Treatments and other prognostic factors in the management of the open abdomen: a systematic review

Purpose: The open abdomen (OA) is an important approach for managing intra-abdominal catastrophes and continues to be the standard of care. Despite this, challenges remain and the technique is still associated with a high incidence of complications and poor outcomes. A systematic review was performed to identify prognostic factors associated with OA management in relation to definitive fascial closure (DFC), mortality and intra-abdominal complications. Methodology: An electronic database search was conducted involving Medline, Excerpta Medica, Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature and Clinicaltrials.gov databases. Results: There were 31 studies included in the final synthesis. Prognostic factors associated with delaying DFC included the presence of deep surgical site infection, fascial necrosis or an intestinal fistula. Failed clearance of the abdomen, failure of fascial closure, unconsciousness and acute renal failure were associated with in-hospital mortality. Failed DFC, large bowel resection and administration of > 5-10 litres or > 10 litres of intravenous fluids in < 48 hours were associated with the development of entero-atmospheric fistula and/or intra-abdominal abscess. The source of infection (small bowel in relation to colon) was associated with the development of a ventral hernia. Fascial closure on or after day 5 or the presence of a bowel anastomosis were associated with the development of an anastomotic leak. Conclusion: The OA has earned a huge amount of popularity in recent decades. Careful selection and management of patients with an OA will aid in avoiding prolonged treatment and facilitate early DFC, decrease mortality and reduce intra-abdominal complications

GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively

A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease

Abstract: Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn’s disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases

Treatments and other prognostic factors in the management of the open abdomen: a systematic review

Purpose: The open abdomen (OA) is an important approach for managing intra-abdominal catastrophes and continues to be the standard of care. Despite this, challenges remain and the technique is still associated with a high incidence of complications and poor outcomes. A systematic review was performed to identify prognostic factors associated with OA management in relation to definitive fascial closure (DFC), mortality and intra-abdominal complications.\ud \ud Methodology: An electronic database search was conducted involving Medline, Excerpta Medica, Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature and Clinicaltrials.gov databases.\ud \ud Results: There were 31 studies included in the final synthesis. Prognostic factors associated with delaying DFC included the presence of deep surgical site infection, fascial necrosis or an intestinal fistula. Failed clearance of the abdomen, failure of fascial closure, unconsciousness and acute renal failure were associated with in-hospital mortality. Failed DFC, large bowel resection and administration of > 5-10 litres or > 10 litres of intravenous fluids in < 48 hours were associated with the development of entero-atmospheric fistula and/or intra-abdominal abscess. The source of infection (small bowel in relation to colon) was associated with the development of a ventral hernia. Fascial closure on or after day 5 or the presence of a bowel anastomosis were associated with the development of an anastomotic leak.\ud \ud Conclusion: The OA has earned a huge amount of popularity in recent decades. Careful selection and management of patients with an OA will aid in avoiding prolonged treatment and facilitate early DFC, decrease mortality and reduce intra-abdominal complications