Ther Adv Med Oncol. 2025 Sep 23;17:17588359251378245. doi: 10.1177/17588359251378245. eCollection 2025.
ABSTRACT
BACKGROUND: Real-world evidence on protective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) against anthracycline- or trastuzumab-induced cardiotoxicity in patients with breast cancer is limited.
OBJECTIVES: To examine the cardioprotective benefits of SGLT2i in older women with early-stage breast cancer (EBC) following anthracycline- and/or trastuzumab-based therapies.
DESIGN: This was a retrospective cohort study using the 2011-2019 SEER-Medicare database.
METHODS: We identified women aged over 65.5 years and diagnosed with stage I-III BC who received anthracycline and/or trastuzumab and subsequently initiated antidiabetic medications. Propensity scores were used to match one new-user episode of SGLT2i with four new-user episodes of other antidiabetic medications (OAMs). The primary outcome was a composite endpoint consisting of heart failure (HF), stroke, myocardial infarction, and arrhythmia. Secondary outcomes included hospitalization due to HF (HHF) and incident HF or cardiomyopathy (CM). Cause-specific hazard ratios (csHR) between SGLT2i and OAMs groups were assessed for each outcome, with all-cause death treated as a competing event.
RESULTS: From 1195 women examined, 1777 new-user episodes were identified. After 1:4 matching, there were 131 episodes in the SGLT2i group and 469 in the OAM group. Covariates were well-balanced between groups. No statistically significant differences were observed in the composite cardiovascular (csHR = 0.71; 95% confidence interval (CI): 0.44-1.15; p = 0.24), HHF (csHR = 0.92; 95% CI: 0.10-8.27; p = 0.94), or incident HF/CM (csHR = 0.77; 95% CI: 0.45-1.34; p = 0.36) outcomes. Results were consistent across individual SGLT2i and clinical subgroups, including those with/without established cardiovascular diseases and those exposed to various cardiotoxic cancer treatments.
CONCLUSION: No significant differences in cardiovascular risks were found between women with EBC who initiated SGLT2i versus OAMs after anthracycline or trastuzumab treatments, which might be due to the limited sample size. Further investigation through clinical trials is necessary to confirm the cardioprotective potential of SGLT2i among patients with EBC.
PMID:41018041 | PMC:PMC12461033 | DOI:10.1177/17588359251378245
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2025 Jul;37(7):693-697. doi: 10.3760/cma.j.cn121430-20250318-00270.
ABSTRACT
Peroxisome proliferator activated receptor-α (PPAR-α) is significantly expressed in various tissues such as the liver, kidney, myocardium, and skeletal muscle, which plays a central role in the development of various diseases by regulating key physiological processes such as energy homeostasis, redox balance, inflammatory response, and ferroptosis. As an important metabolic and excretory organ of the body, renal dysfunction can lead to water and electrolyte imbalance, toxin accumulation, and multiple system complications. The causes of kidney injury are complex and diverse, including acute injury factors (such as ischemia/reperfusion, nephrotoxic drugs, septic shock, and immune glomerulopathy), as well as chronic progressive causes [such as metabolic disease-related nephropathy, hypertensive nephropathy (HN)], and risk factors such as alcohol abuse, obesity, and aging. This review briefly describes the structure, function, and activity regulation mechanism of PPAR-α, systematically elucidates the molecular regulatory network of PPAR-α in the pathological process of kidney injury including acute kidney injury (AKI) such as renal ischemia/reperfusion injury (IRI), drug-induced AKI, sepsis-associated acute kidney injury (SA-AKI), glomerulonephritis, chronic kidney disease (CKD) such as diabetic nephropathy (DN), HN, and other kidney injury, and summarizes the mechanisms related to PPAR-α regulation of kidney injury, including regulation of metabolism, antioxidation, anti-inflammation, anti-fibrosis, and anti-ferroptosis. This review also evaluates PPAR-α's medical value as a novel therapeutic target, and aims to provide theoretical basis for the development of kidney protection strategies based on PPAR-α targeted intervention.
PMID:41017187 | DOI:10.3760/cma.j.cn121430-20250318-00270
Infect Control Hosp Epidemiol. 2025 Sep 29:1-6. doi: 10.1017/ice.2025.10312. Online ahead of print.
ABSTRACT
OBJECTIVE: Diagnostic stewardship of blood culture utilization is important to mitigate the risks associated with unnecessary culturing. Although blood culture algorithms have been studied previously, there is a lack of data on their application among solid organ transplant (SOT) recipients. This study aims to retrospectively apply a blood culture algorithm (initially developed for a non-immunocompromised population) to adult SOT recipients and assess its performance.
METHODS: We conducted a manual retrospective review of adult SOT recipients with a blood culture event (BCE) between February 2022 and January 2024 at a single academic medical center. BCEs were categorized as appropriate, inappropriate, or lacking documentation, according to a previously established institutional blood culture algorithm.
RESULTS: Of 737 BCEs among adult SOT recipients, 185 (25%) were inappropriate. Within the subset of inappropriate BCEs, 178 (96%) yielded negative cultures, while 7 (4%) were deemed contaminants. No true positives were identified. Inappropriate BCEs were most commonly triggered by isolated fever and/or leukocytosis (136, 74%), and lower urinary tract infection (17, 9%). 17 of 18 BCEs due to donor blood culture positivity at the time of organ transplantation resulted in a negative blood culture in the recipient.
DISCUSSION: Once applied retrospectively, our institutional blood culture algorithm did not miss any true positive bloodstream infections among adult SOT recipients. This study provides initial evidence supporting the cautious application of blood culture diagnostic algorithms in adult SOT populations. Further prospective investigations are warranted to validate these findings.
PMID:41020577 | PMC:PMC12483178 | DOI:10.1017/ice.2025.10312
Front Med (Lausanne). 2025 Sep 11;12:1650700. doi: 10.3389/fmed.2025.1650700. eCollection 2025.
ABSTRACT
BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent complication following coronary artery bypass grafting (CABG), significantly impacting patient prognosis and healthcare costs. This study aimed to develop an integrated predictive model for POAF risk stratification to optimize clinical management.
METHODS: We retrospectively analyzed 2,528 patients undergoing 21-gene pharmacogenetic testing for cardiovascular therapy. After stringent data curation, 576 CABG patients were enrolled and randomly allocated into training and test sets. Eight machine learning algorithms were trained using clinical variables and genetic variants. An independent validation set was performed on 61 patients from a subsequent 1,075-patient cohort of 21-gene pharmacogenetic testing.
RESULTS: Eight machine learning algorithms were trained, tested, and validated, with the Gaussian Naive Bayes (GNB) model demonstrating robust performance (Accuracy: 0.81 in test set and 0.79 in independent validation set). SHapley Additive exPlanations analysis identified four key predictors: multivessel CABG (CABGVx ≥ 3), history of heart failure (HFHx), rs5219 (KCNJ11), and prolonged bypass duration (CABGTime). To facilitate clinical translation, we developed an accessible web-based tool (https://www.xingyeyard.site/cabg/) for real-time POAF risk stratification.
CONCLUSION: This GNB-based classifier synergistically integrates Pharmacogenomic and clinical predictors to predict POAF risk following CABG. The combination of rigorous validation and user-centered design positions this model as a valuable clinical decision-support tool for optimizing personalized perioperative care.
PMID:41020232 | PMC:PMC12460236 | DOI:10.3389/fmed.2025.1650700
Front Cardiovasc Med. 2025 Sep 12;12:1601430. doi: 10.3389/fcvm.2025.1601430. eCollection 2025.
ABSTRACT
This comprehensive review examines the complex relationship between human immunodeficiency virus (HIV) and cardiomyopathy, focusing on the underlying molecular mechanisms, clinical manifestations, diagnostic approaches, and treatment strategies. It highlights the significant global health burden posed by HIV and its potential to cause long-term cardiovascular complications. The review investigates the pathogenesis of HIV-associated cardiomyopathy. It elucidates the intricate cellular and molecular pathways involved, including the actions of neutrophils, monocytes, macrophages, and lymphocytes in cardiac inflammation. Key signaling pathways such as TNF-NF-κB and the caspase-1 inflammasome are detailed, as they contribute to cardiac infection and injury. The clinical manifestations of HIV-associated cardiomyopathy are discussed, including fatigue, dyspnea, peripheral edema, and arrhythmias. The review outlines essential diagnostic methods, highlighting the importance of cardiac biomarkers, electrocardiography, and imaging techniques such as echocardiography and cardiac MRI. Treatment strategies are explored, encompassing lifestyle modifications, pharmacological interventions, and advanced therapies. The review underscores the importance of addressing micronutrient deficiencies, particularly selenium, in the management of HIV-associated cardiomyopathy. It also discusses the role of antiretroviral therapy and the potential benefits of intravenous immunoglobulin therapy. Furthermore, this review addresses the evolving perspective on heart transplantation for individuals with HIV. It notes that while HIV was once considered a contraindication for transplantation, recent advancements in antiretroviral therapy have led to a re-evaluation of this stance. Finally, the review identifies future research directions, emphasizing the need for biomarkers to detect at-risk patients, exploration of nutritional factors predisposing individuals to cardiomyopathy, and further investigation into advanced therapies for HIV-associated cardiomyopathy. This review significantly enhances the understanding of HIV-associated cardiomyopathy, providing valuable insights for clinicians and researchers in the fields of infectious diseases and cardiology.
PMID:41019440 | PMC:PMC12465280 | DOI:10.3389/fcvm.2025.1601430
Front Endocrinol (Lausanne). 2025 Sep 11;16:1658780. doi: 10.3389/fendo.2025.1658780. eCollection 2025.
ABSTRACT
OBJECTIVE: Acute or chronic metabolic derangement following solid organ transplantation (SOT) often leads to endocrine complications, which have become more common as survival rates post-SOT have improved. This study was performed to investigate long-term endocrine complications after SOT in children and adolescents.
METHODS: This study included 259 pediatric patients who underwent SOT, including kidney (n = 43), liver (n = 170), lung (n = 5), heart (n = 37), and multi-organ (n = 4), with a minimum follow-up period of 5 years post-transplant. Clinical and endocrinological data were retrospectively collected, including information on growth, obesity, diabetes, dyslipidemia, thyroid disease, bone health, and pubertal development.
RESULTS: Of 259 patients, 203 (78.4%) developed endocrine complications over a median follow-up period of 10.5 years (range, 5.5-16.8). Short stature was common in kidney (58.1%) and multi-organ recipients (100%), whereas the highest rates of obesity were observed in liver recipients (43.5%). Kidney or liver recipients under 13 years of age showed significant improvements in height-standard deviation scores within 5 years post-SOT. Discontinuation of corticosteroids was associated with a reduced risk of short stature 10 years after liver transplantation. Heart recipients had a high prevalence of post-transplant diabetes mellitus (PTDM, 27%). Other endocrine complications included dyslipidemia (40.2%), hypothyroidism (2.8%), and low bone mineral density (31.3%). Among liver recipients, pretransplant obesity was a significant risk factor for development of post-transplant obesity, PTDM, and dyslipidemia. Additionally, liver transplantation at 0-1 years of age increased the risk of obesity, while transplantation at 6-12 years of age, cyclosporine use, and allograft rejection were associated with an increased risk of dyslipidemia.
CONCLUSIONS: This study demonstrates that endocrine and metabolic complications are common in pediatric SOT recipients. Effective surveillance and management of these sequelae are crucial to improve long-term quality of life following SOT.
PMID:41019329 | PMC:PMC12460080 | DOI:10.3389/fendo.2025.1658780
Front Immunol. 2025 Sep 12;16:1633853. doi: 10.3389/fimmu.2025.1633853. eCollection 2025.
ABSTRACT
IMPORTANCE: Preformed donor-specific antibodies (pre-DSAs) are a significant immunologic barrier in solid organ transplantation (SOT), yet their association with post-transplant outcomes lacks consensus, limiting standardized clinical management.
OBJECTIVE: To determine the association between pre-DSA and posttransplant complications, including antibody-mediated rejection (AMR), T cell-mediated rejection (TCMR), graft loss, and patient mortality, with subgroup analyses stratified by organ type and MFI thresholds (1,000 cutoff).
DATA SOURCES: Systematic review of 3,322 studies from PubMed, Embase and the Cochrane Library (from inception to February 2024) following the PRISMA guidelines.
STUDY SELECTION: Sixty-nine observational studies (22,737 transplant recipients; 3,787 pre-DSAs+), including retrospective and prospective cohorts, encompassing kidney (KT) (41 studies), liver (LT) (13), lung (6), heart (3), and other organ transplants.
MAIN OUTCOMES AND MEASURES: Primary: AMR, TCMR, graft loss, patient death.Secondary: Biliary complications, bacteremia, delayed graft function (DGF).
RESULTS: Pre-DSAs positivity conferred significantly elevated risks of AMR (RR = 5.21, 95%CI 4.01-6.79), graft loss (RR = 2.11, 1.72-2.60), and mortality (RR = 1.62, 1.39-1.89) compared with pre-DSAs-negative recipients, with marked heterogeneity across organ types. KTs faced the highest risk of AMR risk (RR = 6.09, 4.39-8.46), whereas LT recipients exhibited elevated mortality (RR = 1.81, 1.30-2.53) but lower AMR rates (RR = 1.81 vs. KT). The thoracic organs (heart/lung) had no significant association with AMR (RR1.32, 0.86-2.03). Stratification by MFI thresholds revealed amplified risks at MFI≥1,000, particularly for AMR (RR = 7.51 vs 4.65 at MFI<1,000; Pinteraction<0.001) and loss of graft (RR = 2.30 vs 1.81; P = .032). KT with MFI≥1,000 had the highest cumulative hazards (AMR: RR = 8.12, 5.94-11.10; graft loss: RR = 2.55, 1.98-3.28), whereas LT recipients with MFI≥1,000 had higher mortality RR = 2.01 (1.44-2.80). Secondary outcomes included increased delayed graft function (DGF: RR = 1.49, 1.12-1.98) in pre-DSA+ patients, driven by KT (RR = 1.82, 1.30-2.55), but no association with T-cell-mediated rejection (TCMR: RR = 1.10, 0.94-1.28).
CONCLUSIONS: Pre-DSAs is a strong independent predictor of AMR and graft loss in SOT, with amplified risks in KT and cohorts with DSA+ MFI≥1,000. These findings advocate for universal pretransplant DSAs screening and DSA+MFI-guided desensitization to prioritize high-risk patients. Organ-specific strategies, intensified AMR surveillance in KTs, and mortality-focused monitoring in LTs, are critical to improving outcomes.
PMID:41019095 | PMC:PMC12463609 | DOI:10.3389/fimmu.2025.1633853
Mol Ther. 2025 Sep 27:S1525-0016(25)00814-7. doi: 10.1016/j.ymthe.2025.09.042. Online ahead of print.
ABSTRACT
Patients with Mucopolysaccharidosis type I Hurler (MPSIH) experience multisystem clinical manifestations which are only partially addressed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study evaluated outcomes from a lentiviral vector (LV)-mediated hematopoietic stem and progenitor cell gene therapy (HSPC-GT) trial (NCT03488394) in 8 MPSIH patients followed up to 4 years post-treatment. Key findings included corneal clouding, hearing loss (HL), carpal tunnel syndrome (CTS) and cardiac evaluations. A retrospective comparison with an external cohort of 9 MPSIH patients undergoing allo-HSCT was performed. All patients are alive at last follow-up, show stable engraftment without graft failure, insertional oncogenesis, or immune responses to the transgene. Notably, at last follow-up 3/8 HSPC-GT patients experienced corneal clouding resolution, while all allo-HSCT patients maintained moderate corneal clouding. 4/8 HSPC-GT patients showed normal hearing function at last follow-up due to improvement (n=3) or stabilization (n=1); 7/9 allo-HSCT patients had mild or moderate HL at baseline, while 2/9 showed moderate HL at last follow-up. No HSPC-GT patients required surgery for CTS developed after HSPC-GT, while 7/9 patients needed such surgery after allo-HSCT. No HSPC-GT patients developed severe cardiomyopathy or valvular disease, while in the HSCT cohort 4/9 patients experienced progression of valvular insufficiency although not requiring valve replacement. Our results indicate a favorable effect of HSPC-GT on MPSIH multisystemic manifestations up to 4-year after treatment; long-term, prospective comparative studies are warranted for definitive conclusions.
PMID:41017152 | DOI:10.1016/j.ymthe.2025.09.042
World J Pediatr Congenit Heart Surg. 2025 Sep 29:21501351251369435. doi: 10.1177/21501351251369435. Online ahead of print.
ABSTRACT
Artificial neochordae crafted from expanded polytetrafluoroethylene are commonly utilized in mitral valve repair. Yet their application in tricuspid valve repair, particularly in the pediatric demographic, remains relatively unexplored. Upon reviewing the available literature, we have identified pediatric patients with tricuspid valve regurgitation, primarily of congenital origin and diagnosed at birth, who underwent repair procedures involving artificial neochordal implantation. Postoperatively, trivial-to-mild tricuspid regurgitation was predominantly observed in most cases. Operative mortality appears to be low, but a reliable estimate of operative mortality rates, early failure, and reoperation was not possible due to incomplete data reporting in the studies reviewed. Moreover, long-term data are not available since in most reports, postoperative evaluation was obtained early after repair. Our review suggests that artificial neochordal repair of the tricuspid valve may be a feasible surgical option to prosthetic valve replacement in pediatric patients. However, comprehensive data and further late follow-up are needed to analyze long-term effectiveness and clinical outcomes.
PMID:41021658 | DOI:10.1177/21501351251369435
Eur Heart J Case Rep. 2025 Sep 2;9(9):ytaf424. doi: 10.1093/ehjcr/ytaf424. eCollection 2025 Sep.
ABSTRACT
BACKGROUND: It was in 1866 when Wilhelm Ebstein first described a rare case of a 19-year-old cyanotic patient with tricuspid valve regurgitation caused by a congenital malformation. Since then, Ebstein's anomaly (EA) has been recognized as a condition that exhibits a diverse clinical course with a formidable challenge for clinicians in terms of diagnosis, management, and prognosis.
CASE SUMMARY: We present a case series of four patients with EA, shedding light on the varied clinical manifestations, treatment approaches, and outcomes that underscore the multifaceted nature of this condition.
DISCUSSION: The management of EA requires a comprehensive and individualized approach in specialized centres. The cardiologists responsible for the long-term care of these patients are faced with various challenging 'dilemmas' in the clinical course of the disease at different stages. The evolving landscape of cardiology offers a promising avenue for improving the outcomes and quality of life of patients with EA.
PMID:41019305 | PMC:PMC12461249 | DOI:10.1093/ehjcr/ytaf424
J Vasc Surg Cases Innov Tech. 2025 Aug 21;11(6):101957. doi: 10.1016/j.jvscit.2025.101957. eCollection 2025 Dec.
ABSTRACT
Isolated unilateral absence of pulmonary artery is a rare congenital malformation and often asymptomatic in adults. However, aneurysm formation in the aortopulmonary collateral vessels carries a potential risk of life-threatening hemorrhage. This case report describes a 79-year-old woman who presented with rupture of a mediastinal collateral aneurysm associated with isolated unilateral absence of pulmonary artery. We discuss the clinical course, including vascular morphology changes, and subsequent endovascular treatment. Notably, this case demonstrates the rupture of a de novo collateral aneurysm rather than a preexisting one.
PMID:41018207 | PMC:PMC12475422 | DOI:10.1016/j.jvscit.2025.101957
Cardiol Young. 2025 Sep 29:1-6. doi: 10.1017/S1047951125109499. Online ahead of print.
ABSTRACT
BACKGROUND: CHD is a major risk factor for acute ischaemic stroke in paediatric patients due to endothelial changes from surgically manipulated vessels, prosthetic material, flow stasis in variable circulations, and hypercoagulability from chronic cyanosis. Stroke recognition in critically or chronically ill patients is challenging, yet rapid identification allows for mechanical thrombectomy to restore cerebral blood flow, particularly in those ineligible for thrombolysis or beyond its therapeutic window. We present a case series highlighting the importance of prompt stroke diagnosis and the role of mechanical thrombectomy in paediatric CHD patients, including children as young as four.
METHODS: We conducted a single-centre retrospective chart review of paediatric CHD patients who experienced thromboembolic stroke and underwent mechanical thrombectomy from July 2018 to March 2024. Data collected included age, stroke territory, maximum Paediatric NIH Stroke Scale (PedNIHSS) score, pre-thrombectomy neurological deficits, and post-thrombectomy outcomes using thrombolysis in cerebral infarction (TICI) scores.
RESULTS: Four CHD patients underwent mechanical thrombectomy for thromboembolic stroke (Table ). They exhibited diverse cardiac anatomies, including two-ventricle and single-ventricle physiology, with a wide age range at presentation.
CONCLUSION: Stroke presentation in CHD patients is variable, necessitating a high index of suspicion. Mechanical thrombectomy is safe and effective in patients as young as four, with no haemorrhagic complications in this series. Further research is needed to develop tailored stroke management guidelines for paediatric CHD patients, particularly younger children and those ineligible for thrombolysis.
PMID:41017363 | DOI:10.1017/S1047951125109499
Cureus. 2025 Aug 26;17(8):e91027. doi: 10.7759/cureus.91027. eCollection 2025 Aug.
ABSTRACT
Fragility hip fractures are increasingly common in elderly patients and are associated with high morbidity and mortality. Cardiovascular comorbidities-including ischaemic heart disease, heart failure, and valvular disease-contribute significantly to poor outcomes. This study aimed to review perioperative cardiac complications in elderly patients undergoing fragility hip fracture repair and evaluate strategies for optimisation, with emphasis on postoperative atrial fibrillation (POAF), acute myocardial infarction (AMI), heart failure, and management of cardiac implantable electronic devices (CIEDs). We conducted a narrative review drawing data from the databases PubMed, Embase, and the Cochrane Library (January 2000-March 2024). The search terms included "hip fracture," "cardiac complications," "postoperative atrial fibrillation," "myocardial infarction," "heart failure," "valvular disease," and "cardiac implantable electronic devices." Guidelines from the National Institute for Health and Care Excellence (NICE), the European Society of Cardiology (ESC), and the American College of Cardiology/American Heart Association (ACC/AHA) were also reviewed. POAF was observed in ~3-4% of elderly hip fracture patients and is associated with significantly higher one-year mortality (60% vs. 19.5%). Risk factors include surgical delay beyond 48 hours and transfusion of >2 units of packed red blood cells. AMI and perioperative heart failure are frequently underdiagnosed due to atypical presentations. CIED management requires multidisciplinary coordination to avoid device malfunction. Cardiac optimisation in fragility hip fracture patients remains challenging due to heterogeneous evidence and variable practice. Development of validated POAF risk prediction tools, standardised treatment protocols, and structured multidisciplinary pathways may help improve outcomes and reduce healthcare burden.
PMID:41018305 | PMC:PMC12462645 | DOI:10.7759/cureus.91027
Mol Ther. 2025 Sep 27:S1525-0016(25)00814-7. doi: 10.1016/j.ymthe.2025.09.042. Online ahead of print.
ABSTRACT
Patients with Mucopolysaccharidosis type I Hurler (MPSIH) experience multisystem clinical manifestations which are only partially addressed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study evaluated outcomes from a lentiviral vector (LV)-mediated hematopoietic stem and progenitor cell gene therapy (HSPC-GT) trial (NCT03488394) in 8 MPSIH patients followed up to 4 years post-treatment. Key findings included corneal clouding, hearing loss (HL), carpal tunnel syndrome (CTS) and cardiac evaluations. A retrospective comparison with an external cohort of 9 MPSIH patients undergoing allo-HSCT was performed. All patients are alive at last follow-up, show stable engraftment without graft failure, insertional oncogenesis, or immune responses to the transgene. Notably, at last follow-up 3/8 HSPC-GT patients experienced corneal clouding resolution, while all allo-HSCT patients maintained moderate corneal clouding. 4/8 HSPC-GT patients showed normal hearing function at last follow-up due to improvement (n=3) or stabilization (n=1); 7/9 allo-HSCT patients had mild or moderate HL at baseline, while 2/9 showed moderate HL at last follow-up. No HSPC-GT patients required surgery for CTS developed after HSPC-GT, while 7/9 patients needed such surgery after allo-HSCT. No HSPC-GT patients developed severe cardiomyopathy or valvular disease, while in the HSCT cohort 4/9 patients experienced progression of valvular insufficiency although not requiring valve replacement. Our results indicate a favorable effect of HSPC-GT on MPSIH multisystemic manifestations up to 4-year after treatment; long-term, prospective comparative studies are warranted for definitive conclusions.
PMID:41017152 | DOI:10.1016/j.ymthe.2025.09.042
Biomaterials. 2025 Sep 20;327:123727. doi: 10.1016/j.biomaterials.2025.123727. Online ahead of print.
ABSTRACT
Up to 1 billion cardiomyocytes (CMs) die during myocardial infarction (MI), leading to permanent muscle loss and devasting functional impacts. Biomaterial therapies have aimed to passively reinforce the infarcted left ventricle (LV), but their therapeutic impact remains limited as they fail to directly address the loss of functional CMs. In this work, we employed a simulation-guided workflow to design an optimized biomaterial support that can be combined with contractile CMs for implantation after MI. A finite element model (FEM) of the LV post-MI was developed and showed longitudinal reinforcement and active contractility improves ejection fraction (EF) post-MI (+3.39 % and +14.97 %, respectively). To this end, we developed a coordinated remuscularization-reinforcement therapy using engineered human myocardium (EHM) composed of human induced pluripotent stem cell-derived CMs (hiPSC-CMs) integrated with a highly aligned electrospun polycaprolactone (PCL) scaffold. Remuscularization (EHM-only), reinforcement (PCL-only) and its coordinated therapy (PCL-EHM) were evaluated in a rat model of MI. We report successful engraftment of the implants onto the heart with significant maturation of hiPSC-CMs after four weeks in vivo (∼7-fold increase of cTnT area and ∼2-fold increase MLC2v area compared to in vitro cultured controls). Using 4D ultrasound (US), we quantified 3D regional strains and found that the benefits of PCL reinforcement on maintaining LV structure and function were additive with remuscularization by EHM. This additive effect was reflected inimproved regional strain after injury when PCL and EHM were delivered as a composite therapy. This work establishes a promising strategy for synergistic reinforcement and remuscularization of the infarcted heart.
PMID:41016348 | DOI:10.1016/j.biomaterials.2025.123727
J Clin Epidemiol. 2025 Sep 26:112001. doi: 10.1016/j.jclinepi.2025.112001. Online ahead of print.
ABSTRACT
OBJECTIVES: To address the limitations of existing models for research and population health applications in older adults with type 2 diabetes, we developed and validated cardiovascular disease (CVD) and heart failure risk models using linked Medicare claims and electronic health records (2013-2020).
STUDY DESIGN AND SETTING: The study included adults >65 years with type 2 diabetes and ≥1 HbA1c measurement before cohort entry (defined as the date of a physician/outpatient visit). Using LASSO and XG-boost machine learning algorithms, we predicted 1-year risks of a composite cardiovascular event (myocardial infarction, stroke, coronary artery revascularization, or hospitalization for heart failure). Separate models were developed for patients with and without baseline CVD using claims-only and claims-EHR predictors. Models were trained on 70% of the data and validated on 30%. Model performance was evaluated using c-statistics for discrimination, scaled Brier scores, and calibration curves. We externally validated the models in Clinformatics commercial and Medicare Advantage claims data.
RESULTS: There were 14,776 patients with baseline CVD [mean (SD) age: 77(8) years] and 10,679 without baseline CVD [mean (SD) age: 74 (7) years]. Claims-only models achieved a c-statistic of 0.75 and a Brier score of 0.09 in patients with baseline CVD, while in those without baseline CVD, the c-statistic was 0.73 and the Brier score was 0.01. For both subgroups, calibration intercepts were ∼0, with slopes ∼1. Claims-EHR models provided similar performance.
CONCLUSION: In older adults with diabetes, our models predicted one-year cardiovascular outcomes with good discrimination and accuracy, independently of CVD history.
PLAIN LANGUAGE SUMMARY: Older adults with type 2 diabetes have a high risk of heart disease, heart failure, and death, yet it is difficult to predict who is most at risk. Most existing prediction tools are designed for use during a single clinic visit, not for large healthcare databases that researchers use to study treatment safety and effectiveness. In this study, we developed computer-based models using Medicare claims data and, for some models, additional information from electronic health records (EHR). These models predicted the chance of having a major heart event or dying within one year. We created separate models for people with and without existing heart disease, because their risk factors differ. Our models accurately predicted risk in both groups. Adding EHR data did not improve performance compared to using claims data alone. This means that claims-only models can still be useful for researchers studying treatments in large healthcare databases. These models can help identify people at higher risk, guide research on diabetes medications, and support better planning for healthcare resources.
PMID:41016516 | DOI:10.1016/j.jclinepi.2025.112001
Eur Respir J. 2025 Sep 28:2501126. doi: 10.1183/13993003.01126-2025. Online ahead of print.
ABSTRACT
BACKGROUND: Bronchiectasis is a common lung condition associated with wide range of infectious, immunological, autoimmune, allergic and genetic conditions. Exacerbations and daily symptoms have the largest impact on patients and healthcare systems, and they are the key focus of treatments. Current practice is heterogeneous globally, and bronchiectasis has historically been a neglected disease. Here, we present evidence-based international guidelines for the management of adults with bronchiectasis.
METHODS: A European Respiratory Society (ERS) Task Force, comprising global experts, a methodologist, and patient representatives, developed clinical practice guidelines in accordance with ERS methodology and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. Systematic literature searches, data extraction, and meta-analysis were performed to generate evidence tables, and recommendations were formulated using the evidence-to-decision framework. A total of 8 PICO (Patient, Intervention, Comparator, Outcomes) questions and 3 narrative questions were developed.
RECOMMENDATIONS: The Task Force recommendations include strong recommendations in favour of airway clearance techniques for most patients with bronchiectasis and pulmonary rehabilitation for those with impaired exercise capacity. We issue a strong recommendation for the use of long-term macrolide treatment for patients at high risk of exacerbations and a strong recommendation in favour of long-term inhaled antibiotics in patients with chronic Pseudomonas aeruginosa infection at high risk of exacerbation. Conditional recommendations support the use of eradication treatment or mucoactive drugs in specific circumstances. We suggest not to routinely use long term oral, non-macrolide antibiotic treatment or inhaled corticosteroids. Additional guidance is also provided on testing for underlying causes, managing exacerbations, and managing the deteriorating patient.
CONCLUSION: The ERS bronchiectasis guidelines provide an evidence-based framework for optimal management of adults with bronchiectasis and serve as a benchmark for evaluating the quality of care.
SCOPE AND OBJECTIVES: The European Respiratory Society (ERS) guidelines for the management of bronchiectasis in adults provide evidence-based recommendations for the care of people with clinically significant bronchiectasis, defined by the presence of permanent dilatation of the bronchi evident on chest CT scan, along with characteristic clinical symptoms. [1] These guidelines are intended for all healthcare professionals involved in the care of adults with bronchiectasis, as well as for policymakers, regulatory authorities, and pharmaceutical companies. Bronchiectasis is a complex and heterogeneous disease; therefore, no guideline can be entirely comprehensive or replace clinical judgement. All guideline recommendations must be interpreted within the specific clinical context in which they are applied. Separate ERS guidelines for the management of bronchiectasis in children exist [2]. Bronchiectasis due to cystic fibrosis (CF) has a distinct evidence base; therefore, guidance for the management of CF is provided elsewhere. [3] Some bronchiectasis-associated conditions also have distinct guidelines for investigation and management, such as primary ciliary dyskinesia (PCD) [4], allergic bronchopulmonary aspergillosis (ABPA) [5] and non-tuberculous mycobacterial (NTM) pulmonary disease [6]. While the present guidelines apply for these conditions, they should be interpreted in conjunction with the relevant syndrome-specific recommendations.
PMID:41016738 | DOI:10.1183/13993003.01126-2025
Int J Cardiovasc Imaging. 2025 Sep 29. doi: 10.1007/s10554-025-03508-5. Online ahead of print.
ABSTRACT
Due to the high mortality and morbidity of patients with aortic and mitral endocarditis, careful monitoring is necessary to recognize an early failure of antibiotic and cardiokinetic therapy and avoid a possible cardiogenic or septic shock. The timing of surgery is crucial for patients in whom medical therapy fails. The aim of our study is to identify potential echocardiographic biomarkers of adverse events in patients with left-sided native valve infective endocarditis. Sixty-four patients with aortic and/or mitral valve dysfunction(AOVD, MVD) from infective endocarditis were studied by three-dimensional transesophageal echocardiography(3DTEE) and transthoracic speckle tracking echocardiography(3DSTE). Sixty-four healthy subjects were selected as controls. Vegetation size and valvular features were assessed by 3DTEE. Standard transthoracic echocardiographic parameters were determined. Global left ventricular(LV) longitudinal strain(3D-LVGLS) and area strain(3D-LVGAS) were measured by 3DSTE. Averaged LV rotation and rotational velocities from the base and apex were obtained and used for calculation of LV twist and torsion. Endpoints were embolism and in-hospital mortality. Maximal vegetation dimension was 10 (4-29) mm if measured by 3DTEE and 7 (4-20) mm if measured by 2DTEE (p = 0.02). Valvular and perivalvular complications were present in 21(33%) and 13(20%) patients. AOVD/MVD patients had decreased GLS (p = 0.011), GAS (p = 0.003) and LVtwist (p = 0.024) compared with control subjects. By multivariate analysis, vegetation mobility(p = 0.001), vegetation size(p = 0.003), perivalvular complications(p = 0.006), and bivalvular vegetations(p = 0.009) were independent predictors of embolic events. Valve-related complications(p = 0.001), vegetation size(p = 0.029), 3D-LVGLS(p = 0.013), and 3D-LVGAS(p = 0.002) were predictive of in-hospital mortality. Using a composite endpoint of both outcomes, ROC curves suggested that 3D valvular and LV function parameters had higher diagnostic accuracy for identifying adverse events than 2D parameters. 3D combined evaluation of vegetation size, regurgitant volume and LV area strain had the highest diagnostic accuracy (AUC 0.89, p = 0.001). Significant improvement in global χ2 value was noted with 3D strain parameters compared with LV ejection fraction for predicting outcome (from 82.3 to 90.5, p = 0.004). 3D combined assessment of anatomical-functional valve characteristics and LV function strain parameters improves the sensitivity of the echocardiographic indices in predicting cardiac morbidity and mortality of left-sided native valve infective endocarditis.
PMID:41016998 | DOI:10.1007/s10554-025-03508-5
Anaesth Crit Care Pain Med. 2025 Sep 26:101617. doi: 10.1016/j.accpm.2025.101617. Online ahead of print.
ABSTRACT
BACKGROUND: New-onset atrial fibrillation (NOAF) occurs in 10% of intensive care unit (ICU) stays and worsens clinical outcomes. Despite its significance, no specific guidelines exist for the general ICU population. Our study investigates potential therapeutic approaches to NOAF, focusing on the rhythmic and haemodynamic outcomes associated with dedicated strategies.
METHODS: In our prospective multicentre cohort study, we included adult patients admitted to 33 ICUs in France, exhibiting at least one episode of NOAF. Exclusions included permanent and post-cardiac/thoracic surgery AF. Data on demographics, clinical history, haemodynamic monitoring, and treatment choice for NOAF episodes were prospectively recorded. Heart rate, blood pressure, and rhythm status were assessed immediately before, at +5, +30, +60 minutes, and +24 hours after NOAF onset.
RESULTS: Between May and December 2019, 453 ICU patients with 735 NOAF episodes were included. Therapeutic approaches included wait-and-see (n = 159 (22%)), IV fluid (n = 338 (46%)), magnesium (n = 299 (41%)), amiodarone (n = 295 (40%)), and beta blockers (n = 73 (10%)); alone or combined in 354 episodes (61%). Electric cardioversion, preferred for poor haemodynamic tolerance, was most effective for sinus rhythm conversion at +1 h (n = 17/30 (57%)). Heart rate and rhythm control were achieved at 87% (n = 588/674) and 80% (n = 259/654) at +24 h, with no significant difference between the strategies. On ICU discharge, 48 (13%) patients remained in AF; independent predictors included age, obesity, prior stroke, and hypercholesterolemia.
CONCLUSIONS: Therapeutic approaches for NOAF in ICU patients were heterogeneous, with nearly a quarter managed by a wait-and-see approach. Most strategies achieved rhythm and rate control within 24 hours. These findings highlight the frequent transient nature of NOAF episodes and support the need for individualized treatment decisions, particularly in unstable patients and those at risk for persistent AF. Trial registration ClinicalTrials.gov NCT03977883 (https://clinicaltrials.gov/study/NCT03977883?term=NCT03977883&rank=1).
PMID:41016469 | DOI:10.1016/j.accpm.2025.101617
Interdiscip Cardiovasc Thorac Surg. 2025 Sep 27:ivaf237. doi: 10.1093/icvts/ivaf237. Online ahead of print.
ABSTRACT
OBJECTIVES: This study aimed to determine whether the anatomical burden of prior percutaneous coronary intervention(PCI) influences long-term outcomes after coronary artery bypass grafting, beyond the impact of intervention presence alone.
METHODS: This retrospective study analyzed consecutive patients undergoing coronary artery bypass grafting at a single institution between 2000 and 2024. The inclusion criteria comprised isolated, non-emergent surgery. Patient categorization was based on prior PCI-treated lesions: none, single, or multiple. The primary endpoint was long-term overall survival. The secondary endpoints included cardiac death, myocardial infarction, stroke, heart failure hospitalization, and repeat revascularization. Long-term outcomes were assessed using Kaplan-Meier analysis and Cox multivariable models, adjusting for 26 clinical factors.
RESULTS: Of 2,442 patients, 1,205 met the inclusion criteria (755 none, 227 single-lesion, 223 multiple-lesion intervention). Over a median follow-up of 12.0 (interquartile range, 11.3-12.9; maximum: 24.2) years, the multiple-lesion intervention group had higher rates of in-hospital acute kidney injury (34.1% vs. 21.1% vs. 24.2%, P = 0.003). Overall survival differed significantly between groups over the follow-up period (log-rank P = 0.004), with 15-year survival rates of 35.8%, 46.0%, and 48.0% for multiple-lesion, single-lesion, and no prior PCI groups, respectively. After adjustment, multiple-lesion intervention was associated with increased risks of cardiac death (adjusted subdistribution hazard ratio: 1.91), myocardial infarction (2.26), and repeat revascularization (1.92) compared with no prior intervention.
CONCLUSIONS: Multiple-lesion PCI was associated with higher long-term risks of cardiac death, myocardial infarction, and repeat revascularization, while stroke risk was similar. Single-lesion PCI showed outcomes comparable to no prior PCI except for higher heart failure hospitalization. These findings require confirmation in larger, multicenter comparative studies to address residual confounding.
PMID:41014500 | DOI:10.1093/icvts/ivaf237