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U.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized.

Sodium–glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and acute myocardial infarction. Individual trials were powered to study composite outcomes in one disease state. We aimed to evaluate the treatment effect of SGLT2 inhibitors on specific clinical endpoints across multiple demographic and disease subgroups.

Patterns and disparities in guideline-directed medical therapy (GDMT) uptake for heart failure with reduced ejection fraction (HFrEF) across rural vs urban regions are not well described.

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Individuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking.

BackgroundParkinson’s disease (PD) is a significant cause of mortality but little is known about the place of death for patients with PD in the USA, a key metric of end-of-life care.MethodologyA trend analysis was conducted for years 2003–2017 using aggregated death certificate data from the Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research) database, with individual-level mortality data from the Mortality Multiple Cause-of-Death Public Use Record available between 2013 and 2017. All natural deaths for which PD was identified as an underlying cause of death were identified. Place of death was categorised as hospital, decedent home, hospice facility, nursing home/long-term care and other.ResultsBetween 2003 and 2017, 346141 deaths were attributed to PD (59% males, 93.7% White). Most deaths occurred in patients aged 75–84 years (43.9%), followed by those aged ≥85 years (40.9 %). Hospital and nursing home deaths decreased from 18% (n=3240) and 52.6% (n=9474) in 2003 to 9.2% (n=2949) and 42% (n=13 429) in 2017, respectively. Home deaths increased from 21.1% (n=3804) to 32.4% (n=10 347) and hospice facility deaths increased from 0.3% (n=47) in 2003 to 8.6% (n=2739) in 2017. Female sex, being married and college education were associated with increased odds of home deaths while Hispanic ethnicity and non-white race were associated with increased odds of hospital deaths.ConclusionHome and hospice facility deaths are gradually increasing in patients with PD. Particular attention should be provided to vulnerable socioeconomic groups that continue to have higher rates of hospital deaths and decreased usage of hospice facilities.

BackgroundIncreasing utilisation of hospice services has been a major focus in oncology, while only recently have cardiologists realised the similar needs of dying patients with heart failure (HF). We examined recent trends in locations of deaths in these two patient populations to gain further insight.MethodsComplete population-level data were obtained from the Mortality Multiple Cause-of-Death Public Use Record from the National Center for Health Statistics database, from 2013 to 2017. Location of death was categorised as hospital, home, hospice facility or nursing facility. Demographic characteristics evaluated by place of death included age, sex, race, ethnicity, marital status and education, and a multivariable logistic regression analysis was performed to analyse possible associations.ResultsAmong 2 780 715 deaths from cancer, 27% occurred in-hospital and 14% in nursing facilities; while among 335 350 HF deaths, 27% occurred in-hospital and 30% in nursing facilities. Deaths occurred at hospice facilities in 14% of patients with cancer, compared with just 8.7% in HF (p=0.001). For both patients with HF and cancer, the proportion of at-home and in-hospice deaths increased significantly over time, with majority of deaths occurring at home. In both cancer and HF, patients of non-Hispanic ethnicity (cancer: OR 1.29, (1.27 to 1.31), HF: OR 1.14, (1.07 to 1.22)) and those with some college education (cancer: OR 1.10, (1.09 to 1.11); HF: OR 1.06, (1.04 to 1.09)) were significantly more likely to die in hospice.ConclusionDeaths in hospital or nursing facilities still account for nearly half of cancer or HF deaths. Although positive trends were seen with utilisation of hospice facilities in both groups, usage remains low and much remains to be achieved in both patient populations.

Heart failure (HF) is a heterogeneous clinical syndrome marked by substantial morbidity and mortality. The natural history of HF is well established; however, epidemiological data are continually evolving owing to demographic shifts, advances in treatment and variations in access to health care. Although the incidence of HF has stabilized or declined in high-income countries over the past decade, its prevalence continues to increase, driven by an ageing population, an increase in risk factors, the effectiveness of novel therapies and improved survival. This rise in prevalence is increasingly noted among younger adults and is accompanied by a shift towards HF with preserved ejection fraction. However, disparities exist in our epidemiological understanding of HF burden and progression in low-income and middle-income countries owing to the lack of comprehensive data in these regions. Therefore, the current epidemiological landscape of HF highlights the need for periodic surveillance and resource allocation tailored to geographically vulnerable areas. In this Review, we highlight global trends in the burden of HF, focusing on the variations across the spectrum of left ventricular ejection fraction. We also discuss evolving population-based estimates of HF incidence and prevalence, the risk factors for and aetiologies of this disease, and outcomes in different geographical regions and populations.

Polypharmacy is common among patients with heart failure with reduced ejection fraction (HFrEF). However, its impact on the use of optimal guideline-directed medical therapy (GDMT) is not well established.

At least half of all patients with heart failure (HF) are affected by frailty, a syndrome that limits an individual ability to recover from acute stressors. While frailty affects up to 90% of patients with HF with preserved ejection fraction, it is also seen in ~30–60% of patients with HF with reduced ejection fraction, with ~26% higher prevalence in women compared with men. The relationship between frailty and HF is bidirectional, with both conditions exacerbating the other. Frailty is further complicated by a higher prevalence of sarcopenia (by ~20%) in HF patients compared with patients without HF, which negatively affects outcomes. Several frailty assessment methods have been employed historically including the Fried frailty phenotype and Rockwood Clinical Frailty Scale to classify HF patients based on the severity of frailty; however, a validated HF‐specific frailty assessment tool does not currently exist. Frailty in HF is associated with a poor prognosis with a 1.5‐fold to 2‐fold higher risk of all‐cause death and hospitalizations compared to non‐frail patients. Frailty is also highly prevalent in patients with worsening HF, affecting >50% of patients hospitalized for HF. Such patients with multiple readmissions for decompensated HF have markedly poor outcomes compared to younger, non‐frail cohorts, and it is hypothesized that it may be due to major physical and functional limitations that limit recovery from an acute episode of worsening HF, a care aspect that has not been addressed in HF guidelines. Frail patients are thought to confer less benefit from therapeutic interventions due to an increased risk of perceived harm, resulting in lower adherence to HF interventions, which may worsen outcomes. Multiple studies report that <40% of frail patients are on guideline‐directed medical therapy for HF, of which most are on suboptimal doses of these medications. There is a lack of evidence generated from randomized trials in this incredibly vulnerable population, and most current practice is governed by post hoc analyses of trials, observational registry‐based data and providers' clinical judgement. The current body of evidence suggests that the treatment effect of most guideline‐based interventions, including medications, cardiac rehabilitation and device therapy, is consistent across all age groups and frailty subgroups and, in some cases, may be amplified in the older, more frail population. In this review, we discuss the characteristics, assessment tools, impact on prognosis and impact on therapeutic interventions of frailty in patients with HF.

Multiple clinical trials have demonstrated significant cardiovascular benefit with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2DM) and heart failure (HF) irrespective of ejection fraction. There are limited data evaluating real-world prescription and practice patterns of SGLT2 inhibitors.

The burden of heart failure among people with type 2 diabetes is increasing globally. People with comorbid type 2 diabetes and heart failure often have worse outcomes than those with only one of these conditions—eg, higher hospitalisation and mortality rates. Therefore, it is essential to implement optimal heart failure prevention strategies for people with type 2 diabetes. A detailed understanding of the pathophysiology underlying the occurrence of heart failure in type 2 diabetes can aid clinicians in identifying relevant risk factors and lead to early interventions that can help prevent heart failure. In this Review, we discuss the pathophysiology and risk factors of heart failure in type 2 diabetes. We also review the risk assessment tools for predicting heart failure incidence in people with type 2 diabetes as well as the data from clinical trials that have assessed the efficacy of lifestyle and pharmacological interventions. Finally, we discuss the potential challenges in implementing new management approaches and offer pragmatic recommendations to help overcome these challenges.

In the CANVAS (Canagliflozin Cardiovascular Assessment Study) program, canagliflozin reduced the risk of heart failure (HF) hospitalization among individuals with type 2 diabetes mellitus (T2DM).

Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).

Initiation and up-titration of guideline-directed medical therapies (GDMTs) for heart failure with reduced ejection fraction (HFrEF) remains suboptimal, in part because of concerns regarding tolerability and adverse events (AEs).

Contamination set off by highly toxic metal ions and dyes is a big threat to the environment and living beings. Various industries like metal plating, mining, pesticides, battery manufacturing, and dyeing release metal ions and toxic dyes directly into the water. It is necessary to remove these toxic substances from the environment. Molecular imprinting technology (MIT) got a lot of attention in the last two decades because of several advantages over conventional adsorption technologies. Molecularly imprinted polymers (MIPs) are compatible with natural antibodies having the highest selectivity due to specific recognition sites for the template molecules. Selectivity is the major advantage of MIP, any targeted heavy metal ions and dyes can be separated efficiently. Various polymerization procedures can be used for the MIP preparation started by self-assembled monomers surrounding the molecules of the template because of the “monomer functional groups and template” interchange. Various studies have been made for the removal of metal ions and dyes from water and excellent results have been attained. Continuous research developments are being done for real applications of MIPs to remove toxic environmental substances that are not only harmful to humans and other organisms but also disturb the ecological balance. This review represents the development of current MIPs, advantages as well as disadvantages exhibited from various angles to complete a roadmap towards industrial and commercial use of MIPs.

In January 2021, vericiguat, a soluble guanylate cyclase stimulator, was approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of cardiovascular death and heart failure (HF) hospitalization among patients with a recent worsening HF event based on the VICTORIA (VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial.

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The fragility index (FI) was proposed as a simplified way to communicate robustness of statistically significant results and their susceptibility to a change of a handful number of events. While this index is intuitive, it is not anchored by a cut-off or a guide for interpretation. We identified cardiovascular trials published in six high impact journals from 2007 to 2021 (500 or more participants and a dichotomous statistically significant primary outcome). We estimated area under curve (AUC) to determine FI value that best predicts whether the treatment effect was precise, defined as adequately powered for a plausible relative risk reduction (RRR) of 25% or 30% or having a CI that is sufficiently narrow to exclude a risk reduction that is too small (close to the null, <0.05). The median FI of 201 included cardiovascular trials was 13 (range 1–172). FI exceeded the number of patients lost to follow-up in 46/201 (22.89%) trials. FI values of 19 and 22 predicted that trials would be precise (powered for RRR of 30% and 25%; respectively, combined with CI that excluded risk reduction <0.05). AUC for meeting these precision criteria was 0.90 (0.86–0.94). In conclusion, FI values that range 19–22 may meet various definitions of precision and can be used as a rule of thumb to suggest that a treatment effect is likely precise and less susceptible to random error. The number of patients lost to follow-up should be presented alongside FI to better illustrate fragility.

The majority of cardiovascular randomized controlled trials (RCTs) test interventions in selected patient populations under explicitly protocol-defined settings. Although these ‘explanatory’ trial designs optimize conditions to test the efficacy and safety of an intervention, they limit the generalizability of trial findings in broader clinical settings. The concept of ‘pragmatism’ in RCTs addresses this concern by providing counterbalance to the more idealized situation underpinning explanatory RCTs and optimizing effectiveness over efficacy. The central tenets of pragmatism in RCTs are to test interventions in routine clinical settings, with patients who are representative of broad clinical practice, and to reduce the burden on investigators and participants by minimizing the number of trial visits and the intensity of trial-based testing. Pragmatic evaluation of interventions is particularly important in cardiovascular diseases, where the risk of death among patients has remained fairly stable over the past few decades despite the development of new therapeutic interventions. Pragmatic RCTs can help to reveal the ‘real-world’ effectiveness of therapeutic interventions and elucidate barriers to their implementation. In this Review, we discuss the attributes of pragmatism in RCT design, conduct and interpretation as well as the general need for increased pragmatism in cardiovascular RCTs. We also summarize current challenges and potential solutions to the implementation of pragmatism in RCTs and highlight selected ongoing and completed cardiovascular RCTs with pragmatic trial designs.

The U.S. population is aging with concurrent increases in heart failure (HF) burden. However, HF-related mortality trends among adults ≥75 years have not been investigated.

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IMPORTANCE: There are limited data on mortality trends in young adults with heart failure (HF). OBJECTIVE: To study the trends in HF-related mortality among young adults. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis used mortality data of young adults aged 15 to 44 years with HF listed as a contributing or underlying cause of death in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1999 to December 2019. Analysis took place in October 2021. EXPOSURES: Age 15 to 44 years with HF listed as a contributing or underlying cause of death. MAIN OUTCOMES AND MEASURES: HF-related age-adjusted mortality rates (AAMR) per 100 000 US population stratified by sex, race and ethnicity, and geographic areas. RESULTS: Between 1999 and 2019, a total of 61 729 HF-related deaths occurred in young adults. Of these, 38 629 (62.0%) were men and 23 460 (38.0%) were women, and 22 156 (35.9%) were Black, 6648 (10.8%) were Hispanic, and 30 145 (48.8%) were White. The overall AAMR per 100 000 persons for HF in young adults increased from 2.36 in 1999 to 3.16 in 2019. HF mortality increased in young men and women, with men having higher AAMRs throughout the study period. AAMR increased for all race and ethnicity groups, with Black adults having the highest AAMRs (6.41 in 1999 and 8.58 in 2019). AAMR for Hispanic adults and White adults increased from 1.62 to 2.04 and 1.83 to 2.45 over the same time period, respectively. Across most demographic and regional subgroups, HF-related mortality stayed stable or decreased between 1999 and 2012, followed by an increase between 2012 and 2019. There were significant regional differences in the burden of HF-related mortality, with states in the upper 90th percentile of HF-related mortality (Oklahoma, South Carolina, Louisiana, Arkansas, Alabama, and Mississippi) having a significantly higher mortality burden compared with those in the bottom tenth percentile. CONCLUSIONS AND RELEVANCE: Following an initial period of stability, HF-related mortality in young adults increased from 2012 to 2019 in the United States. Black adults have a 3-fold higher AAMR compared with White adults, with significant geographic variation. Targeted health policy measures are needed to address the rising burden of HF in young adults, with a focus on prevention, early diagnosis, and reduction in disparities.

The aim of this study was to assess trends in heart failure (HF) hospitalizations among young adults.

IMPORTANCE: Cardiovascular trials have traditionally been underpowered to assess advanced chronic kidney disease (CKD) outcomes, and when included as a secondary end point, trials have used progression of CKD as incidence of some variation of a composite of end-stage kidney disease (ESKD) outcomes. Such outcomes are infrequent or occur late in cardiovascular outcome trials, which highlights the need for alternate markers for assessing the impact of interventions on kidney function at an earlier stage of the disease and, from the prevention perspective, more relevant stage of the disease. OBSERVATIONS: Estimated glomerular filtration rate (eGFR) slope has demonstrated strong association with subsequent progression to ESKD. With adequate sample size, treatment effects in the range of 0.5 to 1.00 mL/min/1.73 m2/y had 96% probability of predicting CKD progression, defined as doubling of serum creatinine, eGFR less than 15 mL/min/1.73 m2, or ESKD. eGFR slope can be used in patients with higher baseline values and may provide CKD progression insights when few hard kidney events are observed, especially in trials with limited follow-up. However, among trials that have determined eGFR slope, significant variations exist regarding inclusion of baseline values, calculation of eGFR values, and the follow-up period, which make it difficult to compare and gauge the incremental benefit of the interventions. There are multiple challenges in computing eGFR slope in cardiovascular trials, such as accounting for initial eGFR dip, nonlinearity, and heteroscedasticity. CONCLUSIONS AND RELEVANCE: eGFR slope may serve as a valuable marker to determine progression of CKD in cardiovascular trials. Further work is required to standardize data collection, follow-up duration, time points for kidney function assessment, and analytic methods to compute eGFR slope in cardiovascular trials.

Biomass-derived fast pyrolysis liquid, also called bio-oil (FPBO), can replace petroleum fuels in thermal devices, but several undesirable properties hinder its widespread application. This paper aims to improve these properties and quantify their effect on its combustion performance. In this study, higher quality bio-oil having similar viscosity and surface tension as FPBO was obtained through the thermo-catalytic reforming bio-oil (TCRBO) process. The effect of fuel chemical composition, thermogravimetric analysis (TGA) residue, fuel volatility, heating value, water content, solid content, and ash content was examined in a 10 kW spray burner. Gas phase emissions and particulate matter (PM) were also measured and compared to its operation on fuel oil #2 for which diesel was used. TCRBO ignited irrespective of the primary air preheat temperature, and its evaporation characteristics (i.e., TGA residue of less than 3%) were more like diesel. TCRBO does not display any flash atomization. Both FPBO and TCRBO displayed coking potential; however, for TCRBO, no coking was observed if the primary air was heated above 110 °C. FPBO droplets were larger in size (∼100 μm) and could not achieve complete burnout due to increasing emissions. TCRBO exhibits lower emissions than FPBO at any given operating point, primarily due to better atomization achieved due to its higher fuel heating value, which reduced the fuel flow rate by almost 40%. FPBO resulted in the highest PM emissions, which can be attributed to the formation of secondary char particles. Higher fuel ash content also contributed to the PM emissions. The reduction in fuel water content (i.e., ∼2 wt %) made the TCRBO flame less susceptible to blow out, and a stable flame was observed without the pilot flame. Swirl and pilot were necessary to stabilize the FPBO flame. The TCRBO’s higher fuel nitrogen content significantly increased its NOxemissions. Overall, thermo-catalytic reforming significantly improved the combustion characteristics of pyrolysis bio-oil. Although TCRBO was obtained from lower quality feedstock (e.g., sewage sludge), its superior combustion performance is attributed to the ability of the TCR process to produce higher quality liquid fuels from various biomass sources.

In this study, we sought to evaluate the association of frailty with the use of optimal guideline-directed medical therapy (GDMT) and outcomes in heart failure with reduced ejection fraction (HFrEF).

Background: Functional health status is increasingly being recognized as a viable endpoint in heart failure (HF) trials. We sought to assess its prognostic impact and relationship with traditional clinical outcomes in patients with HF. Methods: MEDLINE and Cochrane central were searched up to January 2021 for post hoc analyses of trials or observational studies that assessed independent association between baseline health/functional status, and mortality and hospitalization in patients with HF across the range of left ventricular ejection fractions to evaluate the prognostic ability of NYHA class [II, III, IV], KCCQ, MLHFQ, and 6MWD. Hazard ratios (HR) with 95% confidence intervals were pooled. Results: Twenty-two studies were included. Relative to NYHA I, NYHA class II (HR 1.54 [1.16–2.04]; p&lt; 0.01), NYHA class III (HR 2.08 [1.57–2.77]; p&lt; 0.01), and NYHA class IV (HR 2.53 [1.25–5.12]; p= 0.01) were independently associated with increased risk of mortality. 6MWD (per 10 m) was associated with decreased mortality (HR 0.98 [0.98–0.99]; p&lt; 0.01). A 5-point increase in KCCQ-OSS (HR 0.94 [0.91–0.96]; p&lt; 0.01) was associated with decreased mortality. A high MLHFQ score (> 45) was significantly associated with increased mortality (HR 1.30 [1.14–1.47]; p&lt; 0.01). NHYA class, 6MWD (per 10 m), KCCQ-OSS, and MLHFQ all significantly associated with all-cause mortality in patients with HF. Conclusion: Identifying such patients with poor health status using functional health assessment can offer a complementary assessment of disease burden and trajectory which carries a strong prognostic value.

The increase in population and industrialization has intensified water scarcity and stress, and contaminated water bodies. Therefore, the development of advanced water and wastewater treatment technologies has gained global attention from researchers. Adsorption, using natural materials (nano, polymer, and bio) is one of the most cost-effective, less challenging, and well-known technologies for wastewater treatment and improving water quality. Among them, chitosan (CS) has demonstrated a set of unique features, such as biodegradability, eco-friendliness, availability, low cost, and biocompatibility. Hence, this review provides an overview of some recent advancements in the removal of heavy metals, including As (III) and (V), Cd (II), Cu (II), Cr (VI), and Pb (II) by CS-based adsorbents, and their potential effects on human health. It also covers the synthesis of CS-based adsorbents for the elimination of mentioned contaminants in recently reported studies. In addition, this study recommends encountering potential drawbacks by enhancing the adsorption capacity by incorporating functional groups, nanoparticles, and other materials. These modifications may help increase selectivity for specific metal contaminants and synthesize adsorbents that can perform better over a wide range of pH. Insights gained from this study will guide researchers in the future toward optimal water treatment and pollutant elimination strategies.

The authors sought to characterize associations between initiation of metformin and sulfonylurea therapy and clinical outcomes among patients with comorbid heart failure (HF) and diabetes (overall and by ejection fraction [EF] phenotype).

Background: Cephalosporin antibiotics are used to treat bacterial infections in humans and animals. Their excessive usage and massive production rates have led to their presence in the environment, causing serious threats, such as antibiotic resistance. Several methods have been used for the detection and quantification of these antibiotic traces in the environment; among them, sensors have been the most advanced tools that can be very useful for online on-spot detection of these antibiotics. This review briefly discussed electrochemical, colorimetric and biosensors and their use in the detection of trace antibiotics. The provided information gives a brief view of the developed methods that will be helpful in the development of commercially applicable sensing devices for real-time monitoring of antibiotics in the environment. Methods: Research and online content related to the detection of cephalosporin antibiotics were collected. Research methodologies and results were studied and compared. The screening of available data was done by experts, and the most advanced and useful methods were described. A brief introduction to sensing methodologies and the recent advancement in these techniques was reviewed. Results: Different analytical techniques have been used for the detection and quantification of environmental pollutants. Sensors are small-sized devices that have gone through great advancement in recent decades, have leading to highly sensitive and selective tools for trace antibiotic detection. Electrochemical sensors have advantages of high selectivity and robust receptors, while colorimetric sensors provide rapid detection with visible color changes. Biosensors have higher sensitivity and selectivity but are sensitive to environmental changes. There is a great need to develop a simple technique that may combine advantages of all these sensing techniques and can be used in the real world for the screening of antibiotic traces. Conclusion: The recent progress in sensing technology has led to the development of highly sensitive and selective sensors, but they have lab-based applications. We still lack the availability of sensing methodologies that can provide online monitoring of environmental pollutants in the real environment. The recent achievements and inter-disciplinary research have been very fruitful and given hope that we may obtain simple and useful sensing tools for the screening of antibiotic traces in the environment.

This study sought to determine the effect of percutaneous mitral valve annuloplasty with the Carillon device versus guideline-directed medical therapy (GDMT) alone in patients with secondary mitral regurgitation (MR) and severe left ventricular (LV) enlargement.

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit–based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study.

Recent studies have shown that complete blood count (CBC) parameters can effectively predict long-term mortality and re-infarction rates in acute coronary syndrome (ACS). However, the role of these parameters in predicting short term mortality has not been studied extensively. The main objective of this study was to determine whether CBC parameters can predict 30-days mortality and the incidence of major adverse cardiac event (MACE) in ACS patients.

This study sought to determine whether patients with heart failure and reduced ejection fraction (HFrEF) with type 2 diabetes mellitus (T2DM) have similar reverse cardiac remodeling with sacubitril/valsartan as patients without T2DM.

Although it is well established that cigarette smoking is associated with morbidity and mortality in several respiratory infections, data from recent studies suggest that active smokers are underrepresented among patients with COVID-19. This has led to claims that a ‘smoker’s paradox’ may exist in COVID-19, wherein smokers are protected from infection and severe complications of COVID-19. We aimed to review and summarise existing literature in this context. Electronic databases were searched for articles that reported prevalence of smokers among patients with COVID-19 or studied any association of smoking with outcomes among patients with COVID-19. We identified several biases and knowledge gaps which may give the false impression that smoking is protective in COVID-19. As of now, the data supporting smoker’s paradox claims are limited and questionable. Plausible biologic mechanisms by which smoking might be protective in COVID-19 include an anti-inflammatory effect of nicotine, a blunted immune response in smokers (reducing the risk of a cytokine storm in COVID-19) and increased nitric oxide in the respiratory tract (which may inhibit replication of SARS-CoV-2 and its entry into cells). On the other hand, smoking may worsen susceptibility and prognosis in COVID-19, in a manner similar to other respiratory infections. The claims of a protective effect must be viewed with extreme caution by both the general population as well as clinicians. Further investigations into the interaction between smoking and COVID-19 are warranted to accurately assess the risk of contracting COVID-19 among smokers, and progression to mechanical ventilation or death in patients suffering from it.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.With worsening epidemiological trends for both the incidence and prevalence of type 2 diabetes mellitus (T2DM) and heart failure (HF) worldwide, it is critical to implement optimal prevention and treatment strategies for patients with these comorbidities, either alone or concomitantly. Several guidelines and consensus statements have recommended glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter type 2 inhibitors as add-ons to lifestyle interventions with or without metformin in those at high atherosclerotic cardiovascular disease risk. However, these recommendations are either silent about HF or fail to differentiate between the prevention of HF in those at risk versus the treatment of individuals with manifest HF. Furthermore, these documents do not differentiate among those with different HF phenotypes. This distinction, even though important, may not be critical for sodium-glucose cotransporter type 2 inhibitors in view of the consistent data for benefit for both atherosclerotic cardiovascular disease– and HF-related outcomes that have emerged from the regulatory-mandated cardiovascular outcome trials for all sodium-glucose cotransporter type 2 inhibitors and the recent DAPA-HF trial (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction)demonstrating the benefit of dapagliflozin on HF-related outcomes in patients with HF with reduced ejection fraction with or without T2DM. However, the distinction may be crucial for glucagon-like peptide-1 receptor agonists and other antihyperglycemic agents. Indeed, in several of the new statements, glucagon-like peptide-1 receptor agonists are suggested treatment not only for patients with T2DM and atherosclerotic cardiovascular disease, but also in those with manifest HF, despite a lack of evidence for the latter recommendation. Although glucagon-like peptide-1 receptor agonists may be appropriate to use in patients at risk for HF, mechanistic insights and observations from randomized trials suggest no clear benefit on HF-related outcomes and even uncertainty regarding the safety in those with HF with reduced ejection fraction. Conversely, theoretical rationales suggest that these agents may benefit patients with HF with preserved ejection fraction. Considering that millions of patients with T2DM have HF, these concerns have public health implications that necessitate the thoughtful use of these therapies. Achieving this aim will require dedicated trials with these drugs in both patients who have HF with reduced ejection fraction and HF with preserved ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.

Background: The development of new bioimplants with enhanced mechanical and biomedical properties have great impetus for researchers in the field of biomaterials. Metallic materials such as stainless steel 316L (SS316L), applied for bioimplants are compatible to the human osteoblast cells and bear good toughness. However, they suffer by corrosion and their elastic moduli are very high than the application where they need to be used. On the other hand, ceramics such as hydroxyapatite (HAP), is biocompatible as well as bioactive material and helps in bone grafting during the course of bone recovery, it has the inherent brittle nature and low fracture toughness. Therefore, to overcome these issues, a hybrid combination of HAP, SS316L and carbon nanotubes (CNTs) has been synthesized and characterized in the present investigation. Methods: CNTs were acid treated to functionalize their surface and cleaned prior their addition to the composites. The mixing of nano-hydroxyapatite (HAPn), SS316L and CNTs was carried out by nitrogen gas purging followed by the ball milling to insure the homogeneous mixing of the powders. In three compositions, monolithic HAPn, nanocomposites of CNTs reinforced HAPn, and hybrid nanocomposites of CNTs and SS316L reinforced HAPn has been fabricated by spark plasma sintering (SPS) technique. Results: SEM analysis of SPS samples showed enhanced sintering of HAP-CNT nanocomposites, which also showed significant sintering behavior when combined with SS316L. Good densification was achieved in the nanocomposites. No phase change was observed for HAP at relatively higher sintering temperatures (1100°C) of SPS and tricalcium phosphate phase was not detected by XRD analysis. This represents the characteristic advantage with enhanced sintering behavior by SPS technique. Fracture toughness was found to increase with the addition of CNTs and SS316L in HAPn, while hardness initially enhanced with the addition of nonreinforcement (CNTs) in HAPn and then decrease for HAPn-CNT-SS316L hybrid nanocomposites due to presence of SS316L. Conclusions: A homogeneous distribution of CNTs and SPS technique resulted in the improved mechanical properties for HAPn-CNT-SS316L hybrid nanocomposites than other composites and suggested their application as bioimplant materials.