Data Requirement for Animal-Derived Wound Care Devices: Limitations of the 510(k) Regulatory Pathway.

BACKGROUND: Device classification and preclinical data requirements for animal-derived wound care products were recently reviewed by the FDA. Given the possible performance differences for these products, we evaluated the FDA data requirements as well as the published literature for all animal-derived wound care products ever cleared through the FDA. STUDY DESIGN: The publicly available online database was queried for all animal-derived wound products; premarket data requirements for each product were recorded. A PubMed search was conducted to determine the number of published clinical studies for each product, and manufacturer websites were accessed to obtain the price for each product. RESULTS: A total of 132 animal-derived wound products have been cleared by the FDA since the Center for Devices and Radiological Health was established in 1976. Of these, 114 had a publicly available clearance statement online. Preclinical biocompatibility testing was performed in 85 products (74.6%) and referenced in 10 (8.8%). Preclinical animal wound healing testing took place in 17 (14.9%). Only 9 products (7.9%) had clinical safety testing, and no products had clinical effectiveness data. We found no published peer-reviewed clinical data for 97 products (73%). Cost was infrequently available but ranged from $4.79 to $2,178 per unit. CONCLUSIONS: Although the current pathway is appropriate for efficiently clearing new wound care products, clinical effectiveness is not included in the regulatory review process. Wound care products are primarily evaluated by the FDA for safety and biocompatibility. Thus, any claims of clinical effectiveness require independent validation, which is often lacking.

Tertiary lymphoid structures sustain cutaneous B cell activity in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin condition affecting approximately 1% of the US population. HS skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu, the biology and the contribution of these cells in HS pathogenesis are unclear. We aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. Combining histological analysis, single-cell RNA sequencing, and spatial transcriptomics profiling of HS lesions, we defined the tissue microenvironment relative to B cell activity within this disease. Our findings identified tertiary lymphoid structures (TLSs) within HS lesions and described organized interactions among T cells, B cells, antigen-presenting cells, and skin stroma. We found evidence that B cells within HS TLSs actively underwent maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells were primed to support the formation of TLSs and facilitate B cell recruitment during HS. Our data definitively demonstrated the presence of TLSs in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed nonlymphoid tissue.

Feasibility of Gastrografin Use for Adhesive Small Bowel Obstruction in Low-Income Countries.

INTRODUCTION: Small bowel obstruction (SBO) is one of the most common causes for hospital admission in Ethiopia. The use of water-soluble contrast agents (WSCAs) such as Gastrografin to manage adhesive SBO can predict nonoperative resolution of SBO and reduce decision time to surgery and length of hospital stay. However, nothing is known about practice patterns and Gastrografin use in low-income settings. We sought to characterize current management practices, including use of WSCAs, as well as outcomes for patients with SBO in Addis Ababa, Ethiopia. METHODS: We conducted a mixed-methods study consisting of a survey of surgeons throughout Ethiopia and a retrospective record review at five public, tertiary care-level teaching hospitals in Addis Ababa. RESULTS: Of the 76 surgeons who completed the survey, 63% had heard of the use of WSCAs for SBO and only 11% used oral agents for its management. Chart review of 149 patients admitted with SBO showed the most common etiology was adhesion (39.6% of admissions), followed by small bowel volvulus (20.8%). Most patients (83.2%) underwent surgery during their admission. The most common diagnosis in patients who did not require surgery was also adhesion (68.0%), as well as for those who had surgery (33.9%), followed by small bowel volvulus (24.2%). CONCLUSIONS: The etiology of SBO in Ethiopia may be changing, with postoperative adhesions becoming more common than other historically more prevalent causes. Although a Gastrografin protocol as a diagnostic and potentially therapeutic aid for SBO is feasible in this population and setting, challenges can be anticipated, and future studies of protocol implementation and effectiveness are needed to further inform its utility in Ethiopia and other low-income and middle-income countries.

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.

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.

Tertiary Lymphoid Structures Sustain Cutaneous B cell Activity in Hidradenitis Suppurativa.

Background: Hidradenitis suppurativa (HS) skin lesions are highly inflammatory and characterized by a large immune infiltrate. While B cells and plasma cells comprise a major component of this immune milieu the biology and contribution of these cells in HS pathogenesis is unclear. Objective: We aimed to investigate the dynamics and microenvironmental interactions of B cells within cutaneous HS lesions. Methods: We combined histological analysis, single-cell RNA-sequencing (scRNAseq), and spatial transcriptomic profiling of HS lesions to define the tissue microenvironment relative to B cell activity within this disease. Results: Our findings identify tertiary lymphoid structures (TLS) within HS lesions and describe organized interactions between T cells, B cells, antigen presenting cells and skin stroma. We find evidence that B cells within HS TLS actively undergo maturation, including participation in germinal center reactions and class switch recombination. Moreover, skin stroma and accumulating T cells are primed to support the formation of TLS and facilitate B cell recruitment during HS. Conclusion: Our data definitively demonstrate the presence of TLS in lesional HS skin and point to ongoing cutaneous B cell maturation through class switch recombination and affinity maturation during disease progression in this inflamed non-lymphoid tissue.

A Novel Polypropylene Mesh (T-Line®) for Abdominal Wall Repair: Early Experience at Three Centers in the United States.

Mesh suture was initially developed and investigated to overcome suture pull-through in hernia repair. It has a large area compared to standard suture which distributes the load in tissue, reducing stress at the suture/tissue interface and preventing suture from cutting through tissue or the mesh. This report describes our early experience using the new T-line® mesh (Deep Blue Medical Advances, Durham, NC, USA) in patients with incisional and primary ventral hernia repairs. This is a descriptive, retrospective study in 18 patients who underwent abdominal wall repair with T-Line® mesh from November 2020 to November 2021 in three academic centers. T-Line® is a novel moderate-weight macroporous, polypropylene mesh with extensions that are 29 times the cross-sectional area of #0 polypropylene suture. They can be sewn into fascia to anchor the mesh with no need for suture tackers or other devices to fixate the mesh. The median age of the patients was 56.5 years (range 25-83) and the median BMI was 31.7 kg/m2 (range 23.6-51). Twelve patients (66.7%) had primary hernias, and 11 (61.1%) had a recurrent hernia. The median defect area was 117.5 cm2 (range 4-390) and the median mesh area was 449.5 cm2 (range 130-600). The mesh position was onlay in 16 cases (88.9%) and sublay in 2 cases (11.1%). The median operative time was 247 minutes (range 104-395). The median length of stay was six days (range 0-21) with no significant in-hospital complications. One patient had a surgical site infection (5.5%) and two patients developed seromas (11.1%). There were no early hernia recurrences with a median follow-up of 28 days (range 8-307). The T-Line® mesh was shown to be safe and effective for patients with ventral hernia in the short term.

Expert Consensus for Key Features of Operative Reports of Ventral Hernia.

BACKGROUND: Operative reports are important documents; however, standards for critical elements of operative reports are general and often vague. Hernia surgery is one of the most common procedures performed by general surgeons, so the aim of this project was to develop a Delphi consensus on critical elements of a ventral hernia repair operative report. STUDY DESIGN: The Delphi method was used to establish consensus on key features of operative reports for ventral hernia repair. An expert panel was selected and questionnaires were distributed. The first round of voting was open-ended to allow participants to recommend what details should be included. For the second round the questionnaire was distributed with the items that did not have unanimous responses along with free text comments from the first round. RESULTS: Eighteen surgeons were approached, of which 11 completed both rounds. Twenty items were on the initial questionnaire, of which 11 had 100% agreement. Of the remaining 9 items, after the second questionnaire an additional 7 reached consensus. CONCLUSION: Ventral hernia repairs are a common and challenging problem and often require reoperations. Surgeons frequently refer to previous operative notes to guide future procedures, which requires detailed and comprehensive operative reports. This Delphi consensus was able to identify key components needed for an operative report describing ventral hernia repair.

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.

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.

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.

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.

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.

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.

Immunopathogenesis of hidradenitis suppurativa and response to anti-TNF-α therapy.

Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.