CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer

The origin of cancer-associated fibroblasts (CAFs) in cancer remains to be identified. Here, single-cell transcriptomics, in vivo and in vitro studies suggest that CD26+ and CD26- normal fibroblasts transform into distinct CAF subpopulations in mouse models of breast cancer

Intraoperative surgical site infection control and prevention : a position paper and future addendum to WSES intra-abdominal infections guidelines

Correction: Volume: 16 Issue: 1, Article Number: 18 DOI: 10.1186/s13017-021-00361-4Background Surgical site infections (SSI) represent a considerable burden for healthcare systems. They are largely preventable and multiple interventions have been proposed over past years in an attempt to prevent SSI. We aim to provide a position paper on Operative Room (OR) prevention of SSI in patients presenting with intra-abdominal infection to be considered a future addendum to the well-known World Society of Emergency Surgery (WSES) Guidelines on the management of intra-abdominal infections. Methods The literature was searched for focused publications on SSI until March 2019. Critical analysis and grading of the literature has been performed by a working group of experts; the literature review and the statements were evaluated by a Steering Committee of the WSES. Results Wound protectors and antibacterial sutures seem to have effective roles to prevent SSI in intra-abdominal infections. The application of negative-pressure wound therapy in preventing SSI can be useful in reducing postoperative wound complications. It is important to pursue normothermia with the available resources in the intraoperative period to decrease SSI rate. The optimal knowledge of the pharmacokinetic/pharmacodynamic characteristics of antibiotics helps to decide when additional intraoperative antibiotic doses should be administered in patients with intra-abdominal infections undergoing emergency surgery to prevent SSI. Conclusions The current position paper offers an extensive overview of the available evidence regarding surgical site infection control and prevention in patients having intra-abdominal infections.Peer reviewe

World society of emergency surgery (WSES) guidelines for management of skin and soft tissue infections

Skin and soft tissue infections (SSTIs) encompass a variety of pathological conditions ranging from simple superficial infections to severe necrotizing soft tissue infections. Necrotizing soft tissue infections (NSTIs) are potentially life-threatening infections of any layer of the soft tissue compartment associated with widespread necrosis and systemic toxicity. Successful management of NSTIs involves prompt recognition, timely surgical debridement or drainage, resuscitation and appropriate antibiotic therapy. A worldwide international panel of experts developed evidence-based guidelines for management of soft tissue infections. The multifaceted nature of these infections has led to a collaboration among surgeons, intensive care and infectious diseases specialists, who have shared these guidelines, implementing clinical practice recommendations

World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections

Peer reviewe

EZH2 Is Overexpressed in BRCA1-like Breast Tumors and Predictive for Sensitivity to High-Dose Platinum-Based Chemotherapy

Purpose: BRCA1-deficient breast cancers carry a specific DNA copy-number signature (BRCA1-like) and are hypersensitive to DNA double-strand break (DSB) inducing compounds. Here, we explored whether (i) EZH2 is overexpressed in human BRCA1-deficient breast tumors and might predict sensitivity to DSB-inducing drugs; (ii) EZH2 inhibition potentiates cisplatin efficacy in Brca1-deficient murine mammary tumors. Experimental Design: EZH2 expression was analyzed in 497 breast cancers using IHC or RNA sequencing. Weclassified 370 tumors by copy-number profiles as BRCA1-like or non-BRCA1-like and examined its association with EZH2 expression. Additionally, we assessed BRCA1 loss through mutation or promoter methylation status and investigated the predictive value of EZH2 expression in a study population of breast cancer patients treated with adjuvant high-dose platinumbased chemotherapy compared with standard anthracyclinebased chemotherapy. To explore whether EZH2 inhibition by GSK126 enhances sensitivity to platinum drugs in EZH2-overexpressing breast cancers we used a Brca1-deficient mouse model. Results: The highest EZH2 expression was found in BRCA1associated tumors harboring a BRCA1 mutation, BRCA1-promoter methylation or were classified as BRCA1 like. We observed a greater benefit from high-dose platinum-based chemotherapy in BRCA1-like and non-BRCA1-like patients with high EZH2 expression. Combined treatment with the EZH2 inhibitor GSK126 and cisplatin decreased cell proliferation and improved survival in Brca1-deficient mice in comparison with single agents. Conclusions: Our findings demonstrate that EZH2 is expressed at significantly higher levels in BRCA1-deficient breast cancers. EZH2 overexpression can identify patients with breast cancer who benefit significantly from intensified DSB-inducing platinum-based chemotherapy independent of BRCA1-like status. EZH2 inhibition improves the antitumor effect of platinum drugs in Brca1-deficient breast tumors in vivo

Intraoperative surgical site infection control and prevention: a position paper and future addendum to WSES intra-abdominal infections guidelines

Abstract: Background: Surgical site infections (SSI) represent a considerable burden for healthcare systems. They are largely preventable and multiple interventions have been proposed over past years in an attempt to prevent SSI. We aim to provide a position paper on Operative Room (OR) prevention of SSI in patients presenting with intra-abdominal infection to be considered a future addendum to the well-known World Society of Emergency Surgery (WSES) Guidelines on the management of intra-abdominal infections. Methods: The literature was searched for focused publications on SSI until March 2019. Critical analysis and grading of the literature has been performed by a working group of experts; the literature review and the statements were evaluated by a Steering Committee of the WSES. Results: Wound protectors and antibacterial sutures seem to have effective roles to prevent SSI in intra-abdominal infections. The application of negative-pressure wound therapy in preventing SSI can be useful in reducing postoperative wound complications. It is important to pursue normothermia with the available resources in the intraoperative period to decrease SSI rate. The optimal knowledge of the pharmacokinetic/pharmacodynamic characteristics of antibiotics helps to decide when additional intraoperative antibiotic doses should be administered in patients with intra-abdominal infections undergoing emergency surgery to prevent SSI. Conclusions: The current position paper offers an extensive overview of the available evidence regarding surgical site infection control and prevention in patients having intra-abdominal infections

MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling

The limited efficacy of immune checkpoint inhibitor treatment in triple-negative breast cancer (TNBC) patients is attributed to sparse or unresponsive tumor-infiltrating lymphocytes, but the mechanisms that lead to a therapy resistant tumor immune microenvironment are incompletely known. Here we show a strong correlation between MYC expression and loss of immune signatures in human TNBC. In mouse models of TNBC proficient or deficient of breast cancer type 1 susceptibility gene (BRCA1), MYC overexpression dramatically decreases lymphocyte infiltration in tumors, along with immune signature remodelling. MYC-mediated suppression of inflammatory signalling induced by BRCA1/2 inactivation is confirmed in human TNBC cell lines. Moreover, MYC overexpression prevents the recruitment and activation of lymphocytes in both human and mouse TNBC co-culture models. Chromatin-immunoprecipitation-sequencing reveals that MYC, together with its co-repressor MIZ1, directly binds promoters of multiple interferon-signalling genes, resulting in their downregulation. MYC overexpression thus counters tumor growth inhibition by a Stimulator of Interferon Genes (STING) agonist via suppressing induction of interferon signalling. Together, our data reveal that MYC suppresses innate immunity and facilitates tumor immune escape, explaining the poor immunogenicity of MYC-overexpressing TNBCs

Trauma quality indicators: internationally approved core factors for trauma management quality evaluation

Introduction: Quality in medical care must be measured in order to be improved. Trauma management is part of health care, and by definition, it must be checked constantly. The only way to measure quality and outcomes is to systematically accrue data and analyze them. Material and methods: A systematic revision of the literature about quality indicators in trauma associated to an international consensus conference Results: An internationally approved base core set of 82 trauma quality indicators was obtained: Indicators were divided into 6 fields: prevention, structure, process, outcome, post-traumatic management, and society integrational effects. Conclusion: Present trauma quality indicator core set represents the result of an international effort aiming to provide a useful tool in quality evaluation and improvement. Further improvement may only be possible through international trauma registry development. This will allow for huge international data accrual permitting to evaluate results and compare outcomes