Transcatheter and Surgical Aortic Valve Replacement in Patients With Bicuspid Aortic Valve Stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is not widely used in patients with bicuspid aortic valve (BAV) disease and has not yet been studied in randomized clinical trials. We characterized the rate of use and outcomes of TAVR and surgical aortic valve replacement (SAVR) in patients with BAV. METHODS: Adults with BAV stenosis receiving SAVR or TAVR procedures were abstracted from the 2012 to 2019 Nationwide Readmissions Database (NRD). Risk-adjusted analyses were performed with NRD-provided weights and inverse probability of treatment weights (IPTW) to examine the association of treatment strategy on inpatient mortality, complications, and hospitalization resource utilization. Nonelective readmissions within 90 days of discharge and reintervention at the first readmission were also examined. RESULTS: Of an estimated 56 331 patients with BAV requiring aortic valve replacement, 6.8% underwent TAVR. Unadjusted analysis demonstrated higher index hospitalization mortality for TAVR compared with SAVR. Upon risk adjustment using NRD-provided weights, the odds of pacemaker implantation remained significantly higher for TAVR patients compared with SAVR, with no significant difference in mortality. When NRD-provided survey weights were applied, TAVR had higher rates of 90-day readmission. Adjustment with inverse probability of treatment weights resolved these differences between the 2 groups. Regardless of the risk-adjustment method, the odds of reintervention were consistently higher among BAV TAVR patients compared with SAVR. CONCLUSIONS: The present analysis demonstrates comparable in-hospital mortality and morbidity for TAVR and SAVR patients in the moderate-risk era. With increasing TAVR use in BAV, surgeons must further refine selection criteria with consideration of concomitant aortopathy and implications of reintervention.

Management of symptomatic cholelithiasis: a systematic review.

BACKGROUND: Symptomatic cholelithiasis is a common surgical disease and accounts for half of the over one million cholecystectomies performed in the USA annually. Despite its prevalence, only one prior systematic review has examined the evidence around treatment strategies and it contained a narrow scope. The goal of this systematic review was to analyze the clinical effectiveness of treatment options for symptomatic cholelithiasis, including surgery, non-surgical therapies, and ED pain management strategies. METHODS: Literature search was performed from January 2000 through June 2020, and a narrative analysis was performed as studies were heterogeneous. RESULTS: We identified 12 publications reporting on 10 trials (9 randomized controlled trials and 1 observational study) comparing treatment methods. The studies assessed surgery, observation, lithotripsy, ursodeoxycholic acid, electro-acupuncture, and pain-management strategies in the emergency department. Only one compared surgery to observation. CONCLUSION: This work presents the existing data and underscores the current gap in knowledge regarding treatment for patients with symptomatic cholelithiasis. We use these results to suggest how future trials may guide comparisons between the timing of surgery and watchful waiting to create a set of standardized guidelines. Providing appropriate and timely treatment for symptomatic cholelithiasis is important to streamline care for a costly and prevalent disease. TRIAL REGISTRATION: PROSPERO Protocol Number: CRD42020153153.

Rare, Damaging DNA Variants in CORIN and Risk of Coronary Artery Disease: Insights From Functional Genomics and Large-Scale Sequencing Analyses.

BACKGROUND: Corin is a protease expressed in cardiomyocytes that plays a key role in salt handling and intravascular volume homeostasis via activation of natriuretic peptides. It is unknown if Corin loss-of-function (LOF) is causally associated with risk of coronary artery disease (CAD). METHODS: We analyzed all coding CORIN variants in an Italian case-control study of CAD. We functionally tested all 64 rare missense mutations in Western Blot and Mass Spectroscopy assays for proatrial natriuretic peptide cleavage. An expanded rare variant association analysis for Corin LOF mutations was conducted in whole exome sequencing data from 37 799 CAD cases and 212 184 controls. RESULTS: We observed LOF variants in CORIN in 8 of 1803 (0.4%) CAD cases versus 0 of 1725 controls (P, 0.007). Of 64 rare missense variants profiled, 21 (33%) demonstrated <30% of wild-type activity and were deemed damaging in the 2 functional assays for Corin activity. In a rare variant association study that aggregated rare LOF and functionally validated damaging missense variants from the Italian study, we observed no association with CAD-21 of 1803 CAD cases versus 12 of 1725 controls with adjusted odds ratio of 1.61 ([95% CI, 0.79-3.29]; P=0.17). In the expanded sequencing dataset, there was no relationship between rare LOF variants with CAD was also observed (odds ratio, 1.15 [95% CI, 0.89-1.49]; P=0.30). Consistent with the genetic analysis, we observed no relationship between circulating Corin concentrations with incident CAD events among 4744 participants of a prospective cohort study-sex-stratified hazard ratio per SD increment of 0.96 ([95% CI, 0.87-1.07], P=0.48). CONCLUSIONS: Functional testing of missense mutations improved the accuracy of rare variant association analysis. Despite compelling pathophysiology and a preliminary observation suggesting association, we observed no relationship between rare damaging variants in CORIN or circulating Corin concentrations with risk of CAD.

Filtering Facepiece Respirator (N95 Respirator) Reprocessing: A Systematic Review.

IMPORTANCE: The COVID-19 pandemic has resulted in a persistent shortage of personal protective equipment; therefore, a need exists for hospitals to reprocess filtering facepiece respirators (FFRs), such as N95 respirators. OBJECTIVE: To perform a systematic review to evaluate the evidence on effectiveness and feasibility of different processes used for decontaminating N95 respirators. EVIDENCE REVIEW: A search of PubMed and EMBASE (through January 31, 2021) was completed for 5 types of respirator-decontaminating processes including UV irradiation, vaporized hydrogen peroxide, moist-heat incubation, microwave-generated steam, and ethylene oxide. Data were abstracted on process method, pathogen removal, mask filtration efficiency, facial fit, user safety, and processing capability. FINDINGS: Forty-two studies were included that examined 65 total types of masks. All were laboratory studies (no clinical trials), and 2 evaluated respirator performance and fit with actual clinical use of N95 respirators. Twenty-seven evaluated UV germicidal irradiation, 19 vaporized hydrogen peroxide, 9 moist-heat incubation, 10 microwave-generated steam, and 7 ethylene oxide. Forty-three types of N95 respirators were treated with UV irradiation. Doses of 1 to 2 J/cm2 effectively sterilized most pathogens on N95 respirators (>103 reduction in influenza virus [4 studies], MS2 bacteriophage [3 studies], Bacillus spores [2 studies], Escherichia virus MS2 [1 study], vesicular stomatitis virus [1 study], and Middle East respiratory syndrome virus/SARS-CoV-1 [1 study]) without degrading respirator components. Doses higher than 1.5 to 2 J/cm2 may be needed based on 2 studies demonstrating greater than 103 reduction in SARS-CoV-2. Vaporized hydrogen peroxide eradicated the pathogen in all 7 efficacy studies (>104 reduction in SARS-CoV-2 [3 studies] and >106 reduction of Bacillus and Geobacillus stearothermophilus spores [4 studies]). Pressurized chamber systems with higher concentrations of hydrogen peroxide caused FFR damage (6 studies), while open-room systems did not degrade respirator components. Moist heat effectively reduced SARS-CoV-2 (2 studies), influenza virus by greater than 104 (2 studies), vesicular stomatitis virus (1 study), and Escherichia coli (1 study) and preserved filtration efficiency and facial fit for 11 N95 respirators using preheated containers/chambers at 60 °C to 85 °C (5 studies); however, diminished filtration performance was seen for the Caron incubator. Microwave-generated steam (1100-W to 1800-W devices; 40 seconds to 3 minutes) effectively reduced pathogens by greater than 103 (influenza virus [2 studies], MS2 bacteriophage [3 studies], and Staphylococcus aureus [1 study]) and maintained filtration performance in 10 N95 respirators; however, damage was noted in least 1 respirator type in 4 studies. In 6 studies, ethylene oxide preserved respirator components in 16 N95 respirator types but left residual carcinogenic by-product (1 study). CONCLUSIONS AND RELEVANCE: Ultraviolet germicidal irradiation, vaporized hydrogen peroxide, moist heat, and microwave-generated steam processing effectively sterilized N95 respirators and retained filtration performance. Ultraviolet irradiation and vaporized hydrogen peroxide damaged respirators the least. More research is needed on decontamination effectiveness for SARS-CoV-2 because few studies specifically examined this pathogen.

Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas.

[Figure: see text].