Impact of the COVID-19 Pandemic on Infective Endocarditis Management and Outcomes: Analysis of a National Clinical Database.

COVID-19 has widely affected health care delivery, but its impact on the management of infective endocarditis (IE), including valve surgery, is uncertain. We compared the national trends in admissions, demographics, and outcomes of IE before and after COVID-19 onset, using a national sample of IE admissions between 2016 and 2022 from the Vizient Clinical Database. The pre-COVID-19 and post-COVID-19 time periods were separated by the start of the second quarter of 2020, the time during which the COVID-19 pandemic was declared. For all admissions and for admissions involving valve surgery, pre-COVID-19 versus post-COVID-19 baseline characteristics and outcomes were compared using 2-sample t tests or chi-square tests. Propensity score-matched cohorts were similarly compared. Before COVID-19, there were 82,867 overall and 11,337 valve-related surgical admissions, and after COVID-19, there were 45,672 overall and 6,322 valve-related surgical admissions. In the matched analysis for all admissions, the in-hospital mortality increased from 11.4% to 12.4% after COVID-19 onset (p <0.001); in-hospital stroke (4.9% vs 6.0%, p <0.001), myocardial infarction (1.3% vs 1.4%, p = 0.03), and aspiration pneumonia (1.8% vs 2.4%, p <0.001) also increased, whereas other complications remained stable. In the matched analysis of surgical admissions, there was decreased in-hospital mortality (7.7% vs 6.7%, p = 0.03) and intensive care unit stay (8.5 ± 12.5 vs 8.0 ± 12.6 days, p = 0.04); other outcomes remained stable. In conclusion, patients admitted with IE after COVID-19 were more medically complex with worsened outcomes and mortality, whereas patients who underwent valve surgery had stable outcomes and improved mortality despite the pandemic.

Inadequate Adherence to Imaging Surveillance and Medical Management in Patients with Duplex Ultrasound-Detected Carotid Artery Stenosis.

BACKGROUND: It is recommended that patients with ≥50% carotid artery stenosis undergo surveillance imaging and atherosclerotic risk reduction medical therapies, regardless of whether revascularization is performed. The objective of this study was to determine rates of adherence to these recommended measures and to identify risk factors for nonadherence. METHODS: A retrospective analysis was performed of all carotid duplex ultrasound (DUS) from 2016 to 2017 at a single institution. Patients with unilateral or bilateral ≥50% carotid stenosis were included. Primary outcomes were rates and timing of surveillance imaging and medication regimen. Patient and study characteristics were compared using univariate and multivariable analyses. A subgroup analysis of patients with a new finding of carotid stenosis was also performed. RESULTS: Carotid stenosis >50% was detected in 340 patients. Overall, 182 patients (54%) had follow-up imaging (median 261 days [IQR 166-366]) and 158 patients (46%) had no imaging follow-up (NIFU). NIFU patients had similar rates of aspirin use (86% vs. 88%, P = 0.6) and tobacco cessation counseling (71% vs. 71%, P = 0.8) but had less statin use (85% vs. 94%, P = 0.01) compared to those with imaging follow-up. Subsequent carotid revascularization was more common in patients with imaging follow-up (18% vs. 3%, P < 0.001). NIFU patients were less likely to have Medicare or commercial insurance (54% vs. 75%, P < 0.001). The indication for DUS in NIFU patients, compared to those in follow up, was less commonly neurologic symptoms (11% vs. 14%), more commonly other clinical findings (35% vs. 16%), and more commonly as work up before nonvascular surgery (25% vs. 4%, P < 0.001), respectively. NIFU rates decreased with increasing degree of carotid stenosis. Prior carotid intervention, prior DUS, or DUS ordered by a vascular surgeon were characteristics associated with imaging follow-up (P < 0.05 for all). In a subgroup of 160 patients with new carotid stenosis, a majority (64%) had NIFU and statin use was lower in these patients (82% vs. 96%, P = 0.007). On multivariable analysis, preop indication was predictive of NIFU (odds ratio [OR] 8.1 [95% confidence interval, CI 2.5-26.4], P < 0.001) whereas protective factors included: 70-80% stenosis (OR 0.33 [95% CI 0.14-0.76], P = 0.01), study ordered by vascular surgeon (OR 0.40 [95% CI 0.19-0.83], P = 0.01), and Medicare/commercial insurance (OR 0.36 [95% CI 0.2-0.66], P = 0.001). CONCLUSIONS: Nearly half of patients found to have ≥50% carotid stenosis on DUS had no imaging follow-up; these patients were less likely to be on recommended statin therapy. The benefits of nonrevascularization-based treatments for carotid disease require adherence to therapy. Forgoing surveillance imaging in patients with hemodynamically significant carotid stenosis should be a shared decision between provider and patient and does not obviate the need for medical therapies.

Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in nemaline myopathy.

Nemaline myopathy (NM) is the most common form of congenital myopathy that results in hypotonia and muscle weakness. This disease is clinically and genetically heterogeneous, but three recently discovered genes in NM encode for members of the Kelch family of proteins. Kelch proteins act as substrate-specific adaptors for Cullin 3 (CUL3) E3 ubiquitin ligase to regulate protein turnover through the ubiquitin-proteasome machinery. Defects in thin filament formation and/or stability are key molecular processes that underlie the disease pathology in NM; however, the role of Kelch proteins in these processes in normal and diseases conditions remains elusive. Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, nebulin-related anchoring protein (NRAP). KLHL41 binds to the thin filament chaperone NRAP and promotes ubiquitination and subsequent degradation of NRAP, a process that is critical for the formation of mature myofibrils. KLHL41 deficiency results in abnormal accumulation of NRAP in muscle cells. NRAP overexpression in transgenic zebrafish resulted in a severe myopathic phenotype and absence of mature myofibrils demonstrating a role in disease pathology. Reducing Nrap levels in KLHL41 deficient zebrafish rescues the structural and function defects associated with disease pathology. We conclude that defects in KLHL41-mediated ubiquitination of sarcomeric proteins contribute to structural and functional deficits in skeletal muscle. These findings further our understanding of how the sarcomere assembly is regulated by disease-causing factors in vivo, which will be imperative for developing mechanism-based specific therapeutic interventions.