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Impaired insulin signaling is a key feature of type 2 diabetes and is associated with increased ubiquitin-proteasome-dependent protein degradation in skeletal muscle. An extract of Artemisia dracunculus L. (termed PMI5011) improves insulin action by increasing insulin signaling in skeletal muscle. We sought to determine if the effect of PMI5011 on insulin signaling extends to regulation of the ubiquitin-proteasome system. C2C12 myotubes and the KK-Ay murine model of type 2 diabetes were used to evaluate the effect of PMI5011 on steady-state levels of ubiquitylation, proteasome activity and expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are upregulated with impaired insulin signaling. Our results show that PMI5011 inhibits proteasome activity and steady-state ubiquitylation levels in vitro and in vivo. The effect of PMI5011 is mediated by PI3K/Akt signaling and correlates with decreased expression of Atrogin-1 and MuRF-1. Under in vitro conditions of hormonal or fatty acid-induced insulin resistance, PMI5011 improves insulin signaling and reduces Atrogin-1 and MuRF-1 protein levels. In the KK-Ay murine model of type 2 diabetes, skeletal muscle ubiquitylation and proteasome activity is inhibited and Atrogin-1 and MuRF-1 expression is decreased by PMI5011. PMI5011-mediated changes in the ubiquitin-proteasome system in vivo correlate with increased phosphorylation of Akt and FoxO3a and increased myofiber size. The changes in Atrogin-1 and MuRF-1 expression, ubiquitin-proteasome activity and myofiber size modulated by PMI5011 in the presence of insulin resistance indicate the botanical extract PMI5011 may have therapeutic potential in the preservation of muscle mass in type 2 diabetes.

Background/Aims: Endoscopic ultrasound-guided liver biopsy (EUS-LB) is an effective and safe method of procuring liver tissue. The aims of this study were to assess and compare the outcomes and tissue adequacy of a single-pass, single-actuation, wet suction technique between 19 G and 22 G needles in patients undergoing EUS-LB.Methods: We performed a prospective case series study of 20 patients undergoing EUS-LB at a single center between September 2017 and April 2020. The primary objective was to evaluate differences in sample adequacy via a single actuation wet suction technique between a 19 G core needle and a 22 G core needle. Adequacy was gauged by cumulative core biopsy length and the number of portal tracts visualized.Results: The 19 G needle provided a longer core length (2.5 cm vs. 1.2 cm, p<0.0001), more complete portal tracts (5.8 vs. 1.7, p<0.0001), more total tracts (8.8 vs. 3, p<0.0001), and a longer, intact, fragment length (0.75 cm vs. 0.32 cm, p<0.0006). The 19 G needle was superior in providing adequate (60% vs. 5%, p<0.001) and diagnostic pathologic samples (85% vs. 10%, p<0.001).Conclusions: A single-pass, single-actuation, wet suction technique using a 19 G needle is superior to that using a 22 G needle for tissue acquisition and sample adequacy in EUS-LB.

Objectives The value of robotic pancreaticoduodenectomy (RPD) remains undefined. The aim of this retrospective study was to compare and assess clinical outcomes and financial variables of patients undergoing RPD versus open pancreaticoduodenectomy (OPD) at a single high-volume center. Methods The study design is a retrospective analysis of a prospectively maintained database of consecutive PD patients from 2013 to 2019. Clinical variables and total hospital charges were evaluated as an unadjusted and adjusted intention-to-treat analysis. Results A total of 156 patients (54 OPD, 102 RPD) were identified. In the RPD group, patients were significantly older (P = 0.0304) and had shorter length of stay (mean, 7 vs 11.8 days; P < 0.0001) and longer operative times (mean, 352.7 vs 211.5 minutes; P < 0.0001) compared with OPD. There was no significant difference in 90-day readmissions, bleeding, or complications between OPD and RPD. Adjusted charge analyses show no difference in total charges (P = 0.057). Conclusions Robotic pancreaticoduodenectomy is safe, feasible, and valid alternative to OPD. Because of comparable results within each group, randomized trials may be indicated. High-volume RPD centers should collaborate to better understand the differences and advantages over laparoscopic or OPD.

Elevated interleukin-6 (IL-6) levels may correlate with disease severity in COVID-19. We analyzed whether there was an association between elevated IL-6 levels and major adverse cardiac events (MACE) and/or mortality in COVID-19 patients. A retrospective chart review was performed on COVID-19 patients among four hospitals in one health system from March to May 2020, extracting information on baseline characteristics, MACE (i.e., myocardial infarction, stroke, deep venous thrombosis/pulmonary embolism, or shock requiring vasopressor support), mortality, and IL-6 levels. Of the 496 patients hospitalized with COVID-19, 191 patients had an IL-6 level drawn and 68% had elevated IL-6 levels. The elevated IL-6 population had higher odds of developing a MACE compared to the normal IL-6 population ( P < 0.0001, odds ratio [OR] = 5.91, 95% confidence interval [CI] = 2.65–14.11). The elevated IL-6 population also had higher mortality rates (28.2% vs 5%, P = 0.0001, OR = 7.47, 95% CI = 2.19–39.32) and an increased incidence of a MACE and/or mortality (58.78% vs 20.00%, P < 0.0001, OR = 5.7, 95% CI 2.65–12.83) compared to the normal IL-6 population. Elevated IL-6 levels in COVID-19 patients may be associated with MACE and/or mortality. Monitoring IL-6 levels in COVID-19 patients may help risk-stratify patients.

<p><strong>Background</strong></p><p>The hospital readmission rate has been thought to reflect the quality of patient care. Understanding the risk factors for these can guide strategies to reduce them.</p><p><strong>Methods</strong></p><p>Retrospective cohort design that included all the admissions for AMI from October 2011 to September 2014. Primary outcome was 30-day readmission rate. Secondary outcomes were 7-day readmission rate, reasons for readmission and cardiac-related readmission rate. Univariate and multivariate logistic regression were conducted with Hosmer-Lemeshow goodness-of-fit statistics for model calibration and ROC curve for model discrimination.</p><p><strong>Results</strong></p><p>We identified 2958 cases of AMI and 334 readmissions (11.3%). The final sample for analysis included 310 readmitted and 652 non-readmitted patients. The principal causes of readmission were cardiac related (42%), followed by respiratory (15%) and gastrointestinal (11%). Separate analysis for the early readmissions showed the same pattern. 42% of the readmissions happened during the first week and 68% in the first 2 weeks after discharge. Median time for readmission was 10 days. Older age, days from admission to catheterization, complete medical therapy at discharge, diabetes, hypertension, stroke, major psychiatric disorders, insurance status, chronic kidney disease and congestive heart failure were independently associated with 30-day readmission. The final multivariate model discriminated well with a ROC of 0.753 (95% CI 0.72-0.79).</p><p><strong>Conclusion</strong></p><p>Reasons for readmission found in our study were consistent with previous studies. Absolute readmission rates reported in this study were lower than in some prior publications. We present novel and addressable patient risk factors derived from the index admission that can be used to predict readmission.</p>

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