Trasplante cardíaco

Ann Intensive Care. 2025 Jul 2;15(1):88. doi: 10.1186/s13613-025-01508-1.

ABSTRACT

BACKGROUND: Post-cardiac arrest (CA) care guidelines (GLs) have been introduced in 2010 and periodically updated every 5 years since then (in 2015 and 2021). However, the impact of these GLs on patients' outcome remains underexplored. The aim of this study was to comprehensively evaluate and compare the impact of implementation of three consecutive post-CA GLs over 14 years, on patients' survival and neurological recovery.

METHODS: This retrospective cohort study included adult patients resuscitated from CA and admitted to the intensive care unit (ICU) between 2011 and 2024. Patients were stratified into three cohorts based on the GL in use (GL2010, GL2015, and GL2024). Adherence to GL recommendations was assessed across seven macro-areas: coronary angiography, haemodynamic, ventilation, temperature control, general ICU management, multimodal neuroprognostication, and seizure control. Predictors of survival and favourable neurological outcome at ICU discharge were evaluated using multivariate logistic regression with LASSO selection. Outcome up to 6 months was also evaluated.

RESULTS: A total of 275 patients were included over the 14-year period. Survival to ICU discharge increased from 39.5% in cohort 1 to 53.9% in cohort 3, together with favourable neurological outcome that improved from 30.9 to 42.7%. Adherence to GL recommendations significantly improved across most domains, particularly in haemodynamic management (from 32.0% in cohort 1 to 77.3% in cohort 3), temperature control (from 60.6 to 94.4%), and general ICU management (from 56.3 to 77.6%). Among all interventions, adherence to haemodynamic recommendations was independently associated with improved survival (OR = 2.20, 95% CI: 1.01-4.86).

CONCLUSIONS: Following the implementation of updated post-CA care GLs, adherence to recommendations improved, particularly in haemodynamic management. Although no statistically significant improvements in survival or neurological outcomes were observed, these findings highlight the potential value of sustained GL-based care.

PMID:40601206 | DOI:10.1186/s13613-025-01508-1

Interdiscip Cardiovasc Thorac Surg. 2025 Jul 2:ivaf146. doi: 10.1093/icvts/ivaf146. Online ahead of print.

ABSTRACT

OBJECTIVES: Aortic valve repair procedures for aortic valve regurgitation have been progressively adopted in the last decades. We analysed our results with an external ring annuloplasty and/or leaflet repair.

METHODS: From April 2014 to December 2023, 61 consecutive patients underwent aortic valve repair with external Teflon ring annuloplasty. The external ring was made of an 8 to 9 mm Teflon strip, to reduce the annulus diameter between 21 and 23 mm. Cusp effective height (eH) was assessed with a Caliper (not used before 2018) and any cusp prolapse was corrected by free margin plication, to obtain a 9-10 mm eH for all cusps.

RESULTS: 72.1% of patients had severe aortic regurgitation, associated supracoronary aneurysm repair was performed in 42.6%. No operative death occurred, residual AR more-than-moderate was present in one patient only. Eight years overall survival was 97.4 ± 2.6%, freedom from endocarditis 98.3 ± 1.7% and freedom from thromboembolism 100%. Recurrence of severe aortic regurgitation with need for reoperation was predicted by the presence of particularly enlarged aortic annulus (≥ 28 mm, p < 0.01) and the non-routinary use of cusp caliper (p = 0.03).

CONCLUSIONS: The external Teflon ring annuloplasty appears a safe procedure with high overall survival, freedom from endocarditis and freedom from thromboembolism at ten years. Recurrence of severe aortic regurgitation could be related to patient selection and learning curve.

PMID:40600917 | DOI:10.1093/icvts/ivaf146

Clin Transplant. 2025 Jul;39(7):e70222. doi: 10.1111/ctr.70222.

ABSTRACT

BACKGROUND: Primary graft dysfunction (PGD) represents a leading cause of mortality in patients undergoing donation after brain death (DBD) orthotopic heart transplantation (OHT), requiring timely escalation to mechanical circulatory support. There is a lack of nationwide data regarding PGD after donation after circulatory death (DCD). Here, we evaluated the incidence and short-term outcomes of PGD following DCD.

METHODS: Using the UNOS registry between 9/2023 and 9/2024, we identified all adult (≥18 years) recipients of OHT. The incidence and outcomes of moderate-severe PGD (24- and 72-h post-transplant) were compared between DCD and DBD. Predictors for mortality after PGD were analyzed using Cox proportional hazard models. 30-day survival was analyzed using the Kaplan-Meier method.

RESULTS: A total of 5017 patients underwent first-time OHT, among whom 762 (15.2%) received DCD hearts. DCD had a significantly higher incidence of PGD at 24- (7.9% vs. 4.8%; p = 0.001) and 72-h (5.9% vs. 3.3%; p = 0.001) compared to DBD. 30-day (p = 0.3068) survival was not different between DCD and DBD patients with PGD. Similarly, for recipients with PGD at 72 h, 30-day (p = 0.327) survival was comparable. At 72 h, DCD recipients were more likely to be supported on ECMO (p = 0.016). Transplanting DCD organs did not impact PGD-associated mortality at 24- (HR 0.72, p = 0.442) and 72-h (HR 0.74, p = 0.457). Postoperative ECMO was associated with decreased risk of PGD-associated mortality in DCD recipients at 24- (p < 0.0001) and 72-h (p < 0.0001).

CONCLUSIONS: While PGD rates appear higher in DCD, the associated mortality remains comparable to that of DBD. Early support on ECMO may confer survival benefits in DCD recipients with PGD.

PMID:40600382 | DOI:10.1111/ctr.70222

Clin Transplant. 2025 Jul;39(7):e70223. doi: 10.1111/ctr.70223.

ABSTRACT

BACKGROUND: Recommendations remain unclear between a shorter or extended CMV prophylaxis duration in donor seropositive/recipient seronegative (D+/R-) heart transplant recipients. The purpose of our study is to evaluate the effectiveness of a short (less than 145 days) versus extended (145 days or more) duration of CMV prophylaxis with ganciclovir (GCV)/valganciclovir (VGCV) for prevention of CMV viremia in this high-risk patient population.

METHODS: A retrospective cohort study was conducted of adult (age ≥ 18 years) CMV D+/R- heart transplantation recipients who received intravenous (IV) GCV or oral (PO) VGCV after transplant for CMV prophylaxis. CMV viremia/disease, time to CMV viremia/disease, hospitalizations, and mortality within the first year of transplant were assessed.

RESULTS: A total of 55 D+/R- heart transplant recipients were included in this study, with 28 recipients receiving short duration prophylaxis and 27 recipients receiving extended duration. The median (IQR) duration of therapy for the short and extended duration groups was 76 (69-100) and 189 (168-278) days, respectively. There were similar rates of CMV viremia (35.7% vs. 48.1%; p = 0.35) and CMV disease (10.7% vs. 11.1%, p = 0.96) between the short and extended duration prophylaxis groups. The outcomes of time to CMV from transplant, CMV hospitalization, and mortality were also similar between groups.

CONCLUSION: In the present study, no difference was observed in the incidence of CMV viremia within 1 year between short versus extended duration of GCV/VGCV prophylaxis in CMV D+/R- heart transplant recipients. Prospective studies with a larger sample size may be needed to confirm this finding.

PMID:40600369 | DOI:10.1111/ctr.70223

BMC Biotechnol. 2025 Jul 1;25(1):59. doi: 10.1186/s12896-025-00993-3.

ABSTRACT

Myocardial infarction, characterized by insufficient blood supply to the heart, leads to ischemia and hypoxia of myocardial tissues, causing injury and decreased cardiac function. Despite improvements in pharmaceutical and interventional therapies, it remains a leading cause of death worldwide. Human umbilical cord mesenchymal stem cells (hUC-MSCs) play an important role in the repair of infarcted myocardium by promoting angiogenesis, reducing inflammation, secreting growth factors and cytokines. However, the harsh hypoxic microenvironment of infarcted myocardial tissue poses a threat to the survival and function of transplanted hUC-MSCs. In this study, we modified the candidate gene promoter of hUC-MSCs under hypoxic conditions and created a promoter that can respond quickly under hypoxic conditions. We found that the modified promoter significantly promoted the transcription efficiency as hypoxia time increased. This indicates that the engineered hypoxia-response promoter can effectively drive gene expression in a hypoxic environment. Furthermore, the transcription efficiency of the modified promoter under normoxic conditions is lower than that of common promoters in eukaryotic organisms, suggesting that this effect can improve the efficacy and safety of hUC-MSC-based myocardial infarction treatment by ensuring that cells function effectively in the damaged hypoxic area.

PMID:40597956 | PMC:PMC12220557 | DOI:10.1186/s12896-025-00993-3

JHLT Open. 2025 May 29;9:100282. doi: 10.1016/j.jhlto.2025.100282. eCollection 2025 Aug.

ABSTRACT

The Fontan population has increased dramatically owing to advances in medical and surgical therapies, with many living well into adulthood with Fontan circulation. Unfortunately, patients will develop heart failure due to the chronic effects of their altered circulatory system. Management of heart failure in these patients is very complex and requires multi-disciplinary approaches with input from both cardiologists and surgeons. In the case of patients who develop cardiogenic shock, transplantation is often not feasible due to instability. Recently, there has been increased use of ventricular assist devices (VADs) as a bridge to transplantation with promising results. In this work, we briefly review the physiology of Fontan failure, provide criteria for VAD workup, and discuss VAD outcomes in Fontan patients. Finally, we describe a single institution's experience and outcomes with VADs in Fontan patients.

PMID:40599905 | PMC:PMC12209974 | DOI:10.1016/j.jhlto.2025.100282

Acta Clin Croat. 2024 Mar;63(Suppl1):14-17. doi: 10.20471/acc.2024.63.s1.2.

ABSTRACT

Cardiac allograft vasculopathy (CAV) is diffuse concentric narrowing caused by intimal fibriproliferation of the coronary arteries in patients after heart transplantation (HTx). It affects almost one third of patients over the period of 5 years, and more than 50% after 10 years following HTx and remains a common cause of late graft failure and mortality. Percutaneous coronary intervention (PCI) can be attempted for focal disease preferably with drug-eluting stents, but the only definite solution is re-transplantation reserved for selected patients with severe CAV. We report a case of a 33- year-old patient with a newly diagnosed CAV, in which a PCI of circumflex coronary artery was attempted, resulting in a coronary perforation treated by the placement of a covered single stent.

PMID:40599471 | PMC:PMC12207855 | DOI:10.20471/acc.2024.63.s1.2

J Med Life. 2025 May;18(5):428-439. doi: 10.25122/jml-2025-0061.

ABSTRACT

Patients with cancer and severe COVID-19 pneumonia treated with injectable azithromycin and anakinra frequently develop dysglycemia, necessitating initiation of sulfonylurea therapy (gliquidone or glimepiride). We retrospectively reviewed adults (≥30 years) with diabetes and cancer who were hospitalised for COVID-19 at the Central Military Hospital Bucharest and the Matei Bals National Institute between March 2020 and August 2022. All patients completed a 14-day course of azithromycin + anakinra and survived to discharge. Glycaemic control was achieved with fixed-dose gliquidone 30 mg or glimepiride 2, 3, or 6 mg, chosen according to each patient's inflammatory-cardiac profile. Central insulin resistance may lead to the risk of cardiometabolic syndrome through the increase of inflammatory markers (TNF-alpha and PAI-1), treated with gliquidone, in 50 patients with cancer infected with COVID-19, who were dependent on developing immunothrombosis. Peripheral insulin resistance leads to the risk of cardiovascular events through the increase of inflammatory markers, IL-6 and Il-1, treated with glimepiride, in 50 patients with cancer infected with COVID-19.

PMID:40599143 | PMC:PMC12207693 | DOI:10.25122/jml-2025-0061

World J Pediatr Congenit Heart Surg. 2025 Jul 2:21501351251347948. doi: 10.1177/21501351251347948. Online ahead of print.

ABSTRACT

Temporary mechanical circulatory support (tMCS) has been utilized as a bridge to heart transplantation with increasing duration of support. We describe the clinical course of a 14-year-old patient, with TNNT2 and KCNQ1 mutations, requiring Impella 5.5 support for 76 days. We discuss the patient's underlying genetic etiology, potential complications of prolonged tMCS, and the importance of multidisciplinary support. To our knowledge, this is the first published case in which a patient has this specific combination of genetic mutations and the longest published support duration of an Impella 5.5 in a pediatric patient.

PMID:40598957 | DOI:10.1177/21501351251347948

Adv Sci (Weinh). 2025 Jul 1:e06968. doi: 10.1002/advs.202506968. Online ahead of print.

ABSTRACT

Supercooling preservation holds great promise for extending the storage limits of organs. However, supercooled systems are susceptible to stochastic ice nucleation, which can cause fatal damage to the organs. In this study, an organogel interface composed of nanoscale polydimethylsiloxane and dimethyl-silicone oil is proposed, which presents a significant energy barrier for ice nucleation, comparable to that of homogeneous nucleation. The organogel effectively eliminates primary ice nucleation sites, enabling a quasi-homogeneous supercooling preservation system that does not rely on cryoprotectant agents or machine perfusion. Through a series of statistical experiments, this approach is demonstrated to be able to maintain stable supercooling and preserve mouse hearts at -4 °C for up to 72 h. A comprehensive assessment conducted at multiple scales indicates that the 36-h supercooling preservation at -4 °C significantly mitigates cardiac injury by regulating mitochondrial structure and reducing metabolic rates. Utilizing a heart transplantation model with prognostic evaluations extending up to 3 months post-transplantation, supercooling preservation within the quasi-homogeneous system is confirmed, which can double the storage duration compared to clinically applied hypothermic preservation methods.

PMID:40598840 | DOI:10.1002/advs.202506968

BMC Nutr. 2025 Jul 2;11(1):116. doi: 10.1186/s40795-025-01094-2.

ABSTRACT

BACKGROUND/AIM: We conducted the Mendelian Randomization (MR) analysis to investigate the causal relationship between serum saturated fatty acids (SFAs) and the risk of heart stroke (HS).

METHODS: The MRC-IEU Consortium provided summary statistics datasets related to SFAs, encompassing 64,979 individuals of European descent. Genetic variants associated with HF were identified using a GWAS dataset comprising 461,880 participants (cases = 7,055, controls = 454,825) of European descent from the UK Biobank. Generalized summary Mendelian Randomization (GSMR) assessed the potential association. Additionally, we performed a two-sample Mendelian Randomization (TSMR). The odds ratio (OR) with 95% confidence intervals (CIs) was indicated.

RESULTS: The GSMR results suggested no significant between SFA and HS [OR = 1.002, 95% CI: 0.995, 1.009; P-value = 0.752]. TSMR revealed [ORIVW = 1.005, 95% CI: 0.998, 1.012; P-value = 0.169]. MR Egger (Q = 6.14, Q_pvalue = 0.292), IVW (Q = 6.24, Q_pvalue = 0.396; I2 = 18.7%) for heterogeneity test, and Egger intercept = 1.14 × e-4, p-value = 0.792 for pleiotropy test were performed. These findings remained consistent across various Mendelian Randomization methods, including IVW [OR = 1.005, 95% CI: 0.99-1.01, p-value = 0.169], Simple median [OR = 1.009, 95% CI: 0.99-1.02, p-value = 0.08], MR-Egger [OR = 1.001, 95% CI: 0.97-1.03, p-value = 0.97], Robust Adjusted Profile Score [OR = 1.005, 95% CI: 0.99-1.01, p-value = 0.167], MR-Lasso [OR = 1.005, 95% CI: 0.99-1.01, p-value = 0.169], Constrained maximum likelihood (MR-cML) [OR = 1.006, 95% CI: 0.99-1.01, p-value = 0.168], Weighted mode [OR = 1.01, 95% CI: 0.99-1.02, p-value = 0.279], Maximum-likelihood method [OR = 1.005, 95% CI: 0.99-1.01, p-value = 0.158].

CONCLUSION: Our MR study did not yield convincing evidence supporting the association of SFAs with HF risk. Future studies should focus on alternative approaches to investigate this association.

PMID:40598686 | PMC:PMC12218826 | DOI:10.1186/s40795-025-01094-2

J Med Case Rep. 2025 Jul 1;19(1):304. doi: 10.1186/s13256-025-05359-z.

ABSTRACT

BACKGROUND: Nocardia species are opportunistic pathogens typically transmitted through inhalation or direct skin contact, causing various clinical manifestations, particularly in immunocompromised individuals. Nocardia spp. infection with severe clinical manifestations is rare in immunocompetent patients. In immunocompetent patients, complicated clinical presentations-central nervous system involvement, including multiple large and encapsulated brain abscesses with vasogenic edema and countless miliary-like lesions involving the brain, cerebellum, and brain stem-are rare, and treatment with plain antibiotic therapy to complete remission is highly unlikely compared with the emphasized combined neurosurgical interventions.

CASE PRESENTATION: We presented the case of a 67-year-old Iranian male with Nocardia spp. infection, an immunocompetent patient with prolonged and insidious manifestation that involved lung and central nervous system with solitary mature and countless miliary-like brain abscesses. Treatment with high-dose parenteral trimethoprim-sulfamethoxazole and meropenem for 6 weeks, followed by oral trimethoprim-sulfamethoxazole, successfully managed the disease without requiring neurosurgical intervention despite clinical indications. A follow-up brain magnetic resonance imaging showed that treatment led to the shrinkage of brain lesions.

CONCLUSION: We presented a case of Nocardia spp.-infection spp. infection in an immunocompetent patient with no significant history or comorbidities. The patient presented with a central nervous system infection characterized by solitary and miliary-like lesions. This case highlights the importance of considering Nocardia spp. infection as a differential diagnosis, particularly in patients with insidious and complex clinical manifestations. Meanwhile, it seems that more precise neurosurgical indications are necessary.

PMID:40598635 | PMC:PMC12220760 | DOI:10.1186/s13256-025-05359-z

J Transl Med. 2025 Jul 1;23(1):710. doi: 10.1186/s12967-025-06772-0.

ABSTRACT

Heart transplantation (HTx) remains the definitive treatment for patients with end-stage heart disease. Despite the number of HTx performed annually in worldwide continues to increase, complications of HTx still impact the quality of life and long-term prognosis, including rejection, infection, and allograft dysfunction. Endomyocardial biopsy remains the gold standard for monitoring cardiac allograft rejection post-heart transplantation, yet its invasiveness and interobserver error in histologic grading necessitate the development of novel noninvasive biomarkers to elucidate rejection mechanisms and progression. Cardiac allograft vasculopathy, a critical determinant of long-term outcomes, is challenging to detect early via intravascular ultrasound, underscoring the potential of plasma biomarkers for disease surveillance. Omic technologies usually refers to the application of multiple high-throughput screening technologies enabling comprehensive analysis of biological systems at a molecular level. Multi-omics technologies, including genomics(donor-derived cell-free DNA), transcriptomics(microRNAs panels, gene expression profiling), proteomics(cell signaling molecule), and metabolomics(ex situ heart perfusion), have demonstrated significant promise in post-transplant monitoring. These approaches provide personalized risk stratification and mechanical insights into cardiac allograft rejection, primary graft dysfunction, and cardiac allograft vasculopathy. Single-cell omics technologies and machine learning algorithms further resolve cellular heterogeneity and improve predictive modeling, thereby enhancing the clinical translatability of multi-omics data. This comprehensive review synthesizes these advances and highlights the transformative potential of integrating multi-omics with advanced analytics to achieve precision monitoring and therapy in HTx, ultimately improving long-term patient outcomes.

PMID:40598485 | DOI:10.1186/s12967-025-06772-0

Sci Rep. 2025 Jul 1;15(1):21174. doi: 10.1038/s41598-025-07317-7.

ABSTRACT

Recovery and clinical outcomes following organ transplantation may be negatively influenced by psychological distress. Limited reports from recipients indicate that thoughts and feelings related to the donor/transplanted organ - referred to as donor and donation images (DDI) - may be a source of such distress. The term DDI encompasses all thoughts and emotions that organ recipients associate with the donor or the donated organ. However, empirical knowledge of DDI remains limited. This quantitative survey involving 407 participants represents the first and largest study to quantitatively examine DDI in patients after heart transplantation (HTX). The results revealed a very high prevalence of DDI (91%), with occurrences reported intermittently and often clustered around the time of transplantation, both before and after HTX. Psychological distress predicted the occurrence of DDI before and after HTX and almost all emotions experienced and reported pre-HTX were associated with higher odds of pre-HTX DDI, suggesting it may be a concurrent phenomenon of overall emotional activation. Due to the involvement of emotions associated with uncertainty and low personal control, along with high situational control, DDI may be a part of coping. Some reported avoiding DDI suggesting that, sometimes, they might also represent a stressor. Future studies should further investigate the effects of DDI, including its impact on transplant outcome.

PMID:40596616 | PMC:PMC12219023 | DOI:10.1038/s41598-025-07317-7

Sci Rep. 2025 Jul 1;15(1):21214. doi: 10.1038/s41598-025-04405-6.

ABSTRACT

The efficacy of stem cell therapy for ischemic stroke in terms of functional outcomes remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (PROSPERO: CRD42024503763) to assess the efficacy and safety of stem cell therapy for acute/subacute ischemic stroke, focusing on long-term outcomes. Studies of patients undergoing stem cell transplantation within 1 month of stroke onset were included. We searched five databases for publications up to January 17, 2024. Summary data were extracted from published reports. The primary outcome was the modified Rankin Scale (mRS) score. Measures of effect were risk ratios (RRs) with 95% confidence intervals (CIs). A random-effects model was used when I2 was > 25%; otherwise, a fixed-effects model was used. Common serious adverse events were epilepsy, gastrointestinal disorders, and cardiac disorders. The risk of bias was assessed using the Cochrane Risk of Bias tool version 2. In total, 13 trials involving 872 (519 men) patients were included. The 1-year incidence of mRS scores 0-1 was higher in the cell-therapy group (45/195) than that in the control group (23/179; RR = 1.74 [95% CI = 1.09-2.77]; p = 0.020; I2 = 0%). The 90-day incidence of mRS scores 0-2 was also higher (RR = 1.31 [95% CI = 1.01-1.70]; p = 0.044; I2 = 0%). No significant differences were observed in serious adverse events or mortality. Stem cell therapy for acute/subacute ischemic stroke within 1 month of onset is safe and significantly improves long-term functional outcomes, although the mechanisms of action need to be elucidated and treatment protocols standardized to establish stem cell therapy as a standard care option for ischemic stroke.

PMID:40595869 | PMC:PMC12217828 | DOI:10.1038/s41598-025-04405-6

Transl Psychiatry. 2025 Jul 1;15(1):217. doi: 10.1038/s41398-025-03430-3.

ABSTRACT

INTRODUCTION: Major depressive disorder (MDD) is a heterogeneous psychiatric disorder that is a risk factor for cardiovascular diseases. Autonomic dysregulation, estimated as an important correlated pathophysiological cause, was investigated in many studies mainly through a quantitative evaluation of the heart rate variability (HRV).

AIM: The objective of this review was to provide any reproducible insights on autonomic regulation characteristics of MDD through the selection, revision, and joint interpretation of a restricted sample of studies based on systematic criteria.

METHODS: The literature research resulted in thirty eligible articles that reported the comparison of short-term resting-state HRV measures between drug-free MDD patients and healthy controls, excluding subjects affected by cardiovascular diseases.

RESULTS: Most of the reviewed studies reported significant differences between MDD patients and controls in the investigated HRV measures, especially for those that mainly reflect vagal activity. Nonlinear measures, although computed by fewer studies, seem to be more sensitive in detecting autonomic changes in MDD.

CONCLUSIONS: Our findings can be considered as evidence that the intrinsic autonomic state of MDD is characterized by decreased parasympathetic tone, which, interpreted in the context of the polyvagal theory, might be associated with impaired emotion regulation and flexible adjustment in MDD.

PMID:40595479 | PMC:PMC12215732 | DOI:10.1038/s41398-025-03430-3

Commun Med (Lond). 2025 Jul 1;5(1):266. doi: 10.1038/s43856-025-00963-y.

ABSTRACT

BACKGROUND: Cell therapy, particularly using cardiomyocytes, shows significant promise for treating heart failure. Direct reprogramming of somatic cells into cardiomyocytes using small molecules is advantageous due to its efficiency and cost-effectiveness.

METHODS: Human urine-derived cells (hUCs) were transdifferentiated into functional cardiomyocyte-like cells (hCiCMs) using a cocktail of 15 small molecules under xeno-free conditions. Various Characterizations were performed, including immunofluorescence, transmission electron microscopy (TEM), qPCR, single-cell RNA sequencing, patch-clamp recordings, and intracellular Ca²+ measurements. The therapeutic potential was tested in both mouse and porcine models of myocardial infarction (MI).

RESULTS: Reprogramming efficiency achieves 15.08% on day 30, with purity reaching 96.67% on day 60. hCiCMs display cardiomyocyte markers, sarcomeric structures, and abundant mitochondria. Electrophysiological analysis confirms ventricular-like action potentials and regular calcium transients. Single-cell RNA sequencing reveals cardiomyocyte subpopulations resembling 13-week embryonic human heart cells, with gene ontology analysis indicating successful maturation. In the MI model, hCiCM transplantation improves cardiac function, increasing ejection fraction and fractional shortening while reducing fibrosis.

CONCLUSIONS: This study demonstrates the successful reprogramming of hUCs into functional hCiCMs using small molecules under xeno-free conditions, offering a scalable, autologous cell source for cardiac repair with significant potential for regenerative therapies.

PMID:40595290 | PMC:PMC12216017 | DOI:10.1038/s43856-025-00963-y

Sci Rep. 2025 Jul 1;15(1):22327. doi: 10.1038/s41598-025-08315-5.

ABSTRACT

The interactions between CD40 and tumor necrosis factor receptor-associated factor 6 (TRAF6) are implicated in chronic inflammation and fibrosis. Given their poorly understood role in chronic transplant rejection, our study focused on investigating the CD40-TRAF6 interactions in murine models of cardiac transplantation, particularly in relation to cardiac allograft vasculopathy (CAV). We established murine heart transplantation models using BALB/C to C57BL/6 and H-2bm12 to C57BL/6 pairings. A specific antagonist for TRAF6 was administered post-transplantation, either alone or in combination with cyclosporin A (CsA). We analyzed cells infiltrating the cardiac allografts and splenic immune cells. Additionally, We explore the potential mechanistic effects of TRAF6 inhibition in CAV by bone marrow-derived macrophages (BMDMs) co-culture. The inhibition of CD40-TRAF6 interaction significantly prolonged the survival of cardiac allografts. When combined with CsA, this treatment induced long-term survival of the allografts. Specifically, in the H-2bm12 to C57BL/6 heart transplantation model, inhibiting TRAF6 mitigated the development of CAV. This blockade led to a decrease in CD11b + and CD4 + cells within the allografts. In vitro experiments showed that TRAF6 inhibition had limited effects on mixed lymphocyte culture responses and minimally affected the proliferation of naive CD4 + cells activated by CD3/CD28. Furthermore, BMDMs under CD40-TRAF6 inhibition were more likely to differentiate into an anti-inflammatory phenotype, and their migration capability was reduced. Our findings demonstrate that inhibiting the TRAF6 pathway can significantly ameliorate both acute and chronic allograft rejection. The combination with CsA appears to have a synergistic effect, suggesting that targeting the TRAF6 could be a beneficial co-strategy for managing alloimmune responses. Importantly, our results position TRAF6 as a promising complementary target for enhancing outcomes in CAV.

PMID:40595221 | DOI:10.1038/s41598-025-08315-5

Sci Rep. 2025 Jul 1;15(1):20573. doi: 10.1038/s41598-025-06607-4.

ABSTRACT

This study was aimed at developing and internally validating nomograms for predicting mortality during venoarterial-extracorporeal membrane oxygenation (VA-ECMO) and in-hospital mortality risk in patients treated with VA-ECMO. A total of 7260 patients treated with VA-ECMO from January 2017 to December 2023 were extracted from the Chinese society of extra corporeal life support registry database. The entire cohort was randomly assigned to derivation and validation cohorts at a ratio of 2:1. Multivariable Cox proportional hazards regression was conducted using bootstrapping with the likelihood ratio test and Akaike information criterion. Approximately 24% of patients died during VA-ECMO assistance, and 51% died in the hospital. The nomogram PROFIT was constructed with ten pre- and immediately post-ECMO parameters: age, body mass index (BMI), intra-aortic balloon pump before VA-ECMO, history of cardiac arrest, worst mean arterial pressure (MAP), potential of hydrogen (pH) and serum lactate levels before VA-ECMO, site of ECMO installation, peripheral cannulation and distal perfusion. Additionally, nomogram POSITIVE was also established with ten parameters: age, sex, BMI, history of cardiac arrest, MAP, pH, and serum lactate levels before VA-ECMO support, the occurrence of cardiac arrest before VA-ECMO, type of sedation and prior continuous renal replacement therapy. The area under the receiver operating characteristics (AUC) of the nomogram PROFIT (0.72 [95% CI 0.70-0.74]) and POSITIVE (0.71 [95% CI 0.68-0.73]) outperformed the SAVE score, which indicated that the nomograms were capable of effectively identifying patients with a high risk of mortality. Both nomograms demonstrated outstanding discrimination and calibration in derivation and validation cohorts. In patients treated with VA-ECMO, the nomogram PROFIT may serve as a valuable tool for predicting mortality during VA-ECMO assistance, and the nomogram POSITIVE can predict in-hospital mortality with high reliability. However, these tools still require external validation in other patient populations requiring VA-ECMO support.

PMID:40594967 | PMC:PMC12215877 | DOI:10.1038/s41598-025-06607-4

Sci Rep. 2025 Jul 1;15(1):21803. doi: 10.1038/s41598-025-06190-8.

ABSTRACT

A number of cardioprotective pharmacological agents are not effective in diabetic hearts. The role of AGGF1-EPCs therapy in diabetic ischaemia-reperfusion(I/R) injury and the underlying mechanism by which AGGF1 regulates EPCs under hyperglycemia (HG) + hypoxia/reoxygenation (H/R) stress are still unclear. We observed that the damaging effects of HG + H/R on EPCs were abolished by AGGF1. The EPCs implantation therapy successfully restores cardiac functions, inhibits ROS production and fibrosis in diabetic I/R mice. Mechanistically, AGGF1 activates the Nrf2 and induces the activation of downstream antioxidative proteins (HO1, NQO1, and CAT). These data suggest that AGGF1 protein reverses the damaging effects of HG + H/R on EPCs via the antioxidative Nrf2. AGGF1-EPCs therapy is a novel strategy for treating diabetic I/R injury.

PMID:40594882 | PMC:PMC12216187 | DOI:10.1038/s41598-025-06190-8