Catalytic glycosylation for minimally protected donors and acceptors.

Oligosaccharides have myriad functions throughout biological processes1,2. Chemical synthesis of these structurally complex molecules facilitates investigation of their functions. With a dense concentration of stereocentres and hydroxyl groups, oligosaccharide assembly through O-glycosylation requires simultaneous control of site, stereo- and chemoselectivities3,4. Chemists have traditionally relied on protecting group manipulations for this purpose5-8, adding considerable synthetic work. Here we report a glycosylation platform that enables selective coupling between unprotected or minimally protected donor and acceptor sugars, producing 1,2-cis-O-glycosides in a catalyst-controlled, site-selective manner. Radical-based activation9 of allyl glycosyl sulfones forms glycosyl bromides. A designed aminoboronic acid catalyst brings this reactive intermediate close to an acceptor through a network of non-covalent hydrogen bonding and reversible covalent B-O bonding interactions, allowing precise glycosyl transfer. The site of glycosylation can be switched with different aminoboronic acid catalysts by affecting their interaction modes with substrates. The method accommodates a wide range of sugar types, amenable to the preparation of naturally occurring sugar chains and pentasaccharides containing 11 free hydroxyls. Experimental and computational studies provide insights into the origin of selectivity outcomes.

New Insights into the Cooperativity and Dynamics of Dimeric Enzymes.

A survey of protein databases indicates that the majority of enzymes exist in oligomeric forms, with about half of those found in the UniProt database being homodimeric. Understanding why many enzymes are in their dimeric form is imperative. Recent developments in experimental and computational techniques have allowed for a deeper comprehension of the cooperative interactions between the subunits of dimeric enzymes. This review aims to succinctly summarize these recent advancements by providing an overview of experimental and theoretical methods, as well as an understanding of cooperativity in substrate binding and the molecular mechanisms of cooperative catalysis within homodimeric enzymes. Focus is set upon the beneficial effects of dimerization and cooperative catalysis. These advancements not only provide essential case studies and theoretical support for comprehending dimeric enzyme catalysis but also serve as a foundation for designing highly efficient catalysts, such as dimeric organic catalysts. Moreover, these developments have significant implications for drug design, as exemplified by Paxlovid, which was designed for the homodimeric main protease of SARS-CoV-2.

Engineering Carrier Density and Effective Mass of Plasmonic TiN Films by Tailoring Nitrogen Vacancies.

The introduction of nitrogen vacancies has been shown to be an effective way to tune the plasmonic properties of refractory titanium nitrides. However, its underlying mechanism remains debated due to the lack of high-quality single-crystalline samples and a deep understanding of electronic properties. Here, a series of epitaxial titanium nitride films with varying nitrogen vacancy concentrations (TiNx) were synthesized. Spectroscopic ellipsometry measurements revealed that the plasmon energy could be tuned from 2.64 eV in stoichiometric TiN to 3.38 eV in substoichiometric TiNx. Our comprehensive analysis of electrical and plasmonic properties showed that both the increased electronic states around the Fermi level and the decreased carrier effective mass due to the modified electronic band structures are responsible for tuning the plasmonic properties of TiNx. Our findings offer a deeper understanding of the tunable plasmonic properties in epitaxial TiNx films and are beneficial for the development of nitride plasmonic devices.

Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries: The SAFE-AAA Study.

BACKGROUND: Concerns have been raised about the long-term performance of aortic stent grafts for the treatment of abdominal aortic aneurysms, in particular, unibody stent grafts (eg, Endologix AFX AAA stent grafts). Only limited data sets are available to evaluate the long-term risks related to these devices. The SAFE-AAA Study (Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries Study) was designed with the Food and Drug Administration to provide a longitudinal assessment of the safety of unibody aortic stent grafts among Medicare beneficiaries. METHODS: The SAFE-AAA Study was a prespecified, retrospective cohort study evaluating whether unibody aortic stent grafts are noninferior to non-unibody aortic stent grafts with respect to the composite primary outcome of aortic reintervention, rupture, and mortality. Procedures were evaluated from August 1, 2011, through December 31, 2017. The primary end point was evaluated through December 31, 2019. Inverse probability weighting was used to account for imbalances in observed characteristics. Sensitivity analyses were used to evaluate the effect of unmeasured confounding, including assessment of the falsification end points heart failure, stroke, and pneumonia. A prespecified subgroup included patients treated from February 22, 2016, through December 31, 2017, corresponding to the market release of the most contemporary unibody aortic stent grafts (Endologix AFX2 AAA stent graft). RESULTS: Of 87 163 patients who underwent aortic stent grafting at 2146 US hospitals, 11 903 (13.7%) received a unibody device. The average age of the total cohort was 77.0±6.7 years, 21.1% were female, 93.5% were White, 90.8% had hypertension, and 35.8% used tobacco. The primary end point occurred in 73.4% of unibody device-treated patients versus 65.0% of non-unibody device-treated patients (hazard ratio, 1.19 [95% CI, 1.15-1.22]; noninferior P value of 1.00; median follow-up, 3.4 years). Falsification end points were negligibly different between groups. In the subgroup treated with contemporary unibody aortic stent grafts, the cumulative incidence of the primary end point occurred in 37.5% of unibody device-treated patients and 32.7% of non-unibody device-treated patients (hazard ratio, 1.06 [95% CI, 0.98-1.14]). CONCLUSIONS: In the SAFE-AAA Study, unibody aortic stent grafts failed to meet noninferiority compared with non-unibody aortic stent grafts with respect to aortic reintervention, rupture, and mortality. These data support the urgency of instituting a prospective longitudinal surveillance program for monitoring safety events related to aortic stent grafts.

Comparative Effectiveness of Licensed Influenza Vaccines in Preventing Influenza-related Medical Encounters and Hospitalizations in the 2022-2023 Influenza Season Among Adults ≥65 Years of Age.

BACKGROUND: Influenza causes substantial morbidity, particularly among older individuals. Updated data on the effectiveness of currently licensed vaccines in this population are needed. METHODS: At Kaiser Permanente Southern California, we conducted a retrospective cohort study to evaluate comparative vaccine effectiveness (cVE) of high-dose (HD), adjuvanted, and standard-dose (SD) cell-based influenza vaccines, relative to the SD egg-based vaccine. We included adults aged ≥65 years who received an influenza vaccine between 1 August 2022 and 31 December 2022, with follow-up up to 20 May 2023. Primary outcomes were: (1) influenza-related medical encounters and (2) polymerase chain reaction (PCR)-confirmed influenza-related hospitalization. Adjusted hazard ratios (aHR) were estimated by Cox proportional hazards regression, adjusting for confounders using inverse probability of treatment weighting (IPTW). cVE (%) was calculated as (1-aHR) × 100 when aHR ≤1, and ([1/aHR]-1) × 100 when aHR >1. RESULTS: Our study population (n = 495 119) was 54.9% female, 46.3% non-Hispanic White, with a median age of 73 years (interquartile range [IQR] 69-79). Characteristics of all groups were well balanced after IPTW. Adjusted cVEs against influenza-related medical encounters in the HD, adjuvanted, and SD cell-based vaccine groups were 9.1% (95% confidence interval [CI]: .9, 16.7), 16.9% (95% CI: 1.7, 29.8), and -6.3 (95% CI: -18.3, 6.9), respectively. Adjusted cVEs against PCR-confirmed hospitalization in the HD, adjuvanted, and SD cell-based groups were 25.1% (95% CI: .2, 43.8), 61.6% (95% CI: 18.1, 82.0), and 26.4% (95% CI: -18.3, 55.7), respectively. CONCLUSIONS: Compared to the SD egg-based vaccine, HD and adjuvanted vaccines conferred additional protection against influenza-related outcomes in the 2022-2023 season in adults ≥65 years. Our results provide real-world evidence of the comparative effectiveness of currently licensed vaccines.

Understanding the Nonlinear Hammett Relationship in Osmylation of Olefins with OsO4-Amine Ligands: Importance of Singlet-Diradical Character.

Although the concerted [3 + 2] mechanism of osmium-catalyzed asymmetric dihydroxylation has been generally accepted, the unusual nonlinear Hammett relationship induced by amine-type ligands remains unexplained. To understand this, we carried out a density functional theory (DFT) study for the osmylation of substituted styrenes by the following: OsO4, OsO4-pyridine, OsO4-4-cyanopyridine, OsO4-4-pyrrolidinopyridine, and OsO4-quinuclidine. Calculations using the M06 functional successfully reproduce the experimentally observed nonlinear relationships. The transition states exhibit considerable singlet-diradical character, which causes the nonlinear Hammett relationship. Regardless of the presence or absence of an amine-type ligand, an electron donation from styrene to OsO4 is observed, indicating no mechanistic change. Calculations indicate that the electronic interaction between the amine-type ligand and styrene also influences the reaction rate.

Photocatalytic Proton-Coupled Electron Transfer Enabled Radical Cyclization for Isoquinoline-1,3-diones Synthesis.

Radical cyclization has been demonstrated to be an efficient method to access functionalized heterocycles from easily accessible raw materials. Described herein is the development of a photocatalytic proton-coupled electron transfer (PCET) strategy for the synthesis of isoquinoline-1,3-diones using readily prepared naphthalimide (NI)-based organic photocatalysts. The process features free metal-complex photocatalysts, acids, and mild reaction conditions. This mild radical cyclization protocol has a broad substrate scope and can be effectively applied to a variety of medicinally relevant substrates. Furthermore, control experiments were conducted to elucidate the mechanism of this visible light-induced methodology.

A comprehensive understanding of the mechanism of the biomimetic total synthesis of brevianamide A.

Recently, several studies on the chemical synthesis of brevianamide A (BA) were reported. In particular, a highly efficient and remarkably selective synthetic strategy was reported by Lawrence's group. However, a unified mechanistic understanding of these results is still lacking. We have carried out a DFT study and proposed a unified mechanism to understand these experimental results. Starting from intermediate 2, the most favorable reaction sequence is a fast tautomerization, followed by a σ-migration of the base moiety, and a final inverse-electron demanding Diels-Alder reaction, resulting in the formation of the BA product stereoselectively. This reaction mechanism can also be applied to understand the biosynthesis of BA that involves enzymatic catalysis.

An electron donor-acceptor complex-initiated C-H trifluoromethylation and perfluoroalkylation of enamides and quinoxalinones.

Facilitated by an electron donor-acceptor (EDA) complex, an efficient ß-trifluoromethylation and perfluoroalkylation of enamides with Togni reagent or perfluoroalkyl iodides is presented under transition-metal-free, photocatalyst-free and mild reaction conditions. Notably, using this photocatalyst-free strategy, direct trifluoromethylation and perfluoroalkylation of quinoxalin-2(1H)-one derivatives was also achieved via a photoactive electron donor-acceptor complex.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Optical control of butyrylcholinesterase (BChE) activity via photoswitchable azobenzene for potential treatment of Alzheimer's disease.

Photopharmacology is an emerging method in medicinal chemistry to achieve light-controlled drug activity. Azobenzene-based photoswitchable ligands have found widespread application as chemical tools in photopharmacological studies. This study pioneers the design and synthesis of a novel series of photoswitchabled butyrylcholinesterase (BChE) inhibitors, achieved by strategically integrating an azo moiety into an N-benzyl benzamide scaffold. Through a meticulous investigation of the structure-activity relationship (SAR), we discovered that the lead compound, Azo-9, exhibits dynamic cis/trans conformational shifts, dynamically modulating its BChE-binding efficacy. This unique property translates into potential therapeutic benefits, including neuroprotection and cognitive enhancement. Complementary molecular docking simulations underscored the preferential binding of the cis-isomer of Azo-9 to BChE, which was subsequently validated in a glutamate-mediated neuronal injury model. Collectively, Azo-9 emerges as a promising precision tool for Alzheimer's disease (AD) therapy, while also facilitating deeper insights into the disease's underlying mechanisms.

Titanium exposure and gestational diabetes mellitus: associations and potential mediation by perturbation of amino acids in early pregnancy.

BACKGROUND: Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. METHODS: The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. RESULTS: As parameterized in tertiles, titanium showed positive dose-response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. CONCLUSIONS: In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk.

Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study.

BACKGROUND: The recent Maternal Immune Activation (MIA) theory suggests maternal systemic inflammation may serve as a mediator in associations between prenatal maternal adversities and neurodevelopmental diseases in offspring. Given the co-exposure to multiple adversities may be experienced by pregnant person, it is unclear whether a quantitative index can be developed to characterize the inflammation related exposure level, and whether this index is associated with neurodevelopmental delays in offspring. METHODS: Based on Jiangsu Birth Cohort (JBC), a total of 3051 infants were included in the analysis. Inflammation related Prenatal Adversity Index (IPAI) was constructed using maternal data. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, third edition, screening test in one year. Multivariate linear regression and Poisson regression model were performed to analyze the associations between IPAI and neurodevelopment in offspring. RESULTS: Compared with "low IPAI" group, offspring with "high IPAI" have lower scores of cognition, receptive communication, expressive communication, and fine motor. The adjusted ß were - 0.23 (95%CI: -0.42, -0.04), -0.47 (95%CI: -0.66, -0.28), -0.30 (95%CI: -0.49, -0.11), and - 0.20 (95%CI: -0.33, -0.06). Additionally, the elevated risk for noncompetent development of cognition and receptive communication among "high IPAI" group was observed. The relative risk [RR] and 95% confidence interval [CI] were 1.35 (1.01, 1.69) and 1.37 (1.09, 1.72). CONCLUSIONS: Our results revealed a significant association between higher IPAI and lower scores across cognition, receptive communication, expressive communication, and fine motor domains, and an increased risk of noncompetent development in the cognition and receptive communication domains.

Leveraging real-world data to conduct externally controlled trial for rare diseases with count-type endpoints: utilizing multiple entries - a simulation study.

Conducting randomized controlled trials for medications targeting rare diseases presents significant challenges, due to the scarcity of participants and ethical considerations. Under such circumstances, leveraging real-world data (RWD) to generate supporting evidence may be accepted by the regulatory agency. Constructing an external control arm (ECA) from RWD for a single-arm trial has been conducted occasionally. A complication in this design is that patients from RWD may be eligible at multiple time points. Most studies approach this by selecting one time point as the index date for ECA patients. Here, we propose a novel design for externally controlled trials that permits the inclusion of ECA patients at various entry points. Accompanying this design, we make recommendations for statistical methods to account for measured confounders, limited sample size, within-subject correlation, and potential overdispersion inherent in count data. Furthermore, we present an idea for the blinding process for this type of study. We have conducted a series of simulations to assess the performance of the design and statistical methods in terms of bias, type I error, and efficiency, as compared to the approach of selecting only one entry per ECA patient. The study and parameter setup were based on a hypothetical case inspired by a rare disease study. The results indicate that allowing multiple entries for ECA patients can lead to enhanced performance in many aspects. It provides a controlled type I error, robustness against certain model misspecifications, and a moderate power improvement compared with selecting a single entry per ECA patient.

Photoinduced Site-Selective Aryl C-H Borylation with Electron-Donor-Acceptor Complex Derived from B2Pin2 and Isoquinoline.

Due to boron's metalloid properties, aromatic boron reagents are prevalent synthetic intermediates. The direct borylation of aryl C-H bonds for producing aromatic boron compounds offers an appealing, one-step solution. Despite significant advances in this field, achieving regioselective aryl C-H bond borylation using simple and readily available starting materials still remains a challenge. In this work, we attempted to enhance the reactivity of the electron-donor-acceptor (EDA) complex by selecting different bases to replace the organic base (NEt3) used in our previous research. To our delight, when using NH4HCO3 as the base, we have achieved a mild visible-light-mediated aromatic C-H bond borylation reaction with exceptional regioselectivity (rr > 40:1 to single isomers). Compared with our previous borylation methodologies, this protocol provides a more efficient and broader scope for aryl C-H bond borylation through the use of N-Bromosuccinimide. The protocol's good functional-group tolerance and excellent regioselectivity enable the functionalization of a variety of biologically relevant compounds and novel cascade transformations. Mechanistic experiments and theoretical calculations conducted in this study have indicated that, for certain arenes, the aryl C-H bond borylation might proceed through a new reaction mechanism, which involves the formation of a novel transient EDA complex.

Axial Ligand Enables Synthesis of Allenylsilane through Dirhodium(II) Catalysis.

Described herein is a dirhodium(II)-catalyzed silylation of propargyl esters with hydrosilanes, using tertiary amines as axial ligands. By adopting this strategy, a range of versatile and useful allenylsilanes can be achieved with good yields. This reaction not only represents a SN2'-type silylation of the propargyl derivatives bearing a terminal alkyne moiety to synthesize allenylsilanes from simple hydrosilanes, but also represents a new application of dirhodium(II) complexes in catalytic transformation of carbon-carbon triple bond. The highly functionalized allenylsilanes that are produced can be transformed into a series of synthetically useful organic molecules. In this reaction, an intriguing ON-OFF effect of the amine ligand was observed. The reaction almost did not occur (OFF) without addition of Lewis base amine ligand. However, the reaction took place smoothly (ON) after addition of only catalytic amount of amine ligand. Detailed mechanistic studies and density functional theory (DFT) calculations indicate that the reactivity can be delicately improved by the use of tertiary amine. The fine-tuning effect of the tertiary amine is crucial in the formation of the Rh-Si species via a concerted metalation deprotonation (CMD) mechanism and facilitating ß-oxygen elimination.

Genome-wide identification of potential odontogenic genes involved in the dental epithelium-mesenchymal interaction during early odontogenesis.

BACKGROUND: Epithelium-mesenchymal interactions are involved in odontogenic processes. Previous studies have focused on the intracellular signalling regulatory network in tooth development, but the functions of extracellular regulatory molecules have remained unclear. This study aims to explore the gene profile of extracellular proteoglycans and their glycosaminoglycan chains potentially involved in dental epithelium-mesenchymal interactions using high-throughput sequencing to provide new understanding of early odontogenesis. RESULTS: Whole transcriptome profiles of the mouse dental epithelium and mesenchyme were investigated by RNA sequencing (RNA-seq). A total of 1,281 and 1,582 differentially expressed genes were identified between the dental epithelium and mesenchyme at E11.5 and E13.5, respectively. Enrichment analysis showed that extracellular regions and ECM-receptor interactions were significantly enriched at both E11.5 and E13.5. Polymerase chain reaction analysis confirmed that the extracellular proteoglycan family exhibited distinct changes during epithelium-mesenchymal interactions. Most proteoglycans showed higher transcript levels in the dental mesenchyme, whereas only a few were upregulated in the epithelium at both stages. In addition, 9 proteoglycans showed dynamic expression changes between these two tissue compartments. Gpc4, Sdc2, Spock2, Dcn and Lum were expressed at higher levels in the dental epithelium at E11.5, whereas their expression was significantly higher in the dental mesenchyme at E13.5, which coincides with the odontogenic potential shift. Moreover, the glycosaminoglycan biosynthetic enzymes Ext1, Hs3st1/5, Hs6st2/3, Ndst3 and Sulf1 also exhibited early upregulation in the epithelium but showed markedly higher expression in the mesenchyme after the odontogenic potential shift. CONCLUSION: This study reveals the dynamic expression profile of extracellular proteoglycans and their biosynthetic enzymes during the dental epithelium-mesenchymal interaction. This study offers new insight into the roles of extracellular proteoglycans and their distinct sulfation underlying early odontogenesis.

Comparison of Short-Term Outcomes Between Robot-Assisted and Video-Assisted Segmentectomy for Small Pulmonary Nodules: A Propensity Score-Matching Study.

BACKGROUND: Our study aimed to compare the short-term outcomes between robot-assisted segmentectomy (RAS) and video-assisted segmentectomy (VAS) for small pulmonary nodules. METHODS: The study included of 299 segmentectomies (132 RAS and 167 VAS procedures) for small pulmonary nodules between June 2018 and November 2021. The patients were divided into two groups: the RAS group and the VAS group. Propensity score-matching (PSM) analysis was performed to minimize bias. A logistic regression model was performed to identify the independent risk factors associated with complications. RESULTS: Before PSM, the following clinical variables were not balanced: age (P = 0.004), tumor size (P < 0.001), forced expiratory volume for 1 s (FEV1), and FEV1 percentage (P < 0.001). The patients with RAS had a shorter operative time (P = 0.014), less blood loss, a shorter postoperative hospital stay, less use of strong opioids, less drainage on postoperative day 1, and less postoperative total drainage, but more cost (all P < 0.001). Conversion to open surgery was performed for two patients in the VAS group but none in the RAS group. After PSM, 53 pairs were successfully matched. The data again suggested that the patients with RAS had less blood loss, a shorter postoperative hospital stay, and less use of strong opioids, but more cost (all P < 0.001). The operation time also was shorter in the RAS group, with a borderline statistically significant P value (0.053). CONCLUSIONS: In our study, RAS had better short-term outcomes than VAS, indicating a safer and more efficient technique than VAS.

Longitudinal outcomes following peripheral vascular intervention among older persons living with HIV.

BACKGROUND: Persons living with human immunodeficiency virus (HIV, PLWH) have an increased risk of peripheral artery disease (PAD) in comparison to the general population. However, a gap remains in understanding optimal management for this condition. This study assesses longitudinal outcomes associated with peripheral endovascular intervention (PVI) for PAD among PLWH. METHODS: All Medicare fee-for-service patients undergoing femoropopliteal artery PVI between April 1, 2015 and December 31, 2018 were identified and stratified by HIV serostatus. The primary outcome was major adverse limb events (MALE), defined as major amputation or arterial embolism/thrombosis following an index procedure. The subdistribution hazard was used to evaluate the association between HIV serostatus and MALE, accounting for the competing risk of death. Results were adjusted for sociodemographics and major comorbidities. RESULTS: Of 168,553 patients who underwent PVI, 357 (0.21%) were PLWH. The average age was 77.0 ± 7.6 years; 80.3% had hypertension, 70.3% had hyperlipidemia, and 24.6% had tobacco use disorder. Compared to those without HIV, PLWH were younger and had a higher burden of cardiovascular risk factors. MALE were substantially more frequent among PLWH, with a cumulative incidence of 24.6%, compared to 14.5% among those without HIV. The adjusted subdistribution hazard ratio was 1.26 (95% CI 1.00-1.58, p = 0.05). The use of guideline-directed statin therapy was low in both groups in the 90 days following revascularization (57.9% in PLWH vs 58.1% in those without HIV, p = 0.95). CONCLUSION: Among US Medicare beneficiaries, PLWH had poorer long-term outcomes following PVI. Greater attention to the management of symptomatic PAD is warranted for the HIV population, particularly following revascularization.

Comparative performance of distinct frailty measures among patients undergoing percutaneous left atrial appendage closure.

AIMS: Frailty is associated with increased morbidity and mortality in patients undergoing left atrial appendage closure (LAAC). This study aimed to compare the performance of two claims-based frailty measures in predicting adverse outcomes following LAAC. METHODS: We identified patients 66 years and older who underwent LAAC between October 1, 2016, and December 31, 2019, in Medicare fee-for-service claims. Frailty was assessed using the previously validated Hospital Frailty Risk Score (HFRS) and Kim Claims-based Frailty Index (CFI). Patients were identified as frail based on HFRS ≥5 and CFI ≥0.25. RESULTS: Of the 21,787 patients who underwent LAAC, frailty was identified in 45.6% by HFRS and 15.4% by CFI. There was modest agreement between the two frailty measures (kappa 0.25, Pearson's correlation 0.62). After adjusting for age, sex, and comorbidities, frailty was associated with higher risk of 30-day mortality, 1-year mortality, 30-day readmission, long hospital stay, and reduced days at home (p < .01 for all) regardless of the frailty measure used. The addition of frailty to standard comorbidities significantly improved model performance to predict 1-year mortality, long hospital stay, and reduced days at home (Delong p-value < .001). CONCLUSION: Despite significant variation in frailty detection and modest agreement between the two frailty measures, frailty status remained highly predictive of mortality, readmissions, long hospital stay, and reduced days at home among patients undergoing LAAC. Measuring frailty in clinical practice, regardless of the method used, may provide prognostic information useful for patients being considered for LAAC, and may inform shared decision-making in this population.