Adipocyte Na, K-ATPase Signaling Attenuates Experimental Uremic Cardiomyopathy.

Oxidative stress has been shown to cause an alteration of intracellular signaling in adipocytes that may lead to various comorbidities of obesity and cardiovascular complications. Evidence suggests that dysregulation of Na, K-ATPase signaling can contribute to systemic inflammation and redox signaling that leads to various metabolic disturbances. Hence the present study aims to explore the specific role of adipocyte Na, K-ATPase signaling in the amelioration of pathophysiological alterations of experimental uremic cardiomyopathy. Experimental uremic cardiomyopathy was induced by partial nephrectomy (PNx), and adipocyte-specific expression of NaKtide, a peptide that inhibits Na, K-ATPase signaling, was achieved using a lentivirus construct with NaKtide expression driven by an adiponectin promoter. Cardiomyopathy and anemia induced in partial nephrectomy mice were accompanied by an altered molecular phenotype of adipocytes, increased systemic inflammatory cytokines and oxidant stress within 4 weeks. These changes were significantly worsened by the addition of a Western diet (enriched in fat and fructose contents) but were prevented with specific expression of NaKtide in adipocytes. The skeletal muscle-specific expression of NaKtide did not ameliorate the disease phenotype. Adipocyte dysfunction and uremic cardiomyopathy developed in PNx mice, both were significantly ameliorated by the adipocyte-specific expression of NaKtide. These findings suggest that oxidative milieu in the adipocyte has a pivotal role in the development and progression of uremic cardiomyopathy in mice subjected to partial nephrectomy. If confirmed in humans, this may be a lead for future research to explore novel therapeutic targets in chronic renal failure.

COVID-19 and Liver Injury: A Systematic Review and Meta-Analysis.

Background and Aims The prevalence and extent of liver damage in coronavirus disease 2019 (COVID-19) patients remain poorly understood, primarily due to small-sized epidemiological studies with varying definitions of "liver injury". We conducted a meta-analysis to derive generalizable, well-powered estimates of liver injury prevalence in COVID-19 patients. We also aimed to assess whether liver injury prevalence is significantly greater than the baseline prevalence of chronic liver disease (CLD). Our secondary aim was to study whether the degree of liver injury was associated with the severity of COVID-19. Materials and Methods Electronic databases (PubMed and Scopus) were systematically searched in June 2020 for studies reporting the prevalence of baseline CLD and current liver injury in hospitalized COVID-19 patients. Liver injury was defined as an elevation in transaminases >3 times above the upper limit of normal. For the secondary analysis, all studies reporting mean liver enzyme levels in severe versus non-severe COVID-19 patients were included. A random-effects model was used for meta-analysis. Proportions were subjected to arcsine transformation and pooled to derive pooled proportions and corresponding 95% confidence intervals (CIs). Subgroup differences were tested for using the chi-square test and associated p-value. Means and their standard errors were pooled to derive weighted mean differences (WMDs) and corresponding 95% CIs. Results Electronic search yielded a total of 521 articles. After removal of duplicates and reviewing the full-texts of potential studies, a total of 27 studies met the inclusion criteria. Among a cohort of 8,817 patients, the prevalence of current liver injury was 15.7% (9.5%-23.0%), and this was significantly higher than the proportion of patients with a history of CLD (4.9% [2.2%-8.6%]; p < 0.001). A total of 2,900 patients in our population had severe COVID-19, and 7,184 patients had non-severe COVID-19. Serum ALT (WMD: 7.19 [4.90, 9.48]; p < 0.001; I2 = 69%), AST (WMD: 9.02 [6.89, 11.15]; p < 0.001; I2 = 73%) and bilirubin levels (WMD: 1.78 [0.86, 2.70]; p < 0.001; I2 = 82%) were significantly higher in patients with severe COVID-19 when compared to patients with non-severe disease. Albumin levels were significantly lower in patients with severe COVID-19 (WMD: -4.16 [-5.97, -2.35]; p < 0.001; I2 = 95%). Conclusions Patients with COVID-19 have a higher than expected prevalence of liver injury, and the extent of the injury is associated with the severity of the disease. Further studies are required to assess whether hepatic damage is caused by the virus, medications, or both.

Prophylactic Mesh Placement for the Prevention of Incisional Hernia in High-Risk Patients After Abdominal Surgery: A Systematic Review and Meta-Analysis.

Background and objectives In high-risk populations, the efficacy of mesh placement in incisional hernia (IH) prevention after elective abdominal surgeries has been supported by many published studies. This meta-analysis aimed at providing comprehensive and updated clinical implications of prophylactic mesh placement (PMP) for the prevention of IH as compared to primary suture closure (PSC). Materials and methods PubMed, Science Direct, Cochrane, and Google Scholar were systematically searched until March 3, 2020, for studies comparing the efficacy of PMP to PSC in abdominal surgeries. The main outcome of interest was the incidence of IH at different follow-up durations. All statistical analyses were carried out using Review Manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) and Stata 11.0 (Stata Corporation LP, College Station, TX). The data were pooled using the random-effects model, and odds ratio (OR) and weighted mean differences (WMD) were calculated with the corresponding 95% confidence interval (CI). Results A total of 3,330 were identified initially and after duplicate removal and exclusion based on title and abstract, 26 studies comprising 3,000 patients, were included. The incidence of IH was significantly reduced for PMP at follow-up periods of one year (OR= 0.16 [0.05, 0.51]; p=0.002; I2=77%), two years (OR= 0.23 [0.12, 0.45]; p<0.0001; I2=68%), three years (OR= 0.30 [0.16, 0.59]; p=0.0004; I2= 52%), and five years (OR=0.15 [0.03, 0.85]; p=0.03; I2=87%). However, PMP was associated with an increased risk of seroma (OR=1.67 [1.10, 2.55]; p= 0.02; I2=19%) and chronic wound pain (OR=1.71 [1.03, 2.83]; p= 0.04; I2= 0%). No significant difference between the PMP and PSC groups was noted for postoperative hematoma (OR= 1.04 [0.43, 2.50]; p=0.92; I2=0%), surgical site infection (OR=1.09 [0.78, 1.52]; p= 0.62; I2=12%), wound dehiscence (OR=0.69 [0.30, 1.62]; p=0.40; I2= 0%), gastrointestinal complications (OR= 1.40 [0.76, 2.58]; p=0.28; I2= 0%), length of hospital stay (WMD= -0.49 [-1.45, 0.48]; p=0.32; I2=0%), and operating time (WMD=9.18 [-7.17, 25.54]; p= 0.27; I2=80%). Conclusions PMP has been effective in reducing the rate of IH in the high-risk population at all time intervals, but it is associated with an increased risk of seroma and chronic wound pain. The benefits of mesh largely outweigh the risk, and it is linked with positive outcomes in high-risk patients.

Availability of Personal Protective Equipment (PPE) Among US and Pakistani Doctors in COVID-19 Pandemic.

Background The coronavirus disease (COVID-19) pandemic has put an excessive strain on healthcare systems across the globe, causing a shortage of personal protective equipment (PPE). PPE is a precious commodity for health personnel to protect them against infections. We investigated the availability of PPE among doctors in the United States (US) and Pakistan. Methods A cross-sectional study, including doctors from the US and Pakistan, was carried out from April 8 to May 5, 2020. An online self-administered questionnaire was distributed to doctors working in hospitals in the US and Pakistan after a small pilot study. All analysis was done using Statistical Package for Social Science (SPSS) version 23.0 (IBM Corp., Armonk, NY). Results After informed consent, 574 doctors (60.6% from Pakistan and 39.4% from the US) were included in the analysis. The majority of the participants were females (53.3%), and the mean age of the participants was 35.3 ± 10.3 years. Most doctors (47.7%) were from medicine and allied fields. Among the participants, 87.6% of doctors from the US reported having access to masks/N95 respirators, 79.6% to gloves, 77.9% to face-shields or goggles, and 50.4% to full-suit/gown. Whereas, doctors in Pakistan reported to have poor availability of PPE with only 37.4% having access to masks/N95 respirator, 34.5% to gloves, 13.8% to face-shields or goggles, and 12.9% to full-suit/gown. The reuse of PPE was reported by 80.5% and 60.3% physicians from the US and Pakistan, respectively. More doctors from Pakistan (50.6%) reported that they had been forced to work without PPE compared to doctors in the US (7.1%). Conclusion There is a lack of different forms of PPE in the US and Pakistan. Doctors from both countries reported that they had been forced to work without PPE. Compared to the US, more doctors from Pakistan reported having faced discrimination in receiving PPE.

Molecular characterization of SLC24A5 variants and evaluation of Nitisinone treatment efficacy in a zebrafish model of OCA6.

Skin pigmentation is a highly heterogeneous trait with diverse consequences worldwide. SLC24A5, encoding a potent K+ -dependent Na+ /Ca2+ exchanger, is among the known color-coding genes that participate in melanogenesis by maintaining pH in melanosomes. Deficient SLC24A5 activity results in oculocutaneous albinism (OCA) type 6 in humans. In this study, by utilizing a exome sequencing (ES) approach, we identified two new variants [p. (Gly110Arg) and p. (IIe189Ilefs*1)] of SLC24A5 cosegregating with the OCA phenotype, including nystagmus, strabismus, foveal hypoplasia, albinotic fundus, and vision impairment, in three large consanguineous Pakistani families. Both of these variants failed to rescue the pigmentation in zebrafish slc24a5 morphants, confirming the pathogenic effects of the variants. We also phenotypically characterized a commercially available zebrafish mutant line (slc24a5ko ) that harbors a nonsense (p.Tyr208*) allele of slc24a5. Similar to morphants, homozygous slc24a5ko mutants had significantly reduced melanin content and pigmentation. Next, we used these slc24a5ko zebrafish mutants to test the efficacy of nitisinone, a compound known to increase ocular and fur pigmentation in OCA1 (TYR) mutant mice. Treatment of slc24a5ko mutant zebrafish embryos with varying doses of nitisinone did not improve melanin production and pigmentation, suggesting that treatment with nitisinone is unlikely to be therapeutic in OCA6 patients.

Haemorrhage control in the prehospital setting: a scoping review protocol.

INTRODUCTION: Prehospital haemorrhage control has saved thousands of lives in the military over the last decade. While uncontrolled haemorrhage is a leading cause of preventable injury death in the USA for individuals under 45, military prehospital haemorrhage control techniques have not fully translated to the civilian sector in the USA. The effective implementation of haemorrhage control for civilian prehospital trauma is dependent on a more complex array of system and personnel-level factors than the military. OBJECTIVE: This protocol describes the methodology of a scoping review on haemorrhage control strategies in the prehospital setting; specifically, education, logistics and implementation of these strategies. The aim of the review is to identify research gaps and create recommendations for future research surrounding prehospital layperson haemorrhage control. METHODS: The protocol uses the framework published by The Joanna Briggs Institute and Arksey and O'Malley, while following the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols guidelines. The search strategy was refined with the help of a medical librarian. Three peer-reviewed databases (EMBASE, PubMed and Web of Science), databases dedicated to grey literature sources, and reference mining will be used. Two investigators will independently screen and extract data. Discrepancies will be resolved by a third investigator. The extracted data will undergo descriptive analysis of the contextual data and a quantitative analysis using the appropriate statistical methods. In addition, this search strategy will be supplemented by a grey literature search. ETHICS AND DISSEMINATION: Research ethics approval is not required for this scoping review. This scoping review will serve to highlight existing gaps within the literature to guide further research and develop future strategies to improve prehospital haemorrhage management. The results of this review will be presented at relevant national and international conferences and published in a peer-reviewed journal.

The Optimal Length of Stay Associated With the Lowest Readmission Risk Following Surgery.

BACKGROUND: Index length of stay (LOS) and readmissions are viewed as important quality measures. However, these metrics represent competing demands as an inordinate reduction in LOS may lead to unplanned readmissions. We sought to assess the optimal LOS associated with the lowest 90-d readmission rate following discharge after common surgical procedures. MATERIALS AND METHODS: This was a retrospective study relying on Tricare claims. We identified all eligible adult patients (18-64 y) receiving a series of common surgical procedures between 2006 and 2014. We used a generalized additive model with spline regression to determine the optimal LOS associated with the lowest 90-d risk of readmission. RESULTS: Ninety-day readmission rates varied from 6.03% to 34.69%. Most procedures exhibited a logit linear relationship, with the lowest risk of readmission evident on postoperative day-1 and increasing thereafter. Among the more invasive procedures (e.g., esophagectomy and radical cystectomy), a U-shaped relationship was realized, indicating that expedited discharge would increase the potential for readmission as would any extended hospital LOS. For these procedures, the ideal index LOS appeared to be 6-7 d for radical cystectomy and 12-13 d for esophagectomy. CONCLUSIONS: Our results support the practice of discharging patients as soon as clinically feasible after hip and knee arthroplasty, lumbar spine surgery, hernia repair, appendectomy, nephrectomy, and colectomy. Among esophagectomy or radical cystectomy, there is a well-defined optimal index admission period and discharge outside this window appears to be detrimental. Our results suggest that invasive procedures appear to possess a unique "signature" when it comes to optimal LOS.

Effectiveness of Instructional Interventions for Hemorrhage Control Readiness for Laypersons in the Public Access and Tourniquet Training Study (PATTS): A Randomized Clinical Trial.

Importance: Several national initiatives have emerged to empower laypersons to act as immediate responders to reduce preventable deaths from uncontrolled bleeding. Point-of-care instructional interventions have been developed in response to the scalability challenges associated with in-person training. However, to our knowledge, their effectiveness for hemorrhage control has not been established. Objective: To evaluate the effectiveness of different instructional point-of-care interventions and in-person training for hemorrhage control compared with no intervention and assess skill retention 3 to 9 months after hemorrhage control training. Design, Setting, and Participants: This randomized clinical trial of 465 laypersons was conducted at a professional sports stadium in Massachusetts with capacity for 66 000 people and assessed correct tourniquet application by using different point-of-care interventions (audio kits and flashcards) and a Bleeding Control Basic (B-Con) course. Non-B-Con arms received B-Con training after initial testing (conducted from April 2017 to August 2017). Retesting for 303 participants (65%) was performed 3 to 9 months after training (October 2017 to January 2018) to evaluate B-Con retention. A logistic regression for demographic associations was performed for retention testing. Interventions: Participants were randomized into 4 arms: instructional flashcards, audio kits with embedded flashcards, B-Con, and control. All participants received B-Con training to later assess retention. Main Outcomes and Measures: Correct tourniquet application in a simulated scenario. Results: Of the 465 participants, 189 (40.7%) were women and the mean (SD) age was 46.3 (16.1) years. For correct tourniquet application, B-Con (88% correct application [n = 122]; P < .001) was superior to control (n = 104 [16%]) while instructional flashcards (n = 117 [19.6%]) and audio kit (n = 122 [23%]) groups were not. More than half of participants in point-of-care arms did not use the educational prompts as intended. Of 303 participants (65%) who were assessed 3 to 9 months after undergoing B-Con training, 165 (54.5%) could correctly apply a tourniquet. Over this period, there was no further skill decay in the adjusted model that treated time as either linear (odds ratio [OR], 0.98; 95% CI, 0.95-1.03) or quadratic (OR, 1.00; 95% CI, 1.00-1.00). The only demographic that was associated with correct application at retention was age; adults aged 18 to 35 years (n = 58; OR, 2.39; 95% CI, 1.21-4.72) and aged 35 to 55 years (n = 107; OR, 1.77; 95% CI, 1.04-3.02) were more likely to be efficacious than those older than 55 years (n = 138). Conclusions and Relevance: In-person hemorrhage control training for laypersons is currently the most efficacious means of enabling bystanders to act to control hemorrhage. Laypersons can successfully perform tourniquet application after undergoing a 1-hour course. However, only 54.5% retain this skill after 3 to 9 months, suggesting that investigating refresher training or improved point-of-care instructions is critical. Trial Registration: ClinicalTrials.gov Identifier: NCT03479112.

Universal Health Insurance and its association with long term outcomes in Pediatric Trauma Patients.

BACKGROUND: Racial disparities in mortality exist among pediatric trauma patients; however, little is known about disparities in outcomes following discharge. METHODS: We conducted a longitudinal cohort study of children admitted for moderate to severe trauma, covered by TRICARE from 2006 to 2014. Patients were followed up to 90days after discharge. All children <18 years with a primary trauma diagnosis, an Injury Severity Score >9 and 90days of follow-up after discharge were included. Complications, readmissions and utilization of healthcare services up to 90days after discharge were compared between Black and White patients. RESULTS: Of the 5192 children included, majority were White (74.6%, n=3871), with 15.4% Black (n=800) and 10.0% Other (n=521). Most common injuries involved the extremities or the pelvic girdle followed by the head or neck. Complication and readmission rates were 3.6% and 8.9% within 30days of discharge respectively and 4.4% and 9.3% within 90days of discharge. 99.0% of children had at least one outpatient visit by 90days. After adjusting for patient and injury characteristics no significant differences were detected between Black and White children in outcomes after discharge. CONCLUSIONS: Universal insurance may help mitigate disparities in post discharge care in pediatric trauma populations by increasing access to outpatient services overall and within each racial group. Further studies are required to determine the appropriate timing and frequency of follow up care in order to achieve maximum reduction in use of acute care services after discharge.

Race-based differences in duration of stay among universally insured coronary artery bypass graft patients in military versus civilian hospitals.

BACKGROUND: Duration of stay for coronary artery bypass graft operation outcomes differs for black versus white patients, with differences often attributed to insurance. We examined black versus white differences in duration of stay among TRICARE-covered patients undergoing coronary artery bypass graft. METHODS: Patients aged 18-64 years with TRICARE who underwent isolated coronary artery bypass graft (ICD-9CM 36.10-36.20) between 2006-2010 and who identified as black or white race were identified. Negative binomial regression, stratified by sex and military versus civilian facility, examined the duration of stay controlling for patient- and hospital-level factors. RESULTS: Of 3,496 eligible patients, 2,904 underwent coronary artery bypass graft at 682 civilian and 592 at 11 military hospitals. Patients (mean age 56.2 years) were predominantly white (88.9%), male (88.7%), married (88.2%), and retired (87%). Black patients demonstrated longer duration of stay (8.6 vs 7.5 days, P > .001), and overall duration of stay was longer at military facilities (8.1 vs 7.5 days, P = .013). Among the men, mean duration of stay was 14% longer for black patients at civilian hospitals (95% confidence interval 1.07-1.22) with no race-based differences at military facilities. CONCLUSION: Among coronary artery bypass graft patients with TRICARE coverage, black, male patients demonstrated greater duration of stay at civilian facilities. Further work should examine care at military hospitals to elucidate factors that drive the apparent mitigation of race-related variability in duration of stay.

Access to post-discharge inpatient care after lower limb trauma.

BACKGROUND: Most hospitals in the United States are required to provide emergency care to all patients, regardless of insurance status. However, uninsured patients might be unable to access non-acute services, such as post-discharge inpatient care (PDIC). This could result in prolonged acute hospitalization. We tested the hypothesis that insurance status would be independently associated with both PDIC and length of stay (LOS). METHODS: An observational study was undertaken using the California State Inpatient Database (2007-2011), which captures 98% of patients admitted to hospital in California. All patients with a diagnosis of orthopedic lower limb trauma were identified using International Classification of Diseases, 9th Revision, Clinical Modification codes 820-828. Multivariable logistic and generalized linear regression models were used to adjust odds of PDIC and LOS for patient and hospital characteristics. RESULTS: There were 278,573 patients with orthopedic lower limb injuries, 160,828 (57.7%) of which received PDIC. Uninsured patients had lower odds of PDIC (adjusted odds ratio 0.20, 95% confidence interval 0.17-0.24) and significantly longer hospital LOS (predicted mean difference 1.06 [95% confidence interval 0.78-1.34] d) than those with private insurance. CONCLUSIONS: Lack of health insurance is associated with reduced access to PDIC and prolonged hospital LOS. This potential barrier to hospital discharge could reduce the number of trauma beds available for acutely injured patients.

From understanding to action: interventions for surgical disparities.

BACKGROUND: Health care disparities are a well-documented phenomenon. Despite the development and implementation of multiple interventions, disparities in surgery have proven persistent. Thought to arise from a combination of patient, provider, and system-level factors, the objective of this study was to identify what is currently known about factors that influence surgical disparities and elucidate possible interventions to address them across four intervention-based themes: (1) condition-specific targeted interventions; (2) increased reliance on quantitative factors; (3) doctor-patient communication; and (4) cultural humility. DATA SOURCES: Articles were abstracted from PubMed, EMBASE, and the Cochrane Library using controlled keyword vocabulary. CONCLUSIONS: There are various forms of interventions to address surgical disparities, spanning knowledge from disparate fields. Promising efforts have emerged towards the successful alleviation of disparities. In order to move the field of surgery from understanding of disparities towards actions to mitigate them, continued development of meaningful quality improvement initiatives are needed.