RESUMO
We reviewed the cardiac surgical literature for 2023. PubMed displayed almost 34,000 hits for the search term "cardiac surgery AND 2023." We used a PRISMA approach for a results-oriented summary. Key manuscripts addressed the mid- and long-term effects of invasive treatment options in patient populations with coronary artery disease (CAD), comparing interventional therapy (percutaneous coronary intervention [PCI]) with surgery (coronary artery bypass graft [CABG]). The literature in 2023 again confirmed the excellent long-term outcomes of CABG compared with PCI in patients with left main stenosis, specifically in anatomically complex chronic CAD, but even in elderly patients, generating further support for an infarct-preventative effect as a prognostic mechanism of CABG. For aortic stenosis, a previous trend of an early advantage for transcatheter (transcatheter aortic valve implantation [TAVI]) and a later advantage for surgical (surgical aortic valve replacement) treatment was also re-confirmed by many studies. Only the Evolut Low Risk trial maintained an early advantage of TAVI over 4 years. In the mitral and tricuspid field, the number of interventional publications increased tremendously. A pattern emerges that clinical benefits are associated with repair quality, making residual regurgitation not irrelevant. While surgery is more invasive, it currently generates the highest repair rates and longest durability. For terminal heart failure treatment, donor pool expansion for transplantation and reducing adverse events in assist device therapy were issues in 2023. Finally, the aortic diameter related to adverse events and technical aspects of surgery dominated in aortic surgery. This article summarizes publications perceived as important by us. It cannot be complete nor free of individual interpretation, but provides up-to-date information for patient-specific decision-making.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Humanos , Resultado do Tratamento , Fatores de Risco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias/cirurgia , Fatores de Tempo , Ponte de Artéria Coronária/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Medição de RiscoRESUMO
PubMed displayed almost 37,000 hits for the search term "cardiac surgery AND 2022." As before, we used the PRISMA approach and selected relevant publications for a results-oriented summary. We focused on coronary and conventional valve surgery, their overlap with interventional alternatives, and briefly assessed surgery for aorta or terminal heart failure. In the field of coronary artery disease (CAD), key manuscripts addressed prognostic implications of invasive treatment options, classically compared modern interventions (percutaneous coronary intervention [PCI]) with surgery (coronary artery bypass grafting [CABG]), and addressed technical aspects of CABG. The general direction in 2022 confirms the superiority of CABG over PCI in patients with anatomically complex chronic CAD and supports an infarct-preventative effect as underlying mechanism. In addition, the relevance of proper surgical technique to achieve durable graft patency and the need for optimal medical treatment in CABG patients was impressively illustrated. In structural heart disease, the comparisons of interventional and surgical techniques have been characterized by prognostic and mechanistic investigations underscoring the need for durable treatment effects and reductions of valve-related complications. Early surgery for most valve pathologies appears to provide significant survival advantages, and two publications on the Ross operation prototypically illustrate an inverse association between long-term survival and valve-related complications. For surgical treatment of heart failure, the first xenotransplantation was certainly dominant, and in the aortic surgery field, innovations in arch surgery prevailed. This article summarizes publications perceived as important by us. It cannot be complete nor free of individual interpretation, but provides up-to-date information for decision-making and patient information.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Doença da Artéria Coronariana , Cardiopatias , Insuficiência Cardíaca , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Cardiopatias/cirurgia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Insuficiência Cardíaca/etiologiaRESUMO
PubMed displayed more than 35,000 hits for the search term "cardiac surgery AND 2021." We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) approach and selected relevant publications for a results-oriented summary. As in recent years, we reviewed the fields of coronary and conventional valve surgery and their overlap with their interventional alternatives. COVID reduced cardiac surgical activity around the world. In the coronary field, the FAME 3 trial dominated publications by practically repeating SYNTAX, but with modern stents and fractional flow reserve (FFR)-guided percutaneous coronary interventions (PCIs). PCI was again unable to achieve non-inferiority compared with coronary artery bypass graft surgery (CABG) in patients with triple-vessel disease. Survival advantages of CABG over PCI could be linked to a reduction in myocardial infarctions and current terminology was criticized because the term "myocardial revascularization" is not precise and does not reflect the infarct-preventing collateralization effect of CABG. In structural heart disease, new guidelines were published, providing upgrades of interventional treatments of both aortic and mitral valve disease. While for aortic stenosis, transcatheter aortic valve implantation (TAVI) received a primary recommendation in older and high-risk patients; recommendations for transcatheter mitral edge-to-edge treatment were upgraded for patients considered inappropriate for surgery. For heart team discussions it is important to know that classic aortic valve replacement currently provides strong signals (from registry and randomized evidence) for a survival advantage over TAVI after 5 years. This article summarizes publications perceived as important by us. It can neither be complete nor free of individual interpretation, but provides up-to-date information for decision-making and patient information.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Idoso , Estenose da Valva Aórtica/cirurgia , COVID-19 , Doença da Artéria Coronariana/cirurgia , Reserva Fracionada de Fluxo Miocárdico , Humanos , Intervenção Coronária Percutânea , Substituição da Valva Aórtica Transcateter , Resultado do TratamentoRESUMO
This study evaluated the impact of unilateral diaphragm elevation following bilateral lung transplantation on postoperative course. Patient data for all lung transplantations performed at our institution between 01/2010 and 12/2019 were reviewed. Presence of right or left diaphragm elevation was retrospectively evaluated using serial chest X-rays performed while patients were standing and breathing spontaneously. Right elevation was defined by a > 40 mm difference between right and left diaphragmatic height. Left elevation was present if the left diaphragm was at the same height or higher than the right diaphragm. In total, 1093/1213 (90%) lung transplant recipients were included. Of these, 255 (23%) patients exhibited radiologic evidence of diaphragm elevation (right, 55%; left 45%; permanent, 62%). Postoperative course did not differ between groups. Forced expiratory volume in 1 second, forced vital capacity and total lung capacity were lower at 1-year follow-up in patients with permanent than in patients with transient or absent diaphragmatic elevation (P = 0.038, P < 0.001, P = 0.002, respectively). Graft survival did not differ between these groups (P = 0.597). Radiologic evidence of diaphragm elevation was found in 23% of our lung transplant recipients. While lung function tests were worse in patients with permanent elevation, diaphragm elevation did not have any relevant impact on outcomes.
Assuntos
Diafragma , Transplante de Pulmão , Diafragma/diagnóstico por imagem , Volume Expiratório Forçado , Humanos , Pulmão/diagnóstico por imagem , Transplante de Pulmão/efeitos adversos , Estudos Retrospectivos , Capacidade VitalRESUMO
In this retrospective study, we analyzed the presence of any association of three CD4+ CD25high regulatory T-cell subpopulations at 3 weeks after lung transplantation with the later incidence of chronic lung allograft dysfunction and graft survival. Among lung-transplanted patients between January 2009 and April 2018, only patients with sufficient T-cell measurements at 3 weeks after transplantation were included into the study. Putative regulatory T cells were defined as CD4+ CD25high T cells, detected in peripheral blood and further analyzed for CD127low , FoxP3+ , and CD152+ using fluorescence-activated cell sorting (FACS) analysis. Associations of regulatory T cells with chronic lung allograft dysfunction (CLAD) and graft survival were evaluated using Cox analysis. During the study period, 724 (71%) patients were included into the study. Freedom from chronic lung allograft dysfunction (CLAD) and graft survival amounted to 66% and 68% at 5 years. At the multivariable analysis, increasing frequencies of CD127low were associated with better freedom from CLAD (hazard ratio for each 1% increase of %CD127low , HR = 0.989, 95% CI = 0.981-0.996, P = 0.003) and better graft survival (HR = 0.991, 95% CI = 0.984-0.999, P = 0.026). A higher frequency of CD127low regulatory T cells in peripheral blood early after lung transplantation estimated a protective effect against chronic lung allograft dysfunction, mortality, and re-transplantation.
Assuntos
Sobrevivência de Enxerto , Transplante de Pulmão , Citometria de Fluxo , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Estudos Retrospectivos , Linfócitos T ReguladoresRESUMO
Ex vivo lung perfusion (EVLP) has become routine practice in lung transplantation. Still, running periods exceeding 12 hours have not been undertaken clinically to date, and it remains unclear how the perfusion solution for extended running periods should be composed and which parameters may predict outcomes. Twenty-four porcine lungs underwent EVLP for 24 hours using the Organ Care System (OCS). Lungs were ventilated and perfused with STEEN's solution enriched with erythrocytes (n = 8), acellular STEEN's solution (n = 8), or low-potassium dextran (LPD) solution enriched with erythrocytes (n = 8). After 24 hours, the left lungs were transplanted into recipient pigs. After clamping of the contralateral lung, the recipients were observed for 6 hours. The most favorable outcome was observed in organs utilizing STEEN solution enriched with erythrocytes as perfusate, whereas the least favorable outcome was seen with LPD solution enriched with erythrocytes for perfusion. Animals surviving the observation period showed lower peak airway pressure (PAWP) and pulmonary vascular resistance (PVR) during OCS preservation. The results suggest that transplantation of lungs following 24 hours of EVLP is feasible but dependent on the composition of the perfusate. PAWP and PVR during EVLP are early and late predictors of transplant outcome, respectively.
Assuntos
Modelos Animais de Doenças , Circulação Extracorpórea/métodos , Transplante de Pulmão/métodos , Pulmão/fisiologia , Preservação de Órgãos/métodos , Perfusão/métodos , Edema Pulmonar/prevenção & controle , Animais , Soluções para Preservação de Órgãos/administração & dosagem , Suínos , Doadores de TecidosRESUMO
Lung transplantation from donors with fulminant pulmonary arterial embolism as a cause of death remains controversial. An analysis was performed comparing preoperative characteristics and outcomes of 25 donors with a primary diagnosis of pulmonary arterial embolism to 1085 recipients of donor lungs without pulmonary arterial embolism. No early functional impairment of donor lungs with pulmonary embolism was detectable as depicted by the incidence of primary graft dysfunction immediately after surgery (P = 0.66), 24 (P = 0.79), 48 (P = 0.99) and 72 h (P = 0.99) after transplantation. Pulmonary function testing at 1 year (P = 0.003) and at last outpatient control (P < 0.05) showed superior results in the cohort receiving lungs from donors with pulmonary embolism. Incidence of chronic lung allograft dysfunction (CLAD) showed no difference within the first year after lung transplantation, however, 5 year-CLAD free survival was superior in recipients (70.4% vs. 55.1%, P = 0.006) of donor lungs with pulmonary embolism. Overall survival was similar in both groups. Lungs from donors with fulminant pulmonary embolism prior to brain death can safely be used for lung transplantation without impairing postoperative outcomes. Lung function testing shows favorable midterm results in recipients of donor lungs with pulmonary embolism.
Assuntos
Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Pulmão/fisiopatologia , Pulmão/cirurgia , Embolia Pulmonar/fisiopatologia , Adulto , Idoso , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Disfunção Primária do Enxerto , Embolia Pulmonar/mortalidade , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Venoarterial extracorporeal membrane oxygenation support is a well-established tool in the care of severe refractory cardiac and respiratory failure. The application of this support may serve as a bridge to transplant, recovery or to implantation of a ventricular assist device. Venoarterial extracorporeal membrane oxygenation support can be administered through an open surgical access via the common femoral or axillary artery or a percutaneous approach using Seldinger technique. Both techniques may obstruct the blood flow to the lower limb and may cause a significant ischemia with possible limb loss. Malperfusion of the distal limb can be avoided using an ipsilateral distal limb perfusion, which may be established by adding a single-lumen catheter during venoarterial extracorporeal membrane oxygenation treatment to overcome the obstruction. The aim of this study is to distinguish the presence or absence of a distal limb perfusion regarding the incidence of distal limb ischemia. Furthermore, expected risk factors of open and percutaneous femoral venoarterial extracorporeal membrane oxygenation installation were evaluated for the development of distal limb ischemia. METHODS: Between January 2012 and September 2015, 489 patients received venoarterial extracorporeal membrane oxygenation support at our institution. In total, 307 patients (204 male, 103 female) with femoral cannulation were included in the analysis. The cohort was distinguished by the presence (group A; n = 237) or absence (group B; n = 70) of a distal limb perfusion during peripheral venoarterial extracorporeal membrane oxygenation treatment. Furthermore, a risk factor analysis for the development of distal limb ischemia was performed. RESULTS: The main indications for venoarterial extracorporeal membrane oxygenation therapy were a low cardiac output syndrome (LCOS) (53%) and failed weaning of extracorporeal circulation (23%). A total of 23 patients (7.49%) under venoarterial extracorporeal membrane oxygenation support developed severe distal limb malperfusion (3.38% in group A vs 21.42% in group B). Preemptive installation of distal limb perfusion extended the intervention-free intervals to 7.8 ± 19.3 days in group A and 6.3 ± 12.5 in group B. A missing distal limb perfusion (p = 0.001) was identified as a main risk factor for critical limb ischemia. Other comorbidities such as arterial occlusion disease (p = 0.738) were not statistically significantly associated. Surgical intervention due to vascular complications after extracorporeal membrane oxygenation explantation was needed in 14 cases (4.22% in group A and 5.71% in group B). CONCLUSION: We were able to identify the absence of distal limb perfusion as an independent risk factor for the development of critical distal limb ischemia during femoral venoarterial extracorporeal membrane oxygenation treatment. The application of a distal limb perfusion should be considered as a mandatory approach in the context of femoral venoarterial extracorporeal membrane oxygenation treatment regardless of the implantation technique.
Assuntos
Cateterismo , Oxigenação por Membrana Extracorpórea , Extremidades/irrigação sanguínea , Artéria Femoral/cirurgia , Isquemia , Adulto , Idoso , Feminino , Humanos , Isquemia/fisiopatologia , Isquemia/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
This retrospective study presents our 4-year experience of preemptive treatment of early anti-HLA donor specific antibodies with IgA- and IgM-enriched immunoglobulins. We compared outcomes between patients with antibodies and treatment (case patients) and patients without antibodies (control patients). Records of patients transplanted at our institution between March 2013 and November 2017 were reviewed. The treatment protocol included one single 2 g/kg immunoglobulin infusion followed by successive 0.5 g/kg infusions for a maximum of 6 months, usually combined with a single dose of anti-CD20 antibody and, in case of clinical rejection or positive crossmatch, with plasmapheresis or immunoabsorption. Among the 598 transplanted patients, 128 (21%) patients formed the case group and 452 (76%) the control group. In 116 (91%) patients who completed treatment, 106 (91%) showed no antibodies at treatment end. Fourteen (13%) patients showed antibody recurrence thereafter. In case versus control patients and at 4-year follow-up, respectively, graft survival (%) was 79 versus 81 (P = .59), freedom (%) from biopsy-confirmed rejection 57 versus 53 (P = .34), and from chronic lung allograft dysfunction 82 versus 78 (P = .83). After lung transplantation, patients with early donor-specific antibodies and treated with IgA- and IgM-enriched immunoglobulins had 4-year graft survival similar to patients without antibodies and showed high antibody clearance.
Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Imunoglobulinas Intravenosas/administração & dosagem , Isoanticorpos/imunologia , Transplante de Pulmão/métodos , Doadores de Tecidos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Teste de Histocompatibilidade , Humanos , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Imunoglobulinas Intravenosas/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Pleural tubes after coronary artery bypass graft (CABG) surgery usually cause pain resulting interalia in an impact of postoperative breathing. Therefore, the influence of intrapleural lidocaine application through special double-lumen chest tubes with respect to pain relief and lung function was investigated and compared with placebo. METHODS: In this study, 40 patients who underwent CABG got intrapleural injection either with 2% lidocaine (n = 20) or placebo (0.9% saline solution) (n = 20) on the first 2 days after surgery. Pain was measured by pain intensity numeric rating scale (NRS) (0 = no pain; 10 = the most intense pain) and lung function by portable spirometer. RESULTS: On the first postoperative day (POD1), mean pain reduction was NRS 1.9 for the lidocaine group with an improvement of the forced expiratory volume in 1 second (FEV1) of 0.51 L. Similar results were shown on the second postoperative day (POD2) with a decreased pain level of mean NRS 1.65 and an FEV1 improvement of 0.26 L. In comparison, results of the placebo group showed no significant pain reduction, neither on the POD1 (NRS 0.35; p = 0.429) nor on the POD2 (NRS 0.55; p = 0.159). Also, there was no significant influence of FEV1 after placebo on the POD1 (FEV1 = 0.048 L; p = 0.70) or on the POD2 (FEV1 = 0.0135 L; p = 0.925). CONCLUSION: Intrapleural application of lidocaine is a safe and feasible method to reduce drainage-related pain and improving lung function after CABG.
Assuntos
Anestésicos Locais/administração & dosagem , Ponte de Artéria Coronária , Drenagem , Analgesia Interpleural/métodos , Lidocaína/administração & dosagem , Pulmão/efeitos dos fármacos , Dor Pós-Operatória/prevenção & controle , Anestésicos Locais/efeitos adversos , Tubos Torácicos , Ponte de Artéria Coronária/efeitos adversos , Método Duplo-Cego , Drenagem/efeitos adversos , Drenagem/instrumentação , Vias de Administração de Medicamentos , Esquema de Medicação , Volume Expiratório Forçado , Alemanha , Humanos , Analgesia Interpleural/efeitos adversos , Lidocaína/efeitos adversos , Pulmão/fisiopatologia , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Recuperação de Função Fisiológica , Espirometria , Fatores de Tempo , Resultado do TratamentoRESUMO
Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism.
Assuntos
Transplante de Coração/métodos , Transplante de Pulmão/métodos , Tolerância ao Transplante , Aloenxertos/imunologia , Animais , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Tolerância Imunológica , Terapia de Imunossupressão , Leucócitos/metabolismo , Masculino , Baço/citologia , Baço/metabolismo , Suínos , Porco Miniatura , Tacrolimo/farmacologia , Fatores de Tempo , Doadores de Tecidos , Quimeras de Transplante , Transplante HomólogoRESUMO
OBJECTIVES: The management of severe coronary artery disease at the time of a lung transplant remains a challenge. We analysed the short- and long-term outcomes of lung transplant recipients with severe coronary artery disease. METHODS: Records of adult patients who received transplants at our institution between April 2010 and February 2021 were reviewed retrospectively. Severe coronary artery disease was defined as coronary stenosis ≥70% (main stem ≥50%) seen on the coronary angiographic scans performed before or at the time of listing. Patient characteristics, perioperative and long-term outcomes were compared between patients with and without severe coronary artery disease. RESULTS: Among 896 patients who received lung transplants who had undergone coronary angiography before the transplant, 77 (8.5%) had severe coronary artery disease; the remaining 819 (91.5%) did not. Patients with severe coronary artery disease were older (p < 0.0001), more often male (p < 0.0001) and received transplants more often for pulmonary fibrosis (p = 0.0007). The median (interquartile range) follow-up was 46 (20-76) months. At the Cox multivariable analysis, severe coronary artery disease was not associated with death. Patients with pretransplant percutaneous transluminal coronary angioplasty and patients with coronary artery bypass graft surgery concomitant to a transplant had survival equivalent to that of patients without severe coronary artery disease (p = 0.513; p = 0.556). CONCLUSIONS: Severe coronary artery disease was not associated with decreased survival after a lung transplant. Concomitant coronary artery bypass graft surgery and pretransplant percutaneous transluminal coronary angioplasty can be used for revascularization.
Assuntos
Doença da Artéria Coronariana , Transplante de Pulmão , Adulto , Angiografia Coronária , Doença da Artéria Coronariana/cirurgia , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Venous-arterial extracorporeal membrane oxygenation (ECMO) is an established technique for intraoperative cardiopulmonary support in patients undergoing lung transplantation. Patients with pulmonary fibrosis have a higher risk to require it. The aim of this study was to identify risk factors for the need of intraoperative ECMO use. METHODS: Records of patients undergoing lung transplantation for pulmonary fibrosis at our institution between January 2010 and May 2018 were retrospectively reviewed. Univariate logistic regression analysis was used for statistical identification of risk factors. RESULTS: There were 105 patients (34%) who required intraoperative ECMO support (ECMO+ group), and 203 (66%) did not (ECMO- group). Preoperative proof of pulmonary hypertension was identified as a risk factor for intraoperative ECMO support (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.2-6.5; P < .01). Revealed mean pulmonary arterial pressure values exceeding 50 mm Hg and pulmonary vascular resistance values exceeding 9.4 Wood units were identified as risk factors for the need of intraoperative ECMO use with a prediction probability of 70%. Increased recipient body surface area (OR, 0.2; 95% CI, 0.1-0.5; P < .01) emerged as a protective factor against intraoperative ECMO (Hosmer-Lemeshow statistic, P = .71) as well as higher cardiac output (OR, 0.7; 95% CI, 0.6-0.9; P < .01). The postoperative course was more complicated in the ECMO+ group, whereas survival at 5 years did not differ among groups (70% vs 69%, P = .79). CONCLUSIONS: Pulmonary hypertension with elevated pulmonary vascular resistance values predicts the need of intraoperative ECMO in patients receiving lung transplantation for pulmonary fibrosis. Although the postoperative course was more complicated in the ECMO+ group, long-term survival did not differ significantly.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Cuidados Intraoperatórios/métodos , Transplante de Pulmão/métodos , Fibrose Pulmonar/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
We previously induced long-term allograft acceptance in an allogeneic lung transplantation (LTx) model in miniature swine using perioperative non-myeloablative irradiation (IRR) combined with infusion of donor specific alloantigen. In order to improve clinical applicability, we delayed induction with irradiation in this study. Left sided single LTx was performed in minipigs. Group 1 received non-myeloablative irradiation (7Gy thymus and 1.5Gy whole body IRR) before LTx and a perioperative donor specific splenocyte infusion (SpTx). Group 2 received perioperative SpTx but delayed IRR three days after LTx. Group 3 was exposed to delayed IRR without SpTx. Whereas 4 out of 7 animals from the non-delayed group never rejected their grafts and were electively sacrificed on postoperative day (POD) +500, all animals from group 2 rejected their grafts before POD 108. In group 3, 3 out of 8 animals developed long-term allograft acceptance. In all groups, donor leukocyte chimerism peaked up to 20% in peripheral blood one hour after reperfusion of the lung. Group 1 maintained prolonged chimerism beyond POD 7, whereas chimerism levels in groups 2 and 3 decreased continuously thereafter. Delayed irradiation has the potential to improve long-term graft survival, yet not as efficient as a perioperative conditioning protocol.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Pulmão , Aloenxertos , Animais , Sobrevivência de Enxerto , Tolerância Imunológica , Suínos , Porco Miniatura , Quimeras de Transplante , Condicionamento Pré-TransplanteRESUMO
OBJECTIVES: A combined lung and liver transplant in patients with cystic fibrosis (CF) is an uncommon procedure. The goal of this study was to compare long-term outcomes between patients with CF who underwent either a combined lung-liver or a lung-only transplant. METHODS: This is a retrospective single-centre study of patients with CF who underwent a lung transplant between January 2005 and May 2020. Since 2006, our preference for a combined lung-liver transplant was to transplant the liver first and then the lung. Outcomes were compared using the Kaplan-Meier analysis and the log-rank test. Median follow-up was 53 (23-97) months. RESULTS: During the study period, among 357 patients with CF who underwent a lung transplant, 14 (4%) required a lung-liver transplant whereas 343 (96%) had a lung-only transplant. Lung cold ischaemic time was longer in the lung-liver transplant group, but no patient in this group showed primary graft dysfunction at 72 h after the transplant. Prevalence of anti-human leucocyte antigen donor-specific antibodies was 7.1% vs 13.7% in the lung-liver versus the lung-only transplant group (P = 0.42). At 5 years, lung graft survival (78% vs 69%) and freedom from chronic lung allograft dysfunction (79% vs 62%) did not differ between the lung-liver versus the lung-only groups (P = 0.45 and P = 0.55, respectively). Freedom from lung biopsy-confirmed rejection was significantly higher in patients undergoing a lung-liver transplant (91% vs 50%; P = 0.027). CONCLUSIONS: A lung-liver transplant did not impair lung graft function. The lower prevalence of donor-specific antibodies and the better freedom from lung biopsy-confirmed rejection suggest tolerogenic effects of the liver graft.
Assuntos
Fibrose Cística , Transplante de Fígado , Transplante de Pulmão , Fibrose Cística/cirurgia , Humanos , Fígado , Pulmão , Estudos RetrospectivosRESUMO
Introduction: For end-stage lung diseases, double lung transplantation (DLTx) is the ultimate curative treatment option. However, acute and chronic rejection and chronic dysfunction are major limitations in thoracic transplantation medicine. Thus, a better understanding of the contribution of immune responses early after DLTx is urgently needed. Passenger cells, derived from donor lungs and migrating into the recipient periphery, are comprised primarily by NK and T cells. Here, we aimed at characterizing the expression of killer cell immunoglobulin-like receptors (KIR) on donor and recipient NK and T cells in recipient blood after DLTx. Furthermore, we investigated the functional status and capacity of donor vs. recipient NK cells. Methods: Peripheral blood samples of 51 DLTx recipients were analyzed pre Tx and at T0, T24 and 3wk post Tx for the presence of HLA-mismatched donor NK and T cells, their KIR repertoire as well as activation status using flow cytometry. Results: Within the first 3 weeks after DLTx, donor NK and T cells were detected in all patients with a peak at T0. An increase of the KIR2DL/S1-positive subset was found within the donor NK cell repertoire. Moreover, donor NK cells showed significantly higher frequencies of KIR2DL/S1-positive cells (p<0.01) 3wk post DLTx compared to recipient NK cells. This effect was also observed in donor KIR+ T cells 3wk after DLTx with higher proportions of KIR2DL/S1 (p<0.05) and KIR3DL/S1 (p<0.01) positive T cells. Higher activation levels of donor NK and T cells (p<0.001) were detected compared to recipient cells via CD25 expression as well as a higher degranulation capacity upon activation by K562 target cells. Conclusion: Higher frequencies of donor NK and T cells expressing KIR compared to recipient NK and T cells argue for their origin in the lung as a part of a highly specialized immunocompetent compartment. Despite KIR expression, higher activation levels of donor NK and T cells in the periphery of recipients suggest their pre-activation during the ex situ phase. Taken together, donor NK and T cells are likely to have a regulatory effect in the balance between tolerance and rejection and, hence, graft survival after DLTx.
Assuntos
Células Matadoras Naturais/imunologia , Transplante de Pulmão , Pulmão/imunologia , Receptores KIR/sangue , Linfócitos T/imunologia , Adulto , Degranulação Celular , Técnicas de Cocultura , Citotoxicidade Imunológica , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-2/sangue , Células K562 , Células Matadoras Naturais/metabolismo , Pulmão/metabolismo , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores KIR2DL3/sangue , Receptores KIR3DL1/sangue , Linfócitos T/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Over the past decade, extracorporeal membrane oxygenation (ECMO) has replaced cardiopulmonary bypass (CPB) for cardiopulmonary support during lung transplantation at our institution. In this study, we present our experience using intraoperative ECMO in isolated lung transplantation and evaluate its impact on long-term graft function and survival. METHODS: All patients undergoing isolated lung transplantation with or without ECMO support between January 2010 and June 2019 were evaluated. Patients transplanted using CPB were excluded. Peri-operative and follow-up results from our database and patient charts were analyzed. Follow-up continued until September 1, 2019 (median, 3.34 years). RESULTS: In total, 311 of 1,161 lung transplant recipients (27%) received intraoperative ECMO, with 24 (2%) patients further requiring CPB. None of the remaining 826 (71%) patients required intraoperative cardiopulmonary support. ECMO patients exhibited higher pre-transplant surgical risk profiles and endured more complicated early post-operative courses than those without ECMO (in-hospital mortality, 10.9% vs 2.3%; p < 0.001). Inevitably, this resulted in poorer overall graft survival among ECMO recipients (pâ¯=â¯0.0025). However, correcting for patients surviving to hospital discharge, no difference in survival between groups was observed (5-year survival, 71% vs 72%; pâ¯=â¯0.56). Similarly, freedom from chronic lung allograft dysfunction, biopsy-confirmed cellular rejection, or need for pulsed-steroid therapy did not differ between the groups (pâ¯=â¯0.99, pâ¯=â¯0.78, and pâ¯=â¯0.93, respectively). CONCLUSIONS: Compared with patients not requiring cardiopulmonary support, ECMO recipients endured a more complicated peri-operative and early post-operative course. However, among those surviving to hospital discharge, no differences in long-term complications or outcomes were observed.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Cuidados Intraoperatórios/métodos , Transplante de Pulmão/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Experience with the treatment of early donor-specific anti-HLA antibodies (eDSA) after lung transplantation in children is very limited. At our institution, we have treated patients with eDSA since 2013 with successive infusions of intravenous human immunoglobulins (IVIG), combined in some cases with a single dose of Rituximab and plasmapheresis (therapeutic plasma exchange [tPE]) or immunoabsorption. The aim of this study was to present the 6-year results of IVIG-based therapy in pediatric lung recipients. METHODS: Records of pediatric (<18 years old) patients transplanted at our institution between 01/2013 and 03/2019 were reviewed. Outcomes were compared between patients with eDSA treated with IVIG (IVIG group) and without eDSA (control group). Median (interquartile range [IQR]) follow-up amounted to 28 (12-52) months. RESULTS: During the study period, 66 lung-transplanted pediatric patients were included, of which 27 (41%) formed the IVIG group and 38 (57%) the control group. Among the IVIG patients, 14 (52%) patients showed concomitant graft dysfunction (possible clinical antibody-mediated rejection). The median time to eDSA detection was 24 (14-63) days after transplantation. eDSA were cleared in 25 (96%) of the 26 patients which completed treatment. At 3 years, graft survival (%) was 73 vs 85 (P = .65); freedom (%) from chronic lung allograft rejection (CLAD) was 89 vs 78 (P = .82); and from infection 47 vs 31 (P = .15), in IVIG vs control patients, respectively. CONCLUSIONS: After lung transplantation, an IVIG-based treatment for eDSA yielded high eDSA clearance. IVIG and control patients showed similar CLAD-free and graft survival.
Assuntos
Anticorpos/uso terapêutico , Antígenos HLA/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Pulmão , Adolescente , Criança , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Masculino , Doadores de TecidosRESUMO
Hypothermia is a treatment strategy for different clinical conditions and an essential part of cardiopulmonary bypass in complex cardiac procedures. Clinically, cooling patients is achieved via a mattress and heat exchanger integrated into a membrane oxygenator connected to a waterbed using a refrigerator system based on volatile and toxic liquids. Peltier elements are known as environmentally friendly thermoelectric generators that enable rapid warming and cooling. In this paper, we describe the construction of a novel device for rapid and precise control of mouse warming and cooling using thermoelectric Peltier elements. Six male BALB/c mice were subjected to deep hypothermia and were rewarmed under full physiological monitoring. After rewarming, all animals were observed for two hours, and pathology was evaluated in several organs. All animals tolerated the rapid cooling process well and remained active after rewarming. Temperature-relevant changes were seen via electrocardiography, with heart-rate patterns showing a strong linear correlation to body temperature. No myocardial ischaemia was seen. However, two animals experienced bradycardic atrial fibrillation which spontaneously converted to normal sinus rhythm during rewarming. No histological damage was seen in the heart, liver, kidney or lungs. Our device can effectively be used for heat shock and hypothermia studies in mice, and we foresee no obstacles for its application to other small rodents such as hamsters and young rats. In comparison to known experimental and clinical methods of hypothermia, our device is environmentally friendly, cost-effective and easy to handle, allowing precise control and maintenance of body temperatures ranging from 18â to 42â.
RESUMO
OBJECTIVE: Chronic lung allograft dysfunction (CLAD) is a severe complication of lung transplantation limiting long-term survival. We studied correlations between CLAD after clinical lung transplantation and leukocyte-mediated development of transplant arteriosclerosis (TA) in a humanized mouse model. The pericardiophrenic artery was procured from surplus tissue of donor lungs (n = 22) transplanted in our clinical program and was implanted into the abdominal aorta of immune-deficient mice. METHODS: Allogeneic human peripheral blood mononuclear cells (PBMCs) had been procured 1 day after lung transplantation from the respective recipients with or without enriching for CD4+CD25high T cells were used. TA was assessed in mice 28 days later by histology. The respective clinical lung recipients were later divided into 2 groups. Eight patients (36.3%) had developed CLAD 23 ± 5 months after lung transplantation, whereas the remaining 14 (63.6%) did not develop CLAD within 25 ± 5 months. RESULTS: In the PBMC CLAD+ group of mouse experiments, TA was significantly more severe than in the PBMC CLAD- group (39.9% ± 13% vs 14.9% ± 4% intimal thickening; P = .0081). Then, intimal thickening was significantly inhibited in the PBMC+ regulatory T cells CLAD+ group compared with the PBMC CLAD+ group (0.4% ± 4% vs 39.9% ± 13%; P = .003). In the experiments using PBMCs from lung recipients without CLAD, enriching regulatory T cells also suppressed the development of TA (0.9% ± 3% PBMC CLAD- vs 14.9% ± 4% PBMC+ regulatory T cells CLAD-; P = .001). CONCLUSIONS: Lung transplant recipients who later develop CLAD have peripheral leukocytes already at the time of transplant that transfer proinflammatory properties leading to TA in a humanized mouse model. TA remains sensitive to inhibition by autologous regulatory T cells, suggesting a cell therapy-based approach for the prevention of CLAD after lung transplantation.