Transcutaneous vagal nerve simulation to reduce a systemic inflammatory response syndrome and the associated intestinal failure: study protocol of a prospective, two-armed, sham-controlled, double-blinded trial in healthy subjects (the NeuroSIRS-Study).

PURPOSE: Surgery initiates pro-inflammatory mediator cascades leading to a variably pronounced sterile inflammation (SIRS). SIRS is associated with intestinal paralysis and breakdown of intestinal barrier and might result in abdominal sepsis. Technological progress led to the development of a neurostimulator for transcutaneous auricular vagal nerve stimulation (taVNS), which is associated with a decline in inflammatory parameters and peristalsis improvement in rodents and healthy subjects via activation of the cholinergic anti-inflammatory pathway. Therefore, taVNS might be a strategy for SIRS prophylaxis. METHODS: The NeuroSIRS-Study is a prospective, randomized two-armed, sham-controlled, double-blind clinical trial. The study is registered at DRKS00016892 (09.07.2020). A controlled endotoxemia is used as a SIRS-mimicking model. 2 ng/kg bodyweight lipopolysaccharide (LPS) will be administered after taVNS or sham stimulation. The primary objective is a reduction of clinical symptoms of SIRS after taVNS compared to sham stimulation. Effects of taVNS on release of inflammatory cytokines, intestinal function, and vital parameters will be analyzed. DISCUSSION: TaVNS is well-tolerated, with little to no side effects. Despite not fully mimicking postoperative inflammation, LPS challenge is the most used experimental tool to imitate SIRS and offers standardization and reproducibility. The restriction to healthy male volunteers exerts a certain bias limiting generalizability to the surgical population. Still, this pilot study aims to give first insights into taVNS as a prophylactic treatment in postoperative inflammation to pave the way for further clinical trials in patients at risk for SIRS. This would have major implications for future therapeutic approaches.

Update on surgical management of enteroatmospheric fistulae in intestinal failure patients.

PURPOSE OF REVIEW: The surgical management of enteroatmospheric fistula (EAF) in patients with intestinal failure represents a major challenge for a surgical team and requires proficiency in sepsis management, nutritional support and prehabilitation, beside expertise in visceral and abdominal wall surgery. This review provides an update on the current recommendations and evidence. RECENT FINDINGS: Reconstructive surgery should be performed at a minimum of 6-12 months after last laparotomy. Isolation techniques and new occlusion devices may accelerate spontaneous EAF closure in selected cases. Chyme reinfusion supports enteral and parenteral nutrition. Stapler anastomosis and failure to close the fascia increase the risk of EAF recurrence. Posterior component separation, intraoperative fascial tension and biological meshes may be used to accommodate fascial closure. SUMMARY: Timing of reconstructive surgery and previous optimal conservative treatment is vital for favorable outcomes. Wound conditions, nutritional support and general patient status should be optimal before attempting a definitive fistula takedown. Single stage procedures with autologous gut reconstruction and abdominal wall reconstruction can be complex but well tolerated.

The Significance of Visceral Protection in Preventing Enteroatmospheric Fistulae During Open Abdomen Treatment in Patients With Secondary Peritonitis: A Propensity Score-matched Case-control Analysis.

OBJECTIVE: To evaluate the influence of a visceral protective layer (VPL) on the formation of enteroatmospheric fistulae (EAF) in open abdomen treatment (OAT) for peritonitis. BACKGROUND: EAF formation is a severe complication of OAT. Despite the widespread use of OAT, there are no robust evidence-based recommendations for preventing EAF. METHODS: A total of 120 peritonitis patients with secondary peritonitis as a result of a perforation of a hollow viscus or anastomotic insufficiency who had undergone OAT were included, and 14 clinical parameters were recorded in prospective OAT databases at 2 tertiary referral centers. For this analysis, patients with a VPL were assigned to the treatment group and those without a VPL to the control group. Propensity Score (PS) matching was performed. Known risk factors in OAT such as malignant disease, mortality, emergency operation, OAT duration, and fascial closure were matching variables. The influence of VPL on EAF formation was statistically evaluated using logistic regression analysis. RESULTS: With 34 patients in each group, no notable differences were identified with regard to age, sex, underlying disease, mortality, emergency operation, fascial closure, and OAT duration. Overall, a mortality rate of 22.1% for OAT due to peritonitis was observed. Mean OAT duration was approximately 9 days, and secondary fascial closure was achieved in more than two-thirds of all patients. Fascial traction was used in more than 75% of cases. EAF formation was significantly more frequent in the control group (EAF formation: VPL group 2.9% vs control 26.5%; P = 0.00). In the final regression analysis, the use of VPL resulted in a significant reduction in the risk of EAF formation (odds ratio 0.08; 95% confidence interval 0.01-0.71, P = 0.02), which translates to a relative risk reduction of 89.1%. CONCLUSION: VPL effectively prevents EAF formation during OAT in patients with peritonitis. We recommend the consistent use of VPL as part of a standardized OAT treatment algorithm.

Safety and Suitability of the SmartPill® after Abdominal Surgery: Results of the Prospective, Two-Armed, Open-Label PIDuSA Trial.

INTRODUCTION: Postoperative ileus (POI) is a common complication after abdominal surgery. Until today, an evidence-based treatment of prolonged POI is still lacking, which can be attributed to the poor quality of clinical trials. Various different surrogate markers used to define POI severity are considered to be the cause of low-quality trials making it impossible to derive treatment recommendation. The SmartPill®, which is able to record pH values, temperature and pressure after ingestion, could be an ideal tool to measure transit times and peristalsis and therefore analyze POI severity. Unfortunately, the device has no approval for postoperative use due to safety concerns. The primary objective of the study is to determine safety of the SmartPill® in patients undergoing surgery. Secondary objectives were the quality of the recorded data and the suitability of the SmartPill® for analyzing intestinal motility after different surgical procedures. METHODS: The PIDuSA Study is a prospective, 2-arm, open-label trial. At the end of surgery, the SmartPill® was applied to 49 patients undergoing abdominal surgery having a high risk for impaired intestinal motility and 15 patients undergoing extra-abdominal surgery. Patients were visited daily to access safety data of the SmartPill® on the basis of adverse and serious adverse events (AEs/SAEs). Suitability and data quality were investigated by analyzing data completeness and feasibility to determine transit times and peristalsis for all sections of the gastrointestinal tract. RESULTS: In total, 179 AEs and 8 SAEs were recorded throughout the study affecting 42 patients in the abdominal (158 AEs) and 9 patients in the extra-abdominal surgery group (21 AEs, p = 0.061); none of them were device related. Primary capsule failure was observed in 5 patients, ultimately resulting in an impossibility of data analysis in only 3 patients (4.4%). 9% of the recorded data were incomplete due to the patient's incompliance in keeping the receiver close to the body. In 3 patients (4.4%), isolated small bowel transit could not be determined due to pH alterations as a result of prolonged POI. DISCUSSION: Our study demonstrates that the use of the SmartPill® is safe after surgery but requires a reasonable patient compliance to deliver meaningful data. An objective analysis of transit times and peristalsis was possible irrespective of type and site of surgery in over 95% indicating that the SmartPill® has the potential to deliver objective parameters for POI severity in future clinical trials. However, in some patients with prolonged POI, analysis of small bowel transit could be challenging.

HPV-associated anal lesions in HIV+ patients: long-term results regarding quality of life.

PURPOSE: HIV infection and concomitant HPV-associated anal lesions may significantly impact on patients' quality of life (QoL), as they are predicted to have negative effects on health, psyche, and sexuality. MATERIAL AND METHODS: Fifty-two HIV+ patients with HPV-associated anal lesions were enrolled in a survey approach after undergoing routine proctologic assessment and therapy for HPV-associated anal lesions if indicated over a time span of 11 years (11/2004-11/2015). Therapy consisted of surgical ablation and topic treatment. QoL was analyzed using the SF-36 and the CECA questionnaires. RESULTS: Fifty-two of 67 patients (77.6%) were successfully contacted and 29/52 provided full information. The mean age was 43.8 ± 12.8 years. The median follow-up from treatment to answering of the questionnaire was 34 months. Twenty-one percent (6/29) of the patients reported suffering from recurrence of condyloma acuminata, three patients from anal dysplasia (10.3%). In the SF-36, HIV+ patients did not rate their QoL as significantly different over all items after successful treatment of HPV-associated anal lesions. In the CECA questionnaire, patients with persisting HPV-associated anal lesions reported significantly higher emotional stress levels and disturbance of everyday life compared to patients who had successful treatment (71.9/100 ± 18.7 vs. 40.00/100 ± 27.4, p = 0.004). Importantly, the sexuality of patients with anal lesions was significantly impaired (59.8/100 ± 30.8 vs. 27.5/100 ± 12.2, p = 0.032). CONCLUSION: HPV-associated anal lesions impact significantly negative on QoL in HIV+ patients. Successful treatment of HPV-associated anal lesions in HIV+ patients improved QoL. Specific questionnaires, such as CECA, seem to be more adequate than the SF-36 in this setting.

[Inderdisciplinary care of patients with short-bowel-syndrome in Germany: A comparative Cost-of-Illness analysis of in- and outpatient care]. / Interdisziplinäre Betreuung von Patienten mit Kurzdarmsyndrom in Deutschland: Eine Cost-of-Illness-Analyse der stationären und ambulanten Behandlung im Vergleich zum erzielten DRG-Erlös.

INTRODUCTION: Short-bowel-syndrome (SBS) is an often chronic disease with high morbidity. The aim of this study was to evaluate the complexity of SBS treatment and the economic burden on a treating hospital. METHODS: Anonymized data of eleven consecutive SBS patients from the University Hospital of Bonn were included. Parameters of medical resources were considered for year of diagnosis (YOD) and a follow-up (FU) period of three years. Subsequently, costs were evaluated according to the corresponding catalogues. RESULTS: Median inpatient days were 96 days in YOD and decreased to three days in the third year of FU. Median cost of inpatient treatment decreased from approximately 84 500 € auf 3200 €. While major visceral surgery was usually required in the YOD, catheter-associated interventions dominated during further FU. Actual reimbursement according to the G-DRG covered approximately 50 % of inpatient treatment cost, for outpatient care only est. 16.5 % of costs were covered. Annual costs for medication, parenteral nutrition and GLP-2-analogon treatment added up to 6752 €, 48 485 € and 138 442 €, respectively. CONCLUSIONS: The interdisciplinary medical care of SBS-patients is resource-intensive and expensive. The required treatment shifts from the in- to the outpatient sector. Both settings are at present not adequately reimbursed. Hence, this imbalance may endanger adequate care for SBS-patients in the future in times of economic rationale. In concordance with other rare disease management programs, additional measures are needed to provide and improve interdisciplinary treatment of SBS.

[Prognostic Factors of Open Abdomen Treatment in Visceral Surgery]. / Prognosefaktoren der offenen Abdominalbehandlung in der Viszeralchirurgie.

Introduction In general surgery, open abdomen treatment (OAT) is used to treat abdominal compartment syndrome (ACS) and sepsis, often after a primary surgical procedure associated with complications. The results achieved in this patient population may depend on factors that are yet unknown. This study evaluates independent patient-related prognostic factors after OAT. Methods 38 clinical parameters and survival data of 165 consecutive general surgery patients after OAT were entered into a prospective database according to a defined algorithm in order to analyse the underlying surgical pathology, predictors of survival and important aspects of OAT-related morbidity. Independent predictors of survival, OAT-related morbidity and duration of hospital stay were identified. Results Common indications for OAT were peritonitis, haemorrhage and ACS. Median age was 60 years and > 80 % of patients were ASA III/IV; median follow-up was 23 months. Oncologic surgery was performed in 19 % of cases. 30-day and 1-year mortality was 11 % and 34 %, respectively. Malignancy was a negative predictor (OR: 4.63, 95 % CI: 2.00-10.7) while mild obesity (BMI 25-35) and primary fascial closure, which was achieved in 82 % of patients, improved survival (OR: 0.2, 95 % CI: 0.07-0.55; OR: 0.19, 95 % CI: 0.06-0.57). Enteroatmospheric fistula (EAF) and giant hernia with impossible fascial closure were frequent after OAT (19 and 18 %), and malignancy was an independent risk factor for EAF (OR 3.47, CI [95 %]: 1.41-8.53). Vacuum-assisted wound closure or polyglactin mesh interposition did not affect EAF incidence. Conclusions General surgery patients after OAT differ significantly from trauma patients, and mortality as well as long-term morbidity is high. Outcome is greatly determined by independent patient-related factors after OAT. A tailored surgical approach based on objective evidence is needed to further improve the results after OAT.

Current knowledge on regulation and impairment of motility after intestinal transplantation.

PURPOSE OF REVIEW: Understanding the key mechanisms impacting on intestinal graft motility is paramount for successful intestinal transplantation. In this review, we will discuss causes of graft hypomotility and hypermotility, rooted in changes of the intrinsic nervous system, local inflammatory processes, adaptive immune responses, and more. RECENT FINDINGS: Recently, it has been shown that the gut microbiome closely interacts with the structural integrity and rejection processes in the small intestine. After the ischemia/reperfusion injury is overcome, the absence of rejection is important to maintain graft motor function. The interstitial cells of Cajal, with their pacemaker function, play an important role by regulating propulsive intestinal motility in the initial absence of extrinsic signaling. Local inflammatory and immunological changes in the tunica muscularis of transplanted intestines also result in dysmotility, both after ischemia/reperfusion and during rejection. SUMMARY: Motility of the transplanted intestine is crucial for transplant outcome and depends on multiple factors. Extrinsic denervation and changes in the intrinsic intestinal nervous system, local inflammation in the tunica muscularis, acute and chronic rejection, changes in the microbiome with Toll-like receptor activation, stasis of intestinal contents with bacterial translocation, all multifactorially result in impaired graft motility. These factors must be individually acknowledged and addressed to obtain adequate graft function.

Life on the line - Incidence and management of central venous catheter complications in intestinal failure.

BACKGROUND & AIMS: Loss of venous access is threatening for patients with intestinal failure (IF) under long-term parenteral nutrition (PN). We aimed to identify the incidence of central venous catheter (CVC) complications, compare different devices, and analyze interventional recanalizing procedures to restore the patency of occluded CVCs. METHODS: For this retrospective cohort study, patient data from a prospective IF database spanning 16 years was analyzed at a tertiary referral center. Catheter dwell times (CDTs) were distinguished by Kaplan-Meier survival analysis and subgroup analyses were performed for different CVC types (tunneled/port catheters). Specific complications (occlusion, catheter-related infection (CRI), displacement, and material defect) were analyzed. Explantation rates and CDTs were compared. RESULTS: Overall, 193 CVCs in 77 patients with IF under PN could be enrolled (62.524 "CVC-days"). Broviac type "B" was found to be significantly superior to type "A" regarding occlusion, CRI, and material defects (log-rank test: p = 0.05; p = 0.026; p = 0.005 respectively). Port catheters were displaying the highest incidence of CRI (2.13 events/1000 catheter days). Interventional catheter recanalization was performed 91 times and significantly increased the CDT from a median of 131 days (IQR: 62; 258) to 389 days (IQR: 262; 731) (Mann-Whitney-U-test: p= <0.001) without increasing complications. CONCLUSIONS: Different complication rates and CDT were seen depending on CVC type. Tunneled catheters were significantly superior concerning CRI. Interventional catheter recanalization is a viable alternative to fibrinolytics to restore CVC patency, but long-term patency data is scarce.

Access to a simulator is not enough: the benefits of virtual reality training based on peer-group-derived benchmarks--a randomized controlled trial.

BACKGROUND: Virtual reality (VR) simulators are widely used to familiarize surgical novices with laparoscopy, but VR training methods differ in efficacy. In the present trial, self-controlled basic VR training (SC-training) was tested against training based on peer-group-derived benchmarks (PGD-training). METHODS: First, novice laparoscopic residents were randomized into a SC group (n = 34), and a group using PGD-benchmarks (n = 34) for basic laparoscopic training. After completing basic training, both groups performed 60 VR laparoscopic cholecystectomies for performance analysis. Primary endpoints were simulator metrics; secondary endpoints were program adherence, trainee motivation, and training efficacy. RESULTS: Altogether, 66 residents completed basic training, and 3,837 of 3,960 (96.8 %) cholecystectomies were available for analysis. Course adherence was good, with only two dropouts, both in the SC-group. The PGD-group spent more time and repetitions in basic training until the benchmarks were reached and subsequently showed better performance in the readout cholecystectomies: Median time (gallbladder extraction) showed significant differences of 520 s (IQR 354-738 s) in SC-training versus 390 s (IQR 278-536 s) in the PGD-group (p < 0.001) and 215 s (IQR 175-276 s) in experts, respectively. Path length of the right instrument also showed significant differences, again with the PGD-training group being more efficient. CONCLUSIONS: Basic VR laparoscopic training based on PGD benchmarks with external assessment is superior to SC training, resulting in higher trainee motivation and better performance in simulated laparoscopic cholecystectomies. We recommend such a basic course based on PGD benchmarks before advancing to more elaborate VR training.

Don't fear the (small) bite: A narrative review of the rationale and misconceptions surrounding closure of abdominal wall incisions.

Background: The most common complications related to the closure of abdominal wall incisions are surgical site infections, wound dehiscence and the development of an incisional hernia. Several factors relating to the surgical technique and the materials used have been identified and analysed over the years, as mirrored in the current recommendations of the European Hernia Society, but some misconceptions still remain that hinder wide implementation. Method: A literature search was performed in the PubMed and GoogleScholar databases on 15 July 2021 and additionally on 30 March 2022 to include recent updates. The goal was to describe the scientific background behind the optimal strategies for reducing incisional hernia risk after closure of abdominal wall incisions in a narrative style review. Results: An aponeurosis alone, small bites/small steps continuous suture technique should be used, using a slowly resorbable USP 2/0 or alternatively USP 0 suture loaded in a small ½ circle needle. The fascial edges should be properly visualised and tension should be moderate. Conclusion: Despite the reproducibility, low risk and effectiveness in reducing wound complications following abdominal wall incisions, utilisation of the recommendation of the guidelines of the European Hernia Society remain relatively limited. More work is needed to clear misconceptions and disseminate the established knowledge and technique especially to younger surgeons.

Long-term results of teduglutide treatment for chronic intestinal failure - Insights from a national, multi-centric patient home-care service program.

BACKGROUND & AIMS: Teduglutide is a Glucagon-like peptide-2 (GLP-2) agonist indicated for the treatment of patients with parenteral support (PS) dependent short bowel syndrome (SBS) with chronic intestinal failure (cIF). Its application is accompanied by a structured nation-wide home-care service program in Germany. We investigated care characteristics and outcome parameters in a clinical real-world observational setting. METHODS: Data generated within a therapy-accompanying home-care service program for adult SBS-cIF patients were analyzed retrospectively for patients treated up to 1 year (data cut: April 2020). RESULTS: In total, 52 teduglutide-treated patients were included by 6 German cIF centers. At teduglutide administration start, 49/52 patients were on PS, 3 of them without macronutrients. The majority of patients received individualized parenteral nutrition (PN) (n = 32/46), while 13/46 were on commercial premixed bags. PS application was done by patients themselves (37%), home-care nurses (19%), relatives (8%) or by a combination of those (16%). In patients with PS dependency at baseline and available follow-up data (n = 40-44), teduglutide treatment resulted in significantly reduced PN days, caloric needs, infusion time, and infusion volume after 6 and 12 months. After 1 year, reduction of infusion time was positively correlated with a reduction of PN calories and volume; 30 patients (68%) were responders (PS-volume reduction ≥20%), and 6 patients (14%) were completely weaned off PS. Sleep disturbances per night were significantly reduced after 3 months of treatment and stool characteristics improved in consistency and significantly in frequency, while meal frequency remained stable. CONCLUSIONS: Teduglutide treatment associated reduction in PS volume and calories was accompanied by reduced infusion days, infusion times, sleep disturbances, stable oral intake surrogates, and improved stool characteristics, all of these potential parameters for improving quality of life. Furthermore, analyzed care characteristics reflect SBS-cIF treatment as a complex, resource-intensive and demanding task for both, healthcare system and patients.

Long Term Outcome After Open Abdomen Treatment: Function and Quality of Life.

Background: Open abdomen treatment (OAT) is widely accepted to manage severe abdominal conditions such as peritonitis and abdominal compartment syndrome but can be associated with high morbidity and mortality. The main risks in OAT are (1) entero-atmospheric fistula (EAF), (2) failure of primary fascial closure, and (3) incisional hernias. In this study, we assessed the long-term functional outcome after OAT to understand which factors impacted most on quality of life (QoL)/daily living activities and the natural course after OAT. Materials and Methods: After a retrospective analysis of 165 consecutive OAT patients over a period of 10 years (2002-2012) with over 65 clinical parameters that had been performed at our center (1), we initiated a prospective structured follow-up approach. All survivors were invited for a clinical follow-up. Forty complete datasets including clinical and social follow-up with SF-36 scores were available for full analysis. Results: The patients were dominantly male (75%) with a median age of 52 years. Primary fascial closure (PC) was achieved in 9/40 (23%), while in 77% a planned ventral hernia (PVH) approach was followed. A total of 3/4 of the PVH patients underwent a secondary-stage abdominal wall reconstruction (SSR), but 2/3 of these reconstructed patients developed recurrent hernias. Fifty-five percent of the patients with PC developed an incisional hernia, while 20% of all patients developed significant scarring (Vancouver Scar Score >8). Scar pain was described by 15% of the patients as "moderate" [Visual Analog Scale (VAS) 4-6] and by 10% as "severe" (VAS > 7). While hernia presence, PC or PVH, and scarring showed no impact on QoL, male sex and especially EAF formation significantly reduced QoL. Discussion: Despite many advantages, OAT was associated with relevant mortality and morbidity, especially in the early era before the implementation of a structured concept at our center. Follow-up revealed that hernia incidence after OAT and secondary reconstruction were high and that 25% of patients qualifying for a secondary reconstruction either did not want surgery or were unfit. Sex and EAF formation impacted significantly on QoL, which was lower than in the general population. With regard to hernia incidence, new strategies such as prophylactic mesh implantation upon fascial closure should be discussed analogous to other major abdominal procedures.

Normothermic Machine Perfusion (NMP) of the Liver - Current Status and Future Perspectives.

A shortage of available organs for liver transplantation has led transplant surgeons and researchers to seek for innovative approaches in hepatoprotection and improvement of marginal allografts. The most exciting development in the past decade has been continuous mechanical perfusion of livers with blood or preservation solution to mitigate ischemia-reperfusion injury in contrast to the current standard of static cold storage. Two variations of machine perfusion have emerged in clinical practice. During hypothermic oxygenated perfusion the liver is perfused using a red blood cell-free perfusate at 2-10°C. In contrast, normothermic machine perfusion mimics physiologic liver perfusion using a red blood cell-based solution at 35.5-037.5°C, offering a multitude of potential advantages. Putative effects of normothermic perfusion include abrogation of hyperfibrinolysis after reperfusion and inflammation, glycogen repletion, and regeneration of adenosine triphosphate. Research in normothermic machine perfusion focuses on development of biomarkers predicting allograft quality and susceptibility to ischemia-reperfusion injury. Moreover, normothermic perfusion of marginal allografts allows for application of a variety of therapeutic interventions potentially enhancing organ quality. Both methods need to be subjected to translational investigation and evaluation in clinical trials. A clear advantage is transformation of an emergency procedure at night into a planned daytime surgery. Current clinical trials suggest that normothermic perfusion not only increases the use of hepatic allografts but is also associated with milder ischemia-reperfusion injury, resulting in a reduced risk of early allograft dysfunction and less biliary complications, including ischemic cholangiopathy, compared to static cold storage. The aim of this review is to give a concise overview of normothermic machine perfusion and its current applications, benefits, and possible advances in the future.

Electrical vagus nerve stimulation as a prophylaxis for SIRS and postoperative ileus.

Abdominal surgery results in an activation of immune cells of the bowel wall and a consecutive cytokine and nitric oxide (NO) release leading to an inflammation of the muscularis externa and a bowel paralysis, the so-called postoperative ileus (POI). In addition to the local inflammation, major surgical trauma can also lead to a variable pronounced systemic inflammation up to its maximum variant, the systemic inflammatory response syndrome (SIRS), with hypotension, capillary leak and a breakdown of the intestinal barrier function followed by multi-organ dysfunction (MODS). Until now, neither for SIRS nor for POI, a prophylaxis or an evidence-based treatment exists. Since the pioneering work from Kevin Tracey and his group in the late 90s characterizing the role of the vagus nerve in inflammation and describing the cholinergic anti-inflammatory pathway (CAIP) for the first time, substantial efforts have been made in the research field of neuro-immune interactions. Today, the anti-inflammatory potential of vagus nerve stimulation is moving more and more into focus resulting in new therapeutic approaches. This review focuses on the role of the CAIP in the development of SIRS and POI. Furthermore, new therapeutic options like transcutaneous vagus nerve stimulation are highlighted.

Open Abdomen Treatment in Acute Pancreatitis.

Background: Severe acute pancreatitis (SAP) is a heterogeneous and life-threatening disease. While recent guidelines recommend a stepwise approach starting with non-surgical techniques, emergency laparotomy remains inevitable in certain situations. Open abdomen treatment (OAT) may follow, potentially resulting in additional risks for severe morbidity. Causative factors and clinical impact of OAT in SAP are poorly understood and therefore issue of the present study. Materials and Methods: A retrospective analysis of patients admitted to the Department of General, Visceral, Thoracic and Vascular Surgery at University of Bonn suffering from acute pancreatitis (ICD K.85) between 2005 and 2020 was performed. Medical records were screened for demographic, clinical and outcome parameters. Patients who received primary fascial closure (PFC) were compared to those patients requiring OAT. SAP-specific scores were calculated, and data statistically analyzed (P = 0.05). Results: Among 430 patients included, 54 patients (13%) had to undergo emergency laparotomy for SAP. Patients were dominantly male (72%) with a median age of 51 years. Indications for surgery were infected necrosis (40%), suspected bowel perforation (7%), abdominal compartment syndrome (5%), and acute intra-abdominal hemorrhage (3%). While 22 patients (40%) had PFC within initial surgery, 33 patients (60%) required OAT including a median of 12 subsequent operations (SD: 6, range: 1-24). Compared to patients with PFC, patients in the OAT group had significantly fewer biliary SAP (P = 0.031), higher preoperative leukocyte counts (P = 0.017), higher rates of colon resections (P = 0.048), prolonged ICU stays (P = 0.0001), and higher morbidity according to Clavien-Dindo Classification (P = 0.002). Additionally, BISAP score correlated positively with the number of days spent at ICU and morbidity (P = 0.001 and P = 0.000002). Both groups had equal mortality rates. Discussion: Our data suggest that preoperative factors in surgically treated SAP may indicate the need for OAT. The procedure itself appears safe with equal hospitalization days and mortality rates compared to patients with PFC. However, OAT may significantly increase morbidity through longer ICU stays and more bowel resections. Thus, minimally invasive options should be promoted for an uncomplicated and rapid recovery in this severe disease. Emergency laparotomy will remain ultima ratio in SAP while patient selection seems to be crucial for improved clinical outcomes.

Chronic rejection after intestinal transplantation: A systematic review of experimental models.

Intestinal transplantation (ITX) constitutes a salvage treatment for irreversible intestinal failure and failure of parenteral nutrition. Chronic rejection (CR) remains the key obstacle for long-term intestinal graft survival but the pathomechanisms are incompletely understood. This study systematically reviews experimental models addressing CR after ITX in order to summarize current knowledge on CR pathogenesis and identify promising experimental strategies. A systematic literature search was conducted in line with the PRISMA guidelines, and 68 out of 677 articles qualified for the final analysis. The average methodological quality of the studies was suboptimal with 7 out of 11 points as assessed by a modified Oxford Centre for Evidence-Based Medicine score. Histology of the chronically rejected graft was almost universally integrated as outcome parameter but we found significant heterogeneity in utilized transplant techniques, organ preservation, immunosuppression and time points of CR-assessment. Several studies identified cellular and humoral immunologic mechanisms in chronic intestinal rejection. Yet, neither preventive nor therapeutic strategies against CR have been successfully introduced into human intestinal transplantation highlighting the persistent need for optimized experimental models. In this review, we aim to improve the translational value of forthcoming investigations on CR by discussing the experimental status quo and potential innovative approaches.

Recombinant HLA-G as Tolerogenic Immunomodulant in Experimental Small Bowel Transplantation.

The non-classical MHC I paralogue HLA-G is expressed by cytotrophoblast cells and implicated with fetomaternal tolerance by downregulating the maternal adaptive and innate immune response against the fetus. HLA-G expression correlates with favorable graft outcome in humans and recently promising immunosuppressive effects of therapeutic HLA-G in experimental transplantation (skin allograft acceptance) were shown. Consequently, we examined this novel therapeutic approach in solid organ transplantation. In this study, therapeutic recombinant HLA-G5 was evaluated for the first time in a solid organ model of acute rejection (ACR) after orthotopic intestinal transplantation (ITX). Allogenic ITX was performed in rats (Brown Norway to Lewis) with and without HLA-G treatment. It was found that HLA-G treatment significantly reduced histologically proven ACR at both an early and late postoperative timepoint (POD 4/7), concomitant to a functionally preserved graft contractility at POD 7. Interestingly, graft infiltration by myeloperoxidase+ cells was significantly reduced at POD7 by HLA-G treatment. Moreover, HLA-G treatment showed an effect on the allogenic T-cell immune response as assessed by flow cytometry: The influx of recipient-derived CD8+ T-cells into the graft mesenteric lymphnodes at POD7 was significantly reduced while CD4+ populations were not affected. As a potential mechanism of action, an induction of T-reg populations in the mesenteric lymphnodes was postulated, but flow cytometric analysis of classical CD4+/CD25+/FoxP3+Treg-cells showed no significant alteration by HLA-G treatment. The novel therapeutic approach using recombinant HLA-G5 reported herein demonstrates a significant immunosuppressive effect in this model of allogenic experimental intestinal transplantation. This effect may be mediated via inhibition of recipient-derived CD8+ T-cell populations either directly or by induction of non-classical Treg populations.

Trainee satisfaction in surgery residency programs: modern management tools ensure trainee motivation and success.

OBJECTIVE: To assess trainee satisfaction in their surgery residency with a validated instrument and identify the contributing factors. BACKGROUND: Currently, surgery is deemed unattractive by medical students and ignored by many candidates planning to enter an academic career. New insights on the rational for such lack of interest are needed. Job satisfaction is a central concept in organizational and behavioral research that is well understood by large companies such as Google, IBM, and Toyota. Similar assessment can likewise be used to improve trainee satisfaction in surgery residency. METHODS: A survey among 2039 surgery residents was conducted in three European countries analyzing satisfaction at work using the Global Job Satisfaction Instrument (validated in Emergency Room physicians). Crucial factors covering different aspects of surgery residency where identified using the GJS instrument combined with multiple logistic regression analysis. RESULTS: With an overall response rate of 23%, we identified trainee dissatisfaction in one third of residents. Factors affecting satisfaction related almost exclusively to training issues, such as assignment of surgery procedures according to skills (OR 4.2), training courses (OR 2.7), availability of a structured training curriculum (OR 2.4), bedside teaching, and availability of morbidity-mortality conferences (OR 2.3). A good working climate among residents (OR 3.7) and the option for part time work (OR 2.1) were also significant factors for trainee satisfaction. Increased working hours had a modest (OR 0.98)-though cumulative- negative effect. The sex of the trainee was not related to trainee satisfaction. CONCLUSION: Validated measurement of job satisfaction as used in the industry appears to be an efficient tool to assess trainee satisfaction in surgery residency and thereby identify the key contributing factors. Improvement of conceptual training structures and working conditions might facilitate recruitment, decrease drop-out, and attract motivated candidates with possibly better quality of care.