Background Coronavirus Disease 2019 (Covid-19) is expanding worldwide. The characteristics of this infection in patients varies from country to country. To move forward, clinical data on infected patients are needed. Here, we report a comparison between fatalities and recovery of patients with severe Covid-19, based on demographic and clinical characteristics. Methods Between 5 March and 12 May 2020 in Mashhad, Iran, 1278 of 4000 suspected Covid-19 patients were confirmed positive by real-time reverse-transcriptase–polymerase-chain-reaction assay of upper respiratory specimens. We compared the demographic, exposure history and clinical symptoms of 925 survivors and 353 fatal cases with confirmed disease. Results Mean (SD) age for all confirmed patients was 56.9 (18.7) years, 67.1 (15.9) years in fatal cases and 53.0 (18.3) years in survivors. Multivariate logistic regression analysis showed that the outcome of patients was associated with age (odds ratio = 1.049, P = 0.0001, 95% CI = 1.040–1.057). Despite a high burden of Covid-19 infections in the 30–39 and 40–49 year age groups, most of these (89.6 and 87.2%, respectively) recovered. The median (IQR) duration of hospitalization was 9.0 (6.0–14.0) days. The most prevalent co-morbidities were cardiovascular disorders (21%) and diabetes (16.3%). Dyspnoea (72.7%), cough (68.1%) and fever (63.8%) were the most frequent clinical symptoms. Healthcare workers, of whom two (3%) died, comprised 5.2% of infected cases. Combination antiviral and antibiotic therapy was used in 43.0% of cases. Conclusions The characteristics of severe Covid-19 varied substantially between fatal cases and survivors, with diabetes and cardiovascular disorders the most prevalent co-morbidities. In contrast to other studies, there were a higher number of fatalities in younger patients in our setting.

ObjectivesLynch syndrome (LS), a genetically inherited autosomal disorder, increases the incidence of colorectal carcinoma (CRC). We aimed to perform a universal strategy to assess the prevalence and clinicopathological characteristics of early onset CRCs at high risk of LS versus late-onset ones in the Iranian population.SettingA local population-based study from Northeastern Iran.Participants321 consecutive CRCs and pathology specimen screened between 2013 and 2016.Primary and secondary outcome measuresRetrospectively, information regarding the clinical criteria was obtained by interviewing the patients with CRC or, their families. Pathologists tested tumours with immunohistochemistry (IHC) staining of four mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2). Tumours with absent IHC staining of MLH1 were tested for BRAF mutations to exclude sporadic CRCs. Prevalence of early onset CRCs at high risk of LS and familial CRC type X were assessed as primary and secondary outcome measures, respectively.ResultsOf 321 CRCs (13/123 (10.57%), early onset vs 21/198 (10.6%) late-onset) were detected to be MMR-deficient (dMMR). Nine early onset cases and 14 late-onset ones with a loss of MLH1 underwent testing for the BRAF mutation, none of the early onset and four (2.02%) late-onset were recognised as sporadic. The difference in the outcome of IHC-analysis between early and late-onset CRCs at high risk of LS was not statistically significant (p=0.34). Majority of the suspected LS tumours from early onset patients had arisen in distal part (8/11 (72.72%) vs 8/14 (57.14%)), all of which were occurred in the rectum or sigmoid.ConclusionClinically, these findings suggest that in case of limitation for BRAF testing, the practitioner in Iran may consider managing early onset dMMR cases like LS until access to BRAF testing becomes available to them, before germline testing to accurately diagnose LS.

Background Esophageal cancer is the sixth-leading cause of cancer-related deaths worldwide. Cancer stem cells (CSCs) are the main reason for tumor relapse in esophageal squamous cell carcinoma (ESCC). The NOTCH pathway is important in preservation of CSCs, therefore it is possible to target such cells by targeting MAML1 as the main component of the NOTCH transcription machinery. Methods In present study we isolated the CD44+ ESCC CSCs and designed a MAML1-targeted therapy to inhibit the NOTCH signaling pathway. CSCs were isolated using magnetic cell sorting utilizing the CD44 cell surface marker. Several stem cell markers were analyzed in the levels of protein and mRNA expression. The isolated CSCs were characterized in vivo in NUDE mice. Biological role of MAML1 was assessed in isolated CD44+ CSCs. A drug resistance assay was also performed to assess the role of MAML1 in CD44+ CSCs with 5FU resistance. Results The CD44+ CSCs had ability to form tumors in NUDE mice. MAML1 silencing caused a significant decrease (p = 0.019) and ectopic expression caused a significant increase in migration of CD44+ CSCs (p = 0.012). Moreover, MAML1 silencing and ectopic expression significantly increased and decreased 5FU resistance, respectively (p < 0.05). MAML1 silencing significantly increased the number of cells in G1 phase (p = 0.008), and its ectopic expression significantly increased the number of CD44+ CSCS in S phase (p = 0.037). Conclusions MAML1 may be utilized for targeted therapy with a low side effect to eliminate the CD44+ CSCs through inhibition of canonical NOTCH pathway in ESCC patients.

Deregulation of developmental signaling pathways such as Wnt/b-catenin and NOTCH are commonly observed in different cancers. A normal wnt pathway is essential for development and tissue homeostasis to preserve a normal balance between the differentiation and proliferation. PYGO2 is the main transcription factor of wnt pathway, while Msi1 is one of the wnt inhibitors. In this study we assessed the correlation between Msi1 and PYGO2 mRNA expression using Real time polymerase chain reaction in 48 esophageal squamous cell carcinoma (ESCC) patients. Although, there was not any significant correlation between the levels of Msi1 and PYGO2 mRNA expression, we observed a significant correlation between the Msi1 and PYGO2 overexpressed cases and depth of tumor invasion (p = 0.05). In conclusion, despite the role of these markers in tumor depth of invasion there is not any feedback between Msi1 and PYGO2 gene expression in ESCC.