Drug-induced liver injury by glatiramer acetate leading to liver transplant: A case report.

Glatiramer acetate (GA) is a widely used immune-modulating drug in relapsing multiple sclerosis (MS). Although a few cases of drug-induced liver injury during GA therapy have been reported earlier, herein we present the case of a 43-year-old woman with relapsing MS who experienced acute liver failure after GA therapy, ultimately leading to liver transplant.

Gastrointestinal basidiobolomycosis - A rare fungal infection: Challenging to diagnose yet treatable - Case report and literature review.

Gastrointestinal Basidiobolomycosis is a rare manifestation of Basidiobolus ranarum infection. In this report, we present two cases of gastrointestinal Basidiobolomycosis. The first patient presented with obstructive symptoms, fever, and weight loss. The diagnosis of Basidiobolomycosis was not made until after surgery, when Liposomal amphotericin-B combined with itraconazole were administered, leading to the resolution of laboratory markers of inflammation and patient's symptoms. The second case involves a young woman who presented with hematochezia, perianal induration, and abdominal pain. The patient had previously been diagnosed with Crohn's disease and treated accordingly, but her symptoms did not improve. Due to the endemicity of tuberculosis in Iran, the patient was treated for TB but still showed no improvement. However, a perianal biopsy sample revealed the Splendore Hoeppli phenomenon and fungal elements in GMS staining, leading to the diagnosis of gastrointestinal Basidiobolomycosis. Treatment with itraconazole and co-trimoxazole led to a significant improvement in symptoms and laboratory indices after one week, including the resolution of perianal induration. The key takeaway from this report is the importance of considering rare infections in the differential diagnosis of gastrointestinal conditions such as IBD and GI obstruction.

Integrated pan-cancer of AURKA expression and drug sensitivity analysis reveals increased expression of AURKA is responsible for drug resistance.

INTRODUCTION: The AURKA gene encodes a protein kinase involved in cell cycle regulation and plays an oncogenic role in many cancers. The main objective of this study is to analyze AURKA expression in 13 common cancers and its role in prognostic and drug resistance. METHOD: Using the cancer genome atlas (TCGA) as well as CCLE and GDSC data, the level of AURKA gene expression and its role in prognosis and its association with drug resistance were evaluated, respectively. In addition, the expression level of AURKA was assessed in colorectal cancer (CRC) and gastric cancer (GC) samples. Besides, using Gene Expression Omnibus (GEO) data, drugs that could affect the expression level of this gene were also identified. RESULTS: The results indicated that the expression level of AURKA gene in 13 common cancers increased significantly compared to normal samples or it survived poorly (HR >1, p < 0.01) in lung, prostate, kidney, bladder, and uterine cancers. Also, the gene expression data showed increased expression in CRC and GC samples compared to normal ones. The level of AURKA was significantly associated with the resistance to SB 505124, NU-7441, and irinotecan drugs (p < 0.01). Eventually, GEO data showed that JQ1, actinomycin D1, and camptothecin could reduce the expression of AURKA gene in different cancer cell lines (logFC < 1, p < 0.01). CONCLUSION: Increased expression of AURKA is observed in prevalent cancers and associated with poor prognostic and the development of drug resistance. In addition, some chemotherapy drugs can reduce the expression of this gene.

Expression profiling of RTL1 in human breast cancer tissues and cell lines.

Breast cancer (BC) is the most common cancer in females. In this regard, the identification of molecular alterations driving BC is an immediate need for developing effective immunotherapeutic tools. Here we investigated the expression of a placenta-specific protein, Retrotransposon-like 1 (RTL1) in a series of BC tissues and cell lines. RTL1-specific polyclonal antibody was generated and characterized. Using tissue microarray immunohistochemistry, expression of RTL1 in a total of 147 BC and 36 non-malignant breast tissues was investigated and the association of patient's clinicopathological parameters with RTL1 expression was then examined. Expression of RTL1 in four BC cells was assessed by flow cytometry, immunofluorescent staining and Western blotting. We observed a mixture pattern of nuclear and cytoplasmic RTL1 expression in most tissues examined, however nuclear expression was found to be dominant pattern of expression. The level of nuclear RTL1 expression was significantly higher in BC tissues (P < 0.001). A statistically significant association between nuclear RTL1 expression and histological grade and vascular invasion was found (P < 0.001 and P < 0.05). All cell lines expressed RTL1 with varying degrees at their surface. The most invasive BC cell line MDA-MB-231, compared to T-47D, SKBR3 and MCF7 expressed higher levels of RTL1 at their surface. Cells with a low level of surface expression, expressed high levels of intracellular RTL1 expression. Our antibody reacted with a specific band of about 125 KD in normal human placenta and all cell lines examined. In contrast to placenta, two additional bands were also observed in cancer cell lines. Our results showed for the first time that RTL1 is differentially expressed in BC compared to non-malignant breast tissues and is associated with a higher grade and vascular invasion. In BC cells with high metastatic and invasive potential, this antigen is mostly confined to cell surface compartment indicating the possibility of using antibody-based immunotherapy for advanced metastatic BC patients.

Expression and Prognostic Significance of Cancer/Testis Antigens, MAGE-E1, GAGE, and SOX-6, in Glioblastoma: An Immunohistochemistry Evaluation.

BACKGROUND & OBJECTIVE: Glioblastoma is the most common primary malignancy of the brain, the prognosis of which is poor. Immunotherapy with cancer/testis (CT) antigens is a novel therapeutic approach for glioblastoma. This study aimed to investigate the expression rate of MAGE-E1, GAGE, and SOX-6 in glioblastoma tumors using the method of immunohistochemistry (IHC). METHODS: Expression of MAGE-E1, GAGE, and SOX-6 were determined by IHC in 50 paraffin blocks of glioblastoma. The results were compared between variables including age, gender, tumor location, and Karnofsky performance status (Kps) score. Survival analysis was also performed. RESULTS: The expression levels of SOX-6, MAGE-E1, and GAGE were 82%, 78%, and 76%, respectively. The relationship between CT antigens and age, gender, and tumor location was not significant, while the association between MAGE-E1 expression and age was statistically significant (P=0.002). High expression levels of SOX-6 and MAGE-E1 were associated with low Kps scores (P=0.034 and P<0.001, respectively). Survival analysis showed that age >40 and Kps score <80 were associated with significant relationship with shorter survival rate. (P=0.005 and P=0.018, respectively). Expression of MAGE-E1 and GAGE was negatively associated with overall 2-year survival rate (P=0.001 and P=0.021, respectively). CONCLUSION: The expression of all the three CT antigens, especially MAGE-E1 and SOX-6, was high in patients with glioblastoma. It can be concluded that these markers could be ideal targets for immunotherapy in such patients. MAGE-E1 and SOX-6 can be considered as important markers in determining the prognosis of glioblastoma.

Catastrophic Brain Aspergillosis after Liver Transplantation.

Background. Liver transplantation has many complications. Because of receiving immunosuppressive regimens, infectious complications in these patients may have fatal results. Aspergillosis in solid organ recipients is one of the most common fungal infections that usually occur 1 month after transplantation. Aspergillus infection mainly involves the lungs. Although the central nervous system may get involved due to hematogenous spreading from lungs, isolated central nervous system involvement is rarely reported. Case Presentation. The patient was an 8-year-old boy, with a case of Wilson disease, who underwent liver transplantation due to acute fulminant hepatic failure. Four days after the surgery, he was affected by fever, agitation, loss of consciousness, hemiparesis, and focal seizure. Brain MRI showed abscess formation, whereas chest X-ray was normal. Intravenous antibiotics were initiated but the patient's condition was not improving; therefore, surgical drainage of the abscess was performed. The pathological investigation was compatible with aspergillosis. Antifungal therapy with voriconazole was administrated. His symptoms were resolved but unfortunately, brain lesions caused persistent vegetative state. Discussion. Aspergillus is a ubiquitous organism that mainly occurs in immunocompromised patients. Aspergillosis could be prevented by environmental modification such as installing high-efficiency particulate air filters. Chemoprevention with triazoles, echinocandins, and polyenes is also effective. Voriconazole is the drug of choice for aspergillosis treatment. Although voriconazole is a highly effective antifungal drug, cerebral aspergillosis is often fatal.

Pathological Findings of Postmortem Biopsies From Lung, Heart, and Liver of 7 Deceased COVID-19 Patients.

Background. A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been affecting almost all nations around the world. Most infected patients who have been admitted to intensive care units show SARS signs. In this study, we aimed to achieve a better understanding of pathological alterations that take place during the novel coronavirus infection in most presumed affected organs. Methods. We performed postmortem core needle biopsies from lung, heart, and liver on 7 deceased patients who had died of coronavirus disease 2019. Prepared tissue sections were observed by 2 expert pathologists. Results. Diffuse alveolar damage was the main pathologic finding in the lung tissue samples. Patients with hospitalization durations of more than 10 days showed evidence of organization. Multinucleated cells in alveolar spaces and alveolar walls, atypical enlarged cells, accumulation of macrophages in alveolar spaces, and congestion of vascular channels were the other histopathologic alteration of the lung. None of our heart biopsy samples met the criteria for myocarditis. Liver biopsies showed congestion, micro- and macro-vesicular changes, and minimal to mild portal inflammation, in the majority of cases. Conclusions. Similar to the previous coronavirus infection in 2003, the main pathologic finding in the lung was diffuse alveolar damage with a pattern of organization in prolonged cases. The SARS-CoV-2 infection does not cause myocarditis, and the ischemia of myocardium is the most probable justification of the observed pathologic changes in the heart. Liver tissue sections mostly showed nonspecific findings; however, ischemia of the liver can be identified in some cases.

Neuroendocrine tumor of the common bile duct: A case report of extremely rare cause for obstructive jaundice.

INTRODUCTION: Neuroendocrine tumors (NET) of common bile duct are rare. There have been less than 100 cases reported worldwide. PRESENTATION OF CASE: A 37-year-old female patient was referred to our center after six months of abdominal pain with no definite diagnosis. At initial presentation, she complained of increased abdominal pain, nausea, vomiting, oral intolerance to food and icteric sclera. Physical examination and laboratory tests were indicative of pancreatitis. At day four, she took retrograde cholangiopancreatography (ERCP) and a mid CBD stenosis or impacted stone was found. In order to locally investigate the lesion, Endoscopic Ultrasound (EUS) examination was performed which reported 16 × 12 mm isoechoic tumoral lesion at the middle of the CBD. In this regard we decided to perform ERCP-guided brushing biopsy of the lesion. The pathology report was highly suggestive for malignancy. She underwent resection of the mid portion of the CBD with Roux-en-Y hepaticojejunostomy, cholecystectomy and portahepatis lymph node dissection. The pathology report indicated that the CBD lesion was well-differentiated neuroendocrine tumor grade II. DISCUSSION: The exact etiology of developing NET in the bile duct tissues is not clear however cholelithiasis and congenital malformation of the biliary tract has been proposed to cause chronic inflammation with subsequent metaplasia which ultimately transforms into NET. CONCLUSION: As there are very few cases of NETs of the CBD, no definite surgical or medical treatment is proposed. Currently, combination of radical surgical resection and lymph node dissection followed by chemotherapy is the treatment of choice.

Primary rectal choriocarcinoma associated with rectal adenocarcinoma in a woman with a history of ulcerative colitis: Case report.

INTRODUCTION: Primary rectal choriocarcinoma is an extremely rare malignancy. The association of these neoplasms in patients with inflammatory bowel disease (IBD) has not been reported. PRESENTATION OF CASE: A 34-year-old female with history of Ulcerative Colitis (UC) gave birth to a male fetus. She had postpartum bleeding and high level of beta-human chorionic gonadotropin (ßhCG) was detected. Although initial investigations failed to confirm molar pregnancy, abnormal uterine bleeding and high ßhCG level necessitate chemotherapy administration. She did not respond to chemotherapy sessions accordingly. Meanwhile, the patient experienced rectorrhagia and colonoscopy revealed a firm submucosal polypoid lesion 8-10 cm from the anal verge. The multidisciplinary team candidate the patient for total proctocolectomy and ileal pouch anal anastomosis. Although postoperative course was uneventful and ßhCG level dropped but it showed a rising pattern in follow ups. Chemotherapy was planned but there was not suitable response. Unfortunately, the patient passed away 20 months after the initial diagnosis. DISCUSSION: Pathology report indicated the coexistence of moderately differentiated tubular adenocarcinoma and choriocarcinoma. We assume previous history of UC might have put her at higher susceptibility to develop carcinoma and this poorly differentiated carcinoma has led to choriocarcinoma. Considering the fact that in most cases of colorectal choriocarcinoma, choriocarcinomatous differentiation was found alongside colonic adenocarcinoma made dedifferentiation theory to be the most acceptable explanation. CONCLUSION: The adenocarcinoma of the colon and rectum in the setting of IBD may become so dedifferentiated that gain some characteristics of germ cell tumors.

Comparison of Patient-collected and Lab Technician-collected Nasopharyngeal and Oropharyngeal Swabs for Detection of COVID-19 by RT-PCR.

BACKGROUND & OBJECTIVE: A simple approach to prevent close contact in healthcare settings during the COVID-19 outbreak is to train patients to collect their own nasopharyngeal and oropharyngeal swabs and deliver them to medical laboratories to have them processed. The aim of our study was to compare lab technician- with patient- collected oropharyngeal and nasopharyngeal samples for detection of the coronavirus disease 2019 (COVID 19) using rapid real-time polymerase chain reaction (rRT-PCR). METHODS: Fifty adult patients with flu-like symptoms and radiologic findings compatible with atypical pneumonia who were admitted to the infectious diseases ward of Imam Khomeini Hospital Complex, Tehran, Iran, with a clinical diagnosis of COVID-19 from February 28 to April 27 of 2020 were randomly selected and entered in our study. Two sets of naso- and oropharyngeal swabs were collected, one set by a lab technician and the other by the patients, and the COVID-19 rRT-PCR test was performed. RESULTS: Of 50 selected cases, in seven patients all collected naso- and oropharyngeal swabs tested positive, and in 22 patients all samples tested negative for COVID-19 in rRT-PCR. Discrepancies between rRT-PCR results of lab technician- and patient-collected swabs were observed in 12 nasopharyngeal and 13 oropharyngeal specimens. Positive lab technician-collected and negative patient-collected samples were observed in 10 and 5 nasopharyngeal and oropharyngeal specimens, respectively. Negative lab technician-collected and positive patient-collected samples were observed in two and seven nasopharyngeal and oropharyngeal specimens, respectively. The overall percentage of agreement among both nasopharyngeal and oropharyngeal swabs taken by a lab technician and patients was 76% with a kappa value of 0.49 (P=0.001). CONCLUSION: Based on our findings, lab technician-collected naso- and oropharyngeal swabs cannot be replaced by patient-collected ones with regard to COVID-19 rRT-PCR.

Wound Infection with an Unusual Pathogen after Liver Transplantation.

Mucormycosis is a rare and highly invasive fungal infection caused by Mucorales fungi of the class Zygomycetes. Cutaneous mucormycosis typically has a good survival rate when diagnosed early. In this report, we presented a patient with surgical site mucormycosis after liver transplant surgery. Our patient was a 50-year-old man with cirrhosis due to nonalcoholic steatohepatitis who received liver transplant from a deceased donor. On the 8th day of transplant, the patient had fever and purulent discharge from the surgical site. The wound became black and necrotic in the next day. A microbiologic study showed mycelium in wound culture. The smear of the discharge was positive for aseptate hyphae, and the report of fungal culture revealed Rhizopus sp. In the histopathologic examination, mucormycosis was confirmed. The combination of antifungal and surgical debridement was a successful treatment in this case. Cutaneous fungal infections should be considered in the differential diagnosis of any nonhealing or black scar-infected wound that does not respond to broad-spectrum antibiotics.

Assessment of SGO1 and SGO1-AS1 contribution in breast cancer.

Shugoshin-like protein 1 (SGO1) participated in the proper progression of mitosis. This fundamental role has indicated the importance of this gene in the pathogenesis of cancer as a disorder of mitotic cell division. A previous high throughput study of long non-coding RNAs (lncRNAs) expression in lung cancer has identified aberrant expression of SGO1-antisense 1 (SGO1-AS1) in these specimens. In the current study, we quantified expression of SGO1 and SGO1-AS1 in 39 breast cancer tissues and their paired adjacent non-cancerous tissues (ANCTs). Expression of SGO1-AS1 was considerably decreased in tumoral tissues compared with ANCTs (expression ratio = 0.49, P value = 0.03). However, we could not identify significant difference in expression of SGO1 between these two sets of specimens (expression ratio = 2.9, P value = 0.2). Transcript quantities of SGO1-AS1 were associated with age at disease onset (P= 0.01). Expression of either gene was associated with hormone receptors status or clinical features such as grade and stage. There was an inverse correlation between expressions of genes in both sets of samples. Finally, transcript amounts of SGO1-AS1 could distinguish these two sets of samples with accuracy of 63% (P value = 0.03). Our results imply significance of SGO1-AS1 in breast cancer and necessitate conduction of mechanistic studies to find the molecular pathways in this regard.