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The roles of Contactin-2 (CNTN2) and ferroptosis in heart failure and cardiac remodeling remain incompletely understood. CNTN2 was significantly upregulated in hypertrophic cardiomyopathy patients and heart failure mice. In cardiomyocyte specific CNTN2 conditional knockout (CNTN2 cKO) mice, transverse aortic constriction (TAC) induced markedly exacerbated heart failure, cardiac remodeling and ferroptosis compared to control mice. Ferroptosis inhibition substantially attenuated heart failure in CNTN2 cKO mice subjected to TAC, indicating that enhanced ferroptosis contributes to the detrimental effects of CNTN2 deficiency. RNA sequencing identified NUPR1, a ferroptosis repressor, as a downstream molecule of CNTN2. Mechanistically, CNTN2 activated the Lyn/eIF2α/ATF4 pathway to regulate NUPR1. CNTN2 overexpression attenuated Angiotensin II-induced cardiomyocyte ferroptosis and pathological remodeling, whereas these protective effects were abolished by Lyn or NUPR1 inhibitors. We further revealed CNTN2 and Lyn interacted with each other, and that CNTN2 interacted with Lyn through its 1-328aa domain. In vivo NUPR1 overexpression via AAV9 significantly mitigated TAC-induced heart failure and cardiac remodeling in CNTN2 cKO mice. Our study demonstrates that CNTN2 protects against pressure overload induced heart failure and cardiac remodeling by regulating ferroptosis through the Lyn/eIF2α/ATF4/NUPR1 pathway, suggesting CNTN2 as a potential therapeutic target.

The demand for home healthcare services for chronic conditions has increased due to the transition of care from hospitals to the home. This study aimed to adapt a Clinical Practice Guideline (CPG) for home-based nursing care of adult patients with heart failure in the healthcare system of Iran. This study was conducted using a multi-method design within the 10-step framework of the Practice Guidelines Evaluation and Adaptation Cycle (PGEAC). A systematic review was conducted in PubMed, Scopus, Web of Science, and nine publicly accessible CPG databases to find relevant guidelines. Subsequently, a robust CPG was selected based on the Appraisal of Guidelines for Research and Evaluation-II (AGREE-II) checklist. After translating the guideline, a search for supporting evidence was conducted in databases for each guideline recommendation, and the results were classified based on the level of evidence. Next, a qualitative study was conducted to strengthen recommendations with a weak evidence level and uncover additional recommendations and domains. The preliminary draft of the CPG was then evaluated in an expert panel meeting. In the final phase, the adapted CPG was validated through three Delphi rounds. "Adapting Heart Failure Guidelines for Nursing Care in Home Health Settings," was selected as an appropriate CPG with 145 recommendations within five domains. Following translation and evaluation of the evidence level, 26 recommendations were categorized in the weak level of evidence. In the qualitative phase, these recommendations were further examined, and also 26 new recommendations were developed; 12 under the domain of the "Generic care in heart failure" and 14 within two newly identified domains. Twenty-one recommendations were removed during the expert panel meeting, as well as 33 ones in the first Delphi round, due to duplication or not being applicable the Iranian healthcare system. The final adapted CPG included 117 recommendations within six domains. This adapted CPG provides a robust framework for nurses and other healthcare professionals to deliver home healthcare services for Iranian heart failure patients and their families. It can enhance the quality of home-based care, reduce hospital readmissions, improve patients' outcomes, and the cost-effectiveness of home-based care programs.

Unplanned equipment and infrastructure interruptions are a persistent source of radiotherapy service loss, yet prioritization is often based on either downtime burden or risk criticality alone. This study analyzed five years of interruption logs to integrate a standardized failure taxonomy with downtime-based Pareto analysis and FMECA criticality scoring. A harmonized event log captured asset class, subsystem, cause category, operational severity, downtime, and maintainability indicators, including response and repair times. Event burden and downtime distributions were quantified, Pareto rankings were performed at asset, subsystem, and cause levels, and FMECA Risk Priority Numbers were analyzed. Agreement between Pareto and FMECA priorities was assessed using Top-k overlap and Spearman rank correlation. A total of 4200 events produced 16,006.4 h of service loss. Downtime per event was right-skewed, with a median of 0.93 h and an interquartile range of 0.43-2.50 h. Minor events comprised 42.95% of events but accounted for only 4.39% of downtime, whereas critical events represented 6.60% of events but generated 50.93% of downtime. Major events contributed 31.79% of downtime from 19.43% of events. Unit-level burden ranged from 755 to 1707 events and from 2990.9 to 6077.8 h of downtime. Downtime was dominated by LINAC failures, accounting for 60.5%, followed by HDR after loader faults at 15.0%, OIS/network interruptions at 8.6%, CT-sim faults at 6.9%, TPS-related events at 6.0%, and auxiliary infrastructure at 3.0%. The leading subsystem contributors were imaging systems at 1324.7 h, MLC components at 1178.7 h, and software/controls at 1152.5 h. The leading cause categories were hardware wear/aging at 4532.6 h, power instability at 2340.2 h, and vendor part delay at 2212.6 h. Median response times clustered between 0.60 and 0.61 h, while median repair times ranged from 0.62 to 0.86 h. Pareto and FMECA alignment was limited, with a Top-10 overlap of 3/10, a Top-5 overlap of 0/5, and a Spearman correlation of approximately 0.09. Service loss was concentrated in a minority of major and critical episodes. Combining Pareto analysis, which prioritizes lost hours, with FMECA, which identifies rare but high-criticality modes, supports balanced and actionable prioritization for maintenance planning, spare-parts and logistics strategy, power conditioning, and digital infrastructure resilience. Radiotherapy services can be disrupted when equipment fails, which may delay treatment for patients. This study reviewed five years of equipment failure records to understand which problems caused the most service interruptions and how best to prioritize them. This study found that a small number of serious issues caused most delays, and using more than one method helped identify priorities more clearly. This matters because better planning can reduce delays and support safer, more reliable treatment.

Graft failure after allogeneic hematopoietic stem cell transplantation is a life-threatening complication requiring retransplantation. Cord blood is frequently used in this setting, although the optimal conditioning regimen remains unclear. Recently, a modified short-course fludarabine-based conditioning regimen has been used in clinical practice for salvage cord blood retransplantation in Japan.Using Japanese registry data, we analyzed 465 patients with hematologic malignancies who developed graft failure and underwent cord blood retransplantation within 2 months after allogeneic hematopoietic stem cell transplantation between 2008 and 2016. Of these, 84 patients received a modified short-course fludarabine-based conditioning regimen consisting of fludarabine 30 to 90 mg/m2 over 1 to 3 days, cyclophosphamide 2 g/m2, and low-dose total body irradiation (2 Gy).One-year overall survival and progression-free survival were higher with the modified short-course regimen than with other regimens (45.1% vs 29.9%, p = 0.028; 44.0% vs 26.8%, p = 0.008, respectively). Engraftment at day 56 did not differ significantly between groups (64.3% vs 57.4%, p = 0.178).The modified short-course regimen was associated with improved overall and progression-free survival and may represent a feasible option for salvage cord blood retransplantation after graft failure.

Acute heart failure (AHF) is a major cause of emergency department (ED) visits and is associated with significant morbidity and mortality. In Thailand, real-world data on AHF presentations and outcomes in the ED remain limited, particularly in resource-constrained settings. This study aimed to describe the clinical characteristics, treatment, and outcomes of AHF patients in a tertiary care ED in Northeastern Thailand and identify factors associated with in-hospital mortality. We conducted a retrospective cohort study of adult patients (&#x2265;&#x2009;18 years) diagnosed with AHF at the ED of Srinagarind Hospital between October 2021 and March 2023. Patients transferred from other hospitals or who were pregnant were excluded. Clinical data were extracted from electronic health records. The primary outcome was in-hospital mortality. Univariable and multivariable logistic regression analyses were performed to identify factors independently associated with in-hospital mortality. Of 902 eligible AHF patients, the median age was 71 years (IQR: 60-80), and 52.0% were male. The in-hospital mortality rate was 6.0%. Non-survivors were more likely to have a history of congestive heart failure, chronic kidney disease, or cerebrovascular accident, and presented with lower diastolic blood pressure and oxygen saturation. They were also more likely to be triaged as Emergency Severity Index (ESI) level 1 and require ICU admission, ventilatory support, and inotropic support. In multivariable analysis, the need for inotropic support was the only variable independently associated with in-hospital mortality (adjusted OR 3.97; 95% CI 1.91-8.40; p&#x2009;<&#x2009;0.001). In this ED-based cohort, the in-hospital mortality of patients with acute heart failure was comparable to international reports. The need for inotropic support was strongly associated with hospital mortality, likely reflecting severe hemodynamic compromise.

Obesity is a major risk factor for heart failure with preserved ejection fraction (HFpEF). Incretin-based therapies are associated with a reduction in worsening heart failure (HF) events for patients with HF with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), although the time to clinical benefit from these therapies is unknown. PubMed, Embase, and CENTRAL were searched until July 12, 2025 for randomized controlled trials studying incretin-based therapies (semaglutide, tirzepatide) in adults with overweight/obesity and HF with ejection fraction >40%, and &#x2265;52-week follow-up. We extracted study-level data, from which individual participant data (IPD) was reconstructed. To estimate the time to benefit, we iteratively calculated hazard ratios (HR) and 95% confidence intervals (CI) with the dataset truncated for each day of follow-up. We pooled overall results with reconstructed IPD and study-level random-effects meta-analyses. Risk of bias was assessed with RoB 2, and certainty of evidence with GRADE. Four trials, encompassing 4149 participants and a weighted average median follow-up of 2.47 years, were included. Risk of bias was low. Compared to placebo, incretin-based therapies reduced worsening HF or cardiovascular death (HR 0.59, 95% CI 0.45-0.78; moderate certainty). The nominal time to first statistical significance was 126 days (4.1 months), and statistical significance was sustained after day 162 (5.3 months). Incretin-based therapies reduced worsening HF events (HR 0.33, 95% CI 0.20-0.54; high certainty), with sustained significance after day 183 (6.0 months). Incretin-based therapies are associated with reduced HF events in patients with overweight/obesity and HFmrEF/HFpEF, with sustained statistically significant outcome benefits observed from approximately 6 months onwards.

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases and predominantly affects older individuals, yet effective treatments remain limited. The molecular mechanisms linking cardiac aging to HFpEF are not fully understood. Here we show that the transcriptional regulator Sub1 is upregulated in aged hearts and in mouse models of HFpEF. Cardiac overexpression of Sub1 shortens lifespan, exacerbates diastolic dysfunction, and accelerates cardiac aging, whereas Sub1 knockdown delays cardiac aging and alleviates HFpEF features, even when initiated in aged mice. Mechanistically, Sub1 interacted with TAF9b and AROS to stabilize p53 by regulating its ubiquitination and acetylation, thereby promoting cardiomyocyte senescence. Furthermore, disrupting the Sub1-p53 interaction attenuates cardiomyocyte senescence in vitro. These findings identify Sub1 as a contributor to aging-associated HFpEF and provide insight into the molecular links between cardiac aging and disease progression.

Observational studies suggest an association between impaired oral health and cardiovascular disease; however, the directionality and underlying mechanisms remain unclear. In particular, whether heart failure (HF) itself adversely affects oral and periodontal health has not been systematically investigated in large populations or experimental models.We examined the association between HF and self-reported oral health indicators in 502,387 participants of the UK Biobank, including 17,356 individuals with HF defined by ICD-9/10 codes. Multivariable logistic regression models adjusted for demographic factors, cardiovascular comorbidities, systemic inflammation, lifestyle, and socioeconomic status were applied. To explore causality and mechanisms, periodontal tissue remodeling and inflammation were assessed in a murine model of pressure overload-induced HF using transverse aortic constriction (TAC). Periodontal ligament (PDL) space and alveolar bone microarchitecture were quantified by micro-computed tomography, and gingival inflammatory gene expression was analyzed by RT-PCR.HF patients exhibited a significantly higher prevalence of oral health burden compared with controls (51% vs. 40%, p<0.001). HF was associated with a 1.6-fold increased risk of impaired oral health, which remained significant after full adjustment (adjusted OR 1.18, 95% CI 1.14-1.22; p<0.001). In mice, reduced left ventricular ejection fraction following TAC was strongly associated with expansion of the maxillary PDL space (R2 = 0.63, p = 0.009) and alterations in alveolar bone microarchitecture (trabecular thickness R2 = 0.41 p = 0.061, trabecular number R2 = 0.38 p = 0.07). These structural changes were accompanied by increased gingival expression of pro-inflammatory cytokines, including Il1b (SHAM vs. TAC: 1.44 &#xb1; 1.02 vs. 3.39 &#xb1; 1.53,&#xa0;p&#xa0;= 0.06) and TNF-&#x3b1; (SHAM vs. TAC: 1.37 &#xb1; 0.86 vs. 5.71 &#xb1; 1.23,&#xa0;p&#xa0;= 0.002 predominantly in the maxilla.HF is independently associated with impaired oral health in a large population cohort and induces site-specific periodontal inflammation and remodelling in experimental HF. These findings support HF as an upstream driver of compromised oral-periodontal health, challenging the prevailing concept that oral disease primarily contributes to cardiovascular pathology.

Long COVID comprises heterogeneous symptoms that may persist for months to years after acute SARS-CoV-2 infection. While prevalence is well described, less is known about symptom duration and determinants of recovery. We conducted a multicenter longitudinal cohort study across 12 institutions in Korea (December 2022-March 2025), enrolling adults with confirmed infection and uninfected controls. Participants were followed for up to 22 months with repeated assessments of symptoms, vaccination, and comorbidities. Eight common symptoms were analyzed. Time to resolution was estimated using Kaplan-Meier methods and log-normal accelerated failure time models, adjusting for demographic and clinical factors. Results are reported as time ratios (TRs). Among 757 infected participants and 558 controls, respiratory and physical symptoms resolved similarly between groups, whereas systemic and neurological symptoms persisted longer in infected individuals. At one year, 20-25% reported fatigue and 15-20% sleep disturbance versus &#x223c;10% and &#x223c;5% in controls. Infection was associated with &#x223c;50% longer duration of fatigue and sleep disturbance. Individuals aged 40-59 recovered more slowly; other factors showed minimal associations. Persistent long COVID burden is driven by systemic neuro-related symptoms, highlighting the need for targeted, symptom-specific management strategies.

Heart failure (HF) is associated with high hospitalization rates and substantial healthcare costs. Pharmacist-collaborative interventions in HF can optimize medication management and have been shown to reduce hospitalizations, but their economic impact in hospital settings remains unclear. Estimate the healthcare payer cost of pharmacist-collaborative care in patients attending a HF clinic at a large Belgian hospital. A microsimulation model was developed to estimate the healthcare payer cost of pharmacist-collaborative care in patients attending a HF clinic at a large Belgian hospital. The model compared total avoided hospitalization costs and pharmacist-related costs over a one-year horizon. Patient-level variability and parameter uncertainty were incorporated using Monte Carlo simulation. Input parameters, including number needed to treat (NNT) to avoid a hospitalization, pharmacist full-time equivalent (FTE) and annual cost, hospitalization cost, and weekly patient throughput, were represented by probabilistic distributions. Cost impact was summarized as mean, median and 95% credible intervals (CrI). Determinants of cost impact were explored using multivariable linear regression. The NNT threshold for cost neutrality was estimated. Across all simulations, the intervention achieved cost savings in 96.2% of scenarios, with mean annual savings of &#x20ac;93,899 (median &#x20ac;88,834; 95% CrI: &#x20ac;-4,350 to &#x20ac;226,549). Regression analysis indicated that each additional patient managed per week increased annual savings by &#x20ac;16,760 (p < 0.001), and each &#x20ac;1 increase in hospitalization cost increased savings by &#x20ac;17.25 (p < 0.001). In contrast, each one-unit increase in NNT was associated with a decrease in cost savings of &#x20ac;2,115 (p < 0.001). The patient-level NNT required for cost neutrality was 74. Pharmacist-collaborative interventions in HF care are highly likely to generate cost savings, particularly in HF clinics with higher patient throughput or settings with higher hospitalization costs. These quantitative thresholds provide practical guidance for the allocation and scaling of pharmacist resources in multidisciplinary HF programs.

Heart failure (HF) is a common disease among older individuals and is associated with poor quality of life and prognosis. Individuals at risk of developing HF are usually already patients in primary healthcare, but diagnosing HF at an early stage can be challenging. Identifying patients at risk of HF and initiating early treatment is crucial for their outcomes. Using the variables gender, age, multimorbidity (MM) level, and socioeconomic status (SES), we aimed to study the possibility of identifying individuals at high risk of HF diagnosis within two years. A longitudinal registry-based study, including 961,190 inhabitants aged from 20 years onwards without a HF diagnosis living in southern Sweden during 2015. Logistic regression was applied to estimate the OR of HF diagnosis within two years by adjusting for the variables gender, age, MM level, and SES. Linear predictions were made based on models by adding these variables in steps. Each model was compared with the previous model using a likelihood-ratio test. The optimal cutoff point for sensitivity and specificity was calculated using the Youden method. Age had the highest OR of HF diagnosis within two years, followed by MM level, gender, and SES. ROC (Receiver Operating Characteristic) analysis, including these variables in steps, generated an increasing AUC (area under the curve), from 0.5144 to 0.9379. When all four variables were included in the model, an optimal cutoff point according to Youden was established at 1.15%, which predicted the probability with a sensitivity of 87.69% and specificity of 78.48%. The positive predictive value was 4.78%, and the negative predictive value was 99.81% for the whole adult population; for those aged 70 years and older, it was 21.02% and 98.99%; and for those aged 80 years and older, it was 33.62% and 98.09%, respectively. Age was the most important factor for predicting the probability of HF diagnosis within two years in our study, followed by MM level, gender, and SES. These findings may help identify population groups at increased risk of HF in whom targeted case-finding strategies could be evaluated in future studies.

Patients undergoing primary restrictive bariatric metabolic surgery procedures (BMS) are at risk of having suboptimal initial response (SIR) and late postoperative clinical deterioration (LPCD), which can be an indication for conversion. Roux-en-Y gastric bypass (RYGB) is currently the most common conversion procedure. Still, one anastomosis gastric bypass (OAGB) has emerged as a viable alternative conversion procedure to RYGB, due to its relative technical simplicity and easy reversibility. We aim to assess the safety and effectiveness of laparoscopic OAGB as a conversion procedure for managing SIR or LPCD after primary restrictive BMS procedures. A retrospective observational study was conducted at our university hospital between July 2017 and December 2024. It included patients with failed primary restrictive bariatric procedures. All patients underwent conversion to OAGB and were followed for a minimum of 5 years. 115 patients completed the 5-year follow-up. The early postoperative complication rate was 7.6%, and the reoperation rate was 1.6%. After 5 years, late postoperative complications occurred in 11.3% of patients. The mean body mass index loss (BMIL%) was 28.59% and 17.4% of patients had SIR during the study period. Significant improvement in obesity-associated medical problems was observed after 5 years, with remission rates of 70.8% for type 2 diabetes mellitus, 82.4% for dyslipidemia, 64.1% for sleep apnea, and 61.3% for hypertension. OAGB is a safe and effective conversion procedure for the management of SIR and LPCD after restrictive procedures, achieving favorable mid-term outcomes.

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