Lung transplantation despite preformed donor-specific antihuman leukocyte antigen antibodies: a 9-year single-center experience.

Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient's waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA. Records of patients transplanted between February 2013 and May 2022 were reviewed. Outcomes were compared between patients with pfDSA and those without any de novo donor-specific antiHLA antibodies. The median follow-up time was 50 months. Of the 1,043 patients who had undergone lung transplantation, 758 (72.7%) did not develop any early donor-specific antiHLA antibodies, and 62 (5.9%) patients exhibited pfDSA. Among the 52 (84%) patients who completed treatment, pfDSA was cleared in 38 (73%). In pfDSA vs control patients and at 8-year follow-up, respectively, graft survival (%) was 75 vs 65 (P = .493) and freedom from chronic lung allograft dysfunction (%) was 63 vs 65 (P = .525). In lung transplantation, crossing the preformed HLA-antibody barrier is safe using a treatment protocol based on IgGAM. Patients with pfDSA have a good 8-year graft survival rate and freedom from chronic lung allograft dysfunction, similar to control patients.

Impact of total ischaemic time and disease severity class on graft function after bilateral lung transplantation.

OBJECTIVES: Total ischaemic time (IT) is considered a limiting factor in lung transplantation. In this retrospective study, we investigate effects of IT and disease burden on outcomes after bilateral lung transplantation. METHODS: A total of 1298 patients undergoing bilateral lung transplantation between January 2010 and May 2022 (follow-up 100%, median 54 months) were included. Pre-transplant diseases' severity (recipient body mass index, recipient age, previous lung transplantation, Tacrolimus immunosuppression, preoperative recipient extracorporeal membrane oxygenation support, lung volume reduction) for graft failure was individually calculated and-as IT-categorized. Vice versa adjusted Cox models were calculated. Considering competing risks, we assessed cumulative incidences of airway obstructive complications and chronic lung allograft dysfunction with death as competing risk factors for primary graft dysfunction were assessed by binary logistic regression. RESULTS: Higher disease burden significantly accelerated chronic lung allograft dysfunction and death occurrence (P < 0.001); IT did not. IT-adjusted disease burden strata showed 50% graft survival differences at 11 years after transplantation (range 24-74%), disease burden-adjusted IT strata 18% for all and 6% (54-60%) among those above 7 h. All significant primary graft dysfunction risk factors were diagnoses related, IT was not significantly important and odds ratios did not increase with IT. CONCLUSIONS: The eventual graft survival disadvantage that results from an IT between 7 and at least 11 h is negligible in contrast to frequent recipients' disease-based risk levels.

Indications and outcome after lung transplantation in children under 12 years of age: A 16-year single center experience.

OBJECTIVE: Paediatric lung transplantation poses unique management challenges. Experience regarding indications and outcome is scarce, especially in younger children. The primary aim of this study was to investigate outcome after first lung transplantation in children <12 years of age in comparison to adolescents (12-17 years old). METHODS: Records of patients <18 years who underwent first lung transplantation between 01/2005 and 01/2021 were retrospectively reviewed, and compared between children <12 years old and adolescents. Median (IQR) follow-up was 51 (23-91) months. RESULTS: Of the 117 patients underwent first lung transplantation at our institution, of whom 42 (35.8%) patients were <12 years and 75 (64.2%) ≥12 years old. Compared to adolescents, children were more often transplanted for interstitial lung disease (33.3% vs 12%, p = 0.005) and precapillary pulmonary hypertension (28.6% vs 12%, p = 0.025), and required more often intraoperative cardiopulmonary bypass (31% vs 14.7%, p = 0.036) and postoperative ECMO support (47.6% vs 13.3%, p < 0.001). Postoperatively, children required longer ventilation times (78 vs 18 hours, p = 0.009) and longer ICU stay (9.5 vs 3 days, p < 0.001) compared to their older counterparts. Primary graft dysfunction grade 3 at 72 hours (9.5% vs 9.3%, p = 0.999), in-hospital mortality (2.4% vs 6.7%, p = 0.418), graft survival (80% vs 62%, p = 0.479) and freedom from chronic lung allograft dysfunction (76% vs 59%, p = 0.41) at 8-year follow-up did not differ between groups. CONCLUSIONS: Lung transplantation in children under 12 years is challenging due to underlying medical conditions and operative complexity. Nevertheless, outcomes are comparable to those in older children.

Early surgical myocardial revascularization in non-ST-segment elevation acute coronary syndrome.

BACKGROUND: In non-ST-elevation myocardial infarction (NSTEMI) there is no consensus regarding optimal time point for coronary artery bypass grafting (CABG). Recent findings suggest that long-term outcomes are improved in early-revascularized NSTEMI patients. However, it has been stated that early surgery is associated to increased operative risk. In this study, we wanted to elucidate if early CABG in non-ST-elevation acute coronary syndrome can be performed safely. METHODS: We performed a monocentric-prospective observational study within a 2-year interval. A total of 217 consecutive patients (41 female, age 68.9±10.2, ES II 6.62±8.56) developed NSTEMI and underwent CABG. Patients were divided into two groups according to the time point of coronary artery bypass after symptom onset (group A: <72 h; group B: >72 h). Endpoints included 6-month mortality and incidence of MACE (death, stroke or re-infarction). RESULTS: There were no differences regarding mortality between both groups (30 days: group A 2.4% vs. group B 3.7%; P=0.592; 6 months: 8.4% vs. 6.0%; P=0.487). Incidence of MACE in the 6-month follow-up was also similar in both groups (group A: 9.6% vs. 9.7%, P=0.982). Regression analysis revealed as independent risk factors for mortality in the entire cohort ES II OR 1.045 (95% CI: 1.004-1.088). ES II remained an independent prognostic factor in group A OR 1.043 (95% CI: 1.003-1.086) and group B OR 1.032 (95% CI: 1.001-1.063). CONCLUSIONS: Early revascularized patients showed a higher level of illness. However, results of early CABG were comparable to those following delayed revascularization. Moreover, EuroSCORE II was determined as independent risk factors for mortality.

Decellularized mitral valve in a long-term sheep model.

OBJECTIVES: The objective of this study was to evaluate surgical handling, in vivo hemodynamic performance and morphological characteristics of decellularized mitral valves (DMVs) in a long-term sheep model. METHODS: Ovine mitral valves were decellularized using detergents and ß-mercaptoethanol. Orthotopic implantations were performed in 6-month-old sheep (41.3 ± 1.2 kg, n = 11) without annulus reinforcement. Commercially available stented porcine aortic valves [biological mitral valve (BMV), n = 3] were implanted conventionally and used as controls. Valve function was evaluated by transoesophageal echocardiography and explants were investigated by a routine bright field microscopy and immunofluorescent histology. RESULTS: During implantation, 2 DMVs required cleft closure of the anterior leaflet. All valves were competent on water test and early postoperative transoesophageal echocardiography. Six animals (DMV, n = 4; BMV, n = 2) survived 12 months. Six animals died within the first 4 months due to valve-related complications. At 12 months, transoesophageal echocardiography revealed severe degeneration in all BMVs. Macroscopically, BMV revealed calcification at the commissures and leaflet insertion area. Histological examination showed sporadic cells negative for endothelial nitric oxide synthase, von Willebrand factor and CD45 on their surface. In contrast, DMV showed no calcification or stenosis, and the regurgitation was trivial to moderate in all animals. Fibrotic hardening occurred only along the suture line of the valve annulus, immunostaining revealed collagen IV covering the entire leaflet surface and a repopulation with endothelial cells. CONCLUSIONS: Surgical implantation of DMV is feasible and results in good early graft function. Additional in vivo investigations are required to minimize the procedure-related complications and to increase the reproducibility of surgical implantation. Degenerative profile of allogeneic DMV is superior to commercially available porcine aortic prosthesis.

Tissue-engineered mitral valve: morphology and biomechanics †.

OBJECTIVES: The present study aimed at developing tissue-engineered mitral valves based on cell-free ovine mitral allografts. METHODS: The ovine mitral valves (OMVs) (n = 46) were harvested in the local slaughter house. They were decellularized using detergent solutions and DNase. The effectiveness of decellularization was assessed by histological (haematoxylin-eosin, Movat's pentachrome) and immunofluorescent staining (for DNA and α-Gal), and DNA-quantification. To reveal the receptiveness of decellularized tissue to endothelial cells (ECs), the valve leaflets were reseeded with ovine ECs, derived from endothelial progenitor cells in vitro. For assessment of biomechanical properties, uniaxial tensile tests were carried out. RESULTS: Histology and immunofluorescent staining revealed absence of cell nuclei in decellularized leaflets, chordae and papillary muscles. According to the software for immunofluorescence analysis, reduction in DNA and α-Gal was 99.9 and 99.6%, respectively. DNA-quantification showed 71.2% reduction in DNA content without DNase and 96.4% reduction after DNase treatment. Decellularized leaflets were comparable with native in ultimate tensile strain (native, 0.34 ± 0.09 mm/mm, vs decellularized, 0.44 ± 0.1 mm/mm; P = 0.09), and elastin modulus (native, 0.39 ± 0.27, vs decellularized, 0.57 ± 0.55, P = 0.46), had increased ultimate tensile stress (native, 1.23 ± 0.35 MPa, vs decellularized 2.12 ± 0.43 MPa; P = 0.001) and collagen modulus (native, 5.5 ± 1.26, vs decellularized, 8.29 ± 2.9; P = 0.04). After EC seeding, immunofluorescent staining revealed a monolayer of CD31-, eNOS- and vWF-positive cells on the surface of the leaflet, as well as a typical cobble-stone morphology of those cells. CONCLUSIONS: Decellularization of ovine mitral valve results in a mitral valves scaffold with mechanical properties comparable with native tissue, and a graft surface, which can be repopulated by endothelial cells.