Development of a core descriptor set for parastomal hernia repair.

AIM: Parastomal hernia repair is a poorly evidenced area, with uncertainty around the optimum management. There is considerable heterogeneity within the patient cohort, and currently there is no standardization of patient descriptors in the reporting of parastomal hernia repair. The aim of this study was to develop a core descriptor set of key patient characteristics for patients undergoing surgical repair of a parastomal hernia for reporting in all parastomal hernia research. METHOD: A longlist of descriptors was generated from a review of the existing literature. The longlist was discussed with patients with lived experience of parastomal hernia repair. Colorectal, general and hernia surgeons took part in a three-round international modified Delphi process using a nine-point Likert scale to rank the importance of descriptors. Items meeting predetermined thresholds were included in the final set and discussed and ratified at the consensus meeting. RESULTS: Seventy seven respondents completed round one, with 23 (29.8%) completing round three. Eighty six descriptors were rated across the three rounds, with 52 descriptors shortlisted. The consensus meeting ratified a final core descriptor set with 19 descriptors across eight domains: anatomy, contamination, disease, previous treatment, risk factors, symptoms, pathway and other hernia. CONCLUSION: The core descriptor set reflects characteristics that are important to surgeons when reporting on parastomal hernia repair. The use of this agreed core descriptor set may aid the reporting of future studies.

Impact of Trainee Participation on Inguinal Hernia Repair Outcome: A Study Based on the Swedish Hernia Register.

OBJECTIVE: The aim of this study was to investigate whether differences in postoperative outcome exist between open inguinal hernia repairs performed by surgical trainees and those performed by specialist surgeons. SUMMARY OF BACKGROUND DATA: Inguinal hernia repair is the prototype educational surgical procedure. The impact of trainee participation on postoperative outcome is still controversial and despite earlier studies no reliable hernia-specific data exist. METHODS: The study cohort was based on the Swedish Hernia Register and consisted of 61,161 cases of male patients aged 18 years and older with open anterior mesh repair of a primary inguinal hernia between January 1, 2002, and December 31, 2014. The study cohort was selected to represent the typical trainee procedure in Sweden. Primary outcome measures were reoperation due to hernia recurrence and postoperative 30-day complications. RESULTS: Procedures with longer operating times were at a higher risk for reoperation when performed by supervised trainees [57 to 72 minutes: hazard ratio (HR) 1.55, 99% confidence interval (99% CI) 1.05-2.27] or unsupervised trainees (57 to 72 minutes: HR 1.60, 99% CI 1.18-2.17; >72 minutes: HR 1.72, 99% CI 1.25-2.37). The same was true for specialist and trainee-assisted specialists with operating times <43 minutes (HR 1.63, 99% CI 1.25-2.13; HR 1.58, 99% CI 1.09-2.28). Postoperative 30-day complications were generally associated with longer operating times and occurred at all levels of experience. CONCLUSION: Trainee participation in open inguinal repair in combination with longer operating time is a risk factor associated with higher reoperation rates. This calls for a more structured supervision of trainees in an assumedly basic procedure.

Mesh fixation in endoscopic inguinal hernia repair: evaluation of methodology based on a systematic review of randomised clinical trials.

BACKGROUND: The issue of mesh fixation in endoscopic inguinal hernia repair is frequently debated and still no conclusive data exist on differences between methods regarding long-term outcome and postoperative complications. The quantity of trials and the simultaneous lack of high-quality evidence raise the question how future trials should be planned. METHODS: PubMed, EMBASE and the Cochrane Library were searched, using the filters "randomised clinical trials" and "humans". Trials that compared one method of mesh fixation with another fixation method or with non-fixation in endoscopic inguinal hernia repair were eligible. To be included, the trial was required to have assessed at least one of the following primary outcome parameters: recurrence; surgical site infection; chronic pain; or quality-of-life. RESULTS: Fourteen trials assessing 2161 patients and 2562 hernia repairs were included. Only two trials were rated as low risk for bias. Eight trials evaluated recurrence or surgical site infection; none of these could show significant differences between methods of fixation. Two of 11 trials assessing chronic pain described significant differences between methods of fixation. One of two trials evaluating quality-of-life showed significant differences between fixation methods in certain functions. CONCLUSION: High-quality evidence for differences between the assessed mesh fixation techniques is still lacking. From a socioeconomic and ethical point of view, it is necessary that future trials will be properly designed. As small- and medium-sized single-centre trials have proven unable to find answers, register studies or multi-centre studies with an evident focus on methodology and study design are needed in order to answer questions about mesh fixation in inguinal hernia repair.

Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells.

BACKGROUND: In Celiac disease (CD), cytoskeletal integrity of intestinal cells is disrupted by gliadin exposure. This study investigates the role of heat shock protein (Hsp)70 during cytoskeletal recovery in CD by assessing its induction and effects on junctional proteins. METHODS: Using an in-vitro model of CD, cytoskeletal injury and recovery was assessed in gliadin-exposed Caco-2 cells by measuring cellular distribution of ezrin, E-cadherin, and Hsp70 by differential centrifugation. Effects of Hsp70 were tested by an in-vitro repair assay, based on the incubation of injured or recovered cytoskeletal cellular fractions in noncytoskeletal supernatants containing low or high levels of Hsp70, or by transient transfection of Caco-2 cells with Hsp70. RESULTS: Cytoskeletal disruption of ezrin and E-cadherin was demonstrated in gliadin-exposed Caco-2 cells by their significant shift from the cytoskeletal pellet into the noncytoskeletal supernatant fraction. Recovery from gliadin exposure was associated with induction and cytoskeletal redistribution of Hsp70. The in-vitro repair assay delineated direct evidence for HSP-mediated repair by stabilization of junctional proteins by Hsp70. Overexpression of Hsp70 resulted in significantly increased cytoskeletal integrity. CONCLUSION: Our results establish an essential role of HSP-mediated cytoskeletal repair in Caco-2 cells during recovery from in-vitro gliadin exposure.

Case report: rare case of mechanical bowel obstruction due to strangulation by gastric stimulator electrodes.

BACKGROUND: Implantation of a gastric stimulator is a feasible surgical therapy for patients with therapy refractory gastroparesis. In addition it seems to be a promising alternative for treating morbid obesity. We present for the first time the surgical emergency of small bowel obstruction due to strangulation by gastric stimulator electrodes. CASE PRESENTATION: A 59-year-old Caucasian female had undergone implantation of a gastric stimulator to cope with the symptoms of a partial gastroparesis. Eight years after the operation, the patient began to present repeatedly to different hospitals because of abdominal pain and nausea. Symptoms and imaging indicated ileus, which could always be treated conservatively. The underlying pathology could not ultimately be determined and the symptoms were eventually considered gastroparesis-related. After two years the patient was finally referred in circulatory shock due to peritonitis with underlying small bowel obstruction. Emergency laparotomy revealed small bowel strangulation by the gastric stimulator electrodes. CONCLUSION: Repeated presentation of a patient with an unfamiliar treatment modality must raise suspicion of unusual complications. Specialist surgeons treating with innovative methods should provide proper information that is accessible to everyone who might have to treat possible complications.

Weight-Related Outcomes After Revisional Bariatric Surgery in Patients with Non-response After Sleeve Gastrectomy-a Systematic Review.

Weight non-response after sleeve gastrectomy is an emerging issue. This systematic review compared revisional procedures for weight-related outcomes. We searched several databases for relevant articles and included adult patients with revisional bariatric procedures after primary sleeve gastrectomy. Twelve trials with 1046 patients were included, covering five revisional procedures. There were no randomised controlled trials, and 10 studies had a critical risk of bias. Significant variations in inclusion criteria, therapy benchmarks, follow-up schemes, and outcome measurements were observed, preventing meaningful comparison of results. Evidence-based treatment strategies for weight non-response after sleeve gastrectomy cannot be deduced from the current literature. Prospective studies with well-defined indications, standardised techniques, and strict adherence to outcome measurements are needed.

Interleukin-1 receptor-mediated inflammation impairs the heat shock response of human mesothelial cells.

Bioincompatibility of peritoneal dialysis fluids (PDF) limits their use in renal replacement therapy. PDF exposure harms mesothelial cells but induces heat shock proteins (HSP), which are essential for repair and cytoprotection. We searched for cellular pathways that impair the heat shock response in mesothelial cells after PDF-exposure. In a dose-response experiment, increasing PDF-exposure times resulted in rapidly increasing mesothelial cell damage but decreasing HSP expression, confirming impaired heat shock response. Using proteomics and bioinformatics, simultaneously activated apoptosis-related and inflammation-related pathways were identified as candidate mechanisms. Testing the role of sterile inflammation, addition of necrotic cell material to mesothelial cells increased, whereas addition of the interleukin-1 receptor (IL-1R) antagonist anakinra to PDF decreased release of inflammatory cytokines. Addition of anakinra during PDF exposure resulted in cytoprotection and increased chaperone expression. Thus, activation of the IL-1R plays a pivotal role in impairment of the heat shock response of mesothelial cells to PDF. Danger signals from injured cells lead to an elevated level of cytokine release associated with sterile inflammation, which reduces expression of HSP and other cytoprotective chaperones and exacerbates PDF damage. Blocking the IL-1R pathway might be useful in limiting damage during peritoneal dialysis.

A survey among physicians in surgery and anesthesiology departments after the first surge of SARS-CoV-2 infections in Germany : Preparing for further challenges ahead.

BACKGROUND: The SARS-CoV­2 pandemic has extensively challenged healthcare systems all over the world. Many elective operations were postponed or cancelled, changing priorities and workflows in surgery departments. AIMS: The primary aim of this cross-sectional study was to assess the workload and psychosocial burden of surgeons and anesthesiologists, working in German hospitals during the first wave of SARS-CoV­2 infections in 2020. METHODS: Quantitative online survey on the workplace situation including psychosocial and work-related stress factors among resident and board-certified surgeons and anesthesiologists. Physicians in German hospitals across all levels of healthcare were contacted via departments, professional associations and social media posts. RESULTS: Among 154 total study participants, 54% of respondents stated a lack of personal protective equipment in their own wards and 56% reported increased staff shortages since the onset of the pandemic. While routine practice was reported as fully resumed in 71% of surgery departments at the time of the survey, work-related dissatisfaction among responding surgeons and anesthesiologists increased from 24% before the pandemic to 36% after the first wave of infections. As a countermeasure, 94% of participants deemed the establishment of action plans to increase pandemic preparedness and strengthening German public health systems a useful measure to respond to current challenges. CONCLUSION: The aftermath of the first wave of SARS-CoV­2 infections in Germany has left the surgical staff strained, despite temporarily decreased workloads. Overall, a critical review of the altered conditions is indispensable to identify and promote effective solutions and prudent action plans required to address imminent challenges.

Cellular stress-response modulators in the acute rat model of peritoneal dialysis.

Cytotoxicity of peritoneal dialysis fluids (PDF) not only results in cellular injury, but also induces heat-shock proteins (HSP), the main effectors of the cellular stress response. This study investigated effects of modulation of mesothelial HSP expression on peritoneal membrane integrity during acute PDF exposure. In the acute in vivo rat model of peritoneal dialysis (PD), either the HSP coinducer indomethacin or the HSP suppressor quercetin was added to standard PDF (CAPD 3, Fresenius, Germany). HSP-72 expression, number of detached mesothelial cells, and peritoneal protein loss were evaluated at the end of a 4-h dwell time. Compared with pure PDF exposure, addition of indomethacin resulted in increased expression of mesothelial HSP-72, reduced mesothelial cell exfoliation, and reduced peritoneal protein loss. Addition of quercetin resulted in decreased expression of HSP-72, increased mesothelial cell exfoliation, and higher peritoneal protein loss. Differences were statistically significant between indomethacin-treated and quercetin-treated rats. Mesothelial HSP expression was related to markers of peritoneal membrane integrity upon in vivo PDF exposure, consistent with HSP-mediated cytoprotection. These data clearly demonstrate the potential for clinically feasible pharmacologic interventions with the cellular stress response as a novel therapeutic approach to improve PD outcome.

MicroRNA-146: tiny player in neonatal innate immunity?

BACKGROUND: Concise regulation of the Toll signaling pathway is mandatory in neonatal innate immunity. The microRNA-146 family (miR-146a/b) was recently reported to be a regulator of Toll-like receptor 4 (TLR4) through a negative feedback loop mechanism. Acting as a potent regulator, miRNA helps to protect the organism from developing overwhelming proinflammatory immune responses leading to septic shock or chronic inflammatory diseases. OBJECTIVE: We investigated for the first time whether miRNA-146a/b plays a regulatory role in human monocytes derived from infant cord or adult blood, and whether differences in miRNA-146 expression exist. METHODS: Expression profiles of miR-146a/b and TLR4 were studied by real-time PCR upon stimulation with lipopolysaccharide. RESULTS: Both members of the miRNA-146 family showed a time-dependent upregulation. For miR-146a, a statistically higher significant increase was found after 24 h of stimulation in monocytes from cord blood compared to those derived from adults. In contrast, no differences were found for miR-146b and TLR4, respectively. CONCLUSION: We conclude that differences between the negative regulatory role for miR-146a obviously exist in neonatal and adult TLR4 signaling, and suggest that more intense research in the involvement of miRNA in immune regulation will facilitate the understanding of the development and function of the innate immune system of neonates.

HSP-mediated cytoprotection of mesothelial cells in experimental acute peritoneal dialysis.

BACKGROUND: Low biocompatibility of peritoneal dialysis solution (PDS) injures mesothelial cells but also induces heat shock proteins (HSP), the main effectors of the cellular stress response. This study investigated whether overexpression of HSP upon pharmacologic induction results in cytoprotection of mesothelial cells in experimental PD. METHODS: Stress response of mesothelial cells upon exposure to PDS was pharmacologically manipulated using glutamine as a co-inducer. In vitro, HSP-mediated cytoprotection was assessed by simultaneous measurements of HSP expression using Western blot analysis and viability testing using release of lactic dehydrogenase in cultured human mesothelial cells. In vivo, detachment of mesothelial cells from their peritoneal monolayer was assessed following exposure to PDS with and without the addition of glutamine in the acute rat model of PD. RESULTS: In vitro, mesothelial cell viability following exposure to PDS was significantly improved upon pharmacologic co-induction of HSP expression by glutamine (226% +/- 29% vs 190% +/- 19%, p = 0.001). In vivo, mesothelial cell detachment during exposure to PDS was reduced upon pharmacologic induction of HSP expression by glutamine (93 +/- 39 vs 38 +/- 38 cells, p = 0.044), resulting in reduced peritoneal protein loss (75 +/- 7 vs 65 +/- 4 mg, p = 0.045). CONCLUSION: Our results represent the first study of pharmacologic manipulation of HSP expression for cytoprotection of mesothelial cells following acute in vitro and in vivo exposure to PDS. PDS with added glutamine might represent a promising therapeutic approach against low biocompatibility of PDS but needs validation in a chronic PD model.

Stress responses and conditioning effects in mesothelial cells exposed to peritoneal dialysis fluid.

Renal replacement therapy by peritoneal dialysis is frequently complicated by technical failure. Peritoneal dialysis fluids (PDF) cause injury to the peritoneal mesothelial cell layer due to their cytotoxicity. As only isolated elements of the involved cellular processes have been studied before, we aimed at a global assessment of the mesothelial stress response to PDF. Following single or repeated exposure to PDF or control medium, proteomics and bioinformatics techniques were combined to study effects in mesothelial cells (MeT-5A). Protein expression was assessed by two-dimensional gel electrophoresis, and significantly altered spots were identified by MALDI-TOF MS and MS2 techniques. The lists of experimentally derived candidate proteins were expanded by a next neighbor approach and analyzed for significantly enriched biological processes. To address the problem of an unknown portion of false positive spots in 2DGE, only proteins showing significant p-values on both levels were further interpreted. Single PDF exposure resulted in reduction of biological processes in favor of reparative responses, including protein metabolism, modification and folding, with chaperones as a major subgroup. The observed biological processes triggered by this acute PDF exposure mainly contained functionally interwoven multitasking proteins contributing as well to cytoskeletal reorganization and defense mechanisms. Repeated PDF exposure resulted in attenuated protein regulation, reflecting inhibition of stress responses by high levels of preinduced chaperones. The identified proteins were less attributable to acute cellular injury but rather to specialized functions with a reduced number of involved multitasking proteins. This finding agrees well with the concept of conditioning effects and cytoprotection. In conclusion, this study describes the reprogrammed proteome of mesothelial cells during recovery from PDF exposure and adaption to repetitive stress. A broad stress response with a number of highly overlapping processes and multitasking proteins shifts toward a more specific response of only few less overlapping processes.