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BMJ Case Rep. 2025 Jul 1;18(7):e265384. doi: 10.1136/bcr-2025-265384.

ABSTRACT

Viral infections have been associated with acute allograft rejection in solid organ transplant recipients. Influenza infection upregulates host proinflammatory cytokines, suggesting the host immune response can precipitate graft rejection. Pandemic influenza, specifically, was associated with rejection in multiple renal allograft recipients. However, cardiac allograft rejection has not been reported in association with endemic influenza. We present the case of a man in his mid-30s, transplanted 5 years prior, who developed new heart failure 4 weeks after PCR-confirmed influenza A infection. Endomyocardial biopsy revealed concomitant high-grade acute cellular rejection and antibody-mediated rejection. Despite a pretransplant panel reactive antibody of 0%, a negative virtual crossmatch and consistently therapeutic tacrolimus levels, de novo donor-specific antibodies developed. Even with aggressive therapy, he died as a result of graft failure. Transplant recipients must be regularly vaccinated, and clinicians should maintain a high degree of suspicion of graft failure in the immediate aftermath of influenza infection.

PMID:40592589 | DOI:10.1136/bcr-2025-265384

J Heart Lung Transplant. 2025 Jun 24:S1053-2498(25)02036-4. doi: 10.1016/j.healun.2025.06.011. Online ahead of print.

ABSTRACT

BACKGROUND: The forced expiratory volume in one second (FEV1) is the standard measure used to monitor the lung function after lung transplantation. However, little is known about the FEV1 trajectories post transplantation, and their associations with clinical outcomes.

METHODS: Adult patients who received a bilateral lung transplant between January 1, 2010 and January 1, 2021 were included from 15 centres in France, Belgium, Austria and the US. Three French centres formed the development cohort and the remaining centres formed the external validation cohorts. All centres performed routine spirometry measurements commencing shortly after lung transplantation and continuing at regular intervals of maximum three months afterwards. Recipient, donor and transplant characteristics were collected. Latent class mixed models were used to identify FEV1 trajectories. The number of FEV1 trajectories was defined according to the Akaike Information Criterion, Bayesian Information Criterion, the discrimination, the entropy and the interpretability of the model.

FINDINGS: A total of 2305 patients were included with 59 034 FEV1 measurements collected. The median follow-up post-transplantation was 4.3 years (IQR 2.3-6.2). In the development cohort (n=605), the best latent class mixed model identified seven clinically meaningful FEV1 trajectories. Trajectory #1 (25.6%) was characterized by patients with moderate and stable lung function (3-year patient survival = 79.9%); trajectory #2 (24.0%) and #3 (27.3%) were characterized by patients with moderate/high and stable lung function (3-year patient survival = 96.6% and 95.7% respectively); trajectory #4 (3.8%) was characterized by patients with increasing lung function (3-year patient survival = 69.6%); trajectory #5 (11.7%) was characterized by patients with a slow decline (3-year patient survival = 90.1%); and trajectory #6 (3.0%) and #7 (4.6%) were characterized by patients with accelerated decline (3-year patient survival = 33.3% and 59.5 % respectively). Patients belonging to trajectories were associated with gender (p=0.020) and underlying disease (p=0.004). Similar FEV1 trajectories and patient outcomes were identified in the external validation cohorts on the basis of independent analyses. The trajectories were also confirmed in a series of subpopulations. Last, FEV1 value and slope at 1 year post transplant were strongly associated with FEV1 trajectories, in both the development cohort and the external validation cohorts.

INTERPRETATION: We identified and validated FEV1 trajectories that capture different clinical scenarios associated with post-transplant recipient outcomes. Our results may provide the basis for a trajectory-based risk assessment of lung transplant recipients.

FUNDING: "Vaincre la mucoviscidose" grant, the association Grégory Lemarchal, ANR grant, PHRC grant, the FP7 collaborative project, IRSRPL grant, the Fondation du Souffle and PLUTO DITCAP grant from Vaincre la Mucoviscidose and Association Grégory Lemarchal.

PMID:40592371 | DOI:10.1016/j.healun.2025.06.011

Proc Natl Acad Sci U S A. 2025 Jul 8;122(27):e2424529122. doi: 10.1073/pnas.2424529122. Epub 2025 Jul 1.

ABSTRACT

Mitochondrial dysfunction is closely linked to cardiomyocyte injury following myocardial infarction (MI). While mitochondrial transplantation is a promising therapeutic strategy, challenges remain in maintaining mitochondrial structural integrity, enhancing delivery efficiency, and increasing the mitochondrial supply. Herein, we developed a gelated microvesicle-based mitochondria delivery system (Mito@Microgels) for transplanting mesenchymal stem cell mitochondria, addressing the aforementioned issues. Further decoration of phosphatidylserine on the surface of Mito@Microgels boosted cellular uptake efficiency by cardiomyocytes. These Mito@Microgels effectively deliver active mitochondria to cardiomyocytes, improving the mitochondrial network architecture and function and consequently reducing the cellular injury induced by oxidative stress. Moreover, Mito@Microgels attenuated the inflammatory phenotype of macrophages, helping resolve excessive local inflammation. In vivo animal studies using a rat MI model further validated the therapeutic efficacy of the Mito@Microgels, as evidenced by improved myocardial function, prevention of infarcted left ventricular wall thinning, and increased cardiomyocyte survival. Our study introduces an efficient mitochondrial delivery strategy with significant potential for cardiac repair post-MI and other mitochondria-related diseases.

PMID:40591606 | DOI:10.1073/pnas.2424529122

Support Care Cancer. 2025 Jul 1;33(7):646. doi: 10.1007/s00520-025-09706-0.

ABSTRACT

PURPOSE: Social support can ameliorate the challenges faced by childhood cancer survivors and their parents as survivors transition into adulthood. This study examined social support dynamics within adolescent/young adult (AYA)-parent dyads by comparing their support needs and gaps.

METHODS: This qualitative study was conducted in collaboration with a community-based organization serving predominately socioeconomically disadvantaged, Hispanic/Latino (H/L), rural families affected by childhood cancer in California. English- and Spanish-speaking AYA childhood cancer survivors (≥ 15 years old, ≥ 5 years from diagnosis) and parents were interviewed. Transcripts were analyzed qualitatively using applied thematic analysis.

RESULTS: Seven AYA-parent dyads (six H/L and bilingual or Spanish speaking only) were interviewed. AYAs (six male, one female) had a median (min-max) age of 19 (16-23) and were 14 years post-diagnosis (6-17). Forms of social support fell into emotional, instrumental (i.e., tangible assistance), and informational domains. Family and faith were shared sources of emotional support for parents and AYAs. Although AYAs identified parents as consistent sources of emotional support, parents frequently discussed inadequate family support and unmet emotional needs. Parents also more commonly discussed gaps in instrumental support. AYAs often lacked cancer-related knowledge, with parents serving as primary sources of informational support. Parents worried about children's readiness to transition to adult-focused survivorship care.

CONCLUSION: Parents experienced gaps in emotional and instrumental support not noted by AYAs, suggesting parents help buffer these experiences. AYAs' reliance on parents for informational support in the post-treatment period highlights an opportunity to build upon supportive parent-AYA relationships through dyad-focused education to facilitate adult-focused survivorship care transitions.

PMID:40591011 | DOI:10.1007/s00520-025-09706-0

J Clin Invest. 2025 Jul 1;135(13):e172218. doi: 10.1172/JCI172218. eCollection 2025 Jul 1.

ABSTRACT

Coinhibitory receptors function as central modulators of the immune response to resolve T effector activation and/or to sustain immune homeostasis. Here, using humanized SCID mice, we found that neuropilin-2 (NRP2) is inducible on late effector and exhausted subsets of human CD4+ T cells and that it is coexpressed with established coinhibitory molecules including PD-1, CTLA4, TIGIT, LAG3, and TIM3. In murine models, we also found that NRP2 is expressed on effector memory CD4+ T cells with an exhausted phenotype and that it functions as a key coinhibitory molecule. Knockout (KO) of NRP2 resulted in hyperactive CD4+ T cell responses and enhanced inflammation in delayed-type hypersensitivity and transplantation models. After cardiac transplantation, allograft rejection and graft failure were accelerated in global as well as CD4+ T cell-specific KO recipients, and enhanced alloimmunity was dependent on NRP2 expression on CD4+ T effectors but not on CD4+Foxp3+ Tregs. Also, KO Tregs were found to be as efficient as WT cells in the suppression of effector responses in vitro and in vivo. These collective findings identify NRP2 as a potentially novel coinhibitory receptor and demonstrate that its expression on CD4+ T effector cells is of great functional importance in immunity.

PMID:40590224 | DOI:10.1172/JCI172218

Transplant Direct. 2025 Jun 27;11(7):e1828. doi: 10.1097/TXD.0000000000001828. eCollection 2025 Jul.

ABSTRACT

BACKGROUND: Despite treatment of major risk factors such as acute rejection (AR) and organizing pneumonia (OP) in lung transplant recipients, chronic lung allograft dysfunction (CLAD) still develops at high rates, suggesting that traditional methods of assessing response to treatment and resolution remain inadequate. It is unknown whether the degree of molecular allograft injury after treatment of AR/OP modulates the risk of CLAD and death.

METHODS: To evaluate the association of molecular allograft injury after AR/OP with the incidence of CLAD/death, we conducted a multicenter prospective cohort study that included 93 patients who underwent lung transplantation between 2015 and 2022. The degree of molecular allograft injury after AR/OP was quantified by the mean area under the curve of longitudinal measures of plasma donor-derived cell-free DNA (dd-cfDNA).

RESULTS: Over a median follow-up of 5 y, patients who developed CLAD/death had persistently higher levels of dd-cfDNA in the months after AR/OP. In multivariable Cox regression analysis adjusting for patient and transplant risk factors, mean dd-cfDNA levels after AR/OP were independently associated with an increased risk of CLAD/death (adjusted hazard ratio, 2.84; 95% confidence interval, 1.67-4.83; P < 0.001) and remained consistent when accounting for changes in pulmonary function after AR/OP events (hazard ratio, 2.62; 95% confidence interval, 1.53-4.47; P < 0.001).

CONCLUSIONS: The degree of allograft injury on the molecular level after AR/OP events in lung transplant recipients is associated with the risk of developing CLAD or death. This study demonstrates the potential of dd-cfDNA for improving risk stratification and monitoring the resolution and treatment responses of lung allograft injury.

PMID:40590009 | PMC:PMC12208644 | DOI:10.1097/TXD.0000000000001828

Cureus. 2025 May 31;17(5):e85141. doi: 10.7759/cureus.85141. eCollection 2025 May.

ABSTRACT

Chagas cardiomyopathy is a rare but critical cause of nonischemic heart failure, particularly in patients from endemic regions. We present a 48-year-old Spanish-speaking male from Guatemala with hypertension, hyperlipidemia, and heart failure with reduced left ventricular ejection fraction (LVEF, 10%) due to Chagas disease. Despite guideline-directed medical therapy and implantable cardioverter-defibrillator (ICD) placement, he developed cardiogenic shock. Right heart catheterization confirmed severely reduced cardiac output and elevated wedge pressure. He was ineligible for heart transplantation due to limited life expectancy but had no contraindications to left ventricular assist device (LVAD) placement. Following infectious disease clearance and prophylaxis for Trypanosoma cruzi, he successfully underwent LVAD implantation. At one-month follow-up, he showed clinical stability, improved symptoms, and adherence to medical therapy. Our case discusses the role of LVAD as a life-extending option in Chagas cardiomyopathy for non-transplant candidates, emphasizing the importance of multidisciplinary care in managing both cardiac and infectious components.

PMID:40589690 | PMC:PMC12208515 | DOI:10.7759/cureus.85141

Xenotransplantation. 2025 Jul-Aug;32(4):e70063. doi: 10.1111/xen.70063.

ABSTRACT

BACKGROUND: Solid organ xenotransplantation has been approved for clinical trials in the United States. Because of the role of nurses in patient decision-making, it is important to understand the attitudes of the future nursing workforce toward xenotransplantation. This pilot study aimed to investigate the attitudes of adult nursing students toward xenotransplantation.

METHODS: A cross-sectional survey design was used. The online pilot survey was completed by 33 undergraduate adult nursing students at one university in London, England. A minority of the hospitals that students may have had a clinical placement in had a transplant unit. The protocol for this study was reviewed and approved by the university research ethics panel.

RESULTS: Fifty-two percent of students viewed xenotransplantation positively when the risks and outcomes were equal to allotransplantation. Students were most positive toward accepting a liver from an animal source and the most negative toward accepting a heart. There was limited concern about the potential psychosocial effects of xenotransplantation. Students believed that xenotransplantation involved several risks, including immunologic, infection, and raising religious, ethical, and philosophical problems.

CONCLUSION: While participants had a moderately positive view toward xenotransplantation when the risks and outcomes were equal to allotransplantation-this dropped significantly if it produced worse outcomes. Their primary concerns about xenotransplantation were its potential infection risks as well as the ethical, philosophical, and religious problems it raises. The fact that the source organs are genetically engineered made students view xenotransplantation more favorably.

PMID:40589138 | PMC:PMC12209689 | DOI:10.1111/xen.70063

Xenotransplantation. 2025 Jul-Aug;32(4):e70061. doi: 10.1111/xen.70061.

ABSTRACT

Xenotransplantation is becoming an emerging field of interest for the treatment of end-stage heart disease. In fact, the shortage of human heart donors in European countries requires the increasing investigation of alternative strategies such as heart xenotransplantation. Among different limitations in this peculiar field, the experimental pharmacological management of patients who undergo heart xenotransplantation is primarily narrowed by the indications for which these drugs have been previously authorized by international medicines agencies. In fact, many of these medications have been never authorized for transplant rejection therapy, or for xenotransplantation, but their mechanism of action might stop the molecular pathways which are involved in xenograft antibody-mediated rejection. Additionally, drugs costs and supply can restrict their availability for xenotransplantation practice. The aim of this review is to describe the current drugs which have been used in the clinical cases of heart xenotransplantation performed to date, to analyze the indications for which they are authorized, and to evaluate the future medications which might be implemented in heart xenotransplantation field, with a particular focus on the European scenario.

PMID:40589132 | PMC:PMC12209706 | DOI:10.1111/xen.70061

Stud Health Technol Inform. 2025 Jun 26;328:298-301. doi: 10.3233/SHTI250723.

ABSTRACT

Transplantation surgery has grown significantly over the years, from conventional procedures to minimally invasive and robotic-assisted surgery. While traditional methods, are still essential for emergency situations, they often result in longer recovery times, increased patient pain, and higher complication risks. However, robotic-assisted surgery, improves the experience by offering enhanced precision, improved visualization, and reduced surgery invasiveness, thus contributing to shorter recovery periods, less blood loss, and fewer complications for patients. This proceeding aims to explore the integration of robotic systems in transplant surgeries in Saudi Arabia, focusing on the country's recent groundbreaking achievements, such as the world's first fully robotic heart and liver lobe transplants performed at King Faisal Specialist Hospital & Research Centre. Additionally, discusses the advantages of robotic transplantation, such as improved surgical accuracy and patient outcomes, along with the possible challenges like costs, longer operating times, and the need for specialized training. The integration of robotic technology in transplant surgery aligns with Saudi Arabia's Vision 2030 healthcare transformation program, which attempts to advance healthcare services through technological innovations. Despite the challenges, robotic surgery has proven to be a transformative tool in the field of transplantation, offering both patients and surgeons significant benefits.

PMID:40588930 | DOI:10.3233/SHTI250723

Surg Case Rep. 2025;11(1):25-0230. doi: 10.70352/scrj.cr.25-0230. Epub 2025 Jun 25.

ABSTRACT

INTRODUCTION: Coagulation disorders can lead to massive perioperative bleeding regardless of the type of surgery. Their preoperative identification is essential (from a complete history of bleeding tendency) and steps should be taken to mitigate such complications at the time of surgery. Alpha2-plasmin inhibitor (α2-PI) deficiency is a rare congenital coagulation disorder resulting in activation of fibrinolysis and requiring specific treatment with antifibrinolytic agents. Lung transplantation has not been previously reported in a patient with α2-PI deficiency.

CASE PRESENTATION: A 46-year-old female affected by chronic obstructive pulmonary disease with congenital α2-PI deficiency was referred to our hospital for cadaveric lung transplantation. Due to a previous history of intramedullary hemorrhage, we conducted lung transplantation with prophylactic administration of fresh frozen plasma (FFP) and tranexamic acid during surgery. We used the point of care test (POC) rotational thromboelastometry (ROTEM) to diagnose intraoperative coagulopathy. The postoperative course was uneventful, and she was discharged from the hospital 42 days after lung transplantation. Six months have passed since transplant, and she is still attending outpatient clinics in good health and with no record of bleeding episodes.

CONCLUSIONS: Lung transplantation for a patient with α2-PI deficiency was safely performed with the use of planned FFP transfusion and tranexamic acid. A POC ROTEM testing approach to perioperative management was useful during lung transplantation.

PMID:40589561 | PMC:PMC12207097 | DOI:10.70352/scrj.cr.25-0230

Cleft Palate Craniofac J. 2025 Jul 1:10556656251355039. doi: 10.1177/10556656251355039. Online ahead of print.

ABSTRACT

BackgroundMicrotia is a congenital anomaly characterized by malformation of the external ear. The complex chronic conditions (CCC) classification system identifies children with long-standing health problems based on various body systems and disease types. This study utilized the Pediatric Health Information System (PHIS) database to investigate the relationship between microtia and CCCs to guide screening protocols and provide insight into patient-centered treatment.MethodsA retrospective review of PHIS was conducted between 2015 and 2023. Patients were identified with an initial encounter with an associated microtia diagnosis from all participating hospitals. Patient demographics, associated organ system flags, and CCCs were collected and analyzed. Descriptive statistics were performed and effect sizes were calculated to assess associations between variables and microtia complexity.ResultsA total of 20,313 patients with microtia were identified. Of these patients, 11 183 were male (55.1%), non-Hispanic White (n = 8089, 41.9%), or Hispanic (n = 6512, 33.8%). Nearly 40% of diagnoses were associated with at least 1 CCC (n = 8234), and a significant proportion (n = 5715) were noted to have 2 or more CCCs. Cardiovascular diagnoses were among the most common organ system affected (16.8%), followed by gastrointestinal conditions (15.4%).ConclusionThis study highlights a significant correlation between microtia and CCCs. With 40% of patients diagnosed with microtia also presenting with at least 1 CCC, this study underscores the importance of comprehensive medical assessment and care strategies while further supporting the increased correlation of cardiac conditions in this population. This necessitates a re-evaluation of first-line screening modalities for patients presenting with microtia.

PMID:40589417 | DOI:10.1177/10556656251355039

Kyobu Geka. 2025 Jun;78(6):444-447.

ABSTRACT

Pulmonary enteric adenocarcinoma is a rare subtype of adenocarcinoma that was introduced in the 2015 World Health Organization( WHO) Histological Classification and Lung Cancer Treatment Protocol (8th Edition). Distinguishing it from lung metastases of colorectal cancer poses a significant clinical challenge. We report three cases of pulmonary enteric adenocarcinoma with distinct computed tomography(CT) findings. Pulmonary enteric adenocarcinoma typically presents as a large mass, often characterized as substantial and lacking a significant ground glass shadow. However, in the first case, a partially filled nodular shadow was observed;in the second case, a well-difined cystic-like mass shadow was identified;and in the third case, a nodular shadow with an internal cavity was noted.

PMID:40589021

Int J Epidemiol. 2025 Jun 11;54(4):dyaf079. doi: 10.1093/ije/dyaf079.

ABSTRACT

BACKGROUND: Migraine aura without headache was previously described as a benign condition. We investigated an association between migraine aura without headache and risks of stroke, myocardial infarction (MI) or percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), atrial fibrillation or flutter, and composite outcome (MI, PCI, and CABG).

METHODS: We conducted a nationwide, registry-based cohort study in Denmark in 2003-18, which included 755 individuals with typical aura without headache, 11 420 individuals who experience migraine with aura, 13 415 individuals who experience migraine without aura, 12 000 individuals with unspecified migraine, and a comparison cohort of 702 755 individuals aged 15-80 years randomly sampled from the general population. We computed incidence rates (IRs) per 1000 person-years (PYs) of the outcomes and hazard ratios (aHRs) adjusted for age, sex, calendar year, and pre-existing chronic conditions in Cox proportional-hazards regression analyses.

RESULTS: The IR per 1000 PYs among individuals experiencing aura without headache were 4.58 (2.09-7.07) for stroke, 2.10 (0.42-3.79) for MI or PCI, 0.69 (0.00-1.66) for CABG, and 4.95 (2.35-7.54) for atrial fibrillation or flutter. Individuals who experience aura without headache versus the comparator had increased risks of stroke [aHR: 2.58, 95% confidence interval (CI): 1.49-4.44] and atrial fibrillation or flutter (aHR: 2.22, 1.31-3.75). Associations with MI or PCI (aHR: 1.56, 0.70-3.47), CABG (aHR: 2.66, 0.66-10.65), and composite outcome (aHR: 1.65, 95% CI: 0.79-3.46) were in the same direction, but lacked precision.

CONCLUSION: Aura without headache was associated with increased risks of stroke and atrial fibrillation or flutter; associations with remaining outcomes could not be ruled out.

PMID:40587417 | DOI:10.1093/ije/dyaf079

CJC Open. 2025 Mar 26;7(6):777-783. doi: 10.1016/j.cjco.2025.03.016. eCollection 2025 Jun.

ABSTRACT

Patients with chest pain and symptoms of acute coronary syndromes account for > 600,000 emergency department (ED) visits annually in Canada. Of these patients, 85% do not have acute coronary syndromes, and most are discharged from the ED after a thorough evaluation. However, a large proportion of these patients are referred for outpatient cardiac testing after ED discharge, even though their short-term risk of major adverse cardiac events (MACE), including death, new myocardial infarction, and need for revascularization, is very small. These referrals contribute to substantial low-value healthcare utilization, and limit access for those patients who are more likely to benefit from objective testing.Existing risk-prediction tools-developed prior to the advent of new high-sensitivity cardiac troponin assays-were derived in nonrepresentative populations, and when applied to ED patients with low cardiac troponin concentrations, systematically overestimate the short-term risk of MACE.This multicentre prospective cohort study will enroll ED patients with chest pain to derive and validate a novel risk prediction tool that distinguishes patients at low risk of MACE who do not require further cardiac testing from those who may benefit from additional cardiac testing. We will enroll 6500 patients in 13 Canadian EDs and prospectively follow them to ascertain a primary outcome of MACE within 30 days after their index ED encounter. The risk-prediction tool developed in this project will guide the safe, efficient, and appropriate referral of ED patients with chest pain.

CLINICAL TRIAL REGISTRATION: NCT06743672.

PMID:40586028 | PMC:PMC12198596 | DOI:10.1016/j.cjco.2025.03.016

CJC Open. 2025 Mar 22;7(6):719-724. doi: 10.1016/j.cjco.2025.03.012. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Our institution implemented a clinical pathway to facilitate early hospital discharge (EHD) in < 48 hours post-primary percutaneous coronary intervention for low-risk ST elevation myocardial infarction. This study characterizes the exclusion criteria, barriers, safety profile, and patient satisfaction for EHD.

METHODS: We prospectively identified all patients with ST-elevation myocardial infarction between January 2023 and March 2024. Patient characteristics, potential EHD barriers and 30-day readmission rates were recorded. A postdischarge telephone survey assessed patient satisfaction. Patients discharged at ≤ 48 hours formed the EHD cohort; those discharged later comprised the non-EHD cohort. Statistical comparisons were performed using the chi-squared and Mann-Whitney U tests, with logistic regression assessing EHD barriers.

RESULTS: Among 433 STEMI patients, 65% (n = 282) were ineligible for EHD, primarily due to revascularization needs (29%) or infarct-related complications (47%). Of 151 eligible patients, 72% (n = 109) achieved EHD. Afternoon presentations were associated with higher EHD rates (82% vs 61%, odds ratio = 3.5, 95% confidence interval 1.57-7.83, P = 0.002). Rates of 30--day readmission were lower in the EHD cohort (0% vs 7%, P = 0.007). Patient satisfaction (96% vs 95%, P = 0.841), perceived appropriate length of stay (91% vs 82%, P = 0.15), and intention to attend cardiac rehabilitation (63% vs 67%, P = 0.73) were comparable between cohorts.

CONCLUSIONS: Revascularization considerations and infarct-related complications were the most common reason for exclusion. Morning or overnight admissions were potential barriers to EHD, suggesting a role for optimized discharge planning. No adverse impacts on safety or patient satisfaction occurred.

PMID:40586018 | PMC:PMC12198500 | DOI:10.1016/j.cjco.2025.03.012

Theranostics. 2025 Jun 9;15(14):6737-6752. doi: 10.7150/thno.110162. eCollection 2025.

ABSTRACT

Rationale: Myocardial ischemia reperfusion (I/R) injury is a major cause of adverse outcomes following revascularization therapy. Although alterations in metabolic activities during reperfusion have been implicated, the molecular mechanisms underlying the pathogenesis of I/R injury remain elusive. Metaxin 2 (MTX2), initially identified as a core component of protein import complexes, has recently been characterized in diverse cellular functions. Nevertheless, its involvement in myocardial I/R injury has yet to be fully elucidated. In this study, we aim to evaluate the role and the underlying mechanism of MTX2 in I/R injury. Methods: The myocardial I/R model was established, and the protein levels of MTX2 were determined at different time points following coronary occlusion. Loss-of-function and gain-of-function strategies were applied via genetic ablation or intra-myocardial adenovirus injection to ascertain the role of MTX2 in myocardial I/R injury. RNA sequencing, seahorse metabolic analysis, and mass spectrometry were conducted to uncover the underlying molecular mechanisms. Results: We observed that the expression of MTX2 was significantly decreased in I/R hearts. Tamoxifen-induced cardiomyocyte-specific deletion of Mtx2 led to aggravated myocardial I/R injury, resulting in impaired cardiac oxidative phosphorylation and glycolysis. Mechanistically, dimeric PKM2, a less active pyruvate kinase form compared with tetrameric PKM2, was found to be dramatically accumulated in Mtx2 deficiency mice after myocardial I/R surgery. The TOM37 domain of MTX2 interacted directly with PKM2 to promote PKM2 tetramerization, thereby modulating glucose metabolic flux. Pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, rescued the metabolic and functional outcomes of I/R in Mtx2 deficiency mice. Conclusions: Our results identified, for the first time, a cardioprotective role of MTX2 in modulating cardiac glucose metabolism by facilitating PKM2 tetramerization. Targeting metabolic homeostasis by restoring MTX2 might be a promising therapeutic strategy to mitigate myocardial I/R injury.

PMID:40585998 | PMC:PMC12203670 | DOI:10.7150/thno.110162

Multimed Man Cardiothorac Surg. 2025 Jun 30;2025. doi: 10.1510/mmcts.2025.048.

ABSTRACT

Total arterial, anaortic, off-pump coronary artery bypass grafting is seen by many as a complex, specialized operation; however, when broken down into its component parts, it can be approached as multiple reproducible techniques that all trainees should master. These components include skeletonized mammary harvest, construction of composite arterial grafts and off-pump cardiac surgery. In this video tutorial, we describe step-by-step approaches to each of these elements and demonstrate how these principles come together to facilitate an excellent surgical outcome for the patient: revascularization of all diseased coronary arteries with arterial grafts while avoiding arresting the heart or aortic manipulation.

PMID:40583699 | DOI:10.1510/mmcts.2025.048

Acta Pharmacol Sin. 2025 Jun 30. doi: 10.1038/s41401-025-01604-9. Online ahead of print.

ABSTRACT

Circular RNAs (circRNAs) are a distinct class of endogenous RNAs characterized by their covalently closed circular structure. CircRNAs play crucial regulatory roles in various biological processes and pathogenesis. In this study we investigated the role of circRNAs in cardiomyocyte pyroptosis and underlying mechanisms. Ischemia/reperfusion (I/R)-induced myocardial injury was induced in mice by ligation of the left anterior descending coronary artery (LAD). Neonatal mouse cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) assault. By using circRNA microarray, we found that the expression levels of a pyroptosis-related circRNA (designated PYRCR) were markedly decreased in H/R-exposed cardiomyocytes and I/R-injured mouse hearts. Overexpression of PYRCR inhibited cardiomyocyte pyroptosis, attenuated I/R-induced myocardial infarction and ameliorated cardiac function in mice. By RNA pull-down assays coupled with MS analysis followed by molecular validation, we identified developmental regulated GTP-binding protein 2 (DRG2) as the direct downstream target of PYRCR. Cardiac-specific DRG2 knockout mice displayed attenuated pyroptosis and enhanced cardiac function following I/R injury compared to DRG2fl/fl controls. DRG2 directly bound to dynamin-related protein 1 (Drp1), the master regulator of mitochondrial fission, and enhanced its protein stability and expression. Importantly, PYRCR competitively disrupted the DRG2-Drp1 interaction, thereby suppressing DRG2-mediated Drp1 expression and subsequently reducing mitochondrial fission, cardiomyocyte pyroptosis, and myocardial damage. In conclusion, we demonstrate that PYRCR, a novel pyroptosis-related circRNA, protects against I/R-induced myocardial injury through the DRG2-mediated modulation of Drp1 activity, offering promising new therapeutic strategies for preventing cardiac damage mediated by cardiomyocyte pyroptosis.

PMID:40588510 | DOI:10.1038/s41401-025-01604-9

Theranostics. 2025 Jun 9;15(14):6737-6752. doi: 10.7150/thno.110162. eCollection 2025.

ABSTRACT

Rationale: Myocardial ischemia reperfusion (I/R) injury is a major cause of adverse outcomes following revascularization therapy. Although alterations in metabolic activities during reperfusion have been implicated, the molecular mechanisms underlying the pathogenesis of I/R injury remain elusive. Metaxin 2 (MTX2), initially identified as a core component of protein import complexes, has recently been characterized in diverse cellular functions. Nevertheless, its involvement in myocardial I/R injury has yet to be fully elucidated. In this study, we aim to evaluate the role and the underlying mechanism of MTX2 in I/R injury. Methods: The myocardial I/R model was established, and the protein levels of MTX2 were determined at different time points following coronary occlusion. Loss-of-function and gain-of-function strategies were applied via genetic ablation or intra-myocardial adenovirus injection to ascertain the role of MTX2 in myocardial I/R injury. RNA sequencing, seahorse metabolic analysis, and mass spectrometry were conducted to uncover the underlying molecular mechanisms. Results: We observed that the expression of MTX2 was significantly decreased in I/R hearts. Tamoxifen-induced cardiomyocyte-specific deletion of Mtx2 led to aggravated myocardial I/R injury, resulting in impaired cardiac oxidative phosphorylation and glycolysis. Mechanistically, dimeric PKM2, a less active pyruvate kinase form compared with tetrameric PKM2, was found to be dramatically accumulated in Mtx2 deficiency mice after myocardial I/R surgery. The TOM37 domain of MTX2 interacted directly with PKM2 to promote PKM2 tetramerization, thereby modulating glucose metabolic flux. Pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, rescued the metabolic and functional outcomes of I/R in Mtx2 deficiency mice. Conclusions: Our results identified, for the first time, a cardioprotective role of MTX2 in modulating cardiac glucose metabolism by facilitating PKM2 tetramerization. Targeting metabolic homeostasis by restoring MTX2 might be a promising therapeutic strategy to mitigate myocardial I/R injury.

PMID:40585998 | PMC:PMC12203670 | DOI:10.7150/thno.110162