trismus. On examination, the infratemporal fossa was normal but there was a hard, irregular ulcer in the right retromolar area . A punch biopsy of the ulcer found it to be a well-differentiated squamous cell carcinoma. The patient was advised to undergo surgery for this carcinoma, but she did not come in for further follow up.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1006_en.txt

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+A 58-year-old Japanese woman complaining of pain and numbness in her left mandible was referred to our hospital in 2014. For a couple of months prior to her visit, she had been aware of an abnormal sensation in her left mandible, which gradually progressed to mild pain and numbness. She visited a general dental practitioner, who diagnosed her condition as osteomyelitis and referred her to our department. Her medical and family histories were unremarkable. On initial assessment, no obvious systemic symptoms were evident. A panoramic radiograph showed a widening of the periodontal ligament space, periapical bone loss in tooth #37, and a diffuse radiolucent lesion involving the left body of her mandible, with an indistinct cortical margin and ill-defined cortical borders of the inferior alveolar nerve canal . Moreover, the radiograph also showed that tooth #37 had previously been treated endodontically. Therefore, a diagnosis of apical periodontitis was suggested and endodontic treatment was performed; however, her symptoms were not relieved. Consequently, a neoplastic lesion was highly suspected and findings of a biopsy of the apical tissue after extraction of tooth #37 resulted in a histopathological diagnosis of tissue inflammation. However, after the biopsy, a gradual progressive swelling of the left mandible occurred . Computed tomography (CT) showed an enhanced lesion on the left mandible, and magnetic resonance image (MRI) showed abnormally high-intensity signal in the bone marrow, with surrounding soft tissue mass . Therefore, we performed an incisional biopsy of the swollen area, the findings of which resulted in a histopathological diagnosis of osteoblastic-type osteosarcoma of the mandible. She was then scheduled for radical surgery combined with neoadjuvant and adjuvant chemotherapy based on the regimen used in a multi-institutional clinical study of neoadjuvant chemotherapy in extragnathic osteosarcoma (NECO study) in Japan . In the NECO study, neoadjuvant chemotherapy consisted of two courses of high-dose (HD) methotrexate (MTX) followed by a course of cisplatin (CDDP) and adriamycin (ADR) as phase I chemotherapy. After phase I chemotherapy was completed, the response to induction chemotherapy was evaluated. If the treatment response was assessed as complete response (CR), partial response (PR), or stable disease (SD), four courses of HD-MTX and a course of CDDP and ADR were administered. In contrast, if the treatment was assessed on the basis of the response as “not effective, with progressive disease (PD),” the chemotherapy regimen was changed to HD ifosfamide (IFO). Toxic effects during chemotherapy were graded according to the Common Terminology Criteria for Adverse Events Version 4.0. Following neoadjuvant chemotherapy, tumors were assessed using response evaluation criteria in solid tumors (RECIST) after determining their sizes using CT and MRI. In the current patient, the swelling increased rapidly during the phase I neoadjuvant chemotherapy . CT and MRI also revealed marked progression of the lesion , and laboratory data showed marked elevation of serum alkaline phosphatase. On the basis of these data, we assessed the response to neoadjuvant chemotherapy as not effective, with PD. Therefore, the neoadjuvant chemotherapy was suspended and radical surgery took precedence before the lesion grew to an unresectable size. She was then treated with radical surgery consisting of a hemimandibulectomy and reconstruction using a free vascularized latissimus dorsi pedicle flap and rigid titanium reconstruction plate. On histologic examination, the tumor was composed of stellate cells, which were large and atypical . Highly atypical cells produced osteoid and immature bone. Moreover, chondroid matrices were also observed. Taken together, these findings indicated that the therapeutic response was poor, assessed as grade 0 (tumor necrosis area <90%). On postoperative day 25, adjuvant chemotherapy was started. Adjuvant chemotherapy was also performed in accordance with the NECO study regimen, with slight modifications. The adjuvant chemotherapy regimen included two courses of HD-IFO followed by a course of CDDP and ADR, and the same regimen was repeated for a total of three cycles. During chemotherapy, hematologic toxicities, grade 4 leukopenia, and thrombocytopenia were detected and the frequency of febrile neutropenia increased, requiring red blood cell and platelet transfusions and the use of granulocyte-colony stimulating factor. The treatment schedule and our patient’s clinical course are summarized in the Table . No evidence of local recurrence and distant metastasis was found at 14 months follow-up after initial treatment.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1010_en.txt

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+A 49-year-old woman at first consultation presented at our hospital for surveillance of the pancreas because her father (II-3) and her younger brother (III-6) had pancreatic cancer. She had undergone surgery for subarachnoid hemorrhage at 19 years of age because of an arteriovenous malformation. Her family tree revealed that her younger brother died of pancreatic cancer at 33 years of age; he could not be treated through surgery because of his advanced stage with distant metastasis. The patient’s paternal aunt (II-1) also died of pancreatic cancer at 65 years of age. Her father was also diagnosed with advanced-stage pancreatic cancer, which could not be controlled despite chemotherapy.
+In the first genetic counseling session, the patient was informed that she was likely to have FPC, Lynch syndrome, or HBOC syndrome, all of which follow an autosomal dominant inheritance pattern. Therefore, germline multi-gene panel testing using ACTRisk® (ACT Genomics, Co. Ltd. Taipei, Taiwan) was performed to analyze germline variants in this case.
+In the second genetic counseling session, we informed her that the blood genetic test revealed two germline variants. She harbored a heterozygous PALB2 pathogenic variant, NM_024675(PALB2): c.1675_1676inv (p.Gln559*), and a heterozygous NBN pathogenic variant, NM_002485(NBN): c.265C > T (p.Arg89*). These variants are predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Therefore, we advised her to undergo surveillance for breast, ovarian, and pancreatic cancer. Her father died 9 months after her first consultation; however, he had previously provided a blood sample to our department before his death to support her future healthcare. Accordingly, genetic testing of her father’s blood sample was recommended to her.
+In the third genetic counseling session, we explained that her father’s blood revealed the presence of the PALB2 c.1675_1676inv (p.Gln559) pathogenic variant, which was the same as hers. Furthermore, we informed her that her first-degree relatives (FDR) have a 50% chance of testing positive for these variants. Therefore, we recommended genetic counseling for her children at the next session, and she agreed.
+In the fourth genetic counseling session, the patient and her three children, a 28-year-old woman, a 24-year-old man, and a 22-year-old man, presented at our outpatient department. We explained to them that their mother and her father harbored the PALB2 pathogenic variant, which was probably associated with breast, ovarian, pancreatic, and prostate cancer. Furthermore, we informed them that their mother harbored the NBN pathogenic variant, which was potentially associated with breast, ovarian, and pancreatic cancer. Upon surveillance, no issue was noted in the cases’s breasts and ovaries; however, she displayed a branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) in her pancreas. We suggested she continue active surveillance of her breasts, ovaries, and pancreas. Furthermore, her 28-year-old daughter wished to undergo genetic testing because her uncle had died from pancreatic cancer at an early age. Therefore, we performed genetic testing at a single site for the patient’s daughter. Finally, the patient’s daughter underwent genetic counseling and was found to harbor only the NBN c.265C > T(p.Arg89*) pathogenic variant, which was probably associated with breast, ovarian, pancreatic cancer. Thus, the daughter will be recommended to undergo surveillance for breast, ovarian, and pancreatic cancer.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1033_en.txt

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+A 43-year-old woman accidentally found a right breast lump on March 2014, with a diameter of 2 × 2 cm and stabbing pain. The mass was not related to the menstrual cycle. There was no redness, swelling, or rupture of the skin near the lump. No erosion, stabbing pain, pruritus, or discharge of the nipple was observed. In 2016, the tumor became progressively enlarged, and a mass of 3 × 2 cm was found under the right axilla. In March 2017, there was pain in the right axilla with obvious tenderness. Physical examination determined with touch indicated a tough mass of 5 × 3 cm in the right breast (between 7 and 9 o'clock), and the lump was characterized by unpolished surface, obscure boundary, and poor activity. A soft mass of 4 × 2 cm was touched in the right axilla, and no obvious abnormality was found during the rest of the physical examination. Ultrasound examination suggested multiple solid masses in the right breast. The dimensions of the tumor determined between 6 and 11 o'clock were 5.3 × 3.4 cm, which was classified as BI-RADS 4C-5; the dimensions of the mass identified at 10 o'clock were 1.2 × 0.5 cm, which was classified as BI-RADS 4a. The dimensions of enlarged lymph nodes in the right axilla were 1.2 × 0.6 cm. Ultrasound-guided needle biopsy showed an invasive carcinoma of the right breast with fibroadenoma. Surgical treatment was performed on 9 March 2017. Intraoperative sentinel lymph node biopsy found metastatic cancer, and simplified radical mastectomy was performed for right breast cancer. Postoperative pathology showed non-specific invasive carcinoma of the right breast (invasive ductal carcinoma SBR II-III) and mucinous carcinoma of high to medium grade (intraductal carcinoma) of the dimension 3.5 × 1.5 × 3.0 cm, as seen in . The other three lesions were non-special invasive carcinoma (invasive ductal carcinoma SBR II), with the dimensions of 0.7 × 0.7 × 0.5 cm, 1.0 × 0.6 × 0.5 cm, and 1.0 × 0.8 × 0.5 cm. No metastasis was found in the right axillary lymph node (0/15). Positive immunohistochemical staining for ER, PR, HER-2, AR, P53, and Ki 67 was performed. The postoperative stage was pT2N2M0 IIIA, Lumina I B. The chemotherapy regimen was EC-TH chemotherapy, with 8 sessions of chemotherapy completed from April 7, 2017 to September 25, 2017.
+During the follow-up, corresponding examinations were made according to the patient's condition. Between the baseline and eighth chemotherapy sessions, ECG, cardiac ultrasonography and breast ultrasound, chest CT and upper abdomen CT, and ECT were performed in the following order: Chest CT, upper abdomen CT, and cardiac ultrasound were performed at baseline; ECG examination was performed after the first chemotherapy and the third chemotherapy. On the fifth chemotherapy session, none of the above examinations were performed. Chest CT, upper abdomen CT, cardiac ultrasonography, and breast ultrasound were performed during the eight chemotherapy session. Breast ultrasound results showed (1) a right breast surgery, (2) multiple cystic nodules in the left breast, and (3) no enlarged lymph nodes under both axilla and supraclavicular, and the rest of the examination results were normal. Degree II myelosuppression occurred during chemotherapy, and hematology returned to normal after treatment with granulocyte colony-stimulating factor (G-CSF).
+In this case, CMR examinations were performed at the beginning of the first chemotherapy (baseline) and after the third, fifth, and eighth chemotherapy sessions, using a 3.0 T magnetic resonance imager (platform HDxt; General Electric Medical Systems, Waukesha, WI) equipped with an 8-channel phased-array cardiac coil. Standard 2-, 3-, and 4-chamber and left ventricle (LV) short-axis cine images from apical to basal were acquired with fast imaging employing a steady-state acquisition sequence. IVIM imaging was performed with the echo planar imaging (EPI) sequence. LV structural and functional parameters were measured by the Qmass package (Medis® Suite MR), as seen in . IVIM parameters were obtained by using GE Functool 9.4.05a software, as seen in . Cine images of 4-chamber, 2-chamber, left ventricle (LV) short-axis and IVIM images of baseline are shown in . IVIM images of the third, fifth, and eighth chemotherapy sessions are shown in .

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1067_en.txt

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+A 62-year-old woman, G1P1, was referred to a gynecological doctor for a large “vaginal mass”. She did not have abnormal vaginal bleeding but found one vaginal mass by herself 1 month ago. Her age at the beginning of menopause was 52 years old. Her medical and surgical histories were both negative. On gynecological examination, we found that the mass was non-mobile and was 5 × 5 cm2 in size, with a location of approximately 3 cm from the vaginal orifice and closely attached to the vaginal wall. On rectal examination, we found that the mass located on the anterior of the rectal wall was approximately 3 cm from the anal verge. The pelvis MR scan and transvaginal ultrasound results showed a tumor, 5 cm in diameter, was mostly located in the space of the rectovaginal septum, with large portion protruding into the vaginal wall but only a small portion protruding into the rectal wall. Its boundary is clear . Colonoscopy revealed that the root of the tumor was located on the rectal dentate line . The origin of the tumor was uncertain. Based on these examinations, the gastrointestinal doctor and us co-evaluated that if we selected a transvaginal resection, we could intactly excised the tumor with less possible complications such as fecal incontinence or anal sphincter dysfunction due to its special location. The patient refused to radical anal resection for its anal complications. Therefore, we chose transvaginal resection as a better alternative. Under general anesthesia, the patient was placed in a lithotomy position. Epinephrine, diluted at 1:40,000, was injected into the vaginal submucosa for resection. We incised the vaginal mucosa and separated the surrounding tissue until we reached the submucosa, keeping the tumor capsule intact. After exposing the tumor, we confirmed that it was located in the rectovaginal septum and partially encapsulated by the rectal muscle . We mobilized the tumor from the capsule and resected the intact tumor. The defect of rectal muscle was very small but kept the rectal mucosa intact. We vertically stitched the vaginal layers and horizontally stitched the muscular layer of the rectum . The postsurgery biopsy showed spindle-shaped cells were moderate differentiation and regular arrangement with clear margin by pathological examination . The results of histological examination showed that the tumor was positive for CD117, Dog-1, and CD34 . These findings suggest a moderate-risk rectal GIST that required follow-up. The patient recovered quickly. She had not suffered any anal dysfunction nor postoperative vaginal-rectal fistula. She refused to undergo enlarged resection but received imatinib treatment after surgery. She remained tumor-free for 2 years after surgery. She was lost for follow-up thereafter.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1068_en.txt

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+A 69-year-old woman developed a sudden drooping on the left side of the face while having dinner with her family. Her daughter noticed slurred speech and alerted emergency medical services immediately. The patient was pre-announced to the stroke service by the responding emergency medical technician and immediately admitted to the emergency room. Her home medication consisted of pantoprazole only. Upon admission to the emergency room, the patient was alert but slightly confused. Further neurological examination revealed a left-sided hemiparesis and motor speech disorder. The remaining cranial nerves were unaffected. No sensory or coordinative dysfunctions were detected. Muscle stretch reflexes revealed no lateral differences, and plantar reflexes were normal (NIHSS score: 4 points). Shaved hair over the right temple exposed a well-healing, 10-cm-long recent wound. The patient reported having had brain surgery two weeks earlier, but upon further questioning denied a preceding trauma, infection, tumor disease, or cerebral bleeding.
+The non-contrast computed tomography (CT) imaging revealed hypodense areas in the circulation of the middle cerebral artery (MCA) with territorial pattern (mainly pre-Rolandic, but also Rolandic, parietal, and insular branches), moderate swelling, and hemorrhagic transformation of the anterior portion (see Fig. ). A vascular clip in projection on the middle cerebral artery was visible. There was no sign of a subarachnoid hemorrhage (SAH). The CT-angiography revealed no high-grade stenosis or vessel occlusion of the cerebral blood flow in the area of the right middle cerebral artery, even though the presence of a vascular clip reduced reliability of assessment. The cerebral duplex ultrasonography/transcranial Doppler sonography (TCD) showed, in contrast to the left side, markedly increased blood flow velocities in the right MCA with mean values up to 180 cm/s (Vmax up to 300 cm/s), while the blood flow in all of the other cerebral arteries was undisturbed. The increased velocities were traceable along the entire M1 segment as well as in the M2 segments of the right MCA. In contrast to the preoperative transfemoral catheter angiography (TFCA), the subsequent right internal carotid angiogram showed clear signs of vasospasm along the M1 and M2 segments of the right MCA (see Fig. ). However, neither delayed cerebral blood flow nor hypoperfusion were found. A vessel narrowing with consecutive stenosis due to a suboptimally placed clip was ruled out.
+The patient’s recent medical history included the microsurgical treatment of a right-sided MCA aneurysm 12 days prior. The patient had never experienced any episodes of uncommon or severe headaches. The unruptured intracranial aneurysm (UIA) was found incidentally via magnetic resonance imaging ordered after the patient complained of a short period of slight gait disturbances. To avoid an SAH and consecutive complications like vasospasms, the patient elected surgical treatment (see Fig. ). Endovascular management was not feasible due to the configuration of the aneurysm. The review of the operative report and the medical discharge letter attested to an uneventful perioperative course. Clipping was managed by keyhole approach. A craniotomy 30 mm in diameter was performed over the right Sylvian fissure. The aneurysm was dissected after securing proximal control of the distal M1 segment of the right MCA. Temporal clipping of the M1 was not necessary. After clip placement, appropriate flow in all distal segments was confirmed by indocyanine green video-angiography and micro-Doppler. The postoperative imaging showed no sign of decreased cerebral blood flow. The patient was discharged seven days after surgery without neurological deficits. No other vascular diseases were known.
+After admission antithrombotic treatment with acetylsalicylic acid was begun. In accordance with guidelines for the treatment of subarachnoid hemorrhage and vasospasm, nimodipine was added. Periodically performed transcranial duplex sonography showed a further increase of blood flow velocity in the MCA and its branches for four days before a continuous decrease and normalization of flow velocity was observed. Treatment with nimodipine was continued for an additional two weeks. Within this time the symptoms disappeared completely. The patient made a full recovery, which is remarkable in such a major stroke. After 11 days the woman was discharged with no symptoms.

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+A 54-year-old man, heavy smoker without underlying disease, was admitted to the local hospital due to progressive weakness of the lower extremities for 1 month. He had no history any injury. Three months earlier, he experienced low back pain radiating to both legs, predominantly affecting the left side. Furthermore, difficulty in urination and constipation were observed 1 week before admission. Magnetic resonance imaging (MRI) of the lumbosacral and thoracic spine revealed abnormal hyperintense T2 signal, representing spinal cord congestion, extending from the conus medullaris to the level of T7. There was abnormal tortuous and dilated flow void, running from the level of L5 to T12 along anterior surface of the spinal cord . A preliminary diagnosis was SDAVF. The patient was transferred to our institute and admitted for further investigation. The neurological examination revealed the evidence of spastic paraparesis (muscle strength 4/5), the lack of pinprick sensation below L2 level, hyperreflexia, and presence of Babinski sign in the lower extremities.
+Spinal angiography demonstrated the fistula at the level of L2 below the conus medullaris, which is supplied by the PSA originating from the left L1 segmental artery with cranial drainage through the paralleling dilated vein into perimedullary vein. Without selective catheterization into both internal iliac arteries, lower aorta and bilateral common iliac arteries angiography reveals no more supply to the fistula . The ASA arose from the left T6 intercostal artery without supplying to the fistula. Initially, we interpreted that this fistula was filum terminale AVF (FTAVF) which is fed by the ASA supplying from the PSA via the vasa corona. Due to small and long distance of the feeder, the patient underwent surgical treatment. On prone position, total laminectomy of L2 and partial laminectomy of L3 were carried out. After durotomy, the filum terminale (FT) was identified and no fistula or abnormal vessels on it. The fistula is located on the left cauda equina nerve root supplied by the proximal radicular artery with cranial drainage through the enlarged radicular vein. Another enlarged arterialized radicular vein running parallel to another cauda equina nerve root is observed with unknown origin . To avoid nerve root injury by heat, the dilated proximal draining vein near the fistula on the cauda equina nerve root was clipped with small silver clips without using bipolar coagulation. Another radicular vein was left for further investigation. After the operation, the patient showed mild improvement of his symptoms. He could walk with the aid of a walker. He was discharged home 7 days later due to his requesting to do some personal issues at home.
+Follow-up MRI and contrast-enhanced MR angiography (MRA) of the thoracolumbar spine, obtained 3 weeks after the operation, revealed mild regression of spinal cord congestion, and remaining of intradural flow void from L5 to L2. Another SDAVF was found at left S1 neural foramen supplied by the left lateral sacral artery (LSA) originating from the left internal iliac artery with venous drainage into perimedullary veins through the dilated and tortuous radicular vein, probably corresponding with another dilated arterialized radicular vein found during the operation [ and ]. Comparing between preoperative the left L1 segmental artery angiography and postoperative contrast-enhanced MRA, there was the same venous drainage pattern, representing sharing the common medullary venous channel . Spinal angiography and probable embolization in the same setting were scheduled for another week. Few days before hospitalization for further treatment, the patient developed loss of consciousness at home and was sent to the emergency department of the local hospital and intubated promptly. Few minutes later, the patient had a cardiac arrest. Immediate cardiopulmonary resuscitation was performed unsuccessfully. Without an autopsy, the cause of death was still unknown.

data/test_raw_data/en_test/multiclinsum_test_en/fulltext/multiclinsum_test_1072_en.txt

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+An 8 year old girl with tufting enteropathy on long-term parenteral nutrition presented on 3 occasions with central venous catheter infection due to Bacillus species. On each occasion, she had fever after flushing of the central venous catheter. She had initially presented in the first few months of life with chronic watery diarrhoea and impaired growth, and was found to have tufting enteropathy (intestinal epithelial dysplasia) . This is a rare congenital enteropathy, which requires indefinite dependence on parenteral nutrition from early infancy. The child is on regular parenteral nutrition and has had no previous history of significant infections, except for central venous catheter infections with coagulase negative staphylococci. Immunoglobulins, neutrophil and lymphocyte counts were within the normal range. There was no history of significant trauma, injuries or skin infections prior to this episode, except a small cut on her finger which healed very well and was generally well in herself. She lives with her parents and is well cared for. There is no history of contact with plant growth products or animal probiotics at any time.
+The child presented with fever and rigors to her local hospital. Bacillus species was isolated from blood taken from the central venous catheter, which was reported sensitive to flucloxacillin. She was treated with 4 weeks of intravenous flucloxacillin because bacteraemia had persisted despite 14 days of treatment.
+The child was transferred to our hospital with recurrence of fever and rigors, 10 days after stopping the antibiotics. Empirical treatment was started with intravenous cefotaxime and flucloxacillin. Bacillus species was isolated from central venous catheter cultures both before and whilst on cefotaxime and flucloxacillin. This was later identified as Bacillus pumilus at the National Reference Laboratory (Health Protection Agency, Centre For Infection, London). The methods used to identify the organism were gram stain to determine whether spores are produced, short biochemical profile based on ammonia salt sugars, Lecithinase and mannitol (B. pumilus is lecithinase negative and mannitol positive) and DNA sequencing. B pumilus was reported to be sensitive to vancomycin and erythromycin. There were concerns that the patient had previously reacted to systemic vancomycin, so antibiotics were changed to intravenous clindamycin with vancomycin line locks given for 2 weeks. Blood cultures, taken both during and after this treatment, were negative. Echocardiography showed no evidence of vegetations at the tip of the catheter or in the heart.
+Ten days after stopping the intravenous antibiotics the child presented for the third time with fever and rigors. A Bacillus species was again grown from blood taken from the central venous catheter. The central venous catheter was removed after 5 days treatment with intravenous vancomycin and a new central venous catheter was inserted. Subsequent blood cultures were negative and there has been no recurrence of further fever or infections over a 9-month period, suggesting the infection has been eradicated.

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+A 68-year-old female underwent phacoemulsification + intraocular lens implantation + pars plana vitrectomy (PPV) + ILM peeling + 18% sulfur hexafluoride (SF6) tamponade in January 2016 due to an epiretinal membrane and a lamellar MH. Unfortunately, macular hole retinal detachment (MHRD) occurred one month after surgery. She received PPV + extended ILM peeling + silicone oil tamponade in February 2016 and underwent removal of silicone oil in October 2016. The retina had attached well, although the MH became refractory, and her best-corrected visual acuity (BCVA) was 20/500. She underwent two PPV + free ILM flap transplantation + 15% C3F8 treatments in April 2017 and July 2017, with unsatisfactory results. Due to her repeated surgeries, an autologous free ILM flap could not be harvested. We decided to perform a neurosensory retinal free flap transplantation for the repair of this refractory MH after discussion with the patient.
+A standard 25-g, 3-port PPV (Constellation; Alcon) was performed under general anesthesia. Endolaser photocoagulation was applied to outline the retinal free flap at the temporal retina. The neurosensory retinal free flap was approximately twice the diameter of the MH. The retina was cut with vertical scissors along the inner edge of the laser spots and was gently dissected with back-flush needle irrigation until a neurosensory retinal free flap with a 2-MH diameter area was harvested. The infusion was stopped temporarily to prevent turbulent flow. A drop of whole blood was placed within the MH, and the neurosensory retinal free flap was then placed on the blood. We performed fluid-gas exchange and flushed the vitreous cavity with 15% C3F8 at the end of the surgery . All of the techniques were performed under standard 25-g, 3-port PPV. We did not use a bimanual approach under chandelier illumination (see Additional file ). The patient was instructed to maintain a prone position for 14 days postoperatively and to avoid any unnecessary movement.
+Three weeks after surgery, optical coherence tomography (OCT) revealed closure of the MH. The flap was visible on OCT and had filled the MH without overlapping of the neurosensory retina. The 2-month postoperative OCT examination still showed the MH closure. The patient reported an improvement of visual acuity and a decrease in her scotoma area. The patient’s BCVA improved from 20/500 preoperatively to 20/50 at 2 months postoperatively.

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+A 45-year-old woman presented with a thyroid mass and thrombosis in a middle thyroid vein during a physical examination.
+The patient came to hospital because of thyroid mass found in physical examination 3 mo before. She had no symptoms. The patient requested surgery because of the stress.
+The patient was health in the past.
+The patient had no family history of thyroid carcinoma and no history of radiation exposure in childhood.
+The physical examination showed no positive signs.
+Laboratory tests showed that triiodothyronine, free triiodothyronine, thyroxine, thyroglobulin, and thyroid-stimulating hormone levels were within the normal limits.
+A solid nodule in the left lobe of the thyroid by ultrasound examination. Ultrasound examination revealed a medially echoic mass in the middle thyroid vein.
+Subsequent ultrasonography-guided fine-needle aspiration biopsy results indicated an atypical lesion of ambiguous significance, with some actively growing cells (TBSRTC III) and the BRAFV600E mutation not present.

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+A 91-year-old woman presented to our institution with ST-segment elevation myocardial infarction (STEMI). The right radial access was chosen for the performance of percutaneous coronary intervention (PCI). After the introduction of 6 F sheath, there was difficulty in the advancement of 0.035 J wire that was exchanged with a Terumo hydrophilic wire (0.035 × 180) which was advanced easily to the aortic root. Coronary angiography was done and revealed tortuous coronary arteries without significant lesions. Before sheath removal, radial arteriography was done and revealed perforation . Protamine sulfate (1 mg per 100 USP units of heparin) was administered intravenously to reverse the dose of heparin (70 U/kg), and APTT was monitored 15 min after the dose. This was followed by prolonged balloon inflation 2.5/3.0 . The perforation was not sealed so a 7-F-long vascular sheath was inserted to internally tamponade the vessel, and the patient was sent to the coronary care unit for monitoring of the forearm hematoma and the distal pulses . Over the next 3 days, serial radial angiographies were done which revealed the persistence of the perforation. After 4 days, angiography revealed multiple thrombi , and thrombus aspiration was done using Pronto V4 extraction catheter (Vascular Solutions, USA) and was followed by the implantation of a covered stent, which was dislodged, mostly secondary to under expansion, following another run of thrombus aspiration. The stent was successfully snared . Finally, the perforation was sealed spontaneously and there were no signs of intra-arterial thrombi .

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+A 33-year-old Caucasian woman, gravida 3, para 1, was admitted to our clinic. Her obstetric history mentioned a miscarriage and a pregnancy complicated by intrauterine growth restriction, without signs of preeclampsia. At 37 weeks' gestation, cesarean section was performed because of fetal distress. A boy was delivered, weighing 2015 g, with Apgar scores of 9 and 10 at one and five minutes, respectively. Histology of the placenta revealed 10% infarctions and a thrombus in the umbilical cord. Blood analysis after three months showed no hemostatic abnormalities associated with an increased risk of thrombosis.
+Ultrasound examination of the index pregnancy at 112 weeks' gestation showed a dichorionic diamniotic twin pregnancy with measurements consistent with gestational age. The Crown Rump Lengths were 39 mm, consistent with 106 weeks, and 45 mm, consistent with 112 weeks. Nuchal translucency thickness measurements were not performed. No abnormalities of the placenta were documented.
+Her blood pressure was 125/70 mmHg. The pregnancy was complicated by episodes of vaginal bleeding at 16 weeks' gestation. Ultrasound showed one fetus with normal growth and one with early growth restriction and measurements consistent with 13 weeks. An echogenic area was interpreted as blood clots. At 20 weeks' gestation, fetal death of the abnormal fetus was noticed. One week later, the patient was asymptomatic but her blood pressure increased (154/98) which prompted the suspicion of a partial molar pregnancy. An enlarged placenta of 10 cm × 12 cm with some cysts was prominent on the anterior wall. Blood flow had ceased in this placenta. Urinary protein excretion was 2.5 g/L. Maternal serum beta-human-chorionic-gonadotropin (β-hCG) was markedly raised: 423,000 IU/L. Other laboratory investigations were normal.
+The patient was sent to a University Hospital because of early preeclampsia and suspicion of a triploid twin. We decided to perform a chorionic villous biopsy because the placenta of the dead fetus was on the anterior wall. We did not perform a chorionic villous biopsy of the placenta of the healthy twin because no abnormalities were noticed by ultrasound and the placenta was located on the posterior wall.
+Chorionic villus biopsy confirmed triploidy, 69, XXY. Without pharmacological interventions, the blood pressure stabilized, proteinuria decreased, and β-hCG decreased to 222,835 IU/L. At 22 weeks, the patient was discharged. She was reviewed twice a week. Urinary protein excretion was positive until 23 weeks, and blood pressure slowly decreased and normalized at 30 weeks. The β-hCG further decreased to 27,600 IU/L at 33 weeks. Episodes of some vaginal bleeding and cramps occurred up to 28 weeks' gestation. The placenta of the triploid twin was still enlarged until 23 weeks: 8 cm × 12 cm .
+At 35 weeks, the patient developed preeclampsia again and was hospitalized. Her blood pressure increased to 170/105 mmHg and proteinuria to 0.8 g/L. Methyldopa 3 × 250 mg was initiated to control the blood pressure with good result . Blood analysis showed no signs of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. At 38 weeks, a cesarean section was performed for fetal distress. A healthy girl weighing 2,710 g was born with Apgar scores of 9 and 10 at one and five minutes, respectively. The placenta of the triploid fetus was necrotic and as a result of autolysis, no further histologic information on fetus and placenta were available. β-hCG follow-up showed no signs of persistent gestational trophoblastic disease (pGTD). Four days after delivery, the level had already decreased to 440 IU/L.

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+A 79-year-old Japanese woman with a leg oedema visited her primary care physician, 3 months before being admitted to our hospital. Outpatient treatment with diuretics was initiated, but the oedema did not improve. Three days before admission, she experienced palpitations and fatigue, prompting her to again visit her primary care physician. Her laboratory data showed severe anaemia (haemoglobin [Hb], 58 g/L). Hence, she was subsequently admitted to our hospital.
+She had no specific medical or any family history of renal disease. Physical examination revealed moderate leg oedema and kyphosis and no other indications of amyloidosis, such as numbness or signs consistent with polyneuropathy, gastrointestinal symptoms, macroglossia, orthostatic hypotension, purpura, or any changes to the skin. Laboratory data revealed microcytic anaemia (Hb, 50 g/L; mean corpuscular volume, 85.9 fL), hypoalbuminemia (albumin, 2.8 g/dL), and a possible slight decline in kidney function (serum creatinine, 0.64 mg/dL; estimated glomerular filtration rate, 66.9 mL/min/1.73 m2). Serum IgG, IgA, and IgM levels were 794 mg/dL, 1006 mg/dL, and 48 mg/dL, respectively. The serum free light chain (FLC) level for kappa and lambda was 77.4 mg/L and 15.2 mg/L, respectively, and the FLC ratio was 5.09. The brain natriuretic peptide level was 72.7 pg/mL. She also had iron and zinc deficiency. Serum and urine electrophoresis revealed the presence of IgA-kappa type M proteins (immunofixation method; Fig. ). Serum β2-microglobulin was 4.6 mg/L. Bone marrow aspiration revealed a slight proliferation of plasma cells (6.8%). Urinalysis revealed an occult haematuria (1 +) and moderate proteinuria (1.34 g/gCr). Electrocardiography and cardiac ultrasound did not show any changes consistent with cardiomyopathy associated with amyloidosis, such as low voltage, thickening of the ventricular wall, or granular sparkling appearance. The chest radiograph revealed a slight bilateral pleural effusion, and the cardiothoracic rate was deemed to be 56.5%. For treating severe anaemia, red blood cell transfusion was administered in conjunction with iron and zinc supplementation, resulting in an improvement in anaemia (Hb 95 g/L) and her subsequent discharge. After discharge, her urinary protein increased to 5.7 g/gCr, and serum albumin decreased to 2.8 g/dL. The patient was then diagnosed with nephrotic syndrome and a renal biopsy was performed.
+Light microscopy revealed methenamine-positive deposits in the mesangial and paramesangial regions . Some glomeruli were accompanied by segmental sclerosis caused by the deposits. Interstitial fibrosis and tubular atrophy were mild. Immunofluorescence staining was positive for IgA and kappa chains in the expanded mesangial area . The tubular basement membrane was partly granular and positive for kappa chains. Additional Congo red staining showed mild positivity in the glomerular deposits, but only faint birefringence. Immunohistochemical staining of the kappa chains was mildly positive . Furthermore, electron microscopy was conducted with formalin-fixed specimen to evaluate glomerular deposits, which revealed unbranched fibrils in glomerular deposits measuring 10–15 nm .
+LMD-LC–MS/MS revealed that the deposits consisted significant amounts of the kappa constant region of immunoglobulin. Additionally, a small amount of the alpha-1 constant region was also detected along with amyloid-associated proteins . Details of the detected protein and an illustration of globulin are presented in Fig. . The emPAI (exponentially modified protein abundance index) is often used as an index for estimating protein abundance during proteomic analyses using mass-spectrometry. The emPAI value represents the relative amount of each protein contained within the sample . Therefore, a higher value emPAI is indicative of a larger amount of protein, compared to the other proteins in the sample.
+Based on the above findings, the patient was diagnosed with LHCDD and focal amyloid deposition. Skin biopsy did not show amyloid deposition, while gastrointestinal biopsy revealed faint birefringence, suggesting that the patient had systemic amyloidosis. Bone marrow aspiration was repeated, which revealed an increase in the plasma cell population (14.4%). The increase in plasma cell population and a concurrent anaemia indicated multiple myeloma . She did not however present any other myeloma-defining events, such as hypercalcemia, decline in renal function, and bone legions. We started cyclophosphamide 300 mg/m2/day, bortezomib 1.3 mg/m2, and dexamethasone treatment 20 mg/week followed by weekly administration of daratumumab (1, 800 mg/week). After 9 months of treatment, proteinuria improved from 8.0 to approximately 5.0 g/gCr in the absence of decrease in eGFR, indicating a renal response . Serum albumin concentration also gradually increased, leading to a reduction in leg oedema. The reduction in serum M-protein (IgA 467 mg/dL) and the difference between involved and uninvolved FLC (dFLC; 20.8 mg/L) was greater than 50%, but less than 90% (haematological partial response ).

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+A 43-year-old woman visited the Department of Obstetrics and Gynecology because of fluid collection in her cul-de-sac that was incidentally found 6 months ago at a routine health check. She did not complain of any other symptom except for dull abdominal discomfort. During physical examination, a mass-like hardness could be palpated on the level above the umbilicus. Routine blood analysis was within normal limits.
+A computed tomography (CT) scan of the abdomen was performed, and it revealed a 9.0-cm enhancing mass in the omentum at the right upper quadrant of the abdomen. The mass showed a relatively demarcated margin and some minute cystic changes. The radiologist thought the mass was a gastrointestinal stromal tumor (GIST) or neurogenic tumor. Additionally, there was a noted 2.5-cm corpus luteal cyst in the left ovary but otherwise there were no other abnormalities in the abdominal and pelvic cavities. The clinicians decided to excise the mass due to its huge size and to accurately diagnose the tumor.
+In the operative field, the mass was located around the distal antrum along the greater curvature of the stomach but was easily separated from the stomach wall itself. On the other hand, it was densely adhered to the omentum and mesocolon. The tumor was far away from the reproductive organs, such as the uterus and both ovaries, and urinary structures.
+On gross pathological examination, the excised mass measured 9.5 × 8.0 × 7.5 cm. On sectioning, the cut surface of the mass was yellow pink and showed a solid lobular portion and focal small cystic areas. Its margin was well demarcated from the attached omental fat tissue .
+Microscopically, the tumor showed two histologic components. The first cellular part consisted of well-defined nests of round or polygonal epithelial cells and numerous ill-defined lobular islands of epithelial cells with short spindled features . The nests of polygonal epithelial cells were intimately related to the surrounding epithelial cells with short spindled features . In the well-defined nests, the epithelial cells had elongated nuclei and rather pale eosinophilic cytoplasm. Characteristically, many cells showed a longitudinal groove in the nuclei and frequent perinuclear haloes . Their cytologic features were similar to that of normal urothelial cells. Some nests showed cystic changes of varying degrees . The epithelial cells with short spindled features were arranged into ill-defined lobules or scattered singly and showed poorly defined cytoplasmic outlines . In the nuclei, the nuclear chromatin was fine and the nucleoli were small or inconspicuous. The cells also displayed occasional nuclear grooves. Neither cytologic atypia nor mitotic activity was noted in both types of cells. The second component was densely hyalinized fibrous stroma occupying areasbetween the cellular parts. The microscopic features of this tumor as a whole closely resembled an ordinary ovarian Brenner tumor.
+We performed immunohistochemistry on a Leica Bond-Max automatic slide immunostainer (Leica Biosystems Melbourne Pty., Ltd. VIC, Australia) using a standard protocol. The list of antibodies used is as follows: calretinin (Novocastra, diluted 1:200), CK7 (NeoMarkers, 1:400), CK20 (Novocastra, 1: 100), pancytokeratin (Novocastra, 1:100), CD10 (Novocastra, 1:150), CD34 (DAKO, 1:400), DOG-1 (Cell Marque, 1:250), c-KIT (DAKO, 1:300), p63 (Novocastra, 1:100), PAX-8 (Cell Marque, 1:200), SMA (DAKO, 1:400), vimentin (Zymed, 1:200), WT-1 (DAKO, 1:100), uroplakin-III (Cell Marque, 1:50), and GATA-3 (Cell Marque, 1:100).
+The cellular parts, including the urothelium-like cells and spindled epithelial cells were positive for pancytokeratin, p63, and WT-1 but negative for CD34, CD10, CK20, calretinin, c-KIT, DOG-1, and PAX-8. The urothelium-like cells were positive for CK7 but the spindled epithelial cells were negative. The cytoplasm of the urothelium-like cells was weakly to moderately positive for uroplakin-III, and their nuclei were diffusely strongly positive for GATA-3. The immunoprofiles of the urothelial-type cell nests in this tumor were the same as those of ovarian Brenner tumors. The spindled epithelial cells were negative for both uroplakin-III and GATA-3. The stromal cells only showed focal positivity for SMA .
+Using a representative paraffin block of the tumor, we performed mutation analyses for exons 9, 11, 13, and 17 of the c-KIT gene by polymerase chain reaction (GeneAmp PCR System 2700, USA) using a direct sequencing method (Applied Biosystems 3500 Genetic Analyzer, USA). The results of the c-KIT gene mutation analyses were negative.
+After surgery, the patient had recovered well and showed no recurrence during the 17-month follow-up.

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+A 65-year-old man with severe, symptomatic AS was referred to our heart team. The preoperative echocardiography showed a severely degenerated bicuspid AS with a mean gradient of 41 mmHg (LVEF 47%). With an estimated mortality of 10.12% (Euroscore II) based on various severe co-morbidities, the heart-team recommended an interventional aortic valve approach. Because of furthermore severely calcified and stenotic iliac arteries, an approach via left subclavian artery was chosen using a self-expandable valve (Evolut pro+; Medtronic, Minneapolis, Minnesotta, USA).
+The procedure was performed in a hybrid operating room under general anesthesia. A transesophageal echocardiography (TEE) probe was inserted for periprocedural valve assessment. Via an incision in the infraclavicular fossa the left subclavian artery (8 mm in diameter) was exposed and an 8 mm Dacron tube was grafted for vascular access. The delivery sheath was introduced into the Dacron tube without passing the artery. By advancing the TAVI prosthesis under fluoroscopy within the subclavian artery an impediment at the level of the vertebral artery was sensed. The prosthesis was retracted and the location radiographically inspected. There was no severe kinking or harm to the vessel detected. Hence, the valve was reinserted and under slight resistance positioned in the annulus. After uneventful deployment of the prosthesis, function was assessed with TEE. It showed a 6 cm floating cylindrical structure in the course of the TAVI-prosthesis (Additional file ). Suspecting some intravascular damage, a control angiogram was performed, displaying a filling defect of the subclavian artery . We suspected an intimal tear caused by the valve insertion with subsequent dislocation and fixation in the struts of the TAVI-prosthesis. Since this highly mobile structure was considered to be potentially embolic, we proceeded to surgical extraction via sternotomy. Under CPB a median sternotomy was performed and routine cannulation for cardiopulmonary bypass was initiated. After aortic cross-clamping and cardioplegic arrest, aortotomy was performed. The intraoperative inspection revealed an intimal cylinder of the left subclavian artery nailed by the valve stent into the annulus, subsequently being completely removed leaving the correctly implanted TAVI in situ. Postoperatively, valve function (no regurgitation and a mean gradient of 2 mmHg) and blood circulation of the left arm were uncompromised.
+Yet, on postoperative day 4 absence of pulsation of the left-sided radial artery occurred. The CTA scan showed a dissection flap in the proximal left subclavian artery and distal contrast loss . Catheter-based vascular intervention with Fogarty balloon-removal of the dissected intimal flap was performed. Postoperative control revealed return of peripheral pulse on the radial artery . Further postoperative course was uneventful. The patient presented no new cardiac, vascular or neurologic sequelae at discharge.

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+In November 2017, an asymptomatic 14-year-old boy referred to the authors’ hospital for management of right lateral chest wall mass discovered incidently one month earlier. There was no history of trauma. Clinical examination was unremarkable. Plain chest radiography showed a smooth-walled 6.0 × 3.5 cm homogenous right lateral chest wall mass (A). Computed tomographic (CT) scan revealed right lateral extrapleural soft-tissue mass 6.5 × 4.0 × 5.6 cm in size abutting 5th and 6th ribs and filling the 5th intercostal space (B). There were neither cavitation nor calcification within the mass, and the adjacent ribs were not eroded.
+Magnetic resonance imaging (MRI) revealed right extrapulmonary and extrapleural chest wall soft tissue mass. Tl-weighted MRI demonstrated a solid mass with a low signal intensity (C), while T2-weighted MRI demonstrated a homogeneous mass with high signal intensity similar to that of fat tissue (D). Early phases after administration of contrast, showed characteristic heterogeneous enhancement of the tumor that became more uniform during the delayed phase (E and F).
+The angiogram showed a sizeable vascular mass supplied by a branch of the internal mammary artery. That branch was subsequently embolized with Gelfoam pledgets with no further filling on the post-embolization arteriogram.
+The patient underwent an exploratory video-assisted thoracoscopy (VAT) through the right 8th intercostal space anterior axillary line (A and B). Posterolateral thoracotomy revealed well-demarcated mass abutting the 5th and 6th ribs filling the right 5th intercostal space. En bloc resection of the mass involved ribs and the intercostal muscles were performed (C). Chest wall defect was reconstructed using polytetrafluoroethylene (PTFE) patch (GORE-TEX®, DUALMESH®, W. L. Gore & Associates) (D).
+The surgical specimen measured approximately 6 × 4 × 3.5 cm, which included a hemorrhagic, highly vascular, mass that extended from the intercostal muscles to the extra-pleural space (E). Cut section revealed whitish homogenous material. Microscopically, there were homogeneous thick and thin-walled blood vessels with proliferating vascular spaces of capillaries of the cavernous type with intervening fibrous stroma (F). There was no evidence of recurrence at 3 and six months of follow-up.

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+A 37-year-old woman was presented to the emergency room with abrupt severe right upper abdominal pain. The pain was squeezing and started suddenly after breakfast. The pain was not accompanied by vomiting or fever. The patient had previously been treated at the Department of Medicine in Samsung Medical Center with a diagnosis of EGPA. After successful suppression of blood hypereosinophilia with combination of prednisolone and azathioprine in recent months, she had been in the process of tapering prednisolone down to 15 mg per day. However, after dose reduction, her eosinophil counts slowly increased to 1989 cells/µL and levels of aspartate aminotransferase and alanine aminotransferase were elevated from normal to more than 300 U/L with mild abdominal pain. Consequently, her dose of prednisolone was raised back to 60 mg per day. While waiting for admission for further evaluation, abdominal pain brought her to emergency room.
+Five years ago, her first visit was prompted by symptoms of sinusitis, rash and eosinophilia. Three months later, numbness and cutting pain in both upper and lower extremities with fever, myalgia, and asthma developed. A nerve conduction study suggested multifocal sensorimotor neuropathy. Biopsy of the sural nerve revealed ischemic change resulting from vasculitis with prominent eosinophilic infiltration. Although perinuclear anti-neutrophil cytoplasmic antibodies were not detected, the patient was diagnosed as EGPA. After repeated intravenous cyclophosphamide pulse therapy with a high dose of systemic steroids, most symptoms were resolved. Sinusitis, presented as an initial symptom, improved after treatment at an early stage and otolaryngologic complication did not appear afterwards.
+However, whenever the tapering a dose of steroids was attempted, she developed new symptoms such as myalgia and arthralgia. She even experienced dry gangrene in the fingertips of both hands because of arterial thrombosis when her eosinophil count increased up to 6000 cells/µL . Duplex scan for arteries and veins indicated the total occlusion of the right distal ulnar artery and left medial forearm ulnar artery. The study also revealed a total occlusion of both mid-anterior tibial arteries, whereas toes of both feet were intact as other vessels of lower extremities were not involved. Hypercoagulability was thought to be caused either directly or indirectly by hypereosinophilia. We recommended mepolizumab, a monoclonal antibody to interleukin-5 used to interrupt eosinophil production, to reduce eosinophil count. But the patient refused it because of cost. We added aspirin and calcium channel blockers after cardiologic consultation. After the affected fingers were dried up, necrotized fingertips were amputated by orthopedic surgeon.
+Initial vital signs in the ER showed a blood pressure of 85/45 mmHg, a heart rate of 98 beats per minute with a temperature of 36.1’C, and a respiratory rate of 16 breaths per minute. Physical examination revealed mild tenderness in the right upper abdomen without rebound tenderness. The complete blood count revealed leukocytosis of 17,660 white blood cells/µL. Absolute eosinophil count was 1120 cells/µL. The erythrocyte sedimentation rate was 29 mm/hr, CRP was 3.7 mg/dL and total immunoglobulin E was 107 kU/L.
+An abdomen-pelvis CT demonstrated subcapsular hematoma in the right hepatic lobe . Hemoperitoneum probably caused by multifocal hepatic capsular arterial bleeding was also detected. There was no evidence of bowel perforation. In a previous CT scan taken 1 year before, there had been no evidence of any aneurysm changes in the hepatic vessels. A celiac angiogram demonstrated multiple, various sized hepatic aneurysms in both lobes . The small aneurysms resembled the appearance of a string of beads, characteristically observed in polyarteritis nodosa (PAN). Huge aneurysms larger than 1 cm in size were noticed in S7 and S8. Emergency embolization was performed. The huge aneurysm and the aneurysms with bead-like appearance in S7 and S8 were successfully occluded. Although several small aneurysms in S5, S6 and the left lobe still remained, no further embolization was performed to conserve hepatic function.
+Meticulous review of the abdomen-pelvis CT did not reveal evidence of aneurysms in other abdominal organs. After emergency intervention, vital signs became stable and numbness of both hands and feet improved. Based on her clinical course, we strongly recommended to add mepolizumab to control hypereosinophilia and reduce the dose of steroid. After administration of mepolizumab in addition to the previous steroid and cyclophosphamide therapy, eosinophil count became stable and was reduced to a near zero percentage of total white blood cell count.

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+A 48-years old Asian female was referred to our hospital with a recent history of weakness, myalgia and arthralgia. She also complained of anorexia with 3 kg weight loss. She had no past medical history and was free of any medication on admission. At presentation, blood pressure was 180/80 mmHg, heart rate was 91/min, temperature was normal. Heart and lung auscultation, as well as abdominal examination, were normal. She had no skin involvement nor lymphadenopathy or synovitis.
+Biology showed acute kidney injury with serum creatinine at 209 μmol/L. White blood cell count (4.8 G/L) and platelet count (269 G/L) were normal, but anemia with hemoglobin at 7.8 g/dL was present. C-reactive protein was slightly increased (14 mg/dL). Urinalysis revealed glomerular proteinuria (proteinuria to creatinine ratio (P/C) 3.6 g/g) and microscopic hematuria. Kidney ultrasound examination showed normal sized kidneys and excluded obstruction. Thus, we concluded to acute glomerular syndrome and performed immunological laboratory tests. Antinuclear antibodies (ANA) (1/2560), as well as anti-dsDNA (292 UI/mL), anti-SSA and anti-SSB antibodies were detected. Type 3 cryoglobulinemia and complement consumption (decreased C3, C4 and CH50) were also present. Search for lupus anticoagulant, IgG anti-cardiolipin and anti-beta-2GP1 antibodies was negative. Finally, pANCA were detected at 1/2000 titer using IIF. ELISA showed the concomitant presence of MPO, PR3 and lactoferrine ANCAs with a strong positivity for MPO and lactoferrine ANCAs and a low positivity for PR3 ANCAs. ANCA detection using multiplex technology also detected MPO ANCA at high level, and low PR3 ANCA level.
+LN was first considered leading us to perform a kidney biopsy. On optical examination, extra-capillary circumferential cellular or fibro-cellular crescents were observed in 10 of 16 glomeruli. Segmental endocapillary proliferation was absent to very modest, without any lesions of capillary necrosis . Immunofluorescence analysis showed strong and diffuse mesangial and parietal C1q staining with a granular deposition pattern, while IgG, IgA, IgM, and C3 deposits were quite limited, of mesangial topography and only segmental .
+Following biopsy, an immunosuppressive treatment was initiated with an association of steroids, hydoxychloroquine and pulse intravenous cyclophosphamide (CYC, 500 mg every two weeks) according to the Euro-Lupus protocol trial . Under this regimen, a progressive improvement of both her general condition and kidney function was observed. At month 3 from treatment initiation (after the 6th CYC injection), serum creatinine was 116 μmol/L and P/C ratio decreased to 0.50 g/g. Antinuclear antibodies decreased to 1/200, anti-dsDNA antibodies became undetectable, and complement returned within normal range. ANCAs were still detectable although at lower titer using IIF (1/200), with only MPO ANCAs remaining slightly positives at ELISA and multiplex assays.
+At that time, we decided to perform a systematic kidney biopsy to analyze histological response to treatment. On optical examination, only fibrotic crescents were observed in 9/14 glomeruli, none of them being cellular of fibro-cellular. Global lesions of endocapillary proliferation were observed in most glomeruli, without lesions of capillary necrosis . Immunofluorescence analysis showed diffuse mesangial and parietal C1q staining at a lower intensity as compared to the diagnostic biopsy. IgG, IgA, IgM, and C3 deposits remained limited, in their pattern and intensity .
+After the biopsy results, we decided to continue CYC. However, after the 8th CYC injection, the patient developed toxidermia which we attributed to CYC. At that time, we decided to start mycophenolate mofetil (MMF) at 1.5 g/day.
+One year after initial admission and under MMF for 12 months, she has no clinical manifestation of SLE and did not relapse nephritis. Renal function returned to near normal values (serum creatinine of 90 μmol/L, MDRD eGFR 60 mL/min/1.73m2). ANCA detection was negative on IIF evaluation and ELISA, with anti-MPO being still detectable at very low level using multiplex assay. ANA were stable at 1/200, complement was in normal range and search for cryoglobulin was negative.

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+A 53-year-old male from Kerala, South India presented with loose stools, which were watery in nature and without blood, three–four episodes per day for 3 weeks. He complained of vague abdominal pain on and off, decreased appetite and weight loss of 3–4 kg over 1 month. He gave no history of associated fever, vomiting, urticarial rashes, or any respiratory symptoms.
+In addition to having alcohol use disorder, he was a known case of type II diabetes mellitus, hypertension and hyperlipidaemia and was on regular oral medications for the previous 2 years. He also experienced recurrent episodes of stroke, which resulted in a left-sided hemiparesis 2 years previously. He was also diagnosed as having pulmonary tuberculosis (sputum-positive), for which he had been on anti-tubercular therapy (ATT) for the previous 6 months. He denied intravenous (IV) drug abuse or any high-risk sexual behaviour. He was not on steroids or immunosuppressive drugs and gave no history of travel outside the state. He reported consumption of only cooked food and there was no food intolerance. All his family members were reported to be healthy.
+He was a cattle farmer and worked barefoot on his cattle farm; he also had a shallow pond near to his home where he used to grow freshwater fish for consumption. To his knowledge there was no practice of open field human defecation in the farm area.
+He was treated symptomatically at primary health care facilities and since there was no relief, he was referred to this tertiary care centre.
+On clinical examination, he was not febrile and vitals were within normal limits. He had bilateral pitting pedal oedema and macular erythematous rashes over the anterior aspect of both the legs for 2 weeks, which were non-migratory in nature. Systemic examination was normal.
+Routine blood investigations showed decreased haemoglobin (Hb) 9.6 %, elevated total count (TC) 13 600 cells cumm−1 with differential count (DC), polymorphs 90 %, lymphocyte 6 %, eosinophil 2 % and monocytes 2 %, an erythrocyte sedimentation rate (ESR) of 78 mm h−1, and serum electrolytes showed hypokalaemia (potassium – 2.6 meq l−1). His random blood sugar on admission was elevated (274 mg dl−1). He tested negative for viral markers of human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV). Ultrasonography (USG) of the abdomen showed fatty hepatomegaly with focal lesions in the liver, for which computed tomography (CT) of the abdomen and pelvis with contrast was performed. This showed several hypodense lesions involving segment 5 of the liver with mild hepatomegaly. CT of the lungs showed cavitation in the upper lobes of both lungs. Upper gastrointestinal endoscopy was performed, which was normal. Stool was sent for microscopy and bacteriological culture.
+Macroscopically, the stool was watery, yellowish coloured, with no mucus or blood. Wet preparation revealed numerous motile larvae in the rhabditiform stage, which measured 100–400 µm in length×15–20 µm in width and had a short buccal cavity. There were a few oval shaped eggs, ~50–60×30–35 µm in size, with larvae, suggestive of S. stercoralis. There were no pus cells or red blood cells. Stool microscopy following the formal ether concentration technique did not show any additional findings. Stool microscopy was repeated with freshly collected stool samples on three separate occasions, which also demonstrated motile rhabditiform larvae of S. stercoralis . In addition, agar culture method was performed to visualize the positive trail sign. Nearly 2 g of freshly passed stool was placed on an agar plate. The plate was sealed with tape and then incubated at room temperature for 2 days. The plate was later examined and showed a ‘positive trail sign’, that is, there were tracks present as the bacteria were carried over the agar by the migrating larvae. The agar culture method was to be repeated after therapy, if microscopy of stool did not reveal larvae, as it is a more sensitive test for assessing the elimination of the parasite.
+The bacteriological culture of stool yielded Aeromonas sobria, which was sensitive to ciprofloxacin, chloramphenicol, tetracycline and cotrimoxazole. Stool occult blood (Hemospot kit, standard guaiac method, Tulip Diagnostics, Goa, India) and toxin (VIDAS difficile toxin A and B, bioMérieux SA) were negative.
+Hyperinfection syndrome with disseminated strongyloidiasis, alcoholic liver disease, type 2 diabetes mellitus, hypertension, dyslipidaemia and pulmonary tuberculosis.
+Therapy included blood sugar and electrolyte correction and the patient was empirically started on ciprofloxacin intravenously (IV) along with parenteral fluids and other supportive measures.
+Following the stool microscopy report, a stat oral dose of a combination of albendazole 400 mg and ivermectin 6 mg, followed by once daily for 2 days, was given. The patient was continued on ciprofloxacin IV for 4 days. He showed symptomatic improvement by the second day of treatment, his stool became semisolid in consistency and the number of motile larvae in fresh stool showed an appreciable reduction. He was discharged after 4 days on mixtard insulin and oral ciprofloxacin 500 mg twice daily for 3 days.
+The patient was readmitted on the third day of discharge with complaints of fever and recurrence of diarrhoea. His blood sugar value at the time of readmission was again elevated (210 mg dl−1). His total leucocyte count (TLC) was 12 000 cumm−1, with polymorphs 60 %. His blood was sent for culture and empirical therapy was initiated with injected piperacillin/tazobactam and mixtard insulin. Unfortunately, on day 2 of readmission he expired. was isolated from his blood culture 3 days after his readmission, sensitive to cephalosporins, carbapenems, piperacillin/tazobactam and aminoglycosides, but resistant to ciprofloxacin, which he was discharged on for the infection.

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+A 64-year-old male patient was admitted to the hospital because of upper abdominal pain lasting for 1 year.
+The patient had upper abdominal distension and discomfort for more than 1 year, accompanied by poor appetite. After eating, the patient felt upper abdominal fullness and painful discomfort, which could be relieved slightly by resting or taking acid-inhibiting drugs orally. The symptoms were slightly aggravated 3 mo ago, accompanied by weight loss.
+The patient denied any history of hypertension, diabetes, and coronary heart disease; hepatitis, tuberculosis, typhoid fever, malaria, and other infectious diseases; and major trauma, surgery, and drug or food allergies. Vaccination history is unknown. He had a history of smoking and drinking for more than 40 years.
+No significant family history.
+The patient’s weight was 56 kg and his height was 170 cm, with a calculated body mass index of 19.3 kg/cm2. His Karnofsky Performance Scale score was 100. No enlarged superficial lymph nodes were palpable. His abdomen was flat, and there was no gastrointestinal or peristaltic waves. There was mild tenderness in the upper abdomen, but there was no rebound pain. The shifting dullness was negative, and the frequency of borborygmus sounds was 4 times/min.
+Tumor marker levels [carcinoembryonic antigen, cancer antigen (CA)-199, and CA125] and routine laboratory blood test results were within normal ranges.
+Computer tomography examination showed thickening of the gastric angle. Gastroscopic examination was performed, and an ulcer at the gastric horn was found. Then pathological biopsy findings confirmed that the ulcer was a gastric adenocarcinoma (clinical stage: cT1bN0M0).

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+A four-year-old girl presented to the emergency service with painful left hip and fever. There was no previous relevant medical history. There were no other local or systemic symptoms, except for a cervical adenopathy. On physical examination, she walked with a limp, and movements of the left hip were painful (mainly external rotation), but not restricted. Blood exam revealed anemia (Hb 8.7 gr/dL), normal WBC, ESB of 123 mm, and reactive C protein of 149.7 mg/L. An initial X-ray to the pelvis revealed no changes. An ultrasound of the left hip was performed revealing small infusion and synovitis. Guided puncture was then performed being macroscopically compatible with reactive arthritis, and general and bacteriological tests were demanded. Because of the unusual characteristics of the pain, a CT scan to the abdomen and pelvis was performed revealing a left adrenal mass and retroperitoneal adenopathies in the celiac trunk and superior mesenteric artery .
+Despite the painful complaints of the patient, no bone or articular involvement was found in the CT scan. No further alterations were reported in the thoracic CT scan or in peripheral blood smears. Bacteriological examination of the hip effusion was negative. MRI was also performed. The direct myelogram was compatible with infiltration from neuroblastoma. Bone marrow biopsy and cervical adenopathy specimens were collected to perform histological diagnosis. Skeletal scintigraphy demonstrated numerous points of osteoblastic activity compatible with metastatic activity, and the 12 iodine-123 metaiodobenzylguanidine scintigraphy concluded the following: “Abdominal mass with low expression of noradrenergic transporters. Diffuse bone metastasization with high expression of noradrenergic transporters. No other soft tissue involvement was detected.” In the histological report of the cervical adenopathy, the diagnosis of neuroblastoma NOS was performed. Immunohistochemistry revealed extensive expression for synaptophysin and CD56 (NCAM) and absence of expression of myogenin. .
+Bone marrow biopsy revealed extensive metastatic involvement. The patient started chemotherapy two weeks after admission, with 8 cycles of rapid COJEC protocol. After six months of follow-up, the primary tumor was still without criteria for resection, despite a decrease in the metastatic involvement. Given the chemotherapy-related renal toxicity, it was decided to proceed with irinotecan in combination with temozolomide (TEMIRI). After thirteen months of follow-up, no significant regression of the primary tumor occurred, so surgery was contraindicated and the patient was proposed for stem cell treatment.

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+A 58-year-old Japanese man was presented to our out-patient unit complaining of posterior cervical pain. The pain firstly appeared 3 months before the first contact to us without any particular triggers such as trauma. He was relieved from the pain when lying flat; however, he kept working as a plumber and the pain got worse over the time period. A brain computed tomography (CT) was performed 1.5 months after the onset in another clinic and it revealed bilateral subdural effusion , still, no treatment was given at this point. Later on, when he was presented to our hospital, numbness and weakness of extremities also appeared in addition to the progressive posterior cervical pain as well as headache. He had a medical history of hemorrhoid and no particular familial history.
+The patient admitted to our department soon after the initial contact. A hand-held dynamometer revealed his weakened grip strength of both of his hands by 30–40 kg. He was also presented with bilateral muscle weakness in his lower extremities which was 4 of 5 in the Manual Muscle Test (MMT) score , as well as sensory disturbances in his forearms, hands and the posterior surface of thighs on both sides. His Japanese Orthopedic Association (JOA) score was 13.5.
+A fat suppression T2-weighted MRI without gadolinium enhancement of the cervical spine illustrated a fluid collection in the soft tissue spaces of the retrospinal region at C1-C2 level . Additionally, it demonstrated spinal canal stenosis at C3/4 level. Subsequently, a cisternoscintigram and a CT myelogram were performed with intradural injection of 111In-DTPA (Nihon Mediphysics, Tokyo, Japan) and Omnipaque 240® (Daiichi-Sankyo, Tokyo, Japan), an iodine contrast agent, through a lumber puncture. The 111In-DTPA cisternoscintigram clearly revealed CSF leakage into the retrospinal region at C1-C2 level, as well as blockage of the 111In-DTPA at lower level of the cervical spinal canal . Furthermore, the CT myelogram also suggested blockage at lower level of the cervical spinal canal; though it did not demonstrated the sign of CSF at C1-C2 level or any other sites .
+72 h of conservative therapy, including bed rest, intravenous fluid hydration, muscle relaxants and non-steroidal anti-inflammatory drugs, was ineffective at improving his symptoms, and the re-examination of brain CT showed progression of the bilateral subdural effusions to bilateral subdural hematomas .
+After reviewing of his imaging data and confirmation that no other cause presented in development of subdural hematoma along with careful discussions, we gave a diagnosis of intracranial hypotension due to the CSF leakage from C1-C2 level, which might be caused by spinal canal stenosis at C3/4 level. We, therefore, performed burr-hole drainage of the subdural hematoma, blood-patch therapy at C1/2 level and laminoplasty at C3–4, at the same time. In the laminoplasty, CSF flew out from the epidural space subsequently to the opening of lamina, and after sufficient decompression, the CSF flow was reduced in the operation field, without detection and restoration of dural tear (Video). In the blood-patch therapy, an epidural catheter was inserted from the surgical field at C3–4 level to C1-C2 level under x-ray fluoroscopy observation. Approximately 5 ml of autologous blood sampled from patient’s peripheral vein was injected to the epidural site at C1-C2 level and the blood-patch therapy was achieved.
+Postoperative response was significantly favorable. His symptoms completely improved and the imaging features that suggested CSF leak and intracranial hypotension disappeared . He discharged on postoperative day 10 with satisfaction, and no signs of recurrence were observed for 5 months postoperatively up to this point. The patient returned to his daily life as well as his occupation.

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+A 33-year-old female presented 3 months postpartum with a headache of moderate severity and progressive visual loss in both eyes. On examination, the patient's Glasgow coma scale (GCS) was 15/15. Visual field examination showed left homonymous incomplete hemianopia. Her visual acuity was 20/25 in the right eye and 20/30 in the left eye. Her discs and macula were healthy bilaterally. Extraocular movements were intact and pupils were reactive. The rest of her examination was unremarkable. Complete endocrine workup was normal.
+Magnetic resonance imaging (MRI) revealed a large heterogeneous, hyperintense, hemorrhagic right suprasellar extra-axial complex cystic structure measuring 31 × 30 × 90 mm on T1-weighted images. There was mass effect on the adjacent hypothalamus and third ventricle displacing them toward the left and superiorly in addition to the optic pathway. The pituitary stalk was displaced toward the left. The lesion encased the right posterior cerebral artery and displaced the right carotid artery laterally . Computed tomography (CT) arteriography demonstrated a completely thrombosed center. The imaging findings were compatible with suprasellar CM.
+The patient underwent right frontal craniotomy and gross total resection of her suprasellar intrachiasmatic large infiltrative hemorrhagic CM. Organizing blood clots with reactive fibrohistiocytic and inflammatory reaction admixed with some ectatic vascular channels suggestive of a vascular malformation were noted. There were small foci admixed with granulation tissue, showing some dilated cavernous spaces that would be compatible with a vascular malformation such as cavernous angioma. On immunohistochemistry, the lesion was CD163+, CD20 rare, CD3+, CD34+, CD31+, CD38+, CTK−, EMA plasma cells, GFAP−, S100 dendritic cells, SMA vascular smooth muscle.
+The patient had an uneventful operative course. Her visual acuity improved to 20/20 in both eyes. Extraocular muscles showed mild limitation of both eyes in an upward gaze. Otherwise, she was stable with no neurological deficits. Follow-up MRI at 12 months revealed complete removal of the suprasellar hemorrhagic CM with no evidence of a residual lesion or recurrence .

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+A 19-year-old Caucasian man was admitted to our emergency department with a critical ischemia of his right ring finger due to a crushing injury. His finger had been caught between a car and a car-jack while he was working as a mechanic. The first physical examination of the ring finger revealed an open wound of 3 cm on the dorsal side of the middle phalanx. Edges of the wound reached the ulnar and radial digital neurovascular bundle. The patient reported decreased sensibility of the end phalanx including painful range of motion (ROM) but without loss of function of all tendons. We found a restricted finger blood flow detected by nail bed compression in comparison with the uninjured fingers. An X-ray showed an undislocated transverse fracture of the middle phalanx . The patient was immediately transferred to the operating room (OR) where the wound was examined. Severe damage of the surrounding soft tissue was seen. Microscopic examination revealed no defect of the crushed vessels, the radial digital nerve was intact, but an epineural lesion was apparent for the ulnar digital nerve. A minimal osteosynthesis with two Kirschner-wires (K-wires) was performed. X-ray imaging showed an anatomical retention and fixation of the fracture . The dorsal wound of the ring finger was cut out and sutured. The patient was discharged from the hospital on the fourth day without any sign of wound healing disturbance. The ring finger was immobilized with a finger splint including the proximal interphalangeal joint (PIP) and distal interphalangeal joint (DIP).
+The patient was seen five months after initial treatment in our Out-Patient Clinic and reported painful moving of the right ring finger. The examination showed an instability of the middle phalanx with a passive lateral movement. Twenty degrees ulnar deviation of the ring finger with decreased ROM of the PIP joint (E/F 0-0-60˚) was apparent. In addition, the ring finger tended to cross over and overlap the adjacent finger when making a fist. The patient reported that ulna deviation of the ring finger started when K-wires had been removed by an office-based orthopedic surgeon two months after the initial surgery.
+Since that time the finger was fixed again with a splint. He also complained about tingling, coolness and numbness of the injured finger. Since the X-ray showed a nonunion we started treatment with a LIPUS device (Fa. Melmak GmbH, Munich, Germany) three times daily for 20 minutes including the following parameter configuration:
+Average intensity I = 30 mW/cm² (SATA), ultrasound frequency F = 1.5 MHz, signal impulse duration 200 microseconds, repetition rate 1 kHz, effective radiating area 3.88 cm2, temporal average power 117 mW.
+The ring finger was immobilized with a fitted personalized thermoplastic splint for six weeks. Six weeks after LIPUS treatment the patient reported to be without pain when moving his ring finger and clinical examination revealed a slight persistent ulna deviation of five degrees. The clinical examination showed a stable middle phalanx compared to the result six weeks previously. After four weeks of physiotherapy the ROM of the PIP joint was E/F 0-0-85° and the fist closure was full , except for the pre-existent limited ROM of the DIP-Joint (E/F 0-0-15˚). An X-ray confirmed fracture healing and calcification of the soft callus was clearly evident .

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+A 46-year-old male with end-stage renal disease of unknown cause had been on hemodialysis for 3 years when he underwent cadaveric renal transplantation 15 months ago. Except for 3 years of hypertension, there was no other remarkable medical history. The kidneys of donor after brain death were procured by an operation group. However, during harvesting of the donor’s kidneys, a branch of right renal artery to renal superior polar was inadvertently cut off. The artery branch with a diameter 0.3 mm arised from the bifurcation of abdominal aorta and renal artery. Subsequently the severed renal artery branch was anastomosed in situ with 7–0 prolene during the repair of the kidney. Although the lengh of the renal artery branch became little shorter, the major trunk of renal artery was not excessively stretched. The cold and warm ischemia time of the kidney were 5 min and 6 h respectively. The right kidney of donor was transplanted in the right iliac fossa. The donor renal artery with a Carrel patch of donor aorta was anastomosed end-to-side to the recipient right external iliac artery with 6–0 prolene, and renal vein was anastomosed end-to-side to the recipient right external iliac vein with 5–0 prolene, and the graft ureter was anastomosed to the urinary bladder of the recipient with a double J stent. Basiliximab was used as immunity induction on the day of surgery and the fourth day after transplantation. His immunosuppression regimen consisted of tacrolimus, mycophenolate sodium, and prednisolone. His immediate postoperative course was unremarkable. His blood pressure was controlled to 140–156/90–105 mmHg with nicardipine spironolactone, and furosemide y. The 24-h urine volume was between 1937 and 4100 ml, and his renal function. Significantly improved, reaching a creatinine of 151 μmol/L on 11st day posttransplantation. However, from the 12nd day after transplantation his blood pressure began to gradually increase to 170–174/103-109 mmHg.There was no positive presentation on clinical examination and ultrasonograph, and the level of creatinine and urine volume were also stable. So the nicardipine was increased. To our surprise, it was still difficult to control his blood pressure even though three antihypertensive medications (sustained-release nifedipine 60 mg twice daily, urapidil 30 mg twice daily, arotinolol 10 mg twice daily) were administrated. His blood pressure reached to 190/120 mmHg on 20th day after transplantation. There was a decrease in 24-h urine volume with 1620-1725 ml, and mild impairment of renal function with a creatinine of 194 μmol/L. A bruit became audible over the site of the transplanted kidney. Color Doppler ultrasonography indicated a decreased RI in intrarenal arteries and increased blood flow of the transplant renal artery, with RI of 0.45, the peak systolic velocity(PSV) of 305 cm/s and the velocity gradient between stenotic and prestenotic segment of more than 3:1, therefore, a vascular complication of TRAS was suspected. Diagnostic arteriography was performed through a retrograde contralateral femoral artery puncture on 22nd day after transplantation, and it showed a 90% stenosis of transplant renal artery, and the TRAS occurred in the distal site of the anastomosis instead of the anastomosis . We considered that the reconstructional renal artery branch stretched the trunk of renal artery, which resulted in the stenosis distal to the suture line. Two days later, after sufficient preparation renal artery angioplasty was undertaken through a retrograde ipsilateral femoral artery approach. As the stenosis might be high elastic due to the stretch, percutaneous transluminal stent implantation was performed. Because the artery branch situated on the stenosis, bare stent (6 × 14 mm, Express Vascular SD) had to be chosen to avoid effecting the flow of the artery branch. After the bare stent was successfully deployed, a second angiographic evaluation verified the effectiveness of the intervention was obvious. After the interventional treatment, the renal function and urine volume recovered, and his blood pressure was stably controlled to 121/80 mmHg with only two antihypertension (nifedipine and arotinolol). He was discharged on 28 day after transplantation with a creatinine of 108 μmol/L. Changes in clinical parameters over the 1-month treatment period is shown in Table . The patient’s renal function remains stable at clinical follow-up of 15 months.

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+A 25-year-old right-handed male was admitted to our department with a chief complaint of swelling of the dorsal aspect of his right wrist for 3 years. There was no persistent pain in the right wrist. He had not suffered from severe trauma. The patient had undergone an ineffective superficial surgery of the right wrist 2 years earlier and no pathological specimen was sent. The wrist deformity had progressively worsened over the following 2 years. Physical examination showed a range of motion in the wrist of extension to 60°, flexion to 30°, ulnar deviation to 20°, and radial deviation to 0°. The fingers moved normally and functioned normally. Neurological examination of the right hand revealed diminished pain sensation. Apart from that, patients reported an obvious diminishing of pain when injured before. General laboratory tests did not reveal anything specific. X-ray examination confirmed bone resorption of the scaphoid . Magnetic resonance imaging (MRI) examination showed hyperplasia of the surrounding tissue, but no damage to the articular surface of the radiolunate joint . He was at that time diagnosed with synovitis and radiocarpal arthritis. We managed his disease with Four-Corner Arthrodesis and Synoviectomy to alleviate the damage of the joint and preserve motor function. At the time of surgery under general anesthesia, we observed synovial hyperplasia , the collapse of the proximal half of the scaphoid, an intact radiolunate joint surface , wear of the radialis carpal articular surface of radius , and a deformity of dorsal intercalary segment instability (DISI). Following a limited intercarpal arthrodesis, the intraoperative radiograph showed improvement . The wrist was fixed in a functional position, and the patient was then discharged.
+The patient’s right wrist became red, painful, progressively swollen, and immovable over the next 2 months. Imaging indicated increased carpal bone damage . The white blood cell count was 8.81 × 109/L (reference values 4.00 × 109/L–10.00 × 109/L), and the proportion of neutrophils was 65.6% (reference values 50.0%–70.0%). Biopsy results showed no bacteria were cultured. Antinuclear antibody anti-cyclic citrullinated peptide antibodies and rheumatoid factor were negative. Results of acid-fast staining, T-SPOT.TB, and tuberculosis (TB) were both negative. Rheumatoid arthritis, TB arthritis, and infectious diseases were ruled out in this case. Because of the hypalgesia before surgery, a cervical MRI was conducted for further antidiastole, which revealed Chiari II syringomyelia . The patient was eventually diagnosed with destructive NA (syringomyelia), ut refused to undergo carpal and spinal surgery. After 2 months of conservative treatment, the right wrist spontaneously and completely fused and the pain disappeared . During the 1-year follow-up, there was no acute change in the condition . The patient was generally satisfied with the outcomes of the treatment.

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+A 32-year-old woman with a gestational age of 32 wk + 4 d experienced epigastric pain. She was asymptomatic for COVID-19.
+She first experienced pain in the epigastrium 2 h before the initial examination, with a gradual worsening of her condition.
+The patient had no comorbidities and was not taking any chronic medication.
+There was no significant personal or family history.
+Physical examination revealed epigastric pain, with a body temperature of 36.5 °C, blood pressure of 17, 6/11 kPa, and oxygen saturation of 97%. Electrocardiogram (ECG) and cardiotocographic findings were normal. We initially suspected her to have hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP) and performed fetal lung maturity induction while administering 12 mg betamethasone intravenously for 24 h.
+Blood tests results revealed elevated liver enzymes [alanine aminotransferase (ALT): 272.4 IU/L, aspartate transaminase (AST): 159.6 IU/L, and alkaline phosphatase (ALP): 172.8 IU/L], without any findings of viral hepatitis (the samples were negative for hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, Epstein-Barr virus (EBV), human cytomegalovirus (HCMV). Her coagulation parameters were normal; hence other pregnancy-related liver pathologies were excluded. The hepatologist suggested that her condition was most likely related to hepatopathy of unknown etiology. SARS-CoV-2 positivity on reverse transcription-polymerase chain reaction was confirmed, although the patient was asymptomatic.
+The initial ultrasound examination revealed a live fetus without any abnormal findings.
+Over a week, the liver enzymes and platelet count returned to normal levels. On the fourth day of hospitalization, pain developed in the right subcostal region and physical examination revealed a positive Murphy’s sign, while her ECG was normal, D-dimers concentration was above 10000 µg/L, and liver enzymes were slightly elevated (ALT: 372 IU/L; AST: 258 IU/L). Therefore, we ruled out acute coronary syndrome. Abdominal ultrasound examination confirmed no abnormalities in the abdominal organs, a viable fetus, and no free fluid in the abdominal cavity. We administered anticoagulant therapy (0.3 mL low molecular weight heparin every 12 h). The correlation between the laboratory findings and clinical findings was unclear. Within 2 h, the patient developed a collapsed state without trauma and her blood test showed a marked increase in ALT (1789.8 IU/L) and AST (1747.2 IU/L). In addition, lactate dehydrogenase (LD) levels (1671 IU/L) and platelets (88 × 109/L) were highly elevated. Therefore, an emergency cesarean section was planned.

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+The patient was a 48-year-old female with a 20-month history of right-sided orofacial pain. Her main complaint was paroxysmal pain in her auditory canal, pinna, deep in the jaw, and adjacent retromastoid area on the right side. The pain was described as a burning sensation in an area located in the posterior external auditory canal wall and was elicited by chewing, touch, or contact with objects or warm water. It usually lasted for a few seconds to 1–2 min and would remit spontaneously and abruptly. The patient ranked it 10 on the numeric rating scale. She had no odynophagia and was treated with carbamazepine (maximum 1200 mg/day), which proved to be ineffective. Other medications (Sertraline, Amitriptyline, and Pregabalin) also failed to provide clinically significant pain relief. The patient's otoscopic examination was unremarkable bilaterally. There was no sensory loss, facial palsy, or other neurological signs.
+The patient underwent preoperative MRI and MRI angiography, including 3D T2-weighted fast spin echo and 3D constructive interference in the steady-state (CISS) sequences. Images showed the right posterior cerebellar artery crossing the cerebello-pontine cistern [arrow in ] in close contact with the right VII and VIII nerves [arrow in ], near the internal auditory canal.
+A right-sided suboccipital retrosigmoid craniotomy was performed. The patient was put in a left lateral decubitus position, with the head well rotated and fixed in a Mayfield clamp. The dura was opened. Minimal retraction of the cerebellum was performed to achieve cerebrospinal fluid (CSF) drainage. In the cerebello-pontine angle, as shown in , the loop [arrow-head in ] of the PICA was visualized, as well as the close contact between the vascular structure and the VII-VIII nerves complex [* in ]. Additional exploration did not reveal other areas of neurovascular conflict at the roots of the trigeminal nerve or the lower cranial nerves. The artery's arachnoid attachment was dissected, the artery mobilized, and a small Teflon felt was placed to separate the artery from the nerve. Sectioning of the intermediate nerve or excision of the geniculate ganglion (GG) was not necessary.
+Following the decompression, the patient had an uneventful postoperative recovery and the pain resolved immediately with no additional neurological deficits, demonstrating that the compression was the only cause of pain. Postoperative CT scans were unremarkable. Medication was tapered off in the first few weeks after surgery. At 6-months’ follow-up, no further paroxysmal pain had occurred.

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+A 3-year-old girl was transferred to our center for severe cough, shortness of breath, fatigue and fever. Physical examination revealed facial deformities and growth retardation. The patient was diagnosed with hypothyroidism, CHD and PH by examinations at the age of 11 months old. Her transcutaneous finger oxygen saturation was 70%. Echocardiography showed a 0.9cm-wide ASD, a widened pulmonary artery, and severe tricuspid regurgitation . Laboratory tests suggested that NT-proBNP was 3907pg/ml, the C-reaction protein level was 19.83mg/L, and the white blood cell was in the normal range, but the percentage of neutrophils increased to 78.7%, and (respiratory syncytial virus) RSV-IgM was positive. Liver function, kidney function, the level of autoimmune antibodies, and the erythrocyte sedimentation rate were normal. The patient was given anti-infection and cardiotonic drugs as well as respiratory support after admission.
+Meanwhile, the patient underwent right heart catheterization. The results indicated that the mean pulmonary arterial pressure (mPAP, 71mmHg) was markedly increased, the pulmonary vascular resistance (PVR, 27WU) also enlarged, and the pulmonary capillary wedge pressure (PCWP) is normal. Since the ASD was small and the slow flow rate could not result in the tremendous elevation in the pulmonary arterial pressure, the pathogenesis should be further investigated. No obvious abnormalities were found from the results of the pulmonary test, cardiac CTA and other routine etiological examinations in the patient. Nevertheless, the genetic inspection (the accession number for the whole-exome sequencing data is HRA005032) showed that the patient had a KMT2D (ENSMBL reference ID: NM_003482.3) exon 39 c.12209_12210del p.(Ser4070fs) mutation . Based on the genetic results and abnormal countenance, the patient was diagnosed with KS type 1. The patient developed severe PH and poor oxygenation, and she was classified into the high-risk population by risk stratification was. Therefore, she received triple targeted pulmonary vascular pressure reduction treatment, i.e., Ambrisentan (2.5mg once daily) + Tadalafil (10mg once daily) + Remodulin (continuous subcutaneous pumping). The patient was followed up regularly after discharge, but the effect was unsatisfactory. The latest echocardiography reexamination showed no change in the size of the ASD, moderate tricuspid regurgitation, and estimated pulmonary arterial systolic pressure of 96mmHg.

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+A 66-year-old male patient presented with exertional chest tightness, shortness of breath, and right lower limb weakness for two weeks. He was diagnosed with a cardiac mass two months ago in another hospital. He had a history of hypertension from last 20 years which was under control with treatment. He underwent radical rectal surgery for rectal cancer five years ago and experienced intermittent fecal incontinence after surgery. On physical examination, his blood pressure was 124/67 mmHg, temperature 36.6 Co, pulse 64 bpm, RR 20/m. On percussion, the dullness of the left heart border was slightly extended indicating left heart enlargement. On auscultation, heart sounds were normal in all areas with normal rhythm and moist rale in both lung fields. Abdominal ultrasound revealed liver and left renal cyst. The prostate gland was mildly enlarged with calcified plaques. Coronary angiography (CAG) was performed without any remarkable findings. Transthoracic echocardiography (TTE) showed a mitral valve hypoechoic space occupying lesion with clear borders. Color doppler showed no blood flow signals around or inside the cystic mass. Contrast enhanced echo showed no contrast medium perfused into the cyst with moderate mitral regurgitation (MR) and ascending aortic dilation as shown in Fig. . Computed tomography (CT) examination revealed an elliptical low-density filling defect in the mitral valve area of the left atrium with a cross-sectional size of about 2.9*1.2 cm as shown in Fig. . Based on echocardiography, and CT report a preliminary diagnosis of cardiac cystic tumor was made. He underwent thoracoscopic surgery under general anesthesia and a cardiopulmonary bypass. The arterial and venous cannulation was done through the right femoral artery and vein respectively. A 4 cm incision was made in the 4th intercostal space (ICS) at the right anterior axillary line, a 3 cm incision in the 3rd ICS in the mid auxiliary line, and a 3 cm incision in the 2nd ICS in the midclavicular line. The aorta was cross-clamped and the cardiac arrest was achieved with the help of cardioplegia infused through the aortic root. There was no thrombus found in the left atrium. A cyst of about 20*20 mm at the P1 position of the posterior mitral leaflet was observed with mild enlargement of the mitral annulus. The mitral valve showed moderate regurgitation. The cyst was removed and the posterior leaflet of the valve was repaired with a complete semirigid 28 mm annuloplasty ring placed. The saline leakage test showed good competency of the mitral valve. The postoperative histopathology report showed a 2.5*2*0.7 cm gray and white cyst with smooth inner and outer wall. The tissue presented cyst like structure with no clear coated epithelium. There was fibrous hyaline degeneration and mucous degeneration of cystic wall and small foci of hemorrhage which confirmed the diagnosis of the mitral valve blood cyst . The patient recovered well without any complications. The postoperative echocardiography showed no MR. Patient was doing well and was asymptomatic on six months follow up.

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+A 28-year-old Caucasian male presented with fever and myalgia at our emergency department (= day 1). The patient reported having been on vacation on La Réunion until nine days prior, where a medium-level dengue epidemic had been declared by the WHO. His past medical history was uneventful; he was not on any medication. Physical examination revealed a body temperature of 39.7 °C but was otherwise unremarkable. Routine laboratory investigations were without pathological findings except for a C-reactive protein (CRP) of 2.5 mg/dl. Tests for Dengue virus and Chikungunya virus were ordered. The patient received metamizole and was discharged with a daily follow-up schedule which, however, he did not comply with. The microbiological laboratory tests returned negative. After three days, fever subsided and was followed by watery diarrhoea which lasted for three more days. On day 7, the patient had fully recovered.
+On day 8, the patient noticed a weakness in his lower limbs which continuously worsened overnight. Thus, he presented in our neurological clinic the next morning. Physical examination revealed flaccid tetraparesis with a level of strength of 4/5 (MRC scale). Muscle reflexes of the upper limbs and patellar reflexes were decreased, Achilles reflexes were absent bilaterally. There were no sensory deficits; position sense and vibration sense were intact. Cerebrospinal fluid analysis was unremarkable. Electroneurography disclosed reduced amplitudes of compound muscle action potentials in tibial, peroneal and ulnar nerves. Half of the examined nerves displayed increased distal motor latency and total loss of F-waves, while sensory nerve action potentials were normal all over. Hence, pure motor axonal demyelinating polyneuropathy with acute onset, consistent with Guillain-Barré syndrome (GBS) was diagnosed. Furthermore, western blot for serum anti-ganglioside antibodies was highly positive for anti-GM2 IgM antibodies and borderline positive for anti-GM1 IgM antibodies, thus supporting the diagnosis of GBS. The occurrence of GBS raised the suspicion of a recent Campylobacter jejuni infection which was serologically confirmed (Mycoplasma pneumonia, another common trigger of GBS, and Zika virus infection were excluded).
+As the clinical condition deteriorated rapidly with inability to walk occurring within the first 48 h, treatment with intravenous immunoglobulins was initiated (total dose 140 g over 5 days). Clinical nadir was reached after three days and the patient regained independent walking within the first week. He was transferred to a neurorehabilitation institution where he was treated for three weeks. Except for a temporary elevation of transaminases (ALT 661 U/l, AST 126 U/l) and a distortion of the left knee due to several falls, further recovery proceeded without complications.
+In week 10, the patient presented at our clinic again. He complained of fever, loss of appetite, abdominal bloating, constipation and a dull pain in the right lower abdomen. He reported suffering from these symptoms periodically; they had first occurred three weeks ago and lasted for a couple of days, then completely disappeared and reoccurred six days ago. The onset as well as the disappearance of these symptoms was sudden. On enquiry, the patient could not think of any potential triggers preceding these episodes. Diarrhoea had not occurred.
+The patient’s vital signs were all normal except for a body temperature of 38.8 °C. Compared to his first presentation, he had lost 11 kg (15% of his previous body weight). The abdominal examination was pertinent for tenderness on palpation in the right lower quadrant. Broad laboratory investigations were unremarkable apart from an elevated CRP of 8.5 mg/dl and a slightly elevated LDH. Abdominal ultrasound revealed a distinct mesenteric lymphadenopathy with > 10 pathological lymph nodes (max. 4 × 1.6 cm) . The largest mesenteric lymph nodes were found in the right lower quadrant and were painful when pressed with the ultrasound probe. Retroperitoneal, inguinal, supraclavicular, axillary and cervical lymph nodes as well as the appendix and colon appeared normal on ultrasound examination.
+A broad microbiological testing was initiated. While stool cultures remained negative, serology was positive for Y. pseudotuberculosis . Antibiotic treatment was initially started with azithromycin (500 mg p.o., QD, for 3 days) and switched to doxycycline (100 mg p.o., BID, for 10 days) after receiving the serology results.
+On control ultrasound two weeks later (week 12), the lymphadenopathy was clearly regressive in all affected regions with the largest mesenteric lymphnode measuring 2 × 0.7 cm. In a telephone follow-up two months later, the patient reported no further episodes of fever or abdominal symptoms. Regarding GBS, he had not regained his full physical capacity but continued to improve constantly.

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+A 70-year-old man visited our emergency unit with chief complaints of epigastric pain and vomitus niger 2 h after the onset of symptoms. After consultation in our hospital, the patient had black vomit. His blood pressure was 168/109 mmHg, pulse was 73 bpm, and body temperature 36.7 °C. For abdominal findings, he had rebound tenderness, although tenderness was present in the epigastrium. With regard to significant medical history, he had Mallory–Weiss syndrome, high blood pressure, and hyperlipidemia detected 14 years ago, as well as removal of Helicobacter pylori 2 years prior. For relevant lifestyle history, the patient claims to drink five cups of coffee, consumes 360 cc of alcohol each day, and is currently a non-smoker (quit smoking 10 years ago). He is currently medicated with oral antihypertensive agents. Results of his blood tests revealed white blood cell count of 13,560/ml and C-reactive protein of 0.3 mg/dl.
+Contrast computed tomography (CT) revealed empyema and fluid retention in the mediastinum . There were no abnormal findings such as fluid retention and pneumothorax in the thoracic cavity. Upper GI series (with Urografin) detected leakage of contrast media into the mediastinum from the lower intrathoracic esophagus on the left side . We repeated plain CT scans following the upper GI series and confirmed leakage of contrast media into the mediastinum from the site just above the cardia to the tracheal bifurcation. Based on the above findings, the patient was diagnosed with spontaneous esophageal rupture and we decided to perform emergency surgery. Because the location of the perforation was suspected to be the left side of the lower esophagus, the patient’s vital sign was stable, and the area of perforation was localized to the mediastinum, laparoscopic transhiatal simple closure was chosen. We performed the procedure 11 h after the onset of symptoms.
+The ports were inserted using the 5-hole approach. No abnormal findings were found in the abdominal cavity. It was found that contamination was mainly on the left side, and we initially searched for perforation placement from the left side of the esophagus. We removed a volume of tissue equivalent to three quarters of the circumference of the esophagus from the dorsal esophagus to the right dorsal esophagus. A perforation of 2 cm in diameter was observed at the site of the rostral portion at approximately 4 cm from the esophageal hiatus . No intrathoracic perforation was observed. Endoscopy of the upper gastrointestinal tract was performed during surgery, and from the esophageal lumen, it was confirmed that this was the site of perforation. The perforation was closed with three stitches using 3–0 absorbable sutures . Before concluding surgery, the mediastinum was irrigated with saline and two drains were inserted into the subdiaphragm around hiatal space transperitoneally. The total operative time was 178 min, and the total volume of bleeding was 2 ml.
+After surgery, the two drains were used for intermittent suction, and we continued treatment with proton pump inhibitor (30 mg, 2 times a day) and antibiotics (MEPM 1 g, 3 times a day). The patient started ambulation on the first postoperative day. His white cell count was normalized on postoperative day 4. The gastric tube was removed with fluoroscopic guidance. Antibiotics were discontinued on postoperative day 6. Oral intake of food was initiated on postoperative day 7, and after shifting meals to a solid diet, recovery was uneventful. The patient was discharged on postoperative day 15 and continued proton pump inhibitor therapy as an outpatient. Healing cicatrization was found at the site of rupture by endoscopy of the upper gastrointestinal tract . The patient was advised to improve his lifestyle. He showed no signs of recurrence two or more years after surgery.

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+A 36-year-old man was referred to our clinic from his family dentist with a complaint of pain around the anterior maxillary region on the right side. The patient’s medical history was non-contributory. Intraoral examination identified a firm, non-fluctuant mass with no ulceration in the vestibular region between the right upper central incisor and canine . The right upper central and lateral incisors were missing. A computed tomography (CT) showed severe bony resorption between the right upper second premolar and the left upper lateral incisor . Incisional biopsy was performed via vestibular approach. The specimen of the tumor was extirpated with overlying mucosa. During the biopsy, an intact cortex was not observed. The histological diagnosis was moderately differentiated SCC. The connection between the tumor and the overlying mucosa was not observed. Contrast-enhanced computed tomography (CE-CT) revealed a destructive tumor with no cystic lesion, >50 mm in diameter. The tumor pressed the skin around the nasal ala and the nostril of the right side, but no direct connection between the skin and tumor was observed. Although the maxillary sinus and nasal cavity were deformed by the tumor, no abnormal findings were seen for the mucosa of the nasal cavity and maxillary sinus . One swollen and enhanced lymph node was recognized in the submandibular area of the right side. Positron emission tomography (PET) revealed the enhanced lesion in the maxilla and the right submandibular area. There was no evidence of metastatic disease on chest radiography, upper gastric endoscopy or PET. Based on these findings, solid type PIOSCC was diagnosed.
+The patient underwent tumor ablative surgery. After bilateral supraomohyoid neck dissection, the primary tumor was radically excised. The surgical specimen comprised the anterior two-thirds of the hard palate and nasal septum, bilateral inferior nasal conchae and the skin around the nasal ala and nostril of the right side. The surgical defect was reconstructed using a partially double-folded free radial forearm flap and prefabricated denture-based surgical obturator. Microscopic examination of the surgical specimen revealed SCC without cystic component in the maxillary bone. The islands of the tumor cells extended into the bone with no dysplasia or carcinoma in the skin and mucosa of the nasal cavity and maxillary sinus. The dissected surgical specimen of the neck showed one lymph node metastasis of the ipsilateral submandibular region. Although adjuvant radiotherapy was recommended, the patient declined additional treatment. The postoperative course was quite good. Neither recurrence nor metastasis had been found as of 3 years and 1 month postoperatively.

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+A 12-year-old boy was admitted to our hospital for the first time on January 11, 2021 because of dyspnea for 2 wk, left leg pain for 1 wk, and aggravation for 3 d. He also had a fever and occasional cough. On February 24 and April 2, 2021, the patient was admitted to the hospital with a symmetrical, dark red rash on both legs that did not face when pressed, accompanied by ankle swelling and pain.
+The child had a history of respiratory infections prior to labored breathing.
+The child was previously healthy.
+First hospital admission: The patient was 168 cm tall, weighed 76 kg, and had a body mass index (BMI) of 26.9 kg/m2. His vital signs were as follows: Body temperature, 37.4 °C; blood pressure 128/81 mmHg; heart rate, 104 beats per min; respiratory rate 32/min; and SpO2 92% (room air). The patient’s skin was normal, but he displayed slight shortness and exertion of breath. The circumference of his left leg was 39.5 cm and right leg 37.5 cm, and his limb muscle tension was normal.
+Second and third admissions: His legs showed a scattered, symmetrical, pressing dark red rash that did not fade, and both ankles were swollen and painful. On April 4, 2021, the child had decreased pain and temperature sensation in the right plantar, the toe could not bend to the ventral side, and the skin temperature of the right plantar was higher than that of the opposite side.
+His platelet count was 50 × 109/L, and his eosinophil count (EC) was slightly high at 0.63 × 109/L . On the other hand, his D-dimer level was 11.12 μg/mL . Serum potassium was 3.32 mmol/L. On day 8, blood tests showed normal levels of potassium. C4 was slightly high at 0.46 g/L (normal: 0-0.4). Protein C was 50.2% (normal: 75-130). Neuronal enolase was slightly high at 21.96 μg/L (normal: 0-16.3). N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I (TnI) were high at 3116 pg/mL and 0.145 ng/mL, respectively, on January 11, 2021. No abnormalities were found in TnI on January 16, 2021 or in NT-proBNP on January 19, 2021. On February 24, 2021, the patient’s IgE level was significantly high at 531 IU/mL (normal: 0-52). No abnormalities were found in hemoglobin, glucose, lipid, liver function, renal function parameters, C-reactive protein, activated partial thromboplastin time, or protein C. Anti-neutrophil cytoplasmic antibody, antinuclear antibodies, anticardiolipin antibody, HIV tests, hepatitis B, hepatitis C, mycoplasma pneumonia antibody, borrelia, and treponema pallidum were negative. Chlamydia pneumoniae IgG was positive. Human chorionic gonadotropin, alpha-fetoprotein, carcinoembryonic antigen, ferritin, and C3 were within the reference ranges. Allergen IgE detection, food intolerance, stool for Giardia lamblia, cryptosporidium, pinworm, and genetics were negative. On February 26, 2021, the microalbumin level in urine was 13.01 mg/L, but total urinary protein was not found due to the problem of specimen retention. The 24-h urinary total protein and microalbumin levels reviewed at later stages are shown in Figure .
+On January 11, 2021, color Doppler echocardiography revealed right atria and ventricle enlargement, mild tricuspid regurgitation with insufficiency, and pulmonary hypertension. Color Doppler ultrasonography of the blood vessels of the legs showed thrombosis of the superficial femoral vein, popliteal vein, and posterior tibial vein of the left leg . The lung computed tomography (CT) showed scattered wedge-shaped consolidation of both lungs with an outward-facing base and apex pointing to the hilum, a relatively widened pulmonary artery, and pulmonary infarction cannot be excluded. CT angiography of the pulmonary artery showed extensive embolization of both pulmonary arteries with enlargement of the pulmonary artery and the right heart . On February 4, 2021, color Doppler ultrasound of the left lower extremity vein showed patency of blood flow. On April 6, 2021, color Doppler echocardiography showed a plump right atrium, mild tricuspid regurgitation with regurgitation insufficiency, and mild pulmonary hypertension. Bone marrow puncture and cranial and spinal MRI were not performed.

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+A 28-year-old healthy woman, with a family history of breast and ovarian cancer, was referred to our laboratory for multigene testing. Our proband was informed about the significance of molecular testing, provided information about her personal and family history and signed an informed consent form prior to molecular genetic testing and permission for the anonymous use of her data for research purposes and/or scientific publications.
+Genomic DNA was extracted from peripheral blood leukocytes using MagCore® Genomic DNA Whole Blood Kit (RBC Bioscience) according to the manufacturer’s instructions.
+The analysis of genes involved in hereditary cancer predisposition was performed using a solution-based capture approach. Targeted NGS was performed with a panel of 33 genes (Roche NimbleGen SeqCap EZ Choice) [APC (NM_000038.5), ATM (NM_000051.3), BARD1 (NM_000465.2), BMPR1A (NM_004329.2), BRCA1 (NM_007294.2), BRCA2 (NM_000059.3), BRIP1 (NM_032043.2), CDH1 (NM_004360.4), CDK4 (NM_000075.3), CDKN2A (NM_000077.4), CHEK1 (NM_001114121.2), CHEK2 (NM_007194.3), EPCAM (NM_002354.2), MEN1 (NM_000244.3), MLH1 (NM_000249.3), MRE11 (NM_005591.3), MSH2 (NM_000251.2), MSH6 (NM_000179.2), MUTYH (NM_001128425.1), NBN (NM_002485.4), NF1 (NM_000267.3), PALB2 (NM_024675.3), PMS2 (NM_000535.5), PTEN (NM_000314.4), RAD50 (NM_005732.3), RAD51B (NM_133509.3), RAD51C (NM_058216.2), RAD51D (NM_002878.3), RET (NM_020975.4), SMAD4 (NM_005359.5), STK11 (NM_000455.4), TP53 (NM_000546.5), VHL (NM_000551.3)]. The sample preparation was performed according to the manufacturer’s instructions in the SeqCap EZ Choice Library User’s Guide (Roche NimbleGen). Sequencing was carried out using the Miseq Illumina NGS technology and sequence changes were identified and interpreted in the context of a single clinically relevant transcript using the commercially available software suite SeqNext (JSI medical systems GmbH, Germany).
+The clinical significance of variants was further examined using standards and guidelines for the interpretation of sequence variants recommended by the ACMG Laboratory Quality Assurance Committee and the Association for Molecular Pathology (AMP) . The impact of missense substitutions on protein function or structure was analyzed using computational (in silico) predictive algorithms combined with the ensemble mutational impact score of MetaSVM . The effect on splicing was computationally examined using Human Splicing Finder .
+Total RNA was extracted from peripheral blood lymphocytes using Trizol (Invitrogen, Paisley, UK) following standard protocol. cDNA was synthesized using SuperScript™ VILO™ cDNA Synthesis Kit (Thermo Fisher Scientific) as described by the supplier. The resulting cDNA was amplified with the CHEK2 specific primers CHEK2X5F_RNA:5′-ACATCATGTCAAAAACTCTTGGAA-3′ and CHEK2X8-9R_RNA: 5′-CCCCTTCCATCAATTCCAAAACAA-3′ and the PCR-products were purified using NucleoFast® 96 PCR Clean-up kit (Macherey-Nagel GmbH and Co., Düren, Germany). The purified PCR product were used for each sequencing reaction, which was performed using the BigDye® Terminator v1.1 Cycle Sequencing kit (Applied Biosystems, Foster City, CA, USA) and Sequencing reaction products were purified prior to electrophoresis using the Montage™ SEQ96 Sequencing Reaction kit (EMD Millipore Corp., Billerica, MA, USA) and sequenced using an Applied Biosystems 3130 Genetic Analyzer (Applied Biosystems).

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+A 45-year-old female presented to the emergency with complaints of blood-stained stool for 1 day. The patient was apparently well until 7 days back when she developed pain over the right lower abdomen. The pain was colicky in nature, moderate intensity, and non-radiating, with no aggravating or relieving factors. The pain was associated with vomiting for 2 days which was non-bilious, occurred two to three times per day, and contained only food particles. On further inquiry, the patient reported having constipation for 6 months which occurred in an on-and-off pattern. She did not report any pain during defecation nor any protruding mass per rectum. There was no history of melena, anorexia, weight loss, or fever.
+No significant past medical and surgical history.
+No family history of similar presentations exists.
+No significant drug and allergy history. The patient denied the use of tobacco or illicit drugs.

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+A 73 years-old man was admitted to the hospital after experiencing dyspnea and chest tightness for 3 days. He has a 6 years history of gout, 5 years history of coronary heart disease, and a 2 years history of hypertension. He had long been treated for his disease with nifedipine GITS, clonidine, bisoprolol, and febuxostat. In addition, he received a diagnosis of systemic lupus erythematosus (SLE) due to skin erythema, photosensitivity, joint pain, positive for anti-dsDNA (228.65, normal <71 U/mL), anti-ANA (1.80), anti-Ro52 (99, normal <25), and decreases in complement C3 (0.574, normal 0.9–1.8 g/L) and C4 (0.088, normal 0.1–0.4 g/L) 2 years prior to admission and was taking prednisone 10 mg and hydroxychloroquine 100 mg daily, respectively. The patient’s laboratory results are displayed in .
+After admission, the pulmonary computer tomography (CT) scan was performed, and the results revealed pulmonary interstitial changes, pulmonary edema, and a small amount of pleural effusion on both sides, and his blood oxygen saturation was 75% (93% after oxygen inhalation), and the pulmonary infection was treated with cefminox sodium, piperacillin/tazobactam, and meropenem successively. Otherwise, a total of 120 grams of human immunoglobulin were administered to help improve the immune system of the patient.
+The patient was given oral voriconazole (200 mg/day) for 25 days after the patient’s sputum culture revealed Candida albicans infection and the serum (1,3)-β-D-glucan (+) (542 pg/mL, normal <60 pg/mL). Following the administration of voriconazole, we noticed a progressive decline in the patient’s hemoglobin, leukocyte, and platelet counts in the patient’s CBC test , accompanied by symptoms including visual impairment，nausea, vomiting, hiccups, middle and lower abdominal pain, disorders of consciousness, delirium, hallucination, slow response, and subcutaneous ecchymosis. AKI diagnosis criteria were also met by the patient’s oliguria, gradually rising serum creatinine level, aggravated pleural effusion, and lower limb edema. The patient was treated with hemodialysis and intravenous methylprednisolone (40 mg) daily. When renal function, heart failure, pleural effusion, and edema rapidly improved and urine volume returned to above 1,000 mL per day, hemodialysis was discontinued. The patient’s hemoglobin, leukocyte, and platelets gradually increased once the voriconazole was discontinued. At a follow-up of 14 days, we observed that these markers continued to improve.
+During the course of the patient’s treatment, red blood cells (600 mL), fresh frozen plasma (800 mL), and platelet concentrate (400 mL) were transfused. The blood alterations are depicted in , but there was no discernible improvement in stopping the decreasing trend of blood cell count. We performed a bone marrow biopsy the day after discontinuing voriconazole to rule out any potential pathology that might cause hematopenia. Bone marrow aspirate showed active bone marrow hyperplasia. Nucleated cells proliferated actively, and the ratio of granulocytes to red blood cells was 0.387:1. Granular proliferation decreased, accounting for 27.5% of nuclear cells, with primitive cells accounting for 4.5%, the proliferation was mainly characterized by neutrophils, late promyelocytes, rod-shaped nuclei, and lobulated nuclei, with no abnormalities in morphology or size. Erythrocytosis was extremely active, accounting for 71% of nuclear cells, among them, primary red blood accounts for 5.5%, mainly consisting of proliferation of middle and late erythroblasts, imbalance in nuclear and cytoplasmic development, nuclear abnormalities, and megaloblastic transformation of erythroblasts could be observed, the size of mature red blood cells varies significantly, pathological hematopoiesis was very obvious. Megakaryocyte proliferation is very active with maturation disorders. Iron staining: external iron: 2 (+), internal iron: 80% iron granulosa erythrocytes. In addition, genetic testing was negative. Fluorescence in situ hybridization (FISH) was used to perform genetic testing on bone marrow aspirates and did not find any chromosomal abnormalities or gene deletions, including –7/7q–, +8, p53 (17p13.1), EGR1 (5q31), D20S108, etc. Flow cytometry detection of bone marrow showed that 1.6% of myeloid cells were primitive or immature. Microscope (,) indicated that myelodysplastic syndrome (MDS) should be considered, erythroid hyperplasia is significantly active with megaloblastic transformation.
+To ascertain whether the patient had fully recovered, we conducted another bone marrow puncture after a 6 months follow-up. The results of the second bone marrow aspiration revealed a significant reduction in the abnormal proliferation of erythroid, granulocytic, and megakaryocytic cells compared to the first, and no obvious MDS-like bone marrow abnormal proliferation was discovered. Flow cytometry results demonstrated that no significant evidence of acute leukemia, NHL, or high-risk MDS-related immunophenotypic abnormalities were detected. Microscopic results bone marrow test was negative, no indication of MDS (,).
+Overall, when treating the patient with voriconazole during the first-hospital admission, we observed decreases in peripheral blood cells and diagnosed MDS-like changes in bone marrow by bone marrow puncture. After voriconazole withdrawal, drug-related side effects vanished, and the MDS alterations were significantly improved.

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+A 77-year-old woman was admitted to a neighboring hospital presenting with severe anemia and increasing exertional dyspnea. Her hemoglobin level was found to be 6.1 g/dL. Thereafter, she had been receiving medical treatment for congestive heart failure due to severe AS and was receiving repeated blood transfusion for recurrent anemia. GI bleeding was considered as a possible cause of the severe anemia and she was referred to the Gastroenterology Department in our hospital. Upper and lower GI endoscopies revealed angiodysplasia in the transverse colon with visible acute bleeding. Endoscopic hemostasis was successfully performed using hemoclips.
+During hospitalization echocardiography showed severe AS, with a peak aortic pressure gradient of 100 mmHg, and left ventricular ejection fraction of 70%. Although laboratory examinations confirmed mild anemia (hemoglobin level, 10.5 g/dL) after endoscopic hemostasis, a more subtle bleeding disorder could not be detected using global anticoagulation tests. The activity of vWF was normal (155%), but further analysis using gel electrophoresis revealed loss of large vWF multimers, which was a typical finding of acquired type 2A von Willebrand disease . The diagnosis of Heyde syndrome was established and aortic valve replacement was planned on an elective basis. A brain computed tomography (CT) performed as a routine preoperative examination 1 week preoperatively showed no abnormal findings except for mild global cortical atrophy. She also had no previous head injuries.
+Under general anesthesia, the patient underwent surgery through a median sternotomy. Cardiopulmonary bypass was established with ascending aorta and bicaval cannulation. Anticoagulation during cardiopulmonary bypass was maintained with the use of heparin to a target activated clotting time (ACT) of 300 to 400 s. After aortic cross clamping, cardiac arrest was achieved with a cardioplegic solution. The aortic valve was tricuspid and severely calcified. The valve and the calcified nodule were excised, and a 21-mm SOLO SMART stent-less bovine pericardial valve (Sorin Group, Saluggia, Italy) was implanted. Weaning from cardiopulmonary bypass was uneventful and no abnormal high ACT was recognized. Continuous real-time monitoring of regional oxygen saturation in the brain revealed no abnormalities throughout the operation.
+Postoperative hemodynamics were stable, but bilateral dilated pupils and loss of light reflex were noticed by an intensivist soon after intensive care unit admission. Her level of consciousness deteriorated to a Glasgow Coma Scale score of 3 and a Japan Coma Scale of III-300. An emergent brain CT revealed a large right subdural hematoma with severe midline shift . In spite of her poor clinical condition, the decision of immediate surgical drainage was made by the neurosurgeons. Despite prompt surgical evacuation of the hematoma, her neurological condition did not improve. The volume drained from the chest tube was not significant. Recurrent GI bleeding was not observed during the postoperative period. She did not regain consciousness at all and she died 31 days after the cardiac operation.

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+A 74-year-old woman was referred to our hospital and admitted for progressive speech and language difficulties. The patient was unable to recall the names of things or persons and was unable to communicate with others for about 1 year prior to admission, though she was able to shop and do housework without difficulty. She had no significant medical history; however, regarding her family history, her elder brother had developed word-finding difficulty with verbal paraphasia and right-hand limb-kinetic apraxia at the age of 62 years of age, and was diagnosed with CBS at 69 years of age. He had frontal lobe signs such as forced grasping, total aphasia, and right-limb kinetic apraxia; moreover, brain magnetic resonance imaging (MRI) demonstrated frontal and temporal lobar atrophy dominantly affecting the left side . The patient’s brother and parents had passed away; therefore, we could not obtain their detailed clinical information.
+Neurological findings indicated that our patient was lucid, but showed thought laziness. The cranial nerves, including those related to eye movement, were normal. The patient had normal muscle tonus and did not show muscle weakness or involuntary movement, but all extremity tendon reflexes were slightly increased. There was no evidence of sensory impairment or cerebellar ataxia. It was noted that speech required significant effort, was slow and non-fluent, and showed anarthria and aphasia. The patient’s Mini-Mental Scale Examination score was 4/30.
+Language function was assessed using the Western Aphasia Battery (WAB) Japanese edition once and SLTA (standard language test of aphasia) two times within 2 months. The scores of WAB subtests were as follows: spontaneous speech, 13 points; auditory verbal comprehension, 5.5 points; repetition, 0 points; naming, 0 points; reading, 4.3 points; writing, 2.2 points; praxis, 6.8 points; and construction, drawing, block design & calculation, 6.6 points. Raven’s score was 25/37 (average ± standard deviation: 26.9 ± 5.4). Aphasia quotient was 36.8. The results of SLTA were similar to those of WAB. Naming, writing, and repetition were impaired. However, auditory verbal comprehension and reading concerning words and short sentences were relatively preserved. Spatial perception and visual perception were also normal. Verbal comprehension via visual perception was approximately normal. Therefore, it is likely that auditory verbal comprehension was complemented by visual perception. Constructional dysfunction, limb-kinetic apraxia, ideational apraxia, and motor apraxia were not observed. Laboratory blood examinations did not reveal any particular abnormalities that could have caused cognitive dysfunction. Cell counts and protein concentrations in the patient’s cerebrospinal fluid were within normal ranges, and concentrations of tau protein (282 pg/mL) and phosphorylated tau protein (31.3 pg/mL or lower) were also normal. Brain MRI demonstrated cerebral atrophy dominantly affecting the left frontotemporal lobes .
+Clinically, the main patient symptoms were difficulty in verbal expression and non-fluent aphasia in the absence of visual memory impairment or behavioral abnormalities. On this premise, the patient was diagnosed with PPA according to Mesulam’s criteria . Furthermore, the aphasia was classified as non-fluent progressive aphasia because, while speech itself required effort, the patient retained knowledge about objects and the ability to understand words. Brain MRI demonstrated cerebral cortical atrophy dominantly affecting the left frontal and temporal lobes, consistent with previous reports of non-fluent aphasia [, ]. Thus, FTLD was diagnosed according to the patient’s clinical symptoms. Since the patient’s elder brother had been diagnosed with CBS, and similar familial cases of FTLD due to GRN and microtubule-associated protein tau gene (MAPT) mutations had been reported , we performed genetic analyses on the patient.
+Genomic deoxyribonucleic acid (DNA) was extracted from peripheral leukocytes isolated from the patient. The exon/intron boundary of GRN was amplified by polymerase chain reaction (PCR) according to a previously reported method and the PCR products were sequenced in both directions. Briefly, blood was collected into a PAXgene® RNA tube, total ribonucleic acid (RNA) was extracted from the sample, and cDNA was prepared from total RNA by a reverse transcriptase reaction. cDNA was then amplified by reverse transcriptase–polymerase chain reaction (RT-PCR) (forward primer: 5′-ACCCAGGCTGTGTGCTG-3′; reverse primer: 5′-GACAGCCTCTGGGATTGGAC-3′) and the gene expression of GRN was analyzed. Then, the amplified PCR product was extracted and its sequence was analyzed.
+The genetic examination identified a novel mutation (c.1118_1119delCCinsG) in exon10 of GRN, which was thought to cause a frameshift mutation (p.Pro373ArgX38). No pathological mutations of MAPT were identified. The GRN mRNA sequence was analyzed by RT-PCR; however, a mutant allele product was not detected, suggesting degradation of the mutant allele by the nonsense-mediated RNA decay system. Accordingly, haploinsufficiency due to reduced expression of progranulin was considered to be a possible pathogenic mechanism of FTLD in these cases .

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+A 65-year-old woman was referred to our hospital for assessment of a gallbladder tumor that had been detected by abdominal ultrasonography during a medical checkup. She had no symptoms. Contrast-enhanced computed tomography revealed a papillary lesion (25 mm in diameter) in the fundus of the gallbladder with irregular thickening of the gallbladder wall. The boundary between the tumor and liver was unclear, and the wall thickening extended from the fundus to the cystic duct . Endoscopic retrograde cholangiography showed a complete filling defect in the cystic duct . Blood test showed inflammatory maker did not elevate. Serum carcinoembryonic antigen level was 2.1 ng/ml, and serum carbohydrate antigen 19-9 level was 24 U/ml. According to these findings, we diagnosed the tumor as gallbladder cancer invading the liver and cystic duct, and we decided to perform extended cholecystectomy.
+There were no adhesions around the gallbladder, while the gallbladder wall was thickened. The hard tumor was detected at the fundus. Intraoperative ultrasonography revealed the tumor did not invade liver obviously. Inflammation changes were seen around the neck and Calot triangle. After ligation and dissection of the cystic duct at the junction, the intraoperative frozen section of the cystic duct stump and 2 sentinel lymph nodes were negative for malignancy; therefore, we performed extended cholecystectomy with liver bed resection.
+Macroscopic examination of the resected specimen showed a superficially spreading papillary tumor with thick mucus on its surface . The gallbladder wall was diffusely thickened. Pathological examination revealed that the gallbladder neoplasm was composed of atypical cells arranged in a papillary architecture along with the development of fibrovascular stalks. These tall columnar cells contained large amounts of mucus . Ovarian-like stroma was not detected. The nucleolus body was remarkable, but the tumor was noninvasive and showed no evidence of lymph node metastasis. These pathological findings were compatible with ICPN. In immunohistochemical staining, MUC5AC and MUC6 were strongly positive. CK7 and MUC1 were also positive, but not CK20, MUC2, estrogen receptor, and progesterone receptor. Immunohistochemistry indicated that ICPN was predominantly gastric type, with focal pancreatobiliary type. In addition, many lymphocytes and multinucleated giant cells had infiltrated the thickened gallbladder wall with prominent Rokitansky–Aschoff sinuses. These finding were especially seen at the fundus and were indicative of chronic granulomatous changes within the fundus . Based on these pathological findings, we diagnosed the tumor as an ICPN concomitant with XGC.
+The patient was discharged on postoperative day 8 with no complications. She was clinically well with no evidence of recurrence at 3 months after resection.

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+A 70-year-old woman Gravid 12 was referred to the Tumor Clinic of Ghaem Hospital, Mashhad University of Medical Sciences in September 2013. Her symptoms were abdominal pain, loss of appetite, nausea, and vomiting from 20 days ago with a history of moderate hematemesis. No severe disease was observed in her medical records. She looked dehydrated and ill in terms of general appearance. Vital signs were blood pressure 70/50 Hgmm, pulse rate 100/minute, temperature 36.1°C and respiratory rate 14/minute. Laboratory studies detected leukocytes 20000 and PMN 87%. Liver and kidney function tests were normal. She was misdiagnosed with the left bundle block view in ECG and the AF rhythm in auscultation which caused her to undergo medical therapy in CCU. At first admission in hospital, abdominal examination revealed tenderness in the right and left lower quadrant of abdomen without rebound tenderness and guarding, and evidence of rigidity and abdominal distention.
+In sonography evaluation, size of uterus was 133.5 × 80.5 cm with hypoechoic mass 101 × 109 cm in the left lateral of uterine body, which could be probably interpreted as uterine myoma, and some free fluid in peritoneal cavity was also reported. Paracentesis 5 mL suppurative fluid was aspirated under the guidance of sonography. Findings of CT-scan were a round cystic mass with focal calcification at its periphery located in the pelvic cavity with the diameter about 14 × 11.5 cm probably ovarian cyst adenoma ( and ).
+Based on the diagnosis of peritonitis (suppurative fluid aspirated), emergency laparotomy was performed and 700 mL of suppurative fluid in the abdominal cavity with normal appearance bowel and liver was found. The origin of pus draining was a 1 × 1 cm rupture in the anterior wall of uterus. However, there were multiple polypoid tumors in cervical canal yielded stenosis of cervical discharge. After peritoneal irrigation with 5 to 6 L of normal saline, total hysterectomy with bilateral salpango-oophorectomy was performed. Then, the patient received board-spectrum antibiotic. But in recovery image, the patient became oliguria with rise of creatinine level, and decrease of the blood pressure, despite normal hemoglobin level. Despite all medication and efforts performed, the general condition of the patient deteriorated and she expired ten hours after operation probably because of the septic or cardiogenic shock.

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+A 54-year-old Caucasian man with no known previous comorbidity developed sudden-onset severe right-sided calf pain. The pain occurred while he was taking a casual walk in the evening. The pain intensity gradually worsened over the next few hours. The patient also noted progressive swelling of the calf of the right leg, gradually extending to the ankle. He denied trauma and could not recall a history of animal or insect bite. There was also no recent history of immobility. He was on no medication, either prescription or over-the-counter. The symptom onset was spontaneous and unprecipitated. The patient sought initial pain relief and self-medicated with codeine-paracetamol 30/500 mg and ibuprofen 400 mg. Failure to achieve adequate pain relief, along with evolution of symptoms with the development of numbness on the same side below the knee, prompted the patient to seek medical assistance.
+On clinical examination, the patient appeared to be in severe pain. He was afebrile with normal hemodynamic parameters, with a pulse rate of 85 beats per minute. Systolic and diastolic blood pressure measurements were 133 mmHg and 76 mmHg, respectively. Oxygen saturation was 97% on room air. His National Early Warning Score 2 (NEWS2) was 0 based on clinical assessment. Systemic clinical examination was normal. On examination of the lower limbs, the right calf measured 45 cm in circumference and the left calf measured 44 cm in circumference. On visual assessment there was no rubor or blisters. However, the skin appeared tense and stretched. The right leg and calf were tender to the touch. The right-sided dorsal and posterior tibial pulses were present and capillary refill time was < 2 seconds, which was normal. The anterior and peroneal compartment was visually tense, which was more evident with toe movement. A reduction in sensation to light touch was also noted.
+Bedside venous blood gas analysis revealed a normal pH of 7.4 and a normal electrolyte profile, with blood glucose of 5.8 mmol/L (normal reference = 7–11.1). The serum lactate level was 1.6 mmol/L (normal < 1.8). Whole blood analysis revealed hemoglobin of 155 g/L (normal reference = 130–180), with a total white blood cell count of 9.9 × 109/L (normal reference = 3.7–11) and a normal differential count. Platelet count was 275 × 109/L (normal reference = 150–450). Renal and liver function and coagulation parameters were all normal. C-reactive protein was 4.3 mg/L (normal reference = < 5) and the D-dimer level was normal at 327 µg/L (normal reference = 0–500). Considering the clinical context and near normal biochemical parameters, the initial working clinical suspicion was compartment syndrome of the right leg despite the absence of an obvious etiology. This was based on the classical presentation, especially when D-dimers were negative, making deep vein thrombosis unlikely. Urgent magnetic resonance imaging of the lower limbs was done, which revealed gross edema and swelling of the right lateral leg compartment involving the peroneus and longus muscle, consistent with acute lateral compartment syndrome .
+The patient received analgesia with intravenous administration of morphine 5 mg. The leg was kept in an elevated position. Urgent surgical consult was taken, and the patient underwent emergency anterior and peroneal compartment fasciotomy on the same evening of presentation. Subsequently he underwent a second-look washout and graft fasciotomy of the right lateral leg. He had an uncomplicated clinical course and underwent physiotherapy and recovered well, and was discharged 3 days after initial admission with a plan for review in 5 days to assess the graft and in 2 weeks to reassess the fasciotomy site. He was discharged on oral pain relief medication.

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+A 15-year-old boy was diagnosed with spastic diplegia cerebral palsy, Gross Motor Function Classification System level IV, knee flexion contracture, equinus foot, and paralysis of right upper extremity with adduction contracture. His height was 160.0 cm and his weight was 50.2 kg. He underwent tendon fractional release of the bilateral tendons of the semitendinosus muscle, semimembranosus muscle, and biceps femoris muscle. Achilles tendon lengthening was performed on the right equinus foot using Vulpius elongation. His lower limbs were fixed with above knee plaster splints in the knee extended position and intermediate ankle position 2 weeks after surgery, and he subsequently used short leg braces. Preoperative passive range of joint motion values were as follows: right knee 35–130/left knee 20–130, ankle dorsiflexion with knee extension (DKE) 15/15, and ankle dorsiflexion with knee flexion (DKF) 35/35. At 6 postoperative months, range of joint motion was right knee 15–130/left knee 10–130, DKE 15/10, and DKF 25/20. Knee extension range and DKF improved postoperatively. Preoperative manual muscle testing showed the following: knee extension 3/3, knee flexion 4/4, ankle dorsiflexion 1/1, and ankle plantar flexion 1/1. Before surgery, he had begun crawling in the house. Before HAL intervention, he could not move with crawling because of postoperative muscle weakness. It was thought that muscle weakness was due to disuse muscle atrophy after surgery.
+Hybrid Assistive Limb intervention was administered twice during postoperative months 10 and 11 in an outpatient department. Normal outpatient physical therapy was carried out in combination. The patient used the HAL for clinical study type S size (target 145–165 cm). A walking device (All-in-One Walking Trainer; Healthcare Lifting Specialist, Denmark) with a harness was used for safety, and the HAL intervention consisted of walking with the assistance of two physical therapists (Additional files and ). The HAL intervention session lasted 60 min, including rests (10 min) and time for attachment/detachment (20 min). The HAL suit has a hybrid control system comprising the CVC and CAC. The CVC mode of the HAL suit can support the patient’s voluntary motion by providing assistive torque to each joint according to voluntary muscle activity. This study used the CVC mode, which allows the operator to adjust the degree of physical support to the patient’s comfort and gradually reduce support as training progresses. Functional ambulation was assessed with the 10 m-walk test without wearing HAL and video analysis preoperatively and pre- and post- each HAL intervention (Additional files and ). We analyzed one gait cycle of the patient with Dartfish. Walking speed, stride, and cadence in the 10 m-walk test were analyzed. We took a walking video from the sagittal plane and analyzed the video in slow motion, pausing the image to measure the joint angle using the Dartfish Team Pro ver5.5. The angle of the hip, knee, ankle, and trunk in walking and in the gait cycle was analyzed using video. Video images were played back frame by frame, and the phase at the beginning of each gait cycle was confirmed. One gait cycle is defined as the movement starting from initial contact on one side till the next initial contact on the same side. The beginning of the loading response phase is defined as the initial contact, the beginning of mid stance is defined as opposite side toe off, the beginning of terminal stance is defined as heel off, the beginning of pre swing is defined as opposite side initial contact, the beginning of initial swing is defined as toe off, the beginning of the mid swing is defined as intersection of the feet, and the beginning of the terminal stance is defined as the vertical lower leg.
+In the 10 m-walk test, the patient used ankle foot orthosis preoperatively, and did not use orthosis pre- and post-HAL intervention. He used the walker as a walking aid.
+Table shows the results of the 10 m-walk test. Speed, stride, and cadence for walking were almost the same preoperatively and pre-HAL intervention. Post-first HAL intervention, speed, stride, and cadence were increased compared to pre-HAL intervention. This was maintained until the next HAL intervention and further improved after the second HAL intervention. HAL intervention increased walking speed from 21.7 to 32.1 m/min, stride from 0.40 to 0.47 m, and cadence from 54.23 to 68.9 steps/min.
+Ankle angle during walking showed little change because he wore a short leg brace while walking preoperatively. Pre-HAL intervention, the dorsiflexion angle was large in the terminal stance and pre-swing, the plantar flexion angle was large in the initial swing, and there was a large difference between the right and left ankle angle . Post-HAL intervention, range of movement of the ankle joint became more narrow, left-right symmetry increased , and extension angles of the knee in the stance phase increased . Excessive dorsiflexion and plantar flexion of the ankle joint disappeared due to extension of the angle of the knee . His extension angle of the hip did not increase and the trunk was leaning forward . Flexion of the upper limbs was strong due to spastic diplegia; therefore, he walked with the head bent forward. Because of the anteversion position, his hip joint did not show extension in walking . Although the horizontal plane and the hip joint were examined, extension of the hip angle in the pre-swing phase was increased . In the gait cycle, asymmetry between the left and right was prominent preoperatively . Comparing pre- and post-HAL, the proportion of terminal stance in the stance phase and swing phase was increased. Since the length of stride was expanded due to increased extension angles of the knee and hip, the ratio of terminal stance and terminal swing increased .
+After HAL intervention, he was able to crawl and gained the ability to move within his house, similar to his status before operation. There was no adverse event such as fall or fractures during the HAL intervention. The patient was able to walk easily while wearing HAL, and he actively participated in HAL intervention.

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+A 35-year-old woman was found to have a few shadows with GGOs on chest CT in 2012. She was monitored and a shadow in right S10 was found to increase in size, which suggested lung adenocarcinoma. The patient was referred to our hospital for further evaluation. The patient had a history of bronchial asthma. The shadow in right S10 had increased to 14 × 8 mm by 2015 . Other shadows also appeared . After preoperative CT-guided marking, the patient underwent video-assisted thoracoscopic surgery with a right wedge resection of the lower lobe that included the largest nodule in S10 and other nodules. Her postoperative course was uneventful.
+Grossly, the surgical specimen contained pale, somewhat yellow lesions . Histopathological examination of the right S10 lesion and other nodules revealed small- or medium-sized lymphocyte-like cells that were located in the alveolar interseptal spaces. The alveolar walls remained intact . Immunohistochemical staining showed that tumor cells were positive for CD20 (1:400 dilution; DAKO, Carpinteria, CA, USA, Fig. ), CD79a (1:200 dilution; DAKO, Carpinteria, CA, USA), and BCL2 (1:50 dilution; DAKO, Carpinteria, CA, USA, Fig. ) expression and negative for CD10 (1:50 dilution; Novocastra, Newcastle upon Tyne, UK), cyclin D1 (1:75 dilution; DAKO, Carpinteria, CA, USA) and CD30 (1:40 dilution; DAKO, Carpinteria, CA, USA). The lesions were diagnosed as extranodal marginal zone B-cell lymphoma of MALT. The patient has remained well during 12 months of follow up after surgery. Although she did not receive chemotherapy because the MALT lymphoma lesions have been stable without progression, the patient is kept under close observation because of potential progression of the disease.

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+A 54 year old man presented in the emergency department of our hospital with a three weeks history of fever, shivering, abdominal discomfort and watery, unbloody diarrhoea. The patient's medical history was otherwise remarkable for a metabolic syndrome with arterial hypertension, diabetes mellitus type 2 and obesity. His regular medication consisted of metformin and enalapril/hydrochlorothiazide. The clinical examination confirmed a bad general health condition with intermittent fever up to 40°C and shivering. He was hypotensive (85/55 mmHg), had a normal pulse rate and was tachypnoic (20 breaths/min.). The abdomen was distended; showed normal bowel sounds and rebound tenderness – consistent with a diffuse peritonism. Furthermore the clinical examination was unremarkable. Laboratory profile was consistent with systemic inflammation, acute renal failure and hepatopathy. Platelets were low with 41 G/l (normal range 150–450 G/l). Lactate and coagulation parameters were within normal limits. Antibodies for hepatitis A, B and C were negative. Urine analysis was unremarkable. The abdominal computerized tomography (CT scan) showed a big retroperitoneal abscess provoked by a diverticulitis of the sigmoid colon, as well as air in the portal vein system and in the inferior mesenteric vein (pylephlebitis). Ascites and hepatosplenomegaly were present .
+Sepsis due to the described intraabdominal focus was diagnosed and a broad-spectrum antibiotic treatment with intravenous piperacillin/tazobactam and amikacin was started. After administration of fluids blood pressure stabilized. Cultures of ascites fluid were positive for Klebsiella pneumoniae, Escherichia coli and Candida albicans. In blood cultures Escherichia coli, Klebsiella oxytoca and Bacteroides fragilis could be isolated without resistances against piperacillin/tazobactam. In order to treat the intraabdominal growth of Candida albicans high-dose fluconazole was added. The patient was operated on the second hospital day to evacuate the retroperitoneal abscess (Hartmann's operation: sigma resection, generating a colostomy with the proximal end of the descending colon and a blind rectal pouch with the proximal end of the distal segment). Because of anuria haemofiltration was started after surgery. During haemofiltration low doses of unfractionated heparin were administered to keep the filter patent.
+One week later – on day 9 of hospitalisation – secretions from abdominal drainages became bloody and cloudy with an amount of 2000 ml/day. The coagulation profile at this time was: thrombocytes 52 G/l, international normalized ratio (INR) 1.3 (normal range <1.3), prothrombin time (PT) 14.5 s (normal range <11 s), activated partial thromboplastin time (aPTT) 44 s (normal range 25–34 s), fibrinogen 3.2 g/l (normal range 1.7–4 g/l) and factor VII 29% (normal range 70–120%). There was a progressive metabolic acidosis with lactate levels around 6 to 17 mmol/l (normal range <1.8 mmol/l). As the treatment with metformin had been stopped at admission, when lactate levels were within normal limits, the current progressive lactate acidosis was ascribed to ongoing sepsis. With raising inflammatory markers, antibiotic therapy was changed to meropenem and a second laparotomy was performed. A putrid retroperitoneal haematoma was removed. During surgery, diffuse intraabdominal bleeding required extended surgical blood coagulation and the substitution of 1 platelet (TC) and 6 packed red cell concentrates (RC), as well as 7 units of fresh frozen plasma (FFP). At this time the patient received intraoperatively one dose of rFVIIa (70 μg/kg). The coagulation profile at this time was consistent with a DIC with platelets 62 G/l, INR 1.4, PT 16 s, D-Dimers 3.22 μg/ml (normal range <0.5 μg/ml), fibrinogen 1.2 g/l and aPTT 80 s. Because of the sustained bleeding the abdomen was left open to prevent intraabdominal compartment syndrome. Postoperatively high doses of vasoactive drugs had to be administered to maintain circulation. Severe metabolic acidosis (pH 6.9) with a lactate of 22 mmol/l was present because haemofiltration had to be discontinued during surgery. The bleeding remained uncontrolled despite further substitution of 1 TC and 6 RC, 5 FFP, tranexamic acid (Cyclokapron®), protamin hydrochloride (Protamin®) and von Willebrand factor concentrate (Haemate®). Therefore, a second dose of rFVIIa (70 μg/kg) was given. Twelve hours after the second laparotomy – in the morning of day 10 – a third laparotomy was performed. Again, a haematoma with diffuse retroperitoneal bleeding had to be removed. Surgical haemostasis and retroperitoneal cloth packing for tamponade were performed. The patient received intraoperatively 4 EC, 6 FFP and 2 doses of rFVIIa (each 70 μg/kg). After the surgery, the bleeding remained uncontrolled despite the administration of 3 FFP every 8 hours, rFVIIa every 4 hours (35 μg/kg) and TC and RC as needed . The patient died 15 hours after the third operation in multiorgan failure. No autopsy was performed.

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+Our patient was a 42-year-old Tajik, Afghan man with no known medical illness who presented to our institution with lethargy, anorexia, pallor, and progressive abdominal distension that had developed over a duration of 4 months. On examination, the patient was pale, not in distress, and had no lymphadenopathy. His abdominal examination revealed gross splenomegaly crossing the midline with the liver just two finger breadths in the subcostal region. His complete blood count revealed moderate anemia, thrombocytosis, and hyperleukocytosis (450,000 white blood cells per microliter), showing predominance of granulocytes with a bimodal peak of mature neutrophils (68%) and myelocytes (33%). The patient’s blast count was 4% with normal basophil count. The clinical impression at that time was CML in CP based on the initial clinical and hematological evaluation. The patient was counseled to proceed with cytogenetic analysis for confirmation and prognostication of disease, but, due to financial constraints, he opted to start on TKI therapy. Accordingly, the patient was started on conventional imatinib therapy 400 mg/day. Initially, he responded well with resolution of hyperleukocytosis and improvement in hemoglobin and platelet count toward normal, but he did not achieve complete hematological remission. A repeated complete blood count analysis revealed moderate anemia, mild thrombocytopenia, and the presence of >90% blast cells in a total white cell count of 62,000/μl. After detailed counseling, the patient agreed to proceed with cytogenetic analysis, in which the analyzed metaphases of all 20 cells revealed 45,XY, presence of Ph chromosome (9q34;22q11.2), and additional complex chromosomal abnormalities, including deletion of chromosomes 6q23.3 to q27, monosomy 11, monosomy 12, insertion 12p13.3, and a marker chromosome, as shown in Fig. . Ultimately, the patient and his family were advised to proceed with allogeneic bone marrow transplant, considering the patient’s complex karyotype and nonresponsiveness to TKI therapy.

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+A 25-year-old previously well white woman presented with two generalized tonic–clonic seizures, which were preceded by a 2-week history of prodromal flu-like symptoms and nonspecific headache. She was agitated in the emergency department for which she required midazolam.
+Her routine bloods were unremarkable. A computed tomography (CT) scan of her brain showed mild generalized cerebral edema and a magnetic resonance imaging (MRI) showed bilateral temporal lobe lesions involving her hippocampi and amygdala, which were more extensive on the right; this is an appearance in keeping with limbic encephalitis. An electroencephalogram (EEG) showed periodic lateralized epileptiform discharges and slow wave changes, which were maximal in the frontal and temporal regions.
+She was initially treated with acyclovir for possible HSV encephalitis. She also received levetiracetam to prevent seizures. However, she deteriorated over the next week with behavioral changes, memory impairment, hypoventilation, and coma. She was admitted to ICU 9 days after admission for airway support.
+Investigations revealed that her cerebrospinal fluids (CSF) had an elevated lymphocyte count and anti-NMDAR antibodies were strongly positive. Anti-NMDAR antibodies were also detected in her serum. The diagnosis of anti-NMDAR encephalitis was made 11 days after admission. She was commenced on a 5-day course of methylprednisolone, 5 days of plasmapheresis, and 5 days of immunoglobulin administered intravenously. She continued to have features of orofacial dyskinesia (that is, jaw opening and closing, chewing, facial grimacing, lip pouting) and tongue protrusion, which are characteristic features of this illness with autonomic instability; she remained intubated.
+During the search for an ovarian teratoma, an MRI of her abdomen and pelvis showed a left ovarian 2.6 cm simple cyst and a right ovarian 19 mm hemorrhagic cyst with no evidence of a teratoma. A whole body positron emission tomography (PET) scan was negative for malignancy. The serum tumor markers carcinoembryonic antigen (CEA) and CA-125 were also negative.
+A multidisciplinary team discussed with her family the risks and benefits of bilateral oophorectomy including premature menopause, the need for hormone replacement therapy (HRT), and fertility issues balanced with the chances of neurological recovery. A decision was made to proceed with laparoscopic bilateral salpingo-oophorectomy and harvesting of ovarian tissue for cryopreservation, despite no convincing radiological evidence of an ovarian teratoma; the procedure was performed 29 days after admission. Histopathology of her left ovary revealed a mature cystic teratoma/dermoid cyst with mature neuroglial elements resembling a cerebral ventricle . The ovarian teratoma had a prominent inflammatory response associated with the neural/glial elements: cytotoxic T lymphocytes (CD8-positive cells) were prominent; CD4-positive T helper cells and CD20-positive B lymphocytes were also found. This inflammatory response is unusual for teratomas, and points to the cellular immune response involved in our patient’s encephalitis.
+Postoperatively she continued to receive rituximab followed by cyclophosphamide. She started to show signs of improvement with fluctuating level of consciousness: intermittently obeying commands, spontaneous eye opening, mouthing words, and smiling. She suddenly improved and a repeat CT of her head showed some volume loss of her right hippocampus.
+One month later she was oriented with a Glasgow Coma Scale of 15/15 and was transferred to our medical ward where she remained seizure free on levetiracetam. A cognitive screen showed no deficits with a Mini–Mental State Examination (MMSE) score of 26/30, a repeat EEG showed a major reduction in the severity of the slow wave change and the disappearance of epileptogenic activity. A follow-up brain MRI showed developing hippocampal atrophy on the right.
+At 3 months, our patient maintained an excellent recovery, apart from mild short-term memory impairment. She regained strength and was mobilizing independently with no further involuntary movements or seizures. She remained well at 7 months post-diagnosis and was fully independent in all acts of daily living, with some symptomatic improvement in memory, such that her MMSE was 30/30 and her Addenbrooke’s Cognitive Examination score was 98/100. Her EEG had normalized and MRI revealed persistent involutional change to the right hippocampal head. The NMDAR antibodies remained positive in her blood, one year after recovery.

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+A previously healthy 48-year-old woman, with no significant past medical history and no family history of colorectal diseases, presented to the emergency room with abdominal distension, colicky pain, and a history of repeated episodes of lower gastrointestinal hemorrhage for as long as couple of months. She also complained of 8 kg weight loss in the last 2 months. She denied taking any prescription or over-the-counter medications. Clinical examination revealed a malnourished woman in severe distress due to diffuse abdominal tenderness. Signs of colonic obstruction were apparent. Digital rectal examination was indicative for rectal bleeding. Her vital signs were temperature 38°C, pulse 118/min, blood pressure 105/60 mmHg, and respiratory rate 20/min. Blood counts showed Hb 7.4 g/dl and a white blood count of 16.000. Serum electrolytes, liver function tests, and urinalysis were unremarkable. A plain abdominal X-ray and abdominal CT scan confirmed the signs of large bowel obstruction, along with a polypoid mass fully occluding the lumen of the terminal sigmoid colon. The patient was taken to the operating room where a standard left hemicolectomy was performed because of the malignant appearance of the mass and the extensive lymph node involvement that was found intraoperatively .
+Histological examination revealed a branching polypoid lesion characterized by mucosa projections with a central muscular core . Additionally, misplaced mucosa was encountered within the submucosa forming cystic structures, while partly preserved continuity with the polypoid part of the lesion could be demonstrated . The colonic epithelium both of the exophytic and the endophytic component showed extensive adenomatous transformation with high-grade dysplasia . A lesion-restricted transmural Crohn-like inflammation with prominent lymphoid aggregates was also present. The final diagnosis was consistent with a solitary hamartomatous polyp of Peutz-Jeghers type characterized by an inverted component, analogous to colitis cystica profunda, and by extensive high-grade dysplastic changes. The patient had an uneventful postoperative recovery and complete resolution of her symptoms. Follow-up colonoscopy 3 months after surgery showed no abnormal findings. The patient remains free of symptoms.

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+A 53-year-old white man presented to our knee clinic with knee pain. The pain was located in the posteromedial aspect of his left knee and first presented whilst training for a marathon. The pain was a continuous dull ache, which would often wake him from sleep. He had no improvement from conservative management trialled by his general practitioner, which included rest, ice, elevation, orally administered non-steroidal anti-inflammatory drugs, and physiotherapy. There was no history of trauma, locking, or giving way of the knee. He was otherwise fit and well with no medical co-morbidities; he was very active and had not had any previous injuries or surgeries to his left knee.
+A physical examination revealed normal alignment of his knee and hindfoot, no effusion, and an area of point tenderness posteromedially, not over the hamstrings or the pes anserinus. There was full range of movement with a positive medial step off and good tracking of the patella with no gross patellofemoral crepitus. He also did not have any significant ligamentous instability and an examination of his ipsilateral hip joint was normal.
+Plain radiographs taken at the time of presentation did not reveal any significant abnormalities and magnetic resonance imaging (MRI) was organized, which demonstrated the presence of a cord-like structure that originated from the fabella and passed medially, dividing into two parts around the semimembranosus tendon . The superficial part appeared to blend in with the semimembranosus tendon sheath itself, whereas the deeper part was thought to blend in with the superficial fascia of the gracilis and semitendinosus. This was associated with the presence of diffuse thickening of the distal semimembranosus tendon suggesting impingement of the tendon .
+As he continued to be symptomatic, and conservative measures had failed, he underwent a knee arthroscopy which demonstrated a grossly thickened semimembranosus with fluid collection around it. A band arising from the fabella, running transversely across the popliteal fossa and around the semimembranosus tendon was noted, confirming the diagnosis of semimembranosus impingement. This band, thought to be congenital in nature, was divided, and the semimembranosus fully released .
+Postoperatively, he recovered well and was allowed to fully weight bear with crutches. He was followed up at 6 weeks post-surgery, at which time his symptoms had resolved and he was back to training for a marathon.

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+A 83-year-old hypertensive man presented to the Emergency Department for dizziness and hypotension. He was treated by β-blockers (bisoprolol), diuretics (hydrochlorothiazide), ACE inhibitors (valsartan) and platelet inhibitors (lysine acetylsalicylate) for hypertension and arythmia. The patient denied any thoracic pain or recent trauma. Upon admission, blood pressure was 60/40 mmHg on both arms, and hypotension persisted despite a fluid loading of 2.5 L. A vasopressor support was promptly initiated (norepinephrin: 1,2 μg/kg/min). A bradycardia (54 bpm) with decreased cardiac sounds and distended jugular veins were noted. The patient had oliguria and mottled skin. A severe metabolic acidosis was observed (pH: 7.31; BD: -10.4 mmol/L; lactate: 6.76 mmol/L). ALAT level was moderately increased (62 UI/L) without increase in bilirubin or troponin. The electrocardiogram recorded a normal sinus rhythm with an incomplete left bundle branch block. Transthoracic echocardiography disclosed a circumferential pericardial effusion with a compressed right atrium and increased respiratory variations of tricuspidal mitral Doppler velocities. Left ventricular systolic function was normal, without regional wall motion abnormality. Contrast-enhanced thoracic CT scan ruled out an acute dissection of the ascending aorta and confirmed the presence of the circumferential pericardial effusion . A pig-tail catheter was placed within the pericardial sac using the subcostal approach under echocardiographic guidance. There were withdrawn 500 ml of blood, which resulted in a transient improvement of hemodynamics. Rapidly, hypotension resumed despite increasing doses of Norepinephrine (up to 0,7 μg/kg/min) and the pericardial drainage remained productive (450 ml/hour of fresh blood). This prompted a reoperation under extracorporeal circulation. The surgeon confirmed the presence of a hemopericardium with numerous clots in the dependent region of the pericardial sac. An active bleeding was identified at the level of the retroventricular coronary artery and of the epicardial surface which was related to a superficial laceration of the posterolateral wall of the left ventricle. The pericardium was thickened with several "sharping" calcified plaques in the vicinity of the bleeding areas. Hemostatic patches were placed and the posterior aspect of the pericardium was resected and replaced by a pericardial patch. The postoperative course was uneventful. On day 2, vasopressors were stopped and the patient was successfully extubated. The pathologic examination of pericardial plaques disclosed a calcified pericardium without specific tumoral infiltration or inflammatory process . No any sign of a tuberculosis origin was evidenced. One month later, the patient remained asymptomatic. Final diagnosis was a spontaneous cardiac tamponade secondary to a coronary artery injury attributed to a "sharping"calcified pericardial plaque.