Perceptions of Barriers and Facilitators to Reducing Exposure to Secondhand Smoke in the Home: A Qualitative Study With Palestinian-Arab Women in Israel.

INTRODUCTION: Smoking is a collective and complex problem in the Palestinian-Arab community in Israel, where women and children are particularly vulnerable to exposure to secondhand smoke (SHS), especially in the home. AIMS AND METHODS: We undertook this study to better understand women's experiences with SHS exposure in the home and to identify pathways for intervention. Using the grounded theory approach, seven focus groups were conducted with 66 women in different localities across Israel. Purposive and snowball sampling techniques were applied to recruit women who have currently or previously been exposed to smoking in the home. Focus groups were audio-recorded and transcribed verbatim, and data were then coded and analyzed using the constant comparison analysis method to identify emergent themes and subthemes. RESULTS: Three core themes emerged from the discussions. These include women's perceptions of smoking among men and exposure to SHS in the home, the implications of smoking on spousal and social relationships, and the women's experiences in coping with this situation and their suggestions for interventions. We identified additional sub-themes, including the consequences to women's and children's health, as well as the complex interaction between smoking in the home and women's social position, agency, and home ownership. CONCLUSIONS: Women exposed to SHS in the home experience consequences that affect their health and their spousal and social relationships. They also face several personal and societal challenges in tackling this issue. Culturally tailored interventions targeting both communities and households can raise awareness and impact smoking behaviors in the home. IMPLICATIONS: The findings of this study demonstrate the far-reaching consequences of SHS exposure in the home among women who are exposed. The findings contribute to our understanding of smoking contingencies among men and smoking behaviors in the home. This study lays the groundwork for future community and household-based research and interventions. We suggest several critical junctures that may increase response to smoking cessation interventions and to reduce smoking in the home, such as at the time of marriage when the home policy is set, and the adverse effects of exposure on children and other family members, especially those with illness.

Persistence of vitamin D deficiency among Italian patients with acute myocardial infarction.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic. METHODS AND RESULTS: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022). The median 25(OH)D concentration in the overall cohort was 17.15 (10.3-24.7) ng/mL. The median plasma concentrations of 25(OH)D for groups 1, 2, 3, and 4 were 14.45 (7.73-22.58) ng/mL, 17.3 ng/mL (10.33-24.2), 18.95 (11.6-26.73) ng/mL and 19.05 (12.5-27.3) ng/mL, respectively. Although 25(OH)D levels increased over the years, the prevalence of vitamin D deficiency remained high in each group (68.4%, 61.4%, 53.8%, and 52% respectively). Hypovitaminosis D was predicted by the season influence (OR:2.03, p < 0.0001), higher body mass index (OR:1.25; p = 0.001), diabetes mellitus (OR:1.54; p = 0.001), smoking (OR:1.47; p = 0.001), older age (OR:1.07; p = 0.008), higher triglycerides levels (OR:1.02; p = 0.01), and female gender (OR:1.3; p = 0.038). After multivariable adjustment, vitamin D ≤ 20 ng/mL was an independent predictor of mortality. CONCLUSION: Vitamin D deficiency is highly prevalent and persistent in patients with AMI despite a trend towards increasing 25(OH)D concentrations over the years. The frequent lockdowns did not reduce the levels of 25(OH)D in the fourth group. Low levels of 25(OH)D are an independent predictor of mortality.

Cardiac Left Ventricular miRNA-26a Is Downregulated in Ovariectomized Mice, Upregulated upon 17-Beta Estradiol Replacement, and Inversely Correlated with Collagen Type 1 Gene Expression.

Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood. Data in humans is confounded by age and co-morbidities. We investigated the effects of ovariectomy and estrogen replacement on the left ventricular (LV) gene expression of pro-inflammatory and pro-fibrotic factors involved in HFpEF and putative regulating miRNAs. Nine-week-old C57BL/6 female mice were subjected to ovariectomy (OVX) or SHAM operation. OVX and SHAM groups were sacrificed 1-, 6-, and 12-weeks post-surgery (T1/SHAM; T1/OVX; T6/SHAM; T6/OVX, T12/SHAM). 17ß-estradiol (E2) or vehicle (VEH) was then administered to the OVX groups for 6 weeks (T12/OVX/E2; T12/OVX/VEH). Another SHAM group was sacrificed 12-weeks post-surgery. RNA and miRNAs were extracted from the LV apex. An early 3-fold increase in the gene expression of IL-1α, IL-6, Mmp9, Mmp12, Col1α1, and Col3α1 was observed one-week post-surgery in T1/OVX vs. T1/SHAM, but not at later time points. miRNA-26a was lower in T1/OVX vs. T1/SHAM and was inversely correlated with Col1α1 and Col3α1 expression 1-week post-surgery (r = -0.79 p < 0.001; r = -0.6 p = 0.007). miRNAs-26a, 29b, and 133a were significantly higher, while Col1α1, Col3α1, IL-1α, IL-6, Tnfα, Mmp12, and FasL gene expression was significantly lower in E2- compared to vehicle-treated OVX mice. miRNA-26a was inversely correlated with Col3α1 in T12/OVX/ E2 (r = -0.56 p = 0.02). OVX triggered an early increase in the gene expression of pro-inflammatory and pro-fibrotic factors, highlighting the importance of the early phase post-cessation of ovarian function. E2 replacement therapy, even if it was not immediately initiated after OVX, reversed these unfavorable changes and upregulated cardiac miRNA-26a, previously unknown to be affected by menopausal status.

Mild Tricuspid Regurgitation: A Marker of Disease Burden Independently Associated with Increased Mortality.

INTRODUCTION: Tricuspid regurgitation (TR) is a common finding which appears to be associated with a worse prognosis. There are conflicting data regarding the prognostic impact of mild TR. We examined the clinical characteristics and echocardiographic properties of subjects with TR and its impact on clinical outcome with particular emphasis on subjects with mild TR. METHODS: Consecutive echocardiography examinations during 5 years were evaluated for TR severity and outcome including mortality and cardiovascular hospitalizations. RESULTS: The study included 21,429 subjects; 45% of the subjects had mild TR, 15% had moderate TR, and 6.5% had severe TR. Primary organic TR was evident in 7% of the subjects, a percentage that increased with increasing TR severity. TR severity was incrementally associated with older subjects with an increasing number of comorbidities and echocardiographic abnormalities. 29% of the subjects died at a median follow-up duration of 8.7 years. Increasing severity of TR was independently and incrementally associated with mortality. Subjects with mild TR had a 25% increased mortality rate compared to subjects with minimal TR (HR 1.25, 95% CI: 1.12-1.39, p < 0.001) after adjustment for significant clinical parameters. TR severity was also an independent incrementally graded predictor of cardiovascular hospitalization and mortality (mild TR: HR 1.23, 95% CI: 1.12-1.34, p < 0.001). CONCLUSIONS: TR is associated with older and sicker patients with numerous comorbidities. TR severity is a predictor of a worse clinical outcome. Mild TR was independently associated with decreased survival. TR should be considered a marker of a disease burden with a poor prognosis.

Novel N-Acylethanolamide Derivatives Affect Body Weight and Energy Balance.

Introduction - The obesity pandemic is multifactorial. Nutritional, pharmacologic and surgical interventions are limited in reach and efficacy, raising need for new therapeutics. Aims - Characterization of anorexigenic and cognitive effect and central mechanism of action of novel N-acylethanolamide derivatives. Methods - Sabra mice divided to similar experimental groups, injected IP with: oleyl-L-leucinolamide (1 A), linoleyl-L-leucinolamide (4 A), linoleyl-L-valinolamide (5 A), oleyl-oxycarbonyl-L-valinolamide (1 B), oleyl-oxycarbonyl-D-valinolamide (2 B), oleylamine-carbonyl-L-valinolamide (3 B), oleylamine-carbonyl-D-valinolamide (4 B), and oleyl-L-hydroxyvalineamide (5 B). Control group with vehicle. Body weight and food consumption followed for 39 days. Motor activity and cognitive function by open field test and eight-arm maze. Mice sacrificed and mechanism of action investigated by qPCR. The genes analyzed involved in energy balance and regulation of appetite. Catecholamines and serotonin evaluated. Results - Compounds 1 A, 5 A, 1 B-4 B, caused significant weight loss of 4.2-5.6 % and 5 A, 1 B-4 B, improved cognitive function following 8 i. p. injections of 1 mg/kg during 39 days, by different mechanisms. 5 A, 3 B and 4 B decreased food consumption, whereas 1 A, 5 A and 2 B increased motor activity. 1 A, 4 A, 1 B and 3 B elevated SIRT-1, associated with survival. POMC upregulated by 1 B and 2 B, CART by 1 B, 2 B and 1 A. NPY and CAMKK2 downregulated by 5 A. 4 B enhanced 5-HT levels. 4 A, 5 A, 1 B, 4 B, 5 B decreased FAAH, showing long lasting effect. Conclusions - These new compounds might be developed for the treatment of obesity and for improved cognitive function.

Increased estimated fat-free mass and fat mass associated with improved clinical outcome in heart failure.

BACKGROUND: Increased weight measured by body mass index is associated with better clinical outcomes in heart failure (HF). The effect of specific components of body mass on outcome is limited. We evaluated the impact of fat-free mass and fat mass on mortality and cardiovascular hospitalization in a large real-world cohort of patients with chronic HF. METHODS: Body measurements were assessed in patients with chronic HF. Fat-free mass, fat mass and waist circumference were calculated based on specifically derived formulas. RESULTS: The cohort included 6328 HF patients. Mean follow-up was 744 days. Increased body composition indices including body mass index, fat-free mass index and fat mass index, per cent body fat and waist circumference were associated with better survival. Cox regression analysis after adjustment for other significant parameters demonstrated that these indices were all associated with improved survival. The strongest association was seen with fat-free mass index with a graded increase in survival; lowest death in the highest quartile compared to reference second quartile (hazard ratio 0.79, 95% confidence interval 0.67-0.93, P < .01). There was no interaction with sex or HF type. Analysis of the clinical outcome of death and cardiovascular hospitalization demonstrated that a worse prognosis was in the lowest quartile of all the indices. A sensitivity analysis, analysing these indices as continuous parameters using restricted cubic splines, demonstrated a clear continuous association between these indices and increased survival in both sexes. CONCLUSIONS: Body mass including fat-free mass and fat mass was associated with improved survival in patients with HF.

Municipal community centers as healthy settings: evaluation of a real-world health promotion intervention in Jerusalem.

BACKGROUND: This study presents an intervention designed to foster the implementation of health promotion programs within District Municipality Community Centers (DMCCs) in Jerusalem, and the creation of a peer network of healthy settings with a shared aspiration of collaborating and implementing health-promoting policies at the community level. We also present the evaluation strategy, based on the EQUIHP and RE-AIM frameworks. METHODS: Twenty DMCCs completed our program. This evaluation research involved a comprehensive seminar during the first year for DMCCs coordinators, teaching them the principles of health promotion. An educational kit was distributed during the second year. The evaluation strategy included a process evaluation and annual evaluations based on the EQUIHP and RE-AIM frameworks. The EQUIHP tool was divided into four dimensions of evaluation: 1) Framework of health promotion principles, 2) Project development and implementation, 3) Project management, and 4) Sustainability; while the RE-AIM domains included: 1)Reach, 2)Effectiveness, 3)Adoption, 4)Implementation and 5)Maintenance. RESULTS: The program led to high responsiveness among DMCCs and to the implementation of diverse health promotion initiatives, with a participation of approximately 29,191 residents. The EQUIHP evaluation showed an improvement in program quality in Year 2. The final RE-AIM evaluation presented a total median score of 0.61 for all domains, where 0 was non-performance and 1.0 was full performance. The 'Framework of health promotion principles' and 'Reach' components received the highest median score (0.83, 1.0 and 0.87), while the 'Sustainability and 'Maintenance' components received the lowest (0.5). CONCLUSIONS: This innovative program adapts the Healthy Cities approach (initiated by the World Health Organization in 1986) to the development of community center health-promoting settings within the larger municipal framework, training local community center staff members to assess and address local health concerns and build community capacity. The local focus and efforts may help community actors to create health promotion programs more likely to be adopted, feasible in the 'real-world' and able to produce public health impact in the communities where people live. Moreover, collaboration and cooperation among DMCCs may lead to a broader community health vision, forging coalitions that can advocate more powerfully for health promotion. TRIAL REGISTRATION: NIH trial registration number: NCT04470960. Retrospectively registered on: 14/07/2020.

Cardiovascular disease risk factors and health behaviors of ultra-Orthodox Jewish women in Israel: a comparison study.

Objectives: Women from low socio-economic, culturally insular populations are at increased risk for cardiovascular disease (CVD). The ultra-Orthodox Jewish (UOJ) community in Israel is a rapidly growing low socio-economic, insular, cultural-ethnic minority with numerous obstacles to health. The current cross-sectional study investigates CVD-related health behaviors and risk factors in a sample of UOJ females, comparing sample characteristics with the general population. Design: Self-administered questionnaires completed by a cluster randomized sample of 239 UOJ women included demographics, CVD-related health behaviors (consumption of fruit, vegetables, and sweetened beverages; hours of sleep; secondhand smoke exposure; and physical activity engagement) and risk factors (BMI, reported diagnoses of diabetes, high blood pressure, and heart disease). Results: Compared with the general population, UOJ women were less likely to consume 5 fruits and vegetables a day (12.7% vs. 24.3%, p < .001); more likely to consume ≥ 5 cups of sweetened beverages a week (18.6% vs. 12.6%, p = .019), and more likely to sleep <7 hours a night (62.0% vs. 50.6%, p = .002). UOJ women also reported less secondhand smoke exposure (7.2% vs. 51.4%, p < .001) and higher rates of physical activity recommendation adherence (60.1% vs. 25.6%, p < .0001) than the general population. Obesity was higher in UOJ women (24.3% vs. 16.1%, p < .0001). Increased parity and reduced moderate physical activity were associated with increased BMI. Increased parity was also associated with reduced sleep. Grand multiparous women (a 68% prevalence rate), in particular, were more likely to be overweight or obese than women with less than 5 children. Conclusions: This study suggests that health promotion interventions in this population target healthy weight maintenance, nutrition, and physical activity.

Dialysis Therapy for Volume Overload: A Feasible Option to Reduce Heart Failure Hospitalizations in Advanced Heart Failure.

BACKGROUND: Advanced heart failure (HF) carries a high rate of recurrent HF hospitalizations and a very high mortality rate. Mechanical devices and heart transplantation are limited to a select few. Dialysis may be a good alternative for advanced HF patients with volume overload despite maximal pharmacological therapy. OBJECTIVES: To assess the net clinical outcome of peritoneal dialysis or hemodialysis in patients with advanced HF. METHODS: We analyzed all advanced HF patients who were referred for dialysis due to volume overload in our institution. Patients were followed for complications, HF hospitalizations, and survival. RESULTS: We assessed 35 patients; 10 (29%) underwent peritoneal dialysis and 25 (71%) underwent hemodialysis; 71% were male; median (interquartile range) age was 74 (67-78) years. Estimated glomerular filtration rate was 20 (13-32) ml/min per 1.73 m2. New York Heart Association functional capacity was III. Median follow-up time was 719 days (interquartile range 658-780). One-year mortality rate was 8/35 (23%) and overall mortality rate was 16/35 (46%). Three patients (9%) died during the first year due to line or peritoneal dialysis related sepsis, and 6 (17%) died during the entire follow-up. The median number of HF hospitalizations was significantly reduced during the year on dialysis compared to the year prior to dialysis (0.0 [0.0-1.0] vs. 2.0 [0.0-3.0], P < 0.001). CONCLUSIONS: Dialysis is reasonably safe and significantly reduced HF hospitalization in advanced HF patients. Dialysis could be a good alternative for advanced HF patients with intractable volume overload.

Prevalence and impact of concomitant malignancy on outcomes among ambulatory heart failure population.

INTRODUCTION: Heart failure (HF) and cancer are medical conditions with a rising prevalence resulting in increased co-occurrence. We assessed the impact of cancer on clinical outcome in patients with HF and the prognostic impact of specific types of cancers on different HF subpopulations. METHODS: All patients with HF were evaluated for the occurrence of malignant neoplasm at a health maintenance organization and were followed for cardiac-related hospitalizations and death. RESULTS: The study cohort included 7106 HF patients, 1564 of them (22%) had a diagnosis of malignant neoplasm. HF patients with concomitant cancer were older, had more comorbidities and were more likely to have NYHA class III/IV (42% vs. 37%, P < .01), compared with patients with no malignancy. The overall 2-year mortality rate of the entire HF cohort was 23.2%. Survival rate by Kaplan-Meier analysis demonstrated that the presence of a malignancy was directly associated with reduced survival: 67.2 ± 1.2% vs 79.5 ± 0.5%, P < .001. Malignancy was associated with an increase in mortality with a hazard ratio (HR) of 1.36, 95% confidence interval (CI) 1.21-1.54, P < .001. The strongest impact of malignancy on outcomes was related to age; among patients <70 years old, the increase in the risk of mortality was the highest with a HR of 2.07, 95% CI 1.54-2.80, P < .001. CONCLUSIONS: Malignancy is common among patients with HF. Patients with concomitant HF and malignancies have poor outcomes, and the impact of cancer on outcome is stronger among young patients.

Health ambassadors in the workplace: a health promotion intervention mobilizing middle managers and RE-AIM evaluation of outcomes.

BACKGROUND: The workplace provides an ideal setting for health promotion, as adults spend most of their day at work. Middle managers hold a strategic position to lead workplace health promotion. This study evaluates the outcomes of an intensive intervention training middle managers to promote health in the workplace. METHODS: A workshop was designed and conducted to train female middle management employees to construct, implement, and evaluate a health promotion program in their workplace. Semi-structured interviews were carried out post-intervention to assess workplace health promotion outcomes according to the RE-AIM framework, and identify variables contributing to success. Additionally, questionnaires were distributed pre and post-program assessing personal health and self-efficacy changes. RESULTS: Eighteen participants from 13 government offices, who serve 19,560 employees, completed the training course. Nine workplaces had workplace health promotion programs in progress 12 months after the course had ended, of which 8 made health promotion changes in organizational policy. Workplace RE-AIM scores showed that 8 workplaces were high or partial performers, and 5 were low or non-performers. Factors that increased the likelihood of successful interventions included management support, steering committee, comprehensive programming, conducting a needs assessment and flexibility in program implementation in the presence of challenges. Post course, participants reported increased health knowledge related to workplace health promotion (p < 0.001), and increased health promotion self-efficacy (p < 0.05). CONCLUSIONS: Training and continued guidance of middle managers resulted in the design and successful implementation of workplace health promotion interventions. A RE-AIM based assessment was found to be an effective method for evaluating multi-content workplace health promotion programs. Registered at ClinicalTrials.gov, https://www.clinicaltrials.gov , registration number: NCT03295136, registration date: 24/09/2017.

Electrocardiographic Predictors of Morbidity and Mortality in Patients With Acute Myocarditis: The Importance of QRS-T Angle.

BACKGROUND: Acute myocarditis carries a variable prognosis. We evaluated the morbidity and mortality rates in patients with acute myocarditis and admission electrocardiographic predictors of outcome. METHODS AND RESULTS: Patients admitted to a tertiary hospital with a clinical diagnosis of acute myocarditis were evaluated; 193 patients were included. Median follow-up was 5.7 years, 82% were male, and overal median age was 30 years (range 21-39). The most common clinical presentations were chest pain (77%) and fever (53%). The 30-day survival rate was 98.9%. Overall survival during follow-up was 94.3%. The most common abnormalities observed on electrocardiography were T-wave changes (36%) and ST-segment changes (32%). Less frequent changes included abnormal T-wave axis (>105° or < -15°; 16%), abnormal QRS axis (12%), QTc >460 ms (11%), and QRS interval ≥120 ms (5%). Wide QRS-T angle (≥100°) was demonstrated in 13% of the patients and was associated with an increased mortality rate compared with patients with a narrow QRS-T angle (20% vs 4%; P = .007). The rate of heart failure among patients with a wide QRS-T angle was significantly higher (36% vs 10%; P = .001). Cox regression analysis demonstrated that a wide QRS-T angle (≥100°) was a significant independent predictor of heart failure (hazard ratio [HR] 3.20, 95% confidence interval [CI] 1.35-7.59; P < .01) and of the combined end point of death or heart failure (HR 2.56, 95% CI 1.14-5.75; P < .05). CONCLUSIONS: QRS-T angle is a predictor of increased morbidity and mortality in acute myocarditis.

Gender Differences in Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation: Systematic Review and Network Meta-analysis.

BACKGROUND: Studies indicate that women with atrial fibrillation (AF) are less likely to receive anticoagulants despite their higher risk of stroke compared with men. OBJECTIVE: To evaluate whether the efficacy and safety of direct oral anticoagulants (DOACs) differ in women with AF as compared with men. Our secondary aim was to examine gender differences regarding the safety and efficacy of specific DOACs. DATA SOURCES: MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov were searched through March 2017. STUDY SELECTION AND DATA EXTRACTION: Randomized clinical trials that reported on major bleeding and stroke with DOACs in women and men with AF were included. Meta-analysis and network meta-analysis was performed. DATA SYNTHESIS: Five trials met the inclusion criteria. Among 66 389 patients, 37.8% were women. Women treated with DOACs were at higher risk of stroke and systemic embolism compared with men (RR = 1.19; 95% CI = 1.04-1.35; I2 = 10%) but there was a significantly lower risk of major bleeding in women compared with men (RR = 0.86; 95% CI = 0.78-0.94; I2 = 0%). Network meta-analyses suggested differences between various DOACs in men and women. LIMITATIONS: Patient-level data enabling control for differences in baseline risk and head-to-head comparisons between DOACs were not available. Relevance to Patient Care and Clinical Practice: Undertreatment with DOACs among women cannot be justified. CONCLUSION: Women treated with DOACs had a lower rate of major bleeding and higher rate of stroke and systemic emboli compared with men. Further investigation of DOACs, including differences between the DOACs in specific populations is warranted.

Variable clinical expression of a novel FLNC truncating variant in a large family.

BACKGROUND: Variants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13-25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family. METHODS: Molecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7:128496880 [hg19]; NM_001458.5; c.7467_7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases. RESULTS: Seventeen variant carriers were identified: ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited late­gadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall. CONCLUSION: This large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures.

A Pregnant Woman With Severe Symptomatic Aortic Stenosis: How Should We Treat?

A 31-year-old woman with end-stage kidney disease and with a bicuspid aortic valve presented with acute heart failure in the second trimester of pregnancy. The patient received a diagnosis of severe aortic stenosis and chose to continue the pregnancy against medical advice. Following a multidisciplinary team consultation, she underwent urgent transcatheter aortic valve replacement.

Sustained insulin treatment restoring metabolic status, body weight, and cognition in an anorexia nervosa-like animal model in mice.

INTRODUCTION: Anorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment. METHODS: AN-like model was established through dietary restriction (DR). On days 1-25, mice were on DR, and on days 26-31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function. RESULTS: The delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model. CONCLUSION: The PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment."

Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO), predicts future major adverse cardiovascular events after myocardial infarction.

OBJECTIVE: Trimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome. METHODS AND RESULTS: Blood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge. Plasma TMAO was determined by HPLC-MS. The endpoint was a composite three-point MACE (major adverse cardiovascular events), including all-cause mortality, re-infarction, or heart failure (HF) development. Median TMAO concentration on admission was significantly higher than on discharge (respectively, 7.81 [3.47-19.98] vs 3.45 [2.3-4.78] µM, p < 0.001). After estimating the 3.45 µM TMAO cut-off with the analysis of the continuous hazard ratio, we divided our cohort into two groups. The first group included 75 (50.3%) patients whose TMAO levels remained below or decreased under cut-off (low-low/high-low; LL/HL), while the second group included 74 (49.7%) patients whose TMAO levels remained high or increased above the cut-off during hospitalisation (high-high/low-high; HH/LH). During the median 30-month follow-up, 21.5% of patients experienced the composite endpoint. At Kaplan-Meier analysis, a trend of increasing MACE risk was observed in patients in the HH/LH group (p = 0.05). At multivariable Cox analysis, patients from the HH/LH group had more than two times higher risk of MACE during the follow-up than the LL/HL group (HR = 2.15 [95% CI, 1.03-4.5], p = 0.04). Other independent predictors of MACE were older age and worse left ventricular systolic function. CONCLUSION: In patients with AMI, permanently high or increasing TMAO levels during hospitalisation are associated with a higher risk of MACE during long-term follow-up.

Mavacamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From the MAVA-LTE Study, EXPLORER-LTE Cohort.

BACKGROUND: Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed. OBJECTIVES: The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655). METHODS: After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE. Patients received mavacamten 5 mg once daily; adjustments were made based on site-read echocardiograms. RESULTS: Between April 9, 2019, and March 5, 2021, 231 of 244 eligible patients (94.7%) enrolled in MAVA-LTE (mean age: 60 years; 39% female). At data cutoff (August 31, 2021) 217 (93.9%) remained on treatment (median time in study: 62.3 weeks; range: 0.3-123.9 weeks). At 48 weeks, patients showed improvements in left ventricular outflow tract (LVOT) gradients (mean change ± SD from baseline: resting: -35.6 ± 32.6 mm Hg; Valsalva: -45.3 ± 35.9 mm Hg), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (median: -480 ng/L; Q1-Q3: -1,104 to -179 ng/L), and NYHA functional class (67.5% improved by ≥1 class). LVOT gradients and NT-proBNP reductions were sustained through 84 weeks in patients who reached this timepoint. Over 315 patient-years of exposure, 8 patients experienced an adverse event of cardiac failure, and 21 patients had an adverse event of atrial fibrillation, including 11 with no prior history of atrial fibrillation. Twelve patients (5.2%) developed transient reductions in site-read echocardiogram left ventricular ejection fraction of <50%, resulting in temporary treatment interruption; all recovered. Ten patients discontinued treatment due to treatment-emergent adverse events. CONCLUSIONS: Mavacamten treatment showed clinically important and durable improvements in LVOT gradients, NT-proBNP levels, and NYHA functional class, consistent with EXPLORER-HCM. Mavacamten treatment was well tolerated over a median 62-week follow-up.

Acute viral myocarditis: current concepts in diagnosis and treatment.

Acute myocarditis is one of the most challenging diseases to diagnose and treat in cardiology. The true incidence of the disease is unknown. Viral infection is the most common etiology. Modern techniques have improved the ability to diagnose specific viral pathogens in the myocardium. Currently, parvovirus B19 and adenoviruses are most frequently identified in endomyocardial biopsies. Most patients will recover without sequelae, but a subset of patients will progress to chronic inflammatory and dilated cardiomyopathy. The pathogenesis includes direct viral myocardial damage as well as autoimmune reaction against cardiac epitopes. The clinical manifestations of acute myocarditis vary widely--from asymptomatic changes on electrocardiogram to fulminant heart failure, arrhythmias and sudden cardiac death. Magnetic resonance imaging is emerging as an important tool for the diagnosis and follow-up of patients, and for guidance of endomyocardial biopsy. In the setting of acute myocarditis endomyocardial biopsy is required for the evaluation of patients with a clinical scenario suggestive of giant cell myocarditis and of those who deteriorate despite supportive treatment. Treatment of acute myocarditis is still mainly supportive, except for giant cell myocarditis where immunotherapy has been shown to improve survival. Immunotherapy and specific antiviral treatment have yet to demonstrate definitive clinical efficacy in ongoing clinical trials. This review will focus on the clinical manifestations, the diagnostic approach to the patient with clinically suspected acute myocarditis, and an evidence-based treatment strategy for the acute and chronic form of the disease.