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Cardiovasc Revasc Med. 2025 May 30:S1553-8389(25)00284-2. doi: 10.1016/j.carrev.2025.05.031. Online ahead of print.

ABSTRACT

BACKGROUND: High-risk percutaneous coronary intervention (HRPCI) procedures supported by percutaneous left ventricular assist devices (pLVAD) are increasingly common, but existing PCI risk scores were developed in patients across the risk spectrum, including few pLVAD-assisted patients.

OBJECTIVES: Assess the performance of existing PCI risk scores in patients receiving pLVAD-assisted HRPCI and create a novel risk score specific to this group.

METHODS: Patients in the PROTECT III multicenter, observational (46 US centers) study undergoing pLVAD-assisted HRPCI were assessed. The National Cardiovascular Data Registry (NCDR) bedside risk score and the Complex High-Risk Indicated PCI (CHIP-PCI) risk score were calculated for each patient, and their accuracy in predicting in-hospital events was assessed. A novel risk score for in-hospital mortality was created using pre-procedural variables which were significant in univariable and multivariable regressions.

RESULTS: Among 1237 patients, the NCDR bedside risk score showed modest discrimination (C-index 0.71) but poor goodness of fit (R2 = 0.30). The CHIP-PCI score had poor discrimination (C-index 0.61) and reasonable goodness of fit (R2 = 0.62). Five independent predictors of in-hospital mortality were identified: age >80 years, eGFR <30, left main disease, acute myocardial infarction, and left ventricular ejection fraction <30 %. These formed the "HRPCI" risk score (C-index 0.75), which correlated with 30-day mortality (5.4 % vs. 17.0 %, p<0.0001).

CONCLUSIONS: Existing PCI risk scores perform poorly in patients undergoing pLVAD-assisted HRPCI. A novel easily, calculable HRPCI risk score can assist in clinical decision making once validated.

CLINICAL TRIAL INFORMATION: Trial Name: The Global cVAD Study (cVAD). URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2 ClinicalTrial.gov Identifier: NCT04136392.

PMID:40541479 | DOI:10.1016/j.carrev.2025.05.031

FASEB J. 2025 Jun 30;39(12):e70734. doi: 10.1096/fj.202402897RR.

ABSTRACT

ELABELA (ELA) has been identified as a potential cardiovascular protective factor. However, the source of endogenous ELA and its molecular mechanism in myocardial fibrosis inhibition remain incompletely understood. Herein, we found that aerobic exercise significantly improved renal apoptosis caused by MI, inhibited inflammation, attenuated structural damage, enhanced renal function, and increased expression and secretion levels of renal ELA. Aerobic exercise stimulated the circulation of renal-derived ELA to reach the MI heart and played a protective role. Under aerobic exercise intervention, renal-specific Elabela overexpression improved myocardial pathological remodeling, decreased cardiomyocyte apoptosis, and enhanced cardiac function. Renal-specific Elabela knockdown significantly increased cardiac apoptosis, inflammation, and fibrosis levels in MI mice, leading to severe impairment of cardiac function. Following AMPK agonist intervention, ELA expression in HKC cells and culture medium increased in a concentration-dependent manner. ELA-14 significantly activated the APJ-AMPK-Sirt1 signaling pathway and inhibited Tgf-β1 transcription by regulating Sirt1 translocation, and AMPK inhibitor weakened ELA-14 function. In cultured cardiac fibroblasts (CFs), the intervention of ELA-14 significantly inhibited the activity of the TGFβ1-Smad2/3 signaling pathway, downregulated the expression of fibrosis-related proteins, increased apoptosis, and lowered the cell migration rate. After TGFβR1 inhibitor intervention, ELA-14 showed a loss of regulation of CFs. Aerobic exercise stimulates the expression of renal-derived ELA, which reaches the MI heart through blood circulation. Renal-derived ELA partly exerts its antifibrotic effects by activating the APJ-AMPK-Sirt1 pathway and inhibiting the TGFβ1-Smad2/3 signaling pathway, contributing to its cardiac protective effects.

PMID:40540261 | DOI:10.1096/fj.202402897RR

Cardiol Rev. 2025 Jun 20. doi: 10.1097/CRD.0000000000000971. Online ahead of print.

ABSTRACT

Dual antiplatelet therapy is a standard treatment after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS), but the optimal monotherapy agent post-dual antiplatelet therapy remains unclear. Clopidogrel and aspirin are widely used, yet their comparative effectiveness and safety in this patient population have not been fully established. This systematic review and meta-analysis compared the efficacy and safety of clopidogrel and aspirin monotherapy following PCI in patients with ACS. A comprehensive search of PubMed, Embase, and Web of Science was conducted from inception to March 31, 2025. Randomized controlled trials (RCTs) comparing clopidogrel and aspirin monotherapy in adult ACS patients post-PCI were included. Primary outcomes were all-cause death, myocardial infarction (MI), and ischemic stroke. Secondary outcomes included target-vessel and target-lesion revascularization, cardiovascular and noncardiovascular death, and stent thrombosis. The risk of bias was assessed using the Cochrane RoB 2 tool, and the GRADE methodology was applied to evaluate the certainty of evidence. Three RCTs involving 16,056 patients (clopidogrel: 8103; aspirin: 7953) were included. Clopidogrel significantly reduced MI (risk ratio = 0.71; 95% confidence interval: 0.55-0.92; P = 0.01) and target-vessel revascularization (risk ratio = 0.77; 95% confidence interval: 0.60-0.97; P = 0.03). No significant differences were found in all-cause death, ischemic stroke, or other secondary outcomes. Sensitivity analysis suggested a potential reduction in noncardiovascular death favoring clopidogrel. Clopidogrel monotherapy after PCI may offer superior protection against MI and target-vessel revascularization compared with aspirin, with no increased risk of death or stroke.

PMID:40539811 | DOI:10.1097/CRD.0000000000000971

Cytojournal. 2025 May 6;22:49. doi: 10.25259/Cytojournal_12_2025. eCollection 2025.

ABSTRACT

OBJECTIVE: Ischemia-reperfusion (I-R) injury in the myocardium is a considerable challenge in cardiovascular medicine, posing a severe threat to life. Given that galectin-3 possibly regulates myocardial I-R damage, this study aims to investigate the detailed mechanisms underlying galectin-3's effects on myocardial I-R injury.

MATERIAL AND METHODS: The expression levels of galectin-3 in vivo and in vitro myocardial I-R models were determined by Western blot and quantitative real-time polymerase chain reaction. The effects of galectin-3 on inflammatory factors and oxidative stress factors in myocardial I-R were measured with an enzyme-linked immunosorbent assay, and the extent of myocardial tissue damage was assessed using hematoxylin-eosin staining. The influence of galectin-3 on peroxisome proliferator-activated receptor g (PPARg) signaling pathway-related proteins in myocardial I-R was determined by Western blot.

RESULTS: Myocardial I-R damage was associated with increased galectin-3 expression, and the blood levels of creatine kinase-myocardial band and creatine kinase were favorably correlated with the messenger RNA levels of galectin-3 in mice with cardiac I-R damage. The inhibition of galectin-3 alleviated oxidative stress and inflammatory response, and galectin-3 promoted reactive oxygen species production in myocardial I-R cells. Furthermore, the cardiac I-R damage mouse model exhibited decreased expression of proteins linked to the PPARg signaling pathway, but galectin-3 inhibition enhanced the expression of these proteins.

CONCLUSION: Galectin-3 plays a crucial role in exacerbating myocardial I-R injury, and its up-regulation is associated with increased oxidative stress, inflammatory responses, and inhibition of the protective PPARg signaling pathway. The alleviation of these harmful effects by galectin-3 inhibition suggests that targeting galectin-3 is a potential therapeutic method for reducing myocardial I-R injury.

PMID:40539121 | PMC:PMC12178088 | DOI:10.25259/Cytojournal_12_2025

Front Pharmacol. 2025 Jun 5;16:1516836. doi: 10.3389/fphar.2025.1516836. eCollection 2025.

ABSTRACT

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and disability globally. Several studies have shown that 5-lipoxygenase (5-LOX) inhibition reduces leukotriene (LT) release and the inflammatory response, attenuating the development of respiratory diseases, myocardial infarction, and ischemic cerebral injury. However, its role in the pathophysiology of TBI remains unclear.

METHODS: Controlled cortical impact injury was induced to construct a mouse model of TBI. Pericontusional brain tissue samples from sham and TBI mice at 7 days after injury were used for RNA-seq analysis. Altered gene enrichment following TBI, based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, was quantified through real-time polymerase chain reaction (RT-PCR). Immunocytochemistry, Western blotting, and single-cell sequencing experiments were also performed to analyze 5-Lox protein expression. Arachidonic acid (AA) was detected through liquid chromatography mass spectrometry/mass spectrometry. Enzyme-linked immunosorbent assay was used to detect LTB4 release after TBI with or without zileuton treatment. Brain damage, blood-brain barrier disruption, and neuronal apoptosis were detected through histological examination. Neurological outcomes were determined through rotarod and fear conditioning tests.

RESULTS: TBI induced significant upregulation of genes related to the AA metabolic pathway, particularly the AA/5-LOX/LT axis, as verified by RT-PCR. AA and LTB4 production increased significantly after TBI. The expression levels of Pla2g4a, which hydrolyses phospholipids to release AA, and 5-Lox, which in turn act downstream to convert AA to LT, were dramatically upregulated up to 7 days after TBI. 5-LOX accumulated in the cytoplasm of activated ameboid microglial cells. In vivo, 5-LOX inhibition with zileuton blocked LT release and reduced microglial activation and the production of inflammatory cytokines, including Il-1β, Ccl7, Spp1, Ccr1, Ccl2, and Il-10. Zileuton also reduced TBI-induced lipid ROS and neuronal cell apoptosis, ameliorating brain damage compared to the vehicle group and improving neurological outcomes after TBI. Mechanically, TBI-induced LT upregulation may stimulate BV2 microglial activation through the ERK, NF-κB, and Akt pathways.

CONCLUSION: Our findings demonstrated the role of 5-LOX in TBI and its potential as a therapeutic target in TBI treatment.

PMID:40538546 | PMC:PMC12176805 | DOI:10.3389/fphar.2025.1516836

Acta Pharmacol Sin. 2025 Jun 20. doi: 10.1038/s41401-025-01597-5. Online ahead of print.

ABSTRACT

Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac hypertrophy. SMURF2 (SMAD-specific E3 ubiquitin ligase 2) is an important member of NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) family of HECT E3 ubiquitin ligases. In this study we investigated the regulatory role of SMURF2 in cardiac hypertrophy. Experiment models were established in mice by transverse aortic constriction (TAC) in vivo, as well as in neonatal rat cardiomyocytes (NRCMs) by treatment with angiotensin II (Ang II, 1 μM) in vitro. We showed that the expression levels of SMURF2 were significantly elevated in cardiac tissues from patients with cardiac hypertrophy and the two experiment models. In NRCMs, SMURF2 knockdown or treatment with a specific SMURF2 inhibitor heclin (8 μM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, evidenced by reduced mRNA levels of Anp, Bnp and β-Mhc as well as cell surface. Prophylactic or therapeutic administration of heclin (10 mg·kg-1·d-1, i.p., for 5 or 4 weeks) effectively suppressed TAC-induced cardiac hypertrophy, and rescued heart function. We demonstrated that SMURF2 interacted with AXIN1 and increased ubiquitination degradation of AXIN1 in myocardial tissues, activating the Wnt/β-catenin signaling pathway. Heclin inhibited the ubiquitination degradation of AXIN1 by SMURF2 to alleviate cardiac hypertrophy. In conclusion, upregulated SMURF2 leads to AXIN1 ubiquitination and degradation, thereby facilitating the progression of cardiac hypertrophy. SMURF2 inhibitor heclin may serve as a therapeutic strategy for the treatment of cardiac hypertrophy.

PMID:40542282 | DOI:10.1038/s41401-025-01597-5

Aging Clin Exp Res. 2025 Jun 21;37(1):190. doi: 10.1007/s40520-025-03085-6.

NO ABSTRACT

PMID:40542187 | PMC:PMC12181121 | DOI:10.1007/s40520-025-03085-6

Transplant Cell Ther. 2025 Jun 18:S2666-6367(25)01262-X. doi: 10.1016/j.jtct.2025.06.021. Online ahead of print.

ABSTRACT

BACKGROUND: Impaired sexual health is a common long-term issue for female allogeneic hematopoietic stem cell transplant survivors.

OBJECTIVE(S): To compare sexual function among clinically stable female transplant survivors to age-matched healthy female volunteers and to explore the contribution of key post-transplant factors over time on sexual function.

STUDY DESIGN: Secondary analysis of sexual function of female transplant survivors and healthy female volunteers aged 18 to 50 years enrolled in a year-long prospective clinical trial of HPV vaccination. Clinically stable transplant survivors were at least 90 days post-transplant. The general assessment of post-transplant health included assessment for genital and systemic chronic GvHD. Gynecologists assessed for and treated genital chronic GvHD including topical, targeted therapies, assessed ovarian function, performed cervical cancer screening, provided recommendations about contraception and ovarian hormone treatments, and discussed sexual function. Participants completed the Sexual Functioning Questionnaire (SFQ) at enrollment, 7 and 12 months. Genital and systemic chronic graft-versus-host-disease (GvHD), sexual activity, ovarian hormonal status, systemic immunosuppression use, and antidepressant use were prospectively evaluated over time post-transplant and compared to sexual function and health characteristics of healthy females. Comparisons between groups were made using independent t-tests. Transplant complications of systemic or genital chronic graft-versus-host-disease (GvHD), sexual activity, ovarian hormonal status, immunosuppression, and antidepressant use were evaluated over time using linear mixed models for their association with SFQ scores.

RESULTS: Sixty-four females included 20 healthy volunteers and 44 transplant survivors, of whom 23 (52%) were receiving systemic immunosuppressive therapy. At baseline, whether participants were not currently sexually active, had low sexual function or had high sexual function significantly differed between transplant survivors (45% versus 30% versus 20% of 44 women, respectively) and volunteers (20% versus 15% versus 65% of 20 women, respectively, p=0.003). SFQ overall and subscale scores were lower in transplant survivors compared to healthy females at baseline and the difference persisted over time (all p<0.05). Baseline SFQ overall scores were similar between transplant survivors on and off immunosuppression (p=0.09). At one year, survivors had significantly higher SFQ overall and health impact scores (p=0.05 and p<0.001, respectively) and a lower problems score (p=0.04) compared to baseline, but the other subscale scores did not change. At each timepoint, females with genital chronic GvHD had lower SFQ overall scores compared to those without (p=0.04).

CONCLUSION(S): Female transplant survivors participating in an HPV vaccine trial were more likely to have sexual dysfunction at all time points compared to healthy controls and genital chronic GVHD was the most influential driver. Sexual function improved over time in transplant survivors in the context of a whole-person approach to gynecologic post-transplant care.

PMID:40541681 | DOI:10.1016/j.jtct.2025.06.021

Transplant Proc. 2025 Jun 19:S0041-1345(25)00277-5. doi: 10.1016/j.transproceed.2025.05.010. Online ahead of print.

ABSTRACT

The use of marginal kidney donors with congenital morphological anomalies, such as the "horseshoe" kidney, presents itself as a solution to expand the donor pool. The vascular and urinary anatomy of the horseshoe kidney is complex. These patients are more frequently affected by hydronephrosis, vesicoureteral reflux, urinary tract infections, and urolithiasis. The horseshoe kidney can be transplanted "en bloc" or as a single kidney after "splitting." A 54-year-old patient with end-stage renal failure, on hemodialysis for 4 years, was transplanted with a "horseshoe" graft from a deceased cardiac death (DCD) III Maastricht-type donor. The "preoperative" computed tomography (CT) documented the presence of a "horseshoe" kidney, non-divisible due to the presence of a shared lower polar renal artery between both kidneys. There were no anomalies in the collecting systems except for a slight dilation of the right renal pelvis. The distal side of the inferior vena cava was anastomosed end-to-side with the external iliac vein. The left common iliac artery of the donor was sutured end-to-side with the external iliac artery. The ureters were implanted separately after the placement of the Double J (DJ) stents. There were no perioperative complications. Immunosuppressive therapy was induced with ATG and subsequently tacrolimus and mycophenolate mofetil were introduced. In 4 months of follow-up, the patient developed a lymphocele that was drained percutaneously. The DJ stents were removed after 3 months. The donor with a horseshoe kidney, in the absence of a urological pathological history, can be considered for transplantation even in a DCD setting by planning an appropriate preoperative strategy.

PMID:40541506 | DOI:10.1016/j.transproceed.2025.05.010

Am J Respir Crit Care Med. 2025 Jun 20. doi: 10.1164/rccm.202407-1504OC. Online ahead of print.

ABSTRACT

RATIONALE: Particulate matter <=2.5um (PM2.5) adversely impacts patients with fibrotic interstitial lung disease (fILD).

OBJECTIVE: To determine whether PM2.5-associated epigenetic alterations contribute to the environmental pathogenesis of fILD.

METHODS: Retrospective two-cohort study applying satellite-derived PM2.5 and constituent exposure matching to the residential location of patients with fILD. Robust linear regressions evaluated cohort-specific epigenome-wide differential blood DNA methylation with increasing pollutant exposures (Illumina MethylationEPIC BeadChip). Cox and linear regressions evaluated associations of cytosine-phosphate-guanine (CpG) loci with transplant-free survival and lung function. Wilcoxon test evaluated cartilage-associated protein (CRTAP) levels in fILD and control lungs.

RESULTS: The University of Pittsburgh (UPitt) cohort (n=306) had 5-year median PM2.5 exposures of 12.1ug/m3 compared with 5.1ug/m3 in the University of British Columbia (UBC) cohort (n=170). Higher pollutant exposures in the UPitt cohort were associated with lower methylation at cg25354716, annotated to CRTAP, a critical extracellular matrix remodeling enzyme. Higher exposures in the UBC cohort were associated with higher methylation at cg01019301, annotated to TLN2 (talin-2), a cytoskeletal protein involved in fibroblast migration. A 10% increase in cg25354716 methylation was associated with a hazard ratio (HR) of 0.81 for death or lung transplantation in the meta-analyzed cohorts (95%CI 0.69-0.96, p=0.01), whereas the same change in cg01019301 was associated with a HR of 1.36 (95%CI 1.07-1.74, p=0.01). CRTAP protein was more abundant in lungs from patients with fILD compared with donor controls (p<0.001).

CONCLUSIONS: PM2.5 is associated with altered blood DNA methylation in fILD. This work identifies novel pollution-sensitive targets that hold potential for therapeutic modulation in fILD.

PMID:40540633 | DOI:10.1164/rccm.202407-1504OC

Am J Respir Crit Care Med. 2025 Jun 20. doi: 10.1164/rccm.202411-2146OC. Online ahead of print.

ABSTRACT

RATIONALE: Driving pressure is marker of severity and a possible target for lung protection during controlled ventilation, but its value during assisted ventilation is unknown. Inspiratory holds provide an estimate of driving pressure (quasi-static). Expiratory holds provide an estimate of the inspiratory effort, useful to estimate the transpulmonary dynamic driving pressure.

OBJECTIVES: To assess the correlation between driving pressures measured during assisted ventilation and ICU outcomes.

METHODS: Multicenter prospective observational study. Patients with acute hypoxemic respiratory failure were enrolled within 48 hours of triggering the ventilator. Respiratory mechanics were measured daily and the variables of interest averaged over the first three days of partial assistance. ICU outcomes were collected until day 90.

MEASUREMENTS AND MAIN RESULTS: Two-hundred ninety-eight patients from 16 centers were enrolled. Tidal volume, peak airway pressure, positive-end-expiratory-pressure and inspiratory effort during the first three days of assisted ventilation did not differ between survivors and non-survivors. Quasi-static driving pressure and transpulmonary dynamic driving pressure were higher in non-survivors than in survivors (13 [11,14] vs 11 [9,13] cmH2O, p<0.001 and 19 [16,23] vs 16 [13,18] cmH2O, p<0.001, respectively), while compliance normalized to predicted body weight was lower (0.65 [0.54,0.84] vs 0.79 [0.64,0.97] ml/cmH2O/kg, p<0.001). Multivariable analysis confirmed the association with outcome. Over study days, static driving pressure significantly diverged between survivors and non-survivors.

CONCLUSIONS: During assisted ventilation driving pressure and normalized compliance are associated with ICU outcome, despite some overlap. Albeit our study does not allow to estimate if driving pressure is a marker of severity, or a cause of lung injury, it highlights the potential value of monitoring and targeting it during spontaneous assisted breathing.

PMID:40540619 | DOI:10.1164/rccm.202411-2146OC

Cardiovasc Drugs Ther. 2025 Jun 20. doi: 10.1007/s10557-025-07739-5. Online ahead of print.

ABSTRACT

PURPOSE: Cardiovascular diseases (CVDs) continue to be the leading cause of death globally, driven by a complex interplay of genetic, epigenetic, and environmental factors. Traditional risk factors alone fail to explain the individual variability in disease susceptibility and progression. Recent advances in genomics and epigenomics have revealed key molecular mechanisms that regulate cardiovascular function, highlighting the importance of gene network dynamics and epigenetic regulation.

METHODS: This review systematically analyzes peer-reviewed literature from the past decade sourced from electronic databases including PubMed and Google Scholar. It compiles the multifaceted roles of DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs in regulating cardiovascular gene expression, cellular phenotypes, and disease pathogenesis.

RESULTS: DNA methylation influences the transcriptional activity of gene expression associated with atherosclerosis, myocardial infarction, and hypertension, while histone modifications and ATP-dependent chromatin remodeling regulate cardiac hypertrophy, fibrosis, and regeneration. Noncoding RNAs further act as critical regulators of angiogenesis, inflammation, and myocardial remodeling. Therapeutically, these findings have facilitated the development of epigenetic drugs and gene-editing technologies targeting specific molecular pathways involved in CVD progression. Emerging technologies such as CRISPR/Cas9, RNA-based therapies, and small-molecule inhibitors of epigenetic enzymes hold potential for correct abnormal gene expression patterns. Moreover, integrative multi-omics and systems biology approaches are advancing personalized treatment strategies, improving the accuracy and effectiveness of cardiovascular interventions.

CONCLUSION: Collectively, unraveling the complex molecular interactions among gene networks, epigenetic alterations, and targeted therapeutic mapping aims to combat CVD with better precision and efficacy.

PMID:40540082 | DOI:10.1007/s10557-025-07739-5

Adv Sci (Weinh). 2025 Jun 20:e01070. doi: 10.1002/advs.202501070. Online ahead of print.

ABSTRACT

Cardiac fibrosis, a key pathological feature of cardiac remodeling, is a major contributor to mortality in older patients with heart failure. The underlying mechanisms are complex, involving alterations in intercellular communication and chronic inflammation. This study investigates the role of indole-3-propionic acid (IPA) in aging-related myocardial fibrosis and its regulatory effects on autophagy through palmitoyl-protein thioesterase 1 (PPT1). Here, plasma levels of IPA, a tryptophan-derived metabolite, are found to be reduced in older patients with heart failure, and this reduction is associated with deteriorating cardiac function. Notably, IPA supplementation significantly attenuated aging-related myocardial fibrosis. PPT1, a lysosomal enzyme involved in autophagy, is upregulated in macrophages during aging. IPA reversed aging-induced increase in PPT1 expression. Using PPT1flox/flox Lyz2-cre mice, it is demonstrated that macrophage-specific deletion of PPT1 significantly reduced cardiac inflammation and myocardial fibrosis in aged mice. Furthermore, PPT1 silencing in macrophages reduced the expression of myocardial fibrosis markers in vitro. Mechanistically, IPA regulated PPT1 expression to modulate the PI3K-AKT-mTOR pathway, thereby restoring autophagic activity in senescent macrophages and suppressing both inflammation and aging-related myocardial fibrosis. Additionally, IPA influenced the cGAS-STING signaling pathway to regulate PPT1 expression. These findings demonstrate that IPA inhibits PPT1, activates autophagy in macrophages, and mitigates aging-related myocardial fibrosis.

PMID:40539882 | DOI:10.1002/advs.202501070

Ann Pharmacother. 2025 Jun 20:10600280251349570. doi: 10.1177/10600280251349570. Online ahead of print.

ABSTRACT

BACKGROUND: Intravenous (IV) ganciclovir is used in the management of herpesvirus infections, including cytomegalovirus (CMV). Ganciclovir is usually administered inpatient given the need for close monitoring of laboratory parameters.

OBJECTIVE: This study describes our experience with administering IV ganciclovir via an outpatient parenteral antimicrobial therapy (OPAT) program.

METHODS: This is a retrospective review of patients discharged on IV ganciclovir via OPAT at a tertiary medical center from August 2019 to August 2024. Demographics and treatment outcomes were collected.

RESULTS: Ganciclovir was the preferred agent in all patients either due to concern for gastrointestinal absorption or provider preference. Eighteen patients with a median age of 59.5 (interquartile range [IQR]: 53-65) years met criteria. The most common underlying immunocompromising condition was receipt of a transplanted organ in 16 (88.9%) patients, most commonly heart (8 patients) and kidney transplants (7 patients). Median duration of therapy after hospital discharge was 22 (IQR: 20-27) days. Fifteen (83.3%) patients transitioned to valganciclovir on completion of parenteral therapy either as secondary prophylaxis or continuation of therapy. The most common adverse event was leukopenia in 6 (33.3%) patients. One patient developed acute kidney injury (AKI) requiring dose modification and eventual discontinuation.

CONCLUSION AND RELEVANCE: Ganciclovir via OPAT is a viable option in patients requiring an extended duration of IV therapy. In our cohort of 18 patients, only one had early discontinuation of therapy due to ganciclovir-related AKI. Close monitoring of labs and an established OPAT protocol can allow for successful completion of therapy.

PMID:40539855 | DOI:10.1177/10600280251349570

Ann Surg. 2025 Jun 20. doi: 10.1097/SLA.0000000000006804. Online ahead of print.

ABSTRACT

OBJECTIVES: The Minimally Invasive Organ Transplant Consensus Conference (MIOT.CC) aimed to develop evidence-based recommendations for advancing minimally invasive techniques in organ transplantation.

BACKGROUND: Minimally invasive approaches (laparoscopic/robotic) are underutilized in transplantation compared to other specialties, despite potential advantages such as reduced morbidity and faster recovery.

METHODS: The conference Held in Riyadh, Saudi Arabia (December 2024) included international experts in minimally invasive donation and/or transplantation of the kidney, liver, pancreas, lung, heart, and uterus. Using the Danish Model of Consensus, participants reviewed current practice and evidence to formulate recommendations. The process included systematic literature reviews according to PRISMA guidelines and assessment of evidence quality using the GRADE approach.

RESULTS: Minimally invasive approaches consistently reduced postoperative pain, complications, and hospital stay. Specific recommendations were derived for each organ, with particular attention to donor safety and to the expansion of robotic techniques, if appropriately supported by locally available technology and experience.

CONCLUSION: MIOT.CC delineated a framework to disseminate minimally invasive techniques in both organ donation and transplantation. These recommendations can guide centers worldwide to first implement and subsequently optimize minimally invasive approaches through ongoing evaluation and adaptation based on emerging evidence and technological advancements.

PMID:40539268 | DOI:10.1097/SLA.0000000000006804

Front Immunol. 2025 Jun 5;16:1568988. doi: 10.3389/fimmu.2025.1568988. eCollection 2025.

ABSTRACT

BACKGROUND: Although postoperative rejection in transplant patients can be managed with immunosuppressants, their use is associated with some complications due to excessive immunosuppression. Recent animal studies in allotransplantation have suggested that certain ingredients of Chinese herbal medicine can extend transplant survival. However, their effects on transplantation have not been systematically reviewed and analyzed. The aim of this study was to evaluate the effects of herbal medicine ingredients on complications and survival of transplanted organs after heart, liver and kidney transplantation, and to explore the possible mechanism of action.

MATERIALS AND METHODS: Databases, including PubMed, EMBASE, Cochrane Library, Web of Science, Wang Fang, China National Knowledge Infrastructure (CNKI), China Science and Technological Journal Database (VIP) and Chinese Biomedical Literature Database (CBM), were searched up to January 1 2025. Animal studies reporting the effects of Chinese herbal medicine ingredients (HMIs) on postoperative complications and organ transplant survival/outcome were included. Methodological quality was assessed using the SYRCLE risk of bias tool. Meta-analysis was performed using R 4.3 software to assess levels of inflammatory factors, oxidative stress markers, apoptosis markers, indicators of liver/kidney function, median graft survival time and immune cell subsets.

RESULTS AND CONCLUSIONS: A total of 18 studies, involving 357 rodents were included. The overall quality of the included reports was moderate. We found that HMIs enhanced organ graft survival by reducing the Banff score, extending the median survival time (MST), and exerting anti-inflammatory, antioxidant and anti-apoptotic effects. HMIs can also inhibit T cell proliferation, dendritic cell (DC) maturation and increase the proportion of CD4+ regulatory T (Treg) cells. Furthermore, the improvement in liver and kidney function indicators, such as alanine aminotransferase (ALT), aspartate transaminase (AST), Serum creatinine (Scr) and blood urea nitrogen (BUN) also suggested protective effects of HMIs on liver and kidney function. However, the high heterogeneity observed in several analyses highlights the need for standardized experimental designs and further studies to confirm these findings and to explore their underlying mechanisms. Thus, our meta-analysis indicates that HMIs improve transplantation outcomes in animal models. These results lay a solid foundation for translating HMIs into clinical strategies for improving transplantation outcomes.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251002755, identifier crd420251002755.

PMID:40539066 | PMC:PMC12176545 | DOI:10.3389/fimmu.2025.1568988

Front Transplant. 2025 Jun 5;4:1594241. doi: 10.3389/frtra.2025.1594241. eCollection 2025.

ABSTRACT

Evidence for the contribution of non-HLA antibodies on long-term allograft outcome was suggested in early studies by Paul Terasaki and colleagues who showed worse 10-year allograft outcome in HLA identical kidney transplant recipients with a positive panel reactive antibody (PRA) as determined by the micro cytotoxicity assay, in which cells express other targets beside HLA. More recent reports have shown worse graft outcome when antibodies against non-HLA antigens were detected with HLA-donor specific antibodies (HLA-DSA), and even suggest that non-HLA antibodies may serve as precursor to development of HLA antibodies. Unfortunately, the recent studies lack reproducibility, which then leads to skepticism as to the relevance of non-HLA antibody in transplantation outcome. Consequently, routine testing for non-HLA antibody along with monitoring of HLA-DSA as part of a post-transplant immune surveillance protocol is not standard practice. The Sensitization in Transplantation: Assessment of Risk (STAR) workgroup summarized the current literature on this topic, citing differences in cohort characteristics, variability in study design, selection of sample and timepoints for testing and variability in the assays used to detect non-HLA antibodies, as reasons that impact the accurate assessment on the relevance of non-HLA antibodies. However, correlation between test results and outcome can only be determined if the assay in question is detecting the correct analyte. Therefore, here we will make the case for a plan that requires a systematic validation of high-throughput bead-based assays, to include appropriate sequence selection for non-HLA antigenic targets and quality control metrics as a first step to solving this puzzle.

PMID:40538429 | PMC:PMC12176821 | DOI:10.3389/frtra.2025.1594241

Interdiscip Cardiovasc Thorac Surg. 2025 Jun 4;40(6):ivaf139. doi: 10.1093/icvts/ivaf139.

NO ABSTRACT

PMID:40538181 | DOI:10.1093/icvts/ivaf139

PM R. 2025 Jun 19. doi: 10.1002/pmrj.13433. Online ahead of print.

ABSTRACT

BACKGROUND: In-reach rehabilitation is a relatively new model of care available in a small number of Australian public hospitals. These multidisciplinary teams deliver evidence-based structured rehabilitation to carefully selected patients during acute care. There are no published rehabilitation outcomes in heart and/or lung transplant recipients.

OBJECTIVE: To describe the rehabilitation outcomes of a cohort of heart and/or lung transplant recipients.

DESIGN: Retrospective cohort study.

SETTING: One metropolitan institution with the largest heart and lung transplant service in Australia.

PATIENTS: Between 2014 and 2023, a total of 957 heart and/or lung transplants were performed at this institution.

INTERVENTION: In-reach rehabilitation was delivered to selected patients during the 10-year period. However, from 2019 onwards, patients were proactively screened by the rehabilitation team for eligibility as well as referred from the acute transplant teams.

MAIN OUTCOME MEASURES: Functional independence measure (FIM) changes and percentage of patients going to inpatient rehabilitation after completion of acute care.

RESULTS: In-reach rehabilitation was received by 223 (24.3%) patients. With the exception of three patients (who died), the vast majority were able to complete an in-reach rehabilitation program and were discharged to the community (n = 98, 43.9%), inpatient rehabilitation (n = 119, 53.4%), or transferred to another hospital (n = 3, 1.3%), demonstrating feasibility. Across the cohort, the median admission and discharge FIM scores were 77.0 (interquartile range, 60-94.8) and 100 (interquartile range, 77-118), respectively, demonstrating significant functional improvements from start to finish of the in-reach rehabilitation program (p < .001). Over this period, the number of patients discharged to inpatient rehabilitation decreased as a proportion of the total number of transplants (25.7% in 2014, 47.8% in 2017, 34.7% in 2019, 26.2% in 2021, 8.0% in 2023). Proactive rehabilitation screening implemented from 2019 allowed for earlier and longer program delivery to more patients.

CONCLUSIONS: In-reach rehabilitation is feasible in acute care after heart and/or lung transplantation and was associated with functional improvements. The addition of proactive rehabilitation screening appeared to improve the effectiveness of the in-reach rehabilitation program.

PMID:40538100 | DOI:10.1002/pmrj.13433

Innovations (Phila). 2025 Jun 19:15569845251337720. doi: 10.1177/15569845251337720. Online ahead of print.

ABSTRACT

OBJECTIVE: Partial heart transplantation (PHT) is a new procedure that delivers growing heart valve implants for children. However, awareness, attitudes, and perceptions of health care professionals regarding PHT remain unexplored.

METHODS: A national survey was conducted among members of the Congenital Heart Surgical Society, pediatric cardiac intensive care unit (ICU) directors, medical students, and organ procurement organization (OPO) representatives. The survey measured their awareness, perceptions, and attitudes toward PHT. Perceptions and attitudes were measured using a 5-point Likert scale. Statistical comparisons in ranked responses between survey questions were calculated using two-way analysis of variance, with multiple comparisons assessed by a Tukey post hoc test.

RESULTS: There were responses from 95 medical students (12.1%), 32 congenital cardiac surgeons (10.26%), 21 pediatric ICU directors (16.8%), and representatives from 8 OPOs (15%). Prior to survey distribution, 20% of students were aware of PHT. In contrast, almost all congenital heart surgeons (96.88%) and pediatric cardiologists (100%) were aware of PHT. Although surgeons and cardiologists understand the concepts of PHT, cardiologists were less likely to recommend and inform their patients about the procedure if they meet the criteria (Likert scale scores of 4.68 vs 3.14, P = 0.01 and 4.38 vs 3.69, P = 0.01, respectively). Surgeon and cardiologist perceptions regarding the use of PHT for different patient age groups were significantly different (P < 0.001).

CONCLUSIONS: Even though PHT is a relatively recent innovation, it is well known among pediatric cardiac surgeons and pediatric intensive care directors.

PMID:40538051 | DOI:10.1177/15569845251337720