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Survivorship After Cardiogenic Shock
Advances in critical care therapies for patients with cardiogenic shock (CS), including temporary mechanical circulatory support and multidisciplinary shock teams, have led to improved survival to hospital discharge, ranging from 60% to 70%. After their index hospitalization, however, survivors of CS may continue to face cardiac as well as extracardiac sequelae of these therapies and complications for years to come. Most studies in CS have focused primarily on survival, with limited data on long-term recovery measures among survivors. In other forms of critical illness, research indicates that many intensive care unit survivors experience impairments in multiple domains, such as cognitive function, physical ability, and mental health. These impairments, collectively referred to as Post–Intensive Care Syndrome, in turn impact survivors’ quality of life and future prognosis. This review identifies unique aspects of CS–related survivorship, highlights lessons learned from other forms of critical illness, and outlines future research directions to determine specific strategies to enhance recovery and survivorship after CS.
Association Between Delay to First Shock and Successful First-Shock Ventricular Fibrillation Termination in Patients With Witnessed Out-of-Hospital Cardiac Arrest
BACKGROUND: In patients with out-of-hospital cardiac arrest who present with an initial shockable rhythm, a longer delay to the first shock decreases the probability of survival, often attributed to cerebral damage. The mechanisms of this decreased survival have not yet been elucidated. Estimating the probability of successful defibrillation and other factors in relation to the time to first shock may guide prehospital care systems to implement policies that improve patient survival by decreasing time to first shock. METHODS: Patients with a witnessed out-of-hospital cardiac arrest and ventricular fibrillation (VF) as an initial rhythm were included using the prospective ARREST registry (Amsterdam Resuscitation Studies). Patient and resuscitation data, including time-synchronized automated external defibrillator and manual defibrillator data, were analyzed to determine VF termination at 5 seconds after the first shock. Delay to first shock was defined as the time from initial emergency call until the first shock by any defibrillator. Outcomes were the proportion of VF termination, return of organized rhythm, and survival to discharge, all in relation to the delay to first shock. A Poisson regression model with robust standard errors was used to estimate the association between delay to first shock and outcomes. RESULTS: Among 3723 patients, the proportion of VF termination declined from 93% when the delay to first shock was <6 minutes to 75% when that delay was >16 minutes ( P trend <0.001). Every additional minute in VF from emergency call was associated with 6% higher probability of failure to terminate VF (adjusted relative risk, 1.06 [95% CI, 1.04–1.07]), 4% lower probability of return of organized rhythm (adjusted relative risk, 0.96 [95% CI, 0.95–0.98]), and 6% lower probability of surviving to discharge (adjusted relative risk, 0.94 [95% CI, 0.93–0.95]). CONCLUSIONS: Every minute of delay to first shock was associated with a significantly lower proportion of VF termination and return of organized rhythm. This may explain the worse outcomes in patients with a long delay to defibrillation. Reducing the time interval from emergency call to first shock to ≤6 minutes could be considered a key performance indicator of the chain of survival.
Driving Restrictions and Incapacitation Vulnerability Evaluation After ST-Segment–Elevation Myocardial Infarction: DRIVE-STEMI Study
Correction for Tveit et al., Widespread soil bacterium that oxidizes atmospheric methane
Response by Park and Kang to Letter Regarding Article, “Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial”
Burrow collapse is not the only explanation for rapid, noncatastrophic preservation of 3D dinosaurs
Associations of Circulating ANGPTL3, C-Terminal Domain–Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality
BACKGROUND: ANGPTL3/4/8 (angiopoietin-like proteins 3, 4, and 8) are important regulators of LPL (lipoprotein lipase). ANGPTL8 forms complexes with ANGPTL3 and ANGPTL4. ANGPTL4/8 complex formation converts ANGPTL4 from a furin substrate to a plasmin substrate, and both cleavages generate similar C-terminal domain–containing (CD)—ANGPTL4 fragments. Whereas several studies have investigated associations of free ANGPTL proteins with cardiovascular risk, there are no data describing associations of the complexes and CD-ANGPTL4 with outcomes or describing the effects of the complexes on LPL bound to GPIHBP1 (glycosylphosphatidylinositol HDL-binding protein 1). METHODS: Recombinant protein assays were used to study ANGPTL protein and complex effects on GPIHBP1-LPL activity. ANGPTL3/8, ANGPTL3, ANGPTL4/8, and CD-ANGPTL4 were measured with dedicated immunoassays in 2394 LURIC (Ludwigshafen Risk and Cardiovascular Health) study participants undergoing coronary angiography and 6188 getABI study (German Epidemiological Trial on Ankle Brachial Index) participants undergoing ankle brachial index measurement. There was a follow-up for cardiovascular death with a median (interquartile range) duration of 9.80 (8.75–10.40) years in the LURIC study and 7.06 (7.00–7.14) years in the getABI study. RESULTS: ANGPTL3/8 potently inhibited GPIHBP1-LPL activity and showed positive associations with LDL-C (low-density lipoprotein cholesterol) and triglycerides (both P <0.001). However, in neither study did ANGPTL3/8 correlate with cardiovascular death. Free ANGPTL3 was positively associated with cardiovascular death in the getABI study but not the LURIC study. ANGPTL4/8 and especially CD-ANGPTL4 were positively associated with the prevalence of diabetes, CRP (C-reactive protein; all P <0.001), and cardiovascular death in both studies. In the LURIC and getABI studies, respective hazard ratios for cardiovascular mortality comparing the third with the first ANGPTL4/8 tertile were 1.47 (1.15–1.88) and 1.68 (1.25–2.27) when adjusted for sex, age, body mass index, and diabetes. For CD-ANGPTL4, these hazard ratios were 2.44 (1.86–3.20) and 2.76 (2.00–3.82). CONCLUSIONS: ANGPTL3/8 potently inhibited GPIHBP1-LPL enzymatic activity, consistent with its positive association with serum lipids. However, ANGPTL3/8, LDL-C, and triglyceride levels were not associated with cardiovascular death in the LURIC and getABI cohorts. In contrast, concentrations of ANGPTL4/8 and particularly CD-ANGPTL4 were positively associated with inflammation, the prevalence of diabetes, and cardiovascular mortality.
ADMET-AI Enables Interpretable Predictions of Drug-Induced Cardiotoxicity
AL or ATTR Amyloidosis? Never Two Without Three
Correction for van de Water et al., Therapeutic stem cells expressing variants of EGFR-specific nanobodies have antitumor effects
Reply to Emery-Wetherell: Taphonomy of Lujiatun 3D dinosaurs is inconsistent with death and burial by lahars
Streptokinase is dispensable in Streptococcus dysgalactiae subspecies equisimilis infections of human dendritic cells
Abstract In recent years, increased numbers of severe Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections, including necrotizing soft tissue infections (NSTIs), have been reported. One of the main virulence factors of SDSE is streptokinase (Ska). Ska promotes bacterial spread in the tissue through Ska-plasminogen interactions and subsequent activation of plasminogen to plasmin. In this study, the impact of streptokinase on SDSE infections of human monocyte-derived dendritic cells (moDCs) was investigated. MoDCs were infected with SDSE strain S118 and its isogenic mutant lacking streptokinase. All infections were performed with and without human serum to compare direct Ska-mediated as well as plasmin activity-related effects. Intracellular killing kinetics, moDC viability and maturation, as well as the release of pro-inflammatory cytokines were assessed. Irrespective of the strain and experimental conditions, the bacteria were equally phagocytosed and killed. MoDCs remained viable, readily matured and secreted equal amounts of cytokines in response to S118 as well as S118Δska infections. Our data demonstrate that moDCs response to SDSE infections is not affected by Ska or its respective plasminogen activating function.
Evaluation of hesperidin as a potential larvicide against Culex pipiens with computational prediction of its mode of action via molecular docking
Abstract Hesperidin, a natural flavanone glycoside predominantly found in citrus fruits, has gained attention for its wide-ranging biological activities, including potential insecticidal properties. Culex pipiens, commonly known as the northern house mosquito, is a major vector of several human pathogens, such as the West Nile virus and filariasis, making it a key target in the fight against vector-borne diseases. In this study, we evaluated the larvicidal activity of Hesperidin against Culex pipiens larvae, assessing its potential as an alternative to chemical insecticides. Hesperidin demonstrated potent larvicidal effects, with a lethal concentration 50 (LC50) of 570.3 ± 0.04 µg/mL, outperforming the conventional insecticide Chlorpyrifos 588.3 ± 0.28 µg/mL in efficacy. Molecular docking simulations revealed a strong binding affinity between Hesperidin and crucial neuroreceptors in Culex pipiens, particularly acetylcholinesterase (AChE), a key enzyme involved in nerve signal transmission. The interaction between Hesperidin’s hydroxyl groups and the AChE enzyme’s active site suggests that AChE inhibition is the primary mechanism driving Hesperidin’s insecticidal action. These findings position Hesperidin as a promising, environmentally friendly alternative to synthetic insecticides. However, further research is needed to assess its toxicity to non-target organisms and optimize its formulation for broader application in mosquito control.
Predicting branch retinal vein occlusion development using multimodal deep learning and pre-onset fundus hemisection images
Development and validation of a dynamic nomogram to predict alexithymia in young and middle aged stroke patients
Altered expression profile of plasma exosomal microRNAs in exclusive electronic cigarette adult users
Optical genome mapping to decipher the chromosomal aberrations in families seeking for preconception genetic counseling
Distribution changes of Ormosia microphylla under different climatic scenarios
Development and validation of PCR marker array for molecular selection towards spring, vernalization-independent and winter, vernalization-responsive ecotypes of white lupin (Lupinus albus L.)
Abstract White lupin (Lupinus albus L.) is an ancient grain legume that is still undergoing improvement of domestication traits, including vernalization-responsiveness, providing frost tolerance and preventing winter flowering in autumn-sowing agriculture, and vernalization-independence, conferring drought escape by rapid flowering in spring-sowing. A recent genome-wide association study highlighted several loci significantly associated with the most contrasting phenotypes, including deletions in the promoter of the FLOWERING LOCUS T homolog, LalbFTc1, and some DArT-seq/silicoDArT loci. The present study aimed to develop and validate a versatile PCR marker array enabling molecular selection of spring- and winter-type white lupin ecotypes. Candidate DArT-seq and silicoDArT loci were transformed into cleaved amplified polymorphic sequence (CAPS) or derived CAPS markers. Developed markers, together with those previously published for LalbFTc1 INDELs and quantitative trait loci from linkage maps, were implemented for screening of white lupin germplasm panel subjected to 2-year phenotyping of phenology traits. Three DArT-seq, two silicoDArT and seven LalbFTc1 INDEL markers were positively validated, constituting a convenient PCR-based marker assay for rapid and accurate reselection of white lupin germplasm towards early flowering and thermoneutrality or late flowering and vernalization-responsiveness, as well as for tracking high genetic and phenotypic diversity within white lupin landraces, revealed in the present study.