Making it out of hospital alive: the art of open abdomen management – a pilot study

Purpose: In the management of patients with an open abdomen (OA), failure of fascial closure, decreased GCS, and presence of acute renal failure have been identified as having a significant effect on in-hospital mortality. The aim of this study is to develop a probability nomogram in order to predict the likelihood of in-hospital mortality amongst patients being managed with an OA. Methodology: All patients admitted to the Cairns Hospital from 1999 to 2015 that were managed with an OA were identified. Statistical analysis was performed using multivariate logistic regression methods using 54 prognostic factors in regards to in-hospital mortality. Results: A total of 133 patients were managed with an OA. 31 (23%) patients died in-hospital. Four prognostic factors were found to significantly contribute to in-hospital mortality. These included APACHE III score (odds ratio (OR) 1.29), presence of one or more cardiac risk factors (OR 5.00), normal pulse rate (50-80 beats per minute; OR 0.19) and the use of enteral feeding (OR 0.25). Probability nomograms were developed in order to demonstrate a patient's likelihood of in-hospital mortality, as well as identify specific aspects that may improve their overall outcome. Internal validation using receiver operator curve analysis showed an area under the curve of 0.825. Conclusion: Four prognostic factors were identified in regards to in-hospital mortality in patients being managed with an OA. The use of these probability nomograms will not only aid in predicting the likelihood of in-hospital mortality, but also show aspects which can be targeted in order to improve their overall outcome

Making it out of hospital alive: the art of open abdomen management – a pilot study

Purpose: In the management of patients with an open abdomen (OA), failure of fascial closure, decreased GCS, and presence of acute renal failure have been identified as having a significant effect on in-hospital mortality. The aim of this study is to develop a probability nomogram in order to predict the likelihood of in-hospital mortality amongst patients being managed with an OA. Methodology: All patients admitted to the Cairns Hospital from 1999 to 2015 that were managed with an OA were identified. Statistical analysis was performed using multivariate logistic regression methods using 54 prognostic factors in regards to in-hospital mortality. Results: A total of 133 patients were managed with an OA. 31 (23%) patients died in-hospital. Four prognostic factors were found to significantly contribute to in-hospital mortality. These included APACHE III score (odds ratio (OR) 1.29), presence of one or more cardiac risk factors (OR 5.00), normal pulse rate (50-80 beats per minute; OR 0.19) and the use of enteral feeding (OR 0.25). Probability nomograms were developed in order to demonstrate a patient's likelihood of in-hospital mortality, as well as identify specific aspects that may improve their overall outcome. Internal validation using receiver operator curve analysis showed an area under the curve of 0.825. Conclusion: Four prognostic factors were identified in regards to in-hospital mortality in patients being managed with an OA. The use of these probability nomograms will not only aid in predicting the likelihood of in-hospital mortality, but also show aspects which can be targeted in order to improve their overall outcome

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

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

Comparison of breast cancer HER-2 receptor testing with immunohistochemistry and in situ hybridization

Purpose: Human epidermal growth factor receptor–2 (HER2) status can be tested with immunohistochemistry (IHC) and in situ hybridization (ISH). The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guidelines suggest initial HER2 testing using IHC and further testing IHC equivocal cases with ISH. However, many institutions perform both IHC and ISH on the same specimen. This study aims to analyze the concordance between HER2 IHC and ISH in order to evaluate the benefit of repeating HER2 testing on the same breast cancer specimens. Method: Patients diagnosed with invasive breast cancer through BreastScreen NSW Sydney West program between January 2018 and December 2020 were identified and their HER2 IHC and HER2 ISH results on core needle biopsy (CNB) and surgical excisions (SE) were retrospectively collected. Specimens with both IHC and ISH results were then analyzed for agreement and concordance using unweighted kappa values. Equivocal IHC (2+) cases were excluded from concordance analysis. Results: Overall, there were 240 invasive breast cancer specimens (CNB and SE) with both IHC and ISH recorded. Concordance between HER2 IHC and ISH was 100% (95% CI: 96.2–100%; κ = 1.00 (P < 0.001)). Of the IHC equivocal cases (n = 146), 94.5% were ISH negative. Conclusion: There was perfect positive concordance and agreement between non-equivocal IHC and ISH results. This reinforces that IHC alone can be utilized reliably for testing HER2 status of non-equivocal cases consistent with the 2018 ASCO/CAP guidelines