Curr Probl Cardiol. 2025 Jun 30:103125. doi: 10.1016/j.cpcardiol.2025.103125. Online ahead of print.
ABSTRACT
Cardiac amyloidosis (CA) is a once underdiagnosed and often fatal condition that has evolved into a disease with expanding diagnostic and therapeutic possibilities. It is characterized by the extracellular deposition of misfolded amyloid proteins within the myocardium, leading to structural and functional impairment. Advances in understanding the pathophysiology encompassing the amyloid protein misfolding, aggregation and deposition in cardiac tissue as well as the role of genetic factors have been pivotal in driving progress in diagnosis and management. The deposition of amyloid proteins can lead to significant cardiac manifestations, including constrictive cardiomyopathy, heart failure (both preserved and reduced ejection fraction), and arrhythmias particularly atrial fibrillation, contributing to substantial morbidity and mortality. Diagnostic innovations, such as advanced imaging and novel biomarkers, have enabled early detection and precise subtype differentiation, underscoring the need for targeted therapies. Over the past decade, therapeutic advancements have introduced transformative medications that gained FDA approval for the management of transthyretin amyloidosis (ATTR) including transthyretin stabilizers and silencers. Promising strategies like gene editing, antisense oligonucleotides and monoclonal antibodies are currently under investigation. However, managing cardiac manifestations remains challenging, particularly in optimizing euvolemia and rate control in heart failure and atrial fibrillation with limitations in traditional medications. This review explores the evolving landscape of CA, from pathophysiologic insights to innovative therapies, and provides a comprehensive approach to the management of cardiac manifestations to address ongoing challenges this condition.
PMID:40602734 | DOI:10.1016/j.cpcardiol.2025.103125
Int Immunopharmacol. 2025 Jul 1;162:115155. doi: 10.1016/j.intimp.2025.115155. Online ahead of print.
ABSTRACT
BACKGROUND: Immune rejection remains a leading cause of graft loss following organ transplantation, with CD4+ T cells playing a central role in this process. The PI3K/AKT/mTOR signaling pathway is essential for the activation, proliferation, and metabolic reprogramming of CD4+ T cells, making it an attractive therapeutic target. However, the role of Idelalisib (ID), a selective PI3Kδ inhibitor, in transplant immunity remains underexplored.
METHODS: Purified CD4+ T cells from the spleens of C57BL/6 mice were cultured with ID. Activation, proliferation, differentiation and survival were evaluated. A fully mismatched skin and heart transplantation model was used to assess ID's effects on rejection. Histopathology analysis and transcriptomic sequencing were performed.
RESULTS: ID significantly suppressed CD4+ T cell activation, proliferation, and Th1 differentiation, while enhancing cell survival-contrasting with the pro-apoptotic effects observed with the mTOR inhibitor rapamycin (Rapa). In the skin and heart transplantation models, ID reduced acute rejection, extended graft survival, and decreased the proliferation of CD4+ T cells and B cells. Transcriptomic analysis revealed downregulation of genes involved in T cells activation and differentiation (e.g., Zap70, Stat4), as well as markers of glycolysis (e.g., Gapdh, Pfkm). Functional assays confirmed reduced glucose uptake and lactate production in ID-treated cells.
CONCLUSIONS: ID uniquely modulates T cell responses through PI3Kδ inhibition, providing a distinct immunosuppressive mechanism from that of mTOR inhibitors. These findings highlight the therapeutic potential of ID in preventing transplant rejection and reveal a critical link between PI3K signaling and CD4+ T cell metabolism.
PMID:40602262 | DOI:10.1016/j.intimp.2025.115155
Braz J Cardiovasc Surg. 2025 Jul 2;40(5):e20240310. doi: 10.21470/1678-9741-2024-0310.
NO ABSTRACT
PMID:40601830 | DOI:10.21470/1678-9741-2024-0310
Sci Adv. 2025 Jul 4;11(27):eadv4854. doi: 10.1126/sciadv.adv4854. Epub 2025 Jul 2.
ABSTRACT
Cardiovascular diseases are a leading cause of mortality, with limited possibilities for transplantation due to a critical shortage of donor hearts. Replacing the heart with total artificial hearts (TAHs) remains challenging, due to size constraints and energy requirements, among others. To address this, we introduce the LIMO heart, a compact TAH concept based on an efficient soft fluidic transmission system. By reducing actuator volume and enhancing energy transfer, LIMO enables a more compact and efficient design. We developed a soft ventricle prototype using thin-walled pouch actuators that achieve transmission ratios above one via circumferential shrinkage. A fast, cost-effective prototyping method accelerated testing. Experimental results showed high energy transfer efficiency (82 to 91%), and in vitro tests demonstrated promising cardiac outputs of 5.9 liters per minute against aortic pressure and 7.6 liters per minute against pulmonary pressure. These findings represent a step toward a more broadly applicable biventricular soft robotic TAH for treating end-stage heart failure.
PMID:40601721 | DOI:10.1126/sciadv.adv4854
PLoS One. 2025 Jul 2;20(7):e0325668. doi: 10.1371/journal.pone.0325668. eCollection 2025.
ABSTRACT
INTRODUCTION: Heart failure (HF) is among the most prevalent health issues worldwide and is associated with high mortality. Adequate decongestion remain the main clinical challenge in HF management. Sodium glucose cotransporter-2 inhibitors (SGLT-2i) have been recently introduced as a new treatment option in patients with HF irrespective of left ventricular ejection fraction. Although the favorable effects of SGLT-2i are profoundly evident, the underlying mechanisms are not yet well understood. The aim of this study is to provide novel insights into the effects of dapagliflozin, a SGLT-2i with proven cardiovascular benefit, on blood volume profile and vascular function in HF patients who had a recent event of acute decompensated heart failure (ADHF).
METHODS: Eighty adult patients with diagnosis of de novo or chronic HF (NYHA class II-IV), clinically stabilized after an ADHF event and with preserved renal function, who were not on treatment with SGLT-2i, are aimed to be included. The patients are randomized with 1:1 allocation to either dapagliflozin 10 mg p.o. once daily or placebo in addition to guideline-directed medical therapy. The primary outcome is the mean change in plasma volume status (PVS) in the dapagliflozin group compared to placebo. PVS is assessed via optimized carbon monoxide rebreathing technique, a reliable and safe method to measure total hemoglobin mass and to estimate blood volume profile, i.e., blood volume, plasma volume and red blood cell volume. Secondary outcomes include differences between the two study groups regarding blood volume profile, micro- and macro-vascular function assessed by retinal vessel analysis and flow-mediated vasodilation, respectively, changes in body water distribution, quality of life, exercise capacity, echocardiographic and laboratory parameters.
ETHICS AND DISSEMINATION: The study has been approved by the Cantonal Ethics Committee Zurich (BASEC-Nr.:2020-01920, Swissmedic-Nr.:2020DR4175) and has been registered at www.ClinicalTrials.gov (NCT04869124). The results will be published in a peer-reviewed medical journal.
PMID:40601599 | DOI:10.1371/journal.pone.0325668
Eur J Epidemiol. 2025 Jul 2. doi: 10.1007/s10654-025-01258-1. Online ahead of print.
ABSTRACT
The TransplantLines Biobank and Cohort Study (NCT03272841) is an ongoing prospective study conducted at the University Medical Centre Groningen, The Netherlands. TransplantLines aims to identify risk factors and biomarkers associated with health problems following solid organ transplantation and donation. Additionally, the study seeks to develop new interventions to reduce symptom burden and improve long-term outcomes, including health-related quality of life, cardiovascular complications, graft failure, and mortality. It includes recipients of (combined) heart, liver, lung, kidney, pancreas, and small bowel transplants, as well as living liver and kidney donors, and deceased (multi-)organ donors. The biobank contains a wide range of biomaterials including whole blood, serum, EDTA-plasma, buffy coat, 24-h urine samples, faeces, hair, nails, and tissues. Data collection includes physical and cognitive assessments, extensive laboratory analysis, metagenomic sequencing, and questionnaires. TransplantLines, initiated in 2015, consists of 5143 participants as of October 2024, among 2312 (45%) females. The mean age was 50 (± 16) years at transplantation, 55 (± 11) years at living donation and 56 (± 15) years at deceased donation. Both cross-sectional and longitudinal biomaterials and data are included. For recipients, longitudinal biomaterials and data were collected at: pre-transplantation, at transplantation, and at 3, 6, 12, 24, and 60 months post-transplantation. For living donors, data were collected at pre-donation, donation, 3 months post-donation, and/or 5 or 10 years post-donation.
PMID:40601244 | DOI:10.1007/s10654-025-01258-1
Can J Anaesth. 2025 Jul 2. doi: 10.1007/s12630-025-02979-3. Online ahead of print.
ABSTRACT
PURPOSE: Cardiac donation after death determination by circulatory criteria (DCC) can be performed using either 1) direct procurement and perfusion of ex situ organs or 2) normothermic regional perfusion (NRP). Nevertheless, there are concerns regarding the acceptability and ethics of these procedures, particularly NRP in which the blood supply to the brain is surgically interrupted and circulation in the thorax and abdomen is restored prior to heart retrieval. We aimed to understand the perspectives on cardiac donation following DCC of Canadian clinicians who are involved in donation and transplantation.
METHODS: We performed a qualitative descriptive study of 75 clinicians to better understand the perspectives of physicians on cardiac DCC. We purposively sampled clinicians who care for organ donors (N = 51) and those who care for transplant recipients (N = 24) in Canada. We performed thematic analysis to generate themes describing participants' perspectives about cardiac DCC and its implementation in Canada.
RESULTS: We found that the broad support and interest to implement cardiac DCC among the cohort of clinicians interviewed was tempered by their anticipation that other clinicians, donor families, and the public would be less supportive. Donor clinicians were particularly concerned about potential erosion in public trust in the organ donation system as a whole. Participants identified opportunities to address anticipated challenges, including strategies for education and communication around cardiac DCC, staged/gradual introduction of cardiac DCC, and the option for stakeholders (clinicians, donor families, potential transplant recipients) to opt out of participation in cardiac DCC.
CONCLUSIONS: In this qualitative study of clinicians involved in organ donation or transplantation across Canada, we found broad support for cardiac DCC. Nevertheless, we observed several challenges with the implementation of cardiac DCC, particularly concerns of nonsupport by other stakeholders. Participants also identified opportunities to address anticipated barriers.
PMID:40601238 | DOI:10.1007/s12630-025-02979-3
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