Trasplante cardíaco

Circ Heart Fail. 2025 Sep 30:e012787. doi: 10.1161/CIRCHEARTFAILURE.125.012787. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of the current study was to investigate the clinical implications of elevated donor-derived cell-free DNA (dd-cfDNA) levels in heart transplantation recipients without evidence of rejection observed on endomyocardial biopsy.

METHODS: We retrospectively analyzed dd-cfDNA samples from all consecutive heart transplantation recipients between 2019 and 2023, excluding those with multiorgan transplants. Each sample was paired with an endomyocardial biopsy (<30 days). A positive biopsy was defined based on International Society for Heart and Lung Transplantation criteria of ≥1R/1B or pAMR >0. Elevated dd-cfDNA was defined as ≥0.12%, with a subanalysis using a threshold of 0.20%. Graft dysfunction was defined as an ejection fraction<50%. We excluded dd-cfDNA samples with concurrent histologically positive biopsy results, focusing on those with positive dd-cfDNA and negative biopsy findings. A mixed model Cox regression approach was applied to assess for mortality and graft dysfunction.

RESULTS: Of 643 dd-cfDNA samples from 227 patients, 238 samples (37%) from 110 patients showed positive dd-cfDNA results with negative endomyocardial biopsy. The median age was 56 years, with 27% females and 53% White patients. The median time from heart transplantation to sample collection was 5 months (interquartile range, 3-12). Among the positive samples, the median dd-cfDNA level was 0.24% (interquartile range, 0.16%-0.53%) with 63% exceeding 0.20%. A higher prevalence of prior treated antibody-mediated rejection was observed in the dd-cfDNA positive group (15% versus 5%; P=0.002). Patients with elevated dd-cfDNA results ≥ 0.20% demonstrated a near 5-fold increased risk of mortality (hazard ratio, 4.6 [95% CI, 1.6-13.4]; P=0.005) and a 3-fold risk of graft dysfunction (hazard ratio, 3.4 [95% CI, 1.0-11.9]; P=0.054) compared with those with negative dd-cfDNA.

CONCLUSIONS: In our cohort, patients with positive dd-cfDNA levels and negative biopsy results had higher rates of adverse outcomes, including graft dysfunction and mortality.

PMID:41025234 | DOI:10.1161/CIRCHEARTFAILURE.125.012787

World J Gastroenterol. 2025 Oct 7;31(37):110164. doi: 10.3748/wjg.v31.i37.110164.

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a silent epidemic having substantial clinical implications, with liver transplantation being one of the areas most impacted. The increasing prevalence of metabolic fatty liver disease has reduced the quality of available donor organs. While noninvasive methods are increasingly applied to evaluate liver steatosis in deceased donors, liver biopsy remains the gold standard. Many aspects of liver biopsies are not yet fully standardized. Macrovesicular hepatic steatosis is associated with decreased allograft quality and poorer short- and long-term transplant outcomes, especially in moderate and severe steatotic cases. Donation after cardiac arrest further exacerbates these poor outcomes. Matching marginal allografts with suitable recipients based on recipient characteristics is crucial for improving transplant outcomes. Living donor liver transplant is a feasible option for addressing organ shortages. Noninvasive evaluation is preferred for assessing liver health; however, when the results are inconclusive, a liver biopsy is recommended. Lifestyle modifications can improve graft, living donor and recipient outcomes. Analysis of the impact of MASLD on the donor pool and the implementation of new optimization strategies are essential to ensure the sustainability of transplantation as a curative treatment for advanced liver cirrhosis. The aim of this review was to summarize the effect of MASLD on the liver donor population, highlighting how to evaluate steatosis in donors, and to discuss its clinical implications as well as strategies to optimize organ allocation in the MASLD era.

PMID:41025004 | PMC:PMC12476651 | DOI:10.3748/wjg.v31.i37.110164

Respir Res. 2025 Sep 29;26(1):276. doi: 10.1186/s12931-025-03361-z.

ABSTRACT

BACKGROUND: The mechanism of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) remains poorly understood. Fibulin 5, a multifunctional extracellular matrix protein, was reinduced in balloon-injured vessels and may contribute to vascular remodelling. This study aimed to investigate the role and molecular mechanism of action of fibulin 5 in the pathogenesis of CHD-PAH.

METHODS & RESULTS: We found elevated fibulin 5 expression in pulmonary artery smooth muscle cells (PASMCs) from CHD-PAH patients and shunt-induced PAH rats. In vivo, downregulation of fibulin-5 expression by intratracheally delivered adeno-associated viral vectors prevents shunt-associated PAH and associated pulmonary artery remodeling. In vitro, fibulin 5 expression in human PASMCs (hPASMCs) was changed through transduction with lentiviruses. We found fibulin 5 overexpression enhanced TGF-β1-induced proliferation and migration, as assessed by EdU, cell count, and transwell assays. Western blotting showed altered expression of contractile and synthetic phenotype markers. These effects were reversed by the PI3K/AKT inhibitor LY294002, suggesting fibulin 5 acts through the TGF-β1/PI3K/AKT pathway.

CONCLUSIONS: Overall, our data provide new insights into the influence of fibulin 5 on the modification of hPASMC dysfunction and pulmonary artery remodelling in shunt-associated PAH.

PMID:41024156 | PMC:PMC12482218 | DOI:10.1186/s12931-025-03361-z

BMC Infect Dis. 2025 Sep 29;25(1):1205. doi: 10.1186/s12879-025-11648-1.

ABSTRACT

BACKGROUND: Solid organ transplant (SOT) recipients receive immunosuppressive drugs that predispose them to opportunistic infections, including cytomegalovirus (CMV) infection. In these patients, CMV infection can lead to life-threatening consequences, such as transplant rejection. This systematic review and meta-analysis investigated the role of CMV infection in the development of acute rejection in SOT recipients.

METHODS: PubMed, Embase, Scopus, and Web of Science databases were systematically searched for eligible publications until Jan 31, 2025. English-language studies reporting the association between CMV infection and acute rejection in adult SOT recipients were included. Baseline characteristics, transplanted organs, and CMV infection and acute rejection status in SOT recipients were independently extracted by two reviewers. The pooled odds ratio (ORs) with a 95% confidence interval (CI) was calculated using the random effect model.

RESULTS: Overall, 27 studies with 6308 SOT recipients entered the meta-analysis. Acute rejection was significantly higher in SOT recipients with CMV infection than those without CMV infection (OR = 2.02, 95%CI 1.64-2.49, I2 = 40.44%). Acute rejection was significantly higher in recipients of liver (OR = 4.43, 95%CI 2.20-8.92, I2 = 0.00%), kidney (OR = 2.22, 95%CI 1.70-2.89, I2 = 48.72%), and lung (OR = 1.38, 95%CI 1.01-1.90, I2 = 0.00%), if they were infected with CMV. While acute rejection was not significantly associated with CMV infection in heart transplant recipients (OR = 1.49, 95%CI 0.54-4.12, I2 = 18.83%). Furthermore, Egger's test did not indicate any evidence of publication bias (P = 0.7440).

CONCLUSIONS: CMV infection approximately doubles the risk of acute rejection in SOT recipients. This association differs between various organs, with liver transplants indicating the highest risk, followed by kidney and lung transplants.

PMID:41023683 | PMC:PMC12482134 | DOI:10.1186/s12879-025-11648-1

Sci Rep. 2025 Sep 29;15(1):33527. doi: 10.1038/s41598-025-18015-9.

ABSTRACT

Urgent-start peritoneal dialysis (USPD) has been identified as the efficient approach to initiate renal replacement treatment in end-stage renal disease patients. Cardiovascular mortality of urgent dialysis is an important issue. The present work focused on assessing risk factors related to cardiovascular death in USPD patients. We carried out the present multicenter retrospective cohort study in Northeast China, included adults initiating USPD between 2013 and 2019. Follow-up was conducted in every patient till the occurrence events below: technical failure, death, loss-to-follow-up, and renal transplantation. There were altogether 1549 cases enrolled into this work. Among them, 123 encountered cardiovascular death. Upon multivariate regression, predictors of cardiovascular death included advanced age (HR 1.045, 95% CI [1.031, 1.060]; p < 0.001), higher eGFR (HR 1.084, 95% CI [1.052, 1.117]; p = 0.001), combined with DM (HR 1.471, 95% CI [1.026, 2.110]; p = 0.036), and advanced HF stage (class III versus class 0-I, HR 5.262; 95% CI [3.281, 8.437]; p < 0.001; class IV versus class 0-I, HR 6.409; 95% CI [4.145, 9.912]; p < 0.001). In addition, the predictors of cardiovascular death in diabetic USPD patients included advanced age (HR 1.052, 95% CI [1.027, 1.078]; p < 0.001) and advanced HF stages (class III versus class 0-I, HR 7.843; 95% CI [4.249, 14.476]; p < 0.001; class IV versus class 0-I, HR 5.285; 95% CI [2.880, 9.698]; p < 0.001). Moreover, the predictors of cardiovascular death in elderly USPD patients were advanced age (HR 1.045, 95% CI [1.016, 1.075]; p < 0.001) and advanced HF stages (class III versus class 0-I, HR 3.407; 95% CI [1.911, 6.073]; p < 0.001; class IV versus class 0-I, HR 5.039; 95% CI [2.982, 8.516]; p < 0.001). Risk factors related to cardiovascular death included advanced age, higher eGFR, combined with diabetes, and advanced heart failure stages among USPD patients.

PMID:41022908 | PMC:PMC12480178 | DOI:10.1038/s41598-025-18015-9

BMJ Open. 2025 Sep 28;15(9):e104578. doi: 10.1136/bmjopen-2025-104578.

ABSTRACT

INTRODUCTION: Coronary artery bypass grafting (CABG) is a standard treatment for coronary artery disease, particularly in patients with multivessel disease. Connecting the saphenous vein graft (SVG) to the right internal mammary artery (RIMA) instead of the aorta has been proposed as an alternative approach to minimise aortic manipulation and potentially improve graft patency. This study aims to determine whether the RIMA-SVG technique is non-inferior to the conventional Aorta (Ao)-SVG approach in terms of 1-year graft patency, while also comparing perioperative complications and short-term clinical outcomes.

METHODS AND ANALYSIS: This non-inferiority, single-centre, prospective, double-blind, randomised clinical trial will enrol 300 patients undergoing CABG. Participants will be randomised into two surgical groups (RIMA-SVG vs Ao-SVG). The primary outcome is the 1-year SVG patency rate, assessed using coronary CT angiography. Secondary outcomes include perioperative complications, all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE), and surgical site infections occurring during hospitalisation and up to 1 year postoperatively. Randomisation will be computer-generated, and all procedures will be performed by experienced surgeons. Patients will be followed up 12 months post-surgery. Non-inferiority will be established if the upper bound of the one-sided 97.5% CI for the difference in graft occlusion rates is less than the prespecified non-inferiority margin of 10%.

ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Second Hospital of Jilin University (No. 460) and registered at ClinicalTrials.gov (NCT06787651). All participants will provide written informed consent before enrolment. To ensure data integrity and minimise bias, randomisation details will be concealed from researchers until surgery, and data analysts will remain blinded to group assignments. The findings will be disseminated through academic journals and conference presentations to promote knowledge sharing and clinical application in the field of cardiovascular surgery.

TRIAL REGISTRATION NUMBER: NCT06787651.

PMID:41022447 | PMC:PMC12481333 | DOI:10.1136/bmjopen-2025-104578

Transplant Cell Ther. 2025 Sep 27:S2666-6367(25)01475-7. doi: 10.1016/j.jtct.2025.09.042. Online ahead of print.

ABSTRACT

BACKGROUND: Antithymocyte globulin (ATG, Thymoglobulin) infusion may result in infusional side effects (ISEs) resembling cytokine release syndrome.

OBJECTIVE: To determine cytokines associated with ISEs, factors predicting the ISEs, and the impact of ISEs on hematopoietic cell transplant (HCT) outcomes.

STUDY DESIGN AND METHODS: We studied 211 allogeneic HCT recipients who received three infusions of ATG, on day -2, -1 and 0. The focus was on the first infusion. ISE was defined as maximum temperature ≥38°C, maximum heart rate >125/min, minimum systolic blood pressure <90 mmHg, or supplemental oxygen use between the start of the first infusion and the start of the second infusion. In 158 of the 211 patients we determined the post-first infusion serum levels of 34 cytokines using Luminex, and compared the levels in patients with vs without an ISE using signed rank test with Bonferroni correction for multiple comparisons. In all 211 patients we compared those with vs without an ISE in overall survival (OS), relapse-free survival (RFS), and moderate to severe chronic graft-vs-host disease (cGVHD)- and relapse-free survival (cGRFS) using Cox regression, as well as in the incidences of acute GVHD (aGVHD), cGVHD, relapse, and nonrelapse death using Fine-Gray regression.

RESULTS: An ISE occurred in 93 (44%) patients. Levels of the following cytokines were significantly higher in patients with vs without an ISE: interleukin-1 receptor antagonist (IL1-RA) (30166 vs 6394 pg/ml, P<.001), interleukin-6 (IL-6) (188 vs 49 pg/ml, P<.001), and interferon gamma induced protein-10 (IP-10) (106 vs 70 pt/ml, P=.004). Patients with vs without an ISE did not differ in weight, body mass index, day -2 leukocyte, neutrophil, monocyte, or lymphocyte count, post-first infusion ATG level, or ATG area under the time-concentration curve (AUC). Compared to patients without an ISE, patients with an ISE did not have a significantly different OS (hazard ratio (HR)=0.83, P=0.43), RFS (HR=0.85, P=.38), or cGRFS (HR=1.01, P=0.98). There was also no significant difference in the incidence of grade 2-4 aGVHD, grade 3-4 aGVHD, moderate to severe cGVHD, relapse, or nonrelapse death.

CONCLUSION: IL-6, IP-10, and IL1-RA appear to be involved in the pathogenesis of ISEs. ISEs appear to have no significant impact on HCT outcomes.

PMID:41022356 | DOI:10.1016/j.jtct.2025.09.042

J Card Fail. 2025 Sep 27:S1071-9164(25)00381-1. doi: 10.1016/j.cardfail.2025.09.002. Online ahead of print.

ABSTRACT

BACKGROUND: Invasive hemodynamics may facilitate outpatient identification of ambulatory advanced HF. We analyzed cardiac failure risk stratified by four hemodynamic profiles recorded during implantation of the pulmonary artery pressure (PAP) sensor, CardioMEMS™ HF system.

METHODS: This multicenter, retrospective cohort study included HFrEF patients who underwent PAP sensor implantation from 2015 to 2022. Hemodynamic profiles were categorized using the Stevenson HF classification, defining "cold" (impaired systemic perfusion) as cardiac index <2.2L/min/m2; and "wet" (hemodynamic congestion) as pulmonary capillary wedge pressure ≥18mmHg. The primary endpoint was 1-year cardiac failure, including all-cause mortality, inotrope dependence, need for durable VAD or heart transplantation.

RESULTS: Among 512 patients (median age 71 years, 28% female, 77% NYHA class III, median NT-proBNP 2554 pg/mL), the hemodynamic profiles were as follows: 30% Warm-Dry, 22% Warm-Wet, 21% Cold-Dry, and 27% Cold-Wet. Overall, 118 patients (23%) experienced cardiac failure, of which 57 required chronic inotrope, durable VAD implantation, or heart transplantation and 61 died with medical therapy. One-year event-free survival differed across the profiles: Warm-Dry (90%), Warm-Wet (74%), Cold-Dry (80%), and Cold-Wet (61%) (P<0.001). Multivariable analysis (reference: Warm-Dry) showed increased cardiac failure risk in Cold-Wet (adjusted HR [95%CI]: 4.4 [2.4-7.8], P<0.001), Cold-Dry (adjusted HR [95%CI]: 2.2 [1.1-4.2], P=0.019), and Warm-Wet (adjusted HR [95%CI]: 2.8 [1.5-5.4], P=0.001).

CONCLUSION: At time of PAP sensor placement, an abnormal hemodynamic profile - especially Cold-Wet - was associated with increased cardiac failure risk, indicating subgroups who might have already progressed to ambulatory advanced heart failure.

PMID:41022266 | DOI:10.1016/j.cardfail.2025.09.002

Expert Opin Drug Saf. 2025 Sep 30:1-8. doi: 10.1080/14740338.2025.2568242. Online ahead of print.

ABSTRACT

BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, is used for heart failure with reduced ejection fraction. Emerging evidence suggests potential ototoxicity, including hearing loss and vestibular disorders, which remain underreported and poorly characterized.

RESEARCH DESIGN AND METHODS: Our objective was to compare auditory adverse event (AE) reports associated with sacubitril/valsartan versus those associated with lisinopril and losartan. A retrospective active-comparator disproportionality analysis was conducted using individual case safety reports (ICSRs) from the U.S. FDA Adverse Event Reporting System (FAERS) via OpenFDA (2015Q3-2023Q3). The Medical Dictionary for Regulatory Activities (MedDRA) terms identified AEs related to hearing impairment, vestibular disorders, and hypoacusis. Adjusted reporting odds ratios (aRORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age, sex, hypertension, and heart failure. Bayesian methods complemented the analysis.

RESULTS: Among 55,101 ICSRs, 28,091 involved sacubitril/valsartan, with 590 (1.07%) reports of hearing impairment and 4,732 (8.58%) vestibular disorders. Compared to lisinopril, sacubitril/valsartan had higher aRORs for hearing impairment (2.35), vestibular disorders (2.58), and hypoacusis (15.03). Similar elevated risks were found versus losartan. Bayesian analysis confirmed these patterns.

CONCLUSIONS: Sacubitril/valsartan may be associated with a higher risk of auditory AEs than lisinopril and losartan. These findings warrant further confirmation through pharmacoepidemiologic studies.

PMID:41017677 | DOI:10.1080/14740338.2025.2568242

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

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

Heart Lung Circ. 2025 Sep 26:S1443-9506(25)00321-X. doi: 10.1016/j.hlc.2025.04.081. Online ahead of print.

ABSTRACT

BACKGROUND: Orthotopic heart transplantation (OHT) survival rates have improved with advances in immunosuppression over the last 20 years. With these improvements, there has been a greater focus on post-transplant care. Diabetes is common after transplantation and may be pre-existing (type 2 diabetes mellitus [T2DM]) or develop after transplant (post-transplant diabetes mellitus [PTDM]). The aim of this study was to compare the incidence and prevalence of diabetes in OHT recipients in two cohorts separated by 20 years.

METHODS: Retrospective audit comparing the prevalence of T2DM and cumulative 2-year incidence of PTDM in 88 consecutive OHT recipients in 1996-1998 and 141 consecutive OHT recipients in 2015-2018 at the same tertiary referral teaching hospital.

RESULTS: The prevalence of pre-transplant T2DM at the time of OHT increased three-fold between 1998 and 2018, from 6% (n=5) to 18% (n=25) respectively (p=0.009). Similarly, the incidence of PTDM increased from 16% (n=13) in 1998 to 36% (n=42) in 2018 (p=0.001). OHT recipients who developed PTDM were older in 2018 vs 1998 (mean age 52 [±11] vs 44 [±9] years; p=0.03). The mean age was not different between individuals with T2DM between the 1998 and 2018 eras. Body mass index was not different between the 1998 and 2018 eras in any of the diabetes status subgroups.

CONCLUSIONS: The incidence and prevalence of diabetes after OHT at our Australian institution has increased over 20 years. With improved OHT survival and rates of diabetes, endocrinologists should be incorporated into the care teams of heart transplant recipients. Further studies of glucose-lowering therapies in patients with diabetes after transplantation are warranted.

PMID:41015724 | DOI:10.1016/j.hlc.2025.04.081

Eur J Pediatr. 2025 Sep 27;184(10):644. doi: 10.1007/s00431-025-06505-x.

ABSTRACT

PURPOSE: This study aimed to explore the epidemiological features and outcomes of out-of-hospital cardiac arrest (OHCA) among children hospitalized in the pediatric intensive care units (PICUs) after return of spontaneous circulation (ROSC) and to determine the factors associated with the thirty-day survival (TDS) rate.

METHODS: This retrospective cohort study was conducted between January 2016 and December 2022 at two French PICUs and included patients under 18 years old hospitalized with ROSC after OHCA.

RESULTS: During the study period, 53 patients were included, 27 (51%) were males the median age was 4 years old. Drowning (n = 15, 28%) and other causes of respiratory failure (n = 9, 17%) were the most common causes of cardiac arrest. The TDS rate was 38% (n = 20), and 15 patients (75%) of the survivals were considered to have good cognitive function discharged from the PICU. Neurological dysfunction was the most common cause of death including brain death in 19 patients (35%) and withdrawal of life-sustaining therapy due to poor neurological prognosis. Witnessed cardiac arrest and length of low flow < 20 min increased the chances of survival by 4.2-fold and 5.6-fold, respectively. Asystole as the initial rhythm, epinephrine use, severe acidosis, bilateral areflexic mydriasis on admission, liver, and renal failure, and disseminated intravascular coagulation were associated with a lower TDS rate, whereas shockable rhythms were associated with a higher TDS rate.

CONCLUSION: In our study, TDS rate of children hospitalized in the PICU after OHCA with ROSC was 38%. Among most of the survivors the neurological prognosis was good. Further, the data implies that primary prevention and optimal early response remain the key strategies to improve survival after OHCA. In addition, neurological dysfunction was the most common cause of death after ROSC, highlighting the opportunity to increase organ donation for transplantation.

WHAT IS KNOWN: • Out-of-hospital cardiac arrest (OHCA) is a significant cause of morbidity and mortality in children. • Survival rates for pediatric OHCA are low and influenced by age, cause of arrest, bystander CPR, and promptness of advanced life support.

WHAT IS NEW: • Survival after return of spontaneous circulation (ROSC) following OHCA in pediatric patients is being reported for the first time in France. While the survival rate is low, the neurological prognosis of most survivors is good. • Primary prevention and optimal early response are key strategies to improve survival. The high occurrence of brain death among nonsurvivors highlights a potential opportunity for organ donation, which appears to be underutilized.

PMID:41015594 | DOI:10.1007/s00431-025-06505-x

J Heart Lung Transplant. 2025 Sep 25:S1053-2498(25)02281-8. doi: 10.1016/j.healun.2025.09.015. Online ahead of print.

NO ABSTRACT

PMID:41015400 | DOI:10.1016/j.healun.2025.09.015

Lancet. 2025 Sep 24:S0140-6736(25)01635-6. doi: 10.1016/S0140-6736(25)01635-6. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050.

METHODS: Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer.

FINDINGS: In 2023, excluding non-melanoma skin cancers, there were 18·5 million (95% uncertainty interval 16·4 to 20·7) incident cases of cancer and 10·4 million (9·65 to 10·9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57·9% (56·1 to 59·8) of incident cases and 65·8% (64·3 to 67·6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4·33 million (3·85 to 4·78) risk-attributable cancer deaths globally in 2023, comprising 41·7% (37·8 to 45·4) of all cancer deaths. Risk-attributable cancer deaths increased by 72·3% (57·1 to 86·8) from 1990 to 2023, whereas overall global cancer deaths increased by 74·3% (62·2 to 86·2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30·5 million (22·9 to 38·9) cases and 18·6 million (15·6 to 21·5) deaths from cancer globally, 60·7% (41·9 to 80·6) and 74·5% (50·1 to 104·2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90·6% [61·0 to 127·0]) compared with high-income countries (42·8% [28·3 to 58·6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by -5·6% (-12·8 to 4·6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6·5% (3·2 to 10·3).

INTERPRETATION: Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment.

FUNDING: Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation.

PMID:41015051 | DOI:10.1016/S0140-6736(25)01635-6