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For patients with super obesity (BMI 50 kg/mThe MBSAQIP database was queried for primary and revisional BPD/DS (2015-2018). Inclusion criteria were patients ≥ 18 years of age, BMI 50 kg/mThere were 3,378 primary BPD/DS and 487 revisional BPD/DS patients. Primary BPD/DS patients had higher BMI (56.5 [IQR4.4] versus 54.8 [IQR4] kg/mRevisional BPD/DS is associated with higher morbidity than primary BPD/DS in patients with super obesity. These patients should thus be counselled appropriately when choosing a primary or revisional bariatric procedure.

Marginal ulceration (MU) and bleeding are possible complications following laparoscopic Roux-en-Y gastric bypass (RYGB). Our institution utilizes three techniques for performing the gastrojejunal anastomosis (GJA), providing a means to compare postoperative MU and bleeding as it relates to GJA technique. We sought to analyze the incidence of MU and bleeding between the 25-mm end-to-end anastomosis (EEA) stapler, linear stapler (LS), and robotic hand-sewn (RHS) GJA techniques. Electronic health records for all patients who had an upper endoscopy (EGD) after RYGB were queried (2010–2014). Charts were retrospectively reviewed for type of GJA, complications, endoscopic interventions, and smoking and NSAID use. Out of 1112 RYGBs, the GJA was created using an EEA, LS, or RHS approach in 58.6%, 33.6%, and 7.7% of patients, respectively. 17.4% had an EGD (19.9% EEA, 13.9% LS, and 14.0% RHS). Incidence of MU was 7.3% (9.3% EEA, 4.8% LS, and 5.8% RHS). Rates of EGD and MU were significantly higher after EEA vs. LS GJA (p

Jejunojejunal intussusception (JI) is a serious but rare complication that may occur following Roux-en-Y gastric bypass (RYGB) surgery. Causes of JI and best management strategy are not clearly defined. Electronic health records were queried for ICD 9/10 codes for intussusception after RYGB surgery (2009–2019), and charts retrospectively reviewed. Patient demographics, operative technique, presentation, radiology, and JI management were analyzed. Of the 2,327 RYGB patients identified at our institute, 34 (1.5%) were treated for JI. The mean age was 45.0 ± 8.6 years, mean BMI (RYGB surgery) was 43.1 ± 8.2 kg/m2, mean BMI at JI was 28.3 ± 5.8 kg/m2, and 30/34 were female, The mean time between RYGB and JI was 5.5 ± 4.3 years (range 1–17 years). Of the JI patients identified, 9 had operative notes that did not include jejunojejunostomy linear stapler length (JJ-LSL). Of the remaining 25 JI patients, 9 had a 60-mm JJ-LSL and 16 had a 120-mm JJ-LSL. Rate of intussusception was higher in the 120-mm versus 60-mm JJ-LSL group (p

Background Male patients undergoing bariatric surgery have (historically) been considered higher risk than females. The aim of this study was to examine the disparity between genders undergoing laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) procedures and assess gender as an independent risk factor. Methods The MBSAQIP® Data Registry Participant User Files for 2015–2017 was reviewed for patients having primary SG and RYGB. Patients were divided into groups based on gender and procedure. Variables for major complications were grouped together, including but not limited to PE, stroke, and MI. Univariate and propensity matching analyses were performed. Results Of 429,664 cases, 20.58% were male. Univariate analysis demonstrated males were older (46.48 ± 11.96 vs. 43.71 ± 11.89 years, p

PURPOSE Patients undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) are at risk of developing strictures of the gastrojejunal anastomosis (GJA). Several variables can affect this, one of which may be the method of anastomosis. Between 2010 and 2014, our institution utilized three different anastomotic techniques for creating the GJA (25 mm end-to-end circular-stapled (CS), linear-stapled (LS), and robotic hand sewn (HS)). Our objectives were to compare the method of GJA relative to the subsequent development of anastomotic stricture. METHODS We queried our electronic health record for all patients who underwent an upper endoscopy (EGD) after RYGB (2010-2014). Patient charts were retrospectively reviewed for type of GJA, weight loss, complications, interventions, and revisions of the GJA. RESULTS In total, 1112 RYGB were performed at our institute, and 17.4% of patients (194/1112) had an upper endoscopy (EGD). Overall, 3.1% (34/1112) were found to have a stricture of the GJA. Patients undergoing a CS, LS, and HS anastomosis had GJA stricture rates of 4.9%, 0.5%, and 1.2% respectively (CS to LS (p

This article was updated to correct the spelling of Nicholas Dugan’s first name: it is correct as displayed here.

Nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease in the USA. Biopsy has been the standard for determining fibrosis but is invasive, costly, and associated with risk. Previous studies report a calculated "NAFLD fibrosis scores" (cNFS) as a means to overcome the need for biopsy. We compared cNFS versus biopsy-pathological scoring for patients undergoing bariatric surgery.We retrospectively reviewed patients with available preoperative labs and patient information undergoing Roux-en-Y gastric bypass (RYGBP) surgery at a single institution over a 5.5-year period. Biopsy samples were blind scored by a single hepatopathologist and compared with scores calculated using a previously reported cNFS.Of the 225 patients that met the inclusion criteria, the mean body mass index was 44.6 ± 5.4 kg/m(2) and 85 % were female. Using the cNFS, 39.6 % of patients were categorized into low fibrosis, 52 % indeterminate, and 8.4 % high fibrosis groups. Analysis of fibrosis by pathology scoring demonstrated 2 of 89 (2.2 %) and 7 of 110 (3.4 %) had significant fibrosis in the low and intermediate groups, respectively. Conversely, in the high fibrosis group calculated by cNFS, only 6 of 19 (31.6 %) exhibited significant fibrosis by pathology scoring.No definitive model for accurately predicting presence of NAFLD and fibrosis currently exits. Furthermore, under no circumstances should a clinical "NAFLD fibrosis score" replace liver biopsy at this time for RYGBP patients.

Choline dihydrogen phosphate (CDHP) is a low melting point organic salt reported to increase the thermal stability of model proteins. The purpose of the current work was to investigate the effect of CDHP on recombinant human interleukin-2 (rhIL-2) functional and structural integrity, a therapeutic protein used for treating advanced melanoma. Structural integrity and biological activity of rhIL-2 formulated in CDHP was measured below and above thermal midpoint unfolding temperature (Tm) of the protein. Potential biocompatibility was assessed by exposing splenocytes and the B16F10 cell line to CDHP at various concentrations and conditions of pH. Formulation of rhIL-2 in an aqueous 680 mM CDHP pH 7.4 solution preserved rhIL-2 binding activity when the solution was heated to 23.3 °C above Tm. CDHP solutions (≤80 mM), formulated with 0.33% (w/v) NaHCO3 to maintain pH ≥ 7.2, exhibited no cytotoxic activity toward primary splenocytes or B16F10 cells cultures. However, a 10-fold loss in biological activity was observed when rhIL-2 was used in a 30 mM CDHP aqueous solution with NaHCO3 (pH ≥ 7.2) compared to controls without CDHP. Choline DHP increases rhIL-2 thermal stability in the absence of inherent CDHP cytotoxicity. While increased Tm is associated with a diminished rhIL-2 biological activity, the protein retains binding ability.

Recombinant human interleukin-2 (rhIL-2) therapy is approved for treating patients with advanced melanoma yet significant responses are observed in only 10-15% of patients. Interleukin-2 induces Foxp3 expression in activated human CD8 T cells in vitro and expands circulating CD8 Foxp3+ T cells in melanoma patients. Employing IL-2 responsive (B16-F1, B16-BL6, JB/MS, MCA-205) and nonresponsive (JB/RH, B16-F10) subcutaneous tumor mouse models, we evaluated CD8 Foxp3+ T cell distribution and changes in response to rhIL-2 (50,000 U, i.p. or s.q., twice daily for 5 days). In tumor-free mice and subcutaneous tumor-bearing mouse models, CD8 Foxp3+ T cells were a rare but naturally occurring cell subset. Primarily located in skin-draining lymph nodes, CD8 Foxp3+ T cells expressed both activated T cell (CD28(+), CD44(+)) and Treg (CTLA4(+), PD1(lo/var), NKG2A(+/var)) markers. Following treatment with rhIL-2, a dramatic increase in CD8 Foxp3+ T cell prevalence was observed in the circulation and tumor-draining lymph nodes (TD.LNs) of animals bearing IL-2 nonresponsive tumors, while no significant changes were observed in the circulation and TD.LNs of animals bearing IL-2 responsive tumors. These findings suggest expansion of CD8 Foxp3+ T cell population in response to rhIL-2 treatment may serve as an early marker for tumor responsiveness to immunotherapy in an immune competent model. Additionally, these data may provide insight to predict response in patients with melanoma undergoing rhIL-2 treatment.

Laparoscopic ventral hernia repair is commonly performed with mesh prostheses; however, there is no standard for fixation devices used to secure mesh to the abdominal wall. This study is a functional comparison of novel, screw-type absorbable and permanent fixation devices with a traditional titanium fixation device. Fifteen pigs each underwent the laparoscopic placement of two 11 × 14-cm mesh prostheses and were randomized for mesh fixation with either titanium spiral tacks (TS), absorbable screw-type fasteners (SF), or permanent screw-type fasteners (PF) (n = 10 mesh prostheses for each fixation group). Adhesions were assessed laparoscopically at 4 weeks. The fixation devices were also embedded in porcine abdominal rectus muscle for ex vivo mechanical testing along with partial thickness polypropylene suture (PR) as a control group (n = 40 for each group). Maximum pull-off forces were measured. All statistical tests were two-tailed, and a P-value

Bipolar electrosurgical devices are used to generate rapid and efficient hemostasis in a wide range of surgical procedures. Of the factors that influence seal integrity, vessel (artery) diameter has been considered the most important variable. In this study we hypothesized that the relative ratio of the components that form the seal (collagen and elastin) determine the degree of vessel distensibility and play an equally important role in defining seal strength.Porcine carotid, renal, iliac, and femoral arteries were sealed using a bipolar electrosurgical device in vivo. Following removal, arterial diameter was measured and vessels' seals tested for arterial burst pressure (ABPr). Samples were then analyzed histologically and biochemically for collagen and elastin content.Arteries with the highest collagen-elastin ratio (C/E) (renal) consistently demonstrated significantly higher burst pressures than those arteries with lower C/E ratios (iliac and femoral) independent of artery diameter.Using arteries of distinct anatomical origin and physiological function, we demonstrate that total collagen content, and more specifically C/E ratio, in porcine arteries is a more accurate predictor of ABPr than vessel size alone.

These standards1 are recommended for anesthesia professionals throughout the world. They are intended to provide guidance and assistance to anesthesia professionals, their professional societies, hospital and facility administrators, and governments for improving and maintaining the quality and safety of anesthesia care. They were adopted by the World Federation of Societies of Anaesthesiologists on the 13th June 1992, and revisions were ratified on 5th March 2008 and on 19th March 2010. For some anesthesia services, groups, and departments these standards will represent a future goal, while for others they may already have been implemented and be regarded as mandatory. It is recognized that in some settings facing challenges in resources and organization, not even those standards regarded as mandatory are met at present. The provision of anesthesia under such circumstances should be restricted to procedures which are absolutely essential for the urgent or emergency saving of life or limb, and every effort should be made by those responsible for the provision of healthcare in these areas and settings to ensure that the standards are met. Provision of anesthesia care at standards lower than those outlined as mandatory for anesthesia for elective surgical procedures simply cannot be construed as safe acceptable practice. The most important standards relate to individual anesthesia professionals. Monitoring devices play an important part in safe anesthesia as extensions of human senses and clinical skills rather than their replacement. Adopting the standardized language of the World Health Organization, minimum standards that would be expected in all anesthesia care for elective surgical procedures are termed “HIGHLY RECOMMENDED” and these are the functional equivalent of “mandatory” standards. These HIGHLY RECOMMENDED standards, indicated in bold type, are applicable throughout any elective procedure, from patient evaluation until recovery (it is recognized, however, that immediate life-saving measures always take precedence in an emergency). In the judgement of the WFSA, these are the minimum standards for anesthesia for a “necessary” procedure (rather than essential and/or emergency) in settings where resources are extremely limited. This does not imply that these standards on their own are ideal or even acceptable in more adequately resourced settings. These HIGHLY RECOMMENDED (functional equivalent of mandatory) standards and (regarding facilities, equipment, and medications) the parallel prescription for “Level 1” or “basic” infrastructure are relevant to any healthcare environment anywhere in which general or regional anesthetics are administered, but not to a setting where superficial procedures involving local anesthetics only are performed. Additional elements of the anesthesia standards should be implemented as resources, organization, and training permit, yielding this paradigm: See Table 1 for a detailed outline of the integration of the practice standards with the levels of facilities/infrastructure. The goal always in any setting is to practice to the highest possible standards, specifically exceeding those prescribed if that can be accomplished. In spite of some facilities’ limitations, it may be possible to implement elements of the RECOMMENDED standards even in a “basic” setting and, likewise, to implement elements of the Suggested standards even in an “intermediate” setting. The goal is always the best care possible and ongoing improvement by meeting and exceeding the standards for safe practice of anesthesia, starting with all providers meeting the HIGHLY RECOMMENDED standards and striving to meet as many of the RECOMMENDED and Suggested standards as well. Table 1 Guide to Infrastructure, Supplies and Anesthesia Standards at Three Levels of Health Care Facility Infrastructure and Supplies It is anticipated that these standards and the setting/infrastructure specifications will be revised as practice and technology evolve.

Purpose To enhance patient safety through contemporaneous and comprehensive standards for a safe practice of anesthesia that augment, enhance, and support similar standards already published by various countries and that provide a resource for countries that have yet to formulate such standards. Standards development The Safe Anesthesia Working Group of the World Health Organization’s “Safe Surgery Saves Lives” global initiative updated the 1992 International Standards for the Safe Practice of Anaesthesia (Standards) through an iterative process of literature review, consultation, debate, drafting, and refinement. These Standards address, in detail, the organization, support, practices, and infrastructure for anesthesia care. The Standards are grounded in the fundamental principle of safety in anesthesia, i.e., the continuous presence of an appropriately trained, vigilant anesthesia professional. In effect, the use of pulse oximetry during anesthesia is now considered mandatory, with acknowledgement that compromise may be unavoidable in emergencies. At the World Congress of Anaesthesiologists in 2008, drafts were presented for comment, further refinements were made, and the Revised Standards were adopted by the World Federation of Societies of Anaesthesiologists (WFSA). These Revised Standards were posted on the WFSA website for further feedback, and minor revisions followed. The International Standards for a Safe Practice of Anesthesia 2010 were endorsed by the Executive Committee of the WFSA in March 2010. Ongoing periodic revision is planned. Conclusion While they are universally applicable, the 2010 Standards primarily target lesser-resourced areas. They are designed particularly for regions that have yet to formulate or adopt their own standards so as to promote optimum patient outcomes in every anesthetizing location in the world.

Growth/differentiation factor-15(GDF-15) is a divergent TGF-β family member that is expressed following liver injury and carcinogen exposure. GDF-15 expression is highly associated with gastrointestinal cancer stage, size, and metastasis and has been implicated in inhibition of tumor growth and increased tumor invasiveness. The current study sought to determine the effect of GDF-15 ablation on the development of hepatocellular carcinoma (HCC) in vivo. Male mice genetically deleted for the gene encoding GDF-15 (Gdf15 −/− mice) and wild-type controls were exposed to the hepatocarcinogen diethylnitrosamine (DEN). Mice were killed at 6 months of age and their livers dissected and processed for histology. Tumor number and size relative to total liver area examined were determined. At 6 months of age, tumors were identified in 16 of 20 (80%) Gdf15 −/− mice and 16 of 19 wild-type mice (84%). No significant difference in tumor-occupied area was observed in Gdf15 −/− mice versus wild-type mice. In addition, no difference in invasiveness was observed in HCC arising in Gdf15 −/− as compared to wild-type mice. In wild type mice strong immunohistochemical staining for GDF-15 was noted on small HCC foci, whereas a loss of GDF-15 expression was found in a number of advanced HCC tumors. Although highly expressed in association with multiple gastrointestinal cancers, and lost in some advanced HCC, genetic ablation of GDF-15 has no apparent effect on HCC tumor formation rate, growth rate or invasiveness in diethylnitrosamine-induced HCC in vivo.

Several marine macrolide toxins act as potent and specific actin-severing molecules. Recent elucidation of their stereochemistries and modes of interaction with actin has allowed the syntheses of bioactive analogues. Here we used synthetic analogues in a structure-function analysis of ulapualide A, a trisoxazole-based macrolide. Ulapualide A harboured potent actin-depolymerising activity both in cells and in vitro. Its synthetic diastereoisomer was three orders of magnitude less active than the natural toxin and synthetic macrolide fragments lacked actin-capping/ severing activity altogether. Modulation of serum response factor (SRF)-dependent gene expression, as described for other actin-binding toxins, was also examined. Specific changes in response to ulapualide A were not observed, primarily due to its profound effects on cytoskeletal integrity and cell adhesion. Several synthetic fragments of ulapualide A also had no effect on SRF-dependent gene expression. However, inhibition was observed with a molecule corresponding to the extended aliphatic side chain of halichondramide, a structurally related macrolide. These findings indicate that side-chain derivatives of trisoxazole-based macrolides may serve to uncouple gene-regulatory events from actin dynamics.

Background Protein-protein docking, which aims to predict the structure of a protein-protein complex from its unbound components, remains an unresolved challenge in structural bioinformatics. An important step is the ranking of docked poses using a scoring function, for which many methods have been developed. There is a need to explore the differences and commonalities of these methods with each other, as well as with functions developed in the fields of molecular dynamics and homology modelling. Results We present an evaluation of 115 scoring functions on an unbound docking decoy benchmark covering 118 complexes for which a near-native solution can be found, yielding top 10 success rates of up to 58%. Hierarchical clustering is performed, so as to group together functions which identify near-natives in similar subsets of complexes. Three set theoretic approaches are used to identify pairs of scoring functions capable of correctly scoring different complexes. This shows that functions in different clusters capture different aspects of binding and are likely to work together synergistically. Conclusions All functions designed specifically for docking perform well, indicating that functions are transferable between sampling methods. We also identify promising methods from the field of homology modelling. Further, differential success rates by docking difficulty and solution quality suggest a need for flexibility-dependent scoring. Investigating pairs of scoring functions, the set theoretic measures identify known scoring strategies as well as a number of novel approaches, indicating promising augmentations of traditional scoring methods. Such augmentation and parameter combination strategies are discussed in the context of the learning-to-rank paradigm.