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Journal of Infection and Chemotherapy :... Jun 2024Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are...
BACKGROUND
Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are often treated with steroids, require intensive care unit (ICU) treatment, and may therefore be at risk for HCMV infection. However, which factors predispose severely ill patients with COVID-19 to HCMV infection and the prognostic value of such infections remain largely unexplored. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe or critical COVID-19 and evaluate the relationship between HCMV infection and mortality.
METHODS AND FINDINGS
We used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and their contribution to mortality in patients with COVID-19. Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3-1.7% depending on the definition of HCMV infection. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV infection. Furthermore, HCMV infection was associated with patient mortality independent of the observed risk factors for death.
CONCLUSIONS
HCMV infection is a notable complication in patients with severe or critical COVID-19 who are admitted to the ICU or receive steroids, immunosuppressants, and blood transfusion and can significantly increase mortality risk.
PubMed: 38944381
DOI: 10.1016/j.jiac.2024.06.015 -
Clinical Immunology (Orlando, Fla.) Jun 2024Septic cardiomyopathy (SCM) is characterized by an abnormal inflammatory response and increased mortality. The role of efferocytosis in SCM is not well understood. We...
Integrated multi-omics analysis and machine learning developed diagnostic markers and prognostic model based on Efferocytosis-associated signatures for septic cardiomyopathy.
Septic cardiomyopathy (SCM) is characterized by an abnormal inflammatory response and increased mortality. The role of efferocytosis in SCM is not well understood. We used integrated multi-omics analysis to explore the clinical and genetic roles of efferocytosis in SCM. We identified six module genes (ATP11C, CD36, CEBPB, MAPK3, MAPKAPK2, PECAM1) strongly associated with SCM, leading to an accurate predictive model. Subgroups defined by EFFscore exhibited distinct clinical features and immune infiltration levels. Survival analysis showed that the C1 subtype with a lower EFFscore had better survival outcomes. scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) from sepsis patients identified four genes (CEBPB, CD36, PECAM1, MAPKAPK2) associated with high EFFscores, highlighting their role in SCM. Molecular docking confirmed interactions between diagnostic genes and tamibarotene. Experimental validation supported our computational results. In conclusion, our study identifies a novel efferocytosis-related SCM subtype and diagnostic biomarkers, offering new insights for clinical diagnosis and therapy.
PubMed: 38944364
DOI: 10.1016/j.clim.2024.110301 -
International Journal of Cardiology Jun 2024Heart failure is an important cause of mortality and morbidity worldwide. Heart failure with preserved ejection fraction (HFpEF) incidence and prevalence is increasing,... (Review)
Review
Heart failure is an important cause of mortality and morbidity worldwide. Heart failure with preserved ejection fraction (HFpEF) incidence and prevalence is increasing, and the phenotype associated with obesity is the most frequent. Epicardial adipose tissue (EAT) is directly associated with systemic obesity and several previous studies have shown a clear link between EAT and HFpEF. Moreover, the restriction induced by the pericardium is also linked to HFpEF. In this review we will describe the epidemiological association between the pericardium, EAT and HFpEF, how to quantify EAT, what are the pathophysiological mechanism to explain theses association and how can the pericardium and EAT be a treatment target in patients with HFpEF.
PubMed: 38944349
DOI: 10.1016/j.ijcard.2024.132303 -
International Journal of Cardiology Jun 2024The prevalence of HF with preserved ejection raction (HFpEF, with EF ≥50%) is increasing across all populations with high rates of hospitalization and mortality,... (Review)
Review
The prevalence of HF with preserved ejection raction (HFpEF, with EF ≥50%) is increasing across all populations with high rates of hospitalization and mortality, reaching up to 80% and 50%, respectively, within a 5-year timeframe. Comorbidity-driven systemic inflammation is thought to cause coronary microvascular dysfunction and increased epicardial adipose tissue, leading to downstream friborsis and molecular changes in the cardiomyocyte, leading to increased stiffness and diastolic dynsfunction. HFpEF poses unique challenges in terms of diagnosis due to its complex and diverse nature. The diagnosis of HFpEF relies on a combination of clinical assessment, imaging studies, and biomarkers. An additional important step in diagnosing HFpEF involves excluding certain cardiac diagnoses that may be specific underlying causes of HFpEF or may be masquerading as HFpEF and require specific alternative treatment approaches. In addition to administering sodium-glucose cotransporter 2 inhibitors to all patients, the most effective approach to enhance clinical outcomes may involve tailored therapy based on each patient's unique clinical profile. Exercise should be recommended for all patients to improve the quality of life. Glucagon-like peptide-1 1 agonists are a promising treatment option in obese HFpEF patients. Novel approaches targeting inflammation are also in early phase trials.
PubMed: 38944348
DOI: 10.1016/j.ijcard.2024.132304 -
The Science of the Total Environment Jun 2024Prostate cancer (PC) is the second most frequent tumor in men worldwide; however, its etiology remains largely unknown, with the exception of age and family history. The...
BACKGROUND
Prostate cancer (PC) is the second most frequent tumor in men worldwide; however, its etiology remains largely unknown, with the exception of age and family history. The wide variability in incidence/mortality across countries suggests a certain role for environmental exposures that has not yet been clarified.
OBJECTIVE
To evaluate the association between risk of PC (by clinical profile) and residential proximity to pollutant industrial installations (by industrial groups, groups of carcinogens, and specific pollutants released), within the context of a Spanish population-based multicase-control study of incident cancer (MCC-Spain).
METHODS
This study included 1186 controls and 234 PC cases, frequency matched by age and province of residence. Distances from participants' residences to the 58 industries located in the study area were calculated and categorized into "near" (considering different limits between ≤1 km and ≤ 3 km) or "far" (>3 km). Odds ratios (ORs) and 95 % confidence intervals (95%CIs) were estimated using mixed and multinomial logistic regression models, adjusted for potential confounders and matching variables.
RESULTS
No excess risk was detected near the overall industries, with ORs ranging from 0.66 (≤2 km) to 1.11 (≤1 km). However, positive associations (OR; 95%CI) were found, by industrial group, near (≤3 km) industries of ceramic (2.54; 1.28-5.07), food/beverage (2.18; 1.32-3.62), and disposal/recycling of animal waste (2.67; 1.12-6.37); and, by specific pollutant, near plants releasing fluorine (4.65; 1.45-14.91 at ≤1.5 km) and chlorine (5.21; 1.56-17.35 at ≤1 km). In contrast, inverse associations were detected near industries releasing ammonia, methane, dioxins+furans, polycyclic aromatic hydrocarbons, trichloroethylene, and vanadium to air.
CONCLUSIONS
The results suggest no association between risk of PC and proximity to the overall industrial installations. However, some both positive and inverse associations were detected near certain industrial groups and industries emitting specific pollutants.
PubMed: 38944307
DOI: 10.1016/j.scitotenv.2024.174347 -
Delirium in the US: Results from 2023 cross-sectional World Delirium Awareness Day prevalence study.Journal of the Academy of... Jun 2024Delirium is an acute brain dysfunction associated with an increased risk of mortality and future dementia.
IMPORTANCE
Delirium is an acute brain dysfunction associated with an increased risk of mortality and future dementia.
OBJECTIVES
To describe the prevalence of clinically documented delirium in the United States on World Delirium Awareness Day 2023.
DESIGN
Sub-analysis of a prospective, cross-sectional, online, international survey.
SETTING
All healthcare settings were eligible with the exception of operating rooms and outpatient clinics.
PARTICIPANTS
Healthcare clinicians, administrators, and researchers completed the survey.
MAIN OUTCOME AND MEASURE
Prevalence of clinically documented delirium at 8:00 a.m. and 8:00 p.m. on March 15, 2023. Secondary outcomes were related to healthcare delivery. Descriptive statistics are reported. Differences between unit types (non-ICU vs ICU) were examined for all outcomes.
RESULTS
Ninety-one hospital units reported on 1,318/1,213 patients. The prevalence of clinically documented delirium was 16.4% (n=216/1,318) at 8:00 a.m., 17.9% (n=217/1,213) at 8:00 p.m. (p= 0.316) and significantly differed between age groups, reported discipline, unit, and hospital types. Significant differences were identified between non-ICU and ICU settings in the use of delirium-related protocols, non-pharmacologic and pharmacologic management, educational processes, and barriers to evidence-based delirium care.
CONCLUSION
To our knowledge, this is the first epidemiologic survey of clinically documented delirium across two time points in the U.S.. Delirium remains a significant burden and challenge for healthcare systems. The high percentage of units using delirium management protocols suggests administrator and clinician awareness of evidence-based strategies for its detection and mitigation. We provide recommendations for future studies and quality improvement projects to improve clinical recognition and management of delirium.
PubMed: 38944277
DOI: 10.1016/j.jaclp.2024.06.005 -
Progress in Cardiovascular Diseases Jun 2024The function of the right ventricle (RV) is to drive the forward flow of blood to the pulmonary system for oxygenation before returning to the left ventricle. Due to the... (Review)
Review
The function of the right ventricle (RV) is to drive the forward flow of blood to the pulmonary system for oxygenation before returning to the left ventricle. Due to the thin myocardium of the RV, its function is easily affected by decreased preload, contractile motion abnormalities, or increased afterload. While various etiologies can lead to changes in RV structure and function, sudden changes in RV afterload can cause acute RV failure which is associated with high mortality. Early detection and diagnosis of RV failure is imperative for guiding initial medical management. Echocardiographic findings of reduced tricuspid annular plane systolic excursion (<1.7) and RV wall motion (RV S' <10 cm/s) are quantitatively supportive of RV systolic dysfunction. Medical management commonly involves utilizing diuretics or fluids to optimize RV preload, while correcting the underlying insult to RV function. When medical management alone is insufficient, mechanical circulatory support (MCS) may be necessary. However, the utility of MCS for isolated RV failure remains poorly understood. This review outlines the differences in flow rates, effects on hemodynamics, and advantages/disadvantages of MCS devices such as intra-aortic balloon pump, Impella, centrifugal-flow right ventricular assist devices, extracorporeal membrane oxygenation, and includes a detailed review of the latest clinical trials and studies analyzing the effects of MCS devices in acute RV failure.
PubMed: 38944261
DOI: 10.1016/j.pcad.2024.06.009 -
Development of NR0B2 as a therapeutic target for the re-education of tumor associated myeloid cells.Cancer Letters Jun 2024Immune checkpoint blockade (ICB) has had limited utility in several solid tumors such as breast cancer, a major cause of cancer-related mortality in women. Therefore,...
Immune checkpoint blockade (ICB) has had limited utility in several solid tumors such as breast cancer, a major cause of cancer-related mortality in women. Therefore, there is considerable interest in alternate strategies to promote an anti-cancer immune response. A paper co-published in this issue describes how NR0B2, a protein involved in cholesterol homeostasis, functions within myeloid immune cells to modulate the inflammasome and reduce the expansion of immune-suppressive regulatory T cells (T). Here, we develop NR0B2 as a potential therapeutic target. NR0B2 in tumors is associated with improved survival for several cancer types including breast. Importantly, NR0B2 expression is also prognostic of ICB success. Within breast tumors, NR0B2 expression is inversely associated with FOXP3, a marker of T. While a described agonist (DSHN) had some efficacy, it required high doses and long treatment times. Therefore, we designed and screened several derivatives. A methyl ester derivative (DSHN-OMe) emerged as superior in terms of (1) cellular uptake, (2) ability to regulate expected expression of genes, (3) suppression of T expansion using in vitro co-culture systems, and (4) efficacy against the growth of primary and metastatic tumors. This work identifies NR0B2 as a target to re-educate myeloid immune cells and a novel ligand with significant anti-tumor efficacy in preclinical models.
PubMed: 38944231
DOI: 10.1016/j.canlet.2024.217086 -
Current Problems in Cardiology Jun 2024Public health, personal/community health behaviors, health care delivery, and the scientific community have all been impacted by the COVID-19 pandemic and are... (Review)
Review
Public health, personal/community health behaviors, health care delivery, and the scientific community have all been impacted by the COVID-19 pandemic and are consequently poised to consider substantial paradigm shifts that will enhance disease prevention and public health resilience. The current analysis compares the newly developed Lifestyle Health Index (LHI) to U.S. county-level COVID-19 vaccination, infection, and mortality rates. We linked Centers of Disease Control PLACES, the U.S. Community Profile Report, and Nationhood lab databases through common zip-code identifiers to determine the association between county-level LHI scores and COVID-19 outcomes and vaccination status against the backdrop of U.S. regions with distinct cultural phenotypes. There was a statistically significant relationship between a poor LHI, lower COVID-19 vaccination rates and higher COVID-19 infection and mortality rates. There were clear differences in outcomes across the U.S. regions, suggesting distinct regional cultural characteristics may significantly influence health behaviors and outcomes. In the U.S., a syndemic comprising unhealthy lifestyle, chronic disease, and COVID-19 resulted in unnecessary hospitalizations and deaths. Politicization of the pandemic, socioeconomic inequity and regional cultural values meaningfully contributed to the uneven distribution of poor outcomes during this syndemic. Components of the syndemic were avoidable and should not be repeated. Condensed Abstract: The unhealthy lifestyle - chronic disease - COVID-19 U.S. syndemic resulted in unnecessary hospitalizations and deaths. Politicization of the pandemic, socioeconomic inequity and regional cultural values meaningfully contributed to the uneven distribution of poor outcomes during this syndemic. Components of the syndemic were avoidable and should not be repeated.
PubMed: 38944225
DOI: 10.1016/j.cpcardiol.2024.102728 -
Current Problems in Cardiology Jun 2024This study evaluated the relationship between controlling multiple risk factors and diabetes-related heart failure and all-cause mortality, and the extent to which the... (Review)
Review
BACKGROUND
This study evaluated the relationship between controlling multiple risk factors and diabetes-related heart failure and all-cause mortality, and the extent to which the excess risk can be reduced.
METHODS
17,676 patients with diabetes and 69,493 matched non-diabetic control subjects were included in the Kailuan study, with a median follow-up of 11.19 years. The risk factor control was defined by the attainment of target values for systolic blood pressure, body mass index, low-density lipoprotein cholesterol, fasting blood glucose, high-sensitive C-reactive protein and smoking. Fine-Gray and Cox models were used to estimate associations between the degree of risk factor control and risk of heart failure and all-cause mortality respectively.
RESULTS
Among diabetes patients, there was a gradual reduction in the risk of outcomes as the degree of risk factor control increased. For each additional risk factor that was controlled, there was an associated 16% decrease in heart failure risk and a 10% decrease in all-cause mortality risk. Among diabetes patients with ≥5 well-controlled risk factors, the adjusted hazard ratio compared to controls for heart failure and all-cause mortality was 1.25 (95%CI: 0.99-1.56) and 1.17(95%CI: 1.05-1.31) respectively. The protective effect of comprehensive risk factor control on the risk of heart failure was more pronounced in men and those using antihypertensive medications.
CONCLUSIONS
Control for multiple risk factors is associated with reduced heart failure and all-cause mortality risks in a cumulative and sex-specific manner. However, despite optimization of risk factor control, diabetes patients still face increased risks compared to the general population.
PubMed: 38944222
DOI: 10.1016/j.cpcardiol.2024.102737