Trasplante cardíaco

Am J Hematol. 2025 Oct 4. doi: 10.1002/ajh.70074. Online ahead of print.

ABSTRACT

Viscoelastic testing (VET) has evolved significantly since its inception in the mid-20th century, when it was first developed to guide transfusion strategies in trauma and surgical patients. Initially, VET technologies such as TEG and ROTEM assessed clot formation by measuring the mechanical resistance of a pin or piston within a blood sample. Recent advances have introduced automated, cartridge-based systems and novel detection methods-including resonance frequency and ultrasound-based sonorheometry-these new systems allow for more precise, rapid, and user-friendly assessment of clot dynamics at the point of care. VET is now indicated for a wide range of clinical scenarios where complex coagulopathy is anticipated, including trauma, cardiac surgery, liver transplantation, obstetric hemorrhage, and hematologic disorders such as DIC. Its use is expanding into new populations, including pediatric cardiac surgery, patients with inflammatory bowel disease, and those with COVID-19. However, VET remains limited in its ability to reliably detect therapeutic anticoagulants and certain congenital bleeding disorders, such as von Willebrand disease and deficiencies of protein C, S, and antithrombin. Technical limitations, including potential discrepancies between in vitro and in vivo clot formation, and lack of FDA approval for pediatric use have imposed implementation barriers to centers interested in pediatric VET. Looking forward, the integration of VET data with electronic medical records, the development of predictive models, artificial intelligence, and continued innovation in platelet function assessment and detection technologies are poised to enhance the clinical utility of VET. As guidelines and evidence continue to evolve, VET is positioned to become an increasingly important tool for real-time, individualized management of coagulopathy in diverse patient populations.

PMID:41045051 | DOI:10.1002/ajh.70074

Can J Cardiol. 2025 Oct 1:S0828-282X(25)01194-8. doi: 10.1016/j.cjca.2025.09.040. Online ahead of print.

ABSTRACT

Despite major advances in short-term outcomes after heart transplantation, long-term survival remains limited by chronic allograft dysfunction, with cardiac allograft vasculopathy (CAV) being the leading cause of late graft failure and an important cause of all-cause mortality. CAV is a unique and multifactorial form of transplant coronary vasculopathy, driven by a complex interplay of alloimmune responses, innate immune activation, and traditional cardiovascular risk factors. Recent insights from deep profiling of human allograft tissue have revealed the key roles of locally sustained T- and B-cell-mediated inflammation, macrophage-natural killer cell interactions, and chronic immune activation within the graft. These discoveries challenge prior models of systemic immune monitoring and highlight the importance of spatially organized, intragraft immune processes. In parallel, the diagnostic landscape of CAV is rapidly evolving. High-resolution imaging techniques such as optical coherence tomography, and advanced non-invasive tools including coronary computed tomography angiography and positron emission tomography, not only enable earlier and more precise detection of disease but also redefine the usual landscape of CAV diagnosis. New methods for individualized risk stratification, including trajectory modeling and machine learning-enhanced biopsy analysis, are paving the way for more personalized surveillance strategies. While current management remains focused on prevention, novel therapeutic targets are emerging, informed by a deeper understanding of CAV immunopathogenesis. This review provides an up-to-date synthesis of recent advances in CAV, with a focus on pathophysiology, individualized risk assessment, diagnostic innovation, and therapeutic perspectives, underscoring a paradigm shift toward more precise and proactive care in heart transplant recipients.

PMID:41043713 | DOI:10.1016/j.cjca.2025.09.040

Eur J Pharmacol. 2025 Oct 1;1007:178210. doi: 10.1016/j.ejphar.2025.178210. Online ahead of print.

ABSTRACT

Gut microbiome is an emerging contributor to various cardiovascular diseases (CVDs) where gut dysbiosis increases the risk of development and progression of atherosclerosis, coronary artery diseases, hypertension, and heart failure. Microbiota can also affect the metabolism of medications including cardiovascular drugs, resulting in alteration of their pharmacokinetics and pharmacodynamics or producing metabolites which can interfere with response of these drugs. Importantly, CVDs require prolonged pharmacological interventions with medications which may have impacts on the diversity and composition of gut microbiota. Gut microbiota modulation using diets, prebiotics, probiotics, fecal microbiota transplantation, antibiotics, and microbial trimethylamine-lyase inhibitors, has also shown benefits in the management of CVDs where gut microbiota and their metabolites have recently been studied as potential targets for the management of these diseases. Specifically, using innovative microbiota therapies in combination with traditional pharmacological agents have been evaluated for additional benefits in various CVDs. However, assessing the interactions among host factors, gut microbiome, and drug response will be essential for the development of new therapeutic targets for cardiovascular disorders, ultimately hoping better prognosis and patient's quality of life for those affected with CVDs.

PMID:41043575 | DOI:10.1016/j.ejphar.2025.178210

Eur J Cardiothorac Surg. 2025 Oct 3:ezaf333. doi: 10.1093/ejcts/ezaf333. Online ahead of print.

ABSTRACT

OBJECTIVES: Donor-recipient size matching in patients with pulmonary fibrosis may be performed according to the actual total lung capacity (aTLC) as measured by bodyplethysmography, the corrected total lung capacity (cTLC) and the predicted total lung capacity (pTLC). However, there is still no consensus on the ideal matching total lung capacity. Therefore, we aimed to analyze posttransplant outcomes of patients with pulmonary fibrosis listed according to aTLC, cTLC or pTLC.

METHODS: Patient records were retrospectively reviewed and analyzed using Bayesian statistics. Patients with pulmonary fibrosis who underwent double lung transplantation without concomitant lung reduction surgery were included.

RESULTS: Between November 2017 and May 2023, among the 521 patients who underwent lung transplantation at our institution, 122 (24%) were included, 11 (9%) forming the aTLC-group, 21 (17%) forming the cTLC-group and 90 (74%) forming the pTLC-group. Overall patient and graft mortality was decreased in patients who were listed according to aTLC when compared to cTLC (HR 0.11; 95% CrI 0-0.99). However, Bayesian Cox multivariable analysis revealed that this was due to the higher incidence of associated pulmonary hypertension and chronic renal failure in the cTLC group. No difference was seen in incidence of biopsy confirmed rejection and chronic lung allograft dysfunction.

CONCLUSION: Our study showed that listing patients according to aTLC improved mortality when compared to listing according to cTLC, because patients listed according to cTLC had a higher preoperative morbidity.

PMID:41042926 | DOI:10.1093/ejcts/ezaf333

Am J Physiol Renal Physiol. 2025 Oct 3. doi: 10.1152/ajprenal.00259.2025. Online ahead of print.

ABSTRACT

Renal dysfunction leads to critical health conditions, including acute kidney injury (AKI) and chronic kidney disease (CKD), and is a driver of hypertension. Despite their global prevalence and impact, the pathophysiology for all kidney disease subtypes is incompletely understood, therefore, many patients progress to kidney failure, needing dialysis and transplantation. This review highlights the role of pannexins-a family of channel-forming glycoproteins-in renal physiology and pathophysiology. Compared to other organ systems such as the brain and cardiovascular system, relatively little is known about the function of pannexins in the kidney. However, recent findings indicate that pannexins may be potential therapeutic targets in the treatment of hypertension, AKI, and CKD, though further research is needed to fully understand their precise role in renal health and disease.

PMID:41042800 | DOI:10.1152/ajprenal.00259.2025

Kardiol Pol. 2025 Oct 3. doi: 10.33963/v.phj.108922. Online ahead of print.

NO ABSTRACT

PMID:41042212 | DOI:10.33963/v.phj.108922

medRxiv [Preprint]. 2025 Sep 24:2025.09.22.25336215. doi: 10.1101/2025.09.22.25336215.

ABSTRACT

INTRODUCTION: After the 2018 allocation policy change, the rate of listings and transplants with durable LVADs has decreased significantly in favor of bridging patients from temporary mechanical circulatory support to heart transplant. The Organ Procurement and Transplantation Network (OPTN) recently approved a policy, to be implemented in September 2026, stipulating that patients supported by durable LVADs for 6 and 8 years will obtain statuses 3 and 2, respectively.

METHODS: Using OPTN data, we identified all adult heart transplant candidates with a durable LVAD implanted between October 18, 2018 and May 31, 2025. We estimated the cumulative incidence of status upgrades and durable LVAD-related complications, treating transplantation and waitlist removal before experiencing complications as competing events. We also assessed how the composition of the adult heart transplant waitlist on June 1, 2025 would have changed based on the upcoming policy change.

RESULTS: During the study period, 3,881 adult patients were listed for heart transplant with a durable LVAD. 3,182 (82.0%) of the durable LVADs were Abbott HeartMate 3, 568 (14.6%) were Medtronic Heartware HVAD, and 91 (2.3%) were Abbott HeartMate II. Transplant centers submitted a total of 6,924 justifications for status upgrades due to LVAD-related complications (6.3% status 1, 34.3% status 2, and 59.4% status 3) for 1,500 (38.6%) of these patients, with a median of 3 per patient. The cumulative incidence of complications or status upgrades was 38.6% [95% CI (37.1%, 40.2%)]. Nearly all of the 2,381 patients who did not experience any complication or status upgrade during listing were removed from the waitlist by 6 years. Had the upcoming OPTN policy change been implemented on June 1, 2025, the proportion of the waitlist that would have achieved higher priority status instantaneously was 0.06%.

CONCLUSIONS: The cumulative incidence of status upgrades and complications among heart transplant candidates with durable LVADs was nearly 40% within 6 years of device implantation. The upcoming OPTN policy to escalate patients to statuses 3 and 2 after 6 and 8 years of durable LVAD support, respectively, is unlikely to make a meaningful impact on waitlist priority status.

PMID:41040709 | PMC:PMC12485994 | DOI:10.1101/2025.09.22.25336215

J Soc Cardiovasc Angiogr Interv. 2025 Aug 19;4(9):103804. doi: 10.1016/j.jscai.2025.103804. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: Although adverse events (AEs) are common during congenital cardiac catheterization procedures, many have little impact beyond the catheterization laboratory. We sought to identify factors that are associated with an increased length of stay (LOS).

METHODS: A total of 10,882 cases from the C3PO-quality improvement registry dataset from January 2014 to December 2017 admitted electively on the same day of cardiac catheterization were analyzed and independent risk factors for a prolongation of LOS were identified.

RESULTS: Length of stay ranged from 0 to 305 days. The incidence of higher severity AE was significantly higher for cases that had a hospital stay of 2 days or more, compared to those discharged the same day or day 1 after the procedure (15% vs 2%, P < .001). Seven percent of patients without any AE in the cardiac catheterization laboratory had a prolonged LOS of 2 days or more. Significant independent risk factors for a prolongation of LOS included age <1 year, single ventricle diagnosis, cardiac surgery within the last 90 days, a higher hemodynamic vulnerability score, a higher PREDIC3T risk category, a prolonged procedure time, contrast usage >6 mL/kg, operators experience of either <5 or ≥25 years, and operator case volume >200 cases/y. The presence of any level 3bc, 4, or 5 AE had the highest associated odds of an increased LOS (OR, 5.9; 95% CI, 4.6-7.6).

CONCLUSIONS: Prolonged admission after outpatient catheterization is a potential alternative measure of safety after pediatric or congenital cardiac catheterization. It is independently associated not only with patient, procedure, and operator factors that have previously been described to be associated with the risk of AE but also with other factors such as the presence of single ventricle physiology. Further studies are needed to further evaluate its utility.

PMID:41040445 | PMC:PMC12485507 | DOI:10.1016/j.jscai.2025.103804

Innovations (Phila). 2025 Oct 3:15569845251375996. doi: 10.1177/15569845251375996. Online ahead of print.

NO ABSTRACT

PMID:41040037 | DOI:10.1177/15569845251375996

Expert Opin Drug Discov. 2025 Oct 3:1-13. doi: 10.1080/17460441.2025.2562020. Online ahead of print.

ABSTRACT

INTRODUCTION: Cancer cachexia (CC) is a multifactorial syndrome characterized by progressive weight loss, anorexia, and loss of skeletal muscle and fat mass, resulting in reduced quality of life and poor prognosis. Currently, there are no approved pharmacological treatments for CC, highlighting the urgent need for developing novel experimental models.

AREA COVERED: This review covers recent advancements in preclinical models of CC, highlighting their implications for drug discovery and therapeutic development. The literature search was conducted in PubMed up to April 2025.

EXPERT OPINION: CC remains clinically challenging and requires improved translational research and therapeutic strategies. Improved preclinical models, such as personalized patient-derived xenograft models incorporating patient-specific immune profiles and microbiota, hold promise for precision medicine. Identification of standardized extracellular vesicle (EV) derived biomarkers and effective targeting of EV signaling pathways are critical research directions. In addition, clinical validation of appetite regulators such as glucagon-like peptide-1 and growth differentiation factor-15, along with comprehensive approaches integrating diet, exercise, and targeted pharmacological interventions, will be pivotal. Finally, multidisciplinary collaboration is essential to translate these findings into meaningful therapies that will ultimately improve patient prognosis and quality of life.

PMID:41039997 | DOI:10.1080/17460441.2025.2562020

J Hypertens. 2025 Sep 15. doi: 10.1097/HJH.0000000000004151. Online ahead of print.

ABSTRACT

OBJECTIVE: Rarefaction in capillary density is a hallmark of hypertension-mediated microvascular damage. This study aimed to assess the association between clinically accessible inflammatory markers, including the systemic immune-inflammation index (SII), and retinal capillary density, as well as other indicators of microvascular damage.

METHODS: We conducted a cross-sectional analysis of data from 132 consecutive patients with established primary hypertension at the Royal Perth Hospital's tertiary hypertension clinic. All patients underwent noninvasive optical coherence tomographic angiography (OCT-A) for the assessment of retinal capillary density in the foveal region (CDF) and blood sampling for inflammatory markers. We examined the association of the SII - calculated as the product of the neutrophil-lymphocyte ratio and platelet count - and its individual components with retinal capillary rarefaction and other markers of microvascular damage, such as the urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). The results were adjusted for relevant co-variates, including age, sex, 24-h SBP, BMI, antihypertensive medications, lipid levels, and diabetes status.

RESULTS: Retinal capillary rarefaction was associated with increased white cell count, particularly neutrophils, and the SII. Through predictive margin analysis, an optimal cut-off value of 600 x 109/l for SII was determined for median CDF of 34.1 mm2. The analysis showed a reduction in CDF of 1.3 mm2 for every 250 x 109/l increase in SII. Additionally, higher SII levels (≥ 600 x 109/l) were associated with elevated high-sensitivity C-reactive protein (hs-CRP) levels and markers of microvascular damage, such as increased UACR and reduced eGFR.

CONCLUSION: In patients with primary hypertension, SII and related inflammatory markers were associated with retinal rarefaction and renal indices of microvascular damage. SII may serve as a useful clinical marker of microvascular damage in the retinal and renal vascular bed.

PMID:41039760 | DOI:10.1097/HJH.0000000000004151

Orphanet J Rare Dis. 2025 Oct 2;20(1):497. doi: 10.1186/s13023-025-03943-6.

ABSTRACT

OBJECTIVE: To evaluate the clinical outcomes of liver transplantation (LT) in patients with Caroli syndrome.

METHODS: We retrospectively analyzed clinical data from 20 patients diagnosed with Caroli syndrome who underwent LT at Beijing Friendship Hospital, Capital Medical University, between April 2014 and May 2024. Data included baseline characteristics, surgical parameters, complications, and survival. Follow-up concluded in February 2025.

RESULTS: These 20 cases accounted for 1.23% (20/1623) of all LTs during the study period. Thirteen patients received living donor liver transplants (LDLT), and seven received deceased donor liver transplants (DDLT). The cohort included 15 males and 5 females, aged 3–56 years (median 23.3). Common preoperative conditions included cirrhosis (n = 18), portal hypertension (n = 17), polycystic kidney disease (n = 16), and splenomegaly (n = 17). The median APACHE II score was 14; the predicted mortality averaged 26.0%. The median interval from the first major complication (e.g., recurrent cholangitis or decompensation) to LT was 12 months (IQR 4.5–21). No patients underwent cross-match or auxiliary LT; three had concurrent partial splenectomy. Postoperative complications included abdominal hemorrhage (n = 3) and seizures (n = 1). Chronic renal failure occurred in six patients during follow-up, and four experienced acute rejection (three recurrent). Compared with adults, pediatric patients had a higher proportion of females (p = 0.001), while chronic renal failure was more common in adults preoperatively (p = 0.010). Four patients (20%) died: one from heart failure (day 8), one from sudden death (6 months), one from pulmonary infection (1 year), and one from unknown causes (5.2 years). Median follow-up was 74.6 months (range 7-125). One-, three-, and five-year survival rates were 90%, 85%, and 78.5%, respectively.

CONCLUSION: Liver transplantation significantly improves the survival prognosis for patients with Caroli syndrome, but attention to kidney function preservation and individualized immunosuppressive management is critical for optimal outcomes.

PMID:41039418 | PMC:PMC12492817 | DOI:10.1186/s13023-025-03943-6

Lancet Oncol. 2025 Oct;26(10):1382-1392. doi: 10.1016/S1470-2045(25)00399-7.

ABSTRACT

BACKGROUND: The four-stage American Joint Committee on Cancer (AJCC) staging system has been used for almost 50 years for assessing the risk of multiple cancers; the AJCC classification for papillary thyroid cancer is solely based on clinical parameters, and despite updated editions its accuracy remains suboptimal. We aimed to evaluate whether the performance of the AJCC system could be improved by integrating tumour genetic statuses of BRAF and TERT genes.

METHODS: This retrospective multicentre cohort study used patient medical records from 15 medical centres across ten countries for patients (of all ages) with papillary thyroid cancer who had been surgically treated with total thyroidectomy or hemithyroidectomy with or without neck dissection, followed by postoperative radioiodine ablation and appropriate thyroid-stimulating hormone level targeting. Testing for BRAFV600E and TERT promotor (TERTp) mutations was performed on genomic DNA isolated from surgical or cytological specimens of primary papillary thyroid cancer tumours at each centre. Data from all medical centres were pooled for aggregated analyses of the relationship between the genetic status and papillary thyroid cancer-specific mortality for each of the four classical stages of the 7th and 8th editions of the AJCC system (AJCC7E and AJCC8E). The primary endpoint was papillary thyroid cancer-specific mortality, characterised by mortality rates per 1000 person-years.

FINDINGS: Using patients who were treated for papillary thyroid cancer between January 1979, to July 2023 at the 15 centres, our cohort comprised of 4746 patients (3612 [76·1%] females and 1134 [23·9%] males), with median age of 48 years (IQR 37-59; 89 [1·9%] patients aged ≤18 years). For the 4400 patients with available ethnicity data, the majority were Asian (2140 [48·6%]) and 2096 (47·6%) were White. For AJCC7E, compared with the original stages, the genetic duet of BRAFV600E and TERTp mutations was associated with increased mortality in all stages versus the corresponding original stages, although the HR for stage I did not reach statistical significance. Those with wildtype BRAFV600E and TERTp had flat survival curves for stages I-III with AJCC7E and stages I-II of AJCC8E. Patients with dual mutations had reductions in survival across all stages for the AJCC7E (stage I HR 5·96 [95% CI 0·73-48·66]; p=0·10; stage II 5·94 [95% CI 1·42-24·91]; p=0·015; stage III 4·04 [95% CI 1·87-8·70]; p=0·00037; and stage IV 1·79 [95% CI 1·15-2·76]; p=0·0092). TERTp mutation alone was also significantly associated with a significant increase in mortality for stage IV (3·57 [2·01-6·37]; p<0·0001). For AJCC8E, we observed a similar pattern of increased mortality when both mutations were present compared to mortality in the original staging, with significant differences in HR for stages I and II (stage I adjusted HR 10·30 [95% CI 3·43-30·93], p<0·0001; stage II HR 3·95 [95% CI 1·92-8·15]; p=0·00020). Stage III also showed increased mortality with dual mutations, but the increase was not statistically significant (HR 1·77 [0·95-3·31]; p=0·072). In contrast to AJCC7E, the dual mutations did not increase mortality compared with the original stage IV (HR 0·95 [0·47-1·92], p=0·89), but the TERTp mutation did significantly increase mortality in stage IV papillary thyroid cancer (HR 2·75 [1·36-5·58], p=0·0049).

INTERPRETATION: Integrating the genetic statuses of BRAF and TERTp into the AJCC system changes the original risk stages of the AJCC system and significantly improves the accuracy of its mortality risk classification for papillary thyroid cancer.

FUNDING: National Institute on Aging, the Auburn Community Cancer Endowed Chair in Basic Research, the Heart, Breast, and Brain Health Equity Research program, National Institutes of Health, and the American Association for Cancer Research Fellowship 21-40-69-ESTR (USA); Ministry of Health (Czech Republic); Prémio Francisco Augusto da Fonseca Dias e Maria José Melenas da Fonseca para Jovens Investigadores (Portugal); Italian Ministry of Health-Ricerca Corrente (Italy); JSPS KAKENHI (Japan); MINCIENCIAS, L'OREAL-UNESCO-ICETEX-COLCIENCIAS, Universidad del Tolima (Colombia); STRATEGMED2/267398/4/NCBR/2015, the National Centre for Research and Development (Poland); RISBIN IPTEKDOK 2014, Ministry of Health (Indonesia); and the Information and Communications Technology and Future Planning of the Basic Science Research Program via the National Research Foundation of Korea (NRF) funded by the Ministry of Science (Korea).

PMID:41038186 | DOI:10.1016/S1470-2045(25)00399-7

Ann Thorac Surg. 2025 Sep 30:S0003-4975(25)00904-X. doi: 10.1016/j.athoracsur.2025.08.058. Online ahead of print.

NO ABSTRACT

PMID:41038360 | DOI:10.1016/j.athoracsur.2025.08.058

Discov Oncol. 2025 Oct 2;16(1):1797. doi: 10.1007/s12672-025-03676-9.

ABSTRACT

BACKGROUND: Molecular genetic tests are increasingly used to determine the need for surgery in thyroid nodules with indeterminate fine-needle aspiration (FNA) cytopathology. However, the accuracy of these tests remains uncertain. This systematic review and meta-analysis analyze the diagnostic performance of molecular testing in pre-operative FNA biopsies from indeterminate thyroid nodules (ITN).

METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The preoperative FNA cytopathology from patients over 14 years old, and the postoperative histopathology results were extracted. It was also essential to include true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) counts, along with genetic testing results. Sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) were calculated for each molecular panel using a random-effects bivariate model.

RESULTS: Overall, 68 studies (2018–2024) were eligible discussing 7 different panels, from 16 countries. Multigene Point-of-care Test (MPTX v1) demonstrated the strongest ability to rule out malignancies (NLR 0.12; n = 4) and exhibited the highest diagnostic value (DOR 18; n = 4). ThyroSeq v2 Next-Generation Sequencing Test for Thyroid Cancer (ThyroSeq v2) followed with a DOR of 10 (n = 9). The PCR groups(n = 20) could not be merged due to significant methodological heterogeneity.

CONCLUSION: This meta-analysis highlights the role of molecular testing in improving the diagnostic accuracy of indeterminate thyroid nodules, potentially reducing unnecessary surgeries. However, further standardization and validation are needed due to study heterogeneity.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-03676-9.

PMID:41037201 | PMC:PMC12491129 | DOI:10.1007/s12672-025-03676-9

JACC Heart Fail. 2025 Sep 29:102683. doi: 10.1016/j.jchf.2025.102683. Online ahead of print.

NO ABSTRACT

PMID:41037042 | DOI:10.1016/j.jchf.2025.102683

Circulation. 2025 Oct 2. doi: 10.1161/CIRCULATIONAHA.125.074971. Online ahead of print.

ABSTRACT

BACKGROUND: Porcine genome editing has revolutionized xenotransplantation, recently enabling the first pig-to-human heart xenotransplants. However, the xeno-immune response in heart xenografts remains largely unexplored. This study aimed to precisely characterize the xeno-immune response and injury in two heart xenografts, transplanted from 10-gene-edited pigs into brain-dead human recipients.

METHODS: We analyzed xenograft biopsies at 66-hour post-reperfusion using a multimodal phenotyping approach combining: morphological evaluation, immunophenotyping, ultrastructural assessment, automated quantification of multiplex immunofluorescence staining and gene expression profiling. Xenografts before implantation and wild-type pig hearts with and without ischemia reperfusion injury and brain death were used as controls.

RESULTS: Both xenografts showed evidence of endothelial activation and mild microvascular inflammation without capillary C4d deposition. Immune infiltrates were mainly composed of CD15+ and CD68+ innate immune cells. Ultrastructural assessment showed endothelial swelling with occasional intravascular leucocytes. Deep-learning based automated multiplex immunofluorescence analysis confirmed that microvascular inflammation was primarily associated with CD15+ and CD68+ innate immune cells. Both xenografts showed increased expression of genes and pathways associated with monocyte/macrophage activation, neutrophil activation, interferon-gamma response, natural killer cell burden, endothelial activation, apoptosis and injury repair. This phenotype was absent in all control pig hearts, independently from ischemia reperfusion injury and brain death.

CONCLUSIONS: Multimodal phenotyping of pig-to-human heart xenografts revealed early signs of xeno-immune response, characterized by mild innate microvascular inflammation, endothelial activation, and molecular signature characteristic of antibody-mediated rejection. Developing such precision diagnostic system could improve graft monitoring in future clinical settings.

PMID:41036838 | DOI:10.1161/CIRCULATIONAHA.125.074971

Front Med (Lausanne). 2025 Sep 16;12:1631873. doi: 10.3389/fmed.2025.1631873. eCollection 2025.

ABSTRACT

Pulmonary mucormycosis caused by Rhizopus arrhizus is an emergent, fulminant threat in immunocompromised hosts, yet therapeutic success remains elusive when extracorporeal membrane oxygenation (ECMO) is required. While liposomal amphotericin B (L-AMB) is endorsed as first-line therapy, its pharmacokinetics are profoundly altered by ECMO-dilution, circuit sequestration, and impaired lung penetration all conspire to sub-therapeutic exposure. We report the first documented case in which these challenges were systematically overcome. A 52-year-old cardiac-transplant recipient, supported on veno-venous ECMO for refractory hypoxaemia, developed rapidly progressive pneumonia. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid returned a definitive Rhizopus arrhizus signature within 24 h, prompting immediate escalation to high-dose L-AMB (10 mg/kg/day). Therapeutic drug monitoring confirmed sustained trough levels above 7 μg/mL despite a 3.5-fold increase in volume of distribution. Serial mNGS quantification demonstrated a logarithmic decline in fungal reads to undetectable levels by day 10, accompanied by radiological resolution and preserved renal function. After 28 days of intravenous therapy, the patient was discharged on oral isavuconazole with no relapse at 6 months. This case establishes that early pathogen identification by mNGS, coupled with aggressive L-AMB dose optimisation under rigorous pharmacokinetic guidance, can achieve cure of pulmonary mucormycosis even in the most pharmacologically hostile environment of ECMO support.

PMID:41035876 | PMC:PMC12479246 | DOI:10.3389/fmed.2025.1631873

Bioact Mater. 2025 Sep 17;55:114-130. doi: 10.1016/j.bioactmat.2025.06.044. eCollection 2026 Jan.

ABSTRACT

Myocardial infarction (MI) remains a leading cause of heart failure due to the limited regenerative capacity of the adult myocardium. The therapeutic efficacy of current engineered cardiac patches is hindered by their simplistic scaffold composition and lack of structural organization. This study presents a bioactive, anisotropic extracellular matrix (ECM) scaffold derived from human induced pluripotent stem cell-differentiated cardiac fibroblasts (hiPSC-CF-ECM) that combines cardiac-specific proteins and growth factors with complex structural composition. Compared to primary cardiac fibroblast ECM (pri-CF-ECM) and human dermal fibroblast ECM (hDF-ECM), hiPSC-derived cardiomyocytes (hiPSC-CMs) cultured on the cardiac-specific ECM scaffold exhibited enhanced maturation, as confirmed by bulk RNA sequencing, electrophysiological mapping, and optical-based strain analysis. In an immune-competent rat MI model, the hiPSC-CF-ECM transplantation preserved cardiac function, increased ejection fraction, and reduced maladaptive remodeling. These findings highlight hiPSC-CF-ECM as a promising biomimetic scaffold for cardiac tissue engineering and MI treatment.

PMID:41035426 | PMC:PMC12481509 | DOI:10.1016/j.bioactmat.2025.06.044

Anesth Pain Med (Seoul). 2025 Oct 2. doi: 10.17085/apm.25278. Online ahead of print.

NO ABSTRACT

PMID:41035294 | DOI:10.17085/apm.25278