Septic acute kidney injury (AKI) and myocardial dysfunction are leading causes of mortality with no accepted method of therapy. In this study we demonstrate the role of growth differentiating factor 15 (GDF15) in septic AKI and myocardial dysfunction using a murine lipopolysaccharide (LPS)-induced sepsis model and an in vitro cell culture system. Data show that GDF15 deficiency augments inflammatory response and exacerbates renal and cardiac injury induced by LPS, while over-expression of GDF15 protects the kidney and heart from LPS-induced organ dysfunction. Therefore, this study highlights the therapeutic potential of GDF15 in the treatment of endotoxin-induced sepsis.

Clinical practice guideline: evidence, recommendations and algorithm for the preoperative optimization of anemia, hyperglycemia and smoking F or most of the 20th century, the focus of research in surgery was improvements in intraoperative technique, which led to major technical paradigm shifts exemplified by the evolution of transurethral resection of the prostate, 1 laparoscopic cholecystectomy, 2 endovascular aneurysm repair 3 and total mesorectal excision for rectal cancer, 4 among many others. The late 1990s and early 2000s marked a shift in surgical research toward the evidencebased management of patients in the perioperative period, beginning with the Enhanced Recovery After Surgery Group's systematic review of patients undergoing colorectal surgery. 5 That publication introduced a new paradigm focused on the impact that standardized perioperative care could have on patient outcomes such as length of stay, postoperative pain and overall complication rates. 6,7 Although a large body of literature now exists to help guide the intraoperative and perioperative management of surgical patients, our working group believes that the preoperative period, which we define as the 8 weeks

ObjectiveTo identify the advantages and disadvantages that group practices have on patients, physicians and healthcare systems.Study designA scoping review was performed based on the methodology proposed by Arksey and O’Malley, and refined by Levac et al. Titles and abstracts were screened by two reviewers. A quantitative analysis was performed to assess the type, year and region of publication, as well as the population studied. A qualitative descriptive analysis was performed to identify common themes.Study settingMEDLINE, EMBASE and Cochrane databases were searched from database inception to October 2018 for papers which assessed outcomes relevant to the research question.ResultsOur search strategy returned 2408 papers and 98 were included in the final analysis. Most papers were from the USA, were surveys and assessed physician outcomes. Advantages of group practices for patients included improved satisfaction and quality of care. Studies of physicians reported improved quality of life and income, while disadvantages included increased stress due to poor interpersonal relationships. Studies of healthcare systems reported improved efficiency and better utilisation of resources.ConclusionsGroup practices have many benefits for patients and physicians. However, further work needs to be done assessing patient outcomes and establishing the elements that make a group practice successful.

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Toll-like receptors (TLRs) act as initiators and conductors responsible for both innate and adaptive immune responses in organ transplantation. The mammalian target of rapamycin (mTOR) is one of the most critical signaling kinases that affects broad aspects of cellular functions including metabolism, growth, and survival. Recipients (BALB/c) were treated with MyD88, TRIF and mTOR siRNA vectors, 3 and 7 days prior to heart transplantation and 7, 14 and 21 days after transplantation. After siRNA treatment, recipients received a fully MHC-mismatched C57BL/6 heart. Treatment with mTOR siRNA significantly prolonged allograft survival in heart transplantation. Moreover, the combination of mTOR siRNA with MyD88 and TRIF siRNA further extended the allograft survival; Flow cytometric analysis showed an upregulation of FoxP3 expression in spleen lymphocytes and a concurrent downregulation of CD40, CD86 expression, upregulation of PD-L1 expression in splenic dendritic cells in MyD88, TRIF and mTOR treated mice. There is significantly upregulated T cell exhaustion in T cells isolated from tolerant recipients. This study is the first demonstration of preventing immune rejection of allogeneic heart grafts through concurrent gene silencing of TLR and kinase signaling pathways, highlighting the therapeutic potential of siRNA in clinical transplantation.

BACKGROUND: Ligation of the intersphincteric fistula tract is a sphincter-preserving technique for the treatment of anal fistulas. The BioLIFT modification involves the placement of a biologic mesh in the intersphincteric plane. Advocates of this modification state improved healing rates, however evidence for this is lacking, and this approach costs significantly more. OBJECTIVE: The purpose of this study was to compare the healing rates of the ligation of the intersphincteric fistula tract with the BioLIFT. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a tertiary care hospital from April 2008 to April 2018. PATIENTS: All adult patients with transsphincteric anal fistulas were included. Patients were excluded if they had IBD, more than 1 fistula tract operated on simultaneously, or a previous attempt at repair. MAIN OUTCOME MEASURES: The primary outcome was primary healing of the fistula tract, and secondary outcomes included overall success, complications, and time to recurrence. RESULTS: There were 119 cases (75 ligation of the intersphincteric fistula tract and 44 BioLIFTs). One surgeon performed 84% of the BioLIFT cases. The primary healing rate was 75.0% versus 58.7% (p = 0.08), and the complication rate was 22.7% versus 17.3% (p = 0.48; BioLIFT vs ligation of intersphincteric fistula tract). After multivariate logistic regression, the BioLIFT had a significantly better healing rate (OR = 2.38 (95% CI, 1.01–5.62); p = 0.048). Median follow-up was 9 versus 29 weeks (BioLIFT vs ligation of intersphincteric fistula tract). Kaplan–Meier analysis demonstrated no difference in the time to recurrence (p = 0.48). LIMITATIONS: This study was limited by the retrospective nature, different lengths of follow-up, and varying case numbers between the surgeons. CONCLUSIONS: The BioLIFT modification is safe and effective for the treatment of anal fistulas but has a higher cost. This modification warrants additional prospective studies to establish its benefits over the ligation of the intersphincteric fistula tract procedure. See Video Abstract at http://links.lww.com/DCR/B139. COMPARACIÓN DE LIFT VERSUS BIOLIFT PARA EL TRATAMIENTO DE LA FÍSTULA ANAL TRANSFINTERÉRICA: UN ANÁLISIS RETROSPECTIVO ANTECEDENTES: Ligadura del tracto de la fístula interesfintérica es una técnica para preservación del esfínter en el tratamiento de las fístulas anales. La modificación BioLIFT implica la colocación de una malla biológica en el plano interesfintérico. Protagonistas de la modificación mejoraron las tasas de curación, sin embargo, carecen evidencias definitivas y la técnica eleva costos significativamente. OBJETIVO: Comparar las tasas de curación de ligadura del tracto de la fístula interesfintérica con el BioLIFT. DISEÑO: Estudio de cohorte retrospectivo. AMBIENTE CLINICO: Hospital de atención de tercer nivel desde abril de 2008 hasta abril de 2018. PACIENTES: Se incluyeron todos los pacientes adultos con fístulas anales transfinteréricas. Los pacientes fueron excluidos si tenían enfermedad inflamatoria intestinal, más de un tracto fistuloso operado simultáneamente o con un intento previo de reparación. PRINCIPALES MEDIDAS DE VALORACION: El resultado principal fue la curación primaria del tracto fistuloso y los resultados secundarios incluyeron el éxito en general, las complicaciones y tiempo hasta recurrencia. RESULTADOS: Se registraron 119 casos (75 ligaduras del tracto de la fístula interesfintérica y 44 BioLIFT). Un cirujano realizó el 84% de los casos de BioLIFT. La tasa de curación primaria fue del 75.0% vs 58.7%, p = 0.08, y la tasa de complicaciones fue del 22.7% vs 17.3%, p = 0.48 comparando BioLIFT vs ligadura del tracto de la fístula interesfintérica. Después de la regresión logística multivariada, el BioLIFT tuvo una tasa de curación significativamente mejor (OR 2.38 [IC 95% 1.01-5.62], p = 0.048). La mediana de seguimiento fue de 9 vs 29 semanas (BioLIFT vs ligadura del tracto de la fístula interesfintérica). El análisis de Kaplan-Meier no demostró diferencias en el tiempo hasta la recurrencia (p = 0,48). LIMITACIONES: Este estudio estuvo limitado por ser retrospectivo, las diferentes duraciones de seguimiento y el número variable de casos entre los cirujanos. CONCLUSIÓN: La modificación BioLIFT es segura y efectiva para el tratamiento de las fístulas anales pero tiene un costo más alto. Esta modificación amerita más estudios prospectivos para establecer los beneficios sobre ligadura del tracto de la fístula interesfintérica. Consulte Video Resumen en hhttp://links.lww.com/DCR/B139.

Background: Every year, about 13 000 Canadians undergo an ostomy procedure, which requires stoma site marking to create a well-constructed stoma and prevent stoma-related complications. The Canadian Society of Colon and Rectal Surgeons (CSCRS) and Nurses Specialized in Wound, Ostomy and Continence Canada (NSWOCC) created a position statement to provide evidence-based guidance and techniques for stoma site selection. Methods: A task force was formed comprising 20 health care professionals (7 colorectal surgeons from the CSCRS and 13 nurses from NSWOCC) with representation from across Canada. A literature review was performed, with the following databases searched from January 2009 to April 2019: MEDLINE, Embase, Cochrane, PubMed, CINAHL and Google Scholar. After the abstracts were screened, 6 task force members created a draft version of the position statement from the articles retained after full-text review. The draft was submitted to the entire task force for comments, and the ensuing modifications were incorporated. Peer reviewers were then recruited from the CSCRS and NSWOCC; a summary of their comments was reviewed by the task force, and modifications were incorporated to produce the final document. Results: The literature search identified 272 papers, of which 58 were reviewed after duplicates were excluded. After full-text review, 18 papers were included to guide the position statement. From these papers, we created a series of 17 steps for stoma site marking. Four general principles were found to be important for stoma site marking: obtain informed consent, identify important patient factors and landmarks, assess the abdomen and mark the most appropriate location. A 1-page enabler document and video were created as teaching aids and to help with dissemination of the information. Conclusion: This position statement, associated enabler document and video provide evidence-based guidance for stoma site marking in both emergency and elective settings, and should be used by surgeons and nurses specialized in wound, ostomy and continence to identify optimal stoma sites preoperatively.

IntroductionGroup practices have potential benefits for patients, physicians and healthcare systems. Although group practices have been around for many years, research in this area is lacking and generally is centred around the economic benefits that may be realised from group practice. The aim of this scoping review is to identify the impact that group practices have on patients, physicians and healthcare systems to guide further research in this area.Methods and analysisA scoping review will be performed based on the methodology proposed by Arksey and O’Malley and refined by Levac and colleagues. MEDLINE, EMBASE, Cochrane Central and Cochrane Economic Database will be searched from inception to present day to identify relevant studies that assess the impact of group practices on patient care, satisfaction and outcomes; physician quality of life, satisfaction and income and healthcare systems. Titles and abstracts will be screened by two members and the abstraction results charted and verified. Qualitative and quantitative analyses will be performed to identify key themes.Ethics and disseminationResearch ethics board approval is not required for this scoping review. A consultation phase will be used to discuss the results with key stakeholders followed by dissemination at local and national levels. We will also publish the results in a peer-reviewed journal.