Are Surgeons Going to Be Left Holding the Bag? Incisional Hernia Repair and Intra-Peritoneal Non-Absorbable Mesh Implant Complications.

Ventral incisional hernias are common indications for elective repair and frequently complicated by recurrence. Surgical meshes, which may be synthetic, bio-synthetic, or biological, decrease recurrence and, resultingly, their use has become standard. While most patients are greatly benefited, mesh represents a permanently implanted foreign body. Mesh may be implanted within the intra-peritoneal, preperitoneal, retrorectus, inlay, or onlay anatomic positions. Meshes may be associated with complications that may be early or late and range from minor to severe. Long-term complications with intra-peritoneal synthetic mesh (IPSM) in apposition to the viscera are particularly at risk for adhesions and potential enteric fistula formation. The overall rate of such complications is difficult to appreciate due to poor long-term follow-up data, although it behooves surgeons to understand these risks as they are the ones who implant these devices. All surgeons need to be aware that meshes are commercial devices that are delivered into their operating room without scientific evidence of efficacy or even safety due to the unique regulatory practices that distinguish medical devices from medications. Thus, surgeons must continue to advocate for more stringent oversight and improved scientific evaluation to serve our patients properly and protect the patient-surgeon relationship as the only rationale long-term strategy to avoid ongoing complications.

The unrestricted global effort to complete the COOL trial.

BACKGROUND: Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. METHODS: The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. DISCUSSION: OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of "damage control"; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. TRIAL REGISTRATION: National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).

Efficacy of gamification-based smartphone application for weight loss in overweight and obese adolescents: study protocol for a phase II randomized controlled trial.

BACKGROUND: Overweight and obesity are significant public health concerns that are prevalent in younger age cohorts. Preventive or therapeutic interventions are difficult to implement and maintain over time. On the other hand, the majority of adolescents in the United States have a smartphone, representing a huge potential for innovative digitized interventions, such as weight loss programs delivered via smartphone applications. Although the number of available smartphone applications is increasing, evidence for their effectiveness in weight loss is insufficient. Therefore, the proposed study aims to assess the efficacy of a gamification-based smartphone application for weight loss in overweight and obese adolescents. The trial is designed to be a phase II, single-centre, two-arm, triple-blinded, randomized controlled trial (RCT) with a duration of 6 months. METHOD: The intervention consists of a smartphone application that provides both tracking and gamification elements, while the control arm consists of an identically designed application solely with tracking features of health information. The proposed trial will be conducted in an urban primary care clinic of an academic centre in the United States of America, with expertise in the management of overweight and obese adolescents. Eligible adolescents will be followed for 6 months. Changes in body mass index z score from baseline to 6 months will be the primary outcome. Secondary objectives will explore the effects of the gamification-based application on adherence, as well as anthropometric, metabolic and behavioural changes. A required sample size of 108 participants (54 participants per group) was calculated. DISCUSSION: The benefits of the proposed study include mid-term effects in weight reduction for overweight and obese adolescents. The current proposal will contribute to fill a gap in the literature on the mid-term effects of gamification-based interventions to control weight in adolescents. This trial is a well-designed RCT that is in line with the Consolidated Standards of Reporting Trials statement.

Hyperbaric oxygen therapy reduces COX-2 expression in a dimethylhydrazine-induced rat model of colorectal carcinogenesis.

BACKGROUND: A better understanding of oncogenesis mechanisms should result in more effective approaches to colorectal cancer (CRC) treatment and prevention. Hyperbaric oxygen (HBO2) therapy is indicated as adjuvant treatment for infectious diseases as well as hypoxic and inflammatory lesions. The anti-inflammatory effect of HBO2 could reduce colorectal carcinogenesis. METHODS: 48 Wistar rats were randomly divided into the following groups: * G1 - control; * G2 - HBO2 treatment; * G3 - 1,2-dimethylhydrazine (DMH) injection only; * G4 - DMH injection and HBO2 treatment. These groups were further randomly divided into two subgroups: a. euthanasia at six weeks; and. b. euthanasia at 12 weeks. Animals belonging to G2 and G4 were subjected to 15 HBO2 sessions, performed every 24 hours at 2.0 atm absolute pressure, 90 minutes each. Cancer was induced via intraperitoneal injection of DMH in G3 and G4. The aberrant crypt foci index (ACFi), the cell nuclear antigen index (PCNA) and the cyclooxygenase-2 index (iCOX-2) were determined. RESULTS: After DMH administration, ACFi increased and was higher in subgroups euthanized at six weeks than in those sacrificed at 12 weeks (p < 0.001). HBO2 alone (G2) did not affect ACFi (p > or = 0.05). Larger increases of PCNA were detected in G2 versus G3 (p < 0.05). Comparison between G4 and control group mice revealed no differences in PCNA (p > 0.05). COX-2 was overexpressed in G3 (p < 0.0001) compared to G4. CONCLUSION: COX-2 expression was "induced" by DMH and reverted to a "wild"-type level of expression upon exposure to HBO2.

Effect of hyperbaric oxygen therapy on the intestinal ischemia reperfusion injury.

PURPOSE: Adequate tissue oxygenation is essential for healing. Hyperbaric oxygen therapy (HBOT) has potential clinical applications to treat ischemic pathologies, however the exact nature of any protective effects are unclear at present. We therefore investigated the potential role of HBOT in modulating the ischemia/reperfusion (I/R) injury response in intestinal model of I/R injury. METHODS: Male Wistar rats were subjected to surgery for the induction of intestinal ischemia followed by reperfusion. HBOT was provided before and/or after intestinal ischemia. Cell viability in the intestinal tissue was assessed using the MTT assay and by measuring serum malondealdehyde (MDA). Microvascular density and apoptosis were evaluated by immunohistochemistry. RESULTS: The results indicate that HBOT treatment pre- and post-ischemia reduces lesion size to the intestinal tissue. This treatment increases cell viability and reduces the activation of caspase-3, which is associated with increased number of tissue CD34 cells and enhanced VEGF expression. CONCLUSION: The hyperbaric oxygen therapy can limit tissue damage due to ischemia/reperfusion injury, by inducing reparative signaling pathways.