The Interstellar Environment of our Galaxy

We review the current knowledge and understanding of the interstellar medium of our galaxy. We first present each of the three basic constituents - ordinary matter, cosmic rays, and magnetic fields - of the interstellar medium, laying emphasis on their physical and chemical properties inferred from a broad range of observations. We then position the different interstellar constituents, both with respect to each other and with respect to stars, within the general galactic ecosystem.Comment: 39 pages, 12 figures (including 3 figures in 2 parts

Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by radical surgery for locally advanced oesophageal squamous cell carcinoma:meta-analysis

Background: The literature lacks robust evidence comparing definitive chemoradiotherapy (dCRT) with neoadjuvant chemoradiotherapy and surgery (nCRS) for oesophageal squamous cell carcinoma (ESCC). This study aimed to compare long-term survival of these approaches in patients with ESCC.Methods: A systematic review performed according to PRISMA guidelines included studies identified from PubMed, Scopus, and Cochrane CENTRAL databases up to July 2021 comparing outcomes between dCRT and nCRS for ESCC. The main outcome measure was overall survival (OS), secondary outcome was disease-free survival (DFS). A meta-analysis was conducted using random-effects modelling to determine pooled adjusted multivariable hazard ratios (HRs).Results: Ten studies including 14 092 patients were included, of which 30 per cent received nCRS. Three studies were randomized clinical trials (RCTs) and the remainder were retrospective cohort studies. dCRT and nCRS regimens were reported in six studies and surgical quality control was reported in two studies. Outcomes for OS and DFS were reported in eight and three studies respectively. Following meta-analysis, nCRS demonstrated significantly longer OS (HR 0.68, 95 per cent c.i. 0.54 to 0.87, P < 0.001) and DFS (HR 0.50, 95 per cent c.i. 0.36 to 0.70, P < 0.001) compared with dCRT.Conclusion: Neoadjuvant chemoradiotherapy followed by oesophagectomy correlated with improved survival compared with definitive chemoradiation in the treatment of ESCC; however, there is a lack of literature on RCTs

A systematic review of transarterial embolization versus emergency surgery in treatment of major nonvariceal upper gastrointestinal bleeding

Emergency surgery or transarterial embolization (TAE) are options for the treatment of recurrent or refractory nonvariceal upper gastrointestinal bleeding. Surgery has the disadvantage of high rates of postoperative morbidity and mortality. Embolization has become more available and has the advantage of avoiding laparotomy in this often unfit and elderly population

The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01666-x

Predictors and Significance of Readmission after Esophagogastric Surgery:A Nationwide Analysis

Objective: The aim of this study is to identify risk factors for readmission after elective esophagogastric cancer surgery and characterize the impact of readmission on long-term survival. The study will also identify whether the location of readmission to either the hospital that performed the primary surgery (index hospital) or another institution (nonindex hospital) has an impact on postoperative mortality.Background: Over the past decade, the center-volume relationship has driven the centralization of major cancer surgery, which has led to improvements in perioperative mortality. However, the impact of readmission, especially to nonindex centers, on long-term mortality remains unclear.Methods: This was a national population-based cohort study using Hospital Episode Statistics of adult patients undergoing esophagectomy and gastrectomy in England between January 2008 and December 2019.Results: This study included 27,592 patients, of which overall readmission rates were 25.1% (index 15.3% and nonindex 9.8%). The primary cause of readmission to an index hospital was surgical in 45.2% and 23.7% in nonindex readmissions. Patients with no readmissions had significantly longer survival than those with readmissions (median: 4.5 vs 3.8 years; P &lt; 0.001). Patients readmitted to their index hospital had significantly improved survival as compared to nonindex readmissions (median: 3.3 vs 4.7 years; P &lt; 0.001). Minimally invasive surgery and surgery performed in high-volume centers had improved 90-day mortality (odds ratio, 0.75; P &lt; 0.001; odds ratio, 0.60; P &lt; 0.001).Conclusion: Patients requiring readmission to the hospital after surgery have an increased risk of mortality, which is worsened by readmission to a nonindex institution. Patients requiring readmission to the hospital should be assessed and admitted, if required, to their index institution.<br/

Study protocol for a multicentre international collaborative cohort study on the management and outcomes for T1 oesophagogastric cancer (CONGRESS)

Background: Controversy remains surrounding the optimal management of patients with T1N0 early oesophagogastric (OG) cancer. Individual units often see low numbers of patients with very early stage disease; previous publications are limited to smaller institutional cohorts or less granular administrative databases. The endosCopic resectiON, esophaGectomy or gastrectomy foR Early oeSophagogastric cancerS (CONGRESS) collaborative aims to characterise the impact of different management strategies, including endoscopic resection (ER) and radical surgery, with detailed disease and outcome data, for early OG cancer in a large multi-centre cohort study. Methods: An international retrospective cohort study will be performed, including all patients diagnosed with T1N0 OG cancer from 2015 to 2022. Led by local and regional collaborators, centralised anonymised data capture will include all relevant diagnostic, demographic, treatment, and outcome data. Treatment will be compared to current guidelines. For T1a disease, ER may be carried out if clearly confined to the mucosa, well differentiated, ≤2 cm and non-ulcerated. For T1b disease, radical oesophagectomy or gastrectomy may be considered. Discussion: This will be a large-scale international audit to identify and summarise current practice relating to the diagnosis, treatment and outcomes for early OG cancers. It is anticipated that this will allow detailed risk stratification for disease and treatment strategies and will provide the basis for further prospective interventional studies. Trial Registration: In keeping with previous well-established methodology for multi-centre retrospective audits of clinical practice, this study will be approved by local audit committees, as such it does not meet criteria to be and has not been registered with any central registry. Each centre will be responsible for locally registering the audit and obtaining appropriate permissions from local institutional review committees.</p

Novel Textbook Outcomes following emergency laparotomy:Delphi exercise

Background: Textbook outcomes are composite outcome measures that reflect the ideal overall experience for patients. There are many of these in the elective surgery literature but no textbook outcomes have been proposed for patients following emergency laparotomy. The aim was to achieve international consensus amongst experts and patients for the best Textbook Outcomes for non-trauma and trauma emergency laparotomy. Methods: A modified Delphi exercise was undertaken with three planned rounds to achieve consensus regarding the best Textbook Outcomes based on the category, number and importance (Likert scale of 1–5) of individual outcome measures. There were separate questions for non-trauma and trauma. A patient engagement exercise was undertaken after round 2 to inform the final round. Results: A total of 337 participants from 53 countries participated in all three rounds of the exercise. The final Textbook Outcomes were divided into ‘early’ and ‘longer-term’. For non-trauma patients the proposed early Textbook Outcome was ‘Discharged from hospital without serious postoperative complications (Clavien–Dindo ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation or death). For trauma patients it was ‘Discharged from hospital without unexpected transfusion after haemostasis, and no serious postoperative complications (adapted Clavien–Dindo for trauma ≥ grade III; including intra-abdominal sepsis, organ failure, unplanned re-operation on or death)’. The longer-term Textbook Outcome for both non-trauma and trauma was ‘Achieved the early Textbook Outcome, and restoration of baseline quality of life at 1 year’. Conclusion: Early and longer-term Textbook Outcomes have been agreed by an international consensus of experts for non-trauma and trauma emergency laparotomy. These now require clinical validation with patient data

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe