Trasplante cardíaco

Front Immunol. 2025 Jun 6;16:1532325. doi: 10.3389/fimmu.2025.1532325. eCollection 2025.

ABSTRACT

BACKGROUND: Epitranscriptomics, with m6A as the most prevalent in mammals, is a novel treatment target for inflammatory diseases, including cardiovascular diseases. However, little is known about m6A RNA-regulation during myocardial infarction (MI).

METHODS: In this explorative sub-study of the ASSAIL-MI trial, we used whole blood samples from patients with acute ST-elevation MI (STEMI) (n=6) at admission and after 3-7 days, and from healthy control subjects (n=3). RNA was isolated, and m6A sites were analyzed using human m6A single nucleotide resolution microarray analysis. mRNA levels were analyzed using RNA sequencing analysis.

RESULTS: Compared with controls, patients with STEMI had a strikingly different pattern of m6A deposition. In total, 845 m6A methylation sites in whole blood RNA were hypomethylated and 36 were hypermethylated compared with controls. Of the hypomethylated transcripts, 194 transcripts were lower expressed, while 197 transcripts were higher expressed. The m6A pattern changed from an overall hypomethylation at admission to an overall hypermethylation 3-7 day after admission. Anti-inflammatory treatment with tocilizumab further altered the m6A deposition.

CONCLUSIONS: In this hypothesis generating study, m6A deposition differs STEMI patients and healthy controls. The m6A pattern changes over the course of 3-7 days. This response is, at least to some degree, is modulated by blocking the IL-6 receptor. Our data may suggest that this post-transcriptional regulation of RNA is involved in the immune response during STEMI, highlighting its potential as a target for therapy in MI.

PMID:40547027 | PMC:PMC12178860 | DOI:10.3389/fimmu.2025.1532325

Cureus. 2025 May 23;17(5):e84680. doi: 10.7759/cureus.84680. eCollection 2025 May.

ABSTRACT

Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma (NHL) that rarely occurs as a post-transplant lymphoproliferative disorder (PTLD), especially in the elderly. We report a rare case of BL in a male in his 70s who developed BL several years following heart transplantation in the setting of chronic immunosuppression. He initially presented with signs and symptoms of severe hypercalcemia and retroperitoneal lymphadenopathy, which was biopsied to confirm the diagnosis. Treatment was initiated with rituximab and intrathecal methotrexate; however, his hospital course was complicated by a sigmoid microperforation due to a newly formed colonic fistula. This is an unusual case of Epstein-Barr virus (EBV) reactivation causing PTLD and underscores the importance of considering aggressive lymphomas in immunocompromised elderly patients following solid organ transplantation.

PMID:40546500 | PMC:PMC12182806 | DOI:10.7759/cureus.84680

Oral Dis. 2025 Jun 22. doi: 10.1111/odi.70012. Online ahead of print.

ABSTRACT

BACKGROUND: Kidney transplant recipients (KTRs) experience immune modulation, which may lead to graft rejection and other adverse outcomes. Although serum cytokines are well-established systemic immune markers, the role of salivary biomarkers has never been reported in the literature.

OBJECTIVE: To investigate salivary and serum cytokine levels in KTRs and their correlations with clinical outcomes over time.

MATERIALS AND METHODS: We evaluated the same group of 38 KTRs at T1 (< 6 months post-transplantation) and T2 (> 6 months post-transplantation). Samples were analysed with Human 6-Plex Cytokine Panel (Luminex) and clinical data were collected from medical records. Statistical analyses included Wilcoxon tests, Fisher's exact tests, Spearman's correlation, and Benjamini-Hochberg procedure for multiple comparisons (p < 0.05 significant).

RESULTS: Serum cytokines showed lower IFN-γ levels in cardiac events and associations of TNF-α, IL-8, and IL-10 with cytomegalovirus (CMV), BK polyomavirus (BKPyV) viremia and anaemia. Salivary cytokines showed distinct profiles, with elevated levels of TNF-α in anaemia and IL-8 in patients with diarrhoea. Those not experiencing acute rejection in both cases showed reduced salivary IL-8 levels.

CONCLUSIONS: Integrating serum and salivary measurements highlighted the potential of salivary biomarkers, particularly TNF-α and IL-8, in complementing traditional blood-based assays and other invasive monitoring methods in kidney transplantation.

PMID:40545713 | DOI:10.1111/odi.70012

Catheter Cardiovasc Interv. 2025 Jun 22. doi: 10.1002/ccd.31698. Online ahead of print.

ABSTRACT

Cardiogenic shock (CS) remains a high morbidity and mortality condition worldwide frequently complicating acute myocardial infarction (AMI) and decompensated heart failure (HF). Within the management of CS, mechanical circulatory support (MCS) devices play a critical role in maintaining hemodynamic stability, preserving end-organ perfusion and bridging patients through to recovery, implantation of durable support or transplantation. Despite their use, optimal timing of initiation, as well as patient and device selection remain unclear. This review explores the current landscape of MCS devices, surrounding evidence and key distinctions between devices. With increasing acknowledgment for the heterogeneity of CS, understanding the strengths and limitations of each device remains crucial to improving outcomes in this high-risk population.

PMID:40545708 | DOI:10.1002/ccd.31698

Transplantation. 2025 Jun 23. doi: 10.1097/TP.0000000000005377. Online ahead of print.

ABSTRACT

BACKGROUND: There is a growing population of solid organ transplant (SOT) survivors who subsequently require a hematopoietic cell transplant (HCT), although there are limited data on survival, risk factors for SOT graft loss, and death in this cohort.

METHODS: This retrospective Center for International Blood and Marrow Transplant Research study included recipients of SOT followed by HCT between 1989 and 2017. HCT data were merged with organ transplant data from the Organ Procurement and Transplantation Network.

RESULTS: Eighty-three patients with an SOT underwent an HCT. Organs transplanted included heart/lung (thoracic, n = 15), kidney (n = 42), and liver (n = 26); 24 patients (29%) received a living donor graft and 59 (71%) a deceased graft. Forty-one patients (49.4%) received an allogeneic HCT and 42 (50.6%) an autologous HCT. Three-year overall survival (OS) from HCT in the entire cohort was 38.6%. There were no significant differences in OS by SOT type, although 3-y OS appeared lowest in the kidney SOT group at 29.9%, compared with liver SOT at 40.6% and thoracic SOT at 58.2%. The incidence of SOT graft failure 3 y post-HCT was 59.1%. There were no significant differences in SOT graft failure by organ type: 3-y failure probability 67.2% for kidney, 56.5% for liver, and 46.2% for thoracic. Shared risk factors for death and graft failure included HCT indication (leukemia, lymphoma, and nonmalignant diseases), HCT type (allogeneic), and SOT type (kidney).

CONCLUSIONS: Although some SOT recipients may benefit from HCT, the incidence of SOT graft failure was high and OS was poor, particularly after allogeneic HCT.

PMID:40545567 | DOI:10.1097/TP.0000000000005377

Int J Cardiol. 2025 Jun 20:133521. doi: 10.1016/j.ijcard.2025.133521. Online ahead of print.

NO ABSTRACT

PMID:40544878 | DOI:10.1016/j.ijcard.2025.133521

Cardiorenal Med. 2025 Jun 20:1-25. doi: 10.1159/000546924. Online ahead of print.

ABSTRACT

BACKGROUND: Heart failure (HF) prevalence is increasing, and its prognosis worsens in the presence of other comorbidities. Up to 70% of patients develop cardio-renal syndrome (CRS), which is associated with diuretic resistance or kidney deterioration over time. Peritoneal dialysis (PD) for ultrafiltration (PD-UF) could be a potential therapeutic option in CRS, although its long-term outcomes have not been described.

METHODS: Retrospective registry study of the Catalan Renal Registry on patients with PD-UF indication between 2013-2022. Baseline clinical characteristics and follow-up until December/2022 was studied.

RESULTS: Of the 1874 incident patients on PD,198(10.6%) were PD-UF,73.2% of the patients were male and the mean age was70.7±9.3 years. Median eGFR at start was 22.6 [IQR14.8-32.8] ml/min·1.73m2 and 75.0% have an eGFR above 15 ml/min·1.73m2. Previous history of ischemic heart disease, arrhythmia or cardiac surgery was recorded, 57.6% of patients had ≥2 of these pathologies. The most common HF etiology was ischemic heart disease in 21.7% of patients. Median overall patient survival was 21 months [IQR17.3-24.3]. Technique survival at one year was 94.8%, and 27 patients were transferred to other renal replacement therapy (hemodialysis or kidney transplantation). In the cox multivariate analysis, age>75 years (HR 1.76[95%CI 1.20-2.59]), mild frailty (HR2.18[95%CI 1.17-2.59]), severe frailty (HR 17.62[95%CI 1.20-55.48]) and the burden of cardiac disease (2 categories HR 2.17[95%CI 1.05-4.47]; 3 categories HR 2.26 [95%CI 1.05-4.89]) were associated with poor overall survival. Technique survival was associated with eGFR (<30 ml/min·1.73m2 HR 5.64[95%CI 1.32-24.18]) and body mass index (<20 kg/m2 HR 6.53 [95%CI 1.06-40.12]) at baseline.

CONCLUSION: PD-HF is a feasible option in patients with advanced HF and CRS. The complexity of this population increases with older age, frailty and higher cardiac burden.

PMID:40544832 | DOI:10.1159/000546924

Arch Cardiovasc Dis. 2025 Jun 12:S1875-2136(25)00325-0. doi: 10.1016/j.acvd.2025.04.056. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the widespread adoption of percutaneous pulmonary valve implantation, there remains a lack of consensus on the optimal management of peri-interventional and long-term antithrombotic therapies because of a lack of evidence.

AIM: To clarify current practices in peri/postprocedural antithrombotic strategies for percutaneous pulmonary valve implantation.

METHODS: An online survey was submitted to the Interventional Working Group of the Association for European Paediatric and Congenital Cardiology, and was completed by 76 congenital interventional cardiologists in 2023-2024.

RESULTS: Overall, 86% had standardized protocols for anticoagulation/antiaggregation. Intraprocedural heparin administration of 100IU/kg was common (83%), and postprocedural strategies mostly included acetylsalicylic acid (aspirin) (45%) or a combination of antiaggregation and anticoagulation (29%). Long-term strategies comprised antiaggregation (88%), no therapy (11%) and anticoagulation only (1%). Acetylsalicylic acid monotherapy was prescribed by 91%, whereas 9% used dual antiaggregation therapy. Dual antiaggregation therapy was continued for suspicious medical history of thrombotic complication or microthrombi for 3-6 months. Testing for acetylsalicylic acid resistance was infrequent (36%), and only if clinically indicated. When patients had pre-established anticoagulation therapy, 59% changed their strategy. Treatment changes based on valve type were rare (8%). The primary reasons for anticoagulation/antiaggregation were to increase valve longevity (26%) and for both longevity and endocarditis prophylaxis (68%). Acute valve thrombosis was reported in 11 cases.

CONCLUSIONS: The survey reveals variability in practices after percutaneous pulmonary valve implantation. Most interventional cardiologists prefer acetylsalicylic acid for postprocedural and long-term management, whereas dual antiaggregation therapy is sometimes used in specific cases. Anticoagulation is limited to pre-existing therapy cases or isolated experiences for 3 months.

PMID:40544108 | DOI:10.1016/j.acvd.2025.04.056

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