Circular RNA hsa_circ_0000118 promotes atrial fibrosis by regulating the microRNA‑34a‑5p/Smad4 axis
Mol Med Rep. 2025 Dec;32(6):339. doi: 10.3892/mmr.2025.13704. Epub 2025 Oct 3.
ABSTRACT
The regulatory functions and underlying mechanisms of circular RNAs (circRNAs/circs) in atrial fibrillation (AF) are largely unknown. The present study aimed to assess the prognostic roles and potential biological functions of hsa_circ_0000118 in structural remodeling in AF. Gain‑ and loss‑of‑function cell models were established in mouse cardiac fibroblasts. Cell Counting Kit‑8 and Transwell assays were used to analyze the proliferation and migration of cardiac fibroblasts. To evaluate the underlying mechanisms, RNA immunoprecipitation and luciferase reporter assays were performed. hsa_circ_0000118 was demonstrated to be significantly upregulated in atrial tissues of patients with valvular heart disease with AF compared to those without AF. Elevated plasma levels of hsa_circ_0000118 were independently associated with poor prognosis in patients with AF. In vitro, hsa_circ_0000118 promoted collagen I and collagen III expression, and the migration of cardiac fibroblasts. Functional assays demonstrated that hsa_circ_0000118 acted as a competing endogenous RNA of microRNA (miR)‑34a‑5p to reduce the suppressive effect of miR‑34a‑5p on its target Smad4 in cardiac fibroblasts. In conclusion, hsa_circ_0000118 may serve as a non‑invasive prognostic biomarker for AF. The newly identified roles of hsa_circ_0000118 in AF provide a mechanistic understanding of structural remodeling in AF and pave the way towards novel therapies.
PMID:41041848 | DOI:10.3892/mmr.2025.13704
Predicting Successful Weaning from Veno-Arterial ECMO Using Machine Learning
Stud Health Technol Inform. 2025 Oct 2;332:27-31. doi: 10.3233/SHTI251489.
ABSTRACT
Extracorporeal Membrane Oxygenation (ECMO) is a life-saving cardiopulmonary support for patients with acute heart failure. However, the process of weaning from veno-arterial (V-A) ECMO remains complex and risky. We developed a machine learning-based predictive model to assist clinicians in identifying patients with a high probability of successful weaning. This retrospective monocentric study included 122 patients admitted to Rennes University Hospital between January 2020 and January 2023. Data from the eHOP clinical data warehouse were used to train and evaluate various machine learning algorithms, including Random Forest, XGBoost, KNN, SVM, and regularized logistic regressions. The best-performing models showed an AUC of 0.84-0.86, with XGBoost offering the highest results (0.86 [0.72-0.96]). Key predictors included ECMO flow rate, oxygenation fraction (FmO2), and duration of ECMO. While these results are promising, further validation is required before such tools can be translated into clinical decision-making processes.
PMID:41041740 | DOI:10.3233/SHTI251489
Clinical outcomes of liver transplantation in Caroli syndrome: a retrospective analysis
Orphanet J Rare Dis. 2025 Oct 2;20(1):497. doi: 10.1186/s13023-025-03943-6.
ABSTRACT
OBJECTIVE: To evaluate the clinical outcomes of liver transplantation (LT) in patients with Caroli syndrome.
METHODS: We retrospectively analyzed clinical data from 20 patients diagnosed with Caroli syndrome who underwent LT at Beijing Friendship Hospital, Capital Medical University, between April 2014 and May 2024. Data included baseline characteristics, surgical parameters, complications, and survival. Follow-up concluded in February 2025.
RESULTS: These 20 cases accounted for 1.23% (20/1623) of all LTs during the study period. Thirteen patients received living donor liver transplants (LDLT), and seven received deceased donor liver transplants (DDLT). The cohort included 15 males and 5 females, aged 3–56 years (median 23.3). Common preoperative conditions included cirrhosis (n = 18), portal hypertension (n = 17), polycystic kidney disease (n = 16), and splenomegaly (n = 17). The median APACHE II score was 14; the predicted mortality averaged 26.0%. The median interval from the first major complication (e.g., recurrent cholangitis or decompensation) to LT was 12 months (IQR 4.5–21). No patients underwent cross-match or auxiliary LT; three had concurrent partial splenectomy. Postoperative complications included abdominal hemorrhage (n = 3) and seizures (n = 1). Chronic renal failure occurred in six patients during follow-up, and four experienced acute rejection (three recurrent). Compared with adults, pediatric patients had a higher proportion of females (p = 0.001), while chronic renal failure was more common in adults preoperatively (p = 0.010). Four patients (20%) died: one from heart failure (day 8), one from sudden death (6 months), one from pulmonary infection (1 year), and one from unknown causes (5.2 years). Median follow-up was 74.6 months (range 7-125). One-, three-, and five-year survival rates were 90%, 85%, and 78.5%, respectively.
CONCLUSION: Liver transplantation significantly improves the survival prognosis for patients with Caroli syndrome, but attention to kidney function preservation and individualized immunosuppressive management is critical for optimal outcomes.
PMID:41039418 | PMC:PMC12492817 | DOI:10.1186/s13023-025-03943-6
Bayesian modelling of oxygen saturation (SpO(2)) of cardiac patients using the asymmetric generalized error distribution
BMC Pediatr. 2025 Oct 2;25(1):727. doi: 10.1186/s12887-025-06094-6.
ABSTRACT
BACKGROUND: Oxygen saturation (SpO₂) is a crucial parameter for monitoring the health of cardiac patients. It measures the percentage of hemoglobin in the blood that is saturated with Oxygen. The study aims to analyze longitudinal Oxygen saturation (SpO2) levels and identify its determinants among cardiac patients.
METHODS: Bayesian linear mixed-effects model with the asymmetric generalized error distribution (AGED) was used to analyze the data. The data comprises 323 children diagnosed with cardiac disease. AGED outperforms the others distributions and indicates robust and effective choice to analysis the data.
RESULTS: The estimated shape parameters of AGED are significant [Formula: see text] (95% CI: 2.31, 2.58) which is degree of asymmetry, and [Formula: see text] (95% CI: 3.18, 3.46) is associated with peakedness of the distribution. The finding reveals that corrective surgery, pulmonary hypertension, cardiomyopathy, anemia, nutritional status, and hemoglobin levels are significantly associated with Oxygen saturation (SpO2). Pulmonary hypertension, cardiomyopathy, and under nutrition are found to lower SpO2. In contrast, higher hemoglobin and corrective surgery are significantly associated with higher SpO2. The AGED fitted to the data, and found to be important for analyzing data characterized by asymmetry and excess kurtosis.
PMID:41039283 | PMC:PMC12492735 | DOI:10.1186/s12887-025-06094-6
Left Main Disease: The Last Frontier for Medical Therapy in Stable Coronary Artery Disease?
Eur Cardiol. 2025 Sep 15;20:e24. doi: 10.15420/ecr.2025.28. eCollection 2025.
ABSTRACT
Patients with stable coronary artery disease (CAD) involving ≥50% stenosis in the left main coronary artery almost invariably undergo revascularisation. However, there is lack of evidence from contemporary randomised controlled clinical trials (RCTs) supporting the superiority of this approach versus an initial strategy of intensive, multifaceted optimal medical therapy (OMT) directed at dyslipidaemic, hypertensive, thrombotic, metabolic and ischaemic targets. Current clinical practice guidelines still base their recommendations on small subsets of RCTs conducted in the 1970s and early 1980s. Given the lack of survival benefit among patients with stable, multi-vessel coronary artery disease who do versus those do not undergo routine revascularisation in the era of advanced OMT, the question arises whether the current treatment recommendations for left main disease are valid. This issue is of considerable importance; while significant left main disease is found in only 8-10% of diagnostic invasive angiography cases, it is a disease entity associated with a high risk of adverse clinical events and extensive resource use. This article discusses clinical trials data as well as challenges to address this question in the contemporary era. It highlights the complexities of trial planning and execution as it relates to both feasibility and equipoise, study design, choice of trial endpoints and duration of follow-up. The authors conclude there is a compelling need for an RCT to test the hypothesis that the current practice of routine revascularisation for all patients with LMD is superior to an initial strategy of multifaceted OMT with selective use of revascularisation.
PMID:41036022 | PMC:PMC12481371 | DOI:10.15420/ecr.2025.28
Indobufen alleviates apoptosis by the PI3K/Akt/eNOS pathway in myocardial ischemia-reperfusion (I/R) injury
Sci Rep. 2025 Oct 2;15(1):34400. doi: 10.1038/s41598-025-17345-y.
ABSTRACT
Indobufen is a potential antiplatelet drug; the aim of this study was to investigate the pharmacodynamic effects and potential mechanisms of indobufen in a myocardial ischemia/reperfusion (I/R) injury rat model, providing another effective option for the pharmacological prevention of myocardial infarction. In the in vivo model, rats were orally administered indobufen daily. On the fifth day, after 30 min of occlusion of the left anterior descending coronary artery, the rats were reperfused for 2 h. In the in vitro model, the drug was incubated with H9C2 cells for 24 h before the establishment of an oxygen-glucose deprivation/reperfusion (OGD/R) model. Then, the hearts of the rats were collected for TTC staining and myocardial histopathological examination. Creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels in rat plasma and cell supernatants were detected with the appropriate kits. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and apoptosis-related proteins were used to assess myocardial apoptosis. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of p-Akt/Akt and p-eNOS/eNOS. Our results suggest that indobufen ameliorates I/R injury by reducing infarct size, attenuating oxidative stress injury, and inhibiting cardiomyocyte apoptosis. In addition, indobufen increased the expression of p-Akt and p-eNOS in myocardial tissues and H9C2 cells, and LY294002, a specific inhibitor of the PI3K pathway, reversed these protective effects. In conclusion, indobufen reduced myocardial apoptosis and oxidative stress by the PI3K/Akt/eNOS pathway, thereby attenuating MI/R injury and improving cardiac function.
PMID:41038936 | PMC:PMC12491498 | DOI:10.1038/s41598-025-17345-y
Dietary predictors of heart failure with preserved ejection fraction among middle-aged adults in the CARDIA study
Am Heart J Plus. 2025 Sep 17;59:100619. doi: 10.1016/j.ahjo.2025.100619. eCollection 2025 Nov.
ABSTRACT
Heart failure (HF) is among the leading diagnoses for those admitted to the hospital over 65 years old in high-income countries. While there is strong evidence for the use of pharmacological interventions in the treatment of HF with reduced ejection fraction (HFrEF), there is limited evidence for a similar approach to decreasing morbidity and mortality of HF with preserved ejection fraction (HFpEF). This discrepancy highlights the importance of lifestyle change (i.e. diet) for prevention of HFpEF. Given the paucity of data on dietary predictors of HFpEF and the recent changes in diagnostic criteria, we set out to assess the associations of dietary and demographic predictors with HFpEF in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We found that males in their fifties compared to age-matched females had worse measures of diastolic function (e' lateral: 8.47 ± 2.28 vs. 8.98 ± 2.49, p < .001) and myocardial shortening (i.e. GLS: -15.91 ± 2.73 vs -16.98 ± 3.1, p < .001). Each one point of GLS increase was associated with 12 % increase in risk of HFpEF, while HDL intake was found to be protective against HFpEF. We also found that higher dietary HDL intake when individuals were in their fifties was associated with higher (i.e. better) measures of both e' lateral and e' septal velocities. Our data indicate that GLS appears to be a robust predictor of HFpEF and is influenced by dietary behaviors across the lifespan that affect BMI in males and hypertension in females.
PMID:41035498 | PMC:PMC12483684 | DOI:10.1016/j.ahjo.2025.100619
Testosterone therapy is associated with reduced risk of acute kidney injury, kidney failure with renal replacement therapy, and cardiovascular events in men with diabetes and hypogonadism
Cardiovasc Diabetol. 2025 Oct 1;24(1):378. doi: 10.1186/s12933-025-02930-2.
ABSTRACT
BACKGROUND: Testosterone deficiency is common in men with diabetes. Effects of testosterone therapy on kidney failure and cardiovascular outcomes in diabetic men remain poorly understood. Our aim was to assess whether testosterone therapy is associated with reduced risk of acute kidney injury and kidney failure requiring replacement therapy in men with diabetes and hypogonadism compared to matched untreated men with diabetes.
METHODS: Participants were recruited from the TriNetX Research Collaborative network. We identified 26,027 diabetic men with hypogonadism treated with testosterone and matched them 1:1 using propensity score matching to 26,027 untreated diabetic men with hypogonadism. Primary outcomes were acute kidney injury and kidney failure requiring replacement therapy (dialysis or transplantation). Secondary outcomes included myocardial infarction, ischemic stroke, atrial fibrillation, and all-cause mortality. Cox proportional hazard models were used over a mean follow-up of 3.3 years.
RESULTS: Men had a mean age of 58 years (SD 12), with 71% being non-Hispanic White. Testosterone-treated men had significantly lower risk of acute kidney injury (HR: 0.93 [95% CI 0.87-0.98], p = 0.01) and kidney failure with replacement therapy (HR: 0.81 [95% CI 0.72-0.92], p = 0.001) compared to untreated men. Testosterone therapy was also associated with reduced risk of myocardial infarction (HR: 0.85 [95% CI 0.78-0.93], p < 0.0001), ischemic stroke (HR: 0.88 [95% CI 0.80-0.97], p = 0.01), atrial fibrillation (HR: 0.91 [95% CI 0.85-0.98], p = 0.01), and all-cause mortality (HR: 0.85 [95% CI 0.79-0.91], p < 0.0001).
CONCLUSIONS: In this large real-world cohort study, testosterone therapy in diabetic men with hypogonadism was associated with significant reductions in acute kidney injury, kidney failure requiring replacement therapy, major cardiovascular events, and total mortality. These findings suggest that testosterone therapy could be more readily considered for men with diabetes and hypogonadism as a potential intervention to prevent kidney injury.
PMID:41035033 | PMC:PMC12487499 | DOI:10.1186/s12933-025-02930-2
Genetic modification of the AJCC classification of papillary thyroid cancer: an international, multicentre, retrospective cohort study
Lancet Oncol. 2025 Oct;26(10):1382-1392. doi: 10.1016/S1470-2045(25)00399-7.
ABSTRACT
BACKGROUND: The four-stage American Joint Committee on Cancer (AJCC) staging system has been used for almost 50 years for assessing the risk of multiple cancers; the AJCC classification for papillary thyroid cancer is solely based on clinical parameters, and despite updated editions its accuracy remains suboptimal. We aimed to evaluate whether the performance of the AJCC system could be improved by integrating tumour genetic statuses of BRAF and TERT genes.
METHODS: This retrospective multicentre cohort study used patient medical records from 15 medical centres across ten countries for patients (of all ages) with papillary thyroid cancer who had been surgically treated with total thyroidectomy or hemithyroidectomy with or without neck dissection, followed by postoperative radioiodine ablation and appropriate thyroid-stimulating hormone level targeting. Testing for BRAFV600E and TERT promotor (TERTp) mutations was performed on genomic DNA isolated from surgical or cytological specimens of primary papillary thyroid cancer tumours at each centre. Data from all medical centres were pooled for aggregated analyses of the relationship between the genetic status and papillary thyroid cancer-specific mortality for each of the four classical stages of the 7th and 8th editions of the AJCC system (AJCC7E and AJCC8E). The primary endpoint was papillary thyroid cancer-specific mortality, characterised by mortality rates per 1000 person-years.
FINDINGS: Using patients who were treated for papillary thyroid cancer between January 1979, to July 2023 at the 15 centres, our cohort comprised of 4746 patients (3612 [76·1%] females and 1134 [23·9%] males), with median age of 48 years (IQR 37-59; 89 [1·9%] patients aged ≤18 years). For the 4400 patients with available ethnicity data, the majority were Asian (2140 [48·6%]) and 2096 (47·6%) were White. For AJCC7E, compared with the original stages, the genetic duet of BRAFV600E and TERTp mutations was associated with increased mortality in all stages versus the corresponding original stages, although the HR for stage I did not reach statistical significance. Those with wildtype BRAFV600E and TERTp had flat survival curves for stages I-III with AJCC7E and stages I-II of AJCC8E. Patients with dual mutations had reductions in survival across all stages for the AJCC7E (stage I HR 5·96 [95% CI 0·73-48·66]; p=0·10; stage II 5·94 [95% CI 1·42-24·91]; p=0·015; stage III 4·04 [95% CI 1·87-8·70]; p=0·00037; and stage IV 1·79 [95% CI 1·15-2·76]; p=0·0092). TERTp mutation alone was also significantly associated with a significant increase in mortality for stage IV (3·57 [2·01-6·37]; p<0·0001). For AJCC8E, we observed a similar pattern of increased mortality when both mutations were present compared to mortality in the original staging, with significant differences in HR for stages I and II (stage I adjusted HR 10·30 [95% CI 3·43-30·93], p<0·0001; stage II HR 3·95 [95% CI 1·92-8·15]; p=0·00020). Stage III also showed increased mortality with dual mutations, but the increase was not statistically significant (HR 1·77 [0·95-3·31]; p=0·072). In contrast to AJCC7E, the dual mutations did not increase mortality compared with the original stage IV (HR 0·95 [0·47-1·92], p=0·89), but the TERTp mutation did significantly increase mortality in stage IV papillary thyroid cancer (HR 2·75 [1·36-5·58], p=0·0049).
INTERPRETATION: Integrating the genetic statuses of BRAF and TERTp into the AJCC system changes the original risk stages of the AJCC system and significantly improves the accuracy of its mortality risk classification for papillary thyroid cancer.
FUNDING: National Institute on Aging, the Auburn Community Cancer Endowed Chair in Basic Research, the Heart, Breast, and Brain Health Equity Research program, National Institutes of Health, and the American Association for Cancer Research Fellowship 21-40-69-ESTR (USA); Ministry of Health (Czech Republic); Prémio Francisco Augusto da Fonseca Dias e Maria José Melenas da Fonseca para Jovens Investigadores (Portugal); Italian Ministry of Health-Ricerca Corrente (Italy); JSPS KAKENHI (Japan); MINCIENCIAS, L'OREAL-UNESCO-ICETEX-COLCIENCIAS, Universidad del Tolima (Colombia); STRATEGMED2/267398/4/NCBR/2015, the National Centre for Research and Development (Poland); RISBIN IPTEKDOK 2014, Ministry of Health (Indonesia); and the Information and Communications Technology and Future Planning of the Basic Science Research Program via the National Research Foundation of Korea (NRF) funded by the Ministry of Science (Korea).
PMID:41038186 | DOI:10.1016/S1470-2045(25)00399-7
Optimizing Non-intubated ECMO Bridging in Heart Transplantation: The Role of Early Extubation
Ann Thorac Surg. 2025 Sep 30:S0003-4975(25)00904-X. doi: 10.1016/j.athoracsur.2025.08.058. Online ahead of print.
NO ABSTRACT
PMID:41038360 | DOI:10.1016/j.athoracsur.2025.08.058
Comparing the diagnostic accuracy of pre-operative genetic testing for thyroid cancer on fine needle aspiration cytology specimens: a systematic review and meta-analysis of diagnostic accuracy
Discov Oncol. 2025 Oct 2;16(1):1797. doi: 10.1007/s12672-025-03676-9.
ABSTRACT
BACKGROUND: Molecular genetic tests are increasingly used to determine the need for surgery in thyroid nodules with indeterminate fine-needle aspiration (FNA) cytopathology. However, the accuracy of these tests remains uncertain. This systematic review and meta-analysis analyze the diagnostic performance of molecular testing in pre-operative FNA biopsies from indeterminate thyroid nodules (ITN).
METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The preoperative FNA cytopathology from patients over 14 years old, and the postoperative histopathology results were extracted. It was also essential to include true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) counts, along with genetic testing results. Sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) were calculated for each molecular panel using a random-effects bivariate model.
RESULTS: Overall, 68 studies (2018–2024) were eligible discussing 7 different panels, from 16 countries. Multigene Point-of-care Test (MPTX v1) demonstrated the strongest ability to rule out malignancies (NLR 0.12; n = 4) and exhibited the highest diagnostic value (DOR 18; n = 4). ThyroSeq v2 Next-Generation Sequencing Test for Thyroid Cancer (ThyroSeq v2) followed with a DOR of 10 (n = 9). The PCR groups(n = 20) could not be merged due to significant methodological heterogeneity.
CONCLUSION: This meta-analysis highlights the role of molecular testing in improving the diagnostic accuracy of indeterminate thyroid nodules, potentially reducing unnecessary surgeries. However, further standardization and validation are needed due to study heterogeneity.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-03676-9.
PMID:41037201 | PMC:PMC12491129 | DOI:10.1007/s12672-025-03676-9
Risk of Severe Primary Graft Failure Rates After DCD Heart Transplantation by Procurement Strategy: Representative and Actionable?
JACC Heart Fail. 2025 Sep 29:102683. doi: 10.1016/j.jchf.2025.102683. Online ahead of print.
NO ABSTRACT
PMID:41037042 | DOI:10.1016/j.jchf.2025.102683
Characterizing the Immune Response in Pig-to-human Heart Xenografts Using a Multimodal Diagnostic System
Circulation. 2025 Oct 2. doi: 10.1161/CIRCULATIONAHA.125.074971. Online ahead of print.
ABSTRACT
BACKGROUND: Porcine genome editing has revolutionized xenotransplantation, recently enabling the first pig-to-human heart xenotransplants. However, the xeno-immune response in heart xenografts remains largely unexplored. This study aimed to precisely characterize the xeno-immune response and injury in two heart xenografts, transplanted from 10-gene-edited pigs into brain-dead human recipients.
METHODS: We analyzed xenograft biopsies at 66-hour post-reperfusion using a multimodal phenotyping approach combining: morphological evaluation, immunophenotyping, ultrastructural assessment, automated quantification of multiplex immunofluorescence staining and gene expression profiling. Xenografts before implantation and wild-type pig hearts with and without ischemia reperfusion injury and brain death were used as controls.
RESULTS: Both xenografts showed evidence of endothelial activation and mild microvascular inflammation without capillary C4d deposition. Immune infiltrates were mainly composed of CD15+ and CD68+ innate immune cells. Ultrastructural assessment showed endothelial swelling with occasional intravascular leucocytes. Deep-learning based automated multiplex immunofluorescence analysis confirmed that microvascular inflammation was primarily associated with CD15+ and CD68+ innate immune cells. Both xenografts showed increased expression of genes and pathways associated with monocyte/macrophage activation, neutrophil activation, interferon-gamma response, natural killer cell burden, endothelial activation, apoptosis and injury repair. This phenotype was absent in all control pig hearts, independently from ischemia reperfusion injury and brain death.
CONCLUSIONS: Multimodal phenotyping of pig-to-human heart xenografts revealed early signs of xeno-immune response, characterized by mild innate microvascular inflammation, endothelial activation, and molecular signature characteristic of antibody-mediated rejection. Developing such precision diagnostic system could improve graft monitoring in future clinical settings.
PMID:41036838 | DOI:10.1161/CIRCULATIONAHA.125.074971
Pulmonary Rhizopus arrhizus infection treated with high-dose liposomal amphotericin B in a heart transplant recipient under ECMO: a case report
Front Med (Lausanne). 2025 Sep 16;12:1631873. doi: 10.3389/fmed.2025.1631873. eCollection 2025.
ABSTRACT
Pulmonary mucormycosis caused by Rhizopus arrhizus is an emergent, fulminant threat in immunocompromised hosts, yet therapeutic success remains elusive when extracorporeal membrane oxygenation (ECMO) is required. While liposomal amphotericin B (L-AMB) is endorsed as first-line therapy, its pharmacokinetics are profoundly altered by ECMO-dilution, circuit sequestration, and impaired lung penetration all conspire to sub-therapeutic exposure. We report the first documented case in which these challenges were systematically overcome. A 52-year-old cardiac-transplant recipient, supported on veno-venous ECMO for refractory hypoxaemia, developed rapidly progressive pneumonia. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid returned a definitive Rhizopus arrhizus signature within 24 h, prompting immediate escalation to high-dose L-AMB (10 mg/kg/day). Therapeutic drug monitoring confirmed sustained trough levels above 7 μg/mL despite a 3.5-fold increase in volume of distribution. Serial mNGS quantification demonstrated a logarithmic decline in fungal reads to undetectable levels by day 10, accompanied by radiological resolution and preserved renal function. After 28 days of intravenous therapy, the patient was discharged on oral isavuconazole with no relapse at 6 months. This case establishes that early pathogen identification by mNGS, coupled with aggressive L-AMB dose optimisation under rigorous pharmacokinetic guidance, can achieve cure of pulmonary mucormycosis even in the most pharmacologically hostile environment of ECMO support.
PMID:41035876 | PMC:PMC12479246 | DOI:10.3389/fmed.2025.1631873
Human iPSC-derived cardiac-specific extracellular matrix scaffolds for cardiomyocyte maturation and post-myocardial infarction repair
Bioact Mater. 2025 Sep 17;55:114-130. doi: 10.1016/j.bioactmat.2025.06.044. eCollection 2026 Jan.
ABSTRACT
Myocardial infarction (MI) remains a leading cause of heart failure due to the limited regenerative capacity of the adult myocardium. The therapeutic efficacy of current engineered cardiac patches is hindered by their simplistic scaffold composition and lack of structural organization. This study presents a bioactive, anisotropic extracellular matrix (ECM) scaffold derived from human induced pluripotent stem cell-differentiated cardiac fibroblasts (hiPSC-CF-ECM) that combines cardiac-specific proteins and growth factors with complex structural composition. Compared to primary cardiac fibroblast ECM (pri-CF-ECM) and human dermal fibroblast ECM (hDF-ECM), hiPSC-derived cardiomyocytes (hiPSC-CMs) cultured on the cardiac-specific ECM scaffold exhibited enhanced maturation, as confirmed by bulk RNA sequencing, electrophysiological mapping, and optical-based strain analysis. In an immune-competent rat MI model, the hiPSC-CF-ECM transplantation preserved cardiac function, increased ejection fraction, and reduced maladaptive remodeling. These findings highlight hiPSC-CF-ECM as a promising biomimetic scaffold for cardiac tissue engineering and MI treatment.
PMID:41035426 | PMC:PMC12481509 | DOI:10.1016/j.bioactmat.2025.06.044
Effects of immediate extubation in patients after liver transplantation
Anesth Pain Med (Seoul). 2025 Oct 2. doi: 10.17085/apm.25278. Online ahead of print.
NO ABSTRACT
PMID:41035294 | DOI:10.17085/apm.25278
Outcomes of transcatheter patent ductus arteriosus closure in infants weighing 2 to 6 kg
Rev Esp Cardiol (Engl Ed). 2025 Sep 30:S1885-5857(25)00271-3. doi: 10.1016/j.rec.2025.09.011. Online ahead of print.
ABSTRACT
INTRODUCTION AND OBJECTIVES: Transcatheter patent ductus arteriosus (PDA) closure is safe in < 2-kg infants and in ≥ 6-kg patients, but major safety concerns remain when applied to the intermediate weight range. We aimed to assess outcomes of transcatheter PDA closure in 2- to 6-kg infants.
METHODS: An international, multicenter, retrospective cohort study was conducted in 31 tertiary hospitals in 17 countries between 2000 and 2023, investigating all infants who underwent attempted transcatheter PDA closure with a procedural weight of 2-to-6 kg.
RESULTS: Attempted transcatheter PDA closure was performed in 1231 infants (median [Q1-Q3] weight, 4747 [ 3700-5300] g; median age, 132 [ 83-194] days; ex-preterm, n = 581 [56.8%]) with a 95.0% success rate. A composite outcome of procedural failure or major adverse events was observed in 173 (14%) patients, including device embolization in 64 (3.7%), device-induced left pulmonary artery stenosis in 47 (2.7%), and procedural death in 2 (0.2%). Logistic regression model analysis identified a 2- to 3.9-kg procedural weight, increased pulmonary artery pressure, and window-type or tubular ductal morphologies as independent predictors of the composite outcome. Based on propensity score matching analysis, 2- to 3.9-kg infants had a risk ratio of 2.19 (95%CI, 1.25-3.83) for experiencing the composite outcome, compared with 4- to 5.9-kg infants.
CONCLUSIONS: Transcatheter PDA closure in 2- to 6-kg infants was feasible in most patients. Procedural failure or major adverse events occurred in 14% and several independent risk factors were identified, including the 2- to 3.9-kg weight range identified as a higher-risk subgroup. These findings may improve risk stratification and the decision-making process.
PMID:41038445 | DOI:10.1016/j.rec.2025.09.011
Direct percutaneous access of the thoracic duct in a neonate as curative treatment of a high-output life-threatening chylothorax due to thrombotic occlusion of the thoracic duct-venous junction
Pediatr Radiol. 2025 Oct 2. doi: 10.1007/s00247-025-06412-1. Online ahead of print.
ABSTRACT
A life-threatening chylothorax developed in a female neonate after corrective surgery of d-transposition of the great arteries complicated by extensive postoperative thrombosis of the superior vena cava distribution, including at the thoracic duct-venous junction. Emergent percutaneous catheter intervention for thrombus aspiration and transluminal angioplasty was required. Despite therapeutic heparinization, thrombosis persisted. Curative image-guided treatment was twofold: first, the occluded thoracic duct was punctured under ultrasound guidance; then, the thrombus at the thoracic duct-venous junction was mobilized using the Seldinger-technique. Additionally, a venous catheter was placed with the tip at the thoracic duct-venous junction, and local low-dose thrombolysis was administered. This case shows that it is possible to percutaneously access the thoracic duct by direct puncture in a neonate with ultrasound guidance.
PMID:41037148 | DOI:10.1007/s00247-025-06412-1
Thrombus formation in neonates and early infants undergoing congenital heart surgery
Int J Cardiol Congenit Heart Dis. 2025 Aug 27;22:100617. doi: 10.1016/j.ijcchd.2025.100617. eCollection 2025 Dec.
ABSTRACT
OBJECTIVE: This study evaluated thrombus formation and its impact on outcomes in neonates and early infants undergoing congenital heart surgery.
METHODS: Neonates and early infants (≤90 days) undergoing congenital heart surgery with cardiopulmonary bypass from 2001 to 2024 were analyzed. Thrombi were detected by transthoracic echocardiography and cardiac catheterization.
RESULTS: Among 2331 patients, 170 (7.3 %) developed thrombi during hospitalization. Median age at surgery and time to thrombus detection in affected patients were 12 (interquartile range: 7-34) and 7 (interquartile range: 3-15) days, respectively. Among surgical procedures performed in at least 10 patients, thrombi were most frequently observed following tricuspid valve repair (28.6 %), followed by arterial switch operation, ventricular septal defect closure, and aortic arch repair (15.8 %). The most common thrombus location was the superior vena cava in 61 patients, followed by the inferior vena cava in 33, the aorta in 31, and the right atrium in 21 patients. Additional surgical interventions were required in 28 patients. The length of hospital stay was significantly longer in patients with thrombi (27 vs. 15 days, p < 0.001). Independent risk factors for thrombus formation included preoperative cardiopulmonary resuscitation (odds ratio: 2.037, p = 0.001), tricuspid valve repair (odds ratio: 6.206, p < 0.001), and Norwood procedure (odds ratio: 1.558, p = 0.027).
CONCLUSIONS: The incidence of thrombus formation was 7.3 % in neonates and early infants undergoing congenital heart surgery. Thrombus was most frequently observed in the superior vena cava and resulted in prolonged hospitalization. Preoperative cardiopulmonary resuscitation, tricuspid valve repair, and Norwood procedures carried the highest thrombotic risk.
PMID:41035781 | PMC:PMC12483653 | DOI:10.1016/j.ijcchd.2025.100617
Ultrasound-detected postoperative diaphragmatic dysfunction and its association with pulmonary complications. A systematic review and meta-analysis
J Clin Anesth. 2025 Oct 1;107:112027. doi: 10.1016/j.jclinane.2025.112027. Online ahead of print.
ABSTRACT
INTRODUCTION: Postoperative diaphragmatic dysfunction (PDD) is a common complication following major surgeries, contributing to adverse clinical outcomes. Ultrasound-based assessment has emerged as the preferred method for evaluating PDD. We aimed to assess the association between PDD and postoperative pulmonary complications (PPCs) and their relationship with pneumonia.
METHODS: We systematically searched PubMed, Scopus, and Embase for clinical studies assessing PDD via ultrasound. The inclusion period ranged from January 10th, 2025, to March 20th, 2025. Two authors independently selected the investigations according to the following criteria: [1] observational study or randomized clinical trials enrolling adult patients undergoing cardiac, thoracic, or abdominal surgery [2] evaluation of PDD using diaphragmatic excursion (DE) or diaphragmatic thickening fraction (DTF) after surgery, and [3] report an association between PDD and PPCs or pneumonia as clinical outcomes. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. Two authors independently performed data extraction. The Methodological Index for Nonrandomized Studies (MINORS) assessed study quality. The primary outcome was the association between PDD and PPCs. The secondary outcomes evaluated prevalence of PDD and pneumonia as an individual component of PPCs when it was reported separately, and its association with PDD.
RESULTS: The systematic review included 19 studies, and six studies met the criteria for meta-analysis. PDD was significantly associated with higher odds of PPCs (OR 2.99, 95 % CI: 2.01-4.45) and pneumonia (OR 5.41, 95 % CI: 2.36-12.42). No significant publication bias was detected. Heterogeneity was low for both outcomes.
CONCLUSION: Ultrasound-assessed postoperative diaphragmatic dysfunction is significantly associated with higher odds of postoperative pulmonary complications, including pneumonia, highlighting its clinical relevance at the bedside. PDD, assessed via ultrasound, is strongly associated with an increased risk of PPCs and pneumonia in postoperative patients. These findings underscore the importance of routine postoperative diaphragmatic assessment and the potential for targeted interventions to mitigate PDD-related complications. However, the current evidence is constrained by methodological variability and the absence of standardized diagnostic criteria. Future studies should focus on establishing consensus definitions for PDD and ensuring consistent assessment of key clinical outcomes.
PMID:41037871 | DOI:10.1016/j.jclinane.2025.112027