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Motivation: The versatile binding properties of antibodies have made them an extremely important class of biotherapeutics. However, therapeutic antibody development is a complex, expensive, and time-consuming task, with the final antibody needing to not only have strong and specific binding but also be minimally impacted by developability issues. The success of transformer-based language models in protein sequence space and the availability of vast amounts of antibody sequences, has led to the development of many antibody-specific language models to help guide antibody design. Antibody diversity primarily arises from V(D)J recombination, mutations within the CDRs, and/or from a few nongermline mutations outside the CDRs. Consequently, a significant portion of the variable domain of all natural antibody sequences remains germline. This affects the pre-training of antibody-specific language models, where this facet of the sequence data introduces a prevailing bias toward germline residues. This poses a challenge, as mutations away from the germline are often vital for generating specific and potent binding to a target, meaning that language models need be able to suggest key mutations away from germline., Results: In this study, we explore the implications of the germline bias, examining its impact on both general-protein and antibody-specific language models. We develop and train a series of new antibody-specific language models optimized for predicting nongermline residues. We then compare our final model, AbLang-2, with current models and show how it suggests a diverse set of valid mutations with high cumulative probability., Availability and Implementation: AbLang-2 is trained on both unpaired and paired data, and is freely available at https://github.com/oxpig/AbLang2.git., (© The Author(s) 2024. Published by Oxford University Press.)

Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Roguski A et al.)

Irreversible electroporation (IRE) is a minimally thermal tissue ablation modality used to treat solid tumors adjacent to critical structures. Widespread clinical adoption of IRE has been limited due to complicated anesthetic management requirements and technical demands associated with placing multiple needle electrodes in anatomically challenging environments. High-frequency irreversible electroporation (H-FIRE) delivered using a novel single-insertion bipolar probe system could potentially overcome these limitations, but ablation volumes have remained small using this approach. While H-FIRE is minimally thermal in mode of action, high voltages or multiple pulse trains can lead to unwanted Joule heating. In this work, we improve the H-FIRE waveform design to increase the safe operating voltage using a single-insertion bipolar probe before electrical arcing occurs. By uniformly increasing interphase ( d 1 ) and interpulse ( d 2 ) delays, we achieved higher maximum operating voltages for all pulse lengths. Additionally, increasing pulse length led to higher operating voltages up to a certain delay length (  ∼ 25 μs), after which shorter pulses enabled higher voltages. We then delivered novel H-FIRE waveforms via an actively cooled single-insertion bipolar probe in swine liver in vivo to determine the upper limits to ablation volume possible using a single-needle H-FIRE device. Ablations up to 4.62 ± 0.12cm x 1.83 ± 0.05cm were generated in 5 minutes without a requirement for cardiac synchronization during treatment. Ablations were minimally thermal, easily visualized with ultrasound, and stimulated an immune response 24 hours post H-FIRE delivery. These data suggest H-FIRE can rapidly produce clinically relevant, minimally thermal ablations with a more user-friendly electrode design.

Background: Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Of these, approximately 25% will have liver metastasis. We performed 394 microwave ablations (MWAs) and analyzed outcomes for survival and ablation failure., Study Design: We conducted a retrospective review of patients who underwent a surgical MWA at a single-center high-volume institution from October 2006 to September 2022 using a prospectively maintained database. The primary outcome was overall survival., Results: A total of 394 operations were performed on 328 patients with 842 tumors undergoing MWA. Median tumor size was 1.5 cm (range 0.4 to 7.0 cm), with the median number of tumors ablated per operation being 1 (range 1 to 11). A laparoscopic approach was used 77.9% of the time. Concomitant procedures were performed 63% of the time, most commonly hepatectomy (22.3%), cholecystectomy (17.5%), and colectomy (6.6%). Clavien-Dindo grade III or IV complication occurred in 12 patients (3.6%), and all of these patients had undergone concomitant procedures. Mortality within 30 days occurred in 4 patients (1.2%). The rate of incomplete ablation was 1.5% per tumor. Local recurrence occurred at a rate of 6.3% per tumor. Black patients were found to have a higher incidence of incomplete ablation and local recurrence. One-year survival probability was 91% (95% CI 87.9 to 94.3), with a mean overall survival of 57.6 months (95% CI 49.9 to 65.4 months)., Conclusions: Surgical MWA offers a low-morbidity approach to treatment of colorectal liver metastasis, with low rate of failure. This large series reviews the outcomes of MWA as definitive treatment for colorectal liver metastasis., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Microwave ablation is becoming increasingly common for the treatment of liver tumors. Despite numerous studies aimed at identifying risk factors for local recurrence after microwave ablation, a consensus on modifiable risk factors for failure remains elusive, partly because of the limited statistical power of these studies. This study investigated the incidence of technical failure after microwave ablation, encompassing both incomplete ablation and local recurrence, and aimed to identify modifiable factors that reduce technical failure., Methods: This retrospective review included patients who underwent surgical microwave ablation at a high-volume institution between October 2006 and March 2023. Univariate analysis, multivariate analysis, and propensity score matching were performed to identify risk factors for technical failure., Results: A total of 1,613 surgical microwave ablations were performed on 3,035 tumors, with 226 instances (14% per procedure, 7.4% per tumor) of technical failure. Incomplete ablation occurred at a rate of 1.7% per tumor, whereas local recurrence was identified in 6.5% of ablations in per-tumor analysis. Body mass index >25 was significant for failure (odds ratio, 1.50; 95% confidence interval, 1.07-2.11; P < .05), suggesting that more difficult targeting may lead to increased technical failure rates. African American race (odds ratio, 1.62; 95% confidence interval, 1.16-2.27; P < .05), pre-microwave ablation transarterial chemoembolization (odds ratio, 1.54; 95% confidence interval, 1.08-2.21; P < .05), and previous ablation (odds ratio, 1.58; 95% confidence interval, 1.09-2.29; P < .05) were found to be statistically significant., Conclusion: On the basis of the largest microwave ablation database available to date, this study identified novel modifiable and nonmodifiable risk factors of microwave ablation failure. These results can lead to decreasing technical failure rates after microwave ablation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The incidence of obesity in African Americans (AAs) is higher than in non-AA in the USA. Previous studies using large national databases report that AA patients have worse outcomes than non-AA patients., Objectives: To assess perioperative outcomes among AA patients after MBS at a center of excellence (COE) that serves a large, diverse patient population., Setting: University Hospital METHODS: A retrospective analysis was performed on patients undergoing MBS between 2010 and 2020 at our two accredited MBSAQIP (Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program) COEs where the AA population makes up over 35% of the population. Preoperative variables were compared using unpaired t-test or chi-squared test where appropriate. Thirty-day outcomes were compared following propensity score matching (exact algorithm) of demographics and comorbidities., Results: Overall, 5742 patients (AA = 2058, 36%) had Roux-en-Y gastric bypass (AA = 1028, 26%) or sleeve gastrectomy (AA = 1030, 27%). AA patients were more often female (90.2% vs. 80.2%, p < 0.001) and had higher rates of hypertension (56.3% vs. 47.8%, p < 0.001), while non-AA patients had higher rates of hyperlipidemia (27.3% vs. 20.7%, p < 0.001) and obstructive sleep apnea (41.2% vs. 37.1%, p = 0.0024). Matched data showed that AA patients had higher rates of pulmonary embolism (PE) (0.3% vs. 0.1%, p = 0.020) and more emergency department visits (7.0% vs. 5.1%, p = 0.012) but no differences in mortality, readmission, reintervention, or reoperation rates., Conclusions: In a diverse area, AA patients who underwent MBS had similar perioperative outcomes compared to non-AA patients except that they experienced higher rates of PE. They also experienced higher rates of emergency department visits but had similar readmission rates., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Evidence from diverse areas of research including chronobiology, metabolomics and magnetic resonance spectroscopy indicate that energy dysregulation is a central feature of bipolar disorder pathophysiology. In this paper, we propose that mania represents a condition of heightened cerebral energy metabolism facilitated by hyperglycolysis and glutaminolysis. When oxidative glucose metabolism becomes impaired in the brain, neurons can utilize glutamate as an alternative substrate to generate energy through oxidative phosphorylation. Glycolysis in astrocytes fuels the formation of denovo glutamate, which can be used as a mitochondrial fuel source in neurons via transamination to alpha-ketoglutarate and subsequent reductive carboxylation to replenish tricarboxylic acid cycle intermediates. Upregulation of glycolysis and glutaminolysis in this manner causes the brain to enter a state of heightened metabolism and excitatory activity which we propose to underlie the subjective experience of mania. Under normal conditions, this mechanism serves an adaptive function to transiently upregulate brain metabolism in response to acute energy demand. However, when recruited in the long term to counteract impaired oxidative metabolism it may become a pathological process. In this article, we develop these ideas in detail, present supporting evidence and propose this as a novel avenue of investigation to understand the biological basis for mania., (© 2024. The Author(s).)

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

Objectives: Despite efforts to mitigate challenges to advance underrepresented groups (URG) groups' representation in medical education, diversity remains underwhelming. In response to this several mentoring programs to increase diversification within medical education have been implemented. However, the impact of these programs on URG representation across disciplines is unknown. The aim of this review is to evaluate the impact of structured mentoring programs on URGs in undergraduate medical education., Design: Systematic review., Methods: A comprehensive search strategy was performed of electronic databases including PubMed, Ovid Medline, and EMBASE between January and September 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Both qualitative and quantitative outcomes including characteristics of the mentoring structure explored within each study were collected, and differences in study outcomes analyzed., Results: In total 17 studies were included for analysis. Mentoring within URGs resulted in an increase in research opportunities, exam performance, medical specialty applications, and residency matching. Structured feedback yielded positive experiences by both mentors and mentees participating in programs, with both emotional and cultural competence issues explored across studies included for analysis., Conclusions: Mentoring for medical students underrepresented in medicine across mentoring relationships including peer, senior, formal, and informal structures yield positive outcomes within research, academic modules, and career pathways. Future applications of mentoring programs should consider the use of tandem mentoring from both senior and peer mentors to optimize benefits URG students derive from each mentoring relationship., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: There has been widespread international implementation of duration-hour restrictions to prevent surgical resident burnout and promote patient safety and wellbeing of doctors. A variety of Extended-Duration Work Shifts (EDWS) have been implemented, with a variety of studies examining the effect of shift systems on both surgical performance and the stress response unestablished in the literature., Methods: This was a systematic review evaluating the impact of extended working hours on surgical performance, cognitive impairment, and physiological stress responses. The review used PubMed, Ovid Medline, Embase, and Google Scholar search engines between September and October 2021 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Filters including studies carried out after 2002 and published in the English language were applied., Results: In total, 30 studies were included for analysis. General surgery was the most commonly studied rotation, with Neurosurgical, Orthopedic, and ear, nose and throat specialties also included. The majority of studies found no difference or a significant improvement in post-EDWS on simulated performance. EDWS appeared to have the greatest impact on physiological stress markers in junior surgical trainees., Conclusions: Experience appears to confer a protective element in the postcall period, with preservation of skill demonstrated. More experienced clinicians yielded lower levels of physiological markers of stress, although variability in hierarchical workload should be considered. Heterogeneity of findings across physiological, cognitive, and psychomotor assessments highlights the need for robust research on the optimum shift pattern prevents worker burnout and promotes patient safety. Future research to evaluate correlation between stress, on-call workload, and performance in the postcall period is warranted., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study introduces a new method of targeting acidosis (low pH) within the tumor microenvironment (TME) through the use of cathodic electrochemical reactions (CER). Low pH is oncogenic by supporting immunosuppression. Electrochemical reactions create local pH effects when a current passes through an electrolytic substrate such as biological tissue. Electrolysis has been used with electroporation (destabilization of the lipid bilayer via an applied electric potential) to increase cell death areas. However, the regulated increase of pH through only the cathode electrode has been ignored as a possible method to alleviate TME acidosis, which could provide substantial immunotherapeutic benefits. Here, we show through ex vivo modeling that CERs can intentionally elevate pH to an anti-tumor level and that increased alkalinity promotes activation of naïve macrophages. This study shows the potential of CERs to improve acidity within the TME and that it has the potential to be paired with existing electric field-based cancer therapies or as a stand-alone therapy., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date., Aims: To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder., Method: Euthymic individuals with bipolar disorder were recruited to a 6-8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198., Results: Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6-8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication)., Conclusions: The recruitment and retention of euthymic individuals with bipolar disorder to a 6-8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

Introduction: Acetaminophen (APAP) toxicity remains a significant cause of adult and pediatric liver failure in North America and Europe. Previous research has evaluated the impaired mitochondrial function associated with APAP toxicity. The primary aim of this study was to evaluate the effects of APAP toxicity on platelet mitochondrial function using platelet oxygen consumption in a murine model in vivo. Our secondary objectives were to determine the effect of 4-MP on platelet mitochondrial function and hepatic toxicity in the setting of APAP overdose, and to correlate platelet mitochondrial function with other markers of APAP toxicity., Methods: Male C57Bl/6 mice were randomized to receive APAP (300 or 500 mg/kg) or vehicle followed 90 minutes later by either 4-MP (50 mg/kg) or vehicle via intraperitoneal injection. Mice were euthanized 0, 12, or 24 hours later and platelets isolated from cardiac blood and counted. Platelet oxygen consumption (POC) was determined using a closed-system respirometer. Liver injury was assessed by measuring alanine transferase (ALT) and histological evaluation., Results: Injection of 500 mg/kg APAP led to increased POC versus pair-matched control (vehicle) (p < 0.001). Administration of 4-MP did not affect POC in control or 300 mg/kg APAP mice. In mice receiving 500 mg/kg APAP and 4-MP, POC decreased significantly compared to mice receiving 500 mg/kg APAP alone (p < 0.01). Serum and histological analysis confirmed APAP-induced hepatic damage in mice receiving 500 mg/kg APAP and these effects blunted by treatment with 4-MP., Conclusions: Platelet oxygen consumption as a measure of mitochondrial function may be useful as a biomarker of hepatic APAP toxicity in the setting of moderate to severe overdose. Treatment with 4-MP decreases hepatic necrosis and may mitigate the harmful effects of APAP on platelet mitochondrial function detected via POC., (© 2023. American College of Medical Toxicology.)

Antibodies with similar amino acid sequences, especially across their complementarity-determining regions, often share properties. Finding that an antibody of interest has a similar sequence to naturally expressed antibodies in healthy or diseased repertoires is a powerful approach for the prediction of antibody properties, such as immunogenicity or antigen specificity. However, as the number of available antibody sequences is now in the billions and continuing to grow, repertoire mining for similar sequences has become increasingly computationally expensive. Existing approaches are limited by either being low-throughput, non-exhaustive, not antibody specific, or only searching against entire chain sequences. Therefore, there is a need for a specialized tool, optimized for a rapid and exhaustive search of any antibody region against all known antibodies, to better utilize the full breadth of available repertoire sequences. We introduce Known Antibody Search (KA-Search), a tool that allows for the rapid search of billions of antibody variable domains by amino acid sequence identity across either the variable domain, the complementarity-determining regions, or a user defined antibody region. We show KA-Search in operation on the [Formula: see text]2.4 billion antibody sequences available in the OAS database. KA-Search can be used to find the most similar sequences from OAS within 30 minutes and a representative subset of 10 million sequences in less than 9 seconds. We give examples of how KA-Search can be used to obtain new insights about an antibody of interest. KA-Search is freely available at https://github.com/oxpig/kasearch ., (© 2023. The Author(s).)

Background: A significant number of patients with advanced pancreatic cancer are unable to undergo resection due to vascular involvement. Irreversible electroporation (IRE) has shown promise in improving survival. This study sought to assess a novel IRE application whereby IRE was performed pre-resection to alter tissue plasticity and assist tumor removal from underlying vasculature when surgical excision was otherwise precluded., Methods: After multidisciplinary evaluation appropriate patients were consented for IRE therapy. All IRE cases were tracked prospectively using an institutional review board-approved database that was retrospectively queried for patients undergoing IRE-assisted resection (IRE-AR) for pancreatic adenocarcinoma located in the head/uncinate process. Patients who underwent other IRE therapy or had disease location elsewhere were excluded., Results: 5 patients met the study inclusion criteria with a mean tumor size of 3.2 cm (range 2.4-4.1 cm). Using IRE-AR median recurrence free survival was 10.6 months, with 21.6 month overall survival. The average comprehensive complication index score was 23.23. One patient had grade 3 [or higher] complications and there were no 90 day mortalities., Discussion: Employing a high-starting voltage for ablation along resection margins allows for resection when margins are anticipated to be positive. Patients with locally advanced pancreatic adenocarcinoma who underwent IRE-AR had promising outcomes., Conclusion: This study reports IRE-AR as a novel approach for resecting locally advanced pancreatic adenocarcinoma. A prospective trial of IRE-AR for inoperable pancreatic adenocarcinoma will provide additional data for the long-term application of this approach.

Background: Preoperative warm-up regimens are increasingly utilised in the surgical field, however no consensus on benefits of priming across surgical experience has been realised. The aim of this study was to evaluate the impact of simulation preoperative priming on operative performance across levels of resident experience., Methods: A single-blinded randomised control trial was carried out in a regional surgical training centre. Volunteers were randomised to undergo simulated surgical warm-up procedure prior to their first case as primary operator or proceed directly to surgery., Results: Performances of 147 operative procedures were collected over an 18 month period, experience ranging from PGY2-PGY 7. Senior participants consistently outperformed junior residents in unprimed operative cases (p = 0.005). In primed operative performances no significant difference in aggregate performance scores was found (p = 0.07)., Conclusion: Priming confers a greater advantage to junior residents with particular regard to generic surgical skills. Senior residents demonstrate improved self-efficacy scores measured following priming., Competing Interests: Declaration of competing interest This is a conflict of interest statement pertaining to the submission of the manuscript “Preoperative priming results in improved operative performance with less experienced surgeons”. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Surgical revision of biliary enteric anastomoses (BEA) can be a challenging undertaking and a robotic platform may provide advantages that address many of the technical obstacles. We present our technical approach and outcomes for patients undergoing robotic revision of BEA for benign strictures. A retrospective review was performed for robot-assisted benign BEA revision at our institution. Operative details, perioperative metrics, and outcomes are reported. Four patients underwent anastomotic revision following previously failed non-operative management. There were no intraoperative complications, mean length of stay was 4-days, and all patients experienced resolution of presenting clinical signs and symptoms. No patients required reoperation and there was no mortality. Postoperative outcomes were consistent with findings reported for other interventional modalities. Based on our experience we conclude robotic intervention in this context is safe and improves the technical feasibility of this complex procedure.

Objective: The aim of this study was to evaluate the impact of a surgical warm-up using a virtual reality simulator on operative performance., Design: This was a single-blinded cross-over randomized control trial in a single tertiary Orthopedic training center., Participants: Orthopedic trainees were recruited, and each morning participants rostered to theatre were randomized to either undergo a simulated surgical procedure on a virtual reality simulation system prior to their first case as primary operator (priming arm), or to perform their usual preparatory routine for surgery (control arm). Consultant orthopedic trainers were recruited within the orthopedic unit to carry out subjective surgical performance assessments using a validated global rating scale tool on the first case the participant performed on the list as primary operator., Results: Over 3 study periods a total of 151 data points were collected, with 49 matched data points across priming status and procedural level of difficulty. Subjective assessment tools consistently demonstrated improved operative performance by participants following surgical priming (p = 0.001)., Conclusion: This study highlights that introduction of preoperative priming to improve operative preparation, and optimizes operative performance. This has not only implications for improved resident training, but also signals towards beneficial downstream effects on patient outcomes, and theatre list planning., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Obesity rates in Hispanics and African Americans (AAs) are higher than in Caucasians in the USA, yet the rate of metabolic and bariatric surgery (MBS) for weight loss remains lower for both Hispanics and AAs., Methods: Patient demographics and outcomes of adult AA and Hispanic patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedures were analyzed using the MBSAQIP dataset [2015-2018] using unmatched and propensity-matched data., Results: In total, 173,157 patients were included, of whom 98,185 were AA [56.7%] [21,163-RYGB; 77,022-SG] and 74,972 were Hispanic [43.3%] [20,282-RYGB; 54,690-SG]). Preoperatively, the AA cohort was older, had more females, and higher BMIs with higher rates of all tracked obesity-related medical conditions except for diabetes, venous stasis, and prior foregut surgery. Intra- and postoperatively, AAs were more likely to experience major complications including unplanned ICU admission, 30-day readmission/reintervention, and mortality. After propensity matching, the differences in ED visits, treatment for dehydration, 30-day readmission, 30-day intervention, and pulmonary embolism remained for both SG and RYGB cohorts. Progressive renal insufficiency and ventilator use lost statistical significance in both cohorts. Conversely, 30-day reoperation, postoperative ventilator requirement, unplanned intubation, unplanned ICU admission, and mortality lost significance in the RYGB cohort, but not SG patients., Conclusion: Outcomes for AA patients were worse than for Hispanic patients, even after propensity matching. After matching, differences in major complications and mortality lost significance for RYGB, but not SG. These data suggest that outcomes for RYGB may be driven by the presence and severity of pre-existing patient-related factors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Donated platelets are critical components of hemostasis management. Extending platelet storage beyond the recommended guidelines (5 days, 22 °C) is of clinical significance. Platelet coagulation function can be prolonged with resveratrol (Res) or cytochrome c (Cyt c) at 4 °C. We hypothesized that storage under these conditions is associated with maintained aggregation function, decreased reactive oxygen species (ROS) production, increased mitochondrial respiratory function, and preserved morphology. Donated platelets were stored at 22 °C or 4 °C supplemented with 50 μM Res or 100 μM Cyt c and assayed on days 0 (baseline), 5, 7 and 10 for platelet aggregation, morphology, intracellular ROS, and mitochondrial function. Declining platelet function and increased intracellular ROS were maintained by Res and Cyt c. Platelet respiratory control ratio declined during storage using complex I + II (CI + CII) or CIV substrates. No temperature-dependent differences (4 °C versus 22 °C) in respiratory function were observed. Altered platelet morphology was observed after 7 days at 22 °C, effects that were blunted at 4 °C independent of exposure to Res or Cyt c. Storage of platelets at 4 °C with Res and Cyt c modulates ROS generation and platelet structural integrity.

Fatty acid binding protein-4 ( FABP4 ) is not normally expressed in the liver but is induced in alcohol-dependent liver disease (ALD)). This study sought to identify mechanisms whereby ethanol (EtOH) metabolism alters triglyceride accumulation and FABP4 production. Human hepatoma cells which were stably transfected to express alcohol dehydrogenase (ADH) or cytochrome P4502E1 (CYP2E1) were exposed to EtOH in the absence/presence of inhibitors of ADH (4-methylpyrazole) or CYP2E1 (chlormethiazole). Cells were analyzed for free fatty acid (FFA) content and FABP4 mRNA, then culture medium assayed for FABP4 levels. Cell lysates were analyzed for AMP-activated protein kinase-α (AMPKα), Acetyl-CoA carboxylase (ACC), sterol regulatory element binding protein-1c (SREBP-1c), and Lipin-1β activity and localization in the absence/presence of EtOH and pharmacological inhibitors. CYP2E1-EtOH metabolism led to increased FABP4 mRNA/protein expression and FFA accumulation. Analysis of signaling pathway activity revealed decreased AMPKα activation and increased nuclear-SREBP-1c localization following CYP2E1-EtOH metabolism. The role of AMPKα-SREBP-1c in regulating CYP2E1-EtOH-dependent FFA accumulation and increased FABP4 was confirmed using pharmacological inhibitors and over-expression of AMPKα. Inhibition of ACC or Lipin-1β failed to prevent FFA accumulation or changes in FABP4 mRNA expression or protein secretion. These data suggest that CYP2E1-EtOH metabolism inhibits AMPKα phosphorylation to stimulate FFA accumulation and FABP4 protein secretion via an SREBP-1c dependent mechanism.

Objective: The aim of this study was to evaluate the cumulative impact of supervision on technical skills and surrogate stress markers in surgical trainees., Design: This was a quasi-experimental crossover study to evaluate the impact of attending supervision on orthopedic trainee stress response during a simulated surgical procedure. Enrolled residents performed a proximal femoral nail module with the Precision OS system twice; once independently, and once under direct attending supervision, whilst wearing a heart rate monitor. Mean and maximum heart rates were recorded. Simulated performance was assessed using validated simulator-based metrics. Student's t-test was used to evaluate the impact of supervision on trainee heart rate, and performance ranking., Setting: Tertiary trauma center in a Regional Orthopedic Unit PARTICIPANTS: Orthopedic interns and residents within our institution were invited to participate, with 20 participants included for analysis., Results: Both supervised and unsupervised mean heart rate was significantly higher (p = 0.001) than baseline recorded heart rates. Supervised mean and maximum HR were significantly higher than unsupervised HR during module completion (p = 0.015; p = 0.001). Calories burned demonstrated correlation to surrogate stress markers, significantly higher in supervised sessions (p = 0.004). Performance metrics demonstrated superior performance in senior-level participants, with a decrement in performance during supervision, failing to reach significance., Conclusion: The development of accretion of technical and non-technical skills required in surgical training pathways may derive benefit from the use of simulation-based training in surgical residents with both supervised and unsupervised sessions., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The interaction between activated hepatic stellate cells (aHSCs) and macrophages is central to liver fibrosis development. The cargo contained within aHSC exosomes (aHSC-EXOs) and how aHSC-EXOs affect macrophage function is poorly understood., Methods: RNA from aHSC-EXOs was separated into small (<200-basepairs) and large (≥200-basepairs) RNA species, transfected into macrophages, and macrophage IL-6 and TNFα mRNA expression and protein secretion measured. Next generation sequencing was performed on EXOs from rat quiescent and aHSCs and human aHSCs. aHSCs were transfected with siRNA against ectodysplasin-A (EDA), EXOs collected, and their effect on macrophage function analyzed. Human cirrhotic liver was analyzed for EDA mRNA expression and compared to non-tumor liver (NTL)., Results: Transfection with large RNA from aHSC-EXOs stimulated macrophage IL-6 and TNFα mRNA expression and protein secretion. EDA mRNA was highly expressed in aHSCs and transfection of aHSCs with EDA-siRNA decreased aHSC-EXO EDA mRNA and blunted the effect of aHSC-EXOs on macrophage function (IL-6/TNFα expression and macrophage migration). Human cirrhotic liver exhibited high EDA mRNA compared to NTL., Conclusions: HSC activation leads to altered EXO mRNA/miRNA profiles with aHSC-EXOs mRNAs exerting a dominant role in altering macrophage function. Ectodysplasin-A mRNA is an important component in aHSC-EXOs in regulating macrophage function., Competing Interests: Declaration of competing interest The authors have no disclosures to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to identify if experience in arthroscopy confers ambidexterity to the operator and the role of baseline characteristics in arthroscopic simulator performance., Methods: A prospective comparative study was carried out across four regional Orthopaedic training centres. Participants were divided into novice, intermediate or experienced groups based on arthroscopic experience. Baseline demographics including age, sex, handedness, and gaming history were also collected. Following familiarisation with the procedure, participants were asked to complete a simulated task requiring bimanual control consisting of visualisation with camera control and manipulation of highlighted objects using a grasping instrument. One attempt using camera control and grasping accuracy per hand was performed by each participant, with scores for each hand collected for analysis. Performance scores for camera alignment, camera path length, grasper path length and grasping efficiency were collected. Time taken to completion was also noted for each attempt., Results: Fifty-six participants were recruited to the study. A significant difference in grasping efficiency between groups in the dominant hand was demonstrated (p = 0.013). Novices demonstrated laterality with superior performance in grasping efficiency in the dominant hand (p = 0.001). No significant difference was noted between dominant and non-dominant hand performance in the experienced group., Conclusion: Arthroscopic simulation-based training is a valuable learning tool for orthopaedic training. This study demonstrated that experienced orthopaedic surgeons have a greater degree of ambidexterity than intermediate or novice groups, hypothesised by authors to be conferred through conventional orthopaedic training. Dedicated bimanual control tasks to reduce laterality in trainees should be incorporated in simulated surgical curricula., Level of Evidence: III., (© 2022. The Author(s).)

Background: Preoperative warm-up in preparation for surgery is a technique used in recognition of similarities between surgeons and performance based professionals. The aim of this review was to evaluate the use of simulation-based preoperative warm-up on surgical performance in the operating room and its impact on both clinical and patient outcomes., Materials and Methods: A systematic review of the literature was carried out in accordance with PRISMA guidelines between August-September 2021. In total 15 studies were retrieved., Results: Seven studies across general surgery, urology, and vascular surgery used a procedure specific warm-up, with significant improvement in operative performance, rate of errors, radiological and patient-based outcomes. Variables including level of experience and specialty appeared to have no impact on the merits of preoperative warm-up demonstrated., Conclusions: While heterogeneity in the benefit of generic warm-up procedures was noted, procedure specific warm-up methods consistently resulted in significantly better operative outcomes., Competing Interests: Conflict of interest This is a letter pertaining to the submission of the manuscript “Use of procedure specific preoperative warm-up during surgical priming improves operative outcomes: a systematic review”. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property., (Copyright © 2022. Published by Elsevier Inc.)

In this paper, we propose that lithium may exert its therapeutic effect in bipolar disorder by acting on insulin signaling pathways. Specifically, we assess the importance of the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) insulin signaling pathway and we assess how the action of lithium on both glycogen synthase kinase-3 (GSK3) and the phosphatidylinositol cycle may lead to mood stabilization mediated by PI3K/Akt insulin signaling. We also highlight evidence that several other actions of lithium (including effects on Akt, Protein kinase C (PKC), and sodium myo-inositol transporters) are putative mediators of insulin signaling. This novel mode of action of lithium is consistent with an emerging consensus that energy dysregulation represents a core deficit in bipolar disorder. It may also provide context for the significant co-morbidity between bipolar disorder, type 2 diabetes, and other forms of metabolic illness characterized by impaired glucose metabolism. It is suggested that developments in assessing neuronal insulin signaling using extracellular vesicles would allow for this hypothesis to be tested in bipolar disorder patients., (© 2022. The Author(s).)

Motivation: General protein language models have been shown to summarize the semantics of protein sequences into representations that are useful for state-of-the-art predictive methods. However, for antibody specific problems, such as restoring residues lost due to sequencing errors, a model trained solely on antibodies may be more powerful. Antibodies are one of the few protein types where the volume of sequence data needed for such language models is available, e.g. in the Observed Antibody Space (OAS) database., Results: Here, we introduce AbLang, a language model trained on the antibody sequences in the OAS database. We demonstrate the power of AbLang by using it to restore missing residues in antibody sequence data, a key issue with B-cell receptor repertoire sequencing, e.g. over 40% of OAS sequences are missing the first 15 amino acids. AbLang restores the missing residues of antibody sequences better than using IMGT germlines or the general protein language model ESM-1b. Further, AbLang does not require knowledge of the germline of the antibody and is seven times faster than ESM-1b., Availability and Implementation: AbLang is a python package available at https://github.com/oxpig/AbLang., Supplementary Information: Supplementary data are available at Bioinformatics Advances online., (© The Author(s) 2022. Published by Oxford University Press.)

Objectives: This study investigated how the association between metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) diagnosis varies between non-Hispanic African American and white patients. Methods: A retrospective cohort study was performed using electronic medical records from an integrated health care system (2010-2018). Adults with records for all MetS measurements (body mass index, lipids, blood pressure, and blood glucose) in 2011, who did not have a NAFLD diagnosis before their last MetS measurement, were included. Results: The study cohort consisted of 139,336 patients (age 56.1 ± 15.2 years, 57.9% female, 79.4% non-Hispanic white). The rate of NAFLD diagnosis was higher in MetS patients compared with non-MetS patients [adjusted hazards ratio (AHR) = 1.99, 95% CI = 1.91-2.09] with a significant interaction by race (AHR = 2.05, 95% CI = 1.95-2.15 in non-Hispanic whites vs. AHR = 1.76, 95% CI = 1.58-1.96 non-Hispanic African Americans, P  = 0.017). Secondary analyses revealed that the relative NAFLD diagnosis rate was higher in non-Hispanic whites with MetS compared with non-Hispanic African Americans with MetS among females and patients 18-39 years of age and 40-59 years, but not among males and those ≥60 years of age. Conclusions: Non-Hispanic white patients with MetS, particularly females and those <60 years of age, may be at increased risk of NAFLD compared with non-Hispanic African American MetS patients and may benefit from extra attention regarding NAFLD screening.

Background: Hepatic steatosis is an early pathology of alcohol-associated liver disease (ALD). Fatty acid-binding protein-4 (FABP4, a FABP not normally produced in the liver) is secreted by hepatocytes in ALD and stimulates hepatoma proliferation and migration. This study sought to investigate the mechanism[s] by which hepatic ethanol metabolism regulates FABP4 and steatosis., Methods: Human hepatoma cells (HepG2/HuH7) and cells stably transfected to express cytochrome P450 2E1 (CYP2E1), were exposed to ethanol in the absence or presence of chlormethiazole (a CYP2E1-inhibitor; CMZ) and/or EX-527 (a sirtuin-1 [SIRT1] inhibitor). The culture medium was analyzed for ethanol metabolism and FABP4 protein abundance. Cells were analyzed for FABP4 mRNA expression, SIRT1 protein abundance, and neutral lipid accumulation. In parallel, cells were analyzed for forkhead box O1 [FOXO1], β-catenin, peroxisome proliferator-activated receptor-α [PPARα], and lipin-1α protein abundance in the absence or presence of ethanol and pharmacological inhibitors of the respective target proteins., Results: CYP2E1-dependent ethanol metabolism inhibited the amount of SIRT1 protein detected, concomitant with increased FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation, effects abolished by CMZ. Analysis of pathways associated with lipid oxidation revealed increased FOXO1 nuclear localization and decreased β-catenin, PPARα, and lipin-1α protein levels in CYP2E1-expressing cells in the presence of ethanol. Pharmacological inhibition of SIRT1 mimicked the effects of ethanol, while inhibition of FOXO1 abrogated the effect of ethanol on FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation in CYP2E1-expressing cells. Pharmacological inhibition of β-catenin, PPARα, or lipin-1α failed to alter the effects of ethanol on FABP4 or neutral lipid accumulation., Conclusion: CYP2E1-dependent ethanol metabolism inhibits SIRT1-FOXO1 signaling, which leads to increased FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation. These data suggest that FABP4 released from steatotic hepatocytes could play a role in promoting tumor cell expansion in the setting of ALD and represents a potential target for therapeutic intervention., (© 2022 by the Research Society on Alcoholism.)

Introduction: For patients with super obesity (BMI > 50 kg/m 2 ), biliopancreatic diversion/duodenal switch (BPD/DS) can be an effective bariatric operation. Technical challenges and patient safety concerns, however, have limited its use as a primary procedure. This study sought to assess the safety of primary versus revisional BPD/DS., Materials and Methods: The MBSAQIP database was queried for primary and revisional BPD/DS (2015-2018). Inclusion criteria were patients ≥ 18 years of age, BMI > 50 kg/m 2 , and with no concurrent procedures. Preoperative variables were compared using a chi-square test or Wilcoxon two-sample tests. Multivariate logistic or robust linear regression models were used to compare outcomes., Results: There 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/m 2 , p < 0.0001) and had more diabetes mellitus type II (29.1% versus 17.2%, p < 0.0001). Intraoperatively, revisional BPD/DS had longer operative time (165 [IQR47] min versus 139 [IQR100] min, p < 0.0001). After adjusting for preoperative characteristics, there was no difference in 30-day readmission or ED visits (primary 12.9% versus revisional 14.6%), reoperation or reintervention (primary 5.7% versus revisional 7.8%), or mortality (primary 0.4% versus revisional 0.6%). In contrast, the revisional BPD/DS patients had higher odds of major morbidity (primary 3.4% versus revisional 5.3%, OR 1.9, CI 1.1-3.2, p = 0.019)., Conclusions: Revisional 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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The impact of suture type on tensile strength, re-rupture rates and infection risk in Achilles tendon rupture repair is not been well established. The aim of this review is to evaluate existing literature on the associated risk of postoperative infection with absorbable and non-absorbable suture materials in Achilles tendon rupture repair., Methods: A systematic review of search databases PubMed; Google Scholar; and OVID Medline was made to identify studies related to complications associated with Achilles tendon rupture repair. PRISMA guidelines were utilised for this review. Meta-analysis was used to compare rupture rates and infections following rupture repair., Results: 12 studies with a total of 460 patients, 230 in both nonabsorbable and absorbable suture groups were included for analysis. Risk of wound complications was significantly higher in patients with non-absorbable sutures (p < 0.001)., Conclusion: Nonabsorbable braided sutures is associated with the highest risk of postoperative wound complications following Achilles tendon rupture repair., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Roux-en-Y gastric bypass (RYGB) is an established surgical treatment for obesity. Variations in limb length during RYGB procedures have been investigated for optimizing weight loss while minimizing nutritional deficiencies. The role of the total alimentary limb length (TALL; Roux limb plus common channel [CC]), however, is poorly defined., Objective: Compare TALL in RYGB procedures for weight loss outcomes and malnutrition., Setting: Systematic review., Methods: Ovid Medline and PubMed databases were searched for entries between 1993 and 2020. Search terms included "gastric bypass" and "TALL." Two independent reviewers screened the results., Results: A total of 21 studies measured TALL in RYGB. Of these, 4 of 6 reported a relationship between TALL and weight loss. Additionally, 11 studies reported that when TALL was ≤400 cm and CC <200 cm, 3.4% to 63.6% of patients required limb lengthening for protein malnutrition., Conclusions: The majority of studies on RYGB do not report TALL length. There is some evidence that weight loss is affected by shortening TALL, while a TALL ≤400 cm with CC<200 should be avoided due to severe protein malnutrition. More studies on the effect of TALL are needed., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Marginal ulceration (MU) is a common long-term complication following Roux-en-Y gastric bypass (RYGB). The causes of MU after RYGB are multifactorial and include surgical technique of constructing the gastrojejunal anastomosis (GJA). The purpose of this study is to evaluate the relationship between gastric pouch size in RYGB and MU using CT volumetrics., Material and Methods: Patients were retrospectively identified who underwent esophagogastroduodenoscopy (EGD) following RYGB at a tertiary care teaching hospital. Measurement of gastric pouch size was performed using 3-D CT software. Standard statistical methods were used, a univariate comparison was performed between MU and non-MU patients followed by a propensity-matched comparison to control for factors known to affect MU, and a propensity-matched subgroup analysis was also performed., Results: In total, 122 patients met criteria, 57 of which had MU on EGD and 65 who did not. The MU group had more smokers and patients with PPI use than the non-MU group, and the mean time from operation to CT scan was 26.6 months (range: 0-108 months). The MU group had a larger gastric pouch size than the non-MU group (34.1 ± 11.8 versus 20.1 ± 6.8 cm 3 ). When analyzed for matched patient cohorts, this difference remained for the MU group that included smokers and PPI use. When stratified for pouch size, for each 5 cm 3 increase in pouch size, patients had 2.4 times odds increase of MU formation., Conclusions: CT volumetric analysis demonstrated that a larger gastric pouch size was associated with MU following RYGB., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To determine whether the L3-L4 disc angle may be a surrogate marker for global lumbar alignment in thoracolumbar fusion surgery and to explore the relationship between radiographic and patient-reported outcomes after thoracolumbar fusion surgery., Methods: Retrospective chart review was conducted on patients who had undergone a lumbar fusion involving levels from T9 to pelvis. EuroQol-Five Dimension (EQ-5D-3L) scores and adverse events including adjacent-segment disease and degeneration, pseudoarthrosis, proximal junctional kyphosis, stenosis, and reoperation were collected. Pre- and postoperative spinopelvic parameters were measured on weight-bearing radiographs, with the L3-L4 disc angle of novel interest. Univariate logistic and linear regression were performed to assess the associations of radiographic parameters with adverse event incidence and improvement in EQ-5D-3L, respectively., Results: In total, 182 patients met inclusion criteria. Univariable analysis revealed that increased magnitude of L3-L4 disc angle, anterior pelvic tilt, and pelvic incidence measures are associated with increased likelihood of developing postoperative adverse events. Conversely, increased lumbar lordosis demonstrated a decreased incidence of developing a postoperative adverse event. Linear regression showed that radiographic parameters did not significantly correlate with postoperative EQ-5D-3L scores, although scores were significantly improved postfusion in all dimensions except Self-Care (P = 0.51)., Conclusions: L3-L4 disc angle magnitude may serve as a surrogate marker of global lumbar alignment. The degree of spinopelvic alignment did not correlate to improvement in EQ-5D-3L score in the present study, suggesting that quality of life metric change may not be a sensitive or specific marker of postfusion alignment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Irreversible electroporation (IRE) is a non-thermal tumor ablation technology employed to treat solid tumors not amenable to resection or thermal ablation. The IRE systems currently in clinical use deliver electrical pulses via multiple monopolar electrodes. This approach can present significant technical challenges due to the requirement for accurate placement of multiple electrodes and maintenance of parallel electrode alignment during pulse delivery. In this study, we sought to evaluate a novel IRE electrode configuration consisting of a single bipolar electrode with deployable tines. Using commercial finite element software predicted ablation outcomes, thermal damage, ablation sphericity, and energy delivery were calculated for existing monopolar and bipolar electrodes, and bipolar electrodes with either 4 or 8 deployable tines. The bipolar electrodes with tines generated larger predicted ablations compared to existing monopolar (>100%) and bipolar (>10%) arrangements, and the ablation shape using bipolar electrodes with tines were more spherical than those modeled for bipolar electrodes. Thermal damage modeled for bipolar electrodes and bipolar electrodes with tines was less than that of monopolar electrodes (using identical pulse parameters), and bipolar electrodes with tines delivered less energy than monopolar or bipolar electrodes. These studies using a single point of device insertion suggest the potential for developing alternative IRE delivery techniques, and may simplify clinical use and increase the predicted ablation shape/volume., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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 < 0.05), p = NS among CS vs. HS, and LS vs. HS). The rate of GJA revision was 1.5%, 0.5%, and 0.1% (p = NS). In patients who had an EGD, excess BMI loss was 57.4%, 64.6%, and 59.2% (p = NS). In patients symptomatic from strictures, excess BMI loss was 69.4%, 83%, and 63.5% respectively (p = NS)., Conclusion: The anastomotic technique for creating of the GJA may impact the formation of strictures. Based on our experience, gastrojejunostomies created with a 2-mm EEA-stapling technique are at higher risk of strictures., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hepatic stellate cell (HSC) differentiation/activation is central to liver fibrosis and is innately linked to the immune response to liver injury. Exosomes (EXOs) are important means of communication between cell populations. This study sought to characterize EXO release from HSCs and the effect of HSC-EXOs on macrophage cytokine release/function., Methods: Liver from a rat fibrosis model was analyzed for EXO expression and localization. Quiescent and culture-activated rat and mouse HSCs and activated human HSCs were analyzed for microRNA expression. Mouse, rat, and human HSCs were culture-activated and EXOs purified from culture medium prior to addition to macrophages, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) mRNA and protein measured. The effect of activated HSC-EXOs on macrophage migration was assayed., Results: Activation of rat HSCs led to increased EXO production in vivo, an effect mirrored by in vitro rat HSC culture-activation. Culture activation of mouse and rat HSCs led to altered EXO microRNA profiles, with a similar microRNA profile detected in activated human HSCs. Addition of activated HSC-EXOs to macrophages stimulated IL-6 and TNFα mRNA expression and protein secretion in mouse and human macrophages, but not for rat HSC-EXO-macrophages. Addition of human EXOs to macrophages stimulated migration, effects mirrored by the direct addition of rhIL-6 and rhTNFα., Conclusions: HSC-EXOs associate with macrophages and stimulate cytokine synthesis-release and macrophage migration. Constructing a comprehensive understanding of EXO interactions between liver cell populations in the setting of inflammation/fibrosis increases the potential for developing new diagnostic/therapeutic approaches., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Perioperative corticosteroid administration is associated with reduced postoperative nausea, pain, and enhanced recovery after surgery. However, potential complications including wound and periprosthetic joint infections remain a concern for surgeons after total joint arthroplasty (TJA)., Methods: A systematic review of the search databases PubMed, Google Scholar, and EMBASE was made in January 2021 to identify comparative studies evaluating infection risk after perioperative corticosteroid administration in TJA. PRISMA guidelines were used for this review. Meta-analysis was used to assess infection risk in accordance with joint and corticosteroid dosing regimen used., Results: 201 studies were returned after initial search strategy, with 29 included for review after application of inclusion and exclusion criteria. Studies were categorized as using low- or high-dose corticosteroid with single or repeat dosing regimens. Single low-dose corticosteroid administration was not associated with an increased risk of infection (P = .4; CI = 0.00-0.00). Single high-dose corticosteroid was not associated with an increased infection risk (P = .3; CI = 0.00-0.01) nor did repeat low-dose regimens result in increased risk of infection (P = .8; CI = -0.02-0.02). Studies assessing repeat high-dosing regimens reported no increased infection, with small numbers of participants included. No significant risk difference in infection risk was noted in hip (P = .59; CI = -0.03-0.02) or knee (P = .2; CI = 0.00-0.01) arthroplasty. Heterogeneity in patient profiles included in studies to date was noted., Conclusion: Use of perioperative corticosteroid in TJA does not appear to be associated with increased risk of postoperative infection in patients with limited comorbidities. Further research is warranted to evaluate postoperative complications after TJA in these at-risk patient populations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: 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., Methods: 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., Results: 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/m 2 , mean BMI at JI was 28.3 ± 5.8 kg/m 2 , 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 < 0.05). Acute abdominal pain was present in all JI patients and 32/34 had radiologic findings (CT scan) that corroborated for JI. The majority of JI patients were managed operatively (26/34) with 22/26 using laparoscopy (2/22 were converted to open). Intraoperative findings included intussusception (15/26), and 9/26 had other pathologies (internal hernia (2/26), cholecystitis (4/26), marginal ulcer (3/26)). Operative management of JI was either reduction and enteropexy (7/15), reduction only (5/15), or JJ revision (3/15). Recurrence of JI occurred in 7/23 patients, of who 4/7 were managed operatively., Conclusions: In our experience, JI appears to be a relatively rare complication after RYGB surgery. However, for patients developing JI, the majority had a JJ length ≥ 120 mm, and most patients required operative management which was associated with a higher rate of conversion to open and risk of JI recurrence. Reduction only technique had the highest risk of JI recurrence and therefore is not recommended.

Background and Purpose: Operative microwave ablation (MWA) is a safe modality for treating hepatic tumors. The aim of this study is to present our 10-year, single-center experience of operative MWA for neuroendocrine liver metastases (NLM). Methods: A single-institution retrospective review of patients who underwent operative MWA for NLM was performed (2008-2018). Demographics, primary tumor site, operative approach, combined surgical operations, and carcinoid symptoms were recorded. Clinical outcomes for major complications, readmission, and mortality were analyzed 30 days postoperatively. Postablation imaging was evaluated for incomplete ablation/missed lesions, and surveillance imaging reviewed for local, regional, and metastatic recurrence. Results: Of the 50 patients (166 targeted lesions) who received MWA for NLM, 41 (82%) were treated with a minimally invasive approach, and 22 (44%) underwent MWA concomitant with hepatectomy and/or primary tumor resection. Within the study cohort 70% of patients were treated with curative intent with a 77% (27/35) success rate. Carcinoid symptoms were reported in 40% (20/50) of patients preoperatively, and MWA treatment improved symptoms in 19/20 patients. Incomplete ablation occurred in 1/166 treated lesions. Recurrence-free survival at 1 and 5 years was 86% and 28%, respectively. Overall survival at 1 and 5 years was 94% and 70%, respectively (median follow-up 32 months, range 0-116 months). Conclusion: Operative MWA is a versatile modality, which can be safe and effectively performed alone or combined with hepatectomy for NLM, preferably using a minimally invasive approach, to achieve symptom control and possibly improve survival.

Background: 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., Objectives: 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., Methods: 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., Results: 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<0.05). The bleeding rate was 1.5%, [1.1% EEA, 2.1% LS, and 2.3% RHS (p=NS)]. MU within 90 days of RYGB occurred in 4.1%, 0.8%, and 4.7%, respectively (p<0.05 for EEA vs LS only). NSAID and cigarette use were identified in 29.3%, 38.9%, and 60% and 17.2%, 22.2%, and 20%, respectively, for the EEA, LS, and RHS GJA (p=NS)., Conclusion: The method of GJA has an impact on rate of MU formation. A GJA fashioned with a 25-mm EEA stapler tends to have higher rates of EGD and MU.

The advancements in computing and digital localizer technologies has led to the evolving clinical application of image-guided technology for the surgical management of spinal disorders. Image-guided spinal navigation addresses the limitations of fluoroscopy and improves the accurate placement of fixation screws. Several navigation platforms are currently available, each having its own unique advantages and disadvantages. The most recent spinal navigation system developed utilizes machine vision structured light imaging which creates a precise and detailed three-dimensional image of the exposed surface anatomy and co-registers it to a pre-operatively or intra-operatively acquired image. This system improves upon the intraoperative workflow and efficiency of the navigation process. With the continued advancements in machine vision, there is a potential for clinical applications that extend beyond surgical navigation. These applications include reducing the potential for wrong level spine surgery and providing for real-time tracking of spinal deformity correction. As the adoption and clinical experience with navigation continues to expand and evolve, the technology that enables navigation also continues to evolve., Competing Interests: IK declares that he is a consultant for 7D Surgical., (Copyright © 2021 Kalfas.)

Background: Complex abdominal wall reconstruction using biologic mesh can lead to increased recurrence rates, nonincorporation, and high perioperative costs. We developed a novel decellularization method and applied it to porcine muscle fascia to mirror target-tissue architecture. The aims of this study were to analyze mechanical strength and tissue-graft incorporation., Methods: After serial decellularization, muscle-fascia mesh was created and tested for mechanical strength and DNA content. The muscle-fascia mesh was implanted subcutaneously in rats (n = 4/group) and the cohorts killed 1 to 4 weeks later. Explants were examined histologically or immunohistochemically., Results: Mechanical testing demonstrated equivalent strength compared with a commercially available biological mesh (AlloDerm), with mechanical strength attributable to the fascia component. Grafts were successfully implanted with no observable adverse events. Gross necroscopy revealed excellent subdermal scaffold engraftment. Microscopic evaluation identified progressive collagen deposition within the graft, neoangiogenesis, and presence of CD34 positive cells, in the absence of discernable graft rejection., Conclusion: This study confirms a decellularization process can successfully create a DNA-free composite abdominal wall (muscle-fascia) scaffold that can be implanted intraspecies without rejection. Expanding this approach may allow exploitation of the angiogenic capacities of decellularized muscle, concomitant with the inherent strength of decellularized fascia, to perform preclinical analyses of graft strength in animal models in vivo., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Ruptured, or bleeding, hepatocellular carcinoma (rHCC) is a relatively rare disease presentation associated with high acute mortality rates. This study sought to evaluate outcomes following laparoscopic microwave ablation (MWA) and washout in rHCC., Methods: A retrospective single-center review was performed to identify patients with rHCC (2008-2018). The treatment algorithm consisted of transarterial embolization (TAE) or trans-arterial chemoembolization (TACE) followed by laparoscopic MWA and washout., Results: Fifteen patients with rHCC were identified (n = 5 single lesion, n = 5 multifocal disease, n = 5 extrahepatic metastatic disease). Median tumor size was 83 mm (range 5-228 mm), and 10 of 15 underwent TAE or TACE followed by laparoscopic MWA/washout. One patient required additional treatment for bleeding after MWA with repeat TAE. Thirty-day mortality was 6/15. For those patients discharged (n = 9), additional treatments included chemotherapy (n = 5), TACE (n = 3), and/or partial lobectomy (n = 2). Median follow-up was 18.2 months and median survival was 431 days (range 103-832) (one-year survival n = 7; two-year survival n = 4; three-year survival n = 3). Six patients had post-operative imaging from which one patient demonstrated recurrence., Conclusion: Using laparoscopic MWA with washout may offer advantage in the treatment of ruptured HCC. It not only achieves hemostasis but also could have oncologic benefit by targeting local tumor and decreasing peritoneal carcinomatosis risk., (Copyright © 2020. Published by Elsevier Ltd.)

Fatty liver disease (hepatosteatosis) is a common early pathology in alcohol-dependent and obese patients. Fatty acid binding protein-4 (FABP4) is normally expressed in adipocytes and macrophages and functions as a regulator of intracellular lipid movement/storage. This study sought to investigate hepatic FABP4 expression and function in alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC). Using chronic ethanol fed mouse models and patient samples FABP4 expression was analyzed. Human HCC cells, and HCC cells transfected to express CYP2E1, were exposed to ethanol and analyzed for FABP4 expression, or exposed to rhFABP4 (in the absence/presence of ERK, p38-MAPK or JNK1/2 inhibitors) and cell proliferation and migration measured. Hepatosteatotic-ALD mouse models exhibited increased hepatic FABP4 mRNA and protein levels, with FABP4 expression confirmed in hepatocytes. In HCC cells, CYP2E1-dependent ethanol metabolism induced FABP4 expression in vitro and exogenous rhFABP4 stimulated proliferation and migration, effects abrogated by ERK and JNK1/2 inhibition. Increased FABP4 was also detected in ALD/ALD-HCC patients, but not patients with viral hepatitis/HCC. Collectively these data demonstrate ethanol metabolism induces hepatic FABP4 expression and FABP4 promotes hepatoma cell proliferation/migration. These data suggest liver-derived FABP4 may be an important paracrine-endocrine factor during hepatic foci expansion and/or hepatoma progression in the underlying setting of ALD., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Correlating patient outcomes with length of stay (LoS) is an important consideration in metabolic and bariatric surgery. At present, conflicting data exists regarding patient safety for ambulatory (AMB) metabolic and bariatric surgery., Objective: Outcomes for AMB-metabolic and bariatric surgery patients (LoS <1 d) undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were compared with matched patients with LoS ≥1 day (non-AMB) using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) registry., Setting: MBSAQIP national database., Methods: The MBSAQIP registry was queried for patients undergoing SG or RYGB (2015-2017) and patients grouped as AMB/non-AMB. Exclusion criteria included LoS >4 days, age <18 or >75 years, revision surgery, gastric banding, body mass index <35 kg/m 2 , and day of surgery mortality. Variables were combined into major/minor complications and 30-day mortality. Analysis was performed using univariate and multivariate logistic regression and propensity matching., Results: After exclusions were applied 408,895 patients remained (9973 AMB). Overall, 111,279 patients underwent RYGB (1032 AMB) and 297,616 underwent SG (8941 AMB), with similar demographic characteristics and co-morbidities between groups. For AMB patients, there was no increase in 30-day mortality, reoperation, or readmission, and fewer drains were placed versus matched non-AMB patients. In AMB-SG patients more surgical site infections were reported versus non-AMB-SG, although AMB-SG patients had fewer intensive care unit admissions. For AMB-RYGB, no differences in complications were detected versus non-AMB-RYGB., Conclusion: Based on our analysis of the MBSAQIP database, patients undergoing laparoscopic RYGB or SG procedures can be safely discharged on the day of their procedure without increased incidence of mortality, reoperation, or readmission., (Published by Elsevier Inc.)

Background: The incidence of obesity is disproportionally high in African Americans (AA) in the United States. This study compared outcomes for AA patients undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) with non-AA patients., Methods: The MBSAQIP database was reviewed for RYGB and SG patients (2015-2017). Patients were identified as AA or non-AA and grouped to RYGB or SG. Combined and univariate analyses were performed on unmatched/propensity matched populations to assess outcomes., Results: After applying exclusion criteria, 75,409 AA and 354,305 non-AA patients remained. Univariate analysis identified AA-RYGB and AA-SG patients were heavier and younger than non-AA patients. Overall, AA patients tended to have fewer preoperative comorbidities than non-AA patients with the majority of AA comorbidities related to hypertension and renal disease. Analysis of propensity matched data confirmed AA bariatric surgery patients had increased cardiovascular-related disease incidence compared with non-AA patients. Perioperatively, AA-RYGB patients had longer operative times, increased rates of major complications/ICU admission, and increased incidence of 30-day readmission, re-intervention, and reoperation, concomitant with lower rates of minor complications/superficial surgical site infection (SSI) compared with non-AA patients. For SG, AA patients had longer operative times and higher rates of major complications and 30-day readmission, re-intervention, and mortality, coupled with fewer minor complications, superficial/organ space SSI, and leak., Conclusion: African American patients undergoing bariatric surgery are younger and heavier than non-AA patients and present with different comorbidity profiles. Overall, AAs exhibit worse outcomes following RYGB or SG than non-AA patients, including increased mortality rates in AA-SG patients.

Background: The obesity rate for the Hispanic population is significantly higher than that of white, non-Hispanic people in the United States, yet Hispanic people undergo disproportionately fewer metabolic and bariatric surgery procedures. This study used the Metabolic Bariatric Surgery Accreditation and Quality Improvement Program data registry to examine potential differences in preoperative co-morbidities and postoperative outcomes in Hispanic adults undergoing sleeve gastrectomy or Roux-en-Y gastric bypass procedures in the United States., Objectives: To study the presence of the Hispanic paradox in metabolic and bariatric surgery utilizing the MBSAQIP registry., Setting: Academic Teaching Institution., Methods: Participant User Files from the Metabolic Bariatric Surgery Accreditation and Quality Improvement Program were reviewed for patients undergoing sleeve gastrectomy or Roux-en-Y gastric bypass (2015-2017). Patients were grouped by race (Hispanic versus all other races) and primary procedure performed. Variables for major and minor postoperative complications were combined. A univariate analysis was performed on unmatched and propensity-matched cohorts., Results: After applying exclusions, 53,353 (13.7%) Hispanic patients and 335,299 non-Hispanic patients remained. A univariate analysis demonstrated Hispanic patients had the lowest preoperative co-morbidity profile compared with all other races and decreased rates of major and minor postoperative complications. Using matched-cohort data, when complications were assessed and grouped as major/minor complications, rates of major and minor complications in Hispanic patients were lower in the Roux-en-Y gastric bypass group, despite Hispanic patients having higher leak rates. Similarly, there were no differences between Hispanic/non-Hispanic sleeve gastrectomy patients in overall major/minor complication rates despite Hispanic patients exhibiting higher venous thromboembolism and lower bleeding compared with non-Hispanic patients., Conclusion: Hispanic patients undergo disproportionately low rates of metabolic and bariatric surgery procedures and present with lower incidence of preoperative co-morbidities. Additionally, Hispanic patients have the same or decreased incidence of postoperative complications compared with non-Hispanic patients, thereby corroborating the Hispanic paradox., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)