Early-life inflammation primes a T helper 2 cell-fibroblast niche in skin.

Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (TH2) cells within a distinct microanatomical niche. TH2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as TH2-interacting fascial fibroblasts (TIFFs), which expand in response to TH2 cytokines to form subcutaneous fibrous bands. Activation of the TH2-TIFF niche due to neonatal inflammation primes the skin for altered reparative responses to wounding. Furthermore, we identify fibroblasts in healthy human skin that express the TIFF transcriptional signature and detect these cells at high levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a previously unidentified TH2 cell niche in skin and functionally characterize a disease-associated fibroblast population. The results also suggest a mechanism of immunological priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells to establish an immunological set-point in tissues that is maintained throughout life.

Layilin Anchors Regulatory T Cells in Skin.

Regulatory T cells (Tregs) reside in nonlymphoid tissues where they carry out unique functions. The molecular mechanisms responsible for Treg accumulation and maintenance in these tissues are relatively unknown. Using an unbiased discovery approach, we identified LAYN (layilin), a C-type lectin-like receptor, to be preferentially and highly expressed on a subset of activated Tregs in healthy and diseased human skin. Expression of layilin on Tregs was induced by TCR-mediated activation in the presence of IL-2 or TGF-ß. Mice with a conditional deletion of layilin in Tregs had reduced accumulation of these cells in tumors. However, these animals somewhat paradoxically had enhanced immune regulation in the tumor microenvironment, resulting in increased tumor growth. Mechanistically, layilin expression on Tregs had a minimal effect on their activation and suppressive capacity in vitro. However, expression of this molecule resulted in a cumulative anchoring effect on Treg dynamic motility in vivo. Taken together, our results suggest a model whereby layilin facilitates Treg adhesion in skin and, in doing so, limits their suppressive capacity. These findings uncover a unique mechanism whereby reduced Treg motility acts to limit immune regulation in nonlymphoid organs and may help guide strategies to exploit this phenomenon for therapeutic benefit.

Updated guideline for closure of abdominal wall incisions from the European and American Hernia Societies.

BACKGROUND: Incisional hernia is a frequent complication of abdominal wall incision. Surgical technique is an important risk factor for the development of incisional hernia. The aim of these updated guidelines was to provide recommendations to decrease the incidence of incisional hernia. METHODS: A systematic literature search of MEDLINE, Embase, and Cochrane CENTRAL was performed on 22 January 2022. The Scottish Intercollegiate Guidelines Network instrument was used to evaluate systematic reviews and meta-analyses, RCTs, and cohort studies. The GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation) was used to appraise the certainty of the evidence. The guidelines group consisted of surgical specialists, a biomedical information specialist, certified guideline methodologist, and patient representative. RESULTS: Thirty-nine papers were included covering seven key questions, and weak recommendations were made for all of these. Laparoscopic surgery and non-midline incisions are suggested to be preferred when safe and feasible. In laparoscopic surgery, suturing the fascial defect of trocar sites of 10 mm and larger is advised, especially after single-incision laparoscopic surgery and at the umbilicus. For closure of an elective midline laparotomy, a continuous small-bites suturing technique with a slowly absorbable suture is suggested. Prophylactic mesh augmentation after elective midline laparotomy can be considered to reduce the risk of incisional hernia; a permanent synthetic mesh in either the onlay or retromuscular position is advised. CONCLUSION: These updated guidelines may help surgeons in selecting the optimal approach and location of abdominal wall incisions.

An incisional hernia results from a weakness of the abdominal wall muscles that allows fat from the inside or organs to bulge out. These hernias are quite common after abdominal surgery at the site of a previous incision. There is research that discusses different ways to close an incision and this may relate to the chance of hernia formation. The aim of this study was to review the latest research and to provide a guide for surgeons on how best to close incisions to decrease hernia rates. When possible, surgery through small incisions may decrease the risk of hernia formation. If small incisions are used, it may be better if they are placed away from areas that are already weak (such as the belly button). If the incision is larger than 1 cm, it should be closed with a deep muscle-fascia suture in addition to skin sutures. If there is a large incision in the middle of the abdomen, the muscle should be sutured using small stitches that are close together and a slowly absorbable suture should be used. For patients who are at higher risk of developing hernias, when closing the incision, the muscle layer can be strengthened by using a piece of (synthetic) mesh. There is no good research available on recovery after surgery and no clear guides on activity level or whether a binder will help prevent hernia formation.

Preventing Recurrence in Clean and Contaminated Hernias Using Biologic Versus Synthetic Mesh in Ventral Hernia Repair: The PRICE Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to evaluate which mesh type yields lower recurrence and complication rates after ventral hernia repair. SUMMARY BACKGROUND DATA: More than 400,000 ventral hernia repairs are performed annually in the United States. Although the most effective method for repairing ventral hernias involves using mesh, whether to use biologic mesh versus synthetic mesh is controversial. METHODS: Single-blind, randomized, controlled, pragmatic clinical trial conducted from March 2014 through October 2018; 165 patients enrolled with an average follow up of 26 months. Patients were randomized 1:1 to have their ventral hernias repaired using either a biologic (porcine) or synthetic (polypropylene) mesh. The primary study outcome measure was hernia recurrence at 2 years. RESULTS: A total of 165 patients (68 men), mean age 55 years, were included in the study with a mean follow-up of 26 months. An intention-to-treat analysis noted that hernias recurred in 25 patients (39.7%) assigned to biologic mesh and in 14 patients (21.9%) assigned to synthetic mesh (P = 0.035) at 2 years. Subgroup analysis identified an increased rate of hernia recurrence in the biologic versus the synthetic mesh group under contaminated wound conditions (50.0% vs 5.9%; P for interaction = 0.041). Postoperative complication rates were similar for the 2 mesh types. CONCLUSIONS: The risk of hernia recurrence was significantly higher for patients undergoing ventral hernia repair with biologic mesh compared to synthetic mesh, with similar rates of postoperative complications. These data indicate that the use of synthetic mesh over biologic mesh to repair ventral hernias is effective and can be endorsed, including under contaminated wound conditions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02041494.

Enhanced Stress Resilience Training in Surgeons: Iterative Adaptation and Biopsychosocial Effects in 2 Small Randomized Trials.

OBJECTIVE: To determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers. SUMMARY OF BACKGROUND AND DATA: Tailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown. METHODS: In 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity"). RESULTS: Neither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls. CONCLUSIONS: This pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.

Upper Gastrointestinal Endoscopy in an Academic General Surgical Program: Implications for Acute Care Surgeons.

Background. Esophagogastroduodenoscopy (EGD) is an important tool in the evolving specialty of acute care surgery (ACS). Understanding the types of nonelective EGDs performed by ACS groups is important for the development of ACS programs and the training of future general surgeons. Methods. We conducted a retrospective review of all EGDs performed by ACS surgeons at a single urban academic center over a 5-year period (January 2013-December 2018). Results. A total of 495 EGDs were performed, of which 129 (26%) were urgent, nonelective procedures. Patients who underwent urgent EGD were younger than those who underwent elective procedures (median 55 vs 60 years, P = .03), had higher American Society of Anesthesiologists (ASA) classes (median ASA 3 vs 2, P = .0002), and longer hospital stays (median 5 days vs 0 days, P < .0001). The most common indications for urgent endoscopies were the management of leak, dysphagia, or stenosis in patients with a history of foregut surgery, followed by the management of esophageal perforation. The success rate of endoscopic therapy was high (median 88%, interquartile range (IQR) 78-89%). However, some patients required multiple interventions (median 1, IQR 1-3), and patients treated for leaks were less likely to be successfully treated with endoscopic therapy alone than patients treated for other indications (success rate 65% vs 88%, P = .003). Conclusions. Our experience suggests that EGD has an important role in current ACS practice and that endoscopic management is safe and effective in a range of urgent surgical scenarios. Future ACS surgeons should be facile with endoscopic techniques.

Silver microparticles plus fibrin tissue sealant prevents incisional hernias in rats.

BACKGROUND: Open abdominal surgery is frequently complicated by the subsequent development of an incisional hernia. Consequently, more than 400,000 incisional hernia repairs are performed each year, adding over $15 billion per year to U.S. health-care expenditures. While the vast majority of studies have focused on improved surgical techniques or prosthetic materials, we examined the use of metallic silver microparticles to prevent incisional hernia formation through enhanced wound healing. MATERIALS AND METHODS: A rodent incisional hernia model was used. Eighty-two rats were randomly placed into two control groups (saline alone and silver microparticles alone), and three experimental groups (0 mg/cm, 2.5 mg/cm, and 25 mg/cm of silver microparticles applied with a fibrin sealant). Incisional hernia incidence and size, tensile strength, and tissue histology were assessed after 28 days. RESULTS: A significant reduction of both incisional hernia incidence and hernia size was observed between the control groups and 2.5 mg/cm group, and between the control and 25 mg/cm group by nearly 60% and 90%, respectively (P < 0.05). Histological samples showed a noticeable increase in new fibrosis in the treated animals as compared with the controls, whereas the tensile strength between the groups did not differ. CONCLUSIONS: The novel approach of using silver microparticles to enhance wound healing appears to be a safe and effective method to prevent incisional hernias from developing and could herald a new era of medicinal silver use.

Preoperative FOLFIRINOX for borderline resectable pancreatic cancer: Is radiation necessary in the modern era of chemotherapy?

BACKGROUND: No consensus exists regarding the optimal neoadjuvant treatment paradigm for patients with borderline resectable pancreatic cancer (BRPC), including the respective roles of chemotherapy and radiation. METHODS: We performed a retrospective analysis, including detailed pathologic and radiologic review, of pancreatic cancer patients undergoing FOLFIRINOX, with or without radiation therapy (RT), prior to surgical resection at a high-volume academic center over a 4-year period. RESULTS: Of 26 patients meeting inclusion criteria, 22 (84.6%) received FOLFIRINOX alone without RT (median number of treatment cycles = 9). The majority of patients met formal radiographic criteria for BRPC, with the superior mesenteric vein representing the most common vessel involved. R0 resection rate was 90.9%, with 12 patients (54.5%) requiring vascular reconstruction. Treatment response was classified as moderate or marked in 16 patients (72.7%) according to the College of American Pathologists grading system. Estimated median disease-free and overall survival rates are 22.6 months and not reached (NR), respectively. CONCLUSIONS: This is one of the largest series to describe the use of neoadjuvant FOLFIRINOX, without radiation therapy, in patients with BRPC undergoing surgical resection. Given the high R0 resection rates and favorable clinical outcomes with chemotherapy alone, this strategy should be further assessed in prospective study design. J. Surg. Oncol. 2016;114:587-596. © 2016 Wiley Periodicals, Inc.

Quality of life measures and cost analysis of biologic versus synthetic mesh for ventral hernia repair: The Preventing Recurrence in Clean and Contaminated Hernias randomized clinical trial.

BACKGROUND: Although the most durable method for ventral hernia repairs involves using mesh, whether to use biologic mesh versus synthetic mesh remains controversial. This study aimed to compare synthetic and biologic meshes with respect to patient-reported quality of life scores and costs after ventral hernia repair surgeries. METHODS: This study is part of the Preventing Recurrence in Clean and Contaminated Hernias (PRICE) pragmatic randomized control trial conducted from March 2014 through October 2018. Patients were randomized 1:1 to undergo ventral hernia repair using either a biologic or synthetic mesh. The coprimary outcomes were 2-year changes in Visual Analog Scale, Activities Assessment Scale, Hernia-Related Quality-of-Life Survey, and Short-Form 36 Health Survey (SF-36) quality-of-life scores from repair. The secondary outcome was the overall cost per patient. RESULTS: Among the 165 patients included in the study, 82 were randomized to biologic meshes and 83 to synthetic meshes. There were no significant differences in the performance between the 2 mesh types with regard to quality-of-life measures using a mixed model approach. This result was consistent even when performing subgroup analysis based on wound contamination. However, nonparametric tests comparing the differences in quality-of-life measures from preoperative to 24-month postoperative timepoints revealed that the synthetic mesh group showed a greater reduction in disability than biologic mesh for the SF-36 (median [interquartile range] of 20 [5-30] vs 6 [1-20], P = .025). This difference was due to reductions in the physical role limitations (62 [0-100] vs 0 [0-50], P = .018) and the pain (38 [12-50] vs 12 [0-25], P = .012) domains of the SF-36. Overall cost per patient was greater for biologic meshes (mean [95% confidence interval] of $80,420 [$66,485-$94,355] vs $61,036 [$48,946-$73,125], P = .038), regardless of insurance type. CONCLUSION: In this randomized clinical trial, there were no differences in changes in quality-of-life scores at the 2-year timepoint except for the SF-36, where the synthetic mesh may be associated with less pain and physical role limitations than the biologic mesh. Overall costs per patient were less for synthetic than biologic mesh.

Characterizing the global burden of surgical disease: a method to estimate inguinal hernia epidemiology in Ghana.

BACKGROUND: Surgical conditions represent an immense yet underrecognized source of disease burden globally. Characterizing the burden of surgical disease has been defined as a priority research agenda in global surgery. Little is known about the epidemiology of inguinal hernia, a common easily treatable surgical condition, in resource-poor settings. METHODS: Using data from the National Health and Nutrition Examination Survey prospective cohort study of inguinal hernia, we created a method to estimate hernia epidemiology in Ghana. We calculated inguinal hernia incidence and prevalence using Ghanaian demographic data and projected hernia prevalence under three surgical rate and hernia incidence scenarios. Disability adjusted life-years (DALYs) associated with inguinal hernia along with costs for surgical repair were estimated. RESULTS: According to this approach, the prevalence of inguinal hernia in the Ghanaian general population is 3.15% (range 2.79-3.50%). Symptomatic hernias number 530,082 (range 469,501-588,980). The annual incidence of symptomatic hernias is 210 (range 186-233) per 100,000 population. At the estimated Ghanaian hernia repair rate of 30 per 100,000, a backlog of 1 million hernias in need of repair develop over 10 years. The cost of repairing all symptomatic hernias in Ghana is estimated at US $53 million, and US $106 million would be required to eliminate hernias over a 10-year period. Nearly 5 million DALYs would be averted with the repair of prevalent cases of symptomatic hernia in Ghana. CONCLUSIONS: Data generated by our method indicate the extent to which Ghana lacks the surgical capacity to address its significant inguinal hernia disease burden. This approach provides a simple framework for calculating inguinal hernia epidemiology in resource-poor settings that may be used for advocacy and program planning in multiple country contexts.

Biologic Versus Synthetic Mesh in Ventral Hernia Repair: Participant-Level Analysis of Two Randomized Controlled Trials at Twenty-Four to Thirty-Six Months.

Background: Biologic mesh has been used increasingly in complex ventral hernia repair despite limited evidence at low risk of bias supporting its use. Patients and Methods: We performed a participant-level analysis of published randomized controlled trials (RCTs) comparing biologic to synthetic mesh with complex ventral hernia repair at 24 to 36 months. Primary outcome was major complication (composite of mesh infection, recurrence, reoperation, or death) at 24 to 36 months post-operative. Secondary outcomes included length of index hospital stay, surgical site occurrence, surgical site infection, and death. Outcomes were assessed using both frequentist and Bayesian generalized linear regression models. Results: A total of 252 patients from two RCTs were included, 126 patients randomized to the intervention arm of biologic and 126 patients to the control of synthetic mesh with median follow-up of 29 (23, 38) months. Major complication occurred in 33 (33%) patients randomized to biologic, and 39 (38%) patients randomized to synthetic mesh, (relative risk [RR] 0.91, 95% confidence interval [CI] 0.63-1.31; p value = 0.600). Bayesian analysis demonstrated that compared with synthetic mesh, biologic mesh had similar probability of major complications at 24 to 36 months post-operative. The remainder of outcomes demonstrated slight benefit with synthetic mesh as opposed to biologic mesh except for mesh infection. However, under a frequentist framework, no outcome was statistically different. Conclusions: In patients undergoing open ventral hernia repair, there was no benefit for patients receiving biologic versus synthetic mesh at 24 to 36 months post-operative.

Innovations for Incisional Hernia Prevention.

Incisional hernias are the most frequent long-term complication of abdominal surgery, resulting in considerable patient morbidity and increased health care costs. These hernias frequently result from excessive tension concentrated at points along the suture line of the abdominal closure. While ample research is focused on developing improved repair materials, the optimal solution to the problem of incisional hernias is prevention. Accordingly, some investigators have postulated that incisional hernias can be prevented by distributing tension more evenly along the fascial closure. Herein we describe two novel and ingenious strategies for the improved distribution of tension when closing abdomens (T-Line® Hernia Mesh and the REBUILD Bioabsorbable™) that were conceived of and developed by surgeons.

Cost-Effectiveness Analysis of Inguinal Hernia Repair With Mesh Performed by Surgeons and Medical Doctors in Ghana.

OBJECTIVES: Task-sharing is the pragmatic sharing of tasks between providers with different levels of training. To our knowledge, no study has examined the cost-effectiveness of surgical task-sharing of hernia repair in a low-resource setting. This study has aimed to evaluate and compare the cost-effectiveness of mesh repair performed by Ghanaian surgeons and medical doctors (MDs) following a standardized training program. METHODS: This cost-effectiveness analysis included data for 223 operations on adult men with primary reducible inguinal hernia. Cost per surgery was calculated from the healthcare system perspective. Disability weights were calculated using pre- and postoperative pain scores and benchmarks from the Global Burden of Disease Study 2017. RESULTS: The mean cost/disability-adjusted life-year (DALY) averted in the surgeon group was 444.9 United States dollars (USD) (95% confidence interval [CI] 221.2-668.5) and 278.9 USD (95% CI 199.3-358.5) in the MD group (P = .168), indicating that the operation is very cost-effective when performed by both providers. The incremental cost/DALY averted showed that task-sharing with MDs is also very cost-effective (95% bootstrap CI -436.7 to 454.9). The analysis found that increasing provider salaries is cost-effective if productivity remains high. When only symptomatic cases were analyzed, the mean cost/DALY averted reduced to 232.0 USD (95% CI 17.1-446.8) for the surgeon group and 129.7 USD (95% CI 79.6-179.8) for the MD group (P = .348), and the incremental cost/DALY averted increased by 45% but remained robust. CONCLUSIONS: Elective inguinal hernia repair with mesh performed by Ghanaian surgeons and MDs is a low-cost procedure and very cost-effective in the context of the study. To maximize cost-effectiveness, symptomatic patients should be prioritized over asymptomatic patients and a high level of productivity should be maintained.

NKT cells: the culprits of sepsis?

Sepsis is currently a leading cause of death in hospital intensive care units. Previous studies suggest that the pathophysiology of sepsis involves the hyperactivation of complex pro-inflammatory cascades that include the activation of various immune cells and the exuberant secretion of pro-inflammatory cytokines by these cells. Natural killer T-cells (NKT) are a sub-lineage of T cells that share characteristics of conventional T cells and NK cells, and bridge innate and adaptive immunity. More recently, NKT cells have been implicated in microbial immunity, including the onset of sepsis. Moreover, apolipoprotein E (apoE), a component of triglyceride-rich lipoproteins, has been shown to be protective in endotoxemia and gram-negative infections in addition to its well-known role in lipid metabolism. Here, we will review the role of NKT cells in sepsis and septic shock, the immunoregulatory role of apoE in the host immune response to infection, and propose a mechanism for this immunoregulation.

Burden of Ionizing Radiation in the Diagnosis and Management of Necrotizing Pancreatitis.

INTRODUCTION: A step-up endoscopic or percutaneous approach improves outcomes in necrotizing pancreatitis (NP). However, these require multiple radiographic studies and fluoroscopic procedures, which use low-dose ionizing radiation. The cumulative radiation exposure for treatment of NP has not been well defined. METHODS: We conducted a retrospective study of consecutive patients with NP admitted to University of California San Francisco Medical Center from January 2011 to June 2019. We calculated effective doses for fluoroscopic procedures using the dose area product and used the National Cancer Institute tool for computed tomography studies. The primary outcome was the cumulative effective dose (CED). Multivariable logistic regression was used to evaluate risk factors of high exposure (CED > 500 mSv). RESULTS: One hundred seventy-one patients with NP (mean follow-up 40 ± 18 months) underwent a median of 7 (interquartile range [IQR] 5-11) computed tomography scans and 7 (IQR 5-12) fluoroscopic procedures. The median CED was 274 mSv (IQR 177-245) and 30% (51) of patients received high exposure. Risk factors of high exposure include multiorgan failure (aOR 3.47, 95%-CI: 1.53-9.88, P = 0.003), infected necrosis (adjusted odds ratio [aOR] 3.89 95%-CI:1.53-9.88, P = 0.005), and step-up endoscopic approach (aOR 1.86, 95%-CI: 1.41-1.84, P = 0.001) when compared with step-up percutaneous approach. DISCUSSION: Patients with NP were exposed to a substantial amount of ionizing radiation (257 mSv) as a part of their treatment, and 30% received more than 500 mSv, which corresponds with a 5% increase in lifetime cancer risk. Severity of NP and a step-up endoscopic approach were associated with CED > 500 mSv. Further studies are needed to help develop low-radiation treatment protocols for NP, particularly in patients receiving endoscopic therapy.

Apolipoprotein E-mediated immune regulation in sepsis.

Lipids and lipoproteins have emerged as key constituents of the immune response to microbial infection. We, therefore, sought to understand the complex interaction between lipoprotein metabolism and sepsis. Apolipoprotein E (apoE), a component of plasma lipoproteins, has been suggested to bind and traffic Ags for NKT cell activation. However, apoE's role in sepsis has not been demonstrated. In this study, we examined the effect of exogenous apoE in a rat model of septic peritonitis, induced by cecal ligation and puncture. We demonstrate that 48 h after serial injections of apoE, septic mortality increased in a dose-dependent manner. While sepsis resulted in increased splenic and decreased hepatic and circulating NKT cell populations, serial injections of apoE for 24 h after cecal ligation and puncture increased the frequency, cell number, and BrdU uptake in splenic and hepatic NKT cell populations, while concomitantly depleting these populations in the circulation. These changes were correlated with elevated alanine amino transferase levels, an indicator of liver injury. Interestingly, while sepsis increased hepatic T cell apoptosis and necrosis, apoE reversed these changes. apoE also promoted increases in predominantly Th1 cytokine levels in sera and a decrease in IL-4, the main NKT cell-derived Th2 cytokine. Consequently, apoE treatment is associated with increased sepsis-induced mortality, and increased NKT cell frequency and proliferation in the liver and spleen, with concomitant decreases in these NKT cell parameters in the peripheral circulation. apoE treatment also promoted a Th1 cytokine response, increased the degree of liver injury, and decreased apoptosis in hepatic lymphocytes.

NKT cells in sepsis.

Sepsis is currently a leading cause of death in hospital intensive care units. Previous studies suggest that the pathophysiology of sepsis involves the hyperactivation of complex proinflammatory cascades that include the activation of various immune cells and the exuberant secretion of proinflammatory cytokines by these cells. Natural killer T-cells (NKTs) are a sublineage of T cells that share characteristics of conventional T cells and NK cells and bridge innate and adaptive immunity. More recently, NKT cells have been implicated in microbial immunity, including the onset of sepsis. Moreover, apolipoprotein E (apoE), a component of triglyceride-rich lipoproteins, has been shown to be protective in endotoxemia and gram-negative infections in addition to its well-known role in lipid metabolism. Here, we will review the role of NKT cells in sepsis and septic shock, the immunoregulatory role of apoE in the host immune response to infection, and propose a mechanism for this immunoregulation.

Key factors for implementing mindfulness-based burnout interventions in surgery.

BACKGROUND: Burnout and distress are widespread issues in surgical training. While effective interventions are slowly coming to light, little has been published regarding the sustainable implementation of such interventions, including the critical need to identify barriers and enablers. METHODS: Enhanced Stress Resilience Training (ESRT), a mindfulness-based cognitive intervention for surgical trainees, was delivered and studied on three separate occasions. For each, focus groups, field notes, surveys and interviews were collected involving leadership, administrators and participants. Thematic analysis was used in each instance, and across instances, to explore concepts and themes, which were used to identify critical influences effecting implementation. RESULTS: Culture (surrounding the intervention), infrastructure (supporting the intervention) and adaptability (of the intervention) were repeatedly critical influences, guiding iterative adaptation of the intervention, and resulting in sustainability across groups and over time. CONCLUSIONS: Identifying critical influences on intervention feasibility and acceptability can guide intervention refinement and shift sustainable implementation barriers to become enablers, as was the case at our institution. This approach may be useful in other settings.

A Coupled Magnetoelastic Strain Sensor Array for Guiding and Monitoring Hernia Repairs.

OBJECTIVE: Ventral hernia repairs using mesh prosthetics suffer from high recurrence rates, with 10%-20% of repairs failing within three years. Uneven distribution of stress within the implanted mesh prosthetic is thought to contribute to the high recurrence rate. We propose a method for providing quantitative guidance and monitoring of hernia repairs using an array of magnetoelastic strain sensors. METHODS: The magnetoelastic strain sensors presented here are based on a coupled design to achieve measurements with higher signal-to-noise ratio (SNR). A first magnetoelastic element (the transducer) is bonded to the mesh prosthetic and is characterized by a strain-dependent magnetic field. The resonance frequency of a second magnetoelastic element (the resonator) encased in a rigid casing is biased by the transducer element's magneticity and can be measured noninvasively using an external interrogation coil. The coupled magnetoelastic strain sensors are assembled using a combination of photochemical machining, patterning, and heat sealing. RESULTS: The dynamic range of the coupled sensors can be tuned by altering the transducer geometry. Additional spring elements are integrated onto the transducer element to achieve high dynamic range measurements saturating at 74 millistrains. CONCLUSION: A coupled magnetoelastic strain sensor combines a transducer with an encased resonator element to measure strain with high SNR on an implantable flexible hernia mesh substrate. SIGNIFICANCE: This study provides surgeons and researchers with a clinically relevant tool to quantify the strain distributions within implanted mesh prosthetics, with the ultimate goal of reducing the recurrence rate of ventral hernia repairs.

Integrating Robotic Technology Into Resident Training: Challenges and Recommendations From the Front Lines.

PURPOSE: To develop recommendations for improving the integration of robotic technology into today's apprentice-based resident training. METHOD: During a national meeting in 2017, 24 robotic surgeons were interviewed about their experiences integrating robotic technology into resident training. Qualitative thematic analysis of interview notes and recordings revealed themes related to challenges and recommendations. RESULTS: Four themes emerged, each corresponding to a general recommendation for integrating robotic technology into training. The first, surgical techniques versus tools, contrasts faculty's sequential mastery-surgical techniques first, then the robotic tool-with residents' simultaneous learning. The recommendation is to create separate learning opportunities for focused skill acquisition. The second theme, timing of exposure to the robotic tool, describes trainees' initial focus on tool use for basic surgical steps. The recommendation is to increase access to basic robotic cases. The third theme covers the relationship of laparoscopic and robotic surgery. The recommendation is to emphasize similar and dissimilar features during all minimally invasive surgical cases. The fourth theme, use of the dual console (which enables two consoles to operate the robot, the primary determines the secondary's functionality), highlights the unique teaching opportunities this console creates. The recommendation is for surgeons to give verbal guidance so residents completely understand surgical techniques. CONCLUSIONS: Surgical educators should consider technique versus tool, timing of exposure to the tool, overlapping and varying features of robotic and laparoscopic surgery, and use of the dual console as they develop curricula to ensure thorough acquisition and synthesis of all elements of robotic surgery.