Incidence Of Death Research Articles

Reactive Oxygen Species (ROS)-Mediated Antibacterial Oxidative Therapies: Available Methods to Generate ROS and a Novel Option Proposal.

The increasing emergence of multidrug-resistant (MDR) pathogens causes difficult-to-treat infections with long-term hospitalizations and a high incidence of death, thus representing a global public health problem. To manage MDR bacteria bugs, new antimicrobial strategies are necessary, and their introduction in practice is a daily challenge for scientists in the field. An extensively studied approach to treating MDR infections consists of inducing high levels of reactive oxygen species (ROS) by several methods. Although further clinical investigations are mandatory on the possible toxic effects of ROS on mammalian cells, clinical evaluations are extremely promising, and their topical use to treat infected wounds and ulcers, also in presence of biofilm, is already clinically approved. Biochar (BC) is a carbonaceous material obtained by pyrolysis of different vegetable and animal biomass feedstocks at 200-1000 °C in the limited presence of O2. Recently, it has been demonstrated that BC's capability of removing organic and inorganic xenobiotics is mainly due to the presence of persistent free radicals (PFRs), which can activate oxygen, H2O2, or persulfate in the presence or absence of transition metals by electron transfer, thus generating ROS, which in turn degrade pollutants by advanced oxidation processes (AOPs). In this context, the antibacterial effects of BC-containing PFRs have been demonstrated by some authors against Escherichia coli and Staphylococcus aureus, thus giving birth to our idea of the possible use of BC-derived PFRs as a novel method capable of inducing ROS generation for antimicrobial oxidative therapy. Here, the general aspects concerning ROS physiological and pathological production and regulation and the mechanism by which they could exert antimicrobial effects have been reviewed. The methods currently adopted to induce ROS production for antimicrobial oxidative therapy have been discussed. Finally, for the first time, BC-related PFRs have been proposed as a new source of ROS for antimicrobial therapy via AOPs.

Prevalence of cardiovascular implantable electronic devices in children with type 1 myotonic dystrophy.

Type 1 myotonic dystrophy (DM1) is a neuromuscular disorder of multiple organ systems with important electrophysiologic (EP) manifestations, leading to a cumulative incidence of sudden death of 6.6%. Due to genetic anticipation, there is a pediatric subset of this patient population. However, most EP research on DM1 patients has been in adults, making cardiac care for pediatric patients difficult and directed by adult guidelines which often leads to cardiovascular implantable electronic device (CIED) implants. We sought to investigate the prevalence of CIEDs in the pediatric DM1 population. The Vizient® Clinical Data Base was queried from October 2019 to October 2023 for admissions with and without ICD-10 code for myotonic dystrophy (G71.11), with and without codes for presence of a pacemaker or ICD (Z95.0, Z95.810). Patients who were identified were stratified by age: Pediatric (0-21 years) and Adult (22-50 years). Prevalence of CIED in pediatric DM1 was 2.1% and in adult DM1 was 15.8%. When comparing to pediatric and adult patients with CIED and without DM1, the odds ratio for CIED in pediatric DM1 was 48.8, compared to 23.3 for CIED in adult DM1. There are pediatric DM1 patients who have received CIED despite a lack of data to inform this decision-making. Further research will be important to ensure appropriate use of CIED in this population and to develop appropriate guidelines to direct management.

Effectiveness and safety of molnupiravir in the intended-use population: an observational cohort study

ObjectivesPrevious research reported inconsistent results on the efficacy of molnupiravir in treating COVID-19. Moreover, efficacy was not assessed in the intended-use population (IUP), as defined by the FDA. Therefore, we aimed to evaluate the effectiveness and safety of molnupiravir for the treatment of COVID-19 in the IUP. MethodsWe performed a retrospective cohort study on all IUP in Israel's Clalit Health Services from January 16, 2022, to February 16, 2023. The effectiveness outcome was the incidence of hospitalization or death due to COVID-19, and the safety outcome was the incidence of all-cause mortality within 35 days of SARS-CoV-2 infection. Cox-proportional hazard models were used to analyse the data after 1:5 propensity-score matching. ResultsA total of 49 515 patients met the eligibility criteria. Of them, 3957 molnupiravir-treated patients were matched to 19 785 untreated patients. In molnupiravir-treated patients, 70 out of 3957 (5.1 per 10 000 person per day) experienced COVID-19-related hospitalization or death, compared with 699 out of 19 785 untreated patients (10.4 per 10 000 person per day); RR: 0.50 (95% CI, 0.39–0.64). All-cause mortality was also lower in the treated group, with 41 out of 3957 (3.0 per 10 000 person per day) experiencing mortality compared with 414 out of 19 785 untreated patients (6.1 per 10 000 person per day); RR: 0.50 (0.36–0.68). DiscussionIn a real-world cohort of IUP, molnupiravir therapy was associated with a significant reduction in hospitalizations or deaths due to COVID-19 and all-cause mortality.

Empagliflozin’s role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial

BackgroundThe incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH.MethodsParticipants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration.ResultsAn initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01).ConclusionsThe EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population.Trial registrationNCT: 04117763.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

BACKGROUND Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 μmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 μmol/L) compared with placebo (95%CI: -1.5 to -0.9; P &lt; 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P &lt; 0.001), NT-proBNP by 25% (95%CI: 18-32; P &lt; 0.001), and QoL scores by 10 points (95%CI: 7-13; P &lt; 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15–50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.

Knowledge, attitude and practice on water, sanitation and hygiene (WASH) and COVID-19 among households in rural Bangladesh

Enhanced water, sanitation, and hygiene (WASH) conditions can significantly reduce the incidence of communicable diseases and deaths related to diarrhea by up to 65%. The US Centers for Disease Control and Prevention (CDC) advocates regular handwashing with soap and water for at least 20 seconds as an effective measure to mitigate the spread of COVID-19. This study aims to assess rural Bangladeshi households' perceptions and knowledge concerning the COVID-19 pandemic, as well as their understanding, attitudes, and practices regarding water, sanitation, and hygiene. A cross-sectional study was conducted between June 2020 and December 2020 to evaluate knowledge and practices related to safe water, sanitation, personal hygiene, and COVID-19 in rural Bangladesh. Self-administered questionnaires, pre-tested for reliability, were utilized to collect self-reported data, which were subsequently analyzed descriptively. Of the study participants, 66.78% were female, with a mean age of 40. The majority (92.36%) demonstrated adequate knowledge of personal hygiene, although 66.78% had not received hygiene education, and a significant proportion reported low levels of hygiene practices (17.28%). Nearly all respondents (98%) reported having access to a pit latrine, either with or without a seal, yet 63.12% indicated that their toilets become unusable during floods, and 29% admitted to practicing open defecation. While nearly all respondents were aware of the ongoing COVID-19 outbreak, only 46% had a comprehensive understanding of its transmission dynamics. Moreover, knowledge about preventive measures against the pandemic was found to be limited. Despite understanding the importance of handwashing, reported hand hygiene practices were inadequate among rural households. Additionally, a majority reported inadequate management of child feces, household waste, and sludge tanks. While awareness of the COVID-19 pandemic was high, a substantial proportion of respondents lacked understanding of its transmission and prevention methods. Moreover, fewer respondents reported using hand sanitizer when venturing outside for work. Future research should explore the impact of these behaviors on health outcomes and propose targeted interventions to improve hygiene practices. Jahangirnagar University J. Biol. Sci. 12(1 &amp; 2): 11-21, 2023 (June &amp; December)

A Population-Based Matched Cohort Study of Digestive System Cancer Incidence and Mortality in Individuals With and Without Inflammatory Bowel Disease.

To study digestive system cancer risks in individuals with inflammatory bowel diseases (IBDs) in the biologic era. We used population-level administrative and cancer registry data from Ontario, Canada, (1994-2020) to compare people with IBD to matched controls (1:10 by sex and birth year) on trends in age-sex standardized cancer incidence and risk ratios of incident cancers and cancer-related deaths. Among 110,919 people with IBD and 1,109,190 controls, colorectal cancer incidence (per 100,000 person-years) declined similarly in people with ulcerative colitis (average annual percentage change [AAPC] -1.81; 95% confidence interval [CI] -2.48 to -1.156) and controls (AAPC -2.79; 95% CI -3.44 to -2.14), while small bowel cancer incidence rose faster in those with Crohn's disease (AAPC 9.68; 95% CI 2.51-17.3) than controls (AAPC 3.64; 95% CI 1.52-5.80). Extraintestinal digestive cancer incidence rose faster in people with IBD (AAPC 3.27; 95% CI 1.83-4.73) than controls (AAPC -1.87; 95% CI -2.33 to -1.42), particularly for liver (IBD AAPC 8.48; 95% CI 4.11-13.1) and bile duct (IBD AAPC 7.22; 95% CI 3.74-10.8) cancers. Beyond 2010, the incidences (and respective mortality rates) of colorectal (1.60; 95% CI 1.46-1.75), small bowel (4.10; 95% CI 3.37-4.99), bile duct (2.33; 95% CI 1.96-2.77), and pancreatic (1.19; 95% CI 1.00-1.40) cancers were higher in people with IBD. Cancer incidence is declining for colorectal cancer and rising for other digestive cancers in people with IBD. Incidence and mortality remain higher in people with IBD than controls for colorectal, small bowel, bile duct, and pancreatic cancers.

Impact of High-Voltage Device Implantation in Elderly Japanese Patients With Heart Failure as Primary Prevention - Post Hoc Analysis of HINODE.

Despite an increased incidence of chronic heart failure (HF) and sudden cardiac death (SCD), the use of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) is much lower in Japan than in Western countries. The HF Indication and SCD Prevention Trial Japan (HINODE) prospectively assessed the mortality rate, appropriately treated ventricular arrhythmias (VA), and HF in Japanese patients with a higher risk of HF.Methods and Results: HINODE consisted of ICD, CRT-defibrillator (CRT-D), pacing, and non-device treatment cohorts. This subanalysis evaluated the impact of the implantation of high-voltage devices (HVD; ICD and CRT-D) in 171 Japanese patients. We compared all-cause mortality, VA, and HF events between elderly (age >70 years at study enrollment) and non-elderly HVD recipients. The estimated survival rate through 24 months in the HVD cohort was 85.8% (97.5% lower control limit 77.6%). The risk of all-cause mortality was increased for the elderly vs. non-elderly (hazard ratio [HR] 2.82; 95% confidence interval [CI] 1.01-7.91; P=0.039), but did not differ after excluding ICD patients with CRT-D indication (HR 2.32; 95% CI 0.79-6.78; P=0.11). There were no differences in VA and HF event-free rates between elderly and non-elderly HVD recipients (P=0.73 and P=0.55, respectively). Although elderly patients may have a higher risk of mortality in general, the benefit of HVD therapy in this group is comparable to that in non-elderly patients.

Left Ventricular Remodeling in Patients with Low Flow Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Low-flow (LF) aortic stenosis (AS) is common among the elderly and associated with worse outcomes than AS with normal stroke volume. It is unknown whether left ventricular (LV) remodeling identifies patients with LF AS at higher risk of complications.LV remodeling was evaluated in 463 patients with severe LF AS referred for transcatheter aortic valve replacement (TAVR) and classified as adaptive (normal geometry and concentric remodeling) or maladaptive (concentric and eccentric hypertrophy) using American Society of Echocardiography sex-specific criteria. Of these, the 390 who underwent TAVR were followed for the endpoints of heart failure (HF) hospitalization and all-cause mortality.The mean patients age was 79 (74.5-84) years. LV remodeling was adaptive in 57.4% (62 normal geometry, 162 concentric remodeling) and maladaptive in 42.6% (127 concentric hypertrophy, 39 eccentric hypertrophy). During a median follow-up of 3 years, 45 patients (11.5%) were hospitalized for HF and 73 (18.7%) died. After adjustment for widely used echocardiographic parameters, maladaptive remodeling was independently associated with HF hospitalization and death (adjusted HR 1.75, CI 1.03-3.00). There was no significant difference between men and women in the association of maladaptive LV remodeling with the composite outcome (p=0.40 for men and p=0.06 for women).In conclusion, in patients with LF AS, maladaptive LV remodeling prior to TAVR is independently associated with higher incidences of post-procedural HF rehospitalization and death in both men and women. Assessment of LV remodeling has prognostic value over and above LVEF and may improve risk stratification for patients with LF AS.

Melanoma Deaths by Thickness: Most Melanoma Deaths Are Not Attributable to Thin Melanomas

IntroductionPrevious population-based studies have reported that the majority of melanoma mortality is related to patients with thin (≤1 mm Breslow thickness) melanomas. The aim of the present study was to evaluate the relative proportion of melanoma-specific deaths across all stages of melanoma at diagnosis over the past 20 y in the United States. MethodsA review of all cutaneous melanoma cases in the US Surveillance, Epidemiology, and End Results registry from 2004 to 2020 was performed. Breslow thickness was categorized as thin (≤1.0 mm), intermediate (>1-4 mm), or thick (>4 mm). All-cause deaths and melanoma-specific deaths were compared across tumor thickness and stage groups at diagnosis. Survival analysis was performed with nonmelanoma deaths considered as a competing risk to estimate the cumulative incidence of melanoma-specific death. ResultsMost melanoma deaths occurred in patients who initially presented with local disease (53%) compared to regional (36%) or distant (11%) disease (P < 0.001). However, most (66%) of the melanoma-specific deaths in patients who presented with localized disease were in those with intermediate or thick (i.e., Breslow thickness >1.0 mm) primary tumors compared to those with thin melanomas (34%). The cumulative incidence of melanoma-specific death at 10 y in patients with localized thin melanomas at the time of diagnosis was 2.6% (95% confidence intervals 2.5%-2.7%). ConclusionsThe public health burden in terms of melanoma-specific mortality is related to patients with tumors >1 mm Breslow thickness, many of whom have regional and distant metastatic disease at the time of diagnosis, not patients with thin melanomas.

Association between magnesium, erythropoietin resistance and mortality: the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS).

Limited data are now available to evaluate the relationship between serum magnesium level, anemia and mortality in the dialysis population. Using data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phases 5 and 6, we analyzed the association between serum magnesium (s-Mg) levels and the erythropoiesis-stimulating agents resistance index (ERI) as the primary outcome. To estimate the longitudinal relationship, a mixed-effect model was used with ERI at each 4-month period as the dependent variable and quintiles of s-Mg at the previous 4-month period as the independent variable. We also examined incidence of infectious events, and the all-cause and cardiovascular disease (CVD)-related deaths as secondary outcomes by Cox regression with quintiles of s-Mg at baseline. Of the 4776 participants in J-DOPPS, 1650 were included in the analysis. The median of s-Mg at baseline was 2.5 mg/dL. A significant linear association of s-Mg with ERI (P for trend <.001) was revealed. Low and high s-Mg levels were not associated with the clinical outcomes of interest, except for the highest quintile of s-Mg being significantly associated with lower incidence of all-cause mortality and CVD-related deaths compared with the middle (reference) quintile. We observed that lower s-Mg levels subsequently induced higher ERI and that mild higher s-Mg levels were possibly associated with good rather than poor outcomes in Japanese hemodialysis patients. Adjustment of s-Mg levels may be proposed as a new strategy at a low cost and risk to reduce the risk of premature mortality.

RBC transfusion and necrotizing enterocolitis in very preterm infants: a multicenter observational study

The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro–Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.

Survival status and predictors of mortality among cervical cancer patients at oncologic centers in Addis Ababa, Ethiopia: a follow up study

BackgroundCervical cancer (CC) ranks as the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths among women globally. In Addis Ababa, there is a shortage of available evidence concerning the phenomenon of survival time and its predictors among women diagnosed with CC. Therefore, this study aimed to assess the survival status and predictors of mortality among CC patients at oncologic centers in Addis Ababa, Ethiopia.MethodsA facility-based retrospective cohort study was conducted among records of women with cervical cancer enrolled from the 1st of January 2017 to the 30th of December 2022 among 252 cervical cancer patients. Data were collected using a pretested, structured data collection checklist by trained data collectors. The Kaplan–Meier survival curve was used to estimate the survival time of the respondents. The Cox multivariable regression model was carried out to identify predictors of CC. Variables with P-value < 0.05 in multivariable analysis were declared as statistically significant.ResultsThe cumulative proportion of surviving at the end of the 10th and 20th month was 99.6% (95%CI: 97.02, 99.94) and 96.99% (95%CI: 93.41, 98.64), respectively. Similarly, it was 92.67% (95%CI: 87.65, 95.70), 85.9% (95%CI: 78.68, 90.94), 68.0% (95%CI: 57.14, 76.66) and 18.27% (8.38, 31.16) at the end of 30th, 40th, 50th and 60th monthly respectively. The overall median survival time was 54 months (95%CI: 52.6, 55.4). The incidence of death among a cohort of women with CC was 7.34 per 1000 person months. Being anemic (AHR: 4.77; 95%CI: 1.93, 11.77; P-value: 0.001), took a single cancer treatment (AHR: 1.92; 95%CI: 1.01, 3.64; P-value: 0.046) and HIV sero status positive (AHR: 2.05; 95%CI: 1.01, 4.19; P-value: 0.048) were statistically significant in multivariable cox proportional hazard model.Conclusion and recommendationAnemia, treatment initiation and HIV-sero status were independent predictors of mortality among women admitted with CC. It is imperative to enhance early screening initiatives and treatment resources for CC, alongside fostering public awareness through collaboration with various media outlets concerning preventive measures, screening procedures, and treatment alternatives for CC.

Comparative study on the predictive value of TG/HDL-C, TyG and TyG-BMI indices for 5-year mortality in critically ill patients with chronic heart failure: a retrospective study

BackgroundThe triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and triglyceride-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute indicators for insulin resistance (IR). This study aimed to compare the predictive value of these indicators for 5-year mortality in critically ill patients with chronic heart failure (CHF).MethodsCritically ill patients with CHF were identified from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases. The primary outcome was 5-year mortality. The relationship between the three indices and mortality risk was determined using multivariate Cox proportional hazards models, Kaplan–Meier (K‒M) analysis and restricted cubic splines analysis. A receiver operating characteristic (ROC) curve was generated to compare the ability of the three indices to predict mortality. Finally, whether the IR indices would further increase the predictive ability of the basic model including baseline variables with a significance level between survivors and non-survivors was evaluated by ROC curve.ResultsAltogether, 1329 patients with CHF were identified from the databases. Cox proportional hazards models indicated that the TyG index was independently associated with an elevated risk of 5-year mortality (hazard ratio [HR], 1.56; 95% confidence interval [CI] 1.29–1.9), while the TyG-BMI index and TG/HDL-C level were significantly associated with 5-year mortality, with an HR (95% CI) of 1.002 (1.000–1.003) and 1.01 (1.00–1.03), respectively. The K–M analysis revealed that the cumulative incidence of all-cause 5-year death increased with increasing quartiles of the TyG index, TyG-BMI index, or TG/HDL-C ratio. According to the ROC curve, the TyG index outperformed the TyG-BMI and TG/HDL-C ratio at predicting all-cause 5-year mortality (0.608 [0.571–0.645] vs. 0.558 [0.522–0.594] vs. 0.561 [0.524–0.598]). The effect of the TyG index on all-cause mortality was consistent across subgroups, with no significant interaction with randomized factors. Furthermore, adding the TyG index to the basic model for 5-year mortality improved its predictive ability (area under the curve, 0.762 for the basic model vs. 0.769 for the basic model + TyG index); however, the difference was not statistically significant.ConclusionAs continuous variables, all three indices were significantly associated with 5-year mortality risk in critically ill patients with CHF. Although these IR indices did not improve the predictive power of the basic model in patients with CHF, the TyG index appears to be the most promising index (vs. TyG-BMI and TG/HDL-C ratio) for prevention and risk stratification in critically ill patients with CHF.

Assessment of the safety of Roxadustat for cardiovascular events in chronic kidney disease-related anemia using meta-analysis and bioinformatics.

This study compares the cardiovascular risk in anemic chronic kidney disease patients treated with Roxadustat versus erythropoietin stimulating agents (ESAs). It also explores the cardiovascular impact of Roxadustat. We searched PubMed, EMBASE, Cochrane, Scopus, and Web of Science databases up to 13 August 2023, using terms such as "ESA," "Roxadustat," "MACE," "stroke," "death," "myocardial infarction," and "heart failure." Two researchers independently selected and extracted data based on predefined criteria. We assessed the risk of bias with the Cochrane tool and analyzed statistical heterogeneity using the Q and I2 tests. We conducted subgroup analyses by geographical region and performed data analysis with Stata 14.0 and RevMan 5.4 software. Data were sourced from the NCBI database by filtering for "Roxadustat" and "human," and differentially expressed genes were identified using R software, setting the significance at p < 0.01 and a 2-fold logFC, followed by GO enrichment analysis, KEGG pathway analysis, and protein interaction network analysis. A total of 15 articles encompassing 1,43,065 patients were analyzed, including 1,38,739 patients treated with ESA and 4,326 patients treated with Roxadustat. In the overall population meta-analysis, the incidences of Major Adverse Cardiovascular Events (MACE), death, and heart failure (HF) were 13%, 8%, and 4% in the Roxadustat group, compared to 17%, 12%, and 6% in the ESA group, respectively, with P-values greater than 0.05. In the subgroup analysis, the incidences were 13%, 11%, and 4% for the Roxadustat group versus 17%, 15%, and 5% for the ESA group, also with p-values greater than 0.05. Bioinformatics analysis identified 59 differentially expressed genes, mainly involved in the inflammatory response. GO enrichment analysis revealed that these genes are primarily related to integrin binding. The main pathways identified were the TNF signaling pathway, NF-κB signaling pathway, and lipid metabolism related to atherosclerosis. The protein interaction network highlighted IL1B, CXCL8, ICAM1, CCL2, and CCL5 as the top five significantly different genes, all involved in the inflammatory response and downregulated by Roxadustat, suggesting a potential role in reducing inflammation. The meta-analysis suggests that the use of Roxadustat and ESA in treating anemia associated with chronic kidney disease does not significantly alter the likelihood of cardiovascular events in the overall and American populations. However, Roxadustat exhibited a safer profile with respect to MACE, death, and heart failure. The bioinformatics findings suggest that Roxadustat may influence integrin adhesion and affect the TNF and NF-κB signaling pathways, along with lipid and atherosclerosis pathways, potentially reducing inflammation.

The 2024 Noto Peninsula earthquake: Preliminary observations and lessons to be learned

On 1st January 2024 an Mw7.5 earthquake occurred along an active fault across the Noto Peninsula. The tremors generated a wide range of cascading hazards, including geological uplift, liquefaction, landslides, fires and tsunamis. This study offers some preliminary observations on the impacts of the cascading hazards. It also describes the pattern of casualties and the experience of evacuees and the management of evacuation centers. The hazards caused damage to buildings and infrastructure and more than 240 deaths. As usual, most casualties were caused by building collapse, but there was a high incidence of death by hypothermia and cold, which is different from the impact of the 2011 Great East Japan Earthquake and reflects the harsher winter climate of this Noto Peninsula. Tsunamis arrived within a few minutes but killed only two people, which testifies to the high awareness of tsunamis in this area. Severe damage to roads significantly delayed early recovery as transportation was curtailed. This earthquake also showed how the problems of evacuees and evacuation shelters had remained unresolved since the 2011 disaster. The main lessons to be learned from this disaster are that improving the earthquake resistance of buildings is important even in Japan, which has a long history of anti-seismic construction. Special provisions are needed for disasters that occur during peak winter or summer weather. Special plans are required to repair and reopen roads damaged by earthquake and to support vulnerable people in both the short and the long term after disaster.

Snakebites in Three Districts of Rural Areas of Western India during Winter

Abstract Introduction: Snakebite is more of a seasonal problem in the state of Rajasthan, as is so in India. The peak incidence of snakebite occurs in the monsoons, with high frequency also reported during the harvest season. The estimated incidence of snakebite in India is 2–3 million, annually leading to 58,000 deaths. Rajasthan is the largest state by area in India and is one of the states that report a high incidence of death due to venomous snakebite in the One-million Death Study. Since snakebite is largely seen as a seasonal problem mainly concentrated in the rainy and summer seasons, the aim of the study was to assess the incidence and mortality of snakebites in winter. Materials and Methods: A telephonic survey of the snakebites in the rural areas of three selected districts of Rajasthan, Western India, chosen based on climatic and geographic conditions. Calls were made to medical officers/in-charge of different primary care centers (PHC)/community health centers (CHC) to report snakebites in the winter season. Medical officers in PHCs/CHCs were asked to report the number of cases reported, deaths, anti-snake venom (ASV) administration, and serious adverse reactions related to ASV administration. The medical officers were further asked if they were confident while administering ASV or not. Results: A total of two deaths were reported out of 39 snakebites (5.1%). ASV was administered to the majority of them (94.8%) with two of them showing adverse reactions to ASV (5.1%). Majority of the bites were reported from primary health centers. Conclusions: The present study suggests that snakebite is not a seasonal problem with significant cases occurring even during the winter months. The study highlights the need for creating awareness and taking adequate precautions among vulnerable population, even in the winter season. In addition, sentinel surveillance for snakebites could be strengthened at the district level.

Negative expression of CD117 predicted inferior OS and PFS in acute promyelocytic leukemia.

In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117-) in 169 APL patients treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. The median follow-up period was 63.0 months. CD117- was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117- subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117- APL (p = 0.023). By multivariate analysis, CD117- was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) (p = 0.022 and p = 0.014, respectively). To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.

Deaths and major cardiovascular events in patients with lymphoma: Analysis from a French nationwide hospitalization database

BackgroundThere are few data assessing the risk of death and cardiovascular events in patients with lymphoma. AimUsing a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma. MethodsFrom 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed. ResultsAfter adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881–1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049–1.188) remained higher in patients with lymphoma. ConclusionIn this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding.

Comprehensive Summary of Safety Data on Nirsevimab in Infants and Children from All Pivotal Randomized Clinical Trials.

Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks' gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA). Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.