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Introduction: Perforation peritonitis mostly results from the perforation of a diseased viscus. Other causes of perforation include abdominal trauma, ingestion of sharp foreign body and iatrogenic perforation. The diagnosis is mainly based on clinical grounds. Plain abdominal X-rays (erect) may reveal dilated and oedematous intestines with pneumoperitoneum. Ultrasound and CT scan may diagnose up to 72% and 82% of perforation respectively. The present study was carried out to study various etiological factors, modes of clinical presentation, morbidity and mortality patterns of perforation peritonitis presented in the RIMS hospital, Imphal, India. Material and Methods: The study was conducted from September 2010 to August 2012 on 490 cases of perforation peritonitis admitted and treated in the Department of Surgery. Initial diagnosis was made on the basis of detailed history, clinical examination and presence of pneumoperitoneum on erect abdominal X-ray. Results: A total of 490 patients of perforation peritonitis were included in the study, with mean age of 48.28 years. 54.29% patients were below 50 years and 45.71% patients were above 50 years. There were 54.29% male patients and 45.71% female patients. Only 30% patients presented within 24 hours of onset of symptoms, 31.43% patients presented between 24 to 72 hours and 38.57% patients presented 72 hours after the onset of symptoms. Mean duration of presentation was 54.7 hours. Overall 469 patients were treated surgically and 21 patients were managed conservatively. Overall morbidity and mortality recorded in this study were 52.24% and 10% respectively.

Ileosigmoid knot, also known as compound volvulus, is an unusual and a rare cause of intestinal obstruction. We are reporting a case of ileosigmoid knot in a 30-year-old male, who presented with lower abdominal pain. On examination, there was tenderness in the suprapubic area and later, the patient developed features of peritonitis. Exploratory laparotomy revealed a large volume of haemorrhagic fluid with gangrenous sigmoid colon, distended and gangrenous ileum twisted round the base of the sigmoid loop. Gangrenous portion of the ileum and sigmoid colon was resected and end to end anastomosis with Hartmann’s procedure was done.

Introduction: Perforation peritonitis mostly results from the perforation of a diseased viscus. Other causes of perforation include abdominal trauma, ingestion of sharp foreign body and iatrogenic perforation. The diagnosis is mainly based on clinical grounds. Plain abdominal X-rays (erect) may reveal dilated and oedematous intestines with pneumoperitoneum. Ultrasound and CT scan may diagnose up to 72% and 82% of perforation respectively. The present study was carried out to study various etiological factors, modes of clinical presentation, morbidity and mortality patterns of perforation peritonitis presented in the RIMS hospital, Imphal, India. Material and Methods: The study was conducted from September 2010 to August 2012 on 490 cases of perforation peritonitis admitted and treated in the Department of Surgery. Initial diagnosis was made on the basis of detailed history, clinical examination and presence of pneumoperitoneum on erect abdominal X-ray. Results: A total of 490 patients of perforation peritonitis were included in the study, with mean age of 48.28 years. 54.29% patients were below 50 years and 45.71% patients were above 50 years. There were 54.29% male patients and 45.71% female patients. Only 30% patients presented within 24 hours of onset of symptoms, 31.43% patients presented between 24 to 72 hours and 38.57% patients presented 72 hours after the onset of symptoms. Mean duration of presentation was 54.7 hours. Overall 469 patients were treated surgically and 21 patients were managed conservatively. Overall morbidity and mortality recorded in this study were 52.24% and 10% respectively. [ABSTRACT FROM AUTHOR]

Ileosigmoid knot, also known as compound volvulus, is an unusual and a rare cause of intestinal obstruction. We are reporting a case of ileosigmoid knot in a 30-year-old male, who presented with lower abdominal pain. On examination, there was tenderness in the suprapubic area and later, the patient developed features of peritonitis. Exploratory laparotomy revealed a large volume of haemorrhagic fluid with gangrenous sigmoid colon, distended and gangrenous ileum twisted round the base of the sigmoid loop. Gangrenous portion of the ileum and sigmoid colon was resected and end to end anastomosis with Hartmann's procedure was done. [ABSTRACT FROM AUTHOR]

Background: Transradial access is an increasingly popular route for cerebral angiography and neurointerventions. However, obstacles to wider adoption remain, especially for complex interventions typically performed with larger, multiaxial systems such as flow diversion. We sought to analyze the published evidence for transradial flow diversion of intracranial aneurysms., Methods: Using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, a literature review was performed to identify all published reports and studies of transradial flow diversion for intracranial aneurysm. The search was limited from April 2011 to February 2021. Primary outcome was successful completion of the procedure via a transradial approach. Heterogeneity was analyzed with Q and I 2 statistics. Secondary outcomes were transradial access-site complications and other complications., Results: In total, 11 studies involving 290 treated aneurysms were identified; 90.7% of the procedures were completed via the transradial approach. The heterogeneity between studies was high, with an I 2 of 56.9%. There were no transradial access-site complications. The procedural complication rate was 2.41%., Conclusions: Transradial access has a high success rate for both anterior and posterior circulation flow-diversion embolizations. The success rate may be particularly high for posterior circulation and right anterior circulation aneurysms. It has a negligible access-site complication rate. Transradial access is a viable alternative to transfemoral access for flow diversion and should be considered as a first-line approach., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glioblastoma is an aggressive and heterogeneous tumor in which glioblastoma stem cells (GSCs) are at the apex of an entropic hierarchy and impart devastating therapy resistance. The high entropy of GSCs is driven by a permissive epigenetic landscape and a mutational landscape that revokes crucial cellular checkpoints. The GSC population encompasses a complex array of diverse microstates that are defined and maintained by a wide variety of attractors including the complex tumor ecosystem and therapeutic intervention. Constant dynamic transcriptional fluctuations result in a highly adaptable and heterogeneous entity primed for therapy evasion and survival. Analyzing the transcriptional, epigenetic, and metabolic landscapes of GSC dynamics in the context of a stochastically fluctuating tumor network will provide novel strategies to target resistant populations of GSCs in glioblastoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Current management of gliomas involves a multidisciplinary approach, including a combination of maximal safe resection, radiotherapy, and chemotherapy. The use of intraoperative MRI (iMRI) helps to maximize extent of resection (EOR), and use of awake functional mapping supports preservation of eloquent areas of the brain. This study reports on the combined use of these surgical adjuncts., Methods: The authors performed a retrospective review of patients with gliomas who underwent minimal access craniotomy in their iMRI suite (IMRIS) with awake functional mapping between 2010 and 2017. Patient demographics, tumor characteristics, intraoperative and postoperative adverse events, and treatment details were obtained. Volumetric analysis of preoperative tumor volume as well as intraoperative and postoperative residual volumes was performed., Results: A total of 61 patients requiring 62 tumor resections met the inclusion criteria. Of the tumors resected, 45.9% were WHO grade I or II and 54.1% were WHO grade III or IV. Intraoperative neurophysiological monitoring modalities included speech alone in 23 cases (37.1%), motor alone in 24 (38.7%), and both speech and motor in 15 (24.2%). Intraoperative MRI demonstrated residual tumor in 48 cases (77.4%), 41 (85.4%) of whom underwent further resection. Median EOR on iMRI and postoperative MRI was 86.0% and 98.5%, respectively, with a mean difference of 10% and a median difference of 10.5% (p < 0.001). Seventeen of 62 cases achieved an increased EOR > 15% related to use of iMRI. Seventeen (60.7%) of 28 low-grade gliomas and 10 (30.3%) of 33 high-grade gliomas achieved complete resection. Significant intraoperative events included at least temporary new or worsened speech alteration in 7 of 38 cases who underwent speech mapping (18.4%), new or worsened weakness in 7 of 39 cases who underwent motor mapping (18.0%), numbness in 2 cases (3.2%), agitation in 2 (3.2%), and seizures in 2 (3.2%). Among the patients with new intraoperative deficits, 2 had residual speech difficulty, and 2 had weakness postoperatively, which improved to baseline strength by 6 months., Conclusions: In this retrospective case series, the combined use of iMRI and awake functional mapping was demonstrated to be safe and feasible. This combined approach allows one to achieve the dual goals of maximal tumor removal and minimal functional consequences in patients undergoing glioma resection.

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1). Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.

Metabolic dysregulation drives tumor initiation in a subset of glioblastomas harboring isocitrate dehydrogenase (IDH) mutations, but metabolic alterations in glioblastomas with wild-type IDH are poorly understood. MYC promotes metabolic reprogramming in cancer, but targeting MYC has proven notoriously challenging. Here, we link metabolic dysregulation in patient-derived brain tumor-initiating cells (BTIC) to a nexus between MYC and mevalonate signaling, which can be inhibited by statin or 6-fluoromevalonate treatment. BTICs preferentially express mevalonate pathway enzymes, which we find regulated by novel MYC-binding sites, validating an additional transcriptional activation role of MYC in cancer metabolism. Targeting mevalonate activity attenuated RAS-ERK-dependent BTIC growth and self-renewal. In turn, mevalonate created a positive feed-forward loop to activate MYC signaling via induction of miR-33b. Collectively, our results argue that MYC mediates its oncogenic effects in part by altering mevalonate metabolism in glioma cells, suggesting a therapeutic strategy in this setting. Cancer Res; 77(18); 4947-60. ©2017 AACR ., (©2017 American Association for Cancer Research.)

The interleukin-13 receptor alpha2 (IL13Rα2) is a cell surface receptor that is over-expressed by a subset of high-grade gliomas, but not expressed at significant levels by normal brain tissue. For both malignant and non-malignant cells, IL13Rα2 surface expression is reported to be induced by various cytokines such as IL-4 or IL-13 and tumor necrosis factor (TNF). Our group has developed a therapeutic platform to target IL13Rα2-positive brain tumors by engineering human cytotoxic T lymphocytes (CTLs) to express the IL13-zetakine chimeric antigen receptor. We therefore sought to investigate the potential of cytokine stimulation to induce IL13Rα2 cell surface expression, and thereby increase susceptibility to IL13Rα2-specific T cell killing. In the course of these experiments, we unexpectedly found that the commercially available putative IL13Rα2-specific monoclonal antibody B-D13 recognizes cytokine-induced VCAM-1 on glioblastoma. We provide evidence that the induced receptor is not IL13Rα2, because its expression does not consistently correlate with IL13Rα2 mRNA levels, it does not bind IL-13, and it is not recognized by IL13-zetakine CTL. Instead we demonstrate by immunoprecipitation experiments and mass spectrometry that the antigen recognized by the B-D13 antibody following cytokine stimulation is VCAM-1, and that VCAM-1, but not IL13Rα2, is induced on glioma cells by TNF alone or in combination with IL-13 or IL-4. Further evaluation of several commercial B-D13 antibodies revealed that B-D13 is bi-specific, recognizing both IL13Rα2 and VCAM-1. This binding is non-overlapping based on soluble receptor competition experiments, and mass spectrometry identifies two distinct heavy and light chain species, providing evidence that the B-D13 reagent is di-clonal. PE-conjugation of the B-D13 antibody appears to disrupt IL13Rα2 recognition, while maintaining VCAM-1 specificity. While this work calls into question previous studies that have used the B-D13 antibody to assess IL13Rα2 expression, it also suggests that TNF may have significant effects on glioma biology by up-regulating VCAM-1.

Therapeutic responses following adoptive transfer of T cells correlate to levels of long-term T cell persistence. Lymphodepletion and exogenous γc cytokine administration can improve T cell persistence following adoptive transfer, but their effects are not uniform and toxicities are significant. To overcome these limitations, we designed a chimeric γc cytokine receptor (CγCR) composed of Interleukin-7 (IL-7) tethered to IL-7Rα/CD127 that confers exogenous cytokine independent, cell intrinsic, STAT5 cytokine signals. We additionally show that this design is modular in that the IL-2Rβ/CD122 cytoplasmic chain can be exchanged for that of IL-7Rα/CD127, enhancing Shc activity. When expressed in central memory-derived primary human CD8(+) CTL (T(E/CM)), these CγCRs signal according to their corresponding wild-type counterparts to support exogenous cytokine independent viability and homeostatic proliferation, while retaining full effector function. In vivo studies demonstrate that both CγCR-CD127(+) and CγCR-CD122(+) CD8(+) T((E/CM)) engraft in mice and persist in an absence of exogenous cytokine administration. Engrafted CγCR-CD127(+) CD8(+) T(E/CM) preferentially retain central memory marker expression in vivo demonstrating a dichotomy between CD127 versus CD122 signaling. Together, these results suggest that expression of CγCR in therapeutic T cells may aid in the in vivo persistence of these cells, particularly under conditions of limiting homeostatic cytokines., (Copyright © 2013 Elsevier Ltd. All rights reserved.)