The inflammatory response in transgastric surgery: gastric content leak leads to localized inflammatory response and higher adhesive disease

Risk of gastric spillage during transgastric surgery is a potential complication of NOTES procedures. The aim of this study was to determine risk outcomes from gastric spillage in a rat survival model by measuring local and systemic inflammatory markers, adhesive disease, and morbidity. We performed a minilaparotomy with needle aspiration of 2 ml of gastric contents mixed with 2 ml of sterile saline (study group, SG) or 4 ml of sterile saline (control group, CG) injected into the peritoneal cavity of 60 male rats. Inflammatory markers (TNFα, IL-6, and IL-10) were analyzed at 1, 3, 6, and 24 h postoperatively by obtaining plasma levels and peritoneal washings. At necropsy, the peritoneal cavity was examined grossly for adhesions. Adhesions were seen more frequently in the SG versus the CG (100% vs. 33.3%, p < 0.014). There was a significant difference in the peritoneal TNFα levels in the SG compared with the CG, which peaked 1 h after surgery (p < 0.02). Both peritoneal IL-6 and IL-10 levels were higher in the SG versus the CG, which peaked 3 h after surgery (p < 0.005 and p < 0.001, respectively). All peritoneal inflammatory markers returned to undetectable levels at 24 h for both groups. Plasma cytokines were undetectable at all time intervals. The inflammatory response was found to be a localized and not systemic event, with plasma cytokine levels remaining normal while peritoneal washings revealed a brisk, short-lived localized inflammatory response. There was a significantly higher rate of adhesive disease in the SG compared with the CG; this, however did not translate into a difference in apparent clinical outcome. We conclude that gastric leakage in this NOTES rodent model induces a localized inflammatory response, followed by mild to moderate adhesive disease. This may be important in human NOTES

Natural orifice surgery: initial clinical experience

Natural orifice translumenal endoscopic surgery (NOTES) has moved quickly from preclinical investigation to clinical implementation. However, several major technical problems limit clinical NOTES including safe access, retraction and dissection of the gallbladder, and clipping of key structures. This study aimed to identify challenges and develop solutions for NOTES during the initial clinical experience. Under an Institutional Review Board (IRB)-approved protocol, patients consented to a natural orifice operation for removal of either the gallbladder or the appendix via either the vagina or the stomach using a single umbilical trocar for safety and assistance. Nine transvaginal cholecystectomies, one transgastric appendectomy, and one transvaginal appendectomy have been completed to date. All but one patient were discharged on postoperative day 1 as per protocol. No complications occurred. The limited initial evidence from this study demonstrates that NOTES is feasible and safe. The addition of an umbilical trocar is a bridge allowing safe performance of NOTES procedures until better instruments become available. The addition of a flexible long grasper through the vagina and a flexible operating platform through the stomach has enabled the performance of NOTES in a safe and easily reproducible manner. The use of a uterine manipulator has facilitated visualization of the cul de sac in women with a uterus to allow for safe transvaginal access

The DOE E3SM Coupled Model Version 1: Overview and Evaluation at Standard Resolution

This work documents the first version of the U.S. Department of Energy (DOE) new Energy Exascale Earth System Model (E3SMv1). We focus on the standard resolution of the fully coupled physical model designed to address DOE mission-relevant water cycle questions. Its components include atmosphere and land (110-km grid spacing), ocean and sea ice (60 km in the midlatitudes and 30 km at the equator and poles), and river transport (55 km) models. This base configuration will also serve as a foundation for additional configurations exploring higher horizontal resolution as well as augmented capabilities in the form of biogeochemistry and cryosphere configurations. The performance of E3SMv1 is evaluated by means of a standard set of Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima simulations consisting of a long preindustrial control, historical simulations (ensembles of fully coupled and prescribed SSTs) as well as idealized CO2 forcing simulations. The model performs well overall with biases typical of other CMIP-class models, although the simulated Atlantic Meridional Overturning Circulation is weaker than many CMIP-class models. While the E3SMv1 historical ensemble captures the bulk of the observed warming between preindustrial (1850) and present day, the trajectory of the warming diverges from observations in the second half of the twentieth century with a period of delayed warming followed by an excessive warming trend. Using a two-layer energy balance model, we attribute this divergence to the model’s strong aerosol-related effective radiative forcing (ERFari+aci = -1.65 W/m2) and high equilibrium climate sensitivity (ECS = 5.3 K).Plain Language SummaryThe U.S. Department of Energy funded the development of a new state-of-the-art Earth system model for research and applications relevant to its mission. The Energy Exascale Earth System Model version 1 (E3SMv1) consists of five interacting components for the global atmosphere, land surface, ocean, sea ice, and rivers. Three of these components (ocean, sea ice, and river) are new and have not been coupled into an Earth system model previously. The atmosphere and land surface components were created by extending existing components part of the Community Earth System Model, Version 1. E3SMv1’s capabilities are demonstrated by performing a set of standardized simulation experiments described by the Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima protocol at standard horizontal spatial resolution of approximately 1° latitude and longitude. The model reproduces global and regional climate features well compared to observations. Simulated warming between 1850 and 2015 matches observations, but the model is too cold by about 0.5 °C between 1960 and 1990 and later warms at a rate greater than observed. A thermodynamic analysis of the model’s response to greenhouse gas and aerosol radiative affects may explain the reasons for the discrepancy.Key PointsThis work documents E3SMv1, the first version of the U.S. DOE Energy Exascale Earth System ModelThe performance of E3SMv1 is documented with a set of standard CMIP6 DECK and historical simulations comprising nearly 3,000 yearsE3SMv1 has a high equilibrium climate sensitivity (5.3 K) and strong aerosol-related effective radiative forcing (-1.65 W/m2)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151288/1/jame20860_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151288/2/jame20860.pd

Disclosing and responding to cancer "fears" during oncology interviews

Video-excerpts from routine oncology interviews are examined to reveal how patients demonstrate and doctors respond to "fears" about cancer. Vocally and visually, embodied impacts of dealing with dreaded consequences of cancer are apparent when addressing both good and potentially bad cancer news. Even a "brush" with cancer can promote negative and ongoing impacts provoking unresolved illness dilemmas. We reveal how, in the midst of extending answers and initiating concerns, patients exhibit trepidations when volunteering narrative information about their medical history and experience of symptoms. In response, doctors are shown to acknowledge yet exhibit minimal receptiveness to patients' lifeworld disclosures and demonstrations (e.g., redirecting attention away from patients' concerns by offering "textbook" symptoms and related pursuits of biomedical agendas). Discussion focuses on interactional criteria for identifying "fears", patients' lay orientations to medical visits, and implications for refining educational workshops for oncologists.Oncology interviews Conversation analysis Video USA

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery. Thirty 250-g male Sprague–Dawley rats were divided into a study group (SG, n = 15) and a control group (CG, n =15). SG were given 5 mg/kg pantoprazole for 3 days before procedure and another dose 1 h before. CG received saline at similar time points. A mini-laparotomy with gastrotomy was performed. Aspiration of 2.0 cc gastric contents was removed from the stomach and injected into the peritoneal cavity of both groups. Gastric pH and peritoneal pH levels were obtained. Gastric aspirate was sent for culture. White blood cell counts (WBC) were obtained on postoperative days 1, 7, and 14, and C-reactive protein (CRP) levels were obtained on postoperative day 1. At day 14, a necropsy was performed and aerobic and anaerobic cultures of the peritoneal cavity were obtained. There were no deaths in either group. The average gastric pH in the SG was 5.13 versus 3.26 (p = 0.03) in the CG. The average peritoneal pH was similar in both groups. The WBC in the SG was 4.5 vs. 3.5 (1,000 cells/mm) in the CG. There was no elevation in CRP levels in either group. Bacterial cultures were positive in 3/15 (20%) rats in the CG and in 9/15 (60%) in the SG (p = 0.008). Intra-abdominal abscesses were found in 2/15 (13%) rats in the CG and in 5/15 (33%) in the SG (p = 0.08). Pretreatment with a PPI resulted in a higher rate of peritoneal bacterial contamination and abscess formation. The acidic environment of the stomach appears to be protective against infection when intraperitoneal contamination occurs as a result of gastrotomy