Death Events Research Articles

Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium.

Virus-induced cell death is a key contributor to COVID-19 pathology. Cell death induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well studied in myeloid cells but less in its primary host cell type, angiotensin-converting enzyme 2 (ACE2)-expressing human airway epithelia (HAE). SARS-CoV-2 induces apoptosis, necroptosis, and pyroptosis in HAE organotypic cultures. Single-cell and limiting-dilution analysis revealed that necroptosis is the primary cell death event in infected cells, whereas uninfected bystanders undergo apoptosis, and pyroptosis occurs later during infection. Mechanistically, necroptosis is induced by viral Z-RNA binding to Z-DNA-binding protein 1 (ZBP1) in HAE and lung tissues from patients with COVID-19. The Delta (B.1.617.2) variant, which causes more severe disease than Omicron (B1.1.529) in humans, is associated with orders of magnitude-greater Z-RNA/ZBP1 interactions, necroptosis, and disease severity in animal models. Thus, Delta induces robust ZBP1-mediated necroptosis and more disease severity.

Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China

IntroductionPatients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus....

Emergence of large-scale cell death through ferroptotic trigger waves

Large-scale cell death is commonly observed during organismal development and in human pathologies1–5. These cell death events extend over great distances to eliminate large populations of cells, raising the question of how cell death can be coordinated in space and time. One mechanism that enables long-range signal transmission is trigger waves6, but how this mechanism might be used for death events in cell populations remains unclear. Here we demonstrate that ferroptosis, an iron- and lipid-peroxidation-dependent form of cell death, can propagate across human cells over long distances (≥5 mm) at constant speeds (around 5.5 μm min−1) through trigger waves of reactive oxygen species (ROS). Chemical and genetic perturbations indicate a primary role of ROS feedback loops (Fenton reaction, NADPH oxidase signalling and glutathione synthesis) in controlling the progression of ferroptotic trigger waves. We show that introducing ferroptotic stress through suppression of cystine uptake activates these ROS feedback loops, converting cellular redox systems from being monostable to being bistable and thereby priming cell populations to become bistable media over which ROS propagate. Furthermore, we demonstrate that ferroptosis and its propagation accompany the massive, yet spatially restricted, cell death events during muscle remodelling of the embryonic avian limb, substantiating its use as a tissue-sculpting strategy during embryogenesis. Our findings highlight the role of ferroptosis in coordinating global cell death events, providing a paradigm for investigating large-scale cell death in embryonic development and human pathologies.

Carboxyhemoglobin as Potential Biomarker for Cardiac Surgery Associated Acute Kidney Injury

Carboxyhemoglobin (CO-Hb) is a marker of hemolysis and inflammation, both risk factors for cardiac surgery-associated AKI (CSA-AKI). However, the association between CO-Hb and CSA-AKI remains unknown. A retrospective cohort study. Tertiary university-affiliated metropolitan hospital: single center. Adult on-pump cardiac surgery patients from July 2014 to June 2022 (N = 1,698). None. Patients were stratified into quartiles based on CO-Hb levels at intensive care unit (ICU) admission. A progressive increased risk of CSA-AKI was observed with higher CO-Hb levels at ICU admission. On multivariable logistic regression analysis, the highest quartile (CO-Hb ≥ 1.4%) showed an independent association with the occurrence of CSA-AKI (odds ratio 1.45 compared to the lowest quartile [CO-Hb < 1.0%], 95% CI 1.023-2.071; p = 0.038). Compared to patients with CO-Hb <1.4%, patients with CO-Hb ≥ 1.4% at ICU admission had significantly higher postoperative creatinine (135 vs 116 μmol/L, p < 0.001), higher rates of postoperative RRT (6.7% vs 2.3%, p < 0.001) and AKI (p < 0.001) on univariable analysis and shorter time to event for AKI or death (p < 0.001). CO-Hb ≥ 1.4% at ICU admission is an independent risk factor for CSA-AKI, which is easily obtainable and available on routine arterial blood gas measurements. Thus, CO-Hb may serve as a practical and biologically logical biomarker for risk stratification and population enrichment in trials of CSA-AKI prevention.

Prognoses and risk stratification of thrombus-associated events in heart failure patients without atrial fibrillation.

We aim to assess the risk of thrombus-associated events (TAE) in patients with heart failure (HF) without atrial fibrillation (AF) and develop an effective scoring system for a risk stratification model. This retrospective study included 450 patients (median age 64.0years, interquartile range [55.0, 75.0]; 31.6% women) hospitalized for HF without AF and atrial flutter, but with a left ventricular ejection fraction (LVEF)≤55% and New York Heart Association (NYHA) functional class of III-IV. A median follow-up of 47months was conducted. In the present study, TAE during follow-up was independently associated with both all-cause death [hazard ratio (HR) 1.756, 95% confidence interval (CI) 1.324-2.328, P<0.001] and readmission for HF (HR 1.574, 95% CI 1.122-2.208, P=0.009) after adjustment for covariates. Hypertension (HR 1.573, 95% CI 1.018-2.429, P=0.041), atrial arrhythmia excluding AF (AAexAF) (HR 2.041, 95% CI 1.066-3.908, P=0.031), previous ischaemic stroke (HR 2.469, 95% CI 1.576-3.869, P<0.001), and vascular disease (HR 1.658, 95% CI 1.074-2.562, P=0.023) were independently associated with TAE. Age (HR 1.021, 95% CI 1.008-1.033, P=0.001), previous ischaemic stroke (HR 1.685, 95% CI 1.248-2.274, P=0.001), LVEF ([10, 25] vs. [40, 55]) HR 1.925, 95% CI 1.311-2.826, P=0.001; (25, 40] vs. (40, 55] HR 1.084, 95% CI 0.825-1.424, P=0.563), and creatinine clearance rate (Ccr) (HR 0.991, 95% CI 0.986-0.996, P=0.001) were independently associated with composite events of TAE and death (TAE-D). CHA2DS2VASc modestly predicted 5-year TAE [area under the receiver operating characteristic curves (AUC) 0.660, P<0.001 compared with 0.5] and TAE-D (AUC 0.639, P<0.001 compared with 0.5). (C)ACE, formed by incorporating AAexAF, LVEF, and Ccr into CHA2DS2VASc, had higher AUC for predicting 5-year TAE (0.694 vs. 0.660, P=0.018) and TAE-D (0.708 vs. 0.639, P<0.001) compared with CHA2DS2VASc. In patients with HF with reduced ejection fraction (HFrEF), (C)ACE and (C)ACEN [formed by incorporating NYHA into (C)ACE] had higher AUC compared with CHA2DS2VASc in predicting 5-year TAE (0.700 and 0.707 vs. 0.649, P=0.013 and 0.030, respectively) and TAE-D (0.712 and 0.713 vs. 0.622, P<0.001 and <0.001, respectively). The AUC did not improve statistically from (C)ACE to (C)ACEN (0.700 vs. 0.707, P=0.600 for TAE; 0.712 vs. 0.713, P=0.917 for TAE-D). In HF without AF, TAE during follow-up was associated with adverse prognoses. The independent risk factors of TAE or TAE-D improved CHA2DS2-VASc predictive ability, especially in patients with HFrEF. Our findings provide new evidence for TAE risk stratification in HF without AF, potentially guiding prophylactic anticoagulation.

Cardiomyopathy in Duchenne Muscular Dystrophy and the Potential for Mitochondrial Therapeutics to Improve Treatment Response.

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene, resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with the development of cardiomyopathy-the leading cause of death-inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge. There is no cure for DMD; treatment is aimed at delaying disease progression and alleviating symptoms. A comprehensive understanding of the pathophysiological mechanisms is crucial to the development of targeted treatments. While established hypotheses of underlying mechanisms include sarcolemmal weakening, upregulation of pro-inflammatory cytokines, and perturbed ion homeostasis, mitochondrial dysfunction is thought to be a potential key contributor. Several experimental compounds targeting the skeletal muscle pathology of DMD are in development, but the effects of such agents on cardiac function remain unclear. The synergistic integration of small molecule- and gene-target-based drugs with metabolic-, immune-, or ion balance-enhancing compounds into a combinatorial therapy offers potential for treating dystrophin deficiency-induced cardiomyopathy, making it crucial to understand the underlying mechanisms driving the disorder.

Triglyceride-glucose index and the prognosis of patients with heart failure: A meta-analysis.

The triglyceride-glucose index (TyGI) is a novel indicator of insulin resistance, which has been associated with an increased risk of cardiovascular diseases. The aim of this meta-analysis was to determine the association between TyGI and the prognosis of patients with heart failure (HF). Cohort studies relevant to the aim of the meta-analysis were retrieved by searching electronic databases, including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data, incorporating the influence of between-study heterogeneity. Twelve studies involving 20,639 patients with HF were included. Pooled results showed that compared to patients with the lowest category of TyGI at baseline, those with the highest TyGI index were associated with a higher risk of all-cause mortality during follow-up (relative risk [RR] 1.71, 95% confidence interval [CI] 1.46 - 2.00; P < 0.001; I² = 55%). Sensitivity analyses limited to studies after adjustment for confounding factors showed similar results (RR 1.89, 95% CI 1.67 - 2.21; P < 0.001; I² = 13%). Subsequent meta-analyses also showed that a high TyGI at baseline was related to the incidence of cardiovascular death (RR 1.87, 95% CI 1.42 - 2.47; P < 0.001; I² = 57%), HF rehospitalization (RR 1.33, 95% CI 1.04 - 1.69; P < 0.02; I² = 46%), and major adverse cardiovascular events (RR 1.69, 95% CI 1.39 - 2.06; P < 0.001; I² = 17%) during follow-up. In conclusion, a high TyGI may be associated with a poor clinical prognosis for patients with HF.

Effect of low blood pressure on prognosis of acute heart failure

Low blood pressure (BP) is associated with poor outcomes in patients with heart failure (HF). We investigated the influence of initial BP on the prognosis of HF patients at admission, and prescribing patterns of HF medications, such as angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and beta-blockers (BB). Data were sourced from a multicentre cohort of patients admitted for acute HF. Patients were grouped into heart failure reduced ejection fraction (HFrEF) and HF mildly reduced/preserved ejection fraction (HFmrEF/HFpEF) groups. Initial systolic and diastolic BPs were categorized into specific ranges. Among 2778 patients, those with HFrEF were prescribed ACEi, ARB, or BB at discharge, regardless of their initial BP. However, medication use in HFmrEF/HFpEF patients tended to decrease as BP decreased. Lower initial BP in HFrEF patients correlated with an increased incidence of all-cause death and composite clinical events, including HF readmission or all-cause death. However, no significant differences in clinical outcomes were observed in HFmrEF/HFpEF patients according to BP. Initial systolic (< 120 mmHg) and diastolic (< 80 mmHg) BPs were independently associated with a 1.81-fold (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.349–2.417, p < 0.001) and 2.24-fold (OR 2.24, 95% CI 1.645–3.053, p < 0.001) increased risk of long-term mortality in HFrEF patients, respectively. In conclusion, low initial BP in HFrEF patients correlated with adverse clinical outcomes, and BP < 120/80 mmHg independently increased mortality. However, this relationship was not observed in HFmrEF/HFpEF patients.

Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real-World Data.

Results from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy)indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR-CA). However, real-world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR-CA treated with tafamidis in a real-world setting and assess the prognostic role of the New York Heart Association (NYHA) classification. We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR-CA (wild-type or variant) treated with tafamidis. Clinical outcome was tracked through follow-up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan-Meier analysis estimated overall and MACE-free survival including NYHA subgroups (NYHA I/II versus NYHA III). One hundred sixty-seven patients with ATTR-CA (94.6% wild-type) were enrolled and followed for a median of 539 [323-869] days. Median overall survival was not reached. Estimated 1-year, 2-year, and 5-year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (P=0.002). Median MACE-free survival time was 1082 (95% CI, 962-1202) days. MACE-free survival was higher in the NYHA I/II subgroup (P<0.001). With respective hazard ratios of 5.85 (95% CI, 1.48-23.18; P=0.012) and 3.95 (95% CI, 1.99-7.84; P<0.001), NYHA III was an independent predictor of death and MACE. Treatment of ATTR-CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a reliable tool to provide patients with individualized prognostic information.

Association of Anthropometric Indices With Midlife Cardiovascular Risk in Young Individuals Without Obesity and Traditional Risk Factors.

The aim of this study was to assess how early-adulthood body mass index (BMI) and waist circumference (WC) relate to long-term cardiovascular structure, function, and prognosis in individuals without obesity and with low cardiovascular risk factor (CVRF) burden. A total of 2024 participants aged 18 to 30 from the CARDIA (Coronary Artery Risk Development in Young Adults) study, without obesity and with low CVRFs defined as the absence of cardiovascular disease (CVD), diabetes, hypertension, current smoking, and dyslipidemia were included. A CVRF-optimal subgroup was also defined, with blood pressure<120/80 mm Hg, fasting glucose <100 mg/dL, total cholesterol <200, low-density lipoprotein cholesterol <130, and women with high-density lipoprotein cholesterol ≥50 mg/dL. Coronary artery calcification, carotid intima-media thickness, left ventricular mass, left ventricular ejection fraction, longitudinal peak systolic strain, and diastolic function were assessed in midlife. Cox regression was used to calculate hazard ratios of BMI and WC for all-cause death and CVD events. Logistic regression was used to estimate odds ratios for subclinical CVD. Over 33.9 years (median follow-up), 5.2% (n=105) died, and 2.6% (n=52) had CVD events. Each 1-SD BMI increase was associated with 27% (95% CI, 1.10-1.47), 24% (1.08-1.43), 42% (1.20-1.68), 28% (1.05-1.57), 51% (1.20-1.90), and 49% (1.10-2.02) higher odds of coronary artery calcification presence, increased carotid intima-media thickness, left ventricular hypertrophy, reduced left ventricular ejection fraction, low longitudinal peak systolic strain, and diastolic dysfunction, respectively, in the CVRF-low group. Generally, similar associations were found for WC and in the CVRF-optimal subgroup. No significant associations between BMI and WC with CVD and death were found. Elevations in BMI and WC among young low-risk individuals, even within the nonobesity range, are associated with midlife cardiovascular health.

Associations between COVID-19 therapies and outcomes in rural and urban America: A multisite, temporal analysis from the Alpha to Omicron SARS-CoV-2 variants.

To investigate the enduring disparities in adverse COVID-19 events between urban and rural communities in the United States, focusing on the effects of SARS-CoV-2 vaccination and therapeutic advances on patient outcomes. Using National COVID Cohort Collaborative (N3C) data from 2021 to 2023, this retrospective cohort study examined COVID-19 hospitalization, inpatient death, and other adverse events. Populations were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR). Adjustments included demographics, variant-dominant waves, comorbidities, region, and SARS-CoV-2 treatment and vaccination. Statistical methods included Kaplan-Meier survival estimates, multivariable logistic, and Cox regression. The study included 3,018,646 patients, with rural residents constituting 506,204. These rural dwellers were older, had more comorbidities, and were less vaccinated than their urban counterparts. Adjusted analyses revealed higher hospitalization odds in UAR and NAR (aOR 1.07 [1.05-1.08] and 1.06 [1.03-1.08]), greater inpatient death hazard (aHR 1.30 [1.26-1.35] UAR and 1.37 [1.30-1.45] NAR), and greater risk of other adverse events compared to urban dwellers. Delta increased, while Omicron decreased, inpatient adverse events relative to pre-Delta, with rural disparities persisting throughout. Treatment effectiveness and vaccination were similarly protective across all cohorts, but dexamethasone post-ventilation was effective only in urban areas. Nirmatrelvir/ritonavir and molnupiravir better protected rural residents against hospitalization. Despite advancements in treatment and vaccinations, disparities in adverse COVID-19 outcomes persist between urban and rural communities. The effectiveness of some therapeutic agents appears to vary based on rurality, suggesting a nuanced relationship between treatment and geographic location while highlighting the need for targeted rural health care strategies.

Cardiac arrest and cardiogenic shock complicating ST-segment elevation myocardial infarction in China: A retrospective multicenter study

BackgroundData on the effect of cardiac arrest (CA), cardiogenic shock (CS), and their combination on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI) are limited. The present study sought to evaluate the clinical outcomes of STEMI complicated by CA and CS, and to identify the risk factors for CA or CS. MethodsThis study included 7468 consecutive patients with STEMI in China. The patients were divided into 4 groups (CA + CS, CA only, CS only, and No CA or CS). The endpoints were 30-day all-cause death and major adverse cardiovascular events. A Cox proportional hazards regression analysis was performed. ResultsCA, CS, and their combination were noted in 332 (4.4 %), 377 (5.0 %), and 117 (1.6 %) among all patients. During the 30-day follow-up, 817 (10.9 %) all-cause deaths and 964 (12.9 %) major adverse cardiovascular events occurred, and the incidence of all-cause mortality (3.6 %, 62.3 %, 74.1 %, 83.3 %) and major adverse cardiovascular events (5.4 %, 67.1 %, 75.0 %, and 87.2 %) significantly increased in the No CA or CS, CS only, CA only, and CA + CS groups, respectively. In the multivariate Cox regression models, compared with the No CA or CS group, the CA + CS, CA, and CS-only groups were associated with an increased risk of all-cause death and major adverse cardiovascular events. Patients with CA + CS had the highest risk of all-cause death (hazard ratio [HR], 25.259 [95 % confidence interval (CI) 19.221–33.195]) and major adverse cardiovascular events (HR 19.098, 95%CI 14.797–24.648). ConclusionsCA, CS, and their combination were observed in approximately 11 % of Chinese patients with STEMI, and were associated with increased risk for 30-day mortality and major adverse cardiovascular events in Chinese patients with STEMI.

Effect of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation: A retrospective cohort study.

To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation. This retrospective observational cohort study included 196 patients, 75-102-years-old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini-Nutritional Assessment-Short Form (MNA-SF). Patients with MNA-SF scores of 0-11 and 12-14 were included in the malnutrition and nonmalnutrition groups, respectively. The average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p < .05). The incidence of all-cause death in the malnutrition group was higher than that in the nonmalnutrition group (p = .007). Kaplan-Meier curve indicated that malnutrition patients have a higher risk of all-cause death (log-rank test, p = .001) and major bleeding events (p = .017). Multivariate Cox proportional hazard regression analysis corrected for confounders showed that malnutrition was an independent risk factor of all-cause death (HR = 1.780, 95%CI:1.039-3.050, p = .036). The malnutrition group had a significantly high incidence of major bleeding than the nonmalnutrition group (p = .026), and there was no significant difference in the proportion of anticoagulation therapy (p = .082) and the incidence of ischemic stroke/systemic embolism (p = .310) between the two groups. Malnutrition is an independent risk factor of all-cause death in elderly patients with atrial fibrillation. The incidence of major bleeding in malnourished elderly patients with atrial fibrillation is high, and the benefit of anticoagulation therapy is not obvious.

THE APPOINTMENT OF A WASI IN ADMINISTRATION OF TESTATE ESTATES IN MALAYSIA: A LEGAL ANALYSIS

In the event of death, an appointment of a wasi is considered as an important requirement under the law because he plays a vital role in ensuring the deceased’s estate to be managed properly and efficiently. In addition, the appointment of wasi may expedite the process of administration and distribution of property and avoid disputes among the family members of the deceased. In Malaysia, the Rules of Court 2012 does not include the estate of a Muslim dying leaving a will because it does not come within the scope of the Wills Act 1959. However, the existence of will with the appointment of a wasi is valid for application of grant of Probate though the fact it is a Muslim will. Moreover, the appointment of a wasi is not clearly mentioned in any states’ enactment but it is only provided under the statutes of general application such as Probate and Administration Act 1959. Thus, this paper attempts to analyse the laws on the appointment of a wasi in estate administration. This study is based on a qualitative study and its approach is a content analysis methodology. This study reveals that the laws governing the appointment of a wasi in Malaysia involves a dual legal system and it subjects to several legal constraints under federal and state laws. The findings of the study provide room for further improvement with regards to the appointment of a wasi particularly in the administration of Muslim’s estate. The study concludes that there is a lacuna in the existing laws where the appointment of a wasi is not expressly clarified in any state laws except provided in federal laws.

Carbon isotope geochemistry and its geological significance in the Jixian system of the Qishan section, Ordos Basin

Carbon isotopes are important criteria for determining the underground diagenetic evolution and the evolution characteristics of the Earth's surface environment. Because the Mesoproterozoic was between the two great oxidation events, the changes in inorganic carbon isotopes were relatively gentle, making high-resolution sections of inorganic and organic carbon particularly important for global comparisons. To better constrain the isotopic variation and origins of the Mesoproterozoic, in this study, the Qishan section in the Ordos Basin of China was selected for investigation of its sedimentology, petrology, and geochemistry. The results show that the carbon isotope variations of the Jixian Formation carbonates in the Qishan section were generally not significant, with an average value close to 0‰. Similar characteristics were observed in the Luonan section, the Jixian section and the Jixian Group section (a combined section located at the north margin of North China) in the Yanliao Basin. This indicates that the carbon pool in the seawater had not undergone large-scale changes, and that the aquatic environment remained relatively consistent. A short-term negative excursion that appeared in the L2 member of the Longjiayuan Formation, at the same time may be closely related to greater organic carbon retention caused by a short-term event of biological death. It was not ruled out that carbonate minerals converted by 12C-rich produced by diagenetic evolution may had an impact on carbon isotopes during the rock evolution process.

Optimal antiplatelet therapy after revascularization of left subclavian artery during TEVAR

BackgroundThoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is required when treating patients with involvement of LSA. The best antiplatelet therapy after LSA reconstruction is presently uncertain.MethodsThis study retrospectively analyzed 245 type B aortic dissection patients who underwent left subclavian artery revascularization during TEVAR. Out of 245 patients, 159 (64.9%) were in the single antiplatelet therapy (SAPT) group, receiving only aspirin, and 86 (35.1%) were in the dual antiplatelet therapy (DAPT) group, receiving aspirin combined with clopidogrel. During the 6-month follow-up, primary endpoints included hemorrhagic events (general bleeding and hemorrhagic strokes), while secondary endpoints comprised ischemic events (left upper limb ischemia, ischemic stroke, and thrombotic events), as well as death and leakage events. Both univariate and multivariate Cox regression analyses were performed on hemorrhagic and ischemic events, with the Kaplan-Meier method used to generate the survival curve.ResultsDuring the six-month follow-up, the incidence of hemorrhagic events in the DAPT group was higher (8.2% vs. 30.2%, P < 0.001). No significant differences were observed in ischemic events, death, or leakage events among the different antiplatelet treatment schemes. Multivariate Cox regression analysis showed that DAPT (HR: 2.22, 95% CI: 1.07–4.60, P = 0.032) and previous chronic conditions (HR:3.88, 95% CI: 1.24–12.14, P = 0.020) significantly affected the occurrence of hemorrhagic events. Chronic conditions in this study encompassed depression, vitiligo, and cholecystolithiasis. Carotid subclavian bypass (CSB) group (HR:0.29, 95% CI: 0.12–0.68, P = 0.004) and single-branched stent graft (SBSG) group (HR:0.26, 95% CI: 0.13–0.50, P < 0.001) had a lower rate of ischemic events than fenestration TEVAR (F-TEVAR). Survival analysis over 6 months revealed a lower risk of bleeding associated with SAPT during hemorrhagic events (P = 0.043).ConclusionsIn type B aortic dissection patients undergoing LSA blood flow reconstruction after synchronous TEVAR, the bleeding risk significantly decreases with the SAPT regimen, and there is no apparent ischemic compensation within 6 months. Patients with previous chronic conditions have a higher risk of bleeding. The CSB group and SBSG group have less ischemic risk compared to F-TEVAR group.

RECOLLECTION JOURNALISTIC DISCOURSE ON REVEREND OSTAP NYZHANKIVSKYI

The article examines memorial journalism and articles from the newspapers of the Ukrainian diaspora of the second half of the 20th century dedicated to the social and cultural and educational figure, composer, conductor Priest Ostap Nyzhankivskyi. The author highlights the thematic content of the memoir printed sources by Ivan Bodnaruk, Ostap Bobykevych, Osip Zaleskyi, Andriy Kigichak on the pages of "New Path", "America", "Our Call", "Ukrainian Word", "Path of Victory". The biographical material that deepens the biography and milestones of the artist of Eastern Galicia is analyzed. The popularity of the figure of Ostap Nyzhankivskyi is understood in the context of the development of the socio-cultural space of the region on the basis of investigated newspaper articles. The source-scientific, axiological, cognitive value of journalistic articles that "saw the world" in the non-national world space is argued. Prominent descendants of the Nyzhankivskyi family, as well as pages of the artist's life during different years are mentioned and described in the article. In addition, attention is paid to the choral heritage of Ostap Nyzhankivsky thanks to the printed memories of Ivan Bodnaruk. The Nyzhankivskys' family talent for music is outlined, in particular speaking about his son of Nestor Nyzhankivskyi, as well as creative communication with prominent figures Solomiya Krushelnytska, Ivan Franko, Oleksandr Koshyts, that is described in the publication of Ostap Bobykevych. The value of the composer's artistic flair and public activity in the creation of "Lviv Boyan", "Berezhan Boyan", "Stryy Boyan", "Musical Library" which is presented in the publication of Osip Zaleskyi is determined. The tragic events of the priest's death were clarified through the memoirs of Andriy Kigichak. It has been proven that memorial printed sources are valuable archive material in the modern socio-cultural space of Ukraine. It is argued that the analyzed materials will be a respectable basis for researchers of a number of issues from the historical and musical past period of Eastern Galicia of the second half of the 19th century, in particular the activities of the priestly elite of the region in the development of Ukrainian statehood, the creative work of Ostap Nyzhankivskyi, as well as for cultural scientists and musicologists who study sociocultural pages of the period of belonging to the Polish state.

Initial decrease in the lipoprotein(a) level is a novel prognostic biomarker in patients with acute coronary syndrome.

Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular diseases; however, its role in acute coronary syndrome (ACS) remains unclear. To investigate the hypothesis that the Lp(a) levels are altered by various conditions during the acute phase of ACS, resulting in subsequent cardiovascular events. From September 2009 to May 2016, 377 patients with ACS who underwent emergent coronary angiography, and 249 who completed ≥ 1000 d of follow-up were enrolled. Lp(a) levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention (PCI) to 48 h after PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE; cardiac death, other vascular death, ACS, and non-cardiac vascular events). The mean circulating Lp(a) level decreased significantly from pre-PCI (0 h) to 12 h after (19.0 mg/dL to 17.8 mg/dL, P < 0.001), and then increased significantly up to 48 h after (19.3 mg/dL, P < 0.001). The changes from 0 to 12 h [Lp(a)Δ0-12] significantly correlated with the basal levels of creatinine [Spearman's rank correlation coefficient (SRCC): -0.181, P < 0.01] and Lp(a) (SRCC: -0.306, P < 0.05). Among the tertiles classified according to Lp(a)Δ0-12, MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups (66.2% vs 53.6%, P = 0.034). A multivariate analysis revealed that Lp(a)Δ0-12 [hazard ratio (HR): 0.96, 95% confidence interval (95%CI): 0.92-0.99] and basal creatinine (HR: 1.13, 95%CI: 1.05-1.22) were independent determinants of subsequent MACE. Circulating Lp(a) levels in patients with ACS decreased significantly after emergent PCI, and a greater decrease was independently associated with a worse prognosis.

Feasibility study on atrial fibrillation ablation with pulsed field ablation and concomitant occlusion of the left atrial appendage.

Atrial fibrillation (AF) ablation and left atrial appendage occlusion (LAAO) are increasingly performed as individual procedures. Pulsed field ablation (PFA) has significantly reduced procedure duration and may be advantageous for the combined approach. We have launched a programme for simultaneous AF ablation using PFA and LAAO for patients qualifying for both treatments and excluding those with a complex anatomy. We compare procedure duration and fluoroscopy time against individual procedures (either AF ablation or LAAO alone), all performed by the same operators and using consistent technologies. We performed the combined procedure in 10 patients (50% males; median age 70 years) and excluded 2 patients (17%) because of a complex left atrial appendage anatomy. No death, stroke, or major bleeding events, including pericardial effusion, occurred. For single-procedure comparison, 207 AF ablation procedures and 61 LAAO procedures were available. The total median procedure duration was 79 min (range 60-125) for the combined procedure, 71 min (25-241) for individual AF ablation (51 min without and 78 min with 3-dimensional electroanatomic mapping), and 47 min (15-162) for individual LAAO. The respective fluoroscopy times were 21 (15-26), 15 (5-44), and 10 (3-50) min. For the combined procedure, femoral vein access to last PFA application lasted 49 min (34-93) and LAAO added 20 min (15-37). Simultaneous PFA-based AF ablation and LAAO in carefully selected patients is feasible and safe and can be executed within a short overall procedure duration.

COVID-19 in a common woolly monkey (Lagothrix lagothricha): First evidence of fatal outcome in a nonhuman primate after natural SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization in March 2020. Since then, viral spread from humans to animals has occurred worldwide. Nonhuman primates (NHPs) have been found to be susceptible to reverse-zoonosis transmission of SARS-CoV-2, but initial research suggested that platyrrhine primates are less susceptible than catarrhine primates. Here we report the natural SARS-CoV-2 infection of a common woolly monkey (Lagothrix lagothricha) from a wildlife rehabilitation center in Ecuador. The course of the disease, the eventual death of the specimen, and the pathological findings are described. Our results show the susceptibility of a new platyrrhine species to SARS-CoV-2 and provide evidence for the first time of a COVID-19-associated death in a naturally infected NHP. The putative route of transmission from humans, and implications for captive NHPs management, are also discussed. Given that common woolly monkeys are at risk of extinction in Ecuador, further understanding of the potential threat of SARS-CoV-2 to their health should be a conservation priority. A One Health approach is the best way to protect NHPs from a new virus in the same way that we would protect the human population.