Clonal hematopoiesis, cardiovascular events and treatment benefit in 63,700 individuals from five TIMI randomized trials.

Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with an increased risk of cardiovascular (CV) disease in the general population. Currently, it is unclear whether this association is observed in large clinical trial cohorts with a high burden of existing CV disease or whether CV therapies can mitigate CHIP-associated CV risk. To address these questions, we studied 63,700 patients from five randomized trials that tested established therapies for CV disease, including treatments targeting the proteins PCSK9, SGLT2, P2Y12 and FXa. During a median follow-up of 2.5 years, 7,453 patients had at least one CV event (CV death, myocardial infarction (MI), ischemic stroke or coronary revascularization). The adjusted hazard ratio (aHR) for CV events for CHIP+ patients was 1.07 (95% CI: 0.99-1.16, P = 0.08), with consistent risk estimates across each component of CV risk. Significant heterogeneity in the risk of MI was observed, such that CHIP+ patients had a 30% increased risk of first MI (aHR = 1.31 (1.05-1.64), P = 0.02) but no increased risk of recurrent MI (aHR = 0.94 (0.79-1.13), Pint = 0.008), as compared to CHIP- patients. Moreover, no significant heterogeneity in treatment effect between individuals with and without CHIP was observed for any of the therapies studied in the five trials. These results indicate that in clinical trial populations, CHIP is associated with incident but not recurrent coronary events and that the presence of CHIP does not appear to identify patients who will derive greater benefit from commonly used CV therapies.

[Exercise addiction]. / Addiction à l'exercice.

Exercise addiction, although not yet officially recognized, can be defined as the harmful practice of physical exercise, described as a compulsive need, where damage take precedence over the benefits of this practice, with a continuation of this behavior despite the negative consequences. A number of risk factors have been identified, including psychopathological conditions such as eating disorders or other addictions. It is possible to detect this addiction and assess its intensity using multidimensional questionnaires, even the clinical relevance and thresholds of which are still debated. Despite the absence of validated treatments, motivational approaches and cognitive-behavioural therapies can be useful, combined with nutritional management if necessary, as well as management of concomitant disorders.

L'addiction à l'exercice peut être définie par une pratique compulsive de l'exercice physique, où les dommages prennent le pas sur les bienfaits, avec une poursuite du comportement malgré les conséquences négatives. Certains facteurs de risque individuels, environnementaux, et propres au sport ont été identifiés tels que la recherche d'une amélioration des performances, des troubles du comportement alimentaire, ou d'autres addictions. Il est possible de détecter cette addiction et d'en évaluer l'intensité grâce à des questionnaires dont la pertinence clinique et les seuils sont encore discutés. Malgré l'absence de traitements validés, l'approche motivationnelle et les thérapies cognitives et comportementales peuvent être utiles, associées à une prise en charge nutritionnelle si nécessaire, ainsi que le traitement des troubles concomitants.

Silk fibroin as a surfactant for water-based nanofabrication.

Water-based processing plays a crucial role in high technology, especially in electronics, material sciences and life sciences, with important implications in the development of high-quality reliable devices, fabrication efficiency, safety and sustainability. At the micro- and nanoscale, water is uniquely enabling as a bridge between biological and technological systems. However, new approaches are needed to overcome fundamental challenges that arise from the high surface tension of water, which hinders wetting and, thus, fabrication at the bio-nano interface. Here we report the use of silk fibroin as a surfactant to enable water-based processing of nanoscale devices. Even in minute quantities (for example, 0.01 w/v%), silk fibroin considerably enhances surface coverage and outperforms commercial surfactants in precisely controlling interfacial energy between water-based solutions and hydrophobic surfaces. This effect is ascribed to the amphiphilic nature of the silk molecule and its adaptive adsorption onto substrates with diverse surface energy, facilitating intermolecular interactions between unlikely pairs of materials. The approach's versatility is highlighted by manufacturing water-processed nanodevices, ranging from transistors to photovoltaic cells. Its performance is found to be equivalent to analogous vacuum-processed devices, underscoring the utility and versatility of this approach for water-based nanofabrication.

Risk of new-onset diabetes and efficacy of pharmacological weight loss therapy.

AIMS: To develop a clinical risk model to identify individuals at higher risk of developing new-onset diabetes and who might benefit more from weight loss pharmacotherapy. MATERIALS AND METHODS: A total of 21 143 patients without type 2 diabetes at baseline from two TIMI clinical trials of stable cardiovascular patients were divided into a derivation (~2/3) and validation (~1/3) cohort. The primary outcome was new-onset diabetes. Twenty-seven candidate risk variables were considered, and variable selection was performed using multivariable Cox regression. The final model was evaluated for discrimination and calibration, and for its ability to identify patients who experienced a larger benefit from the weight loss medication lorcaserin in terms of risk of new-onset diabetes. RESULTS: During a median (interquartile range) follow-up of 2.3 (1.8-2.7) years, new-onset diabetes occurred in 1013 patients (7.7%). The final model included five independent predictors (glycated haemoglobin, fasting glucose, age, body mass index, and triglycerides/high-density lipoprotein). The clinical risk model showed good discrimination (Harrell's C-indices 0.802, 95% confidence interval [CI] 0.788-0.817 and 0.807, 95% CI 0.788-0.826) in the derivation and validation cohorts. The calibration plot demonstrated adequate calibration (2.5-year area under the curve was 81.2 [79.1-83.5]). While hazard ratios for new-onset diabetes with a weight-loss therapy were comparable across risk groups (annual risks of <1%, 1%-5%, and >5%), there was a sixfold gradient in absolute risk reduction from lowest to highest risk group (p = 0.027). CONCLUSIONS: The developed clinical risk model effectively predicts new-onset diabetes, with potential implications for personalized patient care and therapeutic decision making.

Application of the Win Ratio Method in the ENGAGE AF-TIMI 48 Trial Comparing Edoxaban With Warfarin in Patients With Atrial Fibrillation.

BACKGROUND: Cardiovascular trials often use a composite end point and a time-to-first event model. We sought to compare edoxaban versus warfarin using the win ratio, which offers data complementary to time-to-first event analysis, emphasizing the most severe clinical events. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind, randomized trial in which patients with atrial fibrillation were assigned 1:1:1 to a higher dose edoxaban regimen (60/30 mg daily), a lower dose edoxaban regimen (30/15 mg daily), or warfarin. In an exploratory analysis, we analyzed the trial outcomes using an unmatched win ratio approach. The win ratio for each edoxaban regimen was the total number of edoxaban wins divided by the number of warfarin wins for the following ranked clinical outcomes: 1: death; 2: hemorrhagic stroke; 3: ischemic stroke/systemic embolic event/epidural or subdural bleeding; 4: noncerebral International Society on Thrombosis and Haemostasis major bleeding; and 5: cardiovascular hospitalization. RESULTS: 21 105 patients were randomized to higher dose edoxaban regimen (N=7035), lower dose edoxaban regimen (N=7034), or warfarin (N=7046), yielding >49 million pairs for each treatment comparison. The median age was 72 years, 38% were women, and 59% had prior vitamin K antagonist use. The win ratio was 1.11 (95% CI, 1.05-1.18) for higher dose edoxaban regimen versus warfarin and 1.11 (95% CI, 1.05-1.18) for lower dose edoxaban regimen versus warfarin. The favorable impacts of edoxaban on death (34% of wins) and cardiovascular hospitalization (41% of wins) were the major contributors to the win ratio. Results consistently favored edoxaban in subgroups based on creatine clearance and dose reduction at baseline, with heightened benefit among those without prior vitamin K antagonist use. CONCLUSIONS: In a win ratio analysis of the ENGAGE AF-TIMI 48 trial, both dose regimens of edoxaban were superior to warfarin for the net clinical outcome incorporating ischemic and bleeding events. As the win ratio emphasizes the most severe clinical events, this analysis supports the superiority of edoxaban over warfarin in patients with atrial fibrillation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781391.

Estimating and presenting hazard ratios and absolute risks from a Cox model with complex nonlinear interactions.

Interaction analysis is a critical component of clinical and public health research and represents a key topic in precision health and medicine. In applied settings, however, interaction assessment is usually limited to the test of a product term in a regression model and to the presentation of results stratified by levels of additional covariates. Stratification of results often relies on categorizing or making linearity assumptions for continuous covariates, with substantial loss of precision and of relevant information. In time-to-event analysis, moreover, interaction assessment is often limited to the multiplicative hazard scale by inclusion of a product term in a Cox regression model, disregarding the clinically relevant information that is captured by the absolute risk scale. In this paper we present a user-friendly procedure, based on the prediction of individual absolute risks from the Cox model, for the estimation and presentation of interactive effects on both the multiplicative and additive scales in survival analysis. We describe how to flexibly incorporate interactions with continuous covariates, which potentially operate in a nonlinear fashion, provide software for replicating our procedure, and discuss different approaches to deriving CIs. The presented approach will allow clinical and public health researchers to assess complex relationships between multiple covariates as they relate to a clinical endpoint, and to provide a more intuitive and precise depiction of the results in applied research papers focusing on interaction and effect stratification.

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

Chromosome evolution screens recapitulate tissue-specific tumor aneuploidy patterns.

Whole chromosome and arm-level copy number alterations occur at high frequencies in tumors, but their selective advantages, if any, are poorly understood. Here, utilizing unbiased whole chromosome genetic screens combined with in vitro evolution to generate arm- and subarm-level events, we iteratively selected the fittest karyotypes from aneuploidized human renal and mammary epithelial cells. Proliferation-based karyotype selection in these epithelial lines modeled tissue-specific tumor aneuploidy patterns in patient cohorts in the absence of driver mutations. Hi-C-based translocation mapping revealed that arm-level events usually emerged in multiples of two via centromeric translocations and occurred more frequently in tetraploids than diploids, contributing to the increased diversity in evolving tetraploid populations. Isogenic clonal lineages enabled elucidation of pro-tumorigenic mechanisms associated with common copy number alterations, revealing Notch signaling potentiation as a driver of 1q gain in breast cancer. We propose that intrinsic, tissue-specific proliferative effects underlie tumor copy number patterns in cancer.

Lipoprotein(a), C-Reactive Protein, and Cardiovascular Risk in Primary and Secondary Prevention Populations.

Importance: Elevated lipoprotein(a) (Lp[a]) is a putative causal risk factor for atherosclerotic cardiovascular disease (ASCVD). There are conflicting data as to whether Lp(a) may increase cardiovascular risk only in the presence of concomitant inflammation. Objective: To investigate whether Lp(a) is associated with cardiovascular risk independent of high-sensitivity C-reactive protein (hs-CRP) in both primary and secondary prevention populations. Design, Setting, and Participants: This cohort study uses data from 3 distinct cohorts, 1 population-based cohort and 2 randomized clinical trials. Participants included individuals from the UK Biobank (data from 2006-2010) without prevalent ASCVD, participants in the FOURIER (TIMI 59) trial (data from 2013-2017) who had baseline Lp(a) and hs-CRP data, and participants in the SAVOR-TIMI 53 trial (data from 2010-2013) who had prevalent ASCVD and baseline values for Lp(a) and hs-CRP. The data analysis took place from November 2022 to November 2023. Exposure: Baseline plasma Lp(a), considered either as a continuous variable or dichotomized at 125 nmol/L. Main Outcomes and Measures: Risk of major adverse cardiovascular events (MACE) (composite of cardiovascular death, myocardial infarction [MI], or ischemic stroke), the individual MACE components, and peripheral artery disease (PAD). Results: Among 357 220 individuals in the UK Biobank without prevalent ASCVD, 232 699 (65%) had low hs-CRP (<2 mg/L), and 124 521 (35%) had high hs-CRP (≥2 mg/L) values. In a Cox proportional hazard model adjusted for ASCVD risk factors, higher Lp(a) was associated with increased cardiovascular risk regardless of baseline hs-CRP value for MACE (hs-CRP ≥2 mg/L: hazard ratio [HR] per 50-nmol/L higher Lp[a], 1.05; 95% CI, 1.04-1.07; P < .001; for hs-CRP <2 mg/L: HR, 1.05; 95% CI, 1.04-1.07; P < .001; P = .80 for interaction), as well as MI, ischemic stroke, and PAD individually. Among 34 020 individuals in the FOURIER and SAVOR trials with baseline cardiometabolic disease, there were 17 643 (52%) with low and 16 377 (48%) with high baseline hs-CRP values. In Cox proportional hazard models using aggregated data from FOURIER and SAVOR, higher baseline Lp(a) was associated with increased cardiovascular risk regardless of baseline hs-CRP for MACE (hs-CRP ≥2 mg/L: HR per 50-nmol/L higher Lp[a], 1.02; 95% CI, 1.00-1.05; P = .04; hs-CRP <2 mg/L: HR, 1.05; 95% CI, 1.02-1.08; P < .001; P = .16 for interaction), MI, and PAD. Conclusions and Relevance: In this study, higher levels of Lp(a) were associated with MACE, MI, and PAD in both primary and secondary prevention populations regardless of baseline hs-CRP value.

Novel Polygenic Risk Score and Established Clinical Risk Factors for Risk Estimation of Aortic Stenosis.

Importance: Polygenic risk scores (PRSs) have proven to be as strong as or stronger than established clinical risk factors for many cardiovascular phenotypes. Whether this is true for aortic stenosis remains unknown. Objective: To develop a novel aortic stenosis PRS and compare its aortic stenosis risk estimation to established clinical risk factors. Design, Setting, and Participants: This was a longitudinal cohort study using data from the Million Veteran Program (MVP; 2011-2020), UK Biobank (2006-2010), and 6 Thrombolysis in Myocardial Infarction (TIMI) trials, including DECLARE-TIMI 58 (2013-2018), FOURIER (TIMI 59; 2013-2017), PEGASUS-TIMI 54 (2010-2014), SAVOR-TIMI 53 (2010-2013), SOLID-TIMI 52 (2009-2014), and ENGAGE AF-TIMI 48 (2008-2013), which were a mix of population-based and randomized clinical trials. Individuals from UK Biobank and the MVP meeting a previously validated case/control definition for aortic stenosis were included. All individuals from TIMI trials were included unless they had a documented preexisting aortic valve replacement. Analysis took place from January 2022 to December 2023. Exposures: PRS for aortic stenosis (developed using data from MVP and validated in UK Biobank) and other previously validated cardiovascular PRSs, defined either as a continuous variable or as low (bottom 20%), intermediate, and high (top 20%), and clinical risk factors. Main Outcomes: Aortic stenosis (defined using International Classification of Diseases or Current Procedural Terminology codes in UK Biobank and MVP or safety event data in the TIMI trials). Results: The median (IQR) age in MVP was 67 (57-73) years, and 135 140 of 147 104 participants (92%) were male. The median (IQR) age in the TIMI trials was 66 (54-78) years, and 45 524 of 59 866 participants (71%) were male. The best aortic stenosis PRS incorporated 5 170 041 single-nucleotide variants and was associated with aortic stenosis in both the MVP testing sample (odds ratio, 1.41; 95% CI, 1.37-1.45 per 1 SD PRS; P = 4.6 × 10-116) and TIMI trials (hazard ratio, 1.44; 95% CI, 1.27-1.62 per 1 SD PRS; P = 3.2 × 10-9). Among genetic and clinical risk factors, the aortic stenosis PRS performed comparably to most risk factors besides age, and within a given age range, the combination of clinical and genetic risk factors was additive, providing a 3- to 4-fold increased gradient of risk of aortic stenosis. However, the addition of the aortic stenosis PRS to a model including clinical risk factors only improved risk discrimination of aortic stenosis by 0.01 to 0.02 (C index in MVP: 0.78 with clinical risk factors, 0.79 with risk factors and aortic stenosis PRS; C index in TIMI: 0.71 with clinical risk factors, 0.73 with risk factors and aortic stenosis PRS). Conclusions: This study developed and validated 1 of the first aortic stenosis PRSs. While aortic stenosis genetic risk was independent from clinical risk factors and performed comparably to all other risk factors besides age, genetic risk resulted in only a small improvement in overall aortic stenosis risk discrimination beyond age and clinical risk factors. This work sets the stage for further development of an aortic stenosis PRS.

[The end of dialysis: the weariness to carry on]. / Médecin et patient face à l'arrêt de la dialyse : la fatigue de continuer.

Voluntary cessation of hemodialysis is a common cause of death in dialysis patients, often occurring related to an alteration in their quality of life. At the same time, psychiatric disorders such as depression or anxiety are common and often underestimated among these patients, that accentuate the suffering and complicate compliance with dialysis. In this paper some psychopathological conditions will be addressed, as well as the question of the patient's ambivalence towards dialysis and the clinical and ethical dilemma of caregivers: respect the patient's choice to stop treatment or keep them alive at all costs? A multidisciplinary approach, including palliative care, is essential to support the reflection and make balanced decisions while respecting patient autonomy.

L'arrêt volontaire de l'hémodialyse est une cause fréquente de décès chez les patients dialysés, survenant souvent en lien avec une détérioration de leur qualité de vie. Parallèlement, les conditions psychiatriques comme la dépression ou l'anxiété sont répandues et souvent sous-estimées chez ces patients, en accentuant la souffrance et en compliquant la compliance à la dialyse. Dans cet article, sont abordées certaines conditions psychopathologiques, ainsi que la question de l'ambivalence du patient face à la dialyse et le dilemme clinique et éthique des soignants: respecter le choix du patient d'arrêter le traitement ou le maintenir en vie à tout prix? Une approche pluridisciplinaire, incluant également les soins palliatifs, est essentielle pour accompagner la réflexion et prendre des décisions pondérées dans le respect de l'autonomie des patients.

Pre- and post-treatment in flexor tendon tenolysis: An observational study.

BACKGROUND: Glide deficit of the distal flexors' tendons following primary repair in zone 1-3 are very common. Adhesions of tendons have multi factorial origins and are closely related to the healing of the affected tissues. The surgical practice used to resolve these complications is tenolysis. PURPOSE: The purpose of this study was to identify and compare the Visual Analog Scale (VAS) relate to pain and Total Active Motion (TAM) of adult patients of both sexes undergoing tenolysis surgery. The results will then be compared to existing research to confirm their significance. STUDY DESIGN: Case-series. METHODS: Retrospective data for TAM and pain VAS were extracted from the medical records for 63 patients (73 fingers) who underwent flexor tenolysis between 2017 and 2019. Data were compared pre-operatively and 3 months after surgery. All patients underwent pre- and post-surgery therapy by hand therapists. RESULTS: The sample presented very encouraging improvements, except in the VAS and active range of motion (AROM) of thumb where some patients maintained the same assessment. The fingers reported statistically significant results, whereas the thumb group did not meet significant criteria. Overall, TAM improved from 134.6° to 196.7 and VAS decreased from 2.7 to 1.2. DISCUSSION: According to the results and the data change between pre- and post-treatment, the sample demonstrated improvements in all areas examined, reporting statistically significant results for the fingers with an improvement of TAM of 62.1° with a percentage value (%TAM) of 75.6%. CONCLUSIONS: A specific treatment for this type of surgery is required for the patients so they can return to their daily and working activities. This article can be used as a starting point for further studies.

[Borderline psychiatric disorder in the general hospital : specificity and clinical challenges]. / Personnalité borderline à l'hôpital général : spécificités et défis cliniques.

Borderline personality disorder (BPD) is a psychiatric condition frequently encountered at the general hospital. This article will focus on the multiple presentation of this mental illness in the aforementioned setting, such as chronic somatic disease, multiple physical complaints as well as chronic pain, all of which that could severely alter the life quality. In this context, especially if there is an unsatisfied need for reinsurance, risk taking behavior (self-harm or harming others) may arise, as well as significant rise of medical costs through multiple medical consultations, longer average lengths of stay and additional complementary examinations. Through a variety of recommendations and a better understanding of BPD, a therapeutic link can be established to facilitate management.

Le trouble de la personnalité borderline (TPB) est une condition psychopathologique fréquente à l'hôpital général. Dans cet article, nous abordons le spectre des présentations cliniques intrahospitalières, dont les pathologies somatiques chroniques, les plaintes physiques multiples et les douleurs chroniques. L'ensemble de ces conditions impactent lourdement la qualité de vie des patients atteints d'un TPB. Lorsque les besoins de réassurance ne sont pas satisfaits, peuvent apparaître des comportements auto et hétéro-agressifs, ainsi qu'une augmentation des coûts médicaux, via une hausse des consultations, des durées de séjour à l'hôpital somatique et des examens complémentaires. Grâce à diverses recommandations et à une meilleure connaissance du TPB, un lien thérapeutique facilitant la prise en charge peut être établi.

XEN 45 Gel Stent Implantation in Open Angle Glaucoma: 5-Year Results of a Prospective Study.

PRCIS: XEN 45 Gel Stent is safe and effective for 3 years. The study results provide useful insight into the outcome of XEN 45 Gel Stent surgery over 5 years in daily clinical practice. PURPOSE: To evaluate 5-year outcomes of XEN 45 gel stent implantation (XEN) in patients with open angle glaucoma. METHODS: This is a prospective, single-center, interventional study. XEN implantation either alone (XEN) or combined with phacoemulsification (Phaco + XEN) was performed on 170 consecutive eyes (126 patients) with uncontrolled intraocular pressure (IOP) or disease progression despite medical treatment. "Complete" surgical success at 60 months was defined as unmedicated IOP ≤15 mm Hg and a relative IOP reduction ≥20% from medicated baseline, while "qualified" success allowed fewer ocular hypotensive medications than at baseline. Other definitions of success with various IOP targets were also analyzed. Secondary outcomes included mean IOP and IOP-lowering medication changes and rates of reoperations. RESULTS: Mean age was 78.1±9.2 years, and 70.3% were female. Mean medicated IOP decreased from 19.8±7.7 mm Hg [19.6±7.1 (XEN) vs. 19.8±7.0 mm Hg (Phaco+XEN)] at baseline to 12.6±3.1 mm Hg [12.5± 3.1 (XEN) vs. 12.6±3.1 (Phaco+XEN)] at 5 years (-37.0%; P < 0.001). Medications decreased from 2.0±1.3 [2.0±1.3 (XEN) vs. 2.0±1.3 (Phaco+XEN)] to 0.8±1.1 [0.8±1.1 (XEN) vs. 0.8±1.1 (Phaco + XEN)] (-60%; P <0.001). Needling was performed in 84 eyes (49%), and 19.4% underwent a secondary surgical intervention. Complete success at 3 years was a strong predictor of success at 5 years (odds ratio: 3.06, P <0.01), while needling was associated with higher rates of failure (odds ratio: 3.6, P <0.01). CONCLUSIONS: At 5 years, XEN gel stent implantation was a safe procedure and achieved clinically meaningful IOP and medication reduction. Success at 3 years is a predictor of success at 5 years. Needling correlates with higher failure rates.

Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.

Importance: The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established. Objective: To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk. Design, Setting, and Participants: This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022. Exposures: Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (≥20%). Main Outcomes and Measures: Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death). Results: A total of 330 201 patients (median [IQR] age, 57 [40-74] years; 189 107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy. Conclusions and Relevance: Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.

Respiratory Intensive Care Unit management and efficacy during the COVID-19 outbreak in Naples, Italy.

The World Health Organization declared the Coronavirus Diseases 2019 (COVID-19) outbreak a global pandemic on March 11, 2020. COVID-19 had an impact on over 500 million people worldwide. According to the American Thoracic Society criteria, the respiratory spectrum of this disease ranges from mild illness to severe pneumonia, with the latter occurring in a not insignificant 15% of patients. A rapid increase in the incidence of COVID-19 pneumonia cases has been observed all over the world, resulting in a saturation of the Intensive Care Unit's capacity (ICUs). Because of this impressive outbreak, the ICU beds and invasive mechanical ventilators reached their capacity. Non-invasive supportive care has become an important option for keeping respiratory conditions under control. As a result, proper healthcare resource management was required to ensure adequate patient care. Respiratory Intensive Care Units (RICUs) have become a useful resource for managing complex patients due to a shortage of ICU capacity. This highlighted the importance of RICUs, where patients with moderate to severe respiratory failure can be treated with non-invasive respiratory support rather than being admitted to the ICU. The clinical outcomes and baseline characteristics of patients admitted to the RICU of Cotugno Hospital, a tertiary referral center in Naples (Italy), from January 2021 to October 2021 are described in this report.

Conjugated Polymers for Microwave Applications: Untethered Sensing Platforms and Multifunctional Devices.

In the past two decades, organic electronic materials have enabled and accelerated a large and diverse set of technologies, from energy-harvesting devices and electromechanical actuators, to flexible and printed (opto)electronic circuitry. Among organic (semi)conductors, organic mixed ion-electronic conductors (OMIECs) are now at the center of renewed interest in organic electronics, as they are key drivers of recent developments in the fields of bioelectronics, energy storage, and neuromorphic computing. However, due to the relatively slow switching dynamics of organic electronics, their application in microwave technology, until recently, has been overlooked. Nonetheless, other unique properties of OMIECs, such as their substantial electrochemical tunability, charge-modulation range, and processability, make this field of use ripe with opportunities. In this work, the use of a series of solution-processed intrinsic OMIECs is demonstrated to actively tune the properties of metamaterial-inspired microwave devices, including an untethered bioelectrochemical sensing platform that requires no external power, and a tunable resonating structure with independent amplitude- and frequency-modulation. These devices showcase the considerable potential of OMIEC-based metadevices in autonomous bioelectronics and reconfigurable microwave optics.

Bilateral Nonpenetrating Deep Sclerectomy: Difference in Outcomes Between First- and Second-Operated Eyes at 24 Months.

BACKGROUND/AIM: The aim of this study was to assess the difference in outcome between the first-operated and the second-operated eyes after nonpenetrating deep sclerectomy (DS), and to identify potential success predictors for the second eye. METHODS: This single-surgeon, retrospective study analyzed the outcomes of all bilateral nonsimultaneous DS with at least 24 months of follow-up. Its main outcome measure was surgical success, defined as unmedicated intraocular pressure (IOP) ≤15 mm Hg associated with a relative reduction ≥20%. RESULTS: In all, 104 eyes of 52 patients who underwent bilateral (standalone or combined) DS, within a mean of 344.3±526.3 days of each other, were analyzed. Postoperatively, the mean medicated IOP decreased from 20.7±7.9 (first-operated eyes) and 19.3±6.6 mm Hg (second-operated eyes) at baseline (P=0.107) to 13.8±4.8 [(-33.3%; P<0.001) first-operated eyes) and 12.7±3.8 mm Hg [(-34.2%; P<0.001) second-operated eyes] after 2 years (P=0.619). Postoperative IOP and treatment reduction, respectively, showed fair (r=0.53) and good (r=0.71) levels of correlation between fellow eyes. The rates of complete success were comparable between first-operated and second-operated eyes (32.7% and 40.4%, respectively; P=0.364). At 2 years, among patients whose first-operated eyes were considered a success, 82.4% of surgeries in second eyes were successful (P=0.001). The odds ratio of a second-operated eye experiencing complete success were 6.32 (P=0.011) if the first-operated eye experienced complete success. CONCLUSIONS: The present study demonstrated a strong association between first-operated and second-operated eyes after DS, in terms of surgical outcomes and IOP reduction. In effect, surgical success in the first-operated eye increases the odds of success in the second eye by 6-fold.

Blood gas analyses in hyperbaric and underwater environments: a systematic review.

Pulmonary gas exchange during diving or in a dry hyperbaric environment is affected by increased breathing gas density and possibly water immersion. During free diving, there is also the effect of apnea. Few studies have published blood gas data in underwater or hyperbaric environments: this review summarizes the available literature and was used to test the hypothesis that arterial Po2 under hyperbaric conditions can be predicted from blood gas measurement at 1 atmosphere assuming a constant arterial/alveolar Po2 ratio (a:A). A systematic search was performed on traditional sources including arterial blood gases obtained on humans in hyperbaric or underwater environments. The a:A was calculated at 1 atmosphere absolute (ATA). For each condition, predicted arterial partial pressure of oxygen ([Formula: see text]) at pressure was calculated using the 1 ATA a:A, and the measured [Formula: see text] was plotted against the predicted value with Spearman correlation coefficients. Of 3,640 records reviewed, 30 studies were included: 25 were reports describing values obtained in hyperbaric chambers, and the remaining were collected while underwater. Increased inspired O2 at pressure resulted in increased [Formula: see text], although underlying lung disease in patients treated with hyperbaric oxygen attenuated the rise. [Formula: see text] generally increased only slightly. In breath-hold divers, hyperoxemia generally occurred at maximum depth, with hypoxemia after surfacing. The a:A adequately predicted the [Formula: see text] under various conditions: dry (r = 0.993, P < 0.0001), rest versus exercise (r = 0.999, P < 0.0001), and breathing mixtures (r = 0.995, P < 0.0001). In conclusion, pulmonary oxygenation under hyperbaric conditions can be reliably and accurately predicted from 1 ATA a:A measurements.