Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing

BackgroundWe aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET).MethodsPatients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex.ResultsOne hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction).ConclusionsCombined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics

Contemporary implementation of guideline-directed medical and device therapies in heart failure : Insights from the Central/Eastern Europe Quality of Care Centres Survey

The Central/Eastern Europe (CEE) Quality of Care Centres (QCC) Survey evaluated the implementation of guideline-directed medical therapies (GDMT) and device use at discharge after heart failure (HF) hospitalization in CEE, where GDMT underutilization remains a concern.Between March 2024 and January 2025, 2251 patients (mean age 70.0 years, 60.4% male) were enrolled at discharge from 21 centres across 12 CEE countries. The patient population included HF with reduced ejection fraction (HFrEF) (55.5%), HF with mildly reduced ejection fraction (15.3%) and HF with preserved ejection fraction (27.9%). In the total population, from admission to discharge there was a increase in the use of angiotensin receptor-neprilysin inhibitor (ARNI) (17.1% to 34.3%), beta-blockers (69.4% to 92.4%), mineralocorticoid receptor antagonists (MRA) (44.0% to 82.1%) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) (30.8% to 79.9%), with a reduction in angiotensin-converting enzyme inhibitor (ACEI) use (all p < 0.05). Similar trends were observed across HF phenotypes, including HFrEF (increased use of ARNI, 26.3% to 55.1%, beta-blockers, 69.8% to 95.3%, MRA 49.5% to 89.0%, and SGLT2I 36.2% to 79.8%, and lower ACEI use, all p < 0.05). At discharge, 53.5% of patients received quadruple therapy (63.9% with HFrEF), while ≥50% target doses of titratable drugs were achieved in 18.8% (17.8% in HFrEF). Predictors of GDMT underuse included older age, lower education, living alone, non-ischaemic HF, higher ejection fraction, chronic kidney disease, hypotension, hyperkalaemia, prolonged hospitalization, and residual oedema. Among eligible HFrEF patients, 21.3% were discharged with, or referred for implantable cardioverter-defibrillator, and 17.4% for cardiac resynchronization therapy.The CEE-QCC Survey highlights substantial in-hospital GDMT implementation and up-titration, though device use remains limited. Targeted strategies are needed to enhance guideline implementation and ensure optimal HF care across the CEE region

Cildb: a knowledgebase for centrosomes and cilia

Ciliopathies, pleiotropic diseases provoked by defects in the structure or function of cilia or flagella, reflect the multiple roles of cilia during development, in stem cells, in somatic organs and germ cells. High throughput studies have revealed several hundred proteins that are involved in the composition, function or biogenesis of cilia. The corresponding genes are potential candidates for orphan ciliopathies. To study ciliary genes, model organisms are used in which particular questions on motility, sensory or developmental functions can be approached by genetics. In the course of high throughput studies of cilia in Paramecium tetraurelia, we were confronted with the problem of comparing our results with those obtained in other model organisms. We therefore developed a novel knowledgebase, Cildb, that integrates ciliary data from heterogeneous sources. Cildb links orthology relationships among 18 species to high throughput ciliary studies, and to OMIM data on human hereditary diseases. The web interface of Cildb comprises three tools, BioMart for complex queries, BLAST for sequence homology searches and GBrowse for browsing the human genome in relation to OMIM information for human diseases. Cildb can be used for interspecies comparisons, building candidate ciliary proteomes in any species, or identifying candidate ciliopathy genes

Immune checkpoint inhibitor-associated myocarditis: a novel risk score

Background and aimsImmune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this 'cardiomyotoxicity' are lacking. The main aim of this study was to determine predictors and construct a risk score associated with negative outcomes in patients admitted for ICI myocarditis.MethodsA multicentre registry collected data retrospectively from 17 countries between 2014 and 2023. A multivariable Cox regression model was used to determine risk factors for the primary composite outcome: time to severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardiomuscular symptoms, diagnostics, and treatments. Time-dependent covariates were used, and missing data were imputed. A point-based prognostic risk score was derived and externally validated.ResultsIn 748 patients (67% male, age 23-94 years), 30-day incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17%, respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7), presence of cardiomuscular symptoms (HR 2.6 [1.5-4.2]), low QRS voltage on presenting electrocardiogram (HR for ≤0.5 mV vs &gt;1 mV 1.9 [1.1-3.1]), left ventricular ejection fraction (LVEF) &lt; 50% (HR 1.7 [1.1-2.6]), and incremental troponin elevation (HR 1.8 [1.4-2.4], 2.9 [1.8-4.7], and 4.6 [2.3-9.3], for 20, 200, and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-day primary outcome incidence increased gradually from 4% (risk score = 0) to 81% (risk score ≥ 4). This risk score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low-risk patients who were managed with no immunosuppression resulting in no cardiomyotoxic events.ConclusionsICI-associated myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low QRS voltage, depressed LVEF, and cardiomuscular symptoms. A risk score incorporating these features performed well.Clinical trial registrationNCT04294771 and NCT05454527

Bronchiectasis Exacerbations: Definitions, Causes, and Acute Management

AbstractPulmonary exacerbations (PExs) are events in the course of bronchiectasis which are defined as an increase in disease symptoms lasting a period of a few days. It is established that the tendency toward having PEx is stable throughout the course of the disease. Certain conditions were found to be associated with an increased risk of developing a PEx. Among these are chronic airway infection with Pseudomonas aeruginosa or Aspergillus species, concomitant airway diseases (asthma, chronic obstructive pulmonary disease, and chronic rhinosinusitis), genetic factors such as primary ciliary dyskinesia, and nutritional factors. The immediate events underlying the onset of a PEx are less clearly determined. Although acute changes in bacterial airway composition have been the paradigm for decades, recent microbiome-focused research has not uniformly established such acute changes at the onset of PEx. Other acute changes such as air pollution, viral infection, and changes in bacterial metabolic activity have also been implicated as causes of a PEx. Despite these gaps in our knowledge of the biology of PEx, antimicrobial therapy directed against the identified pathogens in sputum is currently the recommended therapeutic strategy. Various long-term therapies, including antimicrobial and anti-inflammatory strategies, have been proven effective in reducing the frequency of PEx, leading to a recommendation for the use of these strategies in people with frequent PEx.</jats:p

Cardio-toxicity among patients with sarcoma: A Cardio-Oncology Registry.

e22530 Background: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracycline (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutic related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (EF) reduction of &gt; 10%, to a value below 53%. Our objective was to estimate the prevalence of CTRCD among patients with sarcoma, to evaluate echocardiography parameters associated with its development and whether CTRCD is associated with mortality. Methods: Data were collected as part of the International Cardio-Oncology Registry (ICOR), enrolling all patients who were evaluated in the cardio-oncology clinic at our institution. All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. "Preserved EF" group. Results: Among 43 consecutive patients, 6 (14%) developed CTRCD. Elevated left ventricular end systolic diameter (p = 0.007) and a trend of reduced Global Longitudinal Strain (p = 0.092) were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the "Preserved EF" group. In a multivariate analysis, adjusted to age and EF, CTRCD remained a significant predictor for mortality (p = 0.039). Conclusions: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors, and is associated with mortality. Echocardiography parameters may provide an early diagnosis of cardio-toxicity. </jats:p

Treatment of unaccompanied minors in primary care clinics - caregivers' practice and knowledge

Abstract Background By law, the provision of medical treatment to minors in the State of Israel is conditional upon the consent of their parents. In 2004, the Head of the Medical Administration Unit in the Ministry of Health issued Circular No. 4/2004 regarding the treatment of un-accompanied minors in primary care clinics. This circular aims to expand on the law, and permits the treatment of certain minors without parental attendance or consent. The circular does indicate that parents should be notified of the treatment retroactively, and provides cases in which it is possible to avoid notification altogether. The objectives of this study were: (a) to examine the scope of treatment of unaccompanied minors in primary care clinics; (b) to examine caregivers’ knowledge of the provisions of the law and of the circular; and (c) to examine the implementation of the law’s and the circular’s provisions relating to the treatment of unaccompanied minors in primary care clinics in the community. Methods In a cross-sectional study, we surveyed 158 doctors and nurses from primary care clinics of the Haifa and Galilee districts of “Clalit Health Services”. Respondents were selected via a snowball method, with attention to ensuring a heterogeneous clientele and geographic dispersion. Results Treatment seeking by unaccompanied minors is an existing and even widespread phenomenon. The vast majority of unaccompanied minors were in effect treated without parental consent. The main reason for minors’ solitary treatment seeking was parents being busy. In 40% of the cases, where minors were treated without the presence and consent of their parents – parents were not notified of the fact. None of the respondents correctly answered all questions regarding the relevant provisions of the law and circular, and only 10% answered all the questions regarding the circular’s parental notification requirements. Conclusions The Israeli legal arrangement, pertaining to the provision of treatment to minors without the consent of their parents, is vague, unclear to medical and nursing practitioners and limited in terms of the needs of the minors themselves, as well as the needs of the medical system. There is a need for methodical and coherent regulatory thinking on the subject, as well as more thorough education of both nurses and physicians, in order to ensure the rights and interests of minors as well as the rights of their parents

The Role of Speckle Strain Echocardiography in the Diagnosis of Early Subclinical Cardiac Injury in Cancer Patients—Is There More Than Just Left Ventricle Global Longitudinal Strain?

With the improvement in survival rate, cardiotoxicity has emerged as a significant adverse effect of cancer therapy. Early diagnosis of subclinical cardiac injury may allow the initiation of cardioprotective therapy and preventing the interruption of optimal cancer therapy and the development of irreversible cardiac dysfunction. In this article, we review the role of two-dimensional speckle tracking echocardiography (2D-STE), beyond the common left ventricle global longitudinal strain in the diagnosis of early subclinical cardiac injury in patients treated with cancer therapies.</jats:p

Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis.

e15228 Background: Immune checkpoint inhibitors (ICI) have transformed the standard care in cancer treatment. Recent case reports describe ICI-mediated myocarditis with an atypical presentation and fatal potential which lead to permanent interruption of immunotherapy. We aim to characterize ICI-mediated myocarditis and re-introduction to immunotherapy. Methods: We retrospectively evaluated the presentation, severity, and prognosis of patients diagnosed with ICI-mediated myocarditis during 2019, and presented the clinical course and outcomes of patients that were chosen for re-introduction. Results: Among seven patients, only one patient had a history of cardiac disease. The majority were diagnosed with lung adenocarcinoma and treated with anti-programmed death-1 antibody (57%). All patients were treated with single agent ICI. Most patients presented with cardiac symptoms, elevated troponin and typical magnetic resonance imaging; however only 43% had reduced ejection fraction. Five patients were defined as grade I-II and two as grade III-IV. Overall, three patients were chosen for re-introduction with concomitant low dose steroids and weekly troponin follow-up. Two patients diagnosed with grade I/II renewed therapy successfully with no recurrence of symptoms and improvement in disease burden, while the one patient diagnosed with grade III developed worsening of cardiac symptoms after the 1st cycle and therefore therapy was interrupted permanently. Overall, survival was higher among the re-introduction patients (67% vs. 25%). Conclusions: ICI-mediated myocarditis is potentially fatal and leads to permanent interruption of life saving cancer therapy. We imply that re-introduction may be considered in low grade patients; however, better definition of the diagnosis and grading is needed. </jats:p

Additional file 1: of Treatment of unaccompanied minors in primary care clinics - caregivers' practice and knowledge

Question 14: According to the existing law in Israel today, in which of the following scenarios is it permitted to examine and treat a minor without the prior consent of a parent?. Question 15: In which of the following circumstances is it legally permitted not to inform the parents of the fact that the minor has been examined and/or treated without their presence?. (DOCX 16 kb