Regional variation in patient selection, practice patterns, and outcomes based on techniques for carotid artery revascularization in the Vascular Quality Initiative.

OBJECTIVE: Significant regional variation is known with multiple surgical procedures. This study describes regional variation in carotid revascularization within the Vascular Quality Initiative (VQI). METHODS: Data from the VQI carotid endarterectomy (CEA) and carotid artery stenting (CAS) databases from 2016 to 2021 were used. Nineteen geographic VQI regions were divided into three tertiles based on the average annual volume of carotid procedures performed per region (low-volume: 956 cases [range, 144-1382]; medium-volume: 1533 cases [range, 1432-1589]; and high-volume: 1845 cases [range, 1642-2059]). Patients' characteristics, indications for carotid revascularization, practice patterns, and outcomes (perioperative and 1-year stroke/death) of different revascularization techniques were compared between these regional groups. Regression models that adjust for known risk factors and allow for random effects at the center level were used. RESULTS: CEA was the most common revascularization procedure (>60%) across all regional groups. Significant regional variation was observed in the practice of CEA such as variability in the use of shunting, drain placement, stump pressure and electroencephalogram monitoring, intraoperative protamine, and patch angioplasty. For transfemoral CAS, high-volume regions had a higher proportion of asymptomatic patients with <80% stenosis (30.5% vs 27.8%) in addition to higher use of local/regional anesthesia (80.4% vs 76.2%), protamine (16.1% vs 11.8%), and completion angiography (81.6% vs 77.6%) during transfemoral carotid artery stenting (TF-CAS) compared with low-volume regions. For transcarotid artery revascularization (TCAR), high-volume regions were less likely to intervene on asymptomatic patients with <80% stenosis (32.2% vs 35.8%) than low-volume regions. They also had a higher proportion of urgent/emergent procedures (13.6% vs 10.4%) and were more likely to use general anesthesia (92.0% vs 82.1%), completion angiography (67.3% vs 63.0%), and poststent ballooning (48.4% vs 36.8%). For each carotid revascularization technique, no significant differences were noted in perioperative and 1-year outcomes between low-, medium-, and high-volume regions. Finally, there were no significant differences in outcomes between TCAR and CEA across the different regional groups. In all regional groups, TCAR was associated with a 40% reduction in perioperative and 1-year stroke/death compared with TF-CAS. CONCLUSIONS: Despite significant variation in clinical practices for the management of carotid disease, no regional variation exists in the overall outcomes of carotid interventions. TCAR and CEA continue to show superior outcomes to TF-CAS across all VQI regional groups.

Prospective study of emergency medicine provider wellness across ten academic and community hospitals during the initial surge of the COVID-19 pandemic.

BACKGROUND: While COVID-19 has had far-reaching consequences on society and health care providers, there is a paucity of research exploring frontline emergency medicine (EM) provider wellness over the course of a pandemic. The objective of this study was to assess the well-being, resilience, burnout, and wellness factors and needs of EM physicians and advanced practice providers (e.g., nurse practitioners and physician assistants; APPs) during the initial phase of the COVID-19 pandemic. METHODS: A descriptive, prospective, cohort survey study of EM physicians and APPs was performed across ten emergency departments in a single state, including academic and community settings. Participants were recruited via email to complete four weekly, voluntary, anonymous questionnaires comprised of customized and validated tools for assessing wellness (Well Being Index), burnout (Physician Work Life Study item), and resilience (Brief Resilience Scale) during the initial acceleration phase of COVID-19. Univariate and multivariate analysis with Chi-squared, Fisher's Exact, and logistic regression was performed. RESULTS: Of 213 eligible participants, response rates ranged from 31 to 53% over four weeks. Women comprised 54 to 60% of responses. Nonrespondent characteristics were similar to respondents. Concern for personal safety decreased from 85 to 61% (p < 0.001). Impact on basic self-care declined from 66 to 32% (p < 0.001). Symptoms of stress, anxiety, or fear was initially 83% and reduced to 66% (p = 0.009). Reported strain on relationships and feelings of isolation affected > 50% of respondents initially without significant change (p = 0.05 and p = 0.30 respectively). Women were nearly twice as likely to report feelings of isolation as men (OR 1.95; 95% CI 1.82-5.88). Working part-time carried twice the risk of burnout (OR, 2.45; 95% CI, 1.10-5.47). Baseline resilience was normal to high. Provider well-being improved over the four weeks (30 to 14%; p = 0.01), but burnout did not significantly change (30 to 22%; p = 0.39). CONCLUSION: This survey of frontline EM providers, including physicians and APPs, during the initial surge of COVID-19 found that despite being a resilient group, the majority experienced stress, anxiety, fear, and concerns about personal safety due to COVID-19, putting many at risk for burnout. The sustained impact of the pandemic on EM provider wellness deserves further investigation to guide targeted interventions.

Pharmacologic or genetic interference with atrogene signaling protects from glucocorticoid-induced musculoskeletal and cardiac disease.

Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, as long-term treated patients exhibit high incidence of falls, bone fractures, and cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, and the heart, the expression of E3 ubiquitin ligases (atrogenes), known to stimulate the proteasomal degradation of proteins. Activation of Vitamin D receptor (VDR) signaling with the VDR ligands 1,25D3 (calcitriol, 1,25-dihydroxyvitamin D3) or ED (eldecalcitol, 2ß-(3-hydroxypropyloxy)-1,25-dihydroxyvitamin D3) prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of three tissues in vivo. Direct pharmacologic inhibition of the proteasome with carfilzomib also conferred musculoskeletal protection. Genetic loss of the atrogene MuRF1-mediated protein ubiquitination in ∆RING mice afforded temporary or sustained protection from GC excess in bone, or skeletal and heart muscle, respectively. We conclude that the atrogene pathway downstream of MuRF1 underlies GC action in bone, muscle, and the heart, and it can be pharmacologically or genetically targeted to confer protection against the damaging actions of GC simultaneously in the three tissues.

CD147 monoclonal antibody attenuates abdominal aortic aneurysm formation in angiotensin II-Infused apoE-/- mice.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a life threatening vascular disease. Our previous study reported the upregulation of CD147 expression in human aortic aneurysms. OBJECTIVE: In this study, we injected apoE-/- mice intraperitoneally with CD147 monoclonal antibody or IgG control antibody to observe its effect on Angiotensin II (AngII) induced AAA formation. METHODS: ApoE-/- mice were randomly divided into an AngⅡ+CD147 antibody group (n = 20) and an AngⅡ+IgG antibody group (n = 20). The Alzet osmotic minipump was implanted subcutaneously into the backs of mice to infuse AngII (1000 ng/kg/min) for 28 days and subsequently treated with CD147 monoclonal antibody or control IgG mAb (10 µg/mouse/day) beginning one day after surgery. Body weight, food intake, drinking volume and blood pressure were measured weekly throughout the study. After 4 weeks of injection, routine bloodwork measuring liver function, kidney function and lipid levels were recorded. Hematoxylin and eosin (H&E), Masson's trichrome, and Elastic van Gieson (EVG) staining were used to evaluate the pathological changes in blood vessels. In addition, Immunohistochemical assay was used to detect infiltration of inflammatory cells. Tandem mass tag (TMT)-based proteomic analysis was used to define differentially expressed proteins (DEPs) using a p-value < 0.05 and fold change > 1.2 or < 0.83 as the threshold. Subsequently, we conducted protein-protein interaction (PPI) network and GO enrichment analysis to determine the core biological function altered after CD147 antibody injection. RESULTS: The CD147 monoclonal antibody suppresses Ang II-induced AAA formation in apoE-/- mice and reduced aortic expansion, elastic lamina degradation, and inflammatory cells accumulation. Bioinformatics analysis showed that Ptk6, Itch, Casp3, and Oas1a were the hub DEPs. These DEPs in the two group were mainly involved in collagen fibril organization, extracellular matrix organization, and muscle contraction. These data robustly demonstrated that CD147 monoclonal antibody suppresses Ang II-induced AAA formation through reduction of inflammatory response and regulation of the above defined hub proteins and biological processes. Thus, the CD147 monoclonal antibody might be a promising target in the treatment of abdominal aortic aneurysm.

Correlation research of susceptibility single nucleotide polymorphisms and the severity of clinical symptoms in attention deficit hyperactivity disorder.

Objective: To analyze the correlation between susceptibility single nucleotide polymorphisms (SNPs) and the severity of clinical symptoms in children with attention deficit hyperactivity disorder (ADHD), so as to supplement the clinical significance of gene polymorphism and increase our understanding of the association between genetic mutations and ADHD phenotypes. Methods: 193 children with ADHD were included in our study from February 2017 to February 2020 in the Children's ADHD Clinic of the author's medical institution. 23 ADHD susceptibility SNPs were selected based on the literature, and multiple polymerase chain reaction (PCR) targeted capture sequencing technology was used for gene analysis. A series of ADHD-related questionnaires were used to reflect the severity of the disease, and the correlation between the SNPs of specific sites and the severity of clinical symptoms was evaluated. R software was used to search for independent risk factors by multivariate logistic regression and the "corplot" package was used for correlation analysis. Results: Among the 23 SNP loci of ADHD children, no mutation was detected in 6 loci, and 2 loci did not conform to Hardy-Weinberg equilibrium. Of the remaining 15 loci, there were 9 SNPs, rs2652511 (SLC6A3 locus), rs1410739 (OBI1-AS1 locus), rs3768046 (TIE1 locus), rs223508 (MANBA locus), rs2906457 (ST3GAL3 locus), rs4916723 (LINC00461 locus), rs9677504 (SPAG16 locus), rs1427829 (intron) and rs11210892 (intron), correlated with the severity of clinical symptoms of ADHD. Specifically, rs1410739 (OBI1-AS1 locus) was found to simultaneously affect conduct problems, control ability and abstract thinking ability of children with ADHD. Conclusion: There were 9 SNPs significantly correlated with the severity of clinical symptoms in children with ADHD, and the rs1410739 (OBI1-AS1 locus) may provide a new direction for ADHD research. Our study builds on previous susceptibility research and further investigates the impact of a single SNP on the severity of clinical symptoms of ADHD. This can help improve the diagnosis, prognosis and treatment of ADHD.

Longitudinal Prospective Study of Emergency Medicine Provider Wellness Across Ten Academic and Community Hospitals During the Initial Surge of the COVID-19 Pandemic.

Background: While the coronavirus (COVID-19) has had far-reaching consequences on society and health care providers, there is a paucity of research exploring emergency medicine (EM) provider wellness over the course of a pandemic. The objective of this study was to assess the well-being, resilience, burnout, and wellness factors and needs of EM physicians and advanced practice providers (APPs) during the initial phase of the COVID-19 pandemic. Methods: A longitudinal, descriptive, prospective cohort survey study of 213 EM physicians and APPs was performed across ten emergency departments in a single state, including academic and community settings. Participants were recruited via email to complete four weekly, voluntary, anonymous questionnaires comprised of customized and validated tools for assessing wellness (Well Being Index), burnout (Physician Work Life Study item), and resilience (Brief Resilience Scale) during the initial acceleration phase of COVID-19. Univariate and multivariate analysis with Chi-squared, Fisher’s Exact, and logistic regression was performed. Results: Of 213 eligible participants, response rates ranged from 31 to 53% over four weeks. Women comprised 54 to 60% of responses. Nonrespondent characteristics were similar to respondents. Concern for personal safety decreased from 85% to 61% (p<0.001). Impact on basic self-care declined from 66% to 32% (p<0.001). Symptoms of stress, anxiety or fear was initially 83% and reduced to 66% (p=0.009). Reported strain on relationships and feelings of isolation affected >50% of respondents initially without significant change (p=0.05 and p=0.30 respectively). Women were nearly twice as likely to report feelings of isolation as men (OR 1.95; 95%CI 1.82-5.88). Working part-time carried twice the risk of burnout (OR, 2.45; 95% CI, 1.10-5.47). Baseline resilience was normal to high. Provider well-being improved over the four-weeks (30% to 14%; p=0.01), but burnout did not significantly change (30% to 22%; p=0.39). Conclusion: This survey of frontline EM providers during the initial surge of COVID-19 found that despite being a resilient group, the majority experienced stress, anxiety, fear, and concerns about personal safety due to COVID-19, with many at risk for burnout. The sustained impact of the pandemic on EM provider wellness deserves further investigation to guide targeted interventions.