Background:In the context of cardiac surgery, morbid obesity poses several perioperative challenges. Some surgeons consider obesity a relative contraindication for minimally invasive aortic valve replacement (MIAVR) due to anatomical and technical complexities. Although MIAVR is increasingly used in standard-risk populations, evidence supporting its safety and efficacy in morbidly obese patients remains limited. Methods:This retrospective cohort consisted of 920 patients who underwent MIAVR via partial upper ministernotomy at a high-volume cardiac surgery center between 2010 and May 2025. Patients were categorized into three groups based on BMI: Class I obesity (BMI 30-35 kg/m2; n = 164), Class II-III obesity (BMI > 35 kg/m2; n = 54), and a non-obese control group (n = 702). Key clinical outcomes, echocardiographic parameters, postoperative complications, and long-term mortality rates were compared. Additionally, a pairwise meta-analysis was conducted, incorporating five studies to assess outcomes of MIAVR vs. conventional full sternotomy in obese individuals. Results:There were no significant differences in most of postoperative outcomes. However, higher rates of pneumothorax and arrhythmias were observed in Class II-III obesity. Multivariate regression did not identify obesity as an independent predictor of adverse outcomes. Meta-analysis confirmed comparable operative times and a trend toward shorter ICU stays and lower respiratory complications in the MIAVR group. Conclusion:This study argues that (i) obesity alone should not delay, deter, or preclude appropriate candidates from being referred for surgical aortic valve replacement, and (ii) partial upper ministernotomy should be considered the preferred access route in obese patients, as it consistently facilitates recovery without compromising safety.

RATIONALE:Restrictive allograft syndrome (RAS) is a major cause of mortality following lung transplantation due to progressive fibrosis of the lung allograft with no therapeutic options. Knowledge of the cellular and molecular mechanisms driving fibrosis in RAS remains limited. OBJECTIVE:To characterize the cellular and molecular changes in human RAS lungs through single-cell transcriptomic profiling. METHODS:Single-nucleus RNA-sequencing (snRNA-seq) was performed in peripheral lung tissues from 15 RAS patients undergoing lung re-transplantation, and from 9 healthy control lungs. Findings were validated and extended using histologic techniques including immunofluorescence, RNA in situ hybridization, Elastica-van-Gieson immunohistochemistry, quantitative histological analyses, and micro-CT scans. MEASUREMENTS AND MAIN RESULTS:snRNA-seq analysis of RAS lungs revealed previously undescribed aberrant basaloid cells, ectopic COL15A1+ peribronchial vascular endothelial cells (pVECs), and CTHRC1+ fibrotic fibroblasts. Histologic stains disclosed distinctive distribution patterns: aberrant basaloid cells, primarily localized at the fibrotic edge, together with juxtaposed CTHRC1+ fibrotic fibroblasts and ectopic COL15A1+ pVECs form the fibrotic niche of alveolar fibroelastosis (AFE). PRX+ alveolar microvasculature is partially lost in AFE areas. Micro-CT scans revealed changes from pulmonary to systemic perfusion, facilitated by COL15A1+ pVECs. Last, our data reveals potential therapeutic targets in RAS, including integrin αvβ6, activator of TGFβ. CONCLUSION:Considering the multifaceted differences of RAS and idiopathic pulmonary fibrosis, we revealed a surprising general principle of an entity-spanning composition of the fibrotic niche by aberrant basaloid cells localized at the fibrotic edge, ectopic COL15A1+ pVECs and CTHRC1+ fibrotic fibroblasts. This suggests a flexible but cellular pathogenesis-guided transferability of potential therapeutic approaches between progressive fibrotic lung diseases.

OBJECTIVES:This study presents the 5-year experience with a more liberal intraoperative extracorporeal membrane oxygenation (ECMO) elective support in patients with pulmonary fibrosis (PF) undergoing lung transplantation (LTx). METHODS:Patients with PF undergoing LTx between January 2012 and January 2025 were included and sub-divided into the period before and after the implementation of a more liberal intraoperative use of ECMO support in January 2020. Outcomes were compared between elective, non-elective, and no intraoperative ECMO in both periods. Previously-identified parameters as decision criteria for elective ECMO were examined. RESULTS:Overall, 422 PF patients underwent LTx, of whom 273 patients were transplanted before 2020 (elective ECMO, n = 52 (19%); non-elective ECMO, n = 30 (11%); no ECMO, n = 191 (70%)) and 149 patients were transplanted since 2020 (elective intraoperative ECMO, n = 98 (66%); non-elective ECMO, n = 12 (8%); no ECMO, n = 39 (26%)). After 2020, elective ECMO was increasingly used in patients with mean pulmonary arterial pressure >50 mmHg and pulmonary vascular resistance >9.4 WU. However, 8% were not identified based on these parameters and still required non-elective ECMO. Comparing pre- and post-2020, primary graft dysfunction (PGD) grade 3 72 h post-transplant between elective (17% vs 3%, P = .002), non-elective (38% vs 0%, P = .016), and no ECMO (12% vs 3%, P = .078) was significant reduced. One-year graft survival in elective (88.5% vs 95.6%), non-elective (70% vs 91.7%), and no ECMO (92.7% vs 94.9%) showed a trend towards improved survival. CONCLUSIONS:The use of a more liberal, elective intraoperative ECMO support in patients with PF led to an improvement of PGD prevalence and survival early after lung transplantation.

Background/Objectives: Transcatheter aortic valve implantation (TAVI) has become the leading treatment option for patients suffering from aortic valve stenosis aged over 70, except in cases of specific contraindications like bicuspid valves, inappropriate access routes, or endocarditis. Minimally invasive aortic valve replacement (MIAVR) has emerged as a potential way to combine the durability of surgery with reduced procedural trauma. This study aims to assess the safety and feasibility of MIAVR in elderly patients. Methods: A total of 990 patients were included in this retrospective cohort study. Among them, 261 (26%) were aged 70 years or older (elderly cohort), and 729 (74%) were younger than 70 years (younger cohort). All patients were followed for at least 30 days postoperatively, with survival data collected through May 2025. Multivariable logistic regression, linear regression, and Kaplan-Meier survival analyses were performed. Results: Elderly patients were more likely to be female (51% vs. 40%, p = 0.001) and carried a heavier burden of vascular and renal comorbidity: renal impairment 33% vs. 17% and extracardiac arteriopathy 45% vs. 30% (both p < 0.001). Major bleeding occurred more frequently in the elderly cohort (7.7% vs. 4.1%; p = 0.02), as did new permanent pacemaker implantation (10% vs. 5.8%; p = 0.021) and sepsis (3.4% vs. 1.1%; p = 0.012). Rates of stroke, perioperative myocardial infarction, ECMO/right-heart failure, re-thoracotomy, and postoperative dialysis were low and comparable across age groups (all p > 0.20). Overall, 30-day mortality was 2.4% (24/990), with crude mortality approximately threefold higher among patients aged ≥70 years (4.6% vs. 1.6%). Conclusions: Our findings indicate that MIAVR is a feasible and safe surgical option across age groups; Elevated morbidity in elderly patients is primarily due to bleeding, pacemaker implantation, and sepsis, while rates of stroke, renal failure, and myocardial infarction are low.

Measuring C-terminal α1-AT peptides before lung transplantation offers a promising approach for early CLAD risk stratification https://bit.ly/4hneqXr.

Background: Minimally invasive approaches for multivalve surgery have attracted increasing interest; however, data on combined aortic and mitral valve replacement or repair using via right anterior minithoracotomy remain quite limited. This study aimed to evaluate the feasibility, safety, and early outcomes of minimally invasive concomitant aortic and mitral valve replacement or repair using this approach. Methods: This retrospective study included 24 patients who underwent simultaneous aortic and mitral valve procedures via right anterior minithoracotomy. We collected preoperative, intraoperative, and postoperative data, assessing echocardiographic parameters. Early clinical outcomes, complications, and mortality rates were analyzed, with correlations between EuroSCORE II and outcomes explored. Results: The median follow-up was 412 days. All procedures were completed successfully without conversion to sternotomy. Postoperative echocardiography demonstrated a significant reduction in transvalvular gradients, with aortic mean pressure gradient decreasing from 51.3 ± 23.0 mmHg to 6.7 ± 1.7 mmHg (p < 0.001) and mitral mean pressure gradient from 19.3 ± 26.7 mmHg to 4.0 ± 1.4 mmHg (p < 0.001), while left ventricular ejection fraction remained unchanged (p = 0.67). During the study period, one patient died from a non-cardiac cause. EuroSCORE II showed a moderate positive correlation with intensive care unit length of stay (p = 0.011) but not with hospital stay or operative times. Conclusions: Minimally invasive aortic and mitral valve replacement or repair via right anterior minithoracotomy is feasible and was associated with favorable early hemodynamic and clinical outcomes in this single-center cohort.

Background:Fibroblasts are important contributors to collagen deposition in interstitial lung diseases (ILD), but their inflammatory role in acute exacerbation of ILD including idiopathic pulmonary fibrosis is currently undefined. Methods:Using a well-described model of Streptococcus pneumoniae-induced exacerbation of lung fibrosis in mice, we found that platelet-derived growth factor receptor A-positive lung fibroblasts developed an early inflammatory phenotype upon infection, including increased production of serum amyloid A (SAA) proteins, as determined by RNA sequencing, single-cell RNA sequencing and secretome profiling of sorted lung fibroblasts. Results:Lung fibroblasts responded to pneumococcal challenge with increased SAA mRNA and protein levels in vitro. SAA levels were significantly elevated in bronchoalveolar lavage (BAL) and plasma of mice with S. pneumoniae-induced exacerbation of adenoviral vector delivery of active transforming growth factor-β1- or bleomycin-induced lung fibrosis. Antibiotic therapy caused a significant drop in SAA levels in BAL and plasma of mice with infection-driven fibrosis exacerbation. Finally, levels of SAA protein were dramatically increased in plasma of patients with acute exacerbation of ILD, but not in patients without exacerbation. Conclusion:Analysis of plasma levels of SAA protein may aid in the identification of underlying inflammation in patients with ILD who are more likely to deteriorate towards a critical clinical stage during acute exacerbation.

Abstract Background Alveolar type II (AT-II) epithelial cells are essential for alveolar repair, immune regulation, and surfactant secretion. Despite their promise for pulmonary disease modeling, limited access and culture methods hinder translational use. We established a patient-derived 3D AT-II organoid system from fibrotic and non-fibrotic lung tissue to maintain AT-II-associated features, enable cryopreservation, and capture disease-associated metabolic alterations. Methods HT-II-280+ AT-II cells were isolated by magnetic bead sorting from 63 lung tissues (15 idiopathic pulmonary fibrosis, 26 secondary fibrosis, 22 tumor-distant controls). Cells were expanded as organoids in 3D culture from initial passage 0 up to passage 3. AT-II-associated features were assessed by immunofluorescence, flow cytometry, and transmission electron microscopy. Cryopreserved cells were recovered after ≥ 28 days and tested for viability and organoid-forming capacity. Metabolic profiling was performed using extracellular flux assays. Results AT-II cells were successfully (~ 80%) isolated and combined with a serum- free feeder-free culturing approach to reproducibly generated alveolospheres with highly efficient colony formation (> 90% in P1), especially in AT-II cells from fibrotic explants. Primary tissue-derived lung organoids display heterogeneous morphologies and sizes, most prominently in fibrotic-derived cultures, as indicated by histology and microcomputed tomography. Culture conditions were optimized to minimize differentiation towards AT-I cells or dedifferentiated epithelial states with partial basaloid features. Expression of key AT-II-associated markers (proSP-C, HT-II-280), and the presence of lamellar bodies were maintained across passages at the population level. Cryopreservation maintained high viability, organoid-forming capacity, and metabolic activity, enabling long-term storage. Fibrotic organoids exhibited disease-associated metabolic reprogramming characterized by a pronounced glycolytic shift with increased ATP production. Conclusion We established a reproducible cell-line-free 3D culture system from primary human AT-II cells of end-stage ILD lungs to generate patient-derived lung organoids. These organoids maintain AT-II-associated features across passages, remain viable after cryostorage, and capture disease-associated metabolic reprogramming. Fibrotic-derived AT-II cells consistently demonstrated a Warburg-like glycolytic phenotype, reflecting increased energy demand. This scalable model in vitro provides a defined resource for mechanistic studies of epithelial dysfunction in pulmonary diseases and supports biobanking for future precision medicine applications.

BACKGROUND:Surgical access for bilateral lung transplantation (BLTx), including clamshell, sternotomy, and isolated bilateral thoracotomies (IBT), may influence perioperative outcomes. We analyzed the international ECLS Registry to assess the impact of access type on perioperative outcomes and graft survival. METHODS:Adult BLTx performed from January 2016 to August 2024 across 12 centers was reviewed. Patients were grouped as being transplanted through clamshell (n = 451, 37.6%), IBT (n = 624, 52.0%), or sternotomy (n = 125, 10.4%). Three 1:1 propensity score-matched comparisons were performed: clamshell vs IBT, clamshell vs sternotomy, and IBT vs sternotomy. RESULTS:Before matching, baseline characteristics differed significantly across surgical approaches, including BMI (25.2 vs 23.6 vs 24.3 kg/m², p < 0.001), diabetes (19.3% vs 14.9% vs 16.8%, p < 0.001), pulmonary hypertension (4.2% vs 4.8% vs 5.6%, p < 0.001), and intraoperative extracorporeal life support (ECLS) use (p < 0.001). After matching, IBT patients showed longer ischemic times (p< 0.001) but less intraoperative ECLS use, shorter ventilation and ICU stays (p < 0.001), lower reintubation (p = 0.021 vs clamshell; p = 0.045 vs sternotomy), fewer reoperations for bleeding (p = 0.190 vs clamshell; p = 0.018 vs sternotomy), and lower transfusion needs (p< 0.001). At 1 year, IBT was associated with higher pulmonary function and improved unadjusted graft survival than clamshell patients (1-year: 91% vs 86%; 3-year: 74% vs 63%; 5-year: 51% vs 49%; p = 0.007). CONCLUSION:Surgical access in BLTx affects perioperative morbidity and recovery. IBT was associated with improved early/intermediate graft survival compared with clamshell incision, although the absolute difference was attenuated at 5 years. Incision choice should be tailored to patient profile, procedural demands, and institutional expertise.

The concomitant repair of severe pectus excavatum and mitral valve regurgitation presents distinct technical and physiological challenges. Although staged or open combined procedures have been described, a truly single-stage, minimally invasive strategy remains uncommon. We report the case of a 22-year-old woman with a “Grand Canyon–type” pectus excavatum and bileaflet mitral valve prolapse who successfully underwent a concomitant operation combining a modified cross-bar Nuss repair and minimally invasive mitral valve repair. This integrated approach allowed optimal cardiac exposure, restoration of thoracic geometry, and effective valve reconstruction through a right mini-thoracotomy. The patient experienced an uneventful recovery with excellent cosmetic and functional results. This case highlights the feasibility and advantages of a single-stage, single-recovery minimally invasive approach for the correction of concurrent chest wall deformity and valvular disease. Background Pectus excavatum (PE) is the most common anterior chest wall deformity and may lead to significant cardiopulmonary compromise from cardiac compression and displacement. Severe PE can exacerbate right ventricular dysfunction and is frequently associated with mitral valve pathology, including mitral valve prolapse (MVP). Although the Nuss procedure is well established1 for minimally invasive PE repair (MIPER), its use alongside mitral valve surgery in a true single-stage, fully minimally invasive approach is rarely reported. We describe a combined modified cross-bar Nuss repair and minimally invasive mitral valve repair (MIMVR) performed in a single operation to optimize exposure and restore thoracic geometry.

BACKGROUND:Sarcoidosis is a disease of unknown etiology, characterized by the formation of immune cell accumulations (granulomas) in the lung and other tissues. Chronic sarcoidosis may lead to pulmonary fibrosis. AIM:To unravel cellular niches within pulmonary granulomas of patients with chronic sarcoidosis using spatial transcriptomics. METHODS:Spatial transcriptomics using the Visium platform (10x Genomics) was performed on 9 granuloma-containing lung explants from patients with sarcoidosis. Validation of gene expression was performed through immunohistofluorescence protein staining and RNA in situ hybridization. RESULTS:Spatial gene expression covered 30,587 gene expression spots and 173 granulomas. A CD68+ macrophage niche was localized in the center of the granuloma, with a CD3+ T-cell and CD20+ B-cell niche in close proximity, surrounded by a COL3A1+ fibroblast niche. In the Central Granuloma Macrophage niche, expression of the profibrotic macrophage genes SPP1, CHIT1, and CHI3L1 was observed, genes whose expression has recently been described for macrophages in idiopathic pulmonary fibrosis. Additionally, proinflammatory macrophage genes were expressed in the Central Granuloma Macrophage niche, suggesting that macrophages were armed for lysosomal degradation and ready for phagocytosis. Inner granuloma niches showed higher expression of interferon gamma (IFN-γ)-inducible genes. Higher collagen and CTHRC1 expression were observed in fibroblast-containing granuloma niches, characteristics of profibrotic lung remodeling. Ligand-receptor analysis identified proinflammatory and profibrotic interactions between granuloma niches. CONCLUSION:Taken together, macrophages in the center of the sarcoidosis granuloma form an armed-and-ready, hybrid proinflammatory and profibrotic niche, supporting granuloma persistence through continuous IFN-γ stimulation and collagen expression by fibroblasts localized in the periphery of the granuloma.

Abstract Background Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation, and its most frequent phenotype is bronchiolitis obliterans syndrome (BOS), a fibrotic small-airway disease. Mechanistic work has focused on the immune compartment, yet intensified immunosuppression does not alter established disease. Aim To resolve which structural cell states populate the BOS graft and how they are spatially organized during airway obliteration. Methods We profiled explanted lungs from 33 BOS patients undergoing re-transplantation and 33 controls, combining single-nucleus RNA sequencing (14 BOS, 13 controls) with targeted spatial transcriptomics of 108 regions (27 BOS, 24 controls) and multiplex immunofluorescence validation. Single-nucleus data were integrated with a published restrictive allograft syndrome (RAS) atlas. Results Across 175,128 nuclei and 1.67 million spatially resolved cells, BOS lungs harbored a profibrotic circuit of Aberrant Basaloid cells and CTHRC1 + fibrotic fibroblasts previously described in fibrotic lung diseases, including RAS. Spatial mapping identified a CXCL14 + TNC + injury-associated basal cell state arising early in the obliterative cascade, identifying basal cells as their major reservoir. CTHRC1 + fibroblasts expanded subepithelially replacing resident peribronchial fibroblasts, alongside a peribronchial vascular shift toward systemic venous endothelium. The circuit extended beyond the airway wall to the alveolar interface, defining two convergent remodeling fronts. Conclusion BOS engages structural-cell circuits largely shared with RAS and fibrotic lung diseases, but along an airway-centered rather than parenchyma-centered axis. CLAD thus emerges as a spatial rather than cellular spectrum, defined by anatomical distribution more than cell identity. Shared structural programs may therefore be targetable across CLAD phenotypes.

BACKGROUND:Long-term survival after lung transplantation (LTx) remains highly variable, with chronic lung allograft dysfunction (CLAD) as a major limiting factor. CLAD manifests as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) in more than 50% of LTx recipients. In contrast, a subgroup of "super survivors" maintains long-term graft stability for years without immunological complications. These patients show an increased prevalence of alveolar macrophages (AMs), but the mechanisms underlying stable graft function remain unclear. METHODS:Transcriptome profiles of AMs were analyzed in lung tissues of super survivors (n = 15), recipients with BOS or RAS (n = 24), and healthy controls (n = 9) using spatial transcriptomics. AM origin was assessed in sex-mismatched cases (n = 8) using X/Y fluorescence in situ hybridization. RESULTS:In super survivor AMs, upregulated genes were associated with stress control and detoxification (GSTA2, HBA2), innate immune regulation (INAVA), lipid homeostasis (APOE, CES1), and alveolar structure maintenance. Most AMs were donor-derived (61.3%). The majority (78.26%) displayed a pre-activated state with enhanced immune plasticity, while a smaller fraction (13.04%) showed M2-like repair functions. In BOS and RAS lungs, donor-derived AMs (37.4%) were largely replaced by recipient-derived cells. 35.71% of BOS and 56.52% of RAS AMs exhibited a progressive M1-like polarization. Transitional pre-BOS and pre-RAS stages suggested that early post-transplant conditions shape macrophage polarization and influence long-term outcomes. CONCLUSIONS:Stable long-term graft function after LTx is associated with persistence of metabolically adapted donor-derived AMs, whereas CLAD reflects their replacement by inflammatory recipient cells. Preserving protective macrophage populations may help promote a long-term stable immune microenvironment after LTx.

Antibody-mediated rejection (AMR) is an increasingly recognized form of rejection and cause of graft failure after lung transplantation. AMR has been the focus of extensive research over the past decade. Despite growing awareness and recent advances in our understanding of AMR, outcomes remain dismal with a 2-year survival of only 20%. The International Society for Heart and Lung Transplantation convened a multidisciplinary workgroup of experts in AMR to review the most up-to-date research and clinical experience and to update the 2016 definition. The workgroup was divided into 9 subgroups covering a broad range of topics pertaining to AMR and used the modified Delphi method to synthesize a cohesive summary of the literature. A multidimensional definition was developed to enhance precision by reporting the specific presenting features. This Graft, Antibody, and Pathology (GAP) definition is based on the presence of Graft dysfunction, the presence and characteristics of Antibodies, and Pathological findings. The workgroup emphasized that identifying better treatments for AMR is a critical unmet need and proposed that a more precise definition might allow better management by providing a platform for testing and developing new therapies.

OBJECTIVES:This retrospective observational study presents our 12-year experience with early donor-specific antihuman leukocyte antigen antibodies (DSAs) in lung transplantation, comparing outcomes between patients who were positive and negative for early DSAs and presenting the results of early DSA treatment with IgA- and IgM-enriched immunoglobulins (IgGAM). METHODS:Patients transplanted between March 2013 and November 2025 were included. At our institution, since 2013, patients positive for early DSAs with subclinical antibody-mediated rejection (AMR) were treated with successive IgGAM infusions and those with clinical AMR or preformed DSAs additionally with plasmapheresis and a single dose of anti-CD20 antibody. The median follow-up length amounted to 60 (23-102) months. RESULTS:Among the 1384 included patients, 367 (27%) patients showed early DSAs (preformed, n = 95; clinical early AMR, n = 54). At 5 and 10 years, graft and chronic lung allograft dysfunction-free survival (%) were similar in early DSA-positive and -negative patients (P = .861 and P = .448, respectively). Three-hundred -five (91%) patients with early DSAs were treated with an IgGAM-based protocol that cleared early DSAs in 269 (88.8%) of 303 patients who completed treatment. At follow-up, 21 (6%) early DSA-positive and 46 (5%) early DSA-negative patients developed late AMR that was significantly associated with worse graft survival (P < .001) and refractory to therapy. CONCLUSIONS:The detection of early DSAs after lung transplantation was not associated with worse outcomes. Treatment of early DSAs and early AMR might have contributed to this result. Late AMR is associated with worse graft survival.

[This corrects the article DOI: 10.1016/j.jhlto.2024.100132.].