Incidence Of Death Research Articles

Optical coherence tomography (OCT) - versus angiography-guided strategy for percutaneous coronary intervention: a meta-analysis of randomized trials

BackgroundOptical coherence tomography (OCT) guidance in percutaneous coronary intervention (PCI) has been shown to improve procedural outcomes. However, evidence supporting its superiority over angiography-guided PCI in terms of clinical outcomes is still emerging and limited. This study aimed to compare the efficacy and safety of OCT-guided PCI versus angiography‐guided PCI in patients with coronary artery disease (CAD).MethodsA systematic search of electronic databases was conducted to identify randomized control trials (RCTs) comparing the clinical outcomes of OCT-guided and angiography‐guided PCI in patients with CAD. Clinical endpoints including all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), stent thrombosis and major adverse cardiac events (MACE) were assessed.ResultsEleven RCTs, comprising 2,699 patients in the OCT-guided group and 2,968 patients in the angiography-guided group met inclusion criteria. OCT-guided PCI was associated with significantly lower rates of cardiovascular death(RR 0.56; 95%CI: 0.32–0.98; p = 0.04; I2 = 0%), stent thrombosis(RR 0.56; 95%CI: 0.33–0.95; p = 0.03; I2 = 0%), and MACE (RR 0.79; 95%CI: 0.66–0.95; p = 0.01; I2 = 5%). The incidence of all-cause death (RR 0.71; 95%CI: 0.49–1.02; p = 0.06; I2 = 0%), myocardial infarction (RR 0.86; 95%CI: 0.67–1.10; p = 0.22; I2 = 0%) and TLR (RR 0.98; 95%CI: 0.73–1.33; p = 0.91; I2 = 0%) was non-significantly lower in the OCT-guided group.ConclusionsAmong patients undergoing PCI, OCT-guided PCI was associated with lower incidences of cardiovascular death, stent thrombosis and MACE compared to angiography-guided PCI.Trial registrationPROSPERO registration number: CRD42023484342.

Safety and Effectiveness of a Novel Microcatheter in Coronary Chronic Total Occlusions—The BIOMICS Study

BackgroundChronic total occlusion (CTO) remains the most complex anatomical subset of lesions in percutaneous coronary intervention (PCI), often requiring advanced techniques and technologies, including the use of microcatheters. MethodsThe BIOMICS study is a premarket first-in-human prospective, multicenter, open-label, single-arm trial investigating the safety and efficacy of a novel coronary microcatheter (BioMC, Biosensors International) in 100 patients with symptoms of ischemia undergoing elective CTO-PCI. The primary efficacy end point of the study was device success defined according to the CTO-ARC (Chronic Total Occlusion Academic Research Consortium) criteria namely the ability of the microcatheter to successfully facilitate placement of a guide wire beyond the occluded coronary segment. The primary safety end point was the incidence of in-hospital cardiac death or myocardial infarction at hospital discharge. ResultsHundred patients were recruited between March 2022 and January 2023. The primary efficacy end point was achieved in 75% of patients (95% CI, 65.3%-83.1%; P < .0001 for superiority compared to the prespecified performance goal of 54%). The primary safety end point of in-hospital cardiac death or myocardial infarction was observed in 2% of the patients. There were no study device-related coronary perforations or device failures. ConclusionsThe use of a novel coronary microcatheter during CTO-PCI was associated with a high device success and an excellent safety profile.

Insulin resistance, coronary artery lesion complexity and adverse cardiovascular outcomes in patients with acute coronary syndrome

BackgroundInsulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis.MethodA total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson’s correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization.ResultsDuring a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization.ConclusionElevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.

Assessing the effect of automated speed enforcement and comprehensive measures on road safety in Rwanda

Objectives Daily, approximately 3,400 traffic-related deaths occur globally, with over 90% concentrated in low and middle-income countries (LMICs). Notably, Rwanda has one of the highest road traffic death rates in the world (29.7 per 100,000 people) and is the first low-income country to implement a national Automated Speed Enforcement (ASE) policy. The primary goal of this study is to evaluate the effectiveness of ASE cameras in reducing the primary outcome of road traffic deaths and secondary outcomes of serious injury crashes and fatal crashes. Methods The study used data on road traffic deaths, and serious injury and fatal crashes collected by the Rwanda National Police between 2010 and 2022. Interrupted time series (ITS) models were fit to quantify the association between ASE and change in road traffic crash outcomes, adjusted for COVID-19-related variables (such as the start of the pandemic, the closure of schools and bars), along with exposure variables (such as GDP and population), and other concurrent road safety measures (such as road safety campaigns). Results The ITS models show that the implementation of ASE cameras significantly reduced road traffic deaths, serious injury crashes, and fatal crashes at the provincial level. For instance, the implementation of ASE cameras in the whole of Rwanda in April 2021 was significantly associated with a 0.14 (95% CI [0.072, 0.212]) reduction in monthly death incidence, equating to a 38.16% monthly decrease compared to the period before their installation (January 2010-March 2021). Conclusion This study emphasizes the significant association of ASE in Rwanda with improved road traffic crash outcomes, a result that may inform road safety policy in other LMICs. Rwanda has become the first low-income country to implement nationwide scaling of ASE in Africa, paving the way for the generation of valuable evidence on speed-related interventions. In addition to new knowledge generation, African road safety research efforts like this one are opportunities to grow academic and law enforcement cooperations while improving data systems and sources for future research benefits.

The role of cell‐free DNA in non‐invasive diagnosis of urinary tract infection

AbstractUrinary tract infection (UTI) constitutes a pervasive health concern. UTIs are dichotomously classified into upper and lower strata, and further categorized as either complicated or uncomplicated. Upper UTIs predominantly afflict the renal and ureteral domains, typified by conditions exemplified in pyelonephritis, whereas lower UTIs manifest within the confines of the urethra and bladder. The conventional diagnosis of UTIs relies upon clinical manifestations and urine culture. Common symptoms encompass dysuria, frequent micturition, hematuria, and suprapubic discomfort. Urine culture serves to identify the specific pathogens instigating the infection and assess their antibiotic susceptibility. However, this procedural protocol generally necessitates an approximate duration of 24 h, coupled with an additional 24‐h interval for antibiotic susceptibility testing. In contradistinction, the detection of cell‐free DNA (cfDNA) in the circulatory system presents a potential avenue for non‐invasive diagnostic modalities. Notwithstanding, cfDNA emanates from deteriorating cells, affording insights into the extant cellular demise within the organism. Extensive scholarly inquiry has established a positive correlation between cfDNA concentration in the bloodstream and the incidence of cell death in conditions, such as severe traumas, sepsis, aseptic inflammation, myocardial infarction, and stroke. However, limited investigative effort has been devoted to elucidating the diagnostic potential of cfDNA in the context of UTIs. Consequently, the concentration and constitution of plasma cfDNA harbor substantial promise for non‐invasively diagnosing UTIs. In summation, the utilization of cfDNA in UTI diagnosis remains an incipient area of scholarly pursuit, underscoring the imperative for further research to elucidate the prospective role of plasma cfDNA in non‐intrusively discerning UTIs.

Rapid Access From Primary Care to a Multidisciplinary Clinic at Tertiary Care Improves Clinical Outcomes for Patients With Diabetic Foot Ulcers: Results From Diabetic Foot in Primary and Tertiary (DEFINITE) Care's Lower Extremity Amputation Prevention Program (LEAPP) Clinic.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional, multidisciplinary team (MDT) program for patients with diabetic foot ulcers (DFU) within a healthcare cluster in Singapore. This is one of our subgroup analyses within DEFINITE Care, assessing clinical outcomes of lower extremity amputation prevention program (LEAPP), a multidisciplinary diabetic foot clinic, and non-LEAPP patients within the program. From June 2020 to June 2022, 2798 patients within the DEFINITE cohort completed a minimum of 12-month follow up. Of these patients, 20.6% were managed by LEAPP, whereas 79.4% were non-LEAPP patients. Patients in the LEAPP cohort were older with co-existing metabolic conditions and complications of diabetes. Using non-LEAPP cohort as the reference group and after adjusting for age, gender, ethnicity, comorbidities, and medications, there was a significantly lower risk of death (odds ratio [OR] 0.60, P = .001) and composite major lower extremity amputation (LEA) or death (OR 0.66, P = .002) among LEAPP patients at 1 year with longer mean days from enrollment to minor LEA, major LEA, and death. The adjusted 1-year healthcare utilization outcomes for LEAPP patients demonstrated an increase in inpatient admissions, primary care polyclinic visits, hospital specialist outpatient clinic (SOC) visits and elective day surgery procedures. Despite the increased in inpatients admissions, cumulative hospital length of stay in LEAPP patients were lower. This subgroup analysis has demonstrated that the MDT approach to caring for patients with DFU in tertiary centers not only improves mortality by 40%, but also delayed the incidence of minor LEA, major LEA, and death.

Synergistic effect of lipoprotein(a) and high-sensitivity C-reactive protein on the risk of all-cause and cardiovascular death in patients with acute myocardial infarction: a large prospective cohort study.

Although lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (Hs-CRP) are closely associated with the mortality of acute myocardial infarction (AMI), their synergistic effect on the risk of death remains unknown. Therefore, this study aimed to explore the combined effect of Lp(a) and Hs-CRP on the incidence of all-cause and cardiovascular death in AMI patients. A comprehensive cohort study enrolled 912 AMI patients, categorizing them into four groups based on Lp(a) and Hs-CRP levels: Group 1 [Lp(a) < 30 mg/dL & Hs-CRP < 2 mg/L], Group 2 [Lp(a) < 30 mg/dL & Hs-CRP ≥ 2 mg/L], Group 3 [Lp(a) ≥ 30 mg/dL & Hs-CRP < 2 mg/L], and Group 4 [Lp(a) ≥ 30 mg/dL & Hs-CRP ≥ 2 mg/L]. Cox regression analysis, Kaplan-Meier survival analysis and sensitivity analysis were employed to determine the combined effects of Lp(a) and Hs-CRP on the risk of all-cause and cardiovascular death. Over a median observation period of 38.98 months, 217 patients passed away, with 137 deaths attributed to cardiovascular causes. The multivariate Cox regression analysis revealed that in the comprehensively adjusted Model 3, only Lp(a) and the combination of Lp(a) and Hs-CRP exhibited a strong association with cardiovascular death risk. Specifically, for Lp(a) levels ≥ 30 mg/dL compared to < 30 mg/dL, the hazard ratio (HR) was 2.434 with a 95% confidence interval (CI) of 1.653-3.583 (P < 0.001); for log10(Lp(a)), the HR was 2.630 with a 95% CI of 1.530-4.523 (P < 0.001); for Group 4 versus Group 1, the HR was 2.346 with a 95% CI of 1.054-5.220 (P = 0.037); and for Group 4 versus Groups 1 + 2 + 3, the HR was 1.878 with a 95% CI of 1.284-2.748 (P = 0.001). Sensitivity analysis indicated that the synergy between Lp(a) and Hs-CRP continued to be independently associated with the risk of cardiovascular death. For Group 3 versus Group 1, the HR was 3.353 with a 95% CI of 1.133-9.917 (P = 0.029); for Group 4 versus Group 1, the HR was 3.710 with a 95% CI of 1.466-9.392 (P = 0.006); and for Group 4 versus Groups 1 + 2 + 3, the HR was 2.433 with a 95% CI of 1.620-3.656 (P < 0.001). Compared to elevated levels of either Lp(a) or Hs-CRP alone, the concurrent high levels of both significantly increased the risk of cardiovascular death in patients with AMI, underscoring the importance of considering their combined effects in the prognostic management of AMI patients.

Analysis of IL-17A, IL-17F, and miR-146a-5p Prior to Transplantation and Their Role in Kidney Transplant Recipients

Background/Objectives: The balance between regulatory and Th17 cells plays an important role in maintaining the immune tolerance after kidney transplantation (KTx) which is essential for transplantation success, defined as a long graft survival and an absence of organ rejection. The present study aimed to assess whether the pretransplant characteristics of IL-17A and IL-17F, their receptors, as well as miR-146a-5p, an miRNA associated with IL-17A/F regulation, can predict KTx outcomes. Methods: A group of 108 pre-KTx dialysis patients and 125 healthy controls were investigated for single nucleotide substitutions within genes coding for IL-17A, IL-17F, their IL-17RA/RC receptors, and miR-146a-5p. Genotyping was performed using LightSNiP assays. In addition, IL17-A/F serum concentrations were determined using ELISA while miR-146a-5p expression was analyzed by RT-PCR. Results: The IL-17F (rs763780) G allele prevailed in KTx recipients as compared to healthy individuals (OR = 23.59, p &lt; 0.0001) and was associated with a higher IL-17F serum level (p = 0.0381) prior to transplantation. Higher miR-146a-5p expression before KTx was more frequently detected in recipients with an increased IL-17A serum concentration (p = 0.0177). Moreover, IL-17A (rs2275913) GG homozygosity was found to be associated with an increased incidence of deaths before KTx (OR = 4.17, p = 0.0307). T-cell or acute rejection episodes were more frequently observed among patients with the C allele of miR-146a-5p (rs2910164) (OR = 5.38, p = 0.0531). IL17-RA/-RC genetic variants (p &lt; 0.05) seem to be associated with eGFR values. Conclusions: These results imply that IL-17F (rs763780) polymorphism is associated with the serum level of this cytokine and may be related to the risk of renal disease and transplant rejection together with miR-146a-5p (rs2910164), while the IL-17A (rs2275913) genotype may affect patients’ survival before KTx.

Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021

Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4—2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.

Efficacy and safety of stereotactic radiotherapy on elderly patients with stage I-II central non-small cell lung cancer.

Many studies demonstrated the safety and efficacy of SBRT in the treatment of elderly patients with early-stage non-small cell lung cancer (NSCLC). However, those studies focused on patients with peripheral lung cancer. This study aimed to evaluate the clinical efficacy and toxicity of SBRT in elderly patients with stage I-II central NSCLC in single institution. From April 2009 to January 2020, a retrospective study was conducted on patients ≥ 65 years old with stage I-II NSCLC that was centrally localized and treated with SBRT at a single institution. Absolute C-reactive protein (CRP)/albumin ratio (CAR) and body mass index (BMI) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), cancer-specific death, noncancer-specific death, local progression (LP) and distant progression (DP). Stereotactic body radiation treatment (SBRT) was administered to a total of 44 patients. The most common dose fractionation schedule was 60 Gy given in 5 fractions. The median PFS of the cohort was 31 months (95% CI, 19.47-42.53 months). The median OS of all patients was 69 months (95% CI, 33.8-104.2 months). The median time to noncancer-specific death was 54.5 months. The median time to cancer-specific death was 36 months. The cumulative incidences of cancer-specific death at 1 year, 5 years, and 10 years were 11.63% (95%CI, 4.2-23.23%), 42.99% (95%CI, 27.56-57.53%), and 65.94% (95%CI, 45.76-80.1%), respectively. pre-SBRT BMI of ≤ 22.77 (HR 4.60, 95% CI 1.84-11.51, P=0.001) and pre-SBRT CAR of ≤0.91 (HR 5.19, 95% CI 2.15-12.52, P<0.000) were significant predictors of higher OS on multivariable analysis. The median times to LP and DP were 10 months and 11 months, respectively. In terms of acute toxicity, grade 1 including cough (38.64%), radiation pneumonitis (29.55%), anemia (25%), and fatigue (20.45%) was often observed. There was no evidence of grade 4 or 5 acute toxicity. In terms of late toxicity, 2 patients developed grade 1 pulmonary fibrosis during follow-up. This study showed that SBRT can effectively control local tumor progression, and have acceptable toxicity for elderly patients with centrally located stage I-II NSCLC. Lower pre-SBRT BMI and lower pre-SBRT CAR were associated with a decreased risk of cancer-specific death.

Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: AComparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Non-Users.

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. non-use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow-up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24-0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39-0.89; P = 0.0126), and all-cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50-0.95; P = 0.0225) compared with the non-SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.

Risk of prostate cancer death in men diagnosed with prostate cancer at cystoprostat-ectomy. A nationwide population-based study.

One out of three men who undergo cystoprostatectomy for bladder cancer is diagnosed with incidental prostate cancer (PCa) at histopathological examination. Many of these men are PSA tested as part of their follow-up, but it is unclear if this is needed. The aim of this study was to assess the risk of PCa death in these men and the need of PSA-testing during follow-up. Between 2002 and 2020, 1,554 men were diagnosed with PCa after cystoprostatectomy performed for non-metastatic bladder cancer and registered in the National Prostate Cancer Register (NPCR) of Sweden. We assessed their risk of death from PCa, bladder cancer and other causes up to 15 years after diagnosis by use of data in The Cause of Death Register. The use of androgen deprivation therapy (ADT) as a proxy for PCa progression was assessed by fillings in The Prescribed Drug Register. Fifteen years after diagnosis, cumulative incidence of death from PCa was 2.6% (95% CI 2.3%-2.9%), from bladder cancer 32% (95% CI: 30%-34%) and from other causes 40% (95% CI: 36%-44%). Only 35% of men with PCa recorded as primary cause of death in The Cause of Death Register had started ADT before date of death, indicating sticky-diagnosis bias with inflated risk of PCa death. For a large majority of men diagnosed with incidental PCa at cystoprostatectomy performed for bladder cancer, the risk of PCa death is very small so there is no rationale for PSA testing during follow-up.

Titration of Medications After Acute Heart Failure Is Safe, Tolerated, and Effective Regardless of Risk

BackgroundGuideline-directed medical therapy (GDMT) decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF (Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure), high-intensity care (HIC) in the form of rapid uptitration of heart failure (HF) GDMT was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses. ObjectivesThe authors sought to assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable MAGGIC (Meta-Analysis Global Group in Chronic) HF risk score. MethodsIn STRONG-HF, 1,078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) vs usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable. ResultsAmong 1,062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC vs UC group and did not differ by MAGGIC risk score tertiles (interaction nonsignificant). The incidence of all-cause death or HF readmission at day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1, 2, and 3. The HIC arm was at lower risk of all-cause death or HF readmission at day 180 (HR: 0.66; 95% CI: 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR: 0.51; 95% CI: 0.62-0.68 in tertiles 1, 2, and 3; interaction nonsignificant) for all comparisons and continuous (interaction nonsignificant) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction nonsignificant). ConclusionsHIC led to better use of GDMT and lower HF-related morbidity and mortality compared with UC, regardless of the underlying HF risk profile. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies [STRONG-HF]; NCT03412201)

Single-Operator Left atrial appendage Occlusion utilizing Conscious sedation TEE, Lack of Outpatient pre-imaging, and Same-day Expedited discharge (SOLO-CLOSE): A comparison with conventional approach.

Left atrial appendage occlusion (LAAO) with WATCHMAN currently requires preprocedural imaging, general anesthesia, and inpatient overnight admission. We sought to facilitate simplification of LAAO. We describe and compare SOLO-CLOSE (single-operator LAA occlusion utilizing conscious sedation TEE, lack of outpatient pre-imaging, and same-day expedited discharge) with the conventional approach (CA). A single-center retrospective analysis of 163 patients undergoing LAAO between January 2017 and April 2022 was conducted. The SOLO-CLOSE protocol was enacted on December 1, 2020. Before this date,we utilized the CA. The primary efficacy endpoint was defined as successful LAAO with ≤5 mm peri-device leak at time of closure. The primary safety endpoint was the composite incidence of all-cause deaths, any cerebrovascular accident (CVA), device embolization, pericardial effusion, or major postprocedure bleeding within 7 days of the index procedure. Procedure times, 7-day readmission rates, and cost analytics were collected as well. Baseline characteristics were similar in both cohorts. Congestive heart failure (37.5% vs. 11.1%) and malignancy (28.8% vs. 12.5%) were higher in SOLO-CLOSE. Median CHA2D2SVASc score was 5 in both cohorts. The primary efficacy endpoint was met 100% in both cohorts. Primary safety endpoint was similar between cohorts (p = 0.078). Mean procedure time was 30 min shorter in SOLO-CLOSE (p < 0.01). Seven-day readmissions for SOLO-CLOSE was zero. After SOLO-CLOSE implementation, there was a 188% increase in positive contribution margin per case. The SOLO-CLOSE methodology offers similar efficacy and safety when compared to the CA, while improving clinical efficiency, reducing procedural times, and increasing economic benefit.

Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies

ObjectiveTo investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related.Research design and methodsObservational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC.ResultsObservationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10− 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (−0.04 (−0.12, 0.32) and − 0.03 (−0.13, 0.06)), nor of glucose on CRP (−0.01 (−0.08, 0.07) and − 0.00 (−0.14, 0.13)).ConclusionsElevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.

Hypertrophic cardiomyopathy and competitive sports: let 'em play?

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular genetic conditions. Although most patients with HCM typically do well clinically, there is a small but real incidence of sudden cardiac death. A diagnosis of HCM was previously a reason for complete exclusion in sports, particularly competitive sports.However, many of these recommendations are based on expert consensus, and much data has been published in the last decade furthering the scientific knowledge in this area, and allowing athletes who may have been previously excluded the potential to participate in strenuous activities and competitive sports. With recent publications on participation in sports with HCM, as well as an emphasis on shared decision-making, more athletes with HCM are participating in competitive sports, even at a professional level. Even contact sports in the presence of an implantable cardioverter-defibrillator are no longer mutually exclusive in the current era. Previous guidelines were likely overly restrictive for patients with HCM. Although there is a risk of sudden death that cannot be ignored, the potential for shared decision making as well as medical guidance are entering a new era in all aspects of medicine, particularly in sports participation.

COVID-19 Vaccination Strategies in the Endemic Period: Lessons from Influenza.

Coronavirus disease 2019 (COVID-19) is a highly contagious zoonotic respiratory disease with many similarities to influenza. Effective vaccines are available for both; however, rapid viral evolution and waning immunity make them virtually impossible to eradicate with vaccines. Thus, the practical goal of vaccination is to reduce the incidence of serious illnesses and death. Three years after the introduction of COVID-19 vaccines, the optimal vaccination strategy in the endemic period remains elusive, and health authorities worldwide have begun to adopt various approaches. Herein, we propose a COVID-19 vaccination strategy based on the data available until early 2024 and discuss aspects that require further clarification for better decision making. Drawing from comparisons between COVID-19 and influenza vaccination strategies, our proposed COVID-19 vaccination strategy prioritizes high-risk groups, emphasizes seasonal administration aligned with influenza vaccination campaigns, and advocates the co-administration with influenza vaccines to increase coverage.

Zhen-wu-tang protects against myocardial fibrosis by inhibiting M1 macrophage polarization via the TLR4/NF-κB pathway

BackgroundMyocardial fibrosis is a risk factor that contributes to the increase in the incidence of cardiovascular disease and death, posing a significant threat to human health. Zhen-wu-tang (ZWT) is a classical Chinese medicinal recipe that has been extensively used to manage cardiovascular disorders throughout history. However, the fundamental processes involved in its effects were not clear. ObjectiveThis study examined the therapeutic effects of ZWT on myocardial fibrosis induced by isoproterenol (ISO) in mice, the effect of regulation and underlying mechanism on the polarization of M1 macrophage. MethodsIn vivo, a myocardial fibrosis mouse model was induced via intraperitoneal infusion of isoproterenol (ISO). ZWT or captopril (CAP) was administered intragastrically for 30 days. Cardiac function was evaluated by electrocardiogram (ECG) and echocardiography. By analysing myocardial fibrosis pathomorphologically and identifying fibrosis-related indicators, the protective effect of the ZWT on the heart was evaluated. A model of macrophage polarization was established in vitro by activating RAW264.7 cells with lipopolysaccharide (LPS). The regulatory effects of ZWT on macrophage polarization and the signalling pathways involved were examined by immunofluorescence staining, Western blotting (WB), quantitative real-time PCR (qRT-PCR) and siRNA transfection. ResultsZWT improved cardiac function; reduced fibrotic deposition in cardiac tissues; decreased α-SMA, collagen I, and collagen III levels; and inhibited myocardial fibrosis in mice with ISO-induced myocardial fibrosis. Furthermore, the results showed that ZWT could suppress M1 macrophage polarization by downregulating the expression of CD86 and iNOS in vitro and in vivo. Finally, the results confirmed that ZWT could significantly reduce TLR4/NF-κB signalling pathway activation. ConclusionZWT showed therapeutic effects on ISO-induced myocardial fibrosis mice, and reduced M1 macrophages polarization through inhibiting TLR4/NF-κB pathway, suggesting that ZWT is a promising drug for myocardial fibrosis treatment.

Retrospective Analysis of the Integration of Palliative Care Into the Care of Stroke Patients Admitted to a Regional Stroke Center.

Background: Palliative care (PC) aims to enhance the quality of life for patients when confronted with serious illness. As stroke inflicts high morbidity and mortality, the integration of PC within acute stroke care remains an important aspect of quality inpatient care. However, there is a tendency to offer PC to stroke patients only when death appears imminent. We aim to understand why this may be by examining stroke patients admitted to a regional stroke centre who subsequently died and their provision of PC. Methods: We conducted a retrospective single-centre cohort study of patients who died during admission to the regional stroke centre at Sunnybrook Health Sciences Centre (SHSC) in Toronto, Ontario, Canada. Baseline demographics were assessed using means, standard deviations (SD), medians, interquartile ranges (IQR), and proportions. Descriptive statistics, univariate, and multivariate analyses were performed to ascertain relationships between collected variables. Results: Univariate modeling demonstrated that older age, being female, no stroke diagnosis at admission to hospital, ischemic stroke, and comorbidities of cancer or dementia were associated with a higher incidence of palliative medicine consultation (PMC), while admission from an acute care hospital and a Glasgow Coma Scale (GCS) coma classification were associated with a lower incidence of PMC. The multivariate model identified the GCS coma-related category as the only significant factor associated with a higher incidence of death but was non-significantly related to a lower incidence of PMC. Conclusion: These results highlight continued missed opportunities for PC in stroke patients and underscore the need to better optimize PMC.

Treatment-related mortality among children with cancer in Denmark during 2001-2021.

Survival of children with cancer has markedly improved over recent decades, largely due to intensified treatment regimes. The intensive treatment may, however, result in fatal complications. In this retrospective cohort study, we assessed temporal variation in the incidence of treatment-related death and associated risk factors among children diagnosed with cancer in Denmark during 2001-2021. Among all children diagnosed with first incident cancer before age 15 years recorded in the Danish Childhood Cancer Register (n = 3,255), we estimated cumulative incidence of treatment-related death (death in the absence of progressive cancer) within 5 years from diagnosis using Aalen-Johansen estimators and assessed associated risk factors using Cox regression. Among all 3,255 children with cancer, 93 (20% of all 459 deaths) died from treatment. Of these treatment-related deaths, 39 (42%) occurred within 3 months of diagnosis. The 5-year cumulative incidences of treatment-related death were 3.3% during 2001-2010 and 2.5% during 2011-2021 (p = 0.20). During 2011-2021, treatment-related deaths accounted for more than half of all deaths among children with haematological cancers. Risk factors varied according to cancer group and included female sex, age below 1 year at diagnosis, disease relapse, stem cell transplantation, central nervous system involvement, and metastasis at diagnosis. Despite increasing treatment intensities, the incidence of treatment-related death has remained stable during the past 20 years in Denmark. Still, clinical attention is warranted to prevent treatment-related deaths, particularly among children with haematological cancers. Patient characteristics associated with increased treatment-related death risk support patient-specific treatment approaches to avoid these fatalities.