Explore the vast range of titles available.

The Tn3 family is a widespread group of replicative transposons that are notorious for their contribution to the dissemination of antibiotic resistance and the emergence of multiresistant pathogens worldwide. The TnpA transposase of these elements catalyzes DNA breakage and rejoining reactions required for transposition. It also is responsible for target immunity, a phenomenon that prevents multiple insertions of the transposon into the same genomic region. However, the molecular mechanisms whereby TnpA acts in both processes remain unknown. Here, we have developed sensitive biochemical assays for the TnpA transposase of the Tn3-family transposon Tn4430 and used these assays to characterize previously isolated TnpA mutants that are selectively affected in immunity. Compared with wild-type TnpA, these mutants exhibit deregulated activities. They spontaneously assemble a unique asymmetric synaptic complex in which one TnpA molecule simultaneously binds two transposon ends. In this complex, TnpA is in an activated state competent for DNA cleavage and strand transfer. Wild-type TnpA can form this complex only on precleaved ends mimicking the initial step of transposition. The data suggest that transposition is controlled at an early stage of transpososome assembly, before DNA cleavage, and that mutations affecting immunity have unlocked TnpA by stabilizing the protein in a monomeric activated synaptic configuration. We propose an asymmetric pathway for coupling active transpososome assembly with proper target recruitment and discuss this model with respect to possible immunity mechanisms.

Background Post-operative pain management is a critical component of perioperative care. Patients at risk of poorly controlled post-operative pain may benefit from early measures to optimize pain management. We sought to identify risk factors for post-operative pain and opioid consumption in patients undergoing liver resection. Methods This is a multi-institutional prospective nested cohort study of patients undergoing open liver resection. Opioid consumption and pain scores were collected following surgery. To estimate the effects of patient factors on opioid consumption (oral morphine equivalents—OME) and on pain scores (NRS-11), we used generalized linear models and multivariable linear regression model, respectively. Results One hundred and fifty-three patients who underwent open liver resection between 2013 and 2016 were included in the study. The mean patient age was 62.2 years, and 43.3% were female. Younger patients were significantly more likely to use more opioids in the early post-operative period (16.7 OME/10 years, p  < 0.001). Patient factors that were significantly associated with increased NRS-11 pain scores also included younger patient age (difference in pain score of 0.3/10 years with cough and 0.2/10 years at rest, p  < 0.01 for both) as well as a history of analgesic use (difference in pain score of 0.9 with cough and 0.6 at rest, p  < 0.01 and p  = 0.07, respectively). Conclusion Younger patients and those with a history of analgesic use are more likely to report higher post-operative pain and require higher doses of opioids. Early identification of these patients, and measures to better manage their pain, may contribute to optimal perioperative care.

Turnbull and Cutait described abdominoperineal pull-through followed by delayed coloanal anastomosis (DCA) in 1961. DCA could reduce anastomotic leaks, pelvic morbidity and use of stomas. Strong evidence about its clinical benefits is still lacking. This systematic review examined the clinical outcomes of DCA for the treatment of malignant or benign colorectal conditions. A systematic search of electronic medical databases was conducted. Two independent reviewers selected studies, extracted data and assessed risk of bias. The primary outcome was pelvic morbidity (anastomotic leak, pelvic abscess or sepsis, use of stoma). Fecal continence and survival data were also analyzed. From 1,251 citations, we included seven observational studies including 1,124 patients. All included studies were considered at high risk of bias. Two studies comparing DCA with immediate anastomosis reported a significant decrease in anastomotic leak, and pelvic abscess or sepsis. Low rates of pelvic morbidity were reported in the other five studies: anastomotic leak 0–7 %, pelvic abscess 0–11.8 % and pelvic sepsis 6.8–10 %. Rates of permanent stoma after DCA were low in six studies (1–6 %), with one study reporting an incidence of 25 %. Fecal continence was reported as satisfying in all studies. No differences were observed in a comparative setting. Survival data were reported in four studies. Clinical heterogeneity and methodological issues precluded meta-analysis. Based on retrospective evidence, DCA offers a low rate of anastomotic leak, pelvic morbidity and use of stoma, with reasonable fecal continence. Results are encouraging, but prospective studies are needed for comparison with standard of care.

Pancreatic cancer surgery is increasingly regionalized in high-volume centres. Provision of adjuvant chemotherapy in the same institution can place a burden on patients, whereas receiving adjuvant chemotherapy at a different institution closer to home may create disparities in care. This study compared long-term outcomes of patients with pancreatic adenocarcinoma receiving adjuvant chemotherapy at the institution where they had undergone surgery with outcomes for those receiving chemotherapy at a different institution. This was a population-based study of patients receiving adjuvant chemotherapy after resection of pancreatic adenocarcinoma performed at ten designated hepatopancreatobiliary centres in Ontario, Canada, between 2004 and 2014. Patients were divided into those receiving chemotherapy at the same institution as surgery or a different institution from where surgery was performed. The primary outcome was overall survival (OS). Multivariable Cox regression assessed the association between OS and each chemotherapy group, adjusted for potential confounders. Of 589 patients, 374 63·5 per cent) received adjuvant chemotherapy at the same institution as surgery. After adjusting for age, sex, co-morbidity, socioeconomic status, rural living, tumour stage, margin positivity and year of surgery, the location of adjuvant chemotherapy was not independently associated with OS (hazard ratio 1·03, 95 per cent c.i. 0·85 to 1·24). For patients who underwent chemotherapy at a different institution, mean travel distance to receive chemotherapy was less (22·9 km) than that needed for surgery (106·7 km). After pancreatectomy for pancreatic adenocarcinoma at specialized hepatopancreatobiliary surgery centres, OS was not affected by the location of the centre delivering adjuvant chemotherapy. Receiving this treatment in a local centre reduced patients' travel burden.

BackgroundSeveral modalities exist for the management of hepatic neoplasms. Resection, the most effective approach, carries significant risk of hemorrhage. Blood loss may be corrected with red blood cell transfusion (RBCT) in the short term, but may ultimately contribute to negative outcomes.PurposeUsing available literature, we seek to define the frequency and risk factors of blood loss and transfusion following hepatectomy. The impact of blood loss and RBCT on short- and long-term outcomes is explored with an emphasis on peri-operative methods to reduce hemorrhage and transfusion.ResultsFollowing hepatic surgery, 25.2–56.8% of patients receive RBCT. Patients who receive RBCT are at increased risk of surgical morbidity in a dose-dependent manner. The relationship between blood transfusion and surgical mortality is less apparent. RBCT might also impact long-term oncologic outcomes including disease recurrence and overall survival. Risk factors for bleeding and blood transfusion include hemoglobin concentration < 12.5 g/dL, thrombocytopenia, pre-operative biliary drainage, presence of background liver disease (such as cirrhosis), coronary artery disease, male gender, tumor characteristics (type, size, location, presence of vascular involvement), extent of hepatectomy, concomitant extrahepatic organ resection, and operative time. Strategies to mitigate blood loss or transfusion include pre-operative (iron, erythropoietin), intra-operative (vascular occlusion, parenchymal transection techniques, hemostatic agents, antifibrinolytics, low central pressure, hemodilution, autologous blood recycling), and post-operative (normothermia, correction of coagulopathy, optimization of nutrition, restrictive transfusion strategy) methods.ConclusionBlood loss during hepatectomy is common and several risk factors can be identified pre-operatively. Blood loss and RBCT during hepatectomy is associated with post-operative morbidity and mortality. Disease-free recurrence, disease-specific survival, and overall survival may be associated with blood loss and RBCT during hepatectomy. Attention to pre-operative, intra-operative, and post-operative strategies to reduce blood loss and RBCT is necessary.

Background: Surgical program directors (PDs) have been identified as being at high risk for emotional exhaustion and burnout. Consequent PD turnover and discontinuity in leadership can affect faculty and trainee success and well-being and the stability of residency programs. Prior studies have documented factors contributing to nonsurgical PD burnout; however, rates of early attrition and contributing factors in surgical PDs have not been investigated. This study examined factors affecting surgical PD satisfaction, stressors and areas where institutions can improve PD support. Methods: A national cross-sectional study of PDs was performed across all accredited surgical subspecialties. Domains assessed via a web-based survey included PD demographic characteristics and compensation, availability of administrative support for programs, satisfaction with the PD role and factors contributing to PD challenges and burnout. Results: Sixty percent of eligible surgical PDs (81/134) responded to the survey from 12 surgical specialties. Substantial heterogeneity was seen in tenure, compensation models and administrative support. All respondents exceeded their protected time for the PD position, and 66% received less than 0.8 full-time equivalent of administrative support. One-third of respondents (36%) were satisfied with their overall compensation for the position, while 43% were unhappy with compensatory models. Most respondents (70%) enjoyed the PD role, specifically relationships with trainees and the ability to shape the education of future surgeons. Stressors included insufficient administrative support, especially around resident remediation, and inadequate compensation, with 37% of PDs considering leaving the post prematurely. Conclusion: The majority of surgical PDs enjoy the role. However, intersecting factors such as disproportionate time demands, lack of administrative support and inadequate compensation for the role contribute to substantial stress and risk of early attrition. Systematic culture change to support PDs via better defined structural processes and sufficient resources is needed to keep these educators engaged and improve both PDs and trainees experiences.

IntroductionSurgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery.Methods and analysisThis is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts.Ethics and disseminationThis trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov.Trial registration numberClinicalTrials.gov identifier: NCT04549662.

Background: Laparoscopic liver resection (LLR) offers equivalent oncologic outcomes to open resection while reducing complications, hospital stays and costs in selected patients. However, the constraints of laparoscopy along with the inherent technical challenges of liver resection have slowed LLR uptake. To understand how experience supports LLR uptake, we examined the association between surgeons' liver resection volume and the use of LLR for gastrointestinal cancer. Methods: We identified patients who underwent elective liver resection for gastrointestinal cancer (2007-2019) within a health system with regionalized hepatobiliary surgical services. Surgeons' annual liver resection volume, defined using data from 2 years before patients' index surgery, was dichotomized into low (< 30) and high (> 30) volume informed by restricted cubic splines (RCS). We examined the association between surgeons' annual resection volume and LLR with RCS and modified Poisson regression adjusting for patient, procedure and surgeon factors. Results: Seventy-four surgeons performed 5133 liver resections (median patient age 64 yr; 38.7% female), 17.7% of which were performed laparoscopically. High-volume surgeons cared for 37.3% of patients. Low-volume surgeons performed a median of 18 annual resections (interquartile range [IQR] 12.5-30), whereas high-volume surgeons performed 42 (IQR 36-52.5). High-volume surgeons were more likely to utilize LLR (23.6% v. 17.7%, p < 0.001). After adjustment for patient and surgeon factors, high-volume surgeons remained independently associated with the use of laparoscopy (adjusted relative risk 1.30, 95% confidence interval [CI] 1.14-1.48) and increasing surgeon volume associated with higher LLR probability. Conclusion: Patients cared for by high-volume liver surgeons were 30% more likely to receive LLR over open surgery relative to those cared for by low-volume surgeons after adjustment for patient and surgeon characteristics. This indicates that the use of LLR differs on the basis of surgeons' experience with liver resection. These data are important to direct efforts aimed at optimizing the appropriate use and increasing the uptake of LLR, supporting the improvement of patient outcomes.