Analysis of open chromatin regions in bladder cancer links beta-catenin mutations and Wnt signaling with neuronal subtype of bladder cancer

Urothelial carcinoma of the bladder is the most frequent bladder cancer affecting more than 400,000 people each year. Histopathologically, it is mainly characterized as muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC). Recently, the studies largely driven by consortiums such as TCGA identified the mutational landscape of both MIBC and NMIBC and determined the molecular subtypes of bladder cancer. Because of the exceptionally high rate of mutations in chromatin proteins, bladder cancer is thought to be a disease of chromatin, pointing out to the importance of studying epigenetic deregulation and the regulatory landscape of this cancer. In this study, we have analyzed ATAC-seq data generated for MIBC and integrated our findings with gene expression and DNA methylation data to identify subgroup specific regulatory patterns for MIBC. Our computational analysis revealed three MIBC regulatory clusters, which we named as neuronal, non-neuronal and luminal outlier. We have identified target genes of neuronal regulatory elements to be involved in WNT signaling, while target genes of non-neuronal and luminal outlier regulatory regions were enriched in epithelial differentiation and drug metabolism, respectively. Neuronal regulatory elements were determined to be ss -catenin targets (p value=3.59e-08) consisting of genes involved in neurogenesis such as FGF9, and PROX1, and significantly enriched for TCF/LEF binding sites (p value=1e-584). Our results showed upregulation of ss -catenin targets regulated by neuronal regulatory elements in three different cohorts, implicating ss -catenin signature in neuronal bladder cancer. Further, integration with mutation data revealed significantly higher oncogenic exon 3 ss -catenin mutations in neuronal bladder cancer compared to non-neuronal (odds ratio=31.33, p value=1.786e-05). Our results for the first time identify regulatory elements characterizing neuronal bladder cancer and links these neuronal regulatory elements with WNT signaling via mutations in beta -catenin and its destruction complex components

Nosocomial respiratory syncytial virus infections in three cases in a bone marrow transplantation unit Kemik iliǧi nakli ünitesinde yatan üç olguda nozokomiyal solunum sinsityal virus enfeksiyonu

Here we report the spread of respiratory syncytial virus (RSV) infection among three patients, who were hospitalized in an adult hematopoetic stem cell transplantation (HSCT) unit because of hematologic diseases, and effects of RSV infection on post-transplant outcome. The patients were placed into reverse isolation for administration of preparative regimens (high dose chemotherapy) in HSCT unit with high-energy particulate air (HEPA)-filtered single rooms. First case was a 62 years-old man with advanced multiple myeloma, which was refractory to multiple line treatment with high dose steroid including regimens and with secondary acute myelogenous leukaemia (AML); second case was a 45 years-old male patient with multiple myeloma, who had undergone autologous HSCT following high dose chemotherapy; third case was a 52 years-old man with AML that was refractory to multiple line treatment and had undergone allogeneic HSCT from a HLA-matched unrelated donor. Nasopharyngeal aspirate samples were collected from the patients in order to search for RSV positivity. RSV was investigated by in-house nested polymerase chain reaction (PCR) in the first patient and by direct antigen detection method (Monofluoscreen RSV-Biorad, France) in the others. First case had clinical picture of RSV infection just on the HSCT day when high dose chemotherapy has already been given. As RSV-RNA analysis yielded positive result, peroral ribavirin was initiated. Engraftment did not occur in this patient. He developed severe respiratory failure which necessitated mechanical ventilatory support, however, he has succumbed. After the detection of RSV positive index case, weekly screening of RSV in other five patients in the same unit had been performed. Following the first case, after nine and 17 days, respectively, RSV positivity was detected in two more patients. While clinical signs and symptoms of RSV infection developed in second case, third case remained asymptomatic. Both of the following patients had received ribavirin very early at first RSV positivity and recovered from RSV infection. Engraftment did not occur in the last patient who had undergone allogeneic HSCT from a HLA-matched unrelated donor and a second HSCT was performed. As a result, in HSCT patients, early diagnosis of RSV infection by PCR analysis may provide support to postpone immunosupressive treatment and help assesment of the management

Detection of HHV-8 and HPV in laryngeal carcinoma

Objective: In this study we aimed to investigate the presence of human herpesvirus 8 (HHV-8) and human papillomavirus (HPV) in laryngeal carcinoma

Understanding clinical outcomes and factors influencing mortality in intensive care unit patients with COVID-19-associated candidemia

Background: During the COVID pandemic, research has shown an increase in candidemia cases following severe COVID infection and the identification of risk factors associated with candidemia. However, there is a lack of studies that specifically explore clinical outcomes and mortality rates related to candidemia after COVID infection.Objectives: The aim of this international study was to evaluate the clinical outcomes and identify factors influencing mortality in patients who developed candidemia during their COVID infection.Patients/Methods: This study included adult patients (18 years of age or older) admitted to the intensive care unit (ICU) and diagnosed with COVID-associated candidemia (CAC). The research was conducted through ID-IRI network and in collaboration with 34 medical centres across 18 countries retrospectively, spanning from the beginning of the COVID pandemic until December 2021.Results: A total of 293 patients diagnosed with CAC were included. The median age of the patients was 67, and 63% of them were male. The most common Candida species detected was C. albicans. The crude 30-day mortality rate was recorded at 62.4%. The logistic regression analysis identified several factors significantly impacting mortality, including age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07, p < .0005), SOFA score (OR 1.307, 95% CI 1.17-1.45, p < .0005), invasive mechanical ventilation (OR 7.95, 95% CI 1.44-43.83, p < .017) and duration of mechanical ventilation (OR 0.98, 95% CI 0.96-0.99, p < .020).Conclusions: By recognising these prognostic factors, medical professionals can customise their treatment approaches to offer more targeted care, leading to improved patient outcomes and higher survival rates for individuals with COVID-associated candidemia