Image-based assessment of sarcopenic obesity predicts mortality in major trauma.

BACKGROUND: Patients with obesity are also at risk for sarcopenia, which is difficult to recognize in this population. Our study examines whether sarcopenic-obesity (SO) is independently associated with mortality in trauma. METHODS: Using a retrospective database, we performed logistic regression analysis. . Admission CT scans were used to identify SO by calculating the visceral fat to skeletal muscle ratio >3.2. RESULTS: Of 883 patients, the prevalence of SO was 38% (333). Patients with SO were more likely to be male (79% versus 43%, p < 0.001), older (mean 66.5 years versus 46.3 years, p < 0.001), and less likely to have an injury severity score (ISS) ≥ 24 (43% versus 55%, p = 0.0003). Using multivariable logistic regression analysis, SO was independently associated with mortality (OR 2.8; 95% CI 1.6-4.8, p < 0.001). Causal mediation analysis found admission hyperglycemia as a mediator for mortality. CONCLUSIONS: Sarcopenic obesity is an independent predictor of mortality in major trauma.

Loss-of-function SLC30A2 mutants are associated with gut dysbiosis and alterations in intestinal gene expression in preterm infants.

Loss of Paneth cell (PC) function is implicated in intestinal dysbiosis, mucosal inflammation, and numerous intestinal disorders, including necrotizing enterocolitis (NEC). Studies in mouse models show that zinc transporter ZnT2 (SLC30A2) is critical for PC function, playing a role in granule formation, secretion, and antimicrobial activity; however, no studies have investigated whether loss of ZnT2 function is associated with dysbiosis, mucosal inflammation, or intestinal dysfunction in humans. SLC30A2 was sequenced in healthy preterm infants (26-37 wks; n = 75), and structural analysis and functional assays determined the impact of mutations. In human stool samples, 16S rRNA sequencing and RNAseq of bacterial and human transcripts were performed. Three ZnT2 variants were common (>5%) in this population: H346Q, f = 19%; L293R, f = 7%; and a previously identified compound substitution in Exon7, f = 16%). H346Q had no effect on ZnT2 function or beta-diversity. Exon7 impaired zinc transport and was associated with a fractured gut microbiome. Analysis of microbial pathways suggested diverse effects on nutrient metabolism, glycan biosynthesis and metabolism, and drug resistance, which were associated with increased expression of host genes involved in tissue remodeling. L293R caused profound ZnT2 dysfunction and was associated with overt gut dysbiosis. Microbial pathway analysis suggested effects on nucleotide, amino acid and vitamin metabolism, which were associated with the increased expression of host genes involved in inflammation and immune response. In addition, L293R was associated with reduced weight gain in the early postnatal period. This implicates ZnT2 as a novel modulator of mucosal homeostasis in humans and suggests that genetic variants in ZnT2 may affect the risk of mucosal inflammation and intestinal disease.

Nudging patients and surgeons to change ambulatory surgery pain management: Results from an opioid buyback program.

BACKGROUND: Optimal postoperative opioid stewardship combines adequate pain medication to control expected discomfort while avoiding abuse and community diversion of unused prescribed opioids. We hypothesized that an opioid buyback program would motivate patients to return unused opioids, and surgeons will use that data to calibrate prescribing. METHODS: Prospective cohort study of postambulatory surgery pain management at a level II Veterans Affairs rural hospital (2017-2019). Eligible patients were offered $5/unused opioid pill ($50 limit) returned to our Veterans Affairs hospital for proper disposal. After 6 months, buyback data was shared with each surgical specialty. RESULTS: Overall, 934 of 1,880 (49.7%) eligible ambulatory surgery patients were prescribed opioids and invited to participate in the opioid buyback. We had 281 patients (30%) return 3,165 unused opioid pills; this return rate remained constant over the study period. In 2017, 62.4% of patients were prescribed an opioid; after data was shared with providers, prescriptions for opioids were reduced to 50.7% and 38.3% of eligible patients in 2018 and 2019, respectively (P < .0001). The median morphine milligram equivalents prescribed also decreased from 108.8 morphine milligram equivalents in 2017 to 75.0 morphine milligram equivalents in 2018 and sustained at 75.0 morphine milligram equivalents in 2019 (P < .001). Surgical providers, surgeries performed, patient characteristics, and 30-day refill rates were similar throughout the study period. CONCLUSION: A small financial incentive resulted in patients returning unused opioids after ambulatory surgery. Feedback to surgeons regarding opioids returned reduced the proportion of patients prescribed an opioid and the amount of opioid after ambulatory surgery without an increase in refills.

Clinical Empathy for the Surgical Patient: Lessons From W.H. Auden's Prose and Poetry.

Clinical empathy is a professional skill, representing a conscious commitment to showing patients that they are heard, understood, and accepted. Here, we explore ways in which masters of language, such as the mid-20th century poet W. H. Auden, use prose and poetry to teach us the patient's expectations of a truly empathic physician and surgeon.

Incidence, risk factors, and outcomes of early postoperative hyperglycemia in surgical patients: a protocol for a systematic review and meta-analysis.

BACKGROUND: Early postoperative hyperglycemia (POHG) is common and associated with poor postoperative outcomes. Currently, there is no systematic review and meta-analysis that addresses the knowledge gap of the incidence of POHG in surgical patients and that explores the associated risk factors and complications. The objective of this study will be to estimate the pooled incidence, risk factors, and clinical outcomes of early postoperative hyperglycemia in men and women globally. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis of studies reporting the incidence of postoperative hyperglycemia (POHG). We will search PubMed (MEDLINE), Scopus, Web of Science, EMBASE, Cochrane Library, OVID (HEALTH STAR), OVID (MEDLINE), and Joana Briggs Institute EBF Database (from inception onwards). Randomized controlled trials and observational cohort studies reporting the incidence of POHG and conducted in surgical patients will be included. No age, geographical location, study design, or language limits will be applied. The primary outcome will be the incidence of POHG. Secondary outcomes will be risk factors and clinical outcomes of POHG. Two reviewers will independently screen citations, full text articles, and abstract data, extract data, and evaluate the quality and bias of included studies. Discrepancies will be resolved through discussion or consultation with a third researcher. The risk of bias and study methodological quality of included studies will be evaluated by the appropriate Cochrane risk of bias tool for randomized trials and Newcastle-Ottawa Scale for cohort studies. If feasible, we will conduct random effects meta-analysis with a logit transformation of proportions. We will report the probability of postoperative hyperglycemia as a measure of incidence rate, relative risk ratios (RR), and 95% confidence intervals to report the effects of the risk factors and postoperative outcomes. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., age, gender, geographical location, publication year, comorbidities, type of surgical procedure). The Egger test and funnel plots will be used to assess small study effects (publication bias). DISCUSSION: This systematic review and meta-analysis will identify, evaluate, and integrate the evidence on the incidence, risk factors, and outcomes of early POHG in surgical patients. The results of this study can be used to identify populations which may be at particular risk for POHG. Future studies which use this information to better guide post-operative glycemic control in surgical patients could be considered. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020167138.

Macrolets: Outsized Extracellular Vesicles Released from Lipopolysaccharide-Stimulated Macrophages that Trap and Kill Escherichia coli.

Macrophages release a variety of extracellular vesicles (EVs). Here we describe a previously unreported class of EVs that are released from macrophages in response to Escherichia coli endotoxin, lipopolysaccharide (LPS), that we have named "macrolets" since they are extruded as large "droplets" released from macrophages. Morphologically, macrolets are anuclear, bounded by a single lipid membrane and structurally dependent on an actin cytoskeleton. Macrolets are enriched in tetraspanins and separable on this basis from their parent macrophages. Macrolets are distinguished from classic exosomes by their larger size (10-30 µm), discoid shape, and the presence of organelles. Macrolets are rich in both interleukin 6 (IL-6) and interleukin 6 receptor (IL-6R),and are capable of trapping and killing E. coli in association with production of reactive oxygen species. Our observations offer insights into the mechanisms by which macrophage activities may be amplified in sites of infection, inflammation, and healing.

A common genetic variant in zinc transporter ZnT2 (Thr288Ser) is present in women with low milk volume and alters lysosome function and cell energetics.

Suboptimal lactation is a common, yet underappreciated cause for early cessation of breastfeeding. Molecular regulation of mammary gland function is critical to the process lactation; however, physiological factors underlying insufficient milk production are poorly understood. The zinc (Zn) transporter ZnT2 is critical for regulation of mammary gland development and maturation during puberty, lactation, and postlactation gland remodeling. Numerous genetic variants in the gene encoding ZnT2 (SLC30A2) are associated with low milk Zn concentration and result in severe Zn deficiency in exclusively breastfed infants. However, the functional impacts of genetic variation in ZnT2 on key mammary epithelial cell functions have not yet been systematically explored at the cellular level. Here we determined a common mutation in SLC30A2/ZnT2 substituting serine for threonine at amino acid 288 (Thr288Ser) was found in 20% of women producing low milk volume (n = 2/10) but was not identified in women producing normal volume. Exploration of cellular consequences in vitro using phosphomimetics showed the serine substitution promoted preferential phosphorylation of ZnT2, driving localization to the lysosome and increasing lysosome biogenesis and acidification. While the substitution did not initiate lysosome-mediated cell death, cellular ATP levels were significantly reduced. Our findings demonstrate the Thr288Ser mutation in SLC30A2/ZnT2 impairs critical functions of mammary epithelial cells and suggest a role for genetic variation in the regulation of milk production and lactation performance.

Risk factors of perioperative mortality from complicated peptic ulcer disease in Africa: systematic review and meta-analysis.

Introduction: In 2013, peptic ulcer disease (PUD) caused over 300 000 deaths globally. Low-income and middle-income countries are disproportionately affected. However, there is limited information regarding risk factors of perioperative mortality rates in these countries. Objective: To assess perioperative mortality rates from complicated PUD in Africa and associated risk factors. Design: We performed a systematic review and a random-effect meta-analysis of literature describing surgical management of complicated PUD in Africa. We used subgroup analysis and meta-regression analyses to investigate sources of variations in the mortality rates and to assess the risk factors contributing to mortality. Results: From 95 published reports, 10 037 patients underwent surgery for complicated PUD. The majority of the ulcers (78%) were duodenal, followed by gastric (14%). Forty-one per cent of operations were for perforation, 22% for obstruction and 9% for bleeding. The operations consisted of vagotomy (38%), primary repair (34%), resection and reconstruction (12%), and drainage procedures (6%). The overall PUD mortality rate was 6.6% (95% CI 5.4% to 8.1%). It increased to 9.7% (95% CI 7.1 to 13.0) when we limited the analysis to studies published after the year 2000. The correlation was higher between perforated PUD and mortality rates (r=0.41, p<0.0001) than for bleeding PUD and mortality rates (r=0.32, p=0.001). Non-significant differences in mortality rates existed between sub-Saharan Africa (SSA) and North Africa and within SSA. Conclusion: Perioperative mortality rates from complicated PUD in Africa are substantially high and could be increasing over time, and there are possible regional differences.

Exhortation to lose weight prior to complex ventral hernia repair: Nudge or noodge?

BACKGROUND: Exercise and weight loss are recommended for patients with obesity undergoing elective complex ventral hernia repair (cVHR). METHODS: Weight and BMI trajectory data on 230 obese patients undergoing cVHR from 2012 to 2017 were retrospectively analyzed from 12 months prior to first visit with the hernia surgeon to 12 months after surgery. RESULTS: One year prior to initial visit, 76 (33%) patients had lost > 1kg/m2, 98 (43%) had gained> 1kg/m2, and 56 (24%) had no change in body mass index (BMI). Between initial visit and operation, 53 (23%) lost >1kg/m2, 43 (19%) gained, and 134 (58%) had no change. Post-operative hyperglycemia was associated with BMI> 40kg/m2 at time of operation. Twelve months post-operatively, 69 (35%) had lost >1kg/m2, while 52 (26%) had gained, and 108 (47%) had no change. CONCLUSIONS: Exhortations for pre-operative and post-operative weight management are not often successful or sustainable, implying a need for individualized holistic approaches.

The Impact of Minimally Invasive Gastrectomy on Survival in the USA.

BACKGROUND: Minimally invasive surgical approaches for gastric adenocarcinoma are increasing in prevalence. Although recent studies suggest such approaches are associated with improvements in short-term outcomes, long-term outcomes have not been well studied. This study aimed to evaluate the impact of minimally invasive gastrectomy on long-term survival. METHODS: The National Cancer Database (NCDB) was used to identify patients who underwent gastrectomy for adenocarcinoma between 2010 and 2015. Patient characteristics were stratified by open and minimally invasive approaches and compared using chi-square and t tests. Unadjusted survival functions were estimated using Kaplan-Meier methodology. Multivariable modeling of risks factors for survival was analyzed with Cox proportional hazard models. Covariate imbalance was controlled using propensity score matching. RESULTS: The study included 17,449 patients who underwent gastrectomy. Cox proportional hazard modeling demonstrated that minimally invasive surgery improved survival (hazard ratio = 0.86, P < 0.0001). Predictors of worsened survival included community facility type, comorbidities, tumor size, extent of gastrectomy, clinical T and N staging (P < 0.0060 for all). After propensity score matching, minimally invasive surgery had a significantly improved survival at 5 years compared to an open approach, 51.9% versus 47.7% (P < 0.0001). Survival was not significantly different between propensity score-matched patients who received laparoscopic and robotic approaches (P = 0.2611). CONCLUSIONS: Minimally invasive approaches for gastric carcinoma are associated with improved long-term survival. There was no significant difference in survival when comparing laparoscopic to robotic gastrectomy. The mechanisms that drive these improvements deserve further investigation.

Pain and Dysfunction with Sexual Activity after Inguinal Hernia Repair: Systematic Review and Meta-Analysis.

BACKGROUND: The reported incidence rates of sexual dysfunction (SD) and pain with sexual activity (PSA) after inguinal hernia repair in males vary considerably. This meta-analysis explores the rates of SD and PSA after different surgical and anesthesia types to understand patient risk after inguinal hernia repair. STUDY DESIGN: We performed a systematic review and meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to search 3 databases (EMBASE, MEDLINE, and Cochrane Library). We identified retrospective, prospective, and randomized controlled trial studies, published on or before March 1, 2019, reporting on SD and PSA after inguinal hernia repair. We used random-effects models to calculate pooled estimates of incidence rates of SD and PSA after inguinal hernia repair. Subgroup meta-analyses and meta-regression were used to explore sources of variation. RESULTS: A total of 4,884 patients from 12 studies were identified. Study-level median age at the time of repair was 52.3 years old, and study-level median follow-up was 10.5 months. Definitions of SD and PSA focused on completion of intercourse for the former and pain with erection/ejaculation for the latter. The overall incidence of new-onset, postoperative SD was 5.3% (95% CI 3.6% to 7.9%) and of PSA was 9.0% (95% CI 5.8% to 13.6%). Rates of SD associated with minimally invasive surgical (MIS) and open repair were, respectively, 7.8% (95% CI 5.4% to 11.3%) and 3.7% (95% CI 2.0% to 6.8%); rates of PSA were 7.4% (95% CI 4.7% to 11.5%) and 12.5% (95% CI 6.4% to 23.3%), respectively. CONCLUSIONS: Sexual dysfunction and PSA are not rare after inguinal hernia repair. They should be included in preoperative discussions and as standard metrics in reporting outcomes of repair in large cohorts or trials.

Regional, racial, gender, and tumor biology disparities in breast cancer survival rates in Africa: A systematic review and meta-analysis.

BACKGROUND: The survival rates from breast cancer in Africa are poor and yet the incidence rates are on the rise. In this study, we hypothesized that, in Africa, a continent with great disparities in socio-economic status, race, tumor biology, and cultural characteristics, the survival rates from breast cancer vary greatly based on region, tumor biology (hormone receptor), gender, and race. We aimed to conduct the first comprehensive systematic review and meta-analysis on region, gender, tumor-biology and race-specific 5-year breast cancer survival rates in Africa and compared them to 20-year survival trends in the United States. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library to identify studies on breast cancer survival in African published before October 17, 2018. Pooled 5-year survival rates of breast cancer were estimated by random-effects models. We explored sources of heterogeneity through subgroup meta-analyses and meta-regression. Results were reported as absolute difference (AD) in percentages. We compared the survival rates of breast cancer in Africa and the United States. FINDINGS: There were 54 studies included, consisting of 18,970 breast cancer cases. There was substantial heterogeneity in the survival rates (mean 52.9%, range 7-91%, I2 = 99.1%; p for heterogeneity <0.0001). Meta-regression analyses suggested that age and gender-adjusted 5-year survival rates were lower in sub-Saharan Africa compared to north Africa (AD: -25.4%; 95% CI: -34.9 - -15.82%), and in predominantly black populations compared to predominantly non-black populations (AD: -25.9%; 95% CI: 35.40 - -16.43%). Survival rates were 10 percentage points higher in the female population compared to male, but the difference was not significant. Progesterone and estrogen receptor-positive breast cancer subtypes were positively associated with survival (r = 0.39, p = 0.08 and r = 0.24, p = 0.29 respectively), but triple-negative breast cancer was negatively associated with survival. Survival rates are increasing over time more in non-black Africans (55% in 2000 versus 65% in 2018) compared to black Africans (33% in 2000 versus 40% in 2018); but, the survival rates for Africans are still significantly lower when compared to black (76% in 2015) and white (90% in 2015) populations in the United States. CONCLUSION: Regional, sub-regional, gender, and racial disparities exist, influencing the survival rates of breast cancer in Africa. Therefore, region and race-specific public health interventions coupled with prospective genetic studies are urgently needed to improve breast cancer survival in this region.

The Role of Genetic Variant rs13266634 in SLC30A8/ZnT8 in Postoperative Hyperglycemia After Major Abdominal Surgery.

CONTEXT: Following major surgery, postoperative hyperglycemia (POHG) is associated with suboptimal outcomes among patients with diabetes and nondiabetic patients. A specific genetic variant, rs13266634 (c.973C>T; p.ARG325TRP) in zinc transporter SLC30A8/ZnT8, is associated with protection against type 2 diabetes (T2D), suggesting it may be actionable for predicting and preventing POHG. OBJECTIVE: To determine independent and mediated influences of a genetic variant on POHG in patients undergoing a model major operation, complex ventral hernia repair (cVHR). PATIENTS AND DESIGN: For 110 patients (mean body mass index, 34.9 ± 5.8; T2D history, 28%) undergoing cVHR at a tertiary referral center (January 2012 to March 2017), multivariable regression was used to correlate the rs13266634 variant to preoperative clinical, laboratory, and imaging-based indices of liver steatosis and central abdominal adiposity to POHG. Causal mediation analysis (CMA) was used to determine direct and mediated contributions of SLC30A8/ZnT8 status to POHG. RESULTS: Variant rs13266634 was present in 61 patients (55.4%). In univariate models, when compared with patients with homozygous wild-type genotype (C/C, n = 49), rs13266634 was associated with significantly lower risks of POHG (OR, 0.30; 95% CI, 0.14 to 0.67; P = 0.0038). Multivariable regression indicated that the association was independent (OR, 0.39; 95% CI, 0.15 to 0.97; P = 0.040). Additionally, CMA suggested that rs13266634 protects against POHG directly and indirectly through its influence on liver steatosis and central adiposity. CONCLUSIONS: In medically complex patients undergoing major operations, the rs13266634 variant protects against POHG and its associated outcomes, through independent and mediated contributions. In C/C patients undergoing major operations, SLC30A8/ZnT8 may prove useful to stratify the risk of POHG and potentially as a therapeutic target.

Postoperative hyperglycemia in patients undergoing cytoreductive surgery and HIPEC: A cohort study.

BACKGROUND: Hyperglycemia following elective or emergency surgery is generally associated with an increased risk of complications. The impact of hyperglycemia following surgery for peritoneal surface malignancy remains unclear. MATERIALS AND METHODS: Records of patients undergoing cytoreduction and HIPEC for peritoneal surface malignancy were reviewed at two institutions. Postoperative hyperglycemia was defined as serum glucose >140 mg/dl at the first measurement after surgery. Lengths of stay and 30-day complication rates were recorded. RESULTS: There were 115 total patients included, 65 from Institution A (A) and 50 from Institution B (B). Perioperative steroids were given to 55% (A) and 100% (B) of patients, with postoperative hyperglycemia present in 39% and 86% of patients respectively. Complication rates were not significantly different in patients with hyperglycemia versus patients who were normoglycemic at each site [56% vs. 53%, p = 0.8 at (A); 47% vs. 43%, p = 1.0 at (B)]. Infection rates were also similar between groups [16% vs. 13%, p = 0.72 at (A); 14% vs. 29%, p = 0.31 at (B)]. CONCLUSIONS: Rates of hyperglycemia in patients undergoing cytoreduction and HIPEC are high. This likely represents a stress response but does not seem to have the same adverse impact as seen in other abdominal surgical patient populations.

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host-Microbe Interactions.

SCOPE: Greater than 68% of young infants are exposed to dietary zinc (Zn) levels that are higher than the Tolerable Upper Intake Limit. However, the consequences of excess dietary Zn during early life on intestinal function and host-microbe interactions are unknown. METHODS AND RESULTS: Neonatal mice are gavaged with 100 Zn µg d-1 from postnatal day (PN) 2 through PN10 and indices of intestinal function and host-microbe interactions are compared to unsupplemented mice. Excess dietary Zn causes oxidative stress, increases goblet cell number and mucus production, and are associated with increased intestinal permeability and systemic inflammation. Over 900 genes are differentially expressed; 413 genes display a fold-change >1.60. The Gene Ontology Biological processes most significantly affected include biological adhesion, the immune system, metabolic processes, and response to stimulus. Key genes most highly and significantly upregulated include ALDH2, MT1, TMEM6, CDK20, and COX62b, while CALU, ST3GAL4, CRTC2, SLC28A2, and COMMA1 are downregulated. These changes are associated with a microbiome enriched in pathogenic taxa including Pseudomonadales and Campylobacter, and greater expression of bacterial stress response genes. CONCLUSION: Excess dietary Zn may have unforeseen influences on epithelial signaling pathways, barrier function, and luminal ecology in the intestine that may have long-term consequences on intestinal health.

Cost-utility analysis of smoking cessation to prevent operative complications following elective abdominal colon surgery.

BACKGROUND: Smoking is a known risk factor for postoperative complications after colectomy. Using the perspective of the provider, this study evaluated the cost-effectiveness of the pharmacologic interventions for smoking cessation. METHODS: A decision tree model was constructed to represent a provider's decision to provide either bupropion, nicotine replacement therapy, varenicline, or no cessation therapy to all patients presenting for elective colectomy. Incremental cost per quality-adjusted life year (QALY) was the primary outcome. RESULTS: The base case analysis suggests that bupropion is cost-effective with an incremental cost-effectiveness ratio of approximately $75,000 per QALY. Sensitivity analyses established ranges for which each medication might be cost-effective and dominant compared to offering no cessation therapy. CONCLUSIONS: From a provider perspective, offering bupropion for smoking cessation to patients scheduled for elective colon resection is cost-effective. Furthermore, these results provide benchmarks to inform providers about whether targeted, short-term smoking cessation therapies represent good value in colectomies.

Nonalcoholic Fatty Liver Disease as a High-Value Predictor of Postoperative Hyperglycemia and Its Associated Complications in Major Abdominal Surgery.

BACKGROUND: For patients undergoing major abdominal operations, acute postoperative hyperglycemia (POHG) is associated with suboptimal outcomes and higher costs of care. This study was performed to determine whether CT-derived indices of nonalcoholic fatty liver disease (hepatic steatosis) or visceral adiposity may serve as predictors of POHG and its consequences in such patients. STUDY DESIGN: We reviewed records and preoperative abdominal CT images of 129 patients undergoing complex open ventral hernia repair (cVHR) from 2012 to 2016, with 90-day follow-up. Univariate and multivariate regressions were performed to estimate associations between CT-detected steatosis or visceral adiposity with POHG (serum glucose > 140 mg/dL within 48 hours), surgical site occurrence (SSO), and subsequent interventions (SSO-I). RESULTS: Type-2 diabetes (T2D) was present in 23% and POHG in 52%; SSO events occurred in 28% and SSO-I in 21%. Highest-effect associations with POHG were observed for T2D (odds ratio [OR] 21.54; 95% CI 4.85, 95.58), hepatic steatosis (OR 2.20, 95% CI 1.07, 4.52), and waist circumference-to-height ratio (WCHR > 0.65; OR 2.37, 95% CI 1.16, 4.83). After multivariate analysis, the effects of T2D (OR 16.73; CI 5.42, 73.87; p < 0.0001) and steatosis (OR 2.55; CI 1.17, 5.69; p = 0.02) remained independently associated with POHG. Independent associations with SSO were observed for steatosis (OR 3.31; CI 1.41, 8.06; p = 0.007), POHG (OR 2.85; CI 1.17, 7.38; p = 0.024), and WCHR (OR 2.68; CI 1.11, 6.85; p = 0.03). CONCLUSIONS: Image-based indices of chronic metabolic disturbance in the liver and adipose tissues may offer novel opportunities for identifying patients at risk for POHG and those who would benefit from preoperative metabolic optimization.

Delineating the burden of chronic post-operative pain in patients undergoing open repair of complex ventral hernias.

BACKGROUND: After open complex ventral hernia repair (cVHR), chronic pain has a significant impact on quality of life and processes of care. METHODS: Records of 177 patients undergoing cVHR were reviewed in order to characterize the burden of managing postoperative pain in the first post-operative year following open cVHR. RESULTS: In this cohort, 91 patients initiated at least one unsolicited complaint of pain, though phone call (37), unscheduled clinic visit (45) or evaluation in the emergency room (9); among these an actionable diagnosis was found in 38 (41.8%). Among 41 patients who initiated additional unsolicited complaints of pain, an actionable diagnosis was found in only 3 patients. Risk factors for such complaints included pre-operative pain and the use of synthetic mesh. CONCLUSIONS: Even in the absence of an actionable diagnosis, significant resources are utilized in evaluation and management of unsolicited complaints of pain in the first year after cVHR.

Temporally Distinct Regulation of Pathways Contributing to Cardiac Proteostasis During the Acute and Recovery Phases of Sepsis.

BACKGROUND: Cardiac dysfunction is a common manifestation of sepsis and is associated with early increases in inflammation and decreases in myocardial protein synthesis. However, little is known regarding the molecular mechanisms regulating protein homeostasis during the recovery phase after the removal of the septic nidus. Therefore, the purpose of this study was to investigate diverse signal transduction pathways that regulate myocardial protein synthesis and degradation. METHODS: Adult male C57BL/6 mice were used to identify potential mechanisms mediating the acute (24 h) effect of cecal ligation and puncture as well as long-term changes that manifest during the chronic (10 days) recovery phase. RESULTS: Sepsis acutely decreased cardiac protein synthesis that was associated with reduced phosphorylation of S6K1/S6 but not 4E-BP1. Sepsis also decreased proteasome activity, although with no change in MuRF1 and atrogin-1 mRNA expression. Sepsis acutely increased apoptosis (increased caspase-3 and PARP cleavage), autophagosome formation (increased LC3B-II), and canonical inflammasome activity (increased NLRP3, TMS1, cleaved caspase-1). In contrast, during the recovery phase, independent of a difference in food consumption, global protein synthesis was increased, the early repression in proteasome activity was restored to basal levels, whereas stimulation of apoptosis, autophagosome formation, and the canonical inflammasome pathway had abated. However, during recovery there was a selective stimulation of the noncanonical inflammasome pathway as evidenced by activation of caspase-11 with cleavage of Gasdermin D. CONCLUSIONS: These data demonstrate a temporally distinct homeostatic shift in the cardiac proteostatic response to acute infection and recovery.