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PURPOSE: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients. METHODS: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert. RESULTS: An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra-operative antimicrobials); (3) invasive aspergillosis (treatment of culture-negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis). CONCLUSION: This Delphi panel developed consensus-based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients.
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Técnica Delphi , Humanos , Encuestas y Cuestionarios , Corazón Auxiliar/efectos adversos , Consenso , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas , Receptores de Trasplantes , Trasplante de Pulmón/efectos adversos , Antibacterianos/uso terapéutico , Enfermedades TransmisiblesRESUMEN
INTRODUCTION: Re-transplant is an option for those who develop end-stage lung disease due to rejection; however, little data exist following re-transplantation in cystic fibrosis (CF). METHODS: Data from the Canadian CF Registry and US CF Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. Individuals who underwent a 2nd lung transplant between 2005 and 2019 were included. The Kaplan-Meier method was used to estimate the probability of survival post-second transplant at 1, 3, and 5-years. RESULTS: Of those people who were waitlisted for a second transplant (N = 818), a total of 254 (31%) died waiting, 395 (48%) were transplanted and 169 (21%) people were alive on the waitlist. Median survival time after 2nd lung transplant was 3.3 years (95% CI: 2.8-4.1). The 1-, 3- and 5-year survival rates were 77.4% (95% CI: 73.1-82%), 52% (95% CI: 46.7-58%) and 39.4% (95% CI: 34.1-45.6%). CONCLUSIONS: Survival following second lung transplant in CF patients is lower than estimates following the first transplant. Over half of subjects who are potentially eligible for a second transplant die without receiving a second organ. This warrants further investigation.
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Fibrosis Quística , Trasplante de Pulmón , Humanos , Fibrosis Quística/cirugía , Canadá/epidemiología , Pulmón , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Rehabilitation is prescribed to optimize fitness before lung transplantation (LTx) and facilitate post-transplant recovery. Individuals with cystic fibrosis (CF) may experience unique health issues that impact participation. METHODS: Patient and healthcare provider semi-structured interviews were administered to explore perceptions and experiences of rehabilitation before and after LTx in adults with CF. Interviews were analyzed via inductive thematic analysis. RESULTS: Eleven participants were interviewed between February and October 2021 (five patients, median 28 (IQR 27-29) years, one awaiting re-LTx, four following first or second LTx) and six healthcare providers. Rehabilitation was delivered both in-person and virtually using a remote monitoring App. Six key themes emerged: (i) structured exercise benefits both physical and mental health, (ii) CF-specific physiological impairments were a large barrier, (iii) supportive in-person or virtual relationships facilitated participation, (iv) CF-specific evidence and resources are needed, (v) tele-rehabilitation experiences during the COVID-19 pandemic resulted in preferences for a hybrid model and (vi) virtual platforms and clinical workflows require further optimization. There was good engagement with remote data entry alongside satisfaction with virtual support. CONCLUSIONS: Structured rehabilitation provided multiple benefits and a hybrid model was preferred going forward. Future optimization of tele-rehabilitation processes and increased evidence to support exercise along the continuum of CF care are needed.
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COVID-19 , Fibrosis Quística , Trasplante de Pulmón , Humanos , Adulto , Fibrosis Quística/cirugía , Pandemias , Trasplante de Pulmón/métodosRESUMEN
INTRODUCTION: The significance of granuloma in explanted lungs of lung transplant recipients (LTR) on the development of post-transplant mycobacterial infection is unclear. METHODS: A retrospective review comparing LTRs and heart-lung transplant (H-LTR) recipients with granuloma in the explanted lungs between 2000 and 2012 (excluding those LTRs with granuloma due to sarcoidosis) and LTRs or H-LTRs without granuloma. Patients were followed for 2 years post-transplant. RESULTS: A total of 144 LTRs and 4 H-LTRs with granulomas (75 necrotizing and 73 non-necrotizing) and a comparator cohort of 144 LTRs and 4 H-LTRs without granuloma were analyzed. In LTRs with granulomas, identification of infectious organisms was more common by histopathology (35 AFB and 22 fungal) compared to cultures (six NTM and seven fungal) taken around time of the transplant. LTRs with granulomas were more likely to have pre-transplant non-tuberculous mycobacteria (NTM) infection compared to LTRs without granuloma; P < .01. In the multivariate analysis, having granuloma or positive mycobacterial cultures at time of transplant were associated with increased risk of post-transplant mycobacterial infection (HR = 1.8 95% CI [1.024-3.154]; P = .041 and HR = 2.083 95% CI [1.011-4.292]; P = .047). Although there was a trend toward increase mycobacterial disease in those with granulomas P = .056, there was no difference in survival post-transplantation between those with or without granuloma in the explanted lung; P = .886. CONCLUSION: The presence of granuloma in the explanted lungs of LTRs or positive mycobacterial cultures at time of transplant is associated with an increased risk of mycobacterial infection post-transplant.
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Granuloma/microbiología , Enfermedades Pulmonares/microbiología , Trasplante de Pulmón/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/etiología , Femenino , Granuloma/complicaciones , Trasplante de Corazón-Pulmón/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium/aislamiento & purificación , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
RATIONALE: Cytomegalovirus (CMV)-seronegative recipients receiving a seropositive allograft (D+/R-) are at a high risk of developing CMV disease. Our program increased the duration of CMV prophylaxis from 6 to 9 months in May 2013. Here, we present the impact on the incidence of CMV infection, disease, side effects, rejection, and other factors. METHODS: Retrospective cohort of 241 CMV (D+/R-) patients transplanted between January 1, 2008, and December 31, 2017. Blood CMV testing was done according to protocol. All patients received ganciclovir/valganciclovir as prophylaxis. We compared the incidence and timing of CMV infection and disease up to 6 months after cessation of prophylaxis between patients who received 9 months (May 2013 onwards) and a historical control group who received 6 months of prophylaxis (prior to May 2013). CMV infection was defined as detectable CMV viremia in the absence of symptoms. CMV disease was defined as CMV syndrome or tissue-invasive disease. Side effects of prophylaxis and CMV resistance were recorded. RESULTS: A total of 116 patients were included in the 6-month group and 125 in the 9-month group. The extended 9-month CMV prophylaxis delayed the onset of CMV infection (median time to CMV infection after lung transplantation 295 vs 353 days, P < .01) but did not significantly reduce the incidence of CMV infection (65% vs 64%, P = .06, log-rank). The 9-month prophylaxis delayed the onset and decreased the incidence of CMV disease from 50% in the 6-month group to 42% (P = .02 log-rank). There was no difference in the rate of adverse effects (leukopenia in 32% in both groups, P = .53) or development of CMV resistance between the two groups (4 cases in both groups, P = .92). There were no significant differences in overall survival or the rate of chronic lung allograft dysfunction between the groups. CONCLUSIONS: Extending duration of CMV prophylaxis from 6 to 9 months resulted in a delayed and decreased incidence of CMV disease in our lung transplant population. The absolute risk reduction achieved by extended CMV prophylaxis was 8%. The incidence of CMV infection, and ganciclovir resistance and side effects were similar between the two groups. Our results suggest that extending CMV prophylaxis in the highest risk CMV D+/R- group is effective in reducing CMV disease.
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Antivirales/administración & dosificación , Infecciones por Citomegalovirus/prevención & control , Esquema de Medicación , Trasplante de Pulmón/efectos adversos , Profilaxis Pre-Exposición/métodos , Receptores de Trasplantes , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Ganciclovir/administración & dosificación , Ganciclovir/uso terapéutico , Rechazo de Injerto/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante Homólogo , Valganciclovir/administración & dosificación , Valganciclovir/uso terapéuticoAsunto(s)
Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Inmunización Secundaria , Inmunogenicidad Vacunal , SARS-CoV-2/inmunología , Receptores de Trasplantes , Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/inmunología , Humanos , Trasplante de ÓrganosRESUMEN
BACKGROUND: Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU). METHODS: We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge. RESULTS: The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time. CONCLUSIONS: In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).
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Cuidadores/psicología , Enfermedad Crítica/enfermería , Depresión/etiología , Familia/psicología , Adulto , Anciano , Depresión/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Estrés PsicológicoRESUMEN
Telehealth uses videoconferencing to provide long-distance clinical care. Experience with telehealth in the setting of organ transplantation is limited. The purpose of this cohort study was to compare the impact of telehealth vs in-person follow-up of lung transplant recipients. Telehealth eligible patients were three or more years post-transplant and resided in Ontario outside the Greater Toronto Area. Patients with initial telehealth visits between July 1, 2009, and Dec 31, 2014, were retrospectively reviewed to assess outcomes of chronic lung allograft dysfunction progression and mortality until December 31, 2016, compared with eligible patients seen in-person. Of eligible patients (n = 204), 119 (58.3%) were seen via telehealth. Most patients (97%) rated telehealth as equivalent or superior to clinic visits. Telehealth visits resulted in significant out-of-pocket cost savings and travel distance savings for patients. There was no significant difference in mortality from the time of first visit (HR 0.81, 95% CI 0.49-1.32, P = 0.4) or from the time of transplant between groups (HR 0.72, 95% CI 0.43-1.17, P = 0.2). Telehealth can safely and effectively be used in select transplant recipients to increase access to care and reduce time and financial burdens for patients residing greater distances from primary transplant centers.
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Continuidad de la Atención al Paciente/estadística & datos numéricos , Personal de Salud/estadística & datos numéricos , Trasplante de Pulmón/mortalidad , Telemedicina/métodos , Receptores de Trasplantes/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Lung retransplantation is an important therapy for a growing population of lung transplant recipients with graft failure, but detailed outcome data are lacking. METHODS: We conducted a retrospective cohort study of adult lung retransplant in the Toronto Lung Transplant Program from 2001 to 2013 (n = 38). We analyzed the postoperative course, graft function, renal function, microbiology, donor-specific antibodies (DSA), quality of life, and survival compared to a control cohort of primary transplant recipients matched for age and era. RESULTS: Indication for retransplant was chronic lung allograft dysfunction in most retransplant recipients (35/38, 92%). The postoperative course was more complex after retransplant than primary (ventilation time, 8 vs 2 days, P < .01; ICU stay 14 vs 4 days, P < 0.01), and peak lung function was lower (FEV1 2.2L vs 3L, P < .01). Quality of life scores were comparable, as were renal function, microbiology, and donor-specific antibody formation. Median survival was 1988 days after primary and 1475 days after retransplant (P = .39). CONCLUSIONS: Lung retransplantation is associated with a more complex postoperative course and lower peak lung function, but the long-term medical profile is similar to primary transplant. Lung retransplantation can be beneficial for carefully selected candidates with allograft failure.
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Rechazo de Injerto , Supervivencia de Injerto , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/mortalidad , Complicaciones Posoperatorias , Calidad de Vida , Adulto , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Epstein-Barr virus (EBV) D+/R- organ transplant recipients are a high-risk group for developing post-transplant lymphoproliferative disease (PTLD). Little data are available for prevention in the adult EBV mismatched population. We conducted a retrospective study of EBV D+/R- organ transplants performed during 2002-2014. Of the 153 patients identified, 82.4% patients received antiviral prophylaxis with valganciclovir for a median of 4.5 months (range: 0.8-22 months) and 36.6% underwent viral load monitoring in the first post-transplant year. EBV viremia developed in 67.2% monitored patients. In viremic patients, immunosuppression was reduced in 20/37(54.1%) in response to viremia and 17/37 (45.9%) received therapeutic dose valganciclovir. In patients with EBV viremia who received valganciclovir and/or had a reduction in immunosuppression and had sufficient viral load time points (n=31), 28 (90.3%) had a significant decline in viral load at day 14 (median log decline 0.49 (0.24-0.64), P<.001) and at day 30 (0.87 (0.52-1.21), P<.001). PTLD developed in 27 (15%) patients (biopsy proven=25, possible=2) at median 8 months (range: 2.4-130) post-transplant with the majority (81.5%) within the first year. In multivariate analysis, viral load monitoring and use of mycophenolate were associated with a lower incidence of PTLD. Antiviral prophylaxis was not associated with a lower risk of PTLD, but viral load monitoring and use of mycophenolate mofetil were protective.
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Infecciones por Virus de Epstein-Barr/etiología , Rechazo de Injerto/etiología , Herpesvirus Humano 4/patogenicidad , Trastornos Linfoproliferativos/etiología , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias , Viremia/etiología , Adolescente , Adulto , Anciano , ADN Viral , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Receptores de Trasplantes , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: We previously identified factors associated with a greater risk of death post-transplant. The purpose of this study was to develop a clinical tool to estimate the risk of death after transplant based on pre-transplant variables. METHODS: We utilized the Canadian CF registry to develop a nomogram that incorporates pre-transplant clinical measures to assess post-lung transplant survival. The 1-, 3-, and 5-year survival estimates were calculated using Cox proportional hazards models. RESULTS: Between 1988 and 2012, 539 adult Canadians with CF received a lung transplant with 208 deaths in the study period. Four pre-transplant factors most predictive of poor post-transplant survival were older age at transplantation, infection with B. cepacia complex, low FEV1 percent predicted, and pancreatic sufficiency. A nonlinear relationship was found between risk of death and FEV1 percent predicted, age at transplant, and BMI. We constructed a risk calculator based on our model to estimate the 1-, 3-, and 5-year probability of survival after transplant which is available online. CONCLUSIONS: Our risk calculator quantifies the risk of death associated with lung transplant using pre-transplant factors. This tool could aid clinicians and patients in the decision-making process and provide information regarding the timing of lung transplantation.
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Fibrosis Quística/cirugía , Rechazo de Injerto/mortalidad , Trasplante de Pulmón/mortalidad , Complicaciones Posoperatorias/mortalidad , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
RATIONALE: Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear. OBJECTIVES: To describe the incidence, characteristics, and impact of dnDSA after lung transplantation. METHODS: We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011. All patients underwent HLA-antibody testing quarterly pretransplant and at regular intervals over the first 24 months after transplant. The patients received modified immunosuppression depending on their pretransplant sensitization status. Risk factors for dnDSA development, as well as the associations of dnDSA with patient survival and chronic lung allograft dysfunction (CLAD), were determined using multivariable analysis. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of dnDSA was 47% at a median of 86 days (range, 44-185 d) after lung transplantation. Seventy-six percent of recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13-3.69). This association appeared to be driven by the development of DQ-dnDSA. CONCLUSIONS: dnDSA are common after lung transplantation, with the majority being DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients.
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Aloinjertos/inmunología , Bronquiolitis Obliterante/inmunología , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Trasplante de Pulmón/efectos adversos , Pulmón/inmunología , Donantes de Tejidos , Aloinjertos/estadística & datos numéricos , Bronquiolitis Obliterante/epidemiología , Bronquiolitis Obliterante/etiología , Femenino , Rechazo de Injerto/complicaciones , Rechazo de Injerto/epidemiología , Humanos , Inmunosupresores/administración & dosificación , Estimación de Kaplan-Meier , Trasplante de Pulmón/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Ontario/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Distribución por SexoRESUMEN
BACKGROUND: More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP. METHODS: In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital. RESULTS: During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP. CONCLUSIONS: Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).
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Trasplante de Pulmón , Pulmón/fisiología , Perfusión/métodos , Adolescente , Adulto , Anciano , Estudios de Factibilidad , Supervivencia de Injerto , Humanos , Persona de Mediana Edad , Preservación de Órganos/métodos , Estudios Prospectivos , Intercambio Gaseoso Pulmonar , Mecánica Respiratoria , Donantes de Tejidos , Recolección de Tejidos y Órganos , Resistencia Vascular , Adulto JovenRESUMEN
OBJECTIVES: To determine the impact of older donor age (70+ years) on long-term survival and freedom from chronic lung allograft dysfunction in lung transplant (LTx) recipients. METHODS: A retrospective single-center study was performed on all LTx recipients from 2002 to 2017 and a modern subgroup from 2013 to 2017. Recipients were stratified into 4 groups based on donor lung age (<18, 18-55, 56-69, ≥70 years). Donor and recipient characteristics were compared using χ2 tests for differences in proportions and analysis of variance for differences in means. Univariable and multivariable Cox regression was used to describe differences in long-term survival and freedom from chronic lung allograft dysfunction. RESULTS: Between 2002 and 2017, 1600 LTx were performed, 98 of which were performed from donors aged 70 years or older. Recipients of 70+ years donor lungs were significantly older with a mean age of 55.5 ± 12.9 years old (P = .001) and had more Status 3 (urgent) recipients (37.4%, P = .002). After multivariable regression, there were no significant differences in survival or freedom from chronic lung allograft dysfunction between the 4 strata of recipients. CONCLUSIONS: Lung transplantation using donors 70 years old or older can be considered when all other parameters suggest excellent donor lung function without compromising short- or long-term outcomes.
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Trasplante de Pulmón , Donantes de Tejidos , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Factores de Edad , Trasplante de Pulmón/efectos adversos , PulmónRESUMEN
We previously described restrictive allograft syndrome as a form of chronic lung allograft dysfunction, demonstrating restrictive pulmonary function decline. However, the histopathological correlates of restrictive allograft syndrome have yet to be satisfactorily described. We hypothesized that pulmonary pleuroparenchymal fibroelastosis, as has recently been described in bone marrow transplant recipients, may also be present in the lungs of patients with restrictive allograft syndrome. Retrospective review of 493 patients who underwent lung transplantation between 1 January 1996 and 30 June 2009, was conducted. Out of 47 patients with clinical features of restrictive allograft syndrome, 16 had wedge biopsy, re-transplant lung explant, or autopsy lung specimens available for review. All lungs showed varying degrees of pleural fibrosis. Fifteen of 16 showed parenchymal fibroelastosis, characterized by hypocellular collagen deposition with preservation and thickening of the underlying alveolar septal elastic network. The fibroelastosis was predominantly subpleural in distribution, with some cases also showing centrilobular and paraseptal distribution. A sharp demarcation was often seen between areas of fibroelastosis and unaffected lung parenchyma, with fibroblastic foci often present at this interface. Concurrent features of obliterative bronchiolitis were present in 14 cases. Another common finding was the presence of diffuse alveolar damage (13 cases), usually in specimens obtained <1 year after clinical onset of restrictive allograft syndrome. The single specimen in which fibroelastosis was not identified was obtained before the clinical onset of chronic lung allograft dysfunction, and showed features of diffuse alveolar damage. In conclusion, pleuroparenchymal fibroelastosis is a major histopathologic correlate of restrictive allograft syndrome, and was often found concurrently with diffuse alveolar damage. Our findings support a temporal sequence of diffuse alveolar damage followed by the development of pleuroparenchymal fibroelastosis in the histopathologic evolution of restrictive allograft syndrome.
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Enfermedades Pulmonares Intersticiales/etiología , Trasplante de Pulmón/efectos adversos , Pulmón/patología , Pleura/patología , Enfermedades Pleurales/etiología , Adolescente , Adulto , Autopsia , Biopsia , Bronquiolitis Obliterante/etiología , Bronquiolitis Obliterante/patología , Colágeno/análisis , Tejido Elástico/patología , Femenino , Humanos , Pulmón/química , Enfermedades Pulmonares Intersticiales/metabolismo , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Pleura/química , Enfermedades Pleurales/metabolismo , Enfermedades Pleurales/patología , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/patología , Estudios Retrospectivos , Síndrome , Adulto JovenRESUMEN
There is no consensus on the best model of care for individuals with CF to manage the non-pulmonary complications that persist after lung transplant. The CF Foundation virtually convened a group of international experts in CF and lung-transplant care. The committee reviewed literature and shared the post-lung transplant model of care practiced by their programs. The committee then developed a survey that was distributed internationally to both the clinical and individual with CF/family audiences to determine the strengths, weaknesses, and preferences for various models of transplant care. Discussion generated two models to accomplish optimal CF care after transplant. The first model incorporates the CF team into care and proposes delineation of responsibilities for the CF and transplant teams. This model is reliant on outstanding communication between the teams, while leveraging the expertise of the CF team for management of the non-pulmonary manifestations of CF. The transplant team manages all aspects of the transplant, including pulmonary concerns and management of immunosuppression. The second model consolidates care in one center and may be more practical for transplant programs that have expertise managing CF and have access to CF multidisciplinary care team members (e.g., located in the same institution). The best model for each program is influenced by several factors and model selection needs to be decided between the transplant and the CF center and may vary from center to center. In either model, CF lung transplant recipients require a clear delineation of the roles and responsibilities of their providers and mechanisms for effective communication.
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Fibrosis Quística , Trasplante de Pulmón , Humanos , Fibrosis Quística/cirugía , Fibrosis Quística/complicaciones , Trasplante de Pulmón/efectos adversos , Receptores de Trasplantes , Encuestas y Cuestionarios , ConsensoRESUMEN
Background: Morbidity and mortality in lung transplant recipients are often triggered by recurrent aspiration events, potentiated by oesophageal and gastric disorders. Previous small studies have shown conflicting associations between oesophageal function and the development of chronic lung allograft dysfunction (CLAD). Herein, we sought to investigate the relationship between oesophageal motility disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients. Methods: All lung transplant recipients at the Toronto Lung Transplant Program from 2012 to 2018 with available oesophageal manometry testing within the first 7â months post-transplant were included in this study. Patients were categorised according to the Chicago Classification of oesophageal disorders (v3.0). Associations between oesophageal motility disorders with the development of CLAD and allograft failure (defined as death or re-transplantation) were assessed. Results: Of 487 patients, 57 (12%) had oesophagogastric junction outflow obstruction (OGJOO) and 47 (10%) had a disorder of peristalsis (eight major, 39 minor). In a multivariable analysis, OGJOO was associated with an increased risk of CLAD (HR 1.71, 95% CI 1.15-2.55, p=0.008) and allograft failure (HR 1.69, 95% CI 1.13-2.53, p=0.01). Major disorders of peristalsis were associated with an increased risk of CLAD (HR 1.55, 95% CI 1.01-2.37, p=0.04) and allograft failure (HR 3.33, 95% CI 1.53-7.25, p=0.002). Minor disorders of peristalsis were not significantly associated with CLAD or allograft failure. Conclusion: Lung transplant recipients with oesophageal stasis characterised by OGJOO or major disorders of peristalsis were at an increased risk of adverse long-term outcomes. These findings will help with risk stratification of lung transplant recipients and personalisation of treatment for aspiration prevention.
RESUMEN
BACKGROUND: With >700 transplant surgeries performed each year, Toronto General Hospital (TGH) is currently one of the largest adult transplant centers in North America. There is a lack of literature regarding both the identification and management of chronic postsurgical pain (CPSP) after organ transplantation. Since 2014, the TGH Transitional Pain Service (TPS) has helped manage patients who developed CPSP after solid organ transplantation (SOT), including heart, lung, liver, and renal transplants. METHODS: In this retrospective cohort study, we describe the association between opioid consumption, psychological characteristics of pain, and demographic characteristics of 140 SOT patients who participated in the multidisciplinary treatment at the TGH TPS, incorporating psychology and physiotherapy as key parts of our multimodal pain management regimen. RESULTS: Treatment by the multidisciplinary TPS team was associated with significant improvement in pain severity and a reduction in opioid consumption. CONCLUSIONS: Given the risk of CPSP after SOT, robust follow-up and management by a multidisciplinary team should be considered to prevent CPSP, help guide opioid weaning, and provide psychological support to these patients to improve their recovery trajectory and quality of life postoperatively.