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Background: Recent reports have suggested that coronavirus disease 2019 (COVID-19) infection can cause pneumonitis even in the absence of clinical symptoms and COVID-19 associated pulmonary inflammation can persist resulting in long-term fibrosis. This single-center study utilized standardized immunological testing to determine whether lungs from COVID-19 seropositive donors, indicative of past COVID-19 infection, can be safely used for clinical transplantation. Methods: The study included 90 consecutive lung transplant procedures incorporating donor serological testing for past COVID-19 infection. Donors were negative for active COVID-19 infection and met institutional criteria to be used for lung transplantation. The outcomes of lung transplant recipients were compared between donors with and without serological evidence of past COVID-19 infection. Results: No significant difference was found in post-transplant survival rates between recipients of lungs obtained from donors with serological evidence compared to those without. Additionally, there were no significant differences in primary graft dysfunction grade 3 rates or other post-transplant clinical parameters, such as operative time, ischemic time, extracorporeal membrane oxygenation use, intensive care unit stay, and hospital stay. Conclusions: Our findings suggest that lungs from COVID-19 seropositive donors, but not active COVID-19 infection are safe and feasible for transplantation, yielding comparable post-transplant outcomes to donors who are negative COVID-19 antibodies. This study supports the utilization of lungs from donors with historic COVID-19 infection as long as they meet current transplant criteria, potentially addressing the concerns related to the use of such organs.
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The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the "Achilles' heel" of the EVLP due to a more fluid accumulation than in the supine standard position.
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Transplante de Pulmão , Pulmão , Preservação de Órgãos , Perfusão , Estudo de Prova de Conceito , Humanos , Transplante de Pulmão/métodos , Perfusão/métodos , Preservação de Órgãos/métodos , Pulmão/fisiologia , Pulmão/irrigação sanguínea , Pulmão/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Doadores de Tecidos , AdultoRESUMO
INTRODUCTION: Recipients of lung transplants are at heightened risk of developing low bone mineral density (BMD). They also have increased risk of developing osteoporosis-related fractures. This rate of BMD decline is not well characterized. The aim of this manuscript is to characterize the rate of BMD decrease after lung transplant. METHODOLOGY: This is a preliminary retrospective cohort study of 200 patients who received lung transplants. Each patient had pre-transplant dual energy X-ray absorptiometry (DXA) and post-transplant DXA scans on the same DXA scanner. The BMD at each lumbar vertebra, total hip, and femoral neck were recorded. Generalized linear mixed effects models with random intercepts and random slopes were used to model the rate of change of BMD after transplant, adjusting for time since transplant, sex, and sex*time interaction. RESULTS: We found that men had higher baseline BMD than women at all sites (P<0.05 for all). The rate of BMD decrease was fastest at the femoral neck (P<0.05). Men lost BMD at a faster rate (-5.23 x10-5 g/cm2/day) than women at the femoral neck (-2.22 x10-5 g/cm2 /day). CONCLUSION: BMD decreases after lung transplant and occurs faster in men than women.
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Densidade Óssea , Transplante de Pulmão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Absorciometria de Fóton , Osteoporose , Modelos Lineares , Adulto , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Chronic lung allograft dysfunction (CLAD) limits survival following lung transplant, but substantial lung damage occurs before diagnosis by traditional methods. We hypothesized that small airway gene expression patterns could identify CLAD risk before spirometric diagnosis and predict subsequent graft failure. METHODS: Candidate genes from 4 rejection-associated transcript sets were assessed for associations with CLAD or graft failure in a derivation cohort of 156 small airway brushes from 45 CLAD cases and 37 time-matched controls with >1-year stable lung function. Candidate genes not associated with CLAD and time to graft failure were excluded, yielding the Airway Inflammation 2 (AI2) gene set. Area under the receiver operating curve (AUC) for CLAD and competing risks of death or graft failure were assessed in an independent validation cohort of 37 CLAD cases and 37 controls. RESULTS: Thirty-two candidate genes were associated with CLAD and graft failure, comprising the AI2 score, which clustered into 3 subcomponents. The AI2 score identified CLAD before its onset, in early and late post-CLAD brushes, as well as in the validation cohort (AUC 0.69-0.88). The AI2 score association with CLAD was independent of positive microbiology, CLAD stage, or CLAD subtype. However, transcripts most associated with CLAD evolved over time from CLAD onset. The AI2 score predicted time to graft failure and retransplant-free survival in both cohorts (p ≤ 0.03). CONCLUSIONS: This airway inflammation gene score is associated with CLAD development, graft failure, and death. Future studies defining the molecular heterogeneity of airway inflammation could lead to endotype-targeted therapies.
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Background. Varicella-zoster virus (VZV) is a human neurotropic virus which commonly causes infection during childhood, presenting as chickenpox. Later in life it may reactivate as herpes zoster. We report a rare manifestation of reactivation of VZV infection presenting as cutaneous vasculitis and varicella pneumonia in a lung transplant recipient. Case presentation. A 65-year-old man was lung transplanted bilaterally for emphysema and had repeated posttransplant chest infections and colonization with Pseudomonas aeruginosa. Nine months post-transplant he presented with dyspnoea and a cutaneous vasculitis-like eruption with a predilection over face, thorax and distal extremities. Initially, VZV reactivation was not suspected due to absence of the typical vesicular eruptions. The diagnosis was confirmed by VZV PCR from the swabs of the ulcer after skin punch biopsy of a lesion and from bronchoalveolar lavage (BAL). The histology of skin biopsy demonstrated epithelial damage and vascular damage but no typical epithelial virus associated changes. The patient responded to antiviral therapy with total remission of rash and VZV DNA was finally not detectable from repeated BAL after 29 days of therapy. However, the pulmonary radiological features and dyspnoea persisted due to reasons possibly unrelated to the VZV infection. Conclusion. Had it not been for the patient to mention the resemblance of the vasculitic rash with his primary VZV infection, the diagnosis would easily have been overlooked. In this case, the biopsy did not show typical histopathologic findings of VZV-vasculitis. What led the diagnosis was a PCR from the wound swab taken after the punch biopsy. This case serves as a reminder for atypical presentation of common conditions in immunosuppressed patients and that extensive diagnostic sampling may be warranted in this group.
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Lung transplant recipients (LTR) are susceptible to severe COVID-19 and had lower immune responses to primary SARS-CoV-2 vaccination as compared to the general population and to other solid organ transplant recipients. As immunity induced by booster vaccination and natural infection has increased since the beginning of the pandemic in the general population, immunity acquired by LTR is not well documented. Humoral and cellular immunity to SARS-CoV-2 was monitored in February and May 2023 in 30 LTR and compared to that of health care workers (HCW) and nursing home residents (NHR). LTR had significantly lower levels of SARS-CoV-2 binding and neutralizing antibodies and lower IFN-γ responses to Wuhan, Delta and XBB1.5 variants as compared to HCW and NHR. Humoral immunity decreased between the two visits whereas cellular immunity remained more stable. The persistent defect in SARS-CoV-2 immunity in LTR should encourage continued monitoring and preventive measures for this vulnerable population.
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BACKGROUND: Exposure to air pollution post lung transplant has been shown to decrease graft and patient survival. This study examines the impact of air pollution exposure in the first 3 months post-transplant on baseline (i.e. highest) forced expiratory volume in 1s (FEV1) achieved and development of chronic lung allograft dysfunction (CLAD). METHODS: Double-lung transplant recipients (n=82) were prospectively enrolled for comprehensive indoor and personal environmental monitoring at 6- and 12-weeks post-transplant and followed for >4 years. Associations between clinical and exposure variables were investigated using an exposomics approach followed by analysis with a Cox Proportional Hazards model. Multivariable analyses were used to examine the impact of air pollution on baseline % predicted FEV1 (defined as the average of the 2 highest values achieved post-transplant) and risk of CLAD. RESULTS: Multivariable analysis revealed a significant inverse relationship between personal black carbon (BC) levels and baseline % FEV1. The multivariable model indicated that patients with higher-than-median exposure to BC (>350 ng/m3) attained a baseline % FEV1 that was 8.8% lower than those with lower-than-median BC exposure (p = 0.019). Cox proportional hazards model analysis revealed that patients with high personal BC exposure had a 2.4 times higher hazard risk for CLAD than patients with low BC exposure (p = 0.045). CONCLUSIONS: Higher personal BC levels during the first 3 months post-transplant decreases baseline FEV1 and doubles the risk of CLAD. Strategies to reduce BC exposure early following lung transplant may help improve lung function and long-term outcomes.
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Mounier-Kuhn syndrome, characterized by tracheal dilatation due to the loss of elastic fibers and smooth muscle cells, is a rare condition, often leading to recurrent respiratory infections from impaired mucociliary clearance.
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Background: Primary graft dysfunction (PGD) has detrimental effects on recipients following lung transplantation. Here, we determined the contemporary trends of PGD in a national database, factors associated with the development of PGD grade 3 (PGD3) and ex vivo lung perfusion's (EVLP) effect on this harmful postoperative complication. Methods: The United Network for Organ Sharing database was queried from 2015 to 2023, and recipients were stratified into No-PGD, PGD1/2, or PGD3. The groups were analyzed with comparative statistics, and survival was determined with Kaplan-Meier methods. Multivariable Cox regression was used to determine factors associated with increased mortality. PGD3 recipients were then stratified based on EVLP use prior to transplantation, and a 3:1 propensity match was performed to determine outcomes following transplantation. Finally, logistic regression models based on select criteria were used to determine risk factors associated with the development of PGD3 and mortality within 1 year. Results: A total of 21.4% of patients were identified as having PGD3 following lung transplant. Those with PGD3 suffered significantly worse perioperative morbidity, mortality, and had worse long-term survival. PGD3 was also independently associated with increased mortality. Matched EVLP PGD3 recipients had significantly higher use of ECMO postoperatively; however, they did not suffer other significant morbidity or mortality as compared to PGD3 recipients without EVLP use. Importantly, EVLP use prior to transplantation was significantly associated with decreased likelihood of PGD3 development, while having no significant association with early mortality. Conclusions: EVLP is associated with decreased PGD3 development, and further optimization of this technology is necessary to expand the donor pool.
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Hyperammonemia is a metabolic disorder characterized by supraphysiologic ammonia (NH3) concentrations in the blood. Although usually seen in adults with liver disease, hyperammonemia is a notable complication in 4.1% of lung transplants. It is associated with cerebral edema and neurological dysfunction and carries up to 75% mortality in critically ill patients. Opportunistic infections caused by Mycoplasma and Ureaplasma species have been implicated as the cause of this metabolic disturbance. Literature in neonates has shown that renal replacement therapy (RRT) is the best choice for treating patients with neurologic manifestations of hyperammonemia, in cases of NH3 clearance than continuous renal replacement therapy (CRRT). In contrast, continuous venovenous hemodialysis (CVVHD) is usually better tolerated for patients with hemodynamic instability for NH3 clearance. NH3 is a small molecule whose clearance mirrors urea in dialysis. Even though RRT can be a treatment modality for hyperammonemia in adults and neonates, there is very little literature on adults. We present a unique case demonstrating improvement in neurologic manifestations of hyperammonemia by using both IHD and CVVHD in an adult patient.
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INTRODUCTION: Transplants with hearts and lungs from donors with hepatitis C virus (HCV D+) have been proven safe and effective since development of direct-acting antivirals, yet the presence of HCV + persists as a reason to decline organs. METHODS: We identified adult candidates listed January 1, 2015-March 8, 2023 for heart or lung transplant using the Scientific Registry of Transplant Recipients. We identified individual-level and center-level characteristics associated with listing to consider HCV D+ offers using multilevel logistic regression in a multivariable framework. RESULTS: Over the study period, the annual percentage of candidates willing to consider HCV D+ offers increased for both heart (9.5%-74.3%) and lung (7.8%-59.5%), as did the percentage of centers listing candidates for HCV D+ heart (52.9%-91.1%) and lung (32.8%-82.8%) offers. Candidates at centers with more experience with HCV D+ transplants were more likely to consider HCV D+ organ offers. After adjustment, listing center explained 70% and 78% of the residual variance in willingness to consider HCV D+ hearts and lungs, respectively. CONCLUSIONS: Although listing for consideration of HCV D+ offers has increased, it varies by transplant center. Center-level barriers to consideration of HCV D+ organs reduce recipients' transplant access.
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BACKGROUND: To assess changes in bone density and vertebral body height of patients undergoing lung transplant surgery using computed tomography (CT). METHODS: This institutional review board (IRB) approved retrospective observational study enrolled patients with a history of lung transplant who had at least two chest CT scans. Vertebral body bone density (superior, middle, and inferior sections) and height (anterior, middle, and posterior sections) were measured at T1-T12 at baseline and follow up CT scans. Changes in the mean bone density, mean vertebral height, vertebral compression ratio (VBCR), percentage of anterior height compression (PAHC), and percentage of middle height compression (PMHC) were calculated and analyzed. RESULTS: A total of 93 participants with mean age of 58 ± 12.3 years were enrolled. The most common underlying disease that led to lung transplants was interstitial lung diseases (57 %). The inter-scan interval was 34.06 ± 24.8 months. There were significant changes (p-value < 0.05) in bone density at all levels from T3 to T12, with the greatest decline at the T10 level from 163.06 HU to 141.84 HU (p-value < 0.05). The average VBCR decreased from 96.91 to 96.15 (p-value < 0.05). CONCLUSION: Routine chest CT scans demonstrate a gradual decrease in vertebral body bone density over time in lung transplant recipients, along with evident anatomic changes such as vertebral body bone compression. This study shows that utilizing routine chest CT for lung transplant recipients can be regarded as a cost-free tool for assessing the vertebral body bone changes in these patients and potentially aiding in the prevention of complications related to osteoporosis.
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INTRODUCTION: Hepatitis B virus reactivation (HBVr) can occur in solid organ transplant (SOT) recipients with previously inactive hepatitis B virus (HBV) infection. Previous studies have reported that HBVr is generally less than 10% in nonliver SOT recipients with past HBV infection. METHODS: We conducted a retrospective study from January 2018 to August 2023 at Mayo Clinic sites in Arizona, Florida, and Minnesota. We examined the antiviral prophylaxis strategy used and the characteristics of HBVr in hepatitis B core antibody-positive (HBcAb +) nonliver SOT adult recipients. Past HBV infection was defined as HBcAb + / hepatitis B surface antigen (HBsAg) -. Chronic HBV infection was defined as HBcAb + / HBsAg +. RESULTS: A total of 180 nonliver SOT recipients were identified during the study period. Indefinite antiviral prophylaxis was utilized in 77 recipients, and none developed HBVr after transplantation. In 103 recipients without antiviral prophylaxis, the incidence of HBVr was 12% (12/97) and 33% (2/6) in those with past HBV infection and chronic HBV infection. The incidence of HBVr in patients with past HBV infection is 16% (8/50), 15% (3/20), and 5% (1/22) in kidney, heart, and lungs, respectively. HBVr was more frequent in those who received alemtuzumab. Among 14 recipients with HBVr, none had HBV-associated liver failure or death. CONCLUSIONS: Our study observed a higher rate of HBVr (12%) in nonliver SOT recipients with past HBV infection compared to the previous studies. Further studies are needed to identify predictors of HBVr in nonliver SOT recipients and optimize antiviral prophylaxis guidance.
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Antivirais , Vírus da Hepatite B , Hepatite B , Transplante de Órgãos , Ativação Viral , Humanos , Estudos Retrospectivos , Masculino , Feminino , Vírus da Hepatite B/isolamento & purificação , Incidência , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Hepatite B/virologia , Hepatite B/epidemiologia , Seguimentos , Fatores de Risco , Antivirais/uso terapêutico , Prognóstico , Adulto , Medição de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/virologia , IdosoRESUMO
BACKGROUND: Frailty is prevalent in lung transplant (LTx) candidates, but the impact and subsequent frailty trajectory is unclear. This study aimed to investigate frailty over the first year after LTx. METHOD: Post-LTx recipients completed a thrice weekly 12-week directly supervised exercise rehabilitation program. Edmonton Frail Scale (EFS) was used to assess frailty. Primary outcome was 6-Minute Walk Distance (6MWD) measured at pre-LTx, prerehabilitation, postrehabilitation, and 1 year post-LTx. RESULTS: 106 of 139 recruited participants underwent LTx: mean age 58 years, 48% male, 52% with chronic obstructive pulmonary disease. Mean (± SD) frailty scores pre-LTx and 1 year post-LTx were 5.54 ± 2.4 and 3.28 ±1.5. Mean 6MWD improved significantly for all: prerehabilitation 326 m (SD 116), versus postrehabilitation 523 m (SD 101) (p < 0.001) versus 1 year 512 m (SD 120) (p < 0.001). There were significant differences between an EFS > 7 (frail) and EFS ≤ 7 (not frail) for 6MWD, grip strength (GS), anxiety, and depression. Postrehabilitation, there were no significant differences in 6MWD, GS, anxiety, or depression while comparing EFS > 7 versus ≤ 7. At 1 year, there was a significant difference in depression but not 6MWD, GS, or anxiety between those EFS ≤ 7 and > 7 (p = 0.017). CONCLUSION: Participants in a structured post-LTx rehabilitation program improved in functional exercise capacity (6MWD), GS, depression, and anxiety. For frail participants exercise capacity, depression, anxiety, and GS were well managed in rehabilitation with no significant differences between those who were not frail. Pre-LTx frailty may be reversible post-LTx and should not be an absolute contraindication to LTx.
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Fragilidade , Transplante de Pulmão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Seguimentos , Prognóstico , Terapia por Exercício/métodos , Idoso , Fatores de Risco , Qualidade de Vida , Doença Pulmonar Obstrutiva Crônica/reabilitação , Doença Pulmonar Obstrutiva Crônica/cirurgia , Complicações Pós-OperatóriasRESUMO
BACKGROUND: Lung transplantation (LTx) is a crucial therapeutic strategy for patients suffering from end-stage respiratory diseases, necessitating precise donor-recipient size matching to ensure optimal graft function. While standard allocation protocols rely on predicted lung capacity based on factors such as sex, age, and height, a subset of patients with respiratory diseases presents an additional challenge - thoracic or vertebral deformities. These deformities can complicate accurate volume predictions and may impact the success of lung transplantation. METHODS: In this retrospective cohort study of patients who underwent LTx at Tohoku University Hospital between January 2007 and April 2022, with follow-up until October 2022, the primary objective was to assess the influence of thoracic and vertebral deformities on perioperative complications, emphasizing interventions, such as volume reduction surgery. The secondary objective aimed to identify any noticeable impact on long-term prognoses in recipients with these deformities. RESULTS: Of 129 LTx recipients analyzed, 17.8% exhibited thoracic deformities, characterized by pectus excavatum, while 16.3% had vertebral deformities. Perioperative complications, requiring delayed chest closure, tracheostomy, and volume reduction surgery, were more prevalent in the deformity group. Thoracic deformities were notably associated with the need for volume reduction surgery. However, long-term prognoses did not differ significantly between patients with deformities and those without. Vertebral deformities did not appear to significantly impact perioperative or long-term outcomes. CONCLUSIONS: This study highlights the prevalence of thoracic deformities in LTx recipients, correlating with increased perioperative complications, particularly the potential need for volume reduction surgery. Importantly, these deformities do not exert a significant impact on long-term prognoses. Additionally, patients with vertebral deformities, such as scoliosis and kyphosis, appear to be manageable in the context of LTx.
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Transplante de Pulmão , Complicações Pós-Operatórias , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tórax em Funil/cirurgia , Vértebras Torácicas/cirurgia , IdosoRESUMO
While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.
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Biomarcadores , Rejeição de Enxerto , Transplante de Coração , Transplante de Pulmão , Humanos , Biomarcadores/sangue , Biópsia , Ácidos Nucleicos Livres/sangue , Consenso , Europa (Continente) , Perfilação da Expressão Gênica , Rejeição de Enxerto/diagnóstico , Transplante de Pulmão/efeitos adversos , Sociedades MédicasRESUMO
PURPOSE: Currently 80% of lung transplant centers use induction immunosuppression. However, there is a lack of standardization of induction protocols within and across lung transplant centers. This study explores the association of two different induction immunosuppression strategies used at our center [single dose rabbit antithymocyte globulin (rATG) vs. alemtuzumab] compared to no induction with immunologic and clinical outcomes after lung transplantation. METHODS: A total of 174 consecutive lung transplant recipients (LTR) between 2016 and 2019 were included in the analysis. Twenty nine LTR (16.7%) received no induction, 22 LTR (12.6%) received alemtuzumab, 123 LTR (70.6%) received a single dose of rATG; 1.5 mg/kg within 24 h of transplant for induction. All LTR had a negative flow cytometry crossmatch on the day of the transplant. All LTR were assessed for de novo HLA donor-specific antibodies (DSA) development and clinical outcomes, including the risk of acute cellular rejection (ACR), antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), and overall survival post-transplant. RESULTS: The median lung allocation score (LAS) was significantly higher in LTR that did not receive Induction immunosuppression (76; range = 35.3-94.3) compared to induction with rATG (41.6; range = 31.6-91) and alemtuzumab (51; range = 33.1-88.2) (p < 0.001). De novo HLA DSA were detected in 50/174 (28.7%) LTR within 12 months post-transplant. They were detected in 13/29 (44.8%) LTR without induction immunosuppression compared to 28/123 (22.8%) and 9/22 (40.9%) LTR with rATG and alemtuzumab induction, respectively (p = 0.02). The percent freedom from ACR rates between LTR who received alemtuzumab induction was significantly higher compared to LTR who received rATG or no induction at 1 (p = 0.02), 2 (p = 0.01) and 3 (p = 0.05) years post-transplant. In addition, the overall 1-year survival rates were significantly higher in LTR who received rATG or alemtuzumab induction compared to LTR without induction immunosuppression (p = 0.02). CONCLUSION: Induction immunosuppression strategies utilizing rATG or Alemtuzumab have unique and contrasting benefits in LTR. Combination of alemtuzumab induction and a lower dose of maintenance immunosuppression may reduce the incidence of ACR in LTR. Single-dose rATG or alemtuzumab induction immunosuppression may also improve the 1 year overall LTR survival compared to no induction.
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Alemtuzumab , Soro Antilinfocitário , Rejeição de Enxerto , Terapia de Imunossupressão , Transplante de Pulmão , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Masculino , Pessoa de Meia-Idade , Feminino , Soro Antilinfocitário/uso terapêutico , Alemtuzumab/uso terapêutico , Adulto , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Animais , Idoso , Estudos Retrospectivos , Sobrevivência de Enxerto , Coelhos , Resultado do Tratamento , Antígenos HLA/imunologia , Isoanticorpos/sangueRESUMO
BACKGROUND: Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard-of-care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV). METHODS: Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D-/R-), survived <90 days post-LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 109/L), severe leukopenia (WBC ≤ 2.0 × 109/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte-colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post-PPX CMV infection. RESULTS: 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non-lymphocyte-depleting induction (96.6%) and moderate-risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post-transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post-PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high-risk serostatus showed similar trends, though did not reach statistical significance. CONCLUSIONS: In this single-center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post-PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX.
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Introduction: Gout may complicate solid organ transplantation with potentially serious consequences. An accurate prevalence of gout in this population is unknown. Objectives: This study aimed to estimate the prevalence of gout in the heart and/or lung transplantation population through a systematic review and meta-analysis. Methods: MEDLINE, Embase, PsycINFO, CENTRAL and Cochrane Library (inception to February 2022) were searched for studies that reported the prevalence and/or incidence of gout in heart and/or lung transplant recipients. Two authors extracted outcomes data. Data were pooled using a random effects model. Overall quality of evidence was assessed using GRADE. Primary outcomes were the prevalence of pre- or post-transplant gout expressed as a prevalence rate (95% CI). Secondary outcomes included risk factors for gout, adverse events, and therapeutic complications of gout treatment. Results: Ten studies were included. Gout prevalence (PR) was 8% pre-transplant (PR = 0.08; 95% CI: 0.05-0.12; 4 studies n = 651) and 6% post-transplant (PR = 0.06; 95% CI: 0.06-0.06; 10 studies n = 45,298). Post-transplant gout prevalence in heart transplant recipients was almost three times higher than lung transplant recipients (PR = 0.16; 95% CI: 0.13-0.20 vs. PR = 0.06; 95% CI: 0.05-0.06 respectively). Patients with a pre-transplant history of gout had a higher risk of developing post-transplant gout than patients without (RR = 3.61; 95% CI: 2.19-5.95). Factors associated with gout and outcomes for heart and/or lung transplant recipients with gout were comprehensively reviewed from the included studies. Conclusion: Gout is highly prevalent in heart and/or lung transplant patients. Pre-transplant gout is predictive of developing symptomatic post-transplant gout. This has significant implications for management of heart/lung transplant patients. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42020190632).
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OBJECTIVES: To synthesize the clinical experience of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) or pulmonary fibrosis (PF) receiving lung transplantation (LTx) and compare the characteristics and outcomes of COVID-19 and non-COVID-19 LTx patients. METHODS: A literature search of online databases (PubMed, Web of Science, Embase, the Cochrane Library, China Science and Technology Journal Database, and Wan Fang databases) was performed regarding LTx for COVID-19-associated ARDS or PF. This study was registered on PROSPERO (CRD2024507647). RESULTS: Eight eligible studies were included with 478 COVID-19 LTx patients and 163 non-COVID-19 LTx patients. In COVID-19 LTx patients, the pooled hospital mortality and follow-up survival rate was 0.00% (95% CI 0.00-0.03) and 87.40% (95% CI 0.76-0.96). Compared to non-COVID-19 LTx patients, COVID-19 LTx patients were associated with significantly higher rate of primary graft dysfunction (odds ratio [OR] 8.72, 95% CI 3.54-21.47, P < 0.001) but significantly higher follow-up survival rate (OR 2.48, 95% CI 1.02-6.01, P = 0.04), within an overall similar follow-up period. CONCLUSIONS: For patients with COVID-19-associated ARDS or PF, LTx offers acceptable short-term outcomes and is suggested as a viable lifesaving treatment.