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Hispanics/Latinos face specific sociocultural stressors associated with their marginalized status in the United States. While stress is known to cause poor sleep, the differential effects of the specific stressors faced by Hispanics/Latinos have not been evaluated. Using cross-sectional data from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study, we conducted weighted generalized linear models to evaluate the associations of acculturation stress, ethnic discrimination, and chronic moderate/severe stress with self-reported sleep outcomes (insomnia symptoms, daytime sleepiness, sleep duration) in individual and aggregate models adjusted for site, socio-demographics, behavioral, and medical conditions. Participants included 5313 Hispanic/Latino adults; 43.5% ≥ age 45, 54.8% female, and 22.0% US-born. Chronic moderate/severe stress, ethnic discrimination, and acculturation stress were each positively associated with sleep. In the adjusted aggregate model, only chronic moderate/severe stress was associated with insomnia symptoms (exp(b) = 1.07 for each additional stressor, 95% CI = 1.05, 1.09). Both acculturation stress (exp(b) = 1.05 for each additional SD, 95% CI = 1.02, 1.10) and ethnic discrimination (exp(b) = 1.05 for each additional SD, 95% CI = 1.01, 1.08) were associated with daytime sleepiness. Each SD increase in ethnic discrimination related to a 16% and 13% increased prevalence of short (< 7 h) (RRR = 1.16, 95% CI = 1.02, 1.31) and long sleep duration (> 9 h) (RRR = 1.13, 95% CI = 1.00, 1.27), respectively. These associations were consistent across sex. Acculturation stress and ethnic discrimination are associated with poor sleep in Hispanics/Latinos. Future research should explore whether behavioral sleep interventions minimize the impact of sociocultural stressors on sleep.

Objective: To compare one year outcomes after atherectomy, intravascular lithotripsy vs. plain balloon angioplasty before application of drug coated balloons for treating femoropopliteal atherosclerotic disease., Data Sources: MEDLINE, EMBASE, and Cochrane Library were screened until May 2023 for randomised controlled trials., Review Methods: This was a systematic review and network meta-analysis. The inclusion criteria were patients with claudication and those with critical limb threatening ischaemia with lesion characteristics of all lengths, stenosis, calcification, and occlusions. The primary outcome was freedom from target lesion re-intervention at one year. Secondary outcomes were rate of bailout stenting, major amputation, and all cause mortality at one year. Pooled point estimates were calculated with a standard random effects model. Further sensitivity analyses were completed with a mixed treatment Bayesian model. Risk of bias was assessed by the Revised Cochrane Risk of Bias tool 2 (RoB2) and certainty of evidence assessed via the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework., Results: Four RCTs comprising 549 patients (two studies evaluating directional atherectomy, one evaluating rotational atherectomy, one evaluating intravascular lithotripsy against plain balloon angioplasty) were included. The weighted mean length of femoropopliteal lesions was 103.4 ± 6.67 mm. Results of the mixed treatment Bayesian analysis were consistent with pooled analysis for all outcomes. There were no significant differences in freedom from target lesion revascularisation (GRADE, high) (RoB2, low), major amputation (GRADE, low), or mortality (GRADE, moderate). Bailout stenting rates were significantly reduced with intravascular lithotripsy and atherectomy compared with plain balloon angioplasty (RR 0.25, 95% CI 0.07 - 0.89) (GRADE, moderate) (RoB2, low)., Conclusion: This review found that intravascular lithotripsy or atherectomy did not appear to incur a statistically significant advantage in freedom from target lesion revascularisation, major amputation, or mortality rate at one year. There was moderate certainty of evidence that bailout stenting is significantly reduced after vessel preparation with intravascular lithotripsy and atherectomy., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care., Methods: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics., Results: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively., Conclusions: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: SRP has received grant funding through his institution from Bayer Pharmaceuticals, Philips Respironics, and Sommetrics and consulting fees from Apnimed, Bayer Pharmaceuticals, NovaResp Technologies, Philips Respironics, and Powell Mansfield. AVS declares no competing interests. AM is funded by the US National Institutes of Health and reports income related to medical education from Livanova, Zoll, Jazz, and Eli Lilly. ResMed provided a philanthropic donation to the University of California, San Diego.

Plant pathogens, including bacteria, fungi, and viruses, pose significant challenges to the farming community due to their extensive diversity, the rapidly evolving phenomenon of multi-drug resistance (MDR), and the limited availability of effective control measures. Amid mounting global pressure, particularly from the World Health Organization, to limit the use of antibiotics in agriculture and livestock management, there is increasing consideration of engineered nanomaterials (ENMs) as promising alternatives for antimicrobial applications. Studies focusing on the application of ENMs in the fight against MDR pathogens are receiving increasing attention, driven by significant losses in agriculture and critical knowledge gaps in this crucial field. In this review, we explore the potential contributions of silver nanoparticles (AgNPs) and their nanocomposites in combating plant diseases, within the emerging interdisciplinary arena of nano-phytopathology. AgNPs and their nanocomposites are increasingly acknowledged as promising countermeasures against plant pathogens, owing to their unique physicochemical characteristics and inherent antimicrobial properties. This review explores recent advancements in engineered nanocomposites, highlights their diverse mechanisms for pathogen control, and draws attention to their potential in antibacterial, antifungal, and antiviral applications. In the discussion, we briefly address three crucial dimensions of combating plant pathogens: green synthesis approaches, toxicity-environmental concerns, and factors influencing antimicrobial efficacy. Finally, we outline recent advancements, existing challenges, and prospects in scholarly research to facilitate the integration of nanotechnology across interdisciplinary fields for more effective treatment and prevention of plant diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Abstract: The spatial anatomy of hematopoiesis in the bone marrow (BM) has been extensively studied in mice and other preclinical models, but technical challenges have precluded a commensurate exploration in humans. Institutional pathology archives contain thousands of paraffinized BM core biopsy tissue specimens, providing a rich resource for studying the intact human BM topography in a variety of physiologic states. Thus, we developed an end-to-end pipeline involving multiparameter whole tissue staining, in situ imaging at single-cell resolution, and artificial intelligence-based digital whole slide image analysis and then applied it to a cohort of disease-free samples to survey alterations in the hematopoietic topography associated with aging. Our data indicate heterogeneity in marrow adipose tissue (MAT) content within each age group and an inverse correlation between MAT content and proportions of early myeloid and erythroid precursors, irrespective of age. We identify consistent endosteal and perivascular positioning of hematopoietic stem and progenitor cells (HSPCs) with medullary localization of more differentiated elements and, importantly, uncover new evidence of aging-associated changes in cellular and vascular morphologies, microarchitectural alterations suggestive of foci with increased lymphocytes, and diminution of a potentially active megakaryocytic niche. Overall, our findings suggest that there is topographic remodeling of human hematopoiesis associated with aging. More generally, we demonstrate the potential to deeply unravel the spatial biology of normal and pathologic human BM states using intact archival tissue specimens., (© 2023 by The American Society of Hematology.)

Bacteria that cause infectious diseases adopt biofilms as one of their most prevalent lifestyles. Biofilms enable bacteria to tolerate environmental stress and evade antibacterial agents. This bacterial defense mechanism has rendered the use of antibiotics ineffective for the treatment of infectious diseases. However, many highly drug-resistant microbes have rapidly emerged owing to such treatments. Different signaling mechanisms regulate bacterial biofilm formation, including cyclic dinucleotide (c-di-GMP), small non-coding RNAs, and quorum sensing (QS). A cell density-dependent phenomenon, QS is associated with c-di-GMP (a global messenger), which regulates gene expression related to adhesion, extracellular matrix production, the transition from the planktonic to biofilm stage, stability, pathogenicity, virulence, and acquisition of nutrients. The article aims to provide information on inhibiting biofilm formation and disintegrating mature/preformed biofilms. This treatment enables antimicrobials to target the free-living/exposed bacterial cells at lower concentrations than those needed to treat bacteria within the biofilm. Therefore, a complementary action of antibiofilm and antimicrobial agents can be a robust strategic approach to dealing with infectious diseases. Taken together, these molecules have broad implications for human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, a bio-friendly inorganic protein hybrid-based enzyme immobilization system using partially purified Coriolus versicolor laccase (CvLac) was successfully applied to biomass hydrolysis for the enhancement of sugar production aimed at generating biofuels. After four days of incubation, the maximum CvLac production was achieved at 140 U/mg of total protein in the presence of inducers such as copper and wheat bran after four days of incubation. Crude CvLac immobilized through inorganic protein hybrids such as nanoflowers (NFs) using zinc as Zn 3 (PO 4 ) 2 /CvLac hybrid NFs (Zn/CvLac-NFs) showed a maximum encapsulation yield of 93.4% and a relative activity of 265% compared to free laccase. The synthesized Zn/CvLac-NFs exhibited significantly improved activity profiles and stability compared to free enzymes. Furthermore, Zn/CvLac-NFs retained a significantly high residual activity of 96.2% after ten reuse cycles. The saccharification of poplar biomass improved ∼2-fold in the presence of Zn/CvLac-NFs, with an 8-fold reduction in total phenolics compared to the control. The Zn/CvLac-NFs treated biomass hydrolysate showed high biological hydrogen (H 2 ) production and ethanol conversion efficiency of up to 2.68 mol/mol of hexose and 79.0% compared to the control values of 1.27 mol of H 2 /mol of hexose and 58.4%, respectively. The CvLac hybrid NFs are the first time reported for biomass hydrolysis, and a significant enhancement in the production of hydrogen and ethanol was reported. The synthesis of such NFs based on crude forms of diverse enzymes can potentially be extended to a broad range of biotechnological applications., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure., Objectives: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH)., Methods: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH)., Results: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present., Conclusions: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033)., Competing Interests: Funding Support and Author Disclosures This study was sponsored by Corvia Medical Inc. Dr Litwin has received research funding from the department of Veterans Affairs, Corvia, AstraZeneca, V-Wave, Axon Therapeutics, and Eli Lilly all paid to the institution; has received consulting fees from CVRx, Axon Therapeutics, Occlutech, Eli Lilly, and Rivus Pharmaceuticals; and has received travel grants, speaker fees, and advisory board honoraria from NovoNordisk and Roche. Dr Komtebedde is employed by Corvia. Dr Burkhoff has consulted for Corvia. Dr Hasenfuß has consulted for AstraZeneca, Boehringer Ingelheim, Corvia, Impulse Dynamics, Novartis, Servier, Vifor; has received honoraria for lectures from AstraZeneca, Bayer, Impulse Dynamics, Novartis, Pfizer, Servier, and Vifor; and is a co-principal investigator to Impulse Dynamics. Dr Borlaug has received research grants from Corvia, AstraZeneca, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and has received consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Ionis, Lilly, MyoKardia, the National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, DiNAQOR, Tremeau, CellProthera, Moderna, American Regent, Sarepta, Lexicon, AnaCardio, and Akros. Dr Mohan has received research support from Corvia and V-Wave paid to the institution. Dr Kahwash has served as a consultant for Medtronic, Impulse Dynamics, and Cardionomic. Dr Sverdlov has received research grants from the National Heart Foundation of Australia (Future Leader Fellowships 101918 and 106025), Department of Health and Aged Care (Australia): Medical Research Future Fund (MRF2017053), New South Wales Health (Australia), Novartis Australia, Biotronik, RACE Oncology, Bristol Myers Squibb, Roche Diagnostics, and Vifor Pharma; and has received personal fees from Novartis, Bayer, Bristol Myers Squibb, AstraZeneca, Corvia, and Boehringer Ingelheim. Dr Fail has received research support paid to the institution from Corvia and Alleviant. Dr Chung has served as a consultant to Intershunt. Dr Kaye has received research support from Corvia. Dr Hummel has received research grant funding from National Institutes of Health, Veterans Affairs, American Heart Association, Novartis, Pfizer, AstraZeneca, Corvia, and Axon Therapies. Dr Zirlik has received personal consulting fees and honoraria for lectures from Abbott, Abiomed, AstraZeneca, Amarin, Amgen, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimensions, Cardiorentis, Corvia, Daichi Sankyo, Edwards Lifesciences, Eli Lilly, Janssen, Merck, Neucomed, Novo Nordisk, Novartis, Rigel, and Stealth Peptides. Dr Hayward has received research support from Corvia, Medtronic, Abbott, Roche, and Procyrion. Dr Lewis has received research funding from the National Institutes of Health (R01-HL 151841, R01-HL131029, R01-HL159514), American Heart Association (15GPSGC-24800006), Amgen, Cytokinetics, Applied Therapeutics, AstraZeneca, and SoniVie; has received honoraria for advisory boards outside of the current study from Pfizer, Merck, Boehringer Ingelheim, NXT, American Regent, Cyclerion, Cytokinetics, and Amgen; and has received royalties from UpToDate for scientific content authorship related to exercise physiology. Dr Gupta has received research support from the National Institutes of Health, Imara, Corvia, and Astellas Pharma. Dr Cikes has received institutional research grants from Abbott, Novartis, and Pfizer; has received travel grants, speaker fees, and advisory board honoraria from Abbott, Abiomed, Amicus, AstraZeneca, Bayer, Boehringer Ingelheim, GE Healthcare, Krka Pharma, LivaNova, Medtronic, Novartis, Orion Corporation, Pfizer, Sanofi, Swixx BioPharma, and Teva Pharmaceutical Industries, all outside of the present study; and has received research support from Corvia. Dr Gustafsson has received honoraria outside the present study as a consultant for Abbott, Pfizer, Ionis Pharmaceuticals, Bayer, AstraZeneca, and Alnylam; has received speaker fees from Novartis and Orion Pharma; and has received research support from Corvia. Dr Silvestry has received research support from Corvia. Dr Rowin has received research support from Corvia; and has served as a consultant for Cardiovascular Clinical Sciences. Dr Cutlip has received research support from Corvia paid to the institution. Dr Kitzman has received honoraria outside the present study as a consultant for Boehringer Ingelheim, Novo Nordisk, AstraZeneca, Rivus, Keyto, and Novartis; has received grant funding outside the present study from Novartis, Bayer, Novo Nordisk, and AstraZeneca; owns stock in Gilead Sciences; and has received research support from Corvia. Dr Shah has received research grants from the National Institutes of Health (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731, R01 HL149423), Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received personal fees from Abbott, Actelion, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiora, Coridea, CVRx, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Eisai, Imara, Impulse Dynamics, Intellia Therapeutics, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sanofi, Shifamed, Tenax, Tenaya, and United Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Data on the prevalence of sleep-disordered breathing (SDB) in people with HIV are limited. Moreover, whether the associations between SDB and age or BMI differ by HIV status is unknown., Research Question: Is SDB more prevalent in men with HIV than those without HIV, and do the predictors of SDB differ between the two groups?, Study Design and Methods: Home polysomnography was used in the Multicenter AIDS Cohort Study to assess SDB prevalence in men with (n = 466; 92% virologically suppressed) and without (n = 370) HIV. SDB was defined using the oxygen desaturation index (ODI) and the apnea-hypopnea index (AHI), using four definitions: ≥ 5 events/h based on an ODI with a 3% (ODI 3 ) or 4% (ODI 4 ) oxygen desaturation, or an AHI with a 3% oxygen desaturation or EEG arousal (AHI 3a ) or with a 4% oxygen desaturation (AHI 4 )., Results: SDB prevalence was similar in men with and without HIV using the ODI 3 and AHI 3a definitions. However, SDB prevalence was higher in men with than without HIV using the ODI 4 (55.9% vs 47.8%; P = .04) and the AHI 4 definitions (57.9% vs 50.4%; P = .06). Mild and moderate SDB were more common in men with than without HIV. Associations between SDB prevalence and age, race, and BMI were similar in men with and without HIV. Among men with HIV, viral load, CD4 cell count, and use of antiretroviral medications were not associated with SDB prevalence., Interpretation: SDB prevalence was high overall but greater in men with than without HIV using the ODI 4 threshold definition. Efforts to diagnose SDB are warranted in people with HIV, given that SDB is associated with daytime sleepiness and impaired quality of life., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

With a continuously increasing human population is an increasing global demand for food. People in countries with a higher socioeconomic status tend to switch their preferences from grains to meat and high-value foods. Their preference for chicken as a source of protein has grown by 70% over the last three decades. Many studies have shown the role of feed in regulating the animal gut microbiome and its impact on host health. The microbiome absorbs nutrients, digests foods, induces a mucosal immune response, maintains homeostasis, and regulates bioactive metabolites. These metabolic activities are influenced by the microbiota and diet. An imbalance in microbiota affects host physiology and progressively causes disorders and diseases. With the use of antibiotics, a shift from dysbiosis with a higher density of pathogens to homeostasis can occur. However, the progressive use of higher doses of antibiotics proved harmful and resulted in the emergence of multidrug-resistant microbes. As a result, the use of antibiotics as feed additives has been banned. Researchers, regulatory authorities, and managers in the poultry industry have assessed the challenges associated with these restrictions. Research has sought to identify alternatives to antibiotic growth promoters for poultry that do not have any adverse effects. Modulating the host intestinal microbiome by regulating dietary factors is much easier than manipulating host genetics. Research efforts have led to the identification of feed additives, including bacteriocins, immunostimulants, organic acids, phytogenics, prebiotics, probiotics, phytoncides, and bacteriophages. In contrast to focusing on one or more of these alternative bioadditives, an improved feed conversion ratio with enhanced poultry products is possible by employing a combination of feed additives. This article may be helpful in future research towards developing a sustainable poultry industry through the use of the proposed alternatives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The therapeutic benefit of intravesical instillation of hexaminolevulinate (HAL) at the time of transurethral resection of bladder tumor (TURBT) has been demonstrated in multiple studies. The purpose of this study was to prospectively assess the safety of repeated administration of HAL from a phase III pre-trial planned analysis., Materials and Methods: All patients evaluated in the study received at least 1 dose of HAL at the time of office cystoscopy, and a subset of these patients (n = 103, 33.2%) received a second dose a few weeks later at the time of TURBT. Adverse events (AEs) were recorded, and the safety of repeat use of HAL was determined by comparing the proportion of patients with AEs considered causally related to HAL in the surveillance examination compared to the OR examination. Association between categorical variables was tested using Fisher's Exact Test, and a P < 0.05 was considered statistically significant., Results: HAL-related AEs were experienced by 6 patients (2.2%) during surveillance cystoscopy and 3 patients (3.4%) following TURBT (P = 0.76); 181 patients (59.5%) had prior exposure to HAL before enrolling in the study with no difference in the number of AEs when comparing prior exposure to HAL to no prior exposure (P = 0.76). Of the patients who previously received intravesical therapy, 8 (2.9%) had at least 1 AE during surveillance compared to 3 (9.7%) who had no prior intravesical therapy (P = 0.09)., Conclusions: Repeat use of HAL is safe even when administered within a few weeks of receiving a dose of intravesical therapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Previous studies suggesting that OSA may be an independent risk factor for VTE have been limited by reliance on administrative data and lack of adjustment for clinical variables, including obesity., Research Question: Does OSA confer an independent risk of incident VTE among a large clinical cohort referred for sleep-disordered breathing evaluation?, Study Design and Methods: We analyzed the clinical outcomes of 31,309 patients undergoing overnight polysomnography within a large hospital system. We evaluated the association of OSA severity with incident VTE, using Cox proportional hazards modeling accounting for age, sex, BMI, and common comorbid conditions., Results: Patients were of mean age 50.4 years, and 50.1% were female. There were 1,791 VTE events identified over a mean follow-up of 5.3 years. In age- and sex-adjusted analyses, each 10-event/h increase in the apnea-hypopnea index was associated with a 4% increase in incident VTE risk (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06). After adjusting for BMI, this association disappeared (HR, 1.01; 95% CI, 0.99-1.03). In contrast, nocturnal hypoxemia had an independent association with incident VTE. Patients with > 50% sleep time spent with oxyhemoglobin saturation < 90% are at 48% increased VTE risk compared with those without nocturnal hypoxemia (HR, 1.48; 95% CI, 1.16-1.69)., Interpretation: In this large cohort, we found that patients with more severe OSA as measured by the apnea-hypopnea index are more likely to have incident VTE. Adjusted analyses suggest that this association is explained on the basis of confounding by obesity. However, severe nocturnal hypoxemia may be a mechanism by which OSA heightens VTE risk., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to examine the COVID-19 pandemic and its associated impact on the provision of vascular services, and the pattern of presentation and practice in a tertiary referral vascular unit., Methods: This is a retrospective observational study from a prospectively maintained data-base comparing two time frames, Period 1(15th March-30th May 2019-P1) and Period 2(15th March-30th May 2020-P2)All the patients who presented for a vascular review in the 2 timeframes were included. Metrics of service and patient care episodes were collected and compared including, the number of emergency referrals, patient encounters, consultations, emergency admissions and interventions. Impact on key hospital resources such as critical care and imaging facilities during the two time periods were also examined., Results: There was an absolute reduction of 44% in the number of patients who required urgent or emergency treatment from P1 to P2 (141 vs 79). We noted a non-significant trend towards an increase in the proportion of patients presenting with Chronic Limb Threatening Ischaemia (CLTI) Rutherford 5&6 (P=0.09) as well as a reduction in the proportion of admissions related to Aortic Aneurysm (P=0.21). There was a significant absolute reduction of 77% in all vascular interventions from P1 to P2 with the greatest reductions noted in Carotid (P=0.02), Deep Venous (P=0.003) and Aortic interventions (P=0.016). The number of lower limb interventions also decreased though there was a significant increase as a relative proportion of all vascular interventions in P2 (P=0.001). There was an absolute reduction in the number of scans performed for vascular pathology; Duplex scans reduced by 86%(P<0.002), CT scans by 68%(P<0.003) and MRIs by 74%(P<0.009)., Conclusion: We report a decrease in urgent and emergency vascular presentations, admissions and interventions. The reduction in patients presenting with lower limb pathology was not as significant as other vascular conditions, resulting in a significant rise in interventions for CLTI and DFI as a proportion of all vascular interventions. These observations will help guide the provision of vascular services during future pandemics., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The incidence of chronic limb-threatening ischemia in diabetic patients is increasing. The factors influencing outcome after infrapopliteal revascularization in these patients are largely unknown. Therefore, this study aims to identify the impact of perioperative glucose control on the long-term outcomes in this patient cohort, and furthermore to identify other factors independently associated with outcome., Methods: Consecutive diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia were identified. Patients' demographics, procedural details, daily capillary blood glucose, and hemoglobin A1C levels were collected and analyzed against the study end points using Kaplan-Meier and Cox regression analysis., Results: A total of 437 infrapopliteal target vessels were successfully crossed in 203 patients. Amputation-free survival by Kaplan-Meier (estimate (standard error)%) was 74 (3.3)% and 63 (3.7)%, primary patency was 61 (4.2)% and 50 (4.9)%, assisted primary patency was 69 (5.2)% and 55 (6.1)%, and secondary patency was 71 (3.8)% and 59 (4.1)% at 1 year and 2 years, respectively. Cox regression analysis showed high perioperative capillary blood glucose levels to be an independent predictor of binary restenosis (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.31-1.1.78; P = .015). Postprocedural dual-antiplatelet therapy was found to be an independent predictor of amputation-free survival (HR, 1.69; 95% CI, 1.04-2.75; P = .033), and freedom from major adverse limb events (HR: 1.96; 95% CI, 1.16-3.27; P = .023) and baseline estimated glomerular filtration rate was significantly associated with better amputation-free survival (HR, 0.52; 95% CI, 0.31-0.87; P = .014)., Conclusions: Poor perioperative glycemic control is associated with a higher incidence of restenosis after infrapopliteal revascularization in diabetic patients. Dual antiplatelet therapy is associated with better outcomes in this group., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Introduction: Pediatric adrenocortical carcinoma (ACC) is a rare malignancy, encompassing less than 0.2% of all childhood malignancies. Due to the scarcity of this diagnosis, it is often managed according to guidelines established for adults, as there is a lack of reliable evidence regarding optimal adjuvant treatment options for pediatric patients. It is our aim to identify recent treatment trends as well as clinical and tumor characteristics and their impact on overall survival., Methods: Using the National Cancer Data Base (NCDB), this study identified 49 patients under 18 years old with localized ACC (M0) undergoing adrenalectomy from 2004 to 2017. Kaplan-Meier analysis was performed to determine overall survival (OS) from patient characteristics and treatments received. Comparison of survival was performed using the log rank test., Results: The median age of our cohort was 3 years old with a slight female predominance of 61%. The median tumor size was 9.4 cm, and patients older than 4 years were significantly (p = 0.03) more likely to present with larger tumors (11.33 cm vs 8.76 cm). Adjuvant treatment in the form of systemic therapy was administered in 20 of 49 (41%) patients and radiation therapy in 2 of 49 (4%) patients. Three-year OS for patients 4 years old and younger was 92.6% vs 61.8% for those older than 4 years (p = 0.002). Patients presenting with tumor size ≥9 cm had worse three-year OS compared to those with tumors <9 cm (95.24% vs 67.1% respectively, p = 0.02, Fig. 1). In patients with tumors ≥ 9 cm, younger children age 0-4 years had significantly (p = 0.04) higher OS rates than older children age 5-17 years., Conclusions: ACC is a rare pediatric malignancy with a female predominance. Those older than 4 years and those with presenting tumor size ≥9 cm have decreased overall survival rates after adrenalectomy for localized disease. Additionally, children older than 4 have poorer prognosis, even after controlling for larger tumor size. This is the largest contemporary series of localized pediatric ACC to date. However, multi-institutional prospective cohort or randomized-controlled trials are necessary to better evaluate relevant prognostic factors and the role of adjuvant therapies following adrenalectomy., Competing Interests: Conflict of interest The authors have no financial or personal relationships to disclose that could have inappropriately influenced this work., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: The standard protocol for exsanguinating trauma patients involves initial evaluation and resuscitation in the emergency department which then sets the stage for subsequent definitive care and disposition. This involves major coordination and mobilisation of resources which may cause a delay in intervention especially when most of these cases present after office hours. Our centre has employed a second-tier activation system (CHOP protocol) that immediately mobilises all respective trauma specialists including interventional radiologists and allows rapid access to the operating room., Objective: We hypothesised that exsanguinating patients managed by CHOP protocol have better overall outcome and survival., Methods: We identified trauma patients that fulfilled CHOP criteria from 2016 to 2019 and divided them into two groups: preCHOP (standard protocol) and CHOP. Data was extracted from a prospectively maintained trauma registry. Demographics, injury pattern and in-hospital data were analysed. The key outcome studied was the impact of CHOP protocol on the mortality rate. Success and failure of the two groups were analysed using CUSUM methodology., Results: Thirty-seven patients were managed by CHOP protocol since its introduction in March 2018 compared to 36 patients who underwent standard protocol. Majority of the cases were blunt trauma (89% CHOP vs 92% preCHOP). The mean Injury Severity Score was 37 for CHOP group and 39 for preCHOP group. We observed a significant improvement in time to intervention in CHOP patients (78 min vs 113 min), both during and after office hours. CHOP patients had lower mortality compared to preCHOP group (11% vs 31%) and the effectiveness of the protocol was seen in achieving significantly lower mortality compared to the predicted model. CHOP protocol was able to produce a consistent trend of desired outcomes leading to the CUSUM curve exhibiting a sustained downward slope., Conclusion: The CHOP protocol, a relatively novel system in the local context, was able to achieve sustained improved outcomes compared to standard protocol. The CUSUM analysis concurred that implementation of CHOP protocol has helped to achieve consistent desired outcomes. It also suggested that the uptake and use of this protocol has integrated well into the existing workflow., Competing Interests: Declaration of Competing Interest None declared for all authors., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Relationships between dyslipidaemia and leukocyte counts have been investigated in several studies, demonstrating limited evidence of associations in humans. As such, studying a diverse range of cohorts will ensure evidence is robust. This study focused on investigating cross-sectional and longitudinal relationships in three large-scale cohorts., Methods: The cross-sectional analysis included a total of 27,566 participants with valid data on lipid measures and leukocyte counts from three study cohorts: National Health and Nutrition Survey (NHANES), Korean National Health and Nutrition Survey (KNHANES) and Treating to New Targets (TNT) trial. The longitudinal analysis included 9323 participants with valid data on lipid measures and leukocyte counts at baseline and one year with statin treatment. Associations between lipid levels and leukocyte counts were analysed by multivariable linear regression and adjusted for basic demographic and cardiovascular risk factors., Results: Cross-sectional data from NHANES demonstrated the association of lower high-density lipoprotein (HDL) cholesterol and higher triglycerides with higher leukocyte count (0.9% lower and 0.3% higher count per 10 mg/dL increase in HDL cholesterol and triglycerides respectively, both p  < 0.001). Similar trends were found in TNT trial (both p  < 0.001), but not in KNHANES. In the TNT trial, 10 mg/dL increase in triglycerides over one year was also associated with a 0.09 × 10 3 /μL increase in leukocyte count over the same period., Conclusions: The findings of this study are consistent with those of previous human studies, supporting weak yet noteworthy associations between dyslipidaemia and leukocytosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Disparities in sleep health are important but underrecognized contributors to health disparities. Understanding the factors contributing to sleep heath disparities and developing effective interventions are critical to improving all aspects of heath. Sleep heath disparities are impacted by socioeconomic status, racism, discrimination, neighborhood segregation, geography, social patterns, and access to health care as well as by cultural beliefs, necessitating a cultural appropriateness component in any intervention devised for reducing sleep health disparities. Pediatric sleep disparities require innovative and urgent intervention to establish a foundation of lifelong healthy sleep. Tapping the vast potential of technology in improving sleep health access may be an underutilized tool to reduce sleep heath disparities. Identifying, implementing, replicating, and disseminating successful interventions to address sleep disparities have the potential to reduce overall disparities in health and quality of life., (Copyright © 2020 American College of Chest Physicians. All rights reserved.)

Large-scale randomized trials of positive airway pressure (PAP) efficacy have been largely negative but PAP adherence was notably suboptimal across the trials. To address this limitation, evidence-based PAP adherence protocols embedded within the larger trial protocol are recommended. The complexity of such protocols depends on adequacy of resources, including funding and inclusion of behavioral scientist experts on the scientific team, and trial-specific considerations (eg, target population) and methods. Recommendations for optimizing PAP adherence in large-scale trials are set forth that address rigor and reproducibility., Competing Interests: Disclosure Dr A.M. Sawyer has received grant support from NIH, American Nurses Foundation, American Lung Association, and VA HSR&D. Dr D.M. Wallace has no disclosures. Dr L.F. Buenaver discloses grant support from NIH and American Sleep Medicine Foundation. Ms A. Blase is an employee of ResMed Corp. Dr A.J. Watach discloses research training support from NIH (HL07953). Mr B. Saconi has no disclosures. Dr S.R. Patel discloses grant support from NIH (DK120051) and has received grant support from NIH, Bayer Pharmaceuticals, Philips Respironics, and Respicardia. Dr S.T. Kuna discloses grant support from NIH (DK120051). Dr N.M. Punjabi discloses grant support from NIH (NL117167, HL146709, DK120051) and from ResMed and Philips Respironics to Johns Hopkins University., (Published by Elsevier Inc.)

Background and Aims: There is some evidence of a cross-sectional, and possibly causal, relationship of lipid levels with leukocyte counts in mice and humans. This study investigates the cross-sectional and longitudinal relationship of blood lipid and lipoprotein levels with leukocyte counts in the UK Biobank cohort., Methods: The primary cross-sectional analysis included 417,132 participants with valid data on lipid measures and leukocyte counts. A subgroup analysis was performed in 333,668 participants with valid data on lipoprotein(a). The longitudinal analysis included 9058 participants with valid baseline and follow-up data on lipid and lipoprotein levels and leukocyte counts. The association of lipid and lipoprotein levels with leukocyte counts was analysed by multivariable linear regression., Results: Several relationships were significant in both cross-sectional and longitudinal analysis. After adjustment for demographic, socioeconomic and other confounding factors, a higher eosinophil count was associated with lower HDL cholesterol and apolipoprotein A-I concentration (p < 0.001). Higher triglycerides levels were associated with higher total leukocyte, basophil, eosinophil, monocyte and neutrophil counts (all p < 0.01). A higher lymphocyte count was associated with a higher apolipoprotein B level (p < 0.001). In the longitudinal analysis, lipoprotein(a) was inversely associated with basophil count in men but not women (p < 0.001)., Conclusions: Triglyceride levels demonstrate a robust positive association with total and differential leukocyte counts suggesting they may be directly involved in leukogenesis. However, unlike in murine models, the remainder of these relationships is modest, which suggests that cholesterol and lipoproteins are minimally involved in leukogenesis in humans., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: CPAP effectiveness is limited by suboptimal adherence. Prior studies of adherence have focused on middle-aged men., Research Question: Does CPAP adherence vary by age and sex?, Study Design and Methods: Telemonitoring data from a CPAP manufacturer database were used to assess adherence in patients initiating CPAP therapy between November 2015 and October 2018. Analyses were restricted to patients in the United States aged 18 to 90 years., Results: Across 789,260 patients initiated on CPAP (mean age, 55 ± 14 years; 58.2% male), overall adherence by US Centers of Medicare & Medicaid Services criteria was 72.6%, but it varied dramatically by age and sex, ranging from 51.3% in 18- to 30-year-old women to 80.6% in 71- to 80-year-old men. Patterns of use over the first 90 days demonstrated that younger age groups had peak CPAP use by the 2 nd night, with a subsequent decay in use, including abandonment of CPAP, which was greatest among 18- to 30-year-old women. In contrast, older patients steadily increase use, taking more than a week to maximize usage, and then they have much slower decays in use over time. Younger, but not older, patients have lower use of CPAP on weekends compared with weekday nights., Interpretation: CPAP adherence rates vary substantially by demographics, with 18- to 30-year-old women having the lowest adherence. The pattern of use over the first 90 days also varies substantially by age and sex. Further research to understand and address the causes of disparities will be crucial to maximizing the benefits of CPAP therapy., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the effect of implementing standardized opioid prescribing guidelines on prescription patterns for acute pain after ophthalmic surgery in opioid-naïve patients., Design: Quality improvement study., Participants: Ophthalmic surgeons in an academic department of ophthalmology., Methods: Postoperative opioid prescribing patterns were compared before and after the implementation of standardized opioid prescribing guidelines for ophthalmic surgery at an academic institution. Only prescriptions provided to opioid-naïve patients 18 years of age or older were included. Surgeons reached a consensus for standardized prescribing guidelines appropriate for the type of surgery within their subspecialty. Guidelines were disseminated in conjunction with postsurgical pain management education to all ophthalmologists in the department, including trainees. The frequency of opioid prescriptions, the quantity of opioid prescribed (converted to oral morphine equivalent [OME]), and opioid prescription refill rates were compared before and after intervention., Main Outcome Measures: Prescriptions with more than 80 OME, frequency of opioid prescriptions, mean OME, and refill rates., Results: Of 5349 ophthalmic surgeries performed during the 2 assessment periods, 196 (3.7%) were associated with opioid prescriptions for acute postoperative pain. The frequency of opioid prescriptions decreased to 3.0% (81/2736) after intervention compared with 4.4% (115/2613) before intervention (P = 0.005). When opioids were prescribed, the mean OME decreased from 93 (range, 27-500) before intervention to 42 (range, 14-100) after intervention (P = 0.003). The number of prescriptions for more than 80 OME decreased from 56 (2.1%) before intervention to 4 (0.1%) after intervention (P < 0.001). Based on the standardized guidelines, 103 of the 115 (89.6%) preintervention opioid prescriptions would not have adhered to the guidelines, whereas 39 of the 81 (48.1%) postintervention prescriptions did not adhere to the guidelines (P < 0.001). The proportion of refill prescriptions did not differ before and after intervention (P = 0.44)., Conclusions: The process of discussing postsurgical pain management and developing standardized opioid prescribing guidelines reduces overprescribing of opioids after ophthalmic surgery without increasing refill rates. Continued education is required to improve adherence to the prescribing guidelines further., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) includes two instruments to quantify sleep symptoms (sleep disturbance [SDA] and sleep-related impairment [SRI]) in diverse populations across a wide symptom spectrum. However, the responsiveness of PROMIS measures to treatment of sleep disorders is unknown. We examined the responsiveness of the PROMIS sleep scales to the treatment of OSA., Methods: We collected SDA, SRI, and Epworth Sleepiness Scale (ESS) before and after initiation of positive airway pressure (PAP) in patients with type 2 diabetes newly diagnosed with OSA. To compare responsiveness, we compared effect sizes and classifications of symptom improvement using both the reliable change method and thresholds of minimum important difference (MID)., Results: A total of 103 patients completed assessments pre- and post-PAP. SDA, SRI, and ESS scores all declined significantly with PAP therapy. We observed the largest effect size for SDA (-0.64; 95% CI, -0.86 to -0.42), followed by SRI (-0.43; 95% CI, -0.63 to -0.23), and ESS (-0.28; 95% CI, -0.42 to -0.15). More patients experienced the reliable change category of symptom remission categorized by the PROMIS measures (SDA: 23.3%; SRI: 31.1%) relative to the ESS (5.8%) (P < .001 for both). Using the MID, SDA and SRI also classified more patients as improved (SDA: 54.4%; SRI: 49.5%) relative to the ESS (35.0%) (P < .001 for both pairwise comparisons)., Conclusions: PROMIS sleep measures were more likely than the ESS to detect an improvement with PAP therapy. Incorporating PROMIS measures into research and clinical care may provide a more sensitive assessment of symptomatic response to OSA treatment., (Published by Elsevier Inc.)

Purpose: To determine if Scheimpflug tomography pachymetry map and posterior elevation map patterns, central corneal thickness (CCT), and corneal backscatter can predict the prognosis of Fuchs endothelial corneal dystrophy (FECD)., Design: Cross-sectional study with follow-up of outcomes., Participants: Ninety-six eyes (56 subjects) with a range of severity of FECD., Methods: Corneas were graded by cornea specialists according to the area and confluence of guttae and the presence of clinically definite edema. Masked and randomized Scheimpflug imaging pachymetry map and posterior elevation map patterns were assessed by 1 observer for loss of regular isopachs, displacement of the thinnest point of the cornea, and the presence of posterior surface depression. The prognosis of eyes over a 5-year (median) follow-up period was determined based on FECD progression (new onset of clinically definite edema or ≥5% increase in CCT) or intervention by endothelial keratoplasty. Cumulative probabilities of progression and intervention were estimated from survival analyses, with risk factors determined by using Cox proportional hazards models., Main Outcome Measures: Pachymetry map and posterior elevation map patterns, corneal backscatter, and CCT (ultrasonic pachymetry)., Results: In univariate analyses, loss of regular isopachs (hazard ratio [HR], 18.00) displacement of the thinnest point (HR, 11.53), focal posterior surface depression (HR, 10.21), and anterior corneal backscatter (HR, 1.22, per 1-grayscale unit increment), were risk factors for progression or intervention (P < 0.001), whereas CCT (HR, 1.30, per 25-μm increment) was not (P = 0.15). In multivariate analyses, loss of regular isopachs (HR, 11.57; P < 0.001) and displacement of the thinnest point (HR, 5.61; P = 0.02) were independent and clinically important risk factors for progression and intervention. The 5-year cumulative risk of disease progression and intervention was 7%, 48%, and 89% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P <0.001). The 4-year cumulative risk of disease progression and intervention after uncomplicated cataract surgery was 0%, 50%, and 75% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P < 0.001)., Conclusions: Three Scheimpflug tomography pachymetry map and posterior elevation map patterns can predict FECD prognosis independent of CCT. The risk of FECD progression and intervention, including after uncomplicated cataract surgery, increases according to the number of parameters present., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Classic Hodgkin lymphoma (cHL) is a tumor composed of rare, atypical, germinal center-derived B cells (Hodgkin Reed-Sternberg [HRS] cells) embedded within a robust but ineffective inflammatory milieu. The cHL tumor microenvironment (TME) is compartmentalized into "niches" rich in programmed cell death-1 ligand (PD-L1)-positive HRS cells and tumor-associated macrophages (TAMs), which associate with PD-1-positive T cells to suppress antitumor immunity via PD-L1/PD-1 signaling. Despite the exquisite sensitivity of cHL to PD-1 checkpoint blockade, most patients eventually relapse and need therapeutic alternatives. Using multiplex immunofluorescence microscopy with digital image analysis, we found that cHL is highly enriched for non-T-regulatory, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-positive T cells (compared with reactive lymphoid tissues) that outnumber PD-1-positive and lymphocyte-activating gene-3 (LAG-3)-positive T cells. In addition, T cells touching HRS cells are more frequently positive for CTLA-4 than for PD-1 or LAG-3. We further found that HRS cells, and a subset of TAMs, are positive for the CTLA-4 ligand CD86 and that the fractions of T cells and TAMs that are CTLA-4-positive and CD86-positive, respectively, are greater within a 75 μm HRS cell niche relative to areas outside this region (CTLA-4, 38% vs 18% [P = .0001]; CD86, 38% vs 24% [P = .0007]). Importantly, CTLA-4-positive cells are present, and focally contact HRS cells, in recurrent cHL tumors following a variety of therapies, including PD-1 blockade. These results implicate CTLA-4:CD86 interactions as a component of the immunologically privileged niche surrounding HRS cells and raise the possibility that patients with cHL refractory to PD-1 blockade may benefit from CTLA-4 blockade., (© 2019 by The American Society of Hematology.)

Background: Percutaneous transluminal angioplasty (PTA) is a common procedure in patients with peripheral arterial disease (PAD) affecting the femoropopliteal segment (F-P). Biomimetic nitinol stents (Supera peripheral stent, SPS) and drug eluting stents (DES) were designed to improve the longevity of F-P PTA; however, their performance has not been compared in a pragmatic setting, taking atherosclerotic plaque characteristics into account., Methods: Overall, 296 consecutive patients (mean age: 73 y, SD: 11 y, 65% male, 68% with chronic limb threatening ischaemia) who underwent F-P PTA using SPS or DES between 2013 and 2018 were identified from a prospectively maintained institutional database. Patient and plaque characteristics, including F-P plaque characterisation based on computed tomography, were collected; 121 case matched pairs were created using a propensity score based on patient and plaque data., Results: During the median two year follow up, 28% of the cohort (32% SPS vs. 24% DES, p = .07) developed target lesion restenosis (TLR) > 50%. Among the 121 case matched pairs of patients, those with SPS vs. DES were not significantly more likely to develop TLR >50% (31% vs. 27%, p = .34), or stent occlusion (13% vs. 12%, p = .85 - secondary patency rate 87% vs. 88%), have a major amputation (10% vs. 6%, p = .16), require re-intervention (14% vs. 9%, p = .12), or die (7% vs.4%, p = .31). Plaque calcification did not predict restenosis or occlusion in either stent group, both in the matched and non matched populations. Multivariable analysis adjusted for patient and plaque characteristics revealed that the main predictors of restenosis >50% at two years were female sex [odds ratio (OR): 2.05, p = .01], hypertension (OR: 2.10, p = .04) and previous F-P occlusion (OR: 1.35, p = .04)., Conclusion: Medium term results following F-P PTA with either SPS or DES are comparable, regardless of plaque calcification and patient characteristics., (Copyright © 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Short sleep may be a risk factor for atrial fibrillation. However, previous investigations have been limited by lack of objective sleep measurement and small sample size. We sought to determine the association between objectively measured sleep duration and atrial fibrillation., Methods: All 31,079 adult patients undergoing diagnostic polysomnography from 1999 to 2015 at multiple sites within a large hospital network were identified from electronic medical records. Prevalent atrial fibrillation was identified by continuous ECG during polysomnography. Incident atrial fibrillation was identified by diagnostic codes and 12-lead ECGs. Logistic regression and Cox proportional hazards modeling were used to examine the association of sleep duration and atrial fibrillation prevalence and incidence, respectively, adjusting for age, sex, BMI, hypertension, coronary artery disease, cerebrovascular disease, peripheral vascular disease, heart failure, and sleep apnea severity., Results: We identified 404 cases of prevalent atrial fibrillation among 30,061 individuals (mean age ± SD, 51.0 ± 14.5 years; 51.6% women) undergoing polysomnography. After adjustment, each 1-h reduction in sleep duration was associated with a 1.17-fold (95% CI, 1.11-1.30) increased risk of prevalent atrial fibrillation. Among 27,589 patients without atrial fibrillation at baseline, we identified 1,820 cases of incident atrial fibrillation over 4.6 years median follow-up. After adjustment, each 1-h reduction in sleep duration was associated with a 1.09-fold (95% CI, 1.05-1.13) increased risk for incident atrial fibrillation., Conclusions: Short sleep duration is independently associated with prevalent and incident atrial fibrillation. Further research is needed to determine whether interventions to extend sleep can lower atrial fibrillation risk., (Published by Elsevier Inc.)

Objective: To assess the safety and immunogenicity of the MF59-adjuvanted seasonal trivalent inactivated influenza vaccine (aIIV3; Fluad) in children aged 6 months through 5 years who are at risk of influenza complications., Methods: A retrospective analysis was performed to examine unsolicited adverse events (AEs) in an integrated dataset from six randomized clinical studies that compared aIIV3 with non-adjuvanted inactivated influenza vaccines (IIV3). The integrated safety set comprised 10 784 children, of whom 373 (3%) were at risk of influenza complications., Results: The at-risk safety population comprised 373 children aged 6 months through 5 years: 179 received aIIV3 and 194 received non-adjuvanted IIV3 (128 subjects received a licensed IIV3). The most important risk factors were respiratory system illnesses (62-70%) and infectious and parasitic diseases (33-39%). During the treatment period, unsolicited AEs occurred in 54% of at-risk children and 55% of healthy children who received aIIV3; of those receiving licensed IIV3, 59% of at-risk and 62% of healthy subjects reported an unsolicited AE. The most common AEs were infections, including upper respiratory tract infection. Serious AEs (SAEs) were reported in <10% of at-risk subjects, and no vaccine-related SAEs were observed. In the immunogenicity subset (involving 103 participants from one study), geometric mean titers (GMTs) were approximately 2- to 3-fold higher with aIIV3 than with IIV3 for all three homologous strains (A/H1N1, A/H3N2, and B). Seroconversion rates were high for both aIIV3 (79-96%) and IIV3 (83-89%)., Conclusions: In young children at risk of influenza complications, aIIV3 was well-tolerated and had a safety profile that was generally similar to that of non-adjuvanted IIV3. Similar to the not-at-risk population, the immune response in at-risk subjects receiving aIIV3 was increased over those receiving IIV3, suggesting aIIV3 is a valuable option in young children at risk of influenza complications., (Copyright © 2019. Published by Elsevier Ltd.)

Background: There is a scarcity of published data on the global prevalence of obstructive sleep apnoea, a disorder associated with major neurocognitive and cardiovascular sequelae. We used publicly available data and contacted key opinion leaders to estimate the global prevalence of obstructive sleep apnoea., Methods: We searched PubMed and Embase to identify published studies reporting the prevalence of obstructive sleep apnoea based on objective testing methods. A conversion algorithm was created for studies that did not use the American Academy of Sleep Medicine (AASM) 2012 scoring criteria to identify obstructive sleep apnoea, allowing determination of an equivalent apnoea-hypopnoea index (AHI) for publications that used different criteria. The presence of symptoms was not specifically analysed because of scarce information about symptoms in the reference studies and population data. Prevalence estimates for obstructive sleep apnoea across studies using different diagnostic criteria were standardised with a newly developed algorithm. Countries without obstructive sleep apnoea prevalence data were matched to a similar country with available prevalence data; population similarity was based on the population body-mass index, race, and geographical proximity. The primary outcome was prevalence of obstructive sleep apnoea based on AASM 2012 diagnostic criteria in individuals aged 30-69 years (as this age group generally had available data in the published studies and related to information from the UN for all countries)., Findings: Reliable prevalence data for obstructive sleep apnoea were available for 16 countries, from 17 studies. Using AASM 2012 diagnostic criteria and AHI threshold values of five or more events per h and 15 or more events per h, we estimated that 936 million (95% CI 903-970) adults aged 30-69 years (men and women) have mild to severe obstructive sleep apnoea and 425 million (399-450) adults aged 30-69 years have moderate to severe obstructive sleep apnoea globally. The number of affected individuals was highest in China, followed by the USA, Brazil, and India., Interpretation: To our knowledge, this is the first study to report global prevalence of obstructive sleep apnoea; with almost 1 billion people affected, and with prevalence exceeding 50% in some countries, effective diagnostic and treatment strategies are needed to minimise the negative health impacts and to maximise cost-effectiveness., Funding: ResMed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To demonstrate the potential of an MF59-adjuvanted inactivated trivalent seasonal influenza vaccine (aIIV3; Fluad™) to improve the immune response in young children, we review the immunogenicity, efficacy, and safety/tolerability of aIIV3 from a comprehensive clinical development program in a pediatric population with a specific need for improved influenza vaccines., Methods: Data were analyzed from a series of 1 phase Ib, 3 phase II, and 2 phase III studies involving 11,942 children aged 6 months through 5years., Results: The clinical data showed that aIIV3 had statistically significantly greater immunogenicity and efficacy in the prevention of influenza compared to conventional inactivated trivalent seasonal influenza vaccines (IIV3s). The safety profile of aIIV3 was generally similar to that of nonadjuvanted IIV3, apart from an increased frequency of solicited adverse events (AEs) following vaccination. The majority of solicited AEs were mild or moderate in severity and resolved within 1 to 3 days., Conclusions: aIIV3 was well tolerated, with immunogenicity and efficacy exceeding that of conventional IIV3 in children 6 months through 5years of age. The MF59-adjuvanted vaccine has the potential to fulfill an unmet clinical need in the prevention of seasonal influenza in this age group., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The relationship of poor sleep patterns to the increased risk of obesity has been reported, but the results are variable. This study evaluated the association between objectively measured sleep patterns and obesity in a representative adult population of Hispanic/Latino subjects living in the United States., Methods: This cross-sectional study was an analysis of a multicenter, community-based cohort of 2,156 participants aged 18 to 64 years from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Recruitment was conducted in San Diego, California; Chicago, Illinois; Bronx, New York; and Miami, Florida. Models were controlled for age, sex, ethnic background, site, income, education, and apnea-hypopnea index. Seven days of wrist actigraphy data were collected. Obesity was defined as BMI ≥ 30 kg/m 2 , and abdominal obesity was defined as waist circumference ≥ 88 cm in women and ≥ 102 cm in men. Napping was defined as more than one 15-min nap per week., Results: An inverse linear relationship was found between sleep duration and prevalence of obesity (P linear trend ≤ 0.01). A reduction of 1 h sleep increased obesity prevalence by 4.1% (95% CI, 1.6-6.6; P = .002) and abdominal obesity prevalence by 3.6% (95% CI, 1.1-6.1; P = .007). Daytime napping increased obesity prevalence by 10.4% (95% CI, 3.5-17.3; P = .004) and abdominal obesity prevalence by 7.1% (95% CI, 1.0-13.2; P = .02)., Conclusions: In a population of young to older adult Hispanic/Latino subjects, we found an inverse linear association between sleep duration and the prevalence of obesity. Daytime napping was strongly associated with greater adiposity. Interventional and longitudinal studies are needed to better understand how abnormal sleep patterns contribute to the obesity epidemic., (Published by Elsevier Inc.)

Purpose: To determine whether preoperative endothelial cell density (ECD) and postoperative ECD after Descemet stripping automated endothelial keratoplasty (DSAEK) are associated with late endothelial graft failure (LEGF) in the Cornea Preservation Time Study (CPTS)., Design: Cohort study within a multicenter, randomized clinical trial., Participants: A total of 1007 individuals (1223 study eyes), mean age 70 years, undergoing DSAEK for Fuchs' dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE) (6% of eyes) and followed for up to 5 years., Methods: Central ECD was determined by a central image analysis reading center. Preoperative ECD was determined for 1209 eyes that did not fail and 14 eyes that experienced LEGF. The ECD at 6 and 12 months after DSAEK, the change in ECD from preoperative to 6 and 12 months, surgeon-reported operative complications, and postoperative graft dislocation were investigated for an association with LEGFs unrelated to other postoperative events. Univariable and multivariable Cox proportional hazards regression models were used to assess associations., Main Outcome Measures: Late endothelial graft failure and its associations with pre- and postoperative ECD and operative complications., Results: The cumulative probability of LEGF was 1.3% (95% confidence interval [CI], 0.8%-2.4%). Median (interquartile range [IQR]) preoperative ECDs were similar for eyes with LEGF (2523; 2367-3161) cells/mm 2 ) and eyes without failure (2727; 2508-2973) cells/mm 2 ) (P = 0.34). The ECD at 6 months was associated with LEGF (P < 0.001) in time-to-event analyses, whereas preoperative ECD was not (P = 0.55). The cumulative incidence (95% CI) of LEGF was 6.5% (3.0%, 14.0%) for 97 grafts with a 6-month ECD less than 1200 cells/mm 2 , 0.3% (0.0%, 2.4%) for 310 grafts with a 6-month ECD between 1200 and 2000 cells/mm 2 , and 0.6% (0.1%, 2.7%) for 589 grafts with a 6-month ECD greater than 2000 cells/mm 2 . In multivariable analyses, ECD at 6 months and operative complications were both associated with LEGF (P = 0.002 and P = 0.01, respectively), whereas graft dislocation was not (P = 0.61)., Conclusions: In eyes undergoing DSAEK, preoperative ECD is unrelated to LEGF, whereas lower ECD at 6 months is associated with LEGF. Early endothelial cell loss after DSAEK and intraoperative complications should be minimized to improve graft survival., (Copyright © 2019 American Academy of Ophthalmology. All rights reserved.)

Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997., (© 2019 by The American Society of Hematology.)

Objectives: The aim of this study was to perform a comprehensive meta-analysis comparing all therapeutic modalities for intermittent claudication (IC), including best medical therapy (BMT) alone, percutaneous angioplasty (PTA), supervised exercise therapy (SET), and PTA combined with SET, to establish the optimal first-line treatment for IC., Background: IC is a common health problem that limits physical activity, results in decreased quality of life (QoL) and is associated with poor cardiovascular outcomes. Previous meta-analyses have attempted to combine data from randomized trials; however, none have combined data from all possible treatment combinations or synthesized QoL outcomes., Methods: Following a systematic review of the published research (conducted in December 2018) that identified 37 published randomized trials, a network meta-analysis was performed combining all possible IC treatment strategies., Results: Overall, 2,983 patients with IC were included (mean weighted age 68 years, 54.5% men). Comparisons were performed between BMT (n = 688, 28 arms) versus SET (n = 1,189, 35 arms) versus PTA (n = 511, 12 arms) versus PTA plus SET (n = 395, 8 arms). Mean weighted follow-up was 12 months (95% confidence interval: 9 to 23 months). Compared with BMT alone, PTA plus SET outperformed other treatment strategies, with a maximum walking distance gain of 290 m (95% credible interval: 180 to 390 m; p < 0.001). A variety of QoL assessments using validated tools were reported in 15 trials; PTA plus SET was superior to other treatments (Cohen's D = 1.8; 95% credible interval: 0.21 to 3.4)., Conclusions: In addition to BMT, PTA combined with SET seems to be the optimal first-line treatment strategy for IC in terms of maximum walking distance and QoL improvement., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)