Death Events Research Articles

Comparing the outcomes of rheumatic heart disease in pregnancy complicated with and without atrial fibrillation: A propensity score matched analysis

Atrial fibrillation (AF) may increase the risk of adverse maternal and fetal outcomes among pregnant with rheumatic valvular lesions (RHD). We aimed to assess the rate of occurrence of AF in pregnant with RHD and its impact on cardiac and maternal-fetal outcomes compared to those without it. The study group consisted of pregnant women with RHD and AF (cases) and a matched comparison group of pregnant women with RHD but without AF (controls) was derived from the database of pregnant women with RHD receiving care at our center between 2011 and 2021. Incidence of composite adverse outcomes(maternal death, heart failure, or thrombo-embolic events) and pregnancy outcomes were compared between them. Seventy-one (5.1%; 95%CI 4.1%-6.4%) pregnant women with RHD had AF during pregnancy and childbirth, most occurring in the late second or early third trimester. New-onset AF was diagnosed in 34 (47.9%) of them. After matching, the incidence of composite outcome was higher in women with AF (77.5% (95%CI 66.3%-85.7%) compared to women without AF (17.3%(95%CI 13.3%-22.1%), P < .001), with seven (9.9%) maternal deaths among cases and two (0.7%) in controls. Heart failure was the most common adverse cardiac event (26.7% vs. 4.2%, P < .001, cases vs controls). Those with AF had higher odds (adjusted OR 56.6 (14.1-226.8)) of adverse cardiac outcomes after adjusting for other risk factors. The frequency of most non-cardiac pregnancy complications was similar in both groups. However, there was a trend towards a higher rate of miscarriage (16.9% vs. 9.9%), small-for-gestational-age babies(16.3 vs. 9.0%), and cesarean rates(31.9% vs. 18.3%) women with AF compared to those who did not experience AF. Atrial fibrillation in pregnancy among women with RHD was associated with an increased risk of maternal morbidity and mortality, with a trend towards an increase in some non-cardiac pregnancy complications compared to those pregnant women without AF. Our study results provide background data for developing and implementing a pregnancy-specific management strategy tailored to middle-income settings.

Przypadek hrabiego Orgaza - w jakich granicach czasowych można projektować przyszłość po swojej śmierci?

The aim of the article is to determine the temporal boundaries within which one can shape the legal situation of others after one's death. The starting point for these considerations is the case of Count Orgaz, who, in the 14th century, issued a perpetual disposition of benefits in favor of the Parish of St. Thomas in Toledo. The study examines the institution of condition, the 'legatum per damnationem', payments of benefits from family foundations, and 'inter vivos' contracts whose full effectiveness is linked to the death of the party. The research supports the conclusion that when planning for the future after one's death, one can only make dispositions that are binding within a limited temporal scope. The legal system protects both the freedom to dispose of property in the event of death and the freedom of heirs to acquire and maintain property. An exceptional regulation provides the Act on Family Foundations dated January 26, 2023. It creates a basis for establishing a family foundation for the purpose of accumulating assets, managing them in the interest of beneficiaries, and providing benefits on their behalf. As long as the family foundation exists, payments of benefits can be made in accordance with the will of the founder.

Aspects of pharmacotherapy with steroids in SARS-CoV-2 infection (literature review)

In recent years, the SARS-CoV-2 pandemic has posed a significant challenge to global public health. Furthermore, infection with SARS-CoV-2 can result in acute respiratory distress syndrome due to excessive systemic inflammation, leading to multiple organ failure and eventual death. Furthermore, the challenge of reducing excessive systemic inflammation, specifically by decreasing the production of pro-inflammatory cytokines in response to SARS-CoV-2, remains unresolved. The use of glucocorticosteroids for SARS-CoV-2 infection remains controversial. Further research is required to support the routine use of steroids in intensive care protocols for SARS-CoV-2, as the current basis is insufficient. This review provides an analysis of literary sources, guidelines, and modern international recommendations on pathogenetic therapy of SARS-CoV-2 to prevent and eliminate hyperproduction of pro-inflammatory cytokines using glucocorticosteroid agents. The aim of this work is to analyse contemporary literary sources on the clinical and pharmacological justification for the use of glucocorticosteroids in clinical practice for SARS-CoV-2 infection. The scientific literature analysis indicates that glucocorticosteroid therapy cannot be recommended for routine use in therapeutic practice for patients with SARS-CoV-2 infection. Thus, with a mild course of SARS-CoV-2 infection, when the patient does not need oxygen support, glucocorticosteroids are contraindicated. Whereas in severe course, in acute respiratory distress syndrome with severe respiratory failure, their use is absolutely necessary, and they are recommended for mandatory use. There is a need for a generalised definition of the optimal glucocorticosteroid agent, including indications, dosage, and duration of use in SARS-CoV-2 infection therapy programs. Keywords: systemic inflammatory reaction, proinflammatory cytokines, hypothalamic-pituitary-adrenal system, glucocorticosteroids.

Prognostic impact of frailty based on a comprehensive frailty assessment in patients with heart failure.

This study aimed to evaluate the impact of frailty and living function domains based on the Kihon Checklist (KCL), a questionnaire for a comprehensive frailty assessment, on prognosis in patients with acute heart failure (AHF). The Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI) study was a prospective multicentre cohort study enrolling 1061 patients hospitalized for AHF from May 2017 to December 2019 in Japan. We divided patients into three groups according to the severity of frailty using the KCL and compared clinical outcomes after discharge. The primary endpoint was all-cause death, and the secondary outcomes were cardiovascular death, heart failure (HF) rehospitalization, and the composite event of cardiovascular death and HF rehospitalization. Of 936 patients (median age, 81years; 48.9% women) who could be assessed for frailty, we identified frailty in 501 patients (53.5%), prefrailty in 290 patients (31.0%), and non-frailty in 145 patients (15.5%). Compared with prefrail and non-frail patients, frail patients were older (83 vs. 79 and 72years, P<0.001), were more likely to be women (53.9% vs. 43.1% and 43.4%, P=0.005), and were more likely to have a history of previous HF hospitalization (35.4% vs. 25.3% and 19.6%, P<0.001) and multimorbidity (90.8% vs. 81.0% and 73.8%, P<0.001). Frail patients had a lower rate of discharge to home (79.7% vs. 94.8% and 96.5%, P<0.001). During the 2year follow-up period, frail patients had a higher incidence rate of all-cause death, cardiovascular death, and HF rehospitalization (log-rank P<0.001, P<0.001, and P=0.003, respectively). After adjusting for other prognostic factors, multivariate analysis showed that frailty was associated with all-cause death [adjusted hazard ratio (HR): 2.917, 95% confidence interval (CI): 1.326-6.417, P=0.008] and cardiovascular death (adjusted HR: 7.026, 95% CI: 1.700-29.030, P=0.007). Among all domains of the KCL, the cognitive function domain was associated with a higher risk of all-cause death (P=0.004) and cardiovascular death (P<0.001). The depression domain remained associated with a higher risk of HF rehospitalization (P=0.045). The risk for all-cause death increased with an increase in total KCL score (adjusted HR: 1.819, 95% CI: 1.300-2.547, P<0.001). The KCL is a useful tool for risk stratification of adverse outcomes in patients with AHF. Functional declines in psycho-emotional domains including cognitive function and depressed mood contribute to adverse outcomes.

Effect of level of sedation on outcomes in critically ill adult patients: a systematic review of clinical trials with meta-analysis and trial sequential analysis

Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults. Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960. Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83-1.06; p=0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92-1.06; p=0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94-1.09; p=0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected. The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor. None.

Chemokine ligand 18 predicts all-cause mortality in patients hospitalized with chest pain of suspected coronary origin

IntroductionChemokines mediate recruitment and activation of leucocytes. Chemokine ligand 18 (CCL18) is mainly expressed by monocytes/macrophages and dendritic cells. It is highly expressed in chronic inflammatory diseases, and locally in atherosclerotic plaques, particularly at sites of reduced stability, and systemically in acute coronary syndrome patients. Reports on its prognostic utility in the latter condition, including myocardial infarction (MI), are scarce. AimTo assess the utility of CCL18 as a prognostic marker of recurrent cardiovascular events in patients hospitalized with chest pain of suspected coronary origin. MethodsThe population consisted of 871 consecutive chest-pain patients, of whom 386 were diagnosed with acute myocardial infarction (AMI) based on Troponin-T (TnT) levels >50 ng/L. Stepwise Cox regression models, applying normalized continuous loge/SD values, were fitted for the biomarkers with cardiac mortality within 2 years and total mortality within 2 and 7 years as the dependent variables. ResultsPlasma samples from 849 patients were available. By 2 years follow-up, 138 (15.8%) patients had died, of which 86 were cardiac deaths. Univariate analysis showed a positive, significant association between CCL18 and total death [HR 1.55 (95% 1.30–1.83), p < 0.001], and for cardiac death [HR 1.32 (95% 1.06–1.64), p = 0.013]. Associations after adjustment were non-significant. By 7 years follow-up, 332 (38.1%) patients had died. CLL18 was independently associated with all-cause mortality [HR 1.14 (95% CI, 1.01–1.29), p = 0.030], but not with MI (n = 203) or stroke (n = 55). ConclusionCCL18 independently predicts long-term all-cause mortality but had no independent prognostic bearing on short-term cardiac death and CVD events.

Aortic events and relative survival in patients with moderately dilated proximal thoracic aorta

Objectives. This study describes growth, local and remote aortic events, and survival in patients with proximal (root, ascending) aortic diameters just below threshold for operation. Methods. Patients with proximal aortic diameter of 4.5 to 5.4 cm at baseline, were followed with serial computed tomography studies and data collected retrospectively. Aortic growth rate was estimated using mixed effects modelling. Clinical and radiological features associated with outcomes (all-cause death, aortic death, local or remote aortic events (dissection, rupture, intramural hematoma, or intervention)) were assessed with Cox analysis. Survival and freedom from events were estimated using Kaplan-Meier methods. Results. 80 patients underwent 274 CT scans during 265 patient-years. Median proximal aortic growth was 0.2 cm in 3 years. 32 events occurred in 28 patients (35%). Eleven events were local, all elective proximal aortic surgery. Nine events were remote: 5 type B aortic dissections, 3 descending aneurysms undergoing elective repair, and one infrarenal aortic rupture. Twelve patients died, half of type B aortic dissection. Relative survival compared to a matched normal population was 82% (95% confidence limits 55–98%) at 10 years. In Cox analysis, increased descending aortic diameter was an independent predictor of all-cause death (hazard ratio [HR], 1.39) and aortic death (HR 1.96). Conclusions. Descending, but not proximal, aortic growth was predictive of lethal events. The decreased relative survival, the substantial number of remote aortic events and aortic deaths strongly suggest continuous serial CT surveillance of the entire aorta. Other indicators than proximal aortic diameter appear needed to improve management of this patient group.

Silicone Embolism Syndrome Causing Altered Mental Status and Respiratory Failure After an Unlicensed Gluteal Silicone Injection: A Case Report.

Unlicensed cosmetic procedures, which come at increased risk of infection and potential surgical complications, have introduced new challenges in healthcare. Physicians should be aware of presentations that may arise secondary to these procedures. We describe a case in which a previously healthy, 28-year-old female presented with new-onset seizures and acute respiratory distress syndrome (ARDS) in the setting of a recent cosmetic procedure with silicone injections to the gluteal region. The patient's hospital course was complicated by altered mental status, respiratory failure, rapid hemodynamic compromise, and eventual death. In rare cases, one possible complication of cosmetic procedures is silicone embolism syndrome, which is characterized by pneumonitis, alveolar hemorrhage, and ARDS. The patient described in this report also experienced neurologic symptoms including seizure and altered mental status. This is a clinical diagnosis that relies upon thorough history-taking and detailed physical exam. Documentation on this phenomenon is limited, and medical management has not yet been standardized for this condition. Morbidity and mortality remain high.

Prognosis of anemic patients with atrial fibrillation undergoing percutaneous coronary intervention

BackgroundThere are limited data regarding whether anemia is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). MethodsPatients with AF undergoing PCI at 15 institutions between January 2015 and March 2021 were included in this analysis. Based on the baseline hemoglobin levels, moderate to severe anemia was defined as hemoglobin levels <11 g/dL, and mild anemia was defined as hemoglobin levels 11–12.9 g/dL for men and 11–11.9 g/dL for women. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, stent thrombosis, and stroke) and major bleeding events (BARC 3 or 5), were compared among patients with moderate/severe anemia, mild anemia, and no anemia. ResultsIn a total of 746 enrolled patients, 119 (16.0%) and 168 (22.5%) patients presented with moderate/severe and mild anemia. The incidence of MACE (22.5%, 11.0%, and 9.1%, log-rank p < 0.001), all-cause death (20.0%, 7.2%, and 4.8%, log-rank p < 0.001), and major bleeding events (10.7%, 6.5%, and 2.7%, log-rank p < 0.001) were the highest in the moderate/severe anemia group compared with the mild and no anemia groups. Multivariable Cox regression analyses determined moderate/severe anemia as an independent predictor for MACE (p = 0.008), all-cause death (p = 0.005), and major bleeding events (p = 0.031) at 1 year after PCI. ConclusionModerate/severe anemia was significantly associated with the higher incidence of MACE and all-cause death as well as major bleeding events compared with mild and no anemia in AF patients undergoing PCI.

Urologists have a duty to think about occupational urinary cancers

More than 11% of employees are exposed to carcinogens in the usual course of their work. The benefits of recognition as an occupational disease (OD) allow victims of work firstly to benefit from a disability compensation. But there are collective challenges. It is important to understand that accidents at work and recognised OD are not financially covered by health insurance, which is financed by everyone, but by a specific branch, known as “professional risks/occupational risks”, financed by employers alone. Being recognised as having an OD modifies the benefits: 100% coverage of all the costs inherent to the OD, including transport costs, increase of daily allowances, payment of a pension (or of a lump sum if the Permanent Incapacity rate is<10%). A survivor's pension may be paid to the beneficiaries in the event of the patient's death. OD “is presumed to be of occupational origin: any disease designated in a table of OD and contracted under the conditions set out in this table”. Although the declaration of OD must be made by the victim (or his dependents) to the national health insurance fund, it can only exist on condition that a doctor has drawn up a descriptive Initial Medical Certificate (IMC), taking care to use the exact terms of the tables (15 ter and 16 bis) and the professional/occupational origin.

Association between the haemoglobin glycation index (HGI) and clinical outcomes in patients with acute decompensated heart failure

Background A growing number of studies show that people with similar blood glucose levels have different levels of glycosylated haemoglobin (HbA1c), and relying only on HbA1c may lead to clinical decision-making errors. The haemoglobin glycation index (HGI) quantifies the difference in HbA1c among individuals and is strongly linked to the risk of cardiovascular disease. However, the connection between this phenomenon and the poor outcomes of patients with acute decompensated heart failure (ADHF) is currently unknown. Patients and Methods This retrospective, single-centre-based cohort study included 1531 hospitalized patients with ADHF from September 2010 to January 2020. The HGI is calculated from the difference between the observed and predicted HbA1c values [predicted HbA1c = 0.024 × fasting plasma glucose (FPG) (mg/dL)+3.1]. The endpoints examined in the study included all-cause death, cardiovascular (CV) death, and major adverse cardiac events (MACE). We fitted multivariable-adjusted Cox proportional hazard models to investigate the association between the HGI and clinical outcomes. Results During the five-year follow-up, 427 (27.9%) patients died from all causes, 232 (15.6%) from CV death, and 848 (55.4%) from MACE. The restricted cubic spline analysis also showed that the cumulative risk of all-cause and CV deaths decreased linearly with increasing HGI. According to multivariate Cox proportional hazard models, the highest tertile of the HGI was associated with a lower incidence of all-cause and cardiovascular deaths [all-cause death, adjusted hazard ratio (HR): 0.720, 95% confidence interval (CI): 0.563–0.921, p = 0.009; CV death, adjusted HR: 0.619, 95% CI: 0.445–0.861, p = 0.004]. A 1% increase in the HGI was associated with a 12.5% reduction in the risk of all-cause death and a 20.8% reduction in the risk of CV death. Conclusions A high HGI was directly associated with a reduction in all-cause and CV deaths but was not associated with MACE. These findings may be helpful in the management of patients with ADHF.

Diagnosis and treatment of ischemia-producing coronary stenoses improves 5-year survival of patients undergoing major vascular surgery

ObjectivePatients undergoing vascular surgery procedures have poor long-term survival due to coexisting coronary artery disease (CAD), which is often asymptomatic, undiagnosed, and undertreated. We sought to determine whether preoperative diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with postoperative ischemia-targeted coronary revascularization can reduce adverse cardiac events and improve long-term survival following major vascular surgery MethodsIn this observational cohort study of 522 patients with no known CAD undergoing elective carotid, peripheral, or aneurysm surgery we compared two groups of patients. Group I included 288 patients enrolled in a prospective Institutional Review Board-approved study of preoperative coronary CT angiography (CTA) and FFRCT testing to detect silent coronary ischemia with selective postoperative coronary revascularization in addition to best medical therapy (BMT) (FFRCT guided), and Group II included 234 matched controls with standard preoperative cardiac evaluation and postoperative BMT alone with no elective coronary revascularization (Usual Care). In the FFRCT group, lesion-specific coronary ischemia was defined as FFRCT ≤0.80 distal to a coronary stenosis, with severe ischemia defined as FFRCT ≤0.75. Results were available for patient management decisions. Endpoints included all-cause death, cardiovascular death, myocardial infarction (MI), and major adverse cardiovascular events (MACE [death, MI, or stroke]) during 5-year follow-up. ResultsThe two groups were similar in age, gender, and comorbidities. In FFRCT, 65% of patients had asymptomatic lesion-specific coronary ischemia, with severe ischemia in 52%, multivessel ischemia in 36% and left main ischemia in 8%. The status of coronary ischemia was unknown in Usual Care. Vascular surgery was performed as planned in both cohorts with no difference in 30-day mortality. In FFRCT, elective ischemia-targeted coronary revascularization was performed in 103 patients 1 to 3 months following surgery. Usual Care had no elective postoperative coronary revascularizations. At 5 years, compared with Usual Care, FFRCT guided had fewer all-cause deaths (16% vs 36%; hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.60; P < .001), fewer cardiovascular deaths (4% vs 21%; HR, 0.11; 95% CI, 0.04-0.33; P < .001), fewer MIs (4% vs 24%; HR, 0.13; 95% CI, 0.05-0.33; P < .001), and fewer MACE (20% vs 47%; HR, 0.36; 95% CI, 0.23-0.56; P < .001). Five-year survival was 84% in FFRCT compared with 64% in Usual Care (P < .001). ConclusionsDiagnosis of silent coronary ischemia with ischemia-targeted coronary revascularization in addition to BMT following major vascular surgery was associated with fewer adverse cardiovascular events and improved 5-year survival compared with patients treated with BMT alone as per current guidelines.

Prawne rozumienie powstania i ustania swobody woli

Free will is an essential legal idea that determines the nature of legal relations. Free will is essential for private law, as it shapes the mechanisms for entering into contracts, fulfilling obligations, the scope of civil capacity, adherence to the principles of discretion, voluntariness, fairness, etc. The purpose of the paper is to determine the dynamics of freedom of will and to provide a legal justification for the moment of its emergence and termination. The scope of free will is dynamic; it arises at birth and changes throughout life. The scope of free will is related to two main criteria: the level of intelligence and the scope of civil capacity. Minor children, people with limited civil capacity, and incapacitated persons have the lowest level of free will. The scope of free will also vary within a specific civil capacity. Free will may be temporarily suspended when someone is unaware of their actions. A complete, irreversible loss of free will occurs only in the event of death. From that moment on, a person ceases to be a party to legal relations and a legal person.

Ventilator and the Vaccine

During the Covid-19 pandemic, the fat body was caught up in a complicated logics of life and death in the North American context, where “obesity” was regarded as an “underlying condition” for greater risk of severe disease and death from Covid. As such, bodies with high BMIs were refused ICU ventilator care in certain jurisdictions, which fat activists classified as eugenics. At the same time, some vaccination campaigns prioritized people with higher BMIs for scarcely available Covid vaccinations, also on the basis of fat bodies’ higher risk status for Covid death. This paper explores the seeming tension between two articulations of fat during the Covid pandemic, whereby fat bodies were simultaneously worthy of life and of death in the same moment. Using MBembe’s conceptualization of necropolitics, which draws out and expands upon Foucault’s notion of biopolitics, I argue that the two perspectives on fatness operated in tandem, within an overall temporal shift in classification of obesity; from that of a risk factor for eventual death to that of an emergent threat. Such a temporal shift, I argue, relied on well-worn eugenic patterns in Canada, through which “normative” white bodies were prioritized for life through a complex necropolitical practice by which fat bodies were both made live and let die.

Prognostic value of left ventricular mechanical dyssynchrony indices derived from gated myocardial perfusion SPECT in coronary artery disease: a systematic review and meta-analysis.

Left ventricular mechanical dyssynchrony (LVMD) is an important prognostic factor in coronary artery disease. A growing body of evidence indicates that LVMD parameters derived from phase analysis of gated myocardial SPECT may allow risk stratification for future cardiac events. We performed a systematic review and meta-analysis on the prognostic value of LVMD on gated SPECT in patients with coronary artery disease. PubMed, Embase, and the Cochrane library were searched until August 25, 2022, for studies reporting the prognostic value of LVMD on gated SPECT for outcomes of all-cause death, cardiac death, or major adverse cardiovascular event (MACE) in patients with coronary artery disease. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were meta-analytically pooled using a random-effects model. Nine studies (26,750 patients) were included in a qualitative synthesis. Among the SPECT LVMD parameters used in various studies, high phase standard deviation, phase bandwidth, and phase entropy were widely evaluated and reported to be associated with high rates of all-cause death, cardiac death, or MACE. For five studies (23,973 patients) in the quantitative synthesis, the pooled HR of LVMD for predicting MACE was 2.81 (95% CI 2.03-3.88). Studies using combined phase parameters to define LVMD showed higher HRs than a study using phase entropy (p = 0.0180). LVMD from gated myocardial SPECT is a significant prognostic factor for coronary artery disease. Phase analysis of gated SPECT may be useful for accurate risk stratification and could be applied for clinical decision-making in such patients.

Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Autophagy and senescence facilitate the development of antiestrogen resistance in ER positive breast cancer.

Estrogen receptor positive (ER+) breast cancer is the most common breast cancer diagnosed annually in the US with endocrine-based therapy as standard-of-care for this breast cancer subtype. Endocrine therapy includes treatment with antiestrogens, such as selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs). Despite the appreciable remission achievable with these treatments, a substantial cohort of women will experience primary tumor recurrence, subsequent metastasis, and eventual death due to their disease. In these cases, the breast cancer cells have become resistant to endocrine therapy, with endocrine resistance identified as the major obstacle to the medical oncologist and patient. To combat the development of endocrine resistance, the treatment options for ER+, HER2 negative breast cancer now include CDK4/6 inhibitors used as adjuvants to antiestrogen treatment. In addition to the dysregulated activity of CDK4/6, a plethora of genetic and biochemical mechanisms have been identified that contribute to endocrine resistance. These mechanisms, which have been identified by lab-based studies utilizing appropriate cell and animal models of breast cancer, and by clinical studies in which gene expression profiles identify candidate endocrine resistance genes, are the subject of this review. In addition, we will discuss molecular targeting strategies now utilized in conjunction with endocrine therapy to combat the development of resistance or target resistant breast cancer cells. Of approaches currently being explored to improve endocrine treatment efficacy and patient outcome, two adaptive cell survival mechanisms, autophagy, and "reversible" senescence, are considered molecular targets. Autophagy and/or senescence induction have been identified in response to most antiestrogen treatments currently being used for the treatment of ER+ breast cancer and are often induced in response to CDK4/6 inhibitors. Unfortunately, effective strategies to target these cell survival pathways have not yet been successfully developed. Thus, there is an urgent need for the continued interrogation of autophagy and "reversible" senescence in clinically relevant breast cancer models with the long-term goal of identifying new molecular targets for improved treatment of ER+ breast cancer.

Comparative prognostic importance of measures of left atrial structure and function in non-ischaemic dilated cardiomyopathy.

To compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular (CV) death or non-fatal heart failure (HF) events in patients with non-ischaemic dilated cardiomyopathy (DCM). CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm (median age 54 [interquartile range 44-64] years, 61% men, median LVEF 42% [30-51%]) were analysed for measures of LA structure (left atrial maximum volume index [LAVImax], left atrial minimum volume index [LAVImin]) and function (left atrial emptying fraction [LAEF], left atrial reservoir strain [LARS], left atrial conduit strain [LACS] and left atrial booster strain [LABS]). Over median follow-up of 7.4 years, 103 patients (18%) met the primary endpoint. Apart from LACS, each measure of LA structure and function was associated with the primary endpoint after adjusting for other important prognostic variables. The addition of each LA metric to a baseline model containing the same important prognostic covariates improved model discrimination, with LAVImin providing the greatest improvement (C-statistic improvement: 0.702 to 0.738; χ2 test comparing likelihood ratio p < 0.0001; categorical net reclassification index: 0.210 (95% CI 0.023-0.392)). Patients in the highest tercile of LAVImin had similar event rates to those with persistent atrial fibrillation. Measures of LA strain did not enhance model discrimination above LA volumetric measures. Measure of left atrial structure and function offer important prognostic information in patients with DCM and enhance prediction of adverse outcomes. LA strain was not incremental to volumetric analysis for risk prediction.

The legal regime of the share in the authorized capital of a limited liability company acquired by spouses during marriage, during the life of the spouses and after the death of one of the spouses

The authors analyze the legal regime of a share in the authorized capital of a limited liability company acquired during marriage, as well as the legal fate of this share in the event of death of one of the spouses. Acquisition of a share is basic for acquisition of corporate rights to participate in the company. Since the legal regime of joint ownership presupposes the ownership of property without determining the shares of each co-owner, regardless of which spouse is registered in the Unified State Register of Legal Entities, both spouses are members of the company and considered as one subject (legal relationship with multiple persons). Any of the co-owners has the right to act in exercising general corporate rights as an authorized person, forming a single will. Increments received from owning shares (income) go into the common property. After the death of a spouse, the common joint property is transformed into the individual property of the surviving spouse, who receives ½ of the common property of the spouses. The second half of the common property is considered to belong to the deceased spouse, and therefore is included in the inheritance mass and undergoes through the procedure of hereditary succession. The transformation of common joint property into the individual property of the surviving spouse is not a transfer, since in this case there is no termination of the surviving spouse’s property rights. The rules governing the transfer of a share in the authorized capital of the company to third parties are not applicable to such transformation. A share in the authorized capital is an indivisible property, and therefore the legal fate of the share is the same.

Diabetic kidney disease as an independent predictor of long-term adverse outcomes in patients with coronary artery disease and diabetic mellitus.

Diabetic kidney disease (DKD) had been proposed as a contributor in the pathogenesis of coronary artery disease (CAD). However, the relationship of DKD and the long-term adverse outcomes in patients with CAD after percutaneous coronary intervention (PCI) was still undiscovered. Approximately 892 patients with CAD enrolled from January 2012 to December 2016. The patients were divided into two groups, the DKD group (n = 341) and the None DKD group (n = 551). The primary outcome was major adverse cardiac events (MACE) after PCI. The average follow-up time was 1,897 ± 1,276 days. Baseline data showed that some factors were significantly different between the two groups, including age, body mass index, gender (female), hypertension, smoking, stroke history, heart failure, duration of diabetic mellitus (DM), low-density lipoprotein cholesterol, urinary protein/creatinine ratio, serum creatinine, hemoglobin, platelet, antiplatelet, beta blocker, statin, antihypertensive drugs, and insulin (all p < 0.005). There were significant differences between the two groups in MACE, 40.3% vs. 52.2% (p = 0.001), and in cardiovascular death events and all-cause death events (5.6% vs. 20.5%, p < 0.001 and 4.4% vs. 13.5%, p < 0.001, respectively). In the DKD group, the risk of MACE was elevated to 141.9% [hazard ratio (HR) = 1.419, 95% confidence interval (CI): 1.164-1.730, p = 0.001] in the Cox univariable regression analyses; after adjusting co-variables, the Cox multivariable regression analyses demonstrated that DKD was an independent predictor for MACE (HR = 1.291, 95% CI: 1.027-1.624, p = 0.029) in patients with CAD after PCI, as well as in cardiovascular death events (HR = 2.148, 95% CI: 1.292-3.572, p = 0.003) and all-cause death events (HR = 2.229, 95% CI: 1.325-3.749, p = 0.003). This study suggests that DKD is an independent and novel predictor of long-term adverse outcomes in patients with CAD and DM who underwent PCI.