Thrombotic thrombocytopenic purpura following ChAdOx1 nCov-19 vaccination: A case report.

Vaccine-associated thrombotic thrombocytopenic purpura (TTP) is a rare type of acquired TTP recently reported after COVID-19 vaccination. Merely four cases are ascribed to the ChAdOx1 nCoV-19 vaccine in the medical literature till the preparation of this study. In this case report, we describe a 43-year-old man who developed symptoms of TTP four days after receiving the second dose of the ChAdOx1 nCoV-19 vaccine. Peripheral blood smear demonstrated multiple schistocytes. Given a high plasmic score, he received plasma exchange, corticosteroids, and rituximab, and later, low ADAMTS 13 activity and high-titer ADAMTS inhibition antibody confirmed the diagnosis of COVID-19 vaccine-associated TTP. COVID-19 vaccine-associated TTP is an infrequent consequence of SARS-CoV-2 vaccination but with a substantial mortality rate which must be considered as one of the crucial differential diagnoses of post-COVID-19 vaccine thrombocytopenia besides vaccine-induced immune thrombotic thrombocytopenia and Immune thrombocytopenic purpura.

The role of inflammatory miRNA-mRNA interactions in PBMCs of colorectal cancer and obesity patients.

INTRODUCTION: Inflammation is a critical hallmark in obesity and colorectal cancer (CRC). This study aimed to investigate effective microRNA (miRNA)-messenger RNA (mRNA) interactions on inflammatory networks involved in obesity and CRC. METHODS: The literature searches were applied to identify genes expression reported on peripheral blood mononuclear cells (PBMCs) and/or blood of CRC subjects and to find inflammatory miRNA  in blood samples. Furthermore, bioinformatics analysis was utilized to find inflammatory miRNA:mRNA interactions of the genes. Finally, a case-control study was set to investigate the expression of LAMC1 and GNB3 genes besides miR-10b, miR-506-3p, miR-150-5p, and miR-124-3p in CRC and control subjects. RESULTS: The expression of LAMC1 gene in healthy control groups was associated with body mass index (BMI) (p < .05). The level of miR-10b (p < .001), miR-506 (p < .001), and miR-124 (p <. 001) were significantly increased in PBMCs of CRC patients, while they were not associated with BMI. The level of miR-150 was associated with BMI in healthy subjects (p < .05). CONCLUSIONS: The changes in the level of miR-506 and miR-124 in CRC patients may be associated with the regulatory role of these miRNAs on LAMC1 expression. The LAMC1 may be related to BMI, however, more observational studies on other populations are needed.

The importance of regulatory pathway mediated by Circ0001955 in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) has become one of the most common cancers in recent years. Given the importance that non-coding RNAs have recently acquired in various diseases including cancers, we decided to design this study to evaluate the expression levels of circ0001955/miR-145-5p/ONECUT2 axis in CRC. METHODS: After bioinformatics analysis of GEO datasets related to CRC, a putative circ0001955/ miR-145-5p/ ONECUT2 pathway was assumed. Then, the expression levels of these genes were measured in 50 CRC samples and adjacent tissues by qRT- PCR. Also, correlation coefficients, receiver operating characteristic (ROC) curves, and correlation between circ0001955 levels with clinicopathological parameters of patients were analyzed. RESULTS: Circ0001955 and ONECUT2 were considerably up-regulated, while the expression level of miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0001955, miR-145-5p, and ONECUT2. We did not find any significant correlation between circ0001955 expression and clinicopathological parameters. CONCLUSION: Our study showed that circ0001955 is dysregulated in CRC. This finding can open a new window for researchers for a better understanding of the potential pathways involved in CRC pathogenesis and, consequently, to find new treatment pathways.

Association of miRNA targetome variants in LAMC1 and GNB3 genes with colorectal cancer and obesity.

BACKGROUND: Colorectal cancer (CRC) is one of the most common obesity-associated cancers. Inflammation is also considered the most important factor between obesity and CRC. This study aimed to examine miRNAs binding sites variants on inflammatory genes identified using bioinformatics and systematic approach on clinical samples that were collected from CRC patients and controls. METHODS: The candidate variants related to CRC inflammatory genes were obtained from genome-wide association studies and their population-specific haplotypes. The variants were analyzed according to their genomic position on the miRNA targetome. Targetome variants in inflammation-related genes were selected for genetic association study by TaqMan genotyping assay. RESULTS: The GG genotype of rs7473 decreased the risk of obesity (p < 0.05). Heterozygous genotype (GA) of rs1547715 decreased the risk of CRC (p < 0.05). In the rs7473/rs1547715 genotype and haplotype, the frequencies of AA/GA and GG/AA lessened in CRC and obesity, respectively (p < 0.05). CONCLUSIONS: The variants of rs7473 and rs1547715 were associated with obesity and CRC, respectively. The above-mentioned associations could be made based on the interactions of these variants with miRNAs.

Importance of Circ0009910 in colorectal cancer pathogenesis as a possible regulator of miR-145 and PEAK1.

INTRODUCTION: Colorectal cancer (CRC) is one of the most frequent neoplasms in the world. Based on the emerging role of noncoding RNAs, particularly circular RNAs in pathogenesis of cancers, we designed this study to inspect the expression levels of a circ0009910-mediated regulatory pathway in colorectal cancer. METHODS: After bioinformatics analyses and construction of putative circ0009910/ miR-145-5p/PEAK1 pathway, the expression levels of these components were evaluated in 50 CRC tissues and adjacent specimens by quantitative real-time PCR. Moreover, we appraised the correlation coefficients between these transcripts and calculated the correlation between circ0009910 expression levels with clinicopathological features of patients. RESULTS: Circ0009910 and PEAK1 were significantly upregulated, while miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0009910, miR-145-5p, and PEAK1. We also reported considerable correlations between circ0009910 expression and clinicopathological parameters including sex and perineural invasion. Finally, ROC curve analysis showed circ0009910 level as a discriminative biomarker for CRC. CONCLUSION: For the first time, we could introduce circ0009910 as an important biomarker in CRC. Collectively, this investigation helped us to identify a newly diagnosed pathway in CRC that can be a potential axis for designing effective drugs for treatment of CRC patients.

Jejunogastric intussusception: a case report of rare complication of gastrojejunostomy.

Jejunogastric intussusception (JGI) is a rare complication of gastrojejunostomy surgery (<0.1% of cases), yet requires an urgent diagnosis. Mortality rate ranging from 10% to 50% based on delay in diagnosis and surgical intervention. Vomiting, abdominal pain and hematemesis are the most common symptoms. We report a 60 years old man admitted to the emergency department, complaining of epigastric pain and recurrent hematemesis for 3 days. Emergent upper GI endoscopy was done, and gastroenterologist reported a protruded edematous jejunal mucosa with bleeding, which formed a mass-like lesion. Abdominopelvic computed tomography scan also showed a target sign in favor of jejunal intussusception. Midline laparotomy and reduction of jejunal loop was performed and the patient was discharged without any further complications. In patients presented with hematemesis and abdominal pain and history of gastrectomy, JGI must considered as a possible cause because early diagnosis and treatment are necessary to prevent further complications.

Investigation of circRNA-miRNA-mRNA network in colorectal cancer using an integrative bioinformatics approach.

AIM: The aim of this study was to integrate both coding and non-coding available microarray data in the development of colorectal cancer (CRC) with bioinformatics analyses to attain a more inclusive pathobiologic map of their molecular interactions and functions. BACKGROUND: Identification of competing endogenous RNAs (ceRNAs), especially circRNAs, has become a new hotspot in cancer research, although their roles and underlying mechanisms in CRC development remain mostly unknown. METHODS: Microarray data was retrieved from the Gene Expression Omnibus (GEO) database and analyzed. Several bioinformatics tools and databases were applied for further elucidation. Principal component analysis (PCA) was run separately for four datasets. The dysregulated circRNA-miRNA-mRNA, co-expression, and protein-protein interaction (PPI) networks were established. RESULTS: PCA discloses colorectal tumors; normal tissue can be distinguished not only by mRNAs expression profile, but also by both circRNA and miRNA expression profiles. In this study, 14 DE mRNAs, 85 DE miRNAs, and 36 DE circRNAs were identified in CRC tissue and compared with normal tissue. Taking their potential interactions into account, a circRNA-miRNA-mRNA network was constructed. The results disclosed some DE circRNAs with potential oncogenic (circ_0014879) or tumor suppressive (circ_0001666 and circ_0000977) effects. Finally, the PPI network suggests pivotal roles for DOCK2 and PTPRC dysregulation in the progression of CRC, possibly by facilitating tumor escape from immune surveillance. CONCLUSION: The current study proposes a novel regulatory network consisting of DE circRNAs, miRNAs, and mRNAs in CRC development that highlights the roles of DE circRNAs at the upstream of oncotranscriptomic cascade in CRC development, suggesting their potential to be utilized as both prognostic and therapeutic biomarkers.

Pancreatic Neuroendocrine Tumor presenting as a diffuse pancreatic enlargement, case report and review of literature.

Pancreatic neuroendocrine tumors are rare neoplasms that comprise 1-2% of all pancreatic tumors. However, they are the second most common solid pancreatic neoplasms. They have a wide range of imaging appearances and they can show common to very rare imaging presentations. Most of the time they are solitary well-marginated enhancing solid mass arising in a certain aspect of the pancreas. We present a case report of a 41-year-old female who underwent clinical work-up for abdominal pain, loss of appetite and weight loss for the past year. Ultrasound, computed tomography, and magnetic resonance imaging show diffuse homogenous pancreatic enlargement without contour deformity or a focal mass. Lymphoma and autoimmune pancreatitis were suggested based on imaging findings but IGg4 level and other lab data were normal. Endoscopic ultrasonography confirmed the diffuse enlargement of the pancreas without peripheral structures involvement. The pathological results of multiple fine-needle aspiration biopsy from all parts of the enlarged pancreas revealed a low-grade neuroendocrine tumor.

Colonic Mucosal Infiltration of IgG4 Plasma Cells and Ulcerative Colitis: Determinant of Presence, Activity, Extension, and Duration of Disease.

BACKGROUND Infiltration of IgG4 positive plasma cells has been detected in the colonic mucosa of patients with ulcerative colitis (UC). The aim of the study was to investigate the association between colonic mucosal infiltration of IgG4 plasma cells and the presence, activity, extension, and duration of UC. METHODS In this case-control study (2009-2014), 102 subjects (84 with UC/18 controls) were enrolled. Clinical records and rectosigmoid biopsies of UC patients were selected, and biopsies were stained with IgG4 monoclonal antibodies. IgG4 positive plasma cells were counted by a single pathologist. RESULTS Amongst 84 patients with UC, 73.8% had UC without primary sclerosing cholangitis (PSC), and 26.2% had UC with PSC. IgG4 plasma cells were seen in 35 (41.7%) patients with UC and 0% of controls (p = 0.001). The mean amount of IgG4 containing plasma cells was significantly different between active and inactive patients with UC, although it was not significantly different between UC patients with and without PSC. The presence of IgG4 infiltration was significantly associated with the extension and duration of the disease. Furthermore, IgG4 count had a sensitivity/specificity of 78.6%/83.3% for the diagnosis of UC. CONCLUSION Our study revealed the diagnostic role of IgG4 plasma cells in the colonic mucosa of patients with UC and its association with activity, extension, and duration of disease.

A Rare Cause of Gastrointestinal Bleeding in a 65-Year-Old Man with History of Polycythemia Vera.

Polycythemia vera (PV) is classified as a myeloproliferative disorder (MPD). Such patients are prone to both thrombotic and hemorrhagic events. Although gastrointestinal (GI) bleeding is not a prominent manifestation of PV, it would be life threatening and necessitating hospital admission and blood transfusion if it occurs. GI hemorrhage in these patients may be due to Aspirin usage, peptic ulcer disease (PUD), acquired Von Willbrand disease, Dieulafoy lesion (DL), Mallory Weiss tear, and esophageal and gastric varices. DL is an enlarged, thick-walled artery in the muscularis mucosa with a small submucosal defect. In this case report, we describe a 65-year-old man with history of PV presented with a massive upper GI bleeding. After a therapeutic endoscopic hemostasis failure and reoccurrence of bleeding during hospital admission, an abdominal computed tomography (CT) was ordered, which revealed an aberrant artery originated from aorta directly into the stomach. An angiographic embolization was considered for the patient, which was successfully performed. Our patient was complicated by splenic infarction due to splenic collateral arteries embolization and the overwhelming thrombotic tendency of the patient himself due to the history of PV. Fortunately, our patient's signs and symptoms responded to supportive therapies and eventually he discharged well.

MicroRNA-binding site polymorphisms and risk of colorectal cancer: A systematic review and meta-analysis.

Genetic variations in miRNAs binding site might participate in cancer risk. This study aimed to systematically review the association between miRNA-binding site polymorphisms and colorectal cancer (CRC). Electronic literature search was carried out on PubMed, Web of Science (WOS), Scopus, and Embase. All types of observational studies till 30 November 2018 were included. Overall 85 studies (21 SNPs) from two systematic searches were included analysis. The results showed that in the Middle East population, the minor allele of rs731236 was associated with decreased risk of CRC (heterozygote model: 0.76 [0.61-0.95]). The minor allele of rs3025039 was related to increased risk of CRC in East Asian population (allelic model: 1.25 [1.01-1.54]). Results for rs3212986 were significant in overall and subgroup analysis (P < .05). For rs1801157 in subgroup analysis the association was significant in Asian populations (including allelic model: 2.28 [1.11-4.69]). For rs712, subgroup analysis revealed a significant (allelic model: 1.41 [1.23-1.61]) and borderline (allelic model: 0.92 [0.84-1.00]) association in Chinese and Czech populations, respectively. The minor allele of rs17281995 increased risk of CRC in different genetic models (P < .05). Finally, rs5275, rs4648298, and rs61764370 did not show significant associations. In conclusion, minor allele of rs3025039, rs3212986, and rs712 polymorphisms increases the risk of CRC in the East Asian population, and heterozygote model of rs731236 polymorphism shows protective effect in the Middle East population. In Europeans, the minor allele of rs17281995 may increase the risk of CRC, while rs712 may have a protective effect. Further analysis based on population stratifications should be considered in future studies.

Clinical and Pathological Features of Ulcerative Colitis in Patients with and without Clostridium Difficile Infection; An Observational Study.

BACKGROUND A dramatic rise in the rate of clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) has been reported in recent years. METHODS In this observational case control study, 65 patients were included and were divided into two groups of IBD + CDI as case group and IBD without CDI as control group. RESULTS 35 patients who had positive test for clostridium difficile were assigned to the case group. The control group consisted of 30 patients with negative test for clostridium difficile. Pancolitis was seen in the cases more statistically significant than the controls and proctitis was seen more among the controls than the cases (p = 0.001). The cases were on immunosuppressive (p = 0.001) and antibiotic (p = 0.02) therapy more than the controls. Colonoscopic findings revealed more severe and extensive inflammation among the cases versus milder inflammation among the controls, but these differences were not statistically significant (p = 0.2). Colectomy was seen in 10% of controls and none of the cases and this difference was statistically significant (p value = 0.05). More fecal calprotectin were seen among the cases than the controls and this difference was statistically significant (p < 0.05) CONCLUSION This study showed more clostridium difficile infection among the patients on antibiotic or immunosuppressive therapy. Pathological investigation revealed more severe and extensive inflammation among the cases than the controls. Cases had clinically more severe signs and symptoms with higher mayo scores than the controls. ESR (Erythrocyte sedimentation rate) and fecal calprotectin were higher in patients with positive clostridium difficile infection and serum albumin was lower in such patients.

Enterotoxigenic Bacteroides fragilis: A Possible Etiological Candidate for Bacterially-Induced Colorectal Precancerous and Cancerous Lesions.

Enterotoxigenic Bacteroides fragilis (ETBF) produces Bacteroides fragilis toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and colorectal cancer (CRC). In experimental models, ETBF has been shown to contribute to colon carcinogenesis. The present study was conducted to investigate mucosal colonization of ETBF in the colon to find a possible association between the presence of ETBF and precancerous and cancerous lesions. The mucosal biopsies of involved sites were obtained from 68 patients with precancerous and cancerous lesions and 52 healthy controls (HC). The samples were cultured on Bacteroides Bile Esculin agar. Then, specific primers were designed to detect B. fragilis and bft gene using quantitative real-time PCR, and the possible links of ETBF with clinicopathological characteristics was evaluated. Also real-time PCR was performed to detect the bft gene subtypes. Bacteroides fragilis was detected in 51% of the patients and 48% of HCs cultures. The 16SrRNA gene was found to be present in 63 and 81% of the patients and HCs' samples, respectively. Moreover, the bft gene was detected in 47 and 3.8% of the patients and HCs, respectively. Also, B. fragilis was significantly more abundant in the patients' samples compared to those of HCs. In the patient group, higher odds ratio (OR) of ETBF was significantly associated with serrated lesions and adenoma with low-grade dysplasia. The bft1 gene was the most prevalent subtype of bft gene, followed by the bft2 gene. This was the first study in Iran to demonstrate increased positivity of ETBF in patients with precancerous and cancerous lesions. In this study, the bft gene was found to be associated with CRC, especially in the patients with precancerous lesions and initial carcinogenic lesions. Moreover, the results suggest that mucosal BFT exposure is common and could be a risk factor and a screening marker for developing CRC.

Inflammation related miRNAs as an important player between obesity and cancers.

The growing trend in addition to their burden, prevalence, and death has made obesity and cancer two of the most concerning diseases worldwide. Obesity is an important risk factor for common types of cancers where the risk of some cancers is directly related to the obesity. Various inflammatory mechanisms and increased level of pro-inflammatory cytokines have been investigated in many previous studies, which play key roles in the pathophysiology and development of both of these conditions. On the other hand, in the recent years, many studies have individually focused on the biomarker's role and therapeutic targeting of microRNAs (miRNAs) in different types of cancers and obesity including newly discovered small noncoding RNAs (sncRNAs) which regulate gene expression and RNA silencing. This study is a comprehensive review of the main inflammation related miRNAs in obesity/obesity related traits. For the first time, the main roles of miRNAs in obesity related cancers have been discussed in response to the question raised in the following hypothesis; do the main inflammatory miRNAs link obesity with obesity-related cancers regarding their role as biomarkers? Graphical abstractConceptual design of inflammatory miRNAs which provide link between obesity and cancers.

Pain Relieving Effect of Sublingual Glycerol Trinitrate in Renal Colic: a Randomized Placebo-Controlled Trial.

INTRODUCTION: Renal colic is caused by colicky spasms of ureters. As has been shown in previous experiments, glycerol trinitrate (TNG) can inhibit these muscular spasms. OBJECTIVE: This study was performed to assess the pain relieving effect of TNG among patients referred due to renal colic pain to the emergency department (ED). METHODS: This study is a randomized, placebo-controlled study on 60 patients with renal colic who were referred to the ED, who were diagnosed clinically to have renal colic, and their pain was more than 5 based on a visual analogue scale (VAS). The patient's pain was recorded at the moment of clinical diagnosis, and each one received one capsule, either 0.4 mg TNG or placebo, plus a 100 mg indomethacin suppository. The pain score was re-assessed after 5 and 30 min. The values were recorded and compared using SPSS-16 software. RESULTS: Sixty patients with a mean age of 35.75 ± 11.99 years were enrolled (73.3% male). Patients in the two groups were matched for age (p = 0.290), sex (p = 0.559), and the presence of microscopic hematuria (p = 0.292). Pain relief from the start point until the end of the intervention was statistical different in all studied patients (p < 0.05); but the comparison between the two groups showed no significant difference in this regard (p = 0.440). CONCLUSION: It is likely that adding TNG to an indomethacin suppository had no significant effects on better pain management of patients referred with renal colic to the ED.

Squamous cell carcinoma (SCC) arising in esophageal colon interposition.

The idea of using the colon to replace a resected esophagus has a long history. The colon has become a favored organ for esophageal reconstruction in adults with esophageal cancer when the stomach is not suitable or is unavailable. In this article, we introduce an 84-year-old woman that she had surgery 40 years ago and presented with an invasive well differentiated squamous cell carcinoma of colonic origin in reconstructed esophagus.

An Additive Effect of Oral N-Acetyl Cysteine on Eradication of Helicobacter pylori.

Background. Helicobacter pylori is highly adapted to the gastric environment where it lives within or beneath the gastric mucous layer. The aim of this study was to evaluate whether the addition of N-acetyl cysteine to the treatment regimen of H. pylori infection would affect eradication rates of the disease. Methods. A total of 79 H. pylori positive patients were randomized to two therapeutic groups. Both groups received a 14-day course of three-drug regimen including amoxicillin/clarithromycin/omeprazole. Experimental group (38 subjects) received NAC, and control group (41 subjects) received placebo, besides three-drug regimen. H. pylori eradication was evaluated by urea breath test at least 4 weeks after the cessation of therapy. Results. The rate of H. pylori eradication was 72.9% and 60.9% in experimental and control groups, respectively (P = 0.005). By logistic regression modeling, female gender (OR 3.68, 95% CI: 1.06-5.79; P = 0.040) and treatment including NAC (OR 1.88, 95% CI: 0.68-3.15; P = 0.021) were independent factors associated with H. pylori eradication. Conclusion. The results of the present study show that NAC has an additive effect on the eradication rates of H. pylori obtained with three-drug regimen and appears to be a promising means of eradicating H. pylori infection.

FOP: still turning into stone.

Fibrodysplasia ossificans progressiva (FOP) is a rare catastrophic genetic condition of extraskeletal (heterotopic) ossification. One in every two million people is affected worldwide, with no ethnic, racial, gender, or geographic predisposition. Most cases of FOP arise from a spontaneous missense mutation in the gene encoding bone morphogenic protein (BMP) type II receptor (ACVR1/ALK2). Affected individuals are normal at birth apart from malformed great toes. Onset of clinical symptoms is usually in the first decade of life, presenting with episodic emergence of painful rapidly appearing tumor-like soft tissue swellings (flare-ups). Heterotopic bone replaces the skeletal muscles, tendons, ligaments, and connective tissue at the site of the damage through a process of endochondral ossification, causing fixation of joints and permanent limitation of motion. Most affected individuals are confined to wheelchair in the third decade of life. Worldwide rate of misdiagnosis of FOP is very high; clinicians often fail to associate the two classic clinical features of FOP: rapidly developing soft tissue swellings and the abnormal great toes. The current case presents a previously undiagnosed 39-year-old FOP patient, sadly a victim of lack of clinical awareness of this rare condition. As a result of repetitive iatrogenic harm, he has tragically "turned into stone."

Pseudoachalasia: a diagnostic challenge.

Here, we present a case of a 78-year-old man that underwent gastrointestinal endoscopy because of one- month history of dysphagia to liquids and solid foods with accompanying weight loss. On endoscopy, there was distal esophageal stenosis. Multiple biopsies were obtained. Histologic examination of the samples revealed normal tissue. The stenosis was treated by dilatation and abdomino pelvic computed tomography scanning was performed to search for an underlying malignant lesion that showed a mass adjacent to distal esophagus. We did endosonography- guided fine needle aspiration of the mass. It was a squamous cell carcinoma (SCC). Malignancy is a challenging diagnosis in patients with dysphagia and near normal endoscopy. To our knowledge, there are a few reports of SCC to cause it.