Kirklandhong9046

BACKGROUND Median survival for patients with glioblastoma is less than a year. Standard treatment consists of surgical debulking if feasible followed by temozolomide chemo-radiotherapy. The immune checkpoint inhibitor ipilimumab targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and has shown clinical efficacy in preclinical models of glioblastoma. The aim of this study is to explore the addition of ipilimumab to standard therapy in patients with glioblastoma. METHODS/DESIGN Ipi-Glio is a phase II, open label, randomised study of ipilimumab with temozolomide (Arm A) versus temozolomide alone (Arm B) after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma. Planned accrual is 120 patients (Arm A 80, Arm B 40). Endpoints include overall survival, 18-month survival, 5-year survival, and adverse events. The trial is currently recruiting in seven centres in the United Kingdom. TRIAL REGISTRATION ISRCTN84434175. Registered 12 November 2018.BACKGROUND Loeys-Dietz syndrome (LDS) is a systemic connective tissue disease (CTD) associated with a predisposition for intestinal inflammation, food allergy, and failure to thrive, often necessitating nutritional supplementation via gastrostomy tube. Poor wound healing has also been observed in in some patients with CTD, potentially increasing the risk of surgical interventions. We undertook to determine the safety and efficacy of gastrostomy tube placement in this population. METHODS We performed a retrospective cohort study of 10 LDS patients who had a total of 12 gastrostomy tubes placed. RESULTS No procedural complications occurred, although one patient developed buried bumper syndrome in the near post-procedural time period and one patient had a small abscess at a surgical stitch. Most patients exhibited improvements in growth, with a median immediate improvement in BMI Z-score of 0.2 per month following the institution of gastrostomy tube feedings. Those with uncontrolled inflammation due to inflammatory bowel disease or eosinophilic gastrointestinal disease showed the least benefit and in some cases failed to demonstrate significant weight gain despite nutritional supplementation. CONCLUSIONS Gastrostomy tube placement (surgical or endoscopic) is a generally safe and a reasonable therapeutic option for patients with LDS despite their underlying CTD.BACKGROUND Meckel's diverticulum is a remnant of the omphalomesenteric duct. It can lead to intestinal perforation, obstruction and gastrointestinal bleeding. While the internal hernia caused by Meckel's diverticulum is rarely reported. CASE PRESENTATION We report a case of a 45-year old female patient who presented with intestinal obstruction and on laparotomy was found to have Meckel's diverticulum with internal hernia causing intestinal gangrene. Segmental bowel resection was performed and the patient had uneventful recovery. CONCLUSIONS In patients with acute intestinal obstruction without previous abdominal surgery, Meckel's diverticulum and its complications should be suspected.BACKGROUND Before the era of targeted therapies, cytokines were the main therapy for metastatic renal cell carcinoma (mRCC). Our aim was to analyze the changes in treatments and overall survival (OS) of all mRCC patients in Estonia in relation to the introduction of new medications. METHODS All patients with mRCC who started medical therapy in Estonia during the years 2004-2012 were identified using the database of the Estonian Health Insurance Fund. Tumor and treatment data were gathered from medical records. Vital status data were obtained from the Estonian Population Registry. The only available therapy before 2008 was interferon alpha-2A (INFa2A), targeted agents added from 2008. For survival analysis, patients were divided into 2 groups INFa therapy only (group 1) and INFa followed by targeted agents or targeted agents therapy only (group 2). RESULTS Out of 416 identified patients, 380 were eligible for analysis. The most common 1st-line treatments were INFa (55%), sunitinib (32%) and INFa+bevacizumab (13%). SR-717 solubility dmso 28% of patients received 2nd-line therapies and 15% 3rd-line treatments. Median survival of all patients was 13.7 months [95% confidence interval (CI) 11.3-16.2]; 7.6 months (CI 6.4-8.6) for group 1 and 19.8 months (CI 15.6-22.9) for group 2. In multivariate analysis, group 1 had nearly four times higher risk of dying than group 2 [hazard ration (HR) 3.88, 95% CI 2.64-5.72]. CONCLUSIONS The implementation of targeted therapies significantly changed the outcomes of mRCC in Estonia it prolonged median survival, reduced the risk of death and also enlarged the proportion of patients who received medical therapy.BACKGROUND The expression of vascular endothelial growth factor (VEGF)-A/ VAGF receptors (VEGFRs) signaling plays a pivotal role in the tumor angiogenesis and the development of the immunosuppressive tumor microenvironment in glioblastomas. We have previously conducted exploratory clinical studies investigating VEGFRs peptide vaccination with and without multiple glioma oncoantigens in patients with recurrent high-grade gliomas. Recently, an exploratory clinical investigation of VEGFRs peptide vaccination was conducted in patients with progressive neurofibromatosis type 2. Those studies suggested that cytotoxic T lymphocytes (CTLs) induced by the vaccination can directly kill a wide variety of cells associated with tumor growth, including tumor vessels, tumor cells, and immunosuppressive cells expressing VEGFR1 and/or 2. In the present study, synergistic activity of the combination of VEGFRs peptide vaccination with chemotherapy was evaluated. METHODS We performed the first clinical trial to assess VEGFR1 andstudy was the paucity of the number of the samples. Further studies involving more patients are warranted to confirm the findings of this study. TRIAL REGISTRATION This study was registered as UMIN000013381 (University Hospital Medical Information Network-Clinical Trial Registry UMIN-CTR) on 5 March, 2014 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs031180170 on 1 March, 2019.BACKGROUND Interactions between proteins and non-proteic small molecule ligands play important roles in the biological processes of living systems. Thus, the development of computational methods to support our understanding of the ligand-receptor recognition process is of fundamental importance since these methods are a major step towards ligand prediction, target identification, lead discovery, and more. This article presents visGReMLIN, a web server that couples a graph mining-based strategy to detect motifs at the protein-ligand interface with an interactive platform to visually explore and interpret these motifs in the context of protein-ligand interfaces. RESULTS To illustrate the potential of visGReMLIN, we conducted two cases in which our strategy was compared with previous experimentally and computationally determined results. visGReMLIN allowed us to detect patterns previously documented in the literature in a totally visual manner. In addition, we found some motifs that we believe are relevant to protein-ligand interactions in the analyzed datasets.