Systematic review: Histological remission in inflammatory bowel disease. Is ‘complete’ remission the new treatment paradigm? An IOIBD initiative

AbstractBackground and aimsAdvances in the medical management of inflammatory bowel disease (IBD) have altered treatment targets. Endoscopic mucosal healing is associated with better outcomes in IBD, though less is known about the significance of achieving histological remission. Our aim was to perform a systematic review to investigate whether histological or ‘complete’ remission constitutes a further therapeutic target in IBD.MethodsA bibliographic search was performed on the 1st of October 2013 and subsequently on the 1st of March 2014 of online databases (OVID SP MEDLINE, OVID EMBASE, National Pubmed Central Medline, Cochrane Library, ISI, conference abstracts), using MeSH terms and key words: (“inflammatory bowel diseases” OR “crohn disease” OR “ulcerative colitis” OR “colitis”) AND (“mucosal healing” OR “histological healing” OR “pathological healing” OR “histological scoring” OR “pathological scoring”).ResultsThe search returned 2951 articles. 120 articles were cited in the final analysis. There is no validated definition of histological remission in IBD. There are 22 different histological scoring systems for IBD, none of which are fully validated. Microscopic inflammation persists in 16–100% of cases of endoscopically quiescent disease. There is evidence that histological remission may predict risk of complications in ulcerative colitis beyond endoscopic mucosal healing, though data are scarce in Crohn's disease.ConclusionsHistological remission in IBD represents a target distinct from endoscopic mucosal healing, not yet routinely sought in clinical trials or practice. There remains a need for a standardized and validated histological scoring system and to confirm the prognostic value of histological remission as a treatment target in IBD

How to perform gastrointestinal ultrasound: Anatomy and normal findings

Gastrointestinal ultrasound is a practical, safe, cheap and reproducible diagnostic tool in inflammatory bowel disease gaining global prominence amongst clinicians. Understanding the embryological processes of the intestinal tract assists in the interpretation of abnormal sonographic findings. In general terms, the examination principally comprises interrogation of the colon, mesentery and small intestine using both lowfrequency and high-frequency probes. Interpretation of findings on GIUS includes assessment of bowel wall thickness, symmetry of this thickness, evidence of transmural changes, assessment of vascularity using Doppler imaging and assessment of other specific features including lymph nodes, mesentery and luminal motility. In addition to B-mode imaging, transperineal ultrasonography, elastography and contrast-enhanced ultrasonography are useful adjuncts. This supplement expands upon these features in more depth

Review article: the future of microbiome-based therapeutics

Published online 24 May 2022Background: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.Aim: This review summarises the current developments in microbiome- based medicines and provides insight into the next steps required for therapeutic development.Methods: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical inter-ventions. Key literature was identified through Pubmed searches with the following key words, ‘microbiome’, ‘microbiome biomarkers’, ‘probiotics’, ‘prebiotics’, ‘synbiotics’, ‘faecal microbiota transplant’, ‘live biotherapeutics’, ‘microbiome mimetics’ and ‘postbiotics’.Results: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, ra-tionally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics.Conclusions: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.Emily L. Gulliver, Remy B. Young, Michelle Chonwerawong, Gemma L. D'Adamo, Tamblyn Thomason, James T. Widdop, Emily L. Rutten, Vanessa Rossetto Marcelino, Robert V. Bryant, Samuel P. Costello, Claire L. O'Brien, Georgina L. Hold, Edward M. Giles, Samuel C. Forste

Search for the Standard Model Higgs boson decaying into bb¯ produced in association with top quarks decaying hadronically in pp collisions at √s = 8 TeV with the ATLAS detector

A search for Higgs boson production in association with a pair of top quarks (tt¯ H) is performed, where the Higgs boson decays to bb¯, and both top quarks decay hadronically. The data used correspond to an integrated luminosity of 20.3 fb−1 of pp collisions at √s = 8 TeV collected with the ATLAS detector at the Large Hadron Collider. The search selects events with at least six energetic jets and uses a boosted decision tree algorithm to discriminate between signal and Standard Model background. The dominant multijet background is estimated using a dedicated data-driven technique. For a Higgs boson mass of 125 GeV, an upper limit of 6.4 (5.4) times the Standard Model cross section is observed (expected) at 95% confidence level. The best-fit value for the signal strength is μ = 1.6 ± 2.6 times the Standard Model expectation for mH = 125 GeV. Combining all tt¯ H searches carried out by ATLAS at √s = 8 and 7 TeV, an observed (expected) upper limit of 3.1 (1.4) times the Standard Model expectation is obtained at 95% confidence level, with a signal strength μ = 1.7 ± 0.8

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of binary black hole coalescences confidently observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include the effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that have already been identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total source-frame mass M > 70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz emitted gravitational-wave frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place a conservative upper limit for the merger rate density of high-mass binaries with eccentricities 0 < e ≤ 0.3 at 16.9 Gpc−3 yr−1 at the 90% confidence level

Search for the Higgs boson produced in association with a W boson and decaying to four b-quarks via two spin-zero particles in pp collisions at 13 TeV with the ATLAS detector

This paper presents a dedicated search for exotic decays of the Higgs boson to a pair of new spin-zero particles, H → aa, where the particle a decays to b-quarks and has a mass in the range of 20–60 GeV. The search is performed in events where the Higgs boson is produced in association with a W boson, giving rise to a signature of a lepton (electron or muon), missing transverse momentum, and multiple jets from b-quark decays. The analysis is based on the full dataset of pp collisions at √s = 13 TeV recorded in 2015 by the ATLAS detector at the CERN Large Hadron Collider, corresponding to an integrated luminosity of 3.2 fb−1. No significant excess of events above the Standard Model prediction is observed, and a 95% confidence-level upper limit is derived for the product of the production cross section for pp → W H times the branching ratio for the decay H → aa → 4b. The upper limit ranges from 6.2 pb for an a-boson mass ma = 20 GeV to 1.5 pb for ma = 60 GeV

Letter: low muscle mass and disordered eating as causes of osteopenia in inflammatory bowel disease - authors' reply

Abstract not availableR. V. Bryant, and J. M. Andrew