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BACKGROUND: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. AIM: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. METHODS: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. RESULTS: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. CONCLUSION: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.
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BACKGROUND: Minimally invasive (MI) approaches to lung transplantation (LTx) offer the prospect of faster recovery compared to traditional incisions, however, little data exist describing the impact of surgical technique on early outcomes and analgesia use. METHODS: A prospectively maintained institutional registry identified 170 patients who underwent LTx between January, 2017 and June, 2022. Post-COVID acute respiratory distress syndrome, repeat, and multiorgan transplants were excluded (n = 27) leaving 37 MILTx and 106 traditional LTx patients. Propensity score matching by age, sex, body mass index, diagnosis, lung allocation score, double vs. single lung, hypertension, diabetes, and hospitalization status created 37 pairs. RESULTS: Before matching, MILTx patients were more often male (70% vs 43%) and more likely to receive grafts from younger (31 vs 42 years), circulatory death donors (19% vs 6%) compared with traditional LTx patients (all p < 0.05). After matching, there were no differences in graft warm ischemia or operative duration (both p > 0.05). Postoperatively, MILTx experienced shorter intensive care unit (ICU) (4.3 [IQR 3.1-5.5] vs 8.2 [IQR 3.7-10.8] days) and hospital lengths of stay (LOS) (13 [IQR 11-15] vs 17 [IQR 12-25] days) (both p < 0.05). Among patients surviving to discharge, MILTx patients required fewer opioid prescriptions at discharge (38% vs 66%, p = 0.008) and had improved pulmonary function at 3 months (Forced expiratory volume in 1 second 82 [IQR 72-102] vs 77 [IQR 52-88]% predicted; forced vital capacity 78 [IQR 65-92] vs 70 [IQR 62-80]% predicted] (both p < 0.05). CONCLUSION: Minimally invasive LTx techniques demonstrate potential advantages over traditional approaches, including reduced ICU and hospital LOS, lower opioid use on discharge, and improved early pulmonary function.
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Trasplante de Pulmón , Procedimientos Quirúrgicos Mínimamente Invasivos , Humanos , Trasplante de Pulmón/métodos , Masculino , Femenino , Adulto , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Estudios de Cohortes , Estudios Retrospectivos , Sistema de Registros , Tiempo de Internación , Puntaje de Propensión , Analgesia/métodos , Estudios Prospectivos , Dolor Postoperatorio , COVID-19/epidemiologíaRESUMEN
BACKGROUND: Previous studies have demonstrated racial and gender disparities in lung allocation, but contemporary data regarding socioeconomic disparities in post-transplant outcomes are lacking. We evaluated the impact of a composite socioeconomic disadvantage index on post-transplant outcomes. METHODS: The Scientific Registry of Transplant Recipients identified 27,763 adult patients undergoing isolated primary lung transplantation between 2005 and 2020. Zip code-level socioeconomic distress was characterized using the Distressed Communities Index (DCI: 0-no distress, 100-severe distress) based on education level, poverty, unemployment, housing vacancies, median income, and business growth, and patients were stratified into high (DCI ≥60) or low (DCI <60) distressed groups. RESULTS: Recipients from high-distress communities (n = 8006, 28.8%) were younger (59years [interquartile range {IQR} 50-64] vs 61years [IQR 52-66]), less often white (73 vs 85%), less likely to have a college degree (45 vs 59%), and more likely to have public insurance (57 vs 49%, all p < 0.001) compared to those from low-distress communities. Additionally, high-distress recipients were more likely to have group A diagnoses (32 vs 27%) and undergo bilateral lung transplants (72.4 vs 69.3%, all p < 0.001). Post-transplant survival at 5years was 55.7% (95% confidence interval [CI]: 54.4-56.9) in high-distress recipients and 58.2% (95% CI: 57.4-58.9) in low-distress recipients (p = 0.003). After adjustment, high distress level was independently associated with an increased risk of 5-year mortality (hazard ratio:1.09, 95% CI:1.04-1.15). CONCLUSIONS: Recipients from distressed communities are at increased mortality risk following lung transplantation. Efforts should be focused on increased resource allocation and further study to better understand factors which may mitigate this disparity.
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Trasplante de Pulmón , Adulto , Humanos , Estudios Retrospectivos , Modelos de Riesgos Proporcionales , Grupos RacialesRESUMEN
BACKGROUND: Simultaneous lung-kidney transplantation is rarely performed. Contemporary national practice trends and outcomes are unclear. METHODS: From the United Network for Organ Sharing database, we identified 108 lung-kidney transplant recipients (2005-2022). They were compared with isolated lung recipients with pretransplantation dialysis or estimated glomerular filtration rate (eGFR) ≤30 mL/min per 1.73 m2 (n = 372) and isolated non-dialysis-dependent lung recipients with 30 < eGFR < 50 mL/min per 1.73 m2 (n = 1416), respectively. Lung-kidney recipients were also compared with recipients of the contralateral kidney from the same donors (n = 90). RESULTS: Lung-kidney transplantation was performed by 36 centers, with increasing annual volume (1 in 2005, 16 in 2022; P < .01). Forty percent (44/108) of lung-kidney recipients received pretransplantation dialysis, and of those without pretransplantation dialysis, median eGFR was 30.7 mL/min per 1.73 m2. Lung-kidney recipients had improved survival compared with isolated lung recipients with eGFR ≤30 mL/min per 1.73 m2 or pretransplantation dialysis (adjusted hazard ratio, 0.59; 95% CI, 0.38-0.92). However, no survival benefit was observed when lung-kidney recipients were compared with isolated lung recipients with 30 < eGFR < 50 mL/min per 1.73 m2 and no pretransplantation dialysis (adjusted hazard ratio, 0.88; 95% CI, 0.55-1.41). Compared with isolated kidney recipients using the contralateral kidney from the same donors, lung-kidney recipients had a higher risk of kidney allograft loss (adjusted hazard ratio, 3.27; 95% CI, 1.22-8.78), a difference largely accounted for by patient death with a functioning kidney allograft. CONCLUSIONS: Recipients of lung-kidney transplants had improved survival compared with isolated lung recipients with eGFR ≤30 mL/min per 1.73 m2 or pretransplantation dialysis. However, lung-kidney recipients had a higher rate of kidney allograft loss than recipients of the contralateral kidney allograft from the same donors.
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Fallo Renal Crónico , Trasplante de Riñón , Humanos , Estados Unidos/epidemiología , Fallo Renal Crónico/cirugía , Riñón , Diálisis Renal , Tasa de Filtración Glomerular , Pulmón , Supervivencia de Injerto , Estudios RetrospectivosRESUMEN
OBJECTIVES: The development of new human leukocyte antigens (HLAs) and donor-specific antibodies (DSAs) in patients are associated with worse outcomes following lung transplantation. The authors aimed to examine the relationship between blood product transfusion in the first 72 hours after lung transplantation and the development of HLA antibodies, including DSAs. DESIGN: A retrospective observational study. SETTING: At a single academic tertiary center. PARTICIPANTS: Adult lung transplant recipients who underwent transplantation between September 2014 and June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 380 patients were included in this study, and 87 (23%) developed de novo donor-specific antibodies in the first year after transplantation. Eighty-five patients (22%) developed new HLA antibodies that were not donor-specific, and 208 patients (55%) did not develop new HLA antibodies in the first year after transplantation. Factors associated with increased HLA and DSA development included donor pulmonary infection, non-infectious indication for transplant, increased recipient body mass index, and a preoperative calculated panel reactive antibody value above 0. Multivariate analysis identified platelet transfusion associated with an increased risk of de novo HLA antibody development compared to the negative group (odds ratio [OR; 95% CI] 1.18 [1.02-1.36]; p = 0.025). Cryoprecipitate transfusion was associated with de novo DSA development compared to the negative group (OR [95% CI] 2.21 [1.32-3.69] for 1 v 0 units; p = 0.002). CONCLUSIONS: Increased perioperative transfusion of platelets and cryoprecipitate are associated with de novo HLA and DSA development, respectively, in lung transplant recipients during the first year after transplantation.
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Isoanticuerpos , Trasplante de Pulmón , Humanos , Adulto , Rechazo de Injerto , Donantes de Tejidos , Trasplante de Pulmón/efectos adversos , Estudios Retrospectivos , Antígenos HLARESUMEN
Epstein-Barr virus (EBV) reactivation is commonly observed in lung transplant recipients (LTRs). However, cellular immune responses to EBV in adult LTRs have not been well described. We aimed to study CD4/CD8 ratio, EBV-specific T cells polyfunctional responses and phenotypic changes in natural killer (NK) cells in adult LTRs presenting with EBV-associated diseases. The CD4/CD8 ratio was significantly decreased in LTRs with EBV DNAemia compared with LTRs without EBV DNAemia and healthy controls (HCs). Stimulation with EBV lytic antigen BZLF1 peptide pools induced significant individual and polyfunctional responses from CD8+ CD69+ T cells. Frequencies of CD8+ CD69+ T cells expressing CD107a were significantly higher in LTRs without EBV DNAemia than in LTRs with DNAemia. Frequencies of CD8+ CD69+ T cells concurrently expressing CD107a, IFN-γ, and TNF-α were significantly greater in LTRs with and without EBV DNAemia than in HCs. Finally, BZLF1 induced significantly higher frequencies of CD8+ CD69+ T cells expressing CD107a and IFN-γ in LTRs without EBV DNAemia when compared with EBNA3B. Frequency of more differentiated CD56dim CD16pos NK cells was significantly decreased in LTRs with EBV DNAemia and PTLD compared with HCs. In conclusion, we noted the presence of significant changes in circulating cellular immune responses to EBV in adult LTRs.
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Infecciones por Virus de Epstein-Barr , Trasplante de Pulmón , Humanos , Adulto , Herpesvirus Humano 4 , Linfocitos T CD8-positivos , Interferón gamma , Trasplante de Pulmón/efectos adversosRESUMEN
BACKGROUND: It is unclear whether continuing anti-fibrotic therapy until the time of lung transplant increases the risk of complications in patients with idiopathic pulmonary fibrosis. OBJECTIVES: To investigate whether the time between discontinuation of anti-fibrotic therapy and lung transplant in patients with idiopathic pulmonary fibrosis affects the risk of complications. METHODS: We assessed intra-operative and post-transplant complications among patients with idiopathic pulmonary fibrosis who underwent lung transplant and had been treated with nintedanib or pirfenidone continuously for ⩾ 90 days at listing. Patients were grouped according to whether they had a shorter (⩽ 5 medication half-lives) or longer (> 5 medication half-lives) time between discontinuation of anti-fibrotic medication and transplant. Five half-lives corresponded to 2 days for nintedanib and 1 day for pirfenidone. RESULTS: Among patients taking nintedanib (n = 107) or pirfenidone (n = 190), 211 (71.0%) had discontinued anti-fibrotic therapy ⩽ 5 medication half-lives before transplant. Anastomotic and sternal dehiscence occurred only in this group (anastomotic: 11 patients [5.2%], p = 0.031 vs patients with longer time between discontinuation of anti-fibrotic medication and transplant; sternal: 12 patients [5.7%], p = 0.024). No differences were observed in surgical wound dehiscence, length of hospital stay, or survival to discharge between groups with a shorter versus longer time between discontinuation of anti-fibrotic therapy and transplant. CONCLUSION: Anastomotic and sternal dehiscence only occurred in patients with idiopathic pulmonary fibrosis who discontinued anti-fibrotic therapy < 5 medication half-lives before transplant. The frequency of other intra-operative and post-transplant complications did not appear to differ depending on when anti-fibrotic therapy was discontinued. REGISTRATION: clinicaltrials.gov NCT04316780: https://clinicaltrials.gov/ct2/show/NCT04316780.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Humanos , Fibrosis , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/cirugía , Trasplante de Pulmón/efectos adversos , Resultado del TratamientoRESUMEN
Posttransplant lymphoproliferative disorder (PTLD) represents a heterogeneous group of lymphoproliferative diseases occurring in the setting of immunosuppression following hematopoietic stem cells transplant and solid organ transplantation. Despite its overall low incidence, PTLD is a serious complication following transplantation, with a mortality rate as high as 50% in transplant recipients. Therefore, it is important to establish for each transplant recipient a personalized risk evaluation for the development of PTLD based on the determination of Epstein-Barr virus serostatus and viral load following the initiation of immunosuppression. Due to the dynamic progression of PTLD, reflected in the diverse pathological features, different therapeutic approaches have been used to treat this disorder. Moreover, new therapeutic strategies based on the administration of virus-specific cytotoxic T cells have been developed. In this review, we summarize the available data on screening and treatment to suggest a strategy to identify transplant recipients at a higher risk for PTLD development and to review the current therapeutic options for PTLD.
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Shortage of organ donors is an ongoing limiting factor in lung transplantation (LT). Despite increasing prevalence of asymptomatic COVID-19 infection, positive COVID-19 testing from a potential donor remains a contraindication at many LT centers. In this report, we present the outcomes of LT utilizing an algorithm based on donor clinical presentation, and COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) with cycle threshold (Ct) values evaluation. The Ct value threshold for organ acceptance was >35. A total of 8 COVID-positive donors were included. No donor-to-recipient transmissions of COVID-19 were observed. Short-term outcomes were comparable to those reported in pre-COVID literature. Survival-to-date is 100% with median POD of 161 days. Our findings support the safety and efficacy of utilizing our algorithm including Ct value threshold for selection of donors with incidental COVID-19 positive testing.
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COVID-19 , Humanos , COVID-19/diagnóstico , Prueba de COVID-19 , Donantes de Tejidos , Pulmón/diagnóstico por imagen , Reacción en Cadena de la Polimerasa , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.
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COVID-19 , Ácidos Nucleicos , Trasplante de Órganos , Obtención de Tejidos y Órganos , Humanos , SARS-CoV-2 , Comités Consultivos , Donantes de TejidosRESUMEN
BACKGROUND: Frailty, measured as a single construct, is associated variably with poor outcomes before and after lung transplantation. The usefulness of a comprehensive frailty assessment before transplantation is unknown. RESEARCH QUESTION: How are multiple frailty constructs, including phenotypic and cumulative deficit models, muscle mass, exercise tolerance, and social vulnerabilities, measured before transplantation, associated with short-term outcomes after lung transplantation? STUDY DESIGN AND METHODS: We conducted a retrospective cohort study of 515 lung recipients who underwent frailty assessments before transplantation, including the short physical performance battery (SPPB), transplant-specific frailty index (FI), 6-min walk distance (6MWD), thoracic sarcopenia, and social vulnerability indexes. We tested the association between frailty measures before transplantation and outcomes after transplantation using logistic regression to model 1-year survival and zero-inflated negative binomial regression to model hospital-free days (HFDs) in the first 90 days after transplantation. Adjustment covariates included age, sex, native lung disease, transplantation type, lung allocation score, BMI, and primary graft dysfunction. RESULTS: Before transplantation, 51.3% of patients were frail by FI (FI ≥ 0.25) and no patients were frail by SPPB. In multivariate adjusted models that also included FI, SPPB, and 6MWD, greater frailty by FI, but not SPPB, was associated with fewer HFDs (-0.006 per 0.01 unit worsening; 95% CI, -0.01 to -0.002 per 0.01 unit worsening) among discharged patients. Greater SPPB deficits were associated with decreased odds of 1-year survival (OR, 0.51 per 1 unit worsening; 95% CI, 0.28-0.93 per 1 unit worsening). Correlation among frailty measurements overall was poor. No association was found between thoracic sarcopenia, 6MWD, or social vulnerability assessments and short-term outcomes after lung transplantation. INTERPRETATION: Both phenotypic and cumulative deficit models measured before transplantation are associated with short-term outcomes after lung transplantation. Cumulative deficit measures of frailty may be more relevant in the first 90 days after transplantation, whereas phenotypic frailty may have a stronger association with 1-year survival.
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Fragilidad , Trasplante de Pulmón , Sarcopenia , Humanos , Fragilidad/complicaciones , Estudios Retrospectivos , Sarcopenia/epidemiología , Sarcopenia/complicaciones , PulmónRESUMEN
We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.
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Lesión Pulmonar Aguda , Trasplante de Pulmón , Neumonía , Adulto , Humanos , Estudios Prospectivos , Pronóstico , Estudios Retrospectivos , Trasplante de Pulmón/efectos adversos , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Pulmón , Neumonía/epidemiología , Neumonía/etiología , Neumonía/patología , Factores de Riesgo , Estudios de CohortesRESUMEN
BACKGROUND: Cytomegalovirus (CMV) infection is common following thoracic organ transplantation and causes substantial morbidity and mortality. Letermovir is a novel antiviral agent used off-label in this population for CMV prevention. Our goal was to understand patterns of letermovir use and effectiveness when applied for CMV prophylaxis after thoracic transplantation. METHODS: We retrospectively evaluated letermovir use among thoracic transplant recipients at an academic transplant center who initiated letermovir from January 2018 to October2019 for CMV prophylaxis. We analyzed indication, timing, and duration of prophylaxis; tolerability; and occurrence of breakthrough CMV DNAemia and disease. RESULTS: Forty-two episodes of letermovir prophylaxis occurred in 41 patients, including 37 lung and 4 heart transplant recipients. Primary prophylaxis (26/42, 61.9%) was utilized mainly due to myelosuppression (25/26, 96.2%) and was initiated a median of 315 days post-transplant (interquartile range [IQR] 125-1139 days). Sixteen episodes of secondary prophylaxis (16/42, 38.1%) were initiated a median of 695 days post-transplant (IQR 537-1156 days) due to myelosuppression (10/16, 62.5%) or prior CMV resistance (6/16, 37.5%). Median duration of letermovir prophylaxis was 282 days (IQR 131-433 days). Adverse effects required letermovir cessation in 5/42 (11.9%) episodes. Only one episode (2.4%) was complicated by clinically significant breakthrough CMV infection. Transient low-level CMV DNAemia (<450 IU/ml) occurred in 15 episodes (35.7%) but did not require letermovir cessation. CONCLUSIONS: Letermovir was well tolerated and effective during extended prophylactic courses with only one case of breakthrough CMV infection in this cohort of thoracic transplant recipients. Further prospective trials of letermovir prophylaxis in this population are warranted.
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Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Trasplante de Órganos , Acetatos , Antivirales/uso terapéutico , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Quinazolinas , Estudios Retrospectivos , Receptores de TrasplantesRESUMEN
PURPOSE OF REVIEW: Chronic lung allograft dysfunction (CLAD) limits the success of lung transplantation. Among the risk factors associated with CLAD, we recognize pretransplant circulating antibodies against the human leukocyte antigens (HLA), acute cellular rejection (ACR) and antibody-mediated rejection (AMR). This review will summarize current data surrounding management of desensitization, ACR, AMR, and CLAD. RECENT FINDINGS: Strategies in managing in highly sensitized patients waiting for lung transplant include avoidance of specific HLA antigens and reduction of circulating anti-HLA antibodies at time of transplant. Several multimodal approaches have been studied in the treatment of AMR with a goal to clear circulating donor-specific antibodies (DSAs) and to halt the production of new antibodies. Different immunosuppressive strategies focus on influence of the host immune system, particularly T-cell responses, in order to prevent ACR and the progression of CLAD. SUMMARY: The lack of significant evidence and consensus limits to draw conclusion regarding the impact of specific immunosuppressive regimens in the management of HLA antibodies, ACR, and CLAD. Development of novel therapeutic agents and use of multicenter randomized clinical trials will allow to better define patient-specific treatments and improve the length and quality of life of lung transplant recipients.
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Rechazo de Injerto , Aloinjertos/inmunología , Rechazo de Injerto/prevención & control , Antígenos HLA , Humanos , Isoanticuerpos , Trasplante de Pulmón/efectos adversos , Estudios Multicéntricos como Asunto , Calidad de VidaRESUMEN
Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disorder (PTLD) is a serious complication following lung transplant. The extent to which the presence of EBV in PTLD tissue is associated with survival is uncertain. Moreover, whether the heterogeneity in expression of EBV latency programs is related to the timing of PTLD onset remains unexplored. We retrospectively performed a comprehensive histological evaluation of EBV markers at the tissue level in 34 adult lung transplant recipients with early- and late-onset PTLD. Early-onset PTLD, occurring within the first 12 months posttransplant, had higher odds to express EBV markers. The presence of EBV in PTLD was not associated with a difference in survival relative to EBV-negative tumors. However, we found evidence of heterogeneous expression of EBV latency programs, including type III, IIb, IIa, and 0/I. Our study suggests that the heterogeneous expression of EBV latency programs may represent a mechanism for immune evasion in patients with PLTD after lung transplants. The recognition of multiple EBV latency programs can be used in personalized medicine in patients who are nonresponsive to traditional types of chemotherapy and can be potentially evaluated in other types of solid organ transplants.
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Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/genética , Pulmón/virología , Trastornos Linfoproliferativos/virología , Trasplante de Órganos/efectos adversos , Adulto , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/mortalidad , Femenino , Expresión Génica , Humanos , Pulmón/metabolismo , Pulmón/cirugía , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Trasplante de Órganos/mortalidad , Estudios Retrospectivos , Receptores de Trasplantes , Proteínas Virales/genética , Proteínas Virales/metabolismo , Latencia del Virus/genéticaRESUMEN
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication following lung transplant. We studied incidence and risk factors for PTLD in adult lung transplant recipients (LTRs) using the International Society for Heart and Lung Transplantation Registry. METHODS: The International Society for Heart and Lung Transplantation Registry was used to identify adult, first-time, single and bilateral LTRs with at least 1 year of follow-up between 2006 and 2016. Kaplan-Meier method was used to describe the timing and distribution of PTLD. Univariable and multivariable Cox proportional hazards regression models were used to examine clinical characteristics associated with PTLD. RESULTS: Of 19,309 LTRs in the analysis cohort, we identified 454 cases of PTLD. Cumulative incidence of PTLD was 1.1% (95% CIâ¯=â¯1.0%-1.3%) at 1 year and 4.1% (95% CIâ¯=â¯3.6%-4.6%) at 10 years. Of the PTLD cases, 47.4% occurred within the first year following lung transplantation. In the multivariable model, independent risk factors for PTLD included age, Epstein-Barr virus serostatus, restrictive lung diseases, and induction. Risk of PTLD during the first year after transplant increased with increasing age in patients between 45 and 62 years at time of transplantation; the inverse was true for ages <45 years or >62 years. Finally, receiving a donor organ with human leukocyte antigen types A1 and A24 was associated with an increased risk of PTLD, whereas the recipient human leukocyte antigen type DR11 was associated with a decreased risk. CONCLUSIONS: Our study indicates that PTLD is a relatively rare complication among adult LTRs. We identified clinical characteristics that are associated with an increased risk of PTLD.
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Trasplante de Pulmón/efectos adversos , Trastornos Linfoproliferativos/epidemiología , Complicaciones Posoperatorias , Sistema de Registros , Receptores de Trasplantes , Femenino , Estudios de Seguimiento , Salud Global , Humanos , Incidencia , Trastornos Linfoproliferativos/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Viral infections are associated with significant morbidity and mortality in lung transplant recipients. Importantly, several viral infections have been associated with the development of chronic lung allograft dysfunction (CLAD). Community-acquired respiratory viruses (CARV) such as influenza and respiratory syncytial virus (RSV), are frequently associated with acute and chronic rejection. Cytomegalovirus (CMV) remains a significant burden in regards to morbidity and mortality in lung transplant recipients. Epstein-Barr virus (EBV) is mostly involved with the development of post-transplant lymphoproliferative disorder (PTLD), a lymphoid proliferation that occurs in the setting of immunosuppression. On the other hand, the development of direct acting antivirals for hepatitis C virus (HCV) is changing the use of HCV-positive organs in transplantation. In this article we will focus on reviewing common viral infections that have a significant impact on lung transplant recipients looking at epidemiology, prevention and potential treatment.