A Genome-Wide Scan of Ashkenazi Jewish Crohn's Disease Suggests Novel Susceptibility Loci

Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2–4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10−6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10−8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10−9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10−8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10−8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10−9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim

Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction

Introduction Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups

Preventing Multiple-Choice Tests From Impeding Educational Advancement After Acquired Brain Injury

Purpose: The purpose of this article is to present management strategies that can be used to breach barriers created for students with acquired brain injuries by testing the students In the multiple-choice format. Method: This article presents a case study of a high school student with severe hydrocephalus and difficulties with state-mandated reading comprehension tests who was denied exceptional student education services because her grades were so good. Result: Although an honor student who received academic awards, she was never taught how to pass the state reading test and was denied her diploma at graduation. Implications: The cognitive obstacles posed by the multiple-choice format can be specified and treated. In-service training can help school staff and officials to recognize and serve these children promptly so that academic disability can be prevented. © American Speech-Language-Hearing Association

Surgical site infections after emergency hernia repair:substudy from the Management of Acutely Symptomatic Hernia (MASH) study

Introduction: Acutely symptomatic abdominal wall and groin hernias (ASH) are a common acute surgical presentation. There are limited data to guide decisions related to surgical repair technique and use of antibiotics, which can be driven by increased risk of surgical site infection (SSI) in this group. This study aims to report rates of SSI following ASH repair and explore the use of patient-reported outcome measure reporting in this setting.Methods: An 18-week, UK-based, multicentre prospective cohort study (NCT04197271) recruited adults with ASH. This study reports operatively managed patients. Data on patient characteristics, inpatient management, quality of life, complications, and wound healing (Bluebelle score) were collected. Descriptive analyses were performed to estimate event rates of SSI and regression analysis explored the relationship between Bluebelle scores and SSI. The 30 and 90-day follow-up visits assessed complications and quality of life.Results: The MASH study recruited 273 patients, of whom 218 were eligible for this study, 87.2 per cent who underwent open repair. Mesh was used in 123 patients (50.8 per cent). Pre- and postoperative antibiotics were given in 163 (67.4 per cent) and 28 (11.5 per cent) patients respectively. There were 26 reported SSIs (11.9 per cent). Increased BMI, incisional, femoral, and umbilical hernia were associated with higher rates of SSI (P = 0.006). In 238 patients, there was a difference in healthy utility values at 90 days between patients with and without SSI (P = 0.025). Also, when analysing 191 patients with Bluebelle scores, those who developed an SSI had higher Bluebelle values (P &lt; 0.001).Conclusion: SSI is frequent in repair of acutely symptomatic hernia and correlates with BMI and site of hernia

P032 SURGICAL SITE INFECTIONS FOLLOWING EMERGENCY HERNIA REPAIR: A SUB-STUDY FROM THE MASH PROJECT

Acutely symptomatic hernia (ASH) of the abdominal wall and groin are common presentations. Decisions related to repair technique can be driven by contamination and surgical site infection (SSI) risk. The aim of this study is to report rates of SSI following ASH repair, and assess the performance of the Bluebelle wound health questionnaire in this population.This study reports on the operated sub-group of the MASH study. This was a 12 week, UK-based, multi-centre, collaborative, prospective cohort study (NCT04197271) recruited adults with ASH. Hernia site, repair type, wound complications, and Bluebelle questionnaire at 30 &amp; 90 days were captured. Performance of this score was assessed using ROC curves, and regression modelling.223 patients were operated on, and 21 (9.4%) developed SSI within 90 days. Infections were most common in umbilical hernia (16.2%). No infections were seen in ‘simple’ symptomatic hernia. There was no association with either repair type. Bluebelle scores for 109 patients had an area under the curve of 0.807, showing good performance in this population. Regression modelling showed that SSI was most strongly associated with increased Bluebelle score (OR 8.54 (4.27 to 12.80, p &lt; 0.001)). Use of a sutured repair was associated with a lower score (OR -3.79 (-7.19 to -0.39, p = 0.029)).SSI is common after surgical treatment of ASH. Strategies to reduce this are needed. The Bluebelle score appears valid for this population; mesh repair might affect scores independent of SSI.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Published version, accepted version (12 month embargo), submitted versio

Management of Acutely Symptomatic Hernia (MASH) study

Background: Acutely symptomatic abdominal wall and groin hernias are a common reason for acute surgical hospital admissions. There are limited data to guide the treatment of these patients. This study aimed to assess outcomes of emergency hernia surgery and identify common management strategies, to improve care for these high-risk patients.Methods: A 20-week, national multicentre, collaborative, prospective cohort study (NCT04197271) recruited adults with acutely symptomatic abdominal wall and groin hernias across the UK. Data on patient characteristics, inpatient management, quality of life, complications, and wound healing were collected. Follow-up telephone calls at 30 and 90 days were used to assessed complications and quality of life. Descriptive analyses were undertaken to describe the population and outcomes.Results: Twenty-three hospitals recruited 272 eligible patients. Inguinal (37.8 per cent) and umbilical (37.1 per cent) hernias were the most common. Some 13.9 per cent were awaiting elective surgery and 12.8 per cent had previously declined intervention. CT was performed in 47.1 per cent and 81.3 per cent underwent surgical management. Open repairs were carried out in 93.5 per cent, and 92.5 per cent of these were performed under general anaesthesia. Four of 13 laparoscopic procedures were converted to open surgery. Mesh was used in 55.1 per cent of repairs, typically synthetic non-absorbable (87.4 per cent). Complications were infrequent; surgical-site infection (9.4 per cent), delirium (3.2 per cent), and pneumonia (2.3 per cent) were the most common. The 90-day mortality rate was 4.9 per cent. Immediate surgical management was associated with a significant improvement in quality of life at 30 days (median score 0.73–0.82).Conclusion: There is variation in the investigation, management, and surgical technique used to treat acutely symptomatic abdominal wall and groin hernias in the UK. The optimal management strategy for specific acute presentations remains to be established.Presented to the Association of Surgeons in Training Conference, Birmingham, UK, March 2021, the Association of Surgeons of Great Britain and Ireland Congress, May 2021, the World Society of Emergency Surgery, Edinburgh, UK, September 2021, and the European Hernia Society Congress, Copenhagen, Denmark, October 2021

Management of Acutely Symptomatic Hernia (MASH) study

Background: Acutely symptomatic abdominal wall and groin hernias are a common reason for acute surgical hospital admissions. There are limited data to guide the treatment of these patients. This study aimed to assess outcomes of emergency hernia surgery and identify common management strategies, to improve care for these high-risk patients.Methods: A 20-week, national multicentre, collaborative, prospective cohort study (NCT04197271) recruited adults with acutely symptomatic abdominal wall and groin hernias across the UK. Data on patient characteristics, inpatient management, quality of life, complications, and wound healing were collected. Follow-up telephone calls at 30 and 90 days were used to assessed complications and quality of life. Descriptive analyses were undertaken to describe the population and outcomes.Results: Twenty-three hospitals recruited 272 eligible patients. Inguinal (37.8 per cent) and umbilical (37.1 per cent) hernias were the most common. Some 13.9 per cent were awaiting elective surgery and 12.8 per cent had previously declined intervention. CT was performed in 47.1 per cent and 81.3 per cent underwent surgical management. Open repairs were carried out in 93.5 per cent, and 92.5 per cent of these were performed under general anaesthesia. Four of 13 laparoscopic procedures were converted to open surgery. Mesh was used in 55.1 per cent of repairs, typically synthetic non-absorbable (87.4 per cent). Complications were infrequent; surgical-site infection (9.4 per cent), delirium (3.2 per cent), and pneumonia (2.3 per cent) were the most common. The 90-day mortality rate was 4.9 per cent. Immediate surgical management was associated with a significant improvement in quality of life at 30 days (median score 0.73–0.82).Conclusion: There is variation in the investigation, management, and surgical technique used to treat acutely symptomatic abdominal wall and groin hernias in the UK. The optimal management strategy for specific acute presentations remains to be established.Presented to the Association of Surgeons in Training Conference, Birmingham, UK, March 2021, the Association of Surgeons of Great Britain and Ireland Congress, May 2021, the World Society of Emergency Surgery, Edinburgh, UK, September 2021, and the European Hernia Society Congress, Copenhagen, Denmark, October 2021

Adult-onset hearing loss and incident cognitive impairment and dementia – A systematic review and meta-analysis of cohort studies

BackgroundWe comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the evidence for dose-response, risk for various dementia subtypes, and other moderators. Previous meta-analyses were less comprehensive.MethodsWe included cohort studies with participants without dementia and with hearing assessments at baseline, minimum 2 years follow-up and incident cognitive outcomes. We used random-effect models and subgroup and meta-regression on moderator analyses.ResultsWe identified fifty studies (N=1,548,754). Hearing loss (yes/no) was associated with incident dementia risk (HR=1.35 [95% CI = 1.26 – 1.45), mild cognitive impairment (MCI HR=1.29 [95% CI = 1.11 – 1.50]), cognitive decline not specified as MCI or dementia (HR=1.29 [95% CI = 1.17 – 1.42]), and Alzheimer’s disease dementia (ADD, HR=1.56 [95% CI = 1.30 – 1.87]), but not with vascular dementia (HR, 1.30 [95% CI = 0.83 – 2.05]). Each 10-decibel worsening of hearing was associated with a 16% increase in dementia risk (95% CI = 1.07 – 1.27). The effect of hearing loss did not vary across potential moderators.ConclusionsCohort studies consistently support that adult-onset hearing loss increases the risk of incident cognitive decline, dementia, MCI, and ADD