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2.
Pediatr Pulmonol ; 2024 07 11.
Article in English | MEDLINE | ID: mdl-38990104

ABSTRACT

BACKGROUND: Racial and ethnic disparities in pediatric lung transplantation (LTx) related to the shifting cystic fibrosis (CF) population receiving highly effective modulator therapy (HEMT) has not been well investigated. METHODS: The UNOS Registry was queried for patients age 1-25 years undergoing bilateral LTx between 1 January 2012 and 31 December 2021. Race and ethnicity were classified as non-Hispanic White, non-Hispanic Black, Hispanic, or none of the above. The primary outcome was posttransplant mortality. Trends in the association between race/ethnicity and mortality were examined using transplant year as a continuous variable and stratifying year based on introduction of HEMT (triple combination therapy) in November 2019. RESULTS: In the study sample (N = 941), 7% of patients were non-Hispanic Black, 15% were Hispanic, and 2% were some other racial or ethnic group. One hundred (11%) received LTx after approval of triple combination therapy, and 407 (43%) died during follow-up. We identified a statistically significant disparity in mortality hazard (hazard ratio: 1.91; 95% confidence interval: 1.31, 2.80) in non-Hispanic Black compared to non-Hispanic White patients in the pre-triple combination therapy era. CONCLUSIONS: We found higher mortality hazard among non-Hispanic Black compared to non-Hispanic White children undergoing LTx in the United States. Further monitoring of LTx outcomes to identify and address disparities is needed in the current era of triple combination therapy for CF.

3.
Front Immunol ; 15: 1371554, 2024.
Article in English | MEDLINE | ID: mdl-38846942

ABSTRACT

Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area.


Subject(s)
Graft Rejection , Immunosuppression Therapy , Organ Transplantation , Photopheresis , Photopheresis/methods , Humans , Organ Transplantation/adverse effects , Organ Transplantation/methods , Graft Rejection/prevention & control , Graft Rejection/immunology , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Graft Survival
4.
Pediatr Transplant ; 28(2): e14739, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38436533

ABSTRACT

Lung transplantation is considered as the ultimate therapy for children with advanced pulmonary disease. International data show a median conditional 1-year post-transplantation survival of 9.1 years. Recently, antibody-mediated rejection (AMR) has increasingly been recognized as an important cause of allograft dysfunction although pediatric reports are still scarce. Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) are known to play a role in AMR development post-transplant but AMR pathogenesis is still poorly understood. Central to the concept of pulmonary AMR is immune activation with the production of allo-specific B-cells and plasma cells directed against donor lung antigens. The frequency of pulmonary AMR in children is currently unknown. Due to the lack of AMR data in children, the diagnostic approach for pediatric pulmonary AMR is solely based on adult literature. This personal viewpoint article evaluates the rational for the creation of age-based thresholds for different diagnostic categories of pulmonary AMR and data on the management of pulmonary AMR in children. To the authors' knowledge, there have been no randomized controlled trials comparing different management regimes in pulmonary AMR, and thus, management and treatment algorithms for pulmonary AMR in children are only extrapolated from adults. To advance the knowledge of AMR in children, the authors propose that children be included in collaborative, multi-center trials. It is vital that future decisions on internationally agreed upon guidelines for pulmonary AMR take its impact on children into consideration. Research is needed to fill the current knowledge gaps in the field of pulmonary AMR in children focused on optimizing outcomes.


Subject(s)
Antibodies , Lung Transplantation , Adult , Humans , Child , Algorithms , B-Lymphocytes , Histocompatibility Antigens Class II
5.
Ann Am Thorac Soc ; 21(3): 411-420, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37879036

ABSTRACT

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV1) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P = 0.008) and 0.60 (0.48-0.82; P < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak > 49.2% predicted (P < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.


Subject(s)
Cystic Fibrosis , Lung Transplantation , Humans , Exercise Test , Prognosis , Retrospective Studies
6.
Clin Transplant ; 37(6): e15018, 2023 06.
Article in English | MEDLINE | ID: mdl-37218644

ABSTRACT

Pediatric lung transplantation (LTX) remains limited by the scarcity of small donor lungs, particularly in less populated parts of the world. Optimal organ allocation, including the prioritization and ranking of pediatric LTX candidates, and the appropriate matching of pediatric donors to recipients have been crucial elements in improving pediatric LTX outcomes. We aimed to elucidate the various pediatric lung allocation practices worldwide. A global survey of current pediatric solid organ transplantation deceased donation allocation practices was conducted by the International Pediatric Transplant Association (IPTA), and these policies were subsequently analyzed if publicly available, with focus on pediatric lung transplantation. Significant variation was found in lung allocation systems worldwide both in terms of prioritization and distribution for children. Definition of pediatrics varied from <12 years of age to <18 years of age. While several countries performing LTX for young children do not have a formal system to prioritize pediatric candidates, many countries that perform LTX at higher rates do offer prioritization methods for children: including the United States, United Kingdom, France, Italy, Australia, and countries serviced by Eurotransplant. Certain lung allocation practices for pediatrics are highlighted herein, including the newly instituted Composite Allocation Score (CAS) system in the United States, pediatric matching with Eurotransplant, and pediatric prioritization in Spain. The systems highlighted here explicitly aim to provide judicious and high quality LTX care for children.


Subject(s)
Lung Transplantation , Tissue and Organ Procurement , Humans , Child , United States , Child, Preschool , Retrospective Studies , Lung Transplantation/methods , Tissue Donors , United Kingdom , Waiting Lists
7.
Pediatr Pulmonol ; 58(1): 213-221, 2023 01.
Article in English | MEDLINE | ID: mdl-36200536

ABSTRACT

INTRODUCTION: Chronic lung allograft dysfunction (CLAD) continues to negatively impact the survival of pediatric lung transplant (LTx) recipients. Current consensus guidelines are adult-focused. We sought to examine CLAD detection and monitoring practices at pediatric LTx programs. METHODS: We conducted a survey among the International Pediatric Lung Transplant Collaborative. Questions consisted of practitioner's experience, LTx program demographics, and querying tests used for CLAD surveillance and detection. Investigations queried included: chest x-ray (CXR), chest computed tomography (CT), lung magnetic resonance imaging (MRI), ventilation/perfusion scanning, conventional pulmonary function testing (PFT), multiple breath washout (MBW), infant/preschool PFT, bronchoalveolar lavage, transbronchial biopsies (TBBx), or other tissue sampling techniques. Preferences for certain modalities over others were questioned based on a five-point Likert scale. RESULTS: Twenty-four of 25 programs responded. Chest CT and CXR are used generally for both CLAD surveillance and detection. No programs use lung MRI clinically, it may have some utility in the future. While all centers use conventional PFT, MBW, and infant/preschool PFT are used in one-fifth and one-third of centers, respectively. While the majority of programs use TBBx, only 41.7% would obtain a diagnosis based on tissue histopathology over noninvasive techniques if CLAD is suspected. Utilization of biomarkers is still limited. CONCLUSIONS: Our results indicate continued use of conventional PFT along with chest CT and less so CXR for CLAD detection and monitoring in the large majority of centers. Infant/preschool PFT and novel methods such as MBW are used in a few centers only. Respondents agreed there is a timely need for pediatric consensus guidelines on CLAD detection and monitoring.


Subject(s)
Lung Transplantation , Adult , Humans , Child , Child, Preschool , Retrospective Studies , Lung/diagnostic imaging , Transplantation, Homologous , Allografts/diagnostic imaging
8.
J Heart Lung Transplant ; 41(11): 1617-1627, 2022 11.
Article in English | MEDLINE | ID: mdl-35970649

ABSTRACT

BACKGROUND: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. METHODS: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. RESULTS: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. CONCLUSIONS: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.


Subject(s)
Cystic Fibrosis , Frailty , Lung Transplantation , Adult , Humans , Frailty/complications , Cystic Fibrosis/complications , Cystic Fibrosis/surgery , Waiting Lists , Cohort Studies
9.
ERJ Open Res ; 8(3)2022 Jul.
Article in English | MEDLINE | ID: mdl-35898810

ABSTRACT

Bronchiolitis obliterans syndrome (BOS) may develop after either lung or haematopoietic stem cell transplantation (HSCT), with similarities in histopathological features and clinical manifestations. However, there are differences in the contributory factors and clinical trajectories between the two conditions. BOS after HSCT occurs due to systemic graft-versus-host disease (GVHD), whereas BOS after lung transplantation is limited to the lung allograft. BOS diagnosis after HSCT is more challenging, as the lung function decline may occur due to extrapulmonary GVHD, causing sclerosis or inflammation in the fascia or muscles of the respiratory girdle. Treatment is generally empirical with no established effective therapies. This review provides rare insights and commonalities of both conditions, which are not well elaborated elsewhere in contemporary literature, and highlights the importance of cross disciplinary learning from experts in other transplant modalities. Treatment algorithms for each condition are presented, based on the published literature and consensus clinical opinion. Immunosuppression should be optimised, and other conditions or contributory factors treated where possible. When initial treatment fails, the ultimate therapeutic option is lung transplantation (or re-transplantation in the case of BOS after lung transplantation) in carefully selected candidates. Novel therapies under investigation include aerosolised liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies and (in patients with BOS after lung transplantation) B-cell-directed therapies. Effective novel treatments that have a tangible impact on survival and thereby avoid the need for lung transplantation or re-transplantation are urgently required.

10.
Clin Transplant ; 36(4): e14634, 2022 04.
Article in English | MEDLINE | ID: mdl-35244236

ABSTRACT

There has been a shift over decades in the diagnostic indications for lung transplantation in children; in particular, there has been a reduction in the proportion of pediatric cystic fibrosis (CF) patients undergoing lung transplantation early in life, and more transplants occurring in other diagnostic groups. Here, we examine trends in pediatric lung transplantation with regards to indications by analyzing data from the United Network of Organ Sharing, the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, and other sources. Over the past two years, there has been a precipitous decline in both the number of transplants due to CF and the proportion of CF cases relative to the total number of transplants, likely not solely due to the COVID-19 pandemic. In 2020, primary pulmonary arterial hypertension for the first-time surpassed CF as main indication for pediatric lung transplantation in the United States, a finding that is also reflected in international data. We discuss the effect of novel CFTR modulator therapies as a major factor leading to this shifting landscape. Based on our trending, pulmonary hypertension-related diagnoses and pediatric interstitial lung diseases are rising indications, for which we suggest adjustments of consensus guidelines around candidate selection criteria.


Subject(s)
COVID-19 , Cystic Fibrosis , Heart Transplantation , Heart-Lung Transplantation , Lung Transplantation , COVID-19/epidemiology , Child , Cystic Fibrosis/surgery , Humans , Lung Transplantation/adverse effects , Pandemics , Survival Rate , Tissue Donors , United States
11.
Swiss Med Wkly ; 152: w30139, 2022 02 14.
Article in English | MEDLINE | ID: mdl-35201682

ABSTRACT

AIMS OF THE STUDY: Organ donation after circulatory death (DCD) was reintroduced in Switzerland in 2011 and accounts for a third of deceased organ donors today. Controversy persists if DCD transplants are of similar quality to transplants following donation after brain death (DBD), mainly due to warm ischaemia time DCD organs are exposed to. We compared DCD with DBD in Switzerland. METHODS: Data on deceased adults who were referred to and approved for organ donation from 1 September 2011 to 31 December 2019 were retrospectively analysed (217 DCD, 840 DBD donors). We compared DCD and DBD donor/organ characteristics, transplant rates of lungs, liver, kidneys, and pancreas, and early liver and kidney graft function in the recipient. The effect of DCD/DBD on transplant rates (organ transplanted or not) and 72-hour recipient graft function (moderate/good vs delayed graft function / organ loss) was analysed using multivariable logistic regression. Among utilised DCD donors, we analysed the effect of functional warm ischaemia time (FWIT) and donor age on 72-hour post-transplant liver and kidney graft function, also using multivariable logistic regression. RESULTS: DCD donors were more often male (64.5% vs 56.8% p = 0.039), presented with heart disease (36.4% vs 25.5%, p <0.001), were resuscitated before hospital admission (41.9% vs 30.7%, p = 0.006), and died from anoxia (41.9% vs 23.9%). Kidney function before transplantation was comparable, lung, liver and pancreas function were poorer in DCD than DBD. Eighty-one and 91% of approved DCD and DBD donors were utilised (p <0.001). Median FWIT in DCD was 29 minutes (interquartile range 25-35). DCD transplant rates ranged from 4% (pancreas) to 73% (left kidney) and were all lower compared with DBD. Seventy-two-hour liver graft function was comparable between DCD and DBD (94.2% vs 96.6% moderate/good, p = 0.199). DCD kidney transplants showed increased risk of delayed graft function or early organ loss (odds ratios 8.32 and 5.05; 95% confidence intervals CI 5.28-13.28 and 3.22-7.95; both p <0.001, for left and right kidney transplants, respectively). No negative effect of prolonged FWIT or higher donor age was detected. CONCLUSION: Despite less favourable donor/organ characteristics compared with donation after brain death, donation after circulatory death donors are increasingly referred and today provide an important source for scarce transplants in Switzerland. We identified a higher risk for delayed graft function or early organ loss for DCD kidney transplants, but not for DCD liver transplants. When carefully selected and allowed for other risk factors in organ allocation, prolonged functional warm ischaemia time or higher age in donation after circulatory death does not seem to be associated with impaired graft function early after transplantation.


Subject(s)
Brain Death , Tissue and Organ Procurement , Adult , Aged , Death , Graft Survival , Humans , Male , Retrospective Studies , Switzerland , Tissue Donors
12.
Pediatr Transplant ; 26(5): e14235, 2022 08.
Article in English | MEDLINE | ID: mdl-35060251

ABSTRACT

BACKGROUND: COVID-19 vaccination has been successful in decreasing rates of SARS-CoV-2 infection in areas with high vaccine uptake. Cases of breakthrough SARS-CoV-2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID-19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID-19 vaccine formulations. Importantly, Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine studies have now included children as young as 5 years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5- to 11-year-old age group. METHODS: Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID-19 vaccine data with focus on pediatric solid organ transplant (SOT)-specific issues. RESULTS: This review provides an overview of current COVID-19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge. CONCLUSIONS: Further studies of COVID-19 vaccination in pediatric SOT recipients are needed to better understand post-vaccine COVID-19 T-cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID-19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID-19 poses to pediatric solid organ transplant recipients.


Subject(s)
COVID-19 , Organ Transplantation , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Child , Child, Preschool , Humans , SARS-CoV-2 , Transplant Recipients , Vaccination
13.
PLoS One ; 16(9): e0257852, 2021.
Article in English | MEDLINE | ID: mdl-34555108

ABSTRACT

BACKGROUND: We have recently reported reduced physical activity (PA) in people with cystic fibrosis (pwCF) with and without lung transplantation (LTX) during a 6-week stringent lockdown in Switzerland. This follow-up study explores the impact of coronavirus-2019 disease (COVID-19) related pandemic restrictions on individuals' therapy regimens and health-related aspects in pwCF. METHODS: We conducted a cross-sectional web-based national survey in Spring 2021. The survey included questions on daily PA, airway clearance and inhalation therapy, questions on COVID-19-compatible symptoms, diagnostic tests and vaccination status, and enquired health-related aspects covering the pandemic period between March 2020 to April 2021. RESULTS: 193 individuals with CF (53% female; 25% LTX recipients) participated. Among pwCF, 10 reported COVID-19 (n = 2 LTX recipients), two subjects were hospitalized, no invasive ventilation required, no deaths. The clinical course was generally mild. Overall, 46% reported less PA during the pandemic, mostly due to closed fitness facilities (85%), lack of motivation (34%), and changes in daily structures (21%). In contrast, 32/193 (17%) pwCF were able to increase their PA levels: 12 (38%) and 11 (34%) reported undertaking home-based training and outdoor activities more frequently; 6 (19%) reported an increase in routine PA, and another 3 (9%) started new activities. Among pwCF without LTX, 5% and 4% reported to undertake less airway clearance and inhalation therapy, respectively. CONCLUSIONS: Our study reveals unfavorable consequences of COVID-19 pandemic restrictions on PA of pwCF with unknown long-term consequences for their overall physical fitness and lung health. Strategies to overcome this undesirable situation are needed; increased uptake of telehealth PA programs and virtual exercise classes to promote PA participation might be one promising approach along with vaccination of pwCF and their close contacts.


Subject(s)
COVID-19/epidemiology , Cystic Fibrosis/physiopathology , Exercise/physiology , Pandemics/statistics & numerical data , Adolescent , Adult , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Lung Transplantation/statistics & numerical data , Male , Middle Aged , Motivation/physiology , Surveys and Questionnaires , Switzerland , Young Adult
14.
Pulm Ther ; 7(2): 377-393, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34406641

ABSTRACT

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian people and is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein. It is a multisystem disorder; however, CF lung disease causes most of its morbidity and mortality. Although survival for CF has improved over time due to a multifaceted symptomatic management approach, CF remains a life-limiting disease. For individuals with progressive advanced CF lung disease (ACFLD), lung transplantation is considered the ultimate treatment option if compatible with goals of care. Since 2012, newer drugs, called CFTR modulators, have gradually become available, revolutionizing CF care, as these small-molecule drugs target the underlying defect in CF that causes decreased CFTR protein synthesis, function, or stability. Because of their extremely high efficacy and overall respectable tolerability, CFTR modulator drugs have already proven to have a substantial positive impact on the lives of individuals with CF. Individuals with ACFLD have generally been excluded from initial clinical trials. Now, however, these drugs are being used in clinical practice in selected individuals with ACFLD, showing promising results, although randomized controlled trial data for CFTR modulators in this subgroup of patients are lacking. Such data need to be gathered, ideally in randomized controlled trials including patients with ACFLD. Furthermore, the efficacy and tolerability of the newer modulator therapies in individuals with ACFLD need to be monitored, and their impact on lung disease progression and the need for lung transplantation as the ultimate therapy call for an objective evaluation in larger patient cohorts. As of today, guidelines for referral and listing of lung transplant candidates with CF have not incorporated the status of the new CFTR modulator therapies in the referral and listing process. The purpose of this review article, therefore, is threefold: first, to describe the effects of new therapies, with a focus on the subgroup of individuals with ACFLD; second, to provide an update on the recent outcomes after lung transplantation for individuals with CF; and third, to discuss the referral, evaluation, and timing for lung transplantation as the ultimate therapeutic option in view of the new treatments available in CF.

15.
Pediatr Transplant ; 25(6): e14031, 2021 09.
Article in English | MEDLINE | ID: mdl-34076928

ABSTRACT

BACKGROUND: Population-level COVID-19 immunization will play a key role in slowing down the SARS-CoV-2 pandemic on a global scale and protect the most at-risk individuals. Thanks to a formidable universal effort, several SARS-CoV-2 vaccines have been marketed less than a year since the first documented COVID-19 case, with promising safety, efficacy, and immunogenicity results in adults. As children were not included in the initial trials, no vaccine is currently approved for individuals <16 years of age. Similarly, immunosuppressed individuals, such as solid organ transplant recipients, were excluded from initial vaccine trials, limiting the understanding of vaccine immunogenicity and safety in this at-risk population. Thus, data regarding COVID-19 vaccination in pediatric solid organ transplantation recipients are currently lacking. METHODS: Members of the International Pediatric Transplant Association review the current general status of COVID-19 vaccines focusing on pediatric-specific issues. RESULTS: This review provides an overview of COVID-19 vaccines in pediatric SOT recipients and highlights the current paucity of data in both pediatric and transplant settings in terms of safety, immunogenicity, and clinical efficacy. CONCLUSIONS: Vaccine trials including children and transplant recipients are underway and will be necessary to characterize COVID-19 vaccine safety, immunogenicity, and efficacy, which will determine potential future research directions.


Subject(s)
COVID-19 Vaccines , Organ Transplantation , COVID-19 Vaccines/immunology , Child , Forecasting , Humans
16.
Clin Transplant ; 35(7): e14335, 2021 07.
Article in English | MEDLINE | ID: mdl-33948997

ABSTRACT

Chronic organ shortage remains the most limiting factor in lung transplantation. To overcome this shortage, a minority of centers have started with efforts to reintroduce donation after circulatory death (DCD). This review aims to evaluate the experimental background, the current international clinical experience, and the further potential and challenges of the different DCD categories. Successful strategies have been implemented to reduce the problems of warm ischemic time, thrombosis after circulatory arrest, and difficulties in organ assessment, which come with DCD donation. From the currently reported results, controlled-DCD lungs are an effective and safe method with good mid-term and even long-term survival outcomes comparable to donation after brain death (DBD). Primary graft dysfunction and onset of chronic allograft dysfunction seem also comparable. Thus, controlled-DCD lungs should be ceased to be treated as marginal and instead be promoted as an equivalent alternative to DBD. A wide implementation of controlled-DCD-lung donation would significantly decrease the mortality on the waiting list. Therefore, further efforts in establishment of legislation and logistics are crucial. With regard to uncontrolled DCD, more data are needed analyzing long-term outcomes. To help with the detailed assessment and improvement of uncontrolled or otherwise questionable grafts after retrieval, ex-vivo lung perfusion is promising.


Subject(s)
Lung Transplantation , Tissue and Organ Procurement , Brain Death , Death , Graft Survival , Humans , Lung , Retrospective Studies , Tissue Donors
17.
Healthcare (Basel) ; 9(4)2021 Apr 12.
Article in English | MEDLINE | ID: mdl-33921523

ABSTRACT

Although transplantation medicine is not new, there is a clinically justified gap in the existing literature with respect to the psychological processing of lung transplants. The present study aims to examine whether lung transplantation leads to an actualization of psychological, e.g., oral-sadistic fantasies. Following a qualitative approach, 38 lung transplant patients were interviewed three times within the first six months after transplantation. Data analysis focused on identifying unconscious and conscious material. The inter-rater reliability for all codes was calculated using Krippendorff's Alpha (c-α-binary = 0.94). Direct and implicit evidence of a so-called transplantation complex was detected e.g., regarding the "incorporation" of the dead donor and his lungs. These processes occur predominantly at an imaginary level and are related to the body. Our findings emphasize that such psychological aspects should be borne in mind in the psychological treatment of lung-transplant patients in order to improve the processing of lung transplants, and that this might have a positive effect on patient adherence.

18.
Swiss Med Wkly ; 151: w20413, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33580706

ABSTRACT

AIMS OF THE STUDY: The lack of suitable donor organs limits the number of solid organ transplants. Patients who underwent cardiopulmonary resuscitation (CPR) after cardiac arrest may represent a sizeable subgroup of deceased organ donors, as they often progress to brain death or have life-sustaining therapy withdrawn. We aimed to quantify deceased organ donation after CPR in Switzerland for the first time by analysing the characteristics of potential and utilised organ donors after CPR. METHODS: Data on deceased adult and paediatric patients who were reported to and approved by Swisstransplant for organ donation were analysed, including both donation after brain death (DBD) and donation after controlled cardiocirculatory death (cDCD) from 2016 to 2018. We analysed baseline characteristics of potential donors who underwent CPR in the context of their hospitalisation, as compared with donors without prior CPR. Considering the varying characteristics between these two donor groups, we assessed the effect of CPR on different allocation outcomes (donor and organ utilisation, organ yield per utilised donor) using multivariable regression. Additionally, we present selected CPR circumstances and compared different subgroups of CPR donors according to duration of CPR and duration of no-flow time. RESULTS: Of the 461 deceased potential organ donors included in the analysis, 173 (37.5%) underwent CPR. CPR donors were, on average, younger (median age 53 vs 62, p <0.001), had different causes of death (p <0.001), and were more often of the cDCD type (30.1% vs 18.4%, p = 0.004) as compared with non-CPR donors. Of the 173 CPR donors, 152 (87.9%) could be utilised (minimum one organ transplanted), and in the multivariable analysis, utilisation rate was higher in the CPR donor group than in the non-CPR donor group (odds ratio 3.3, 95% confidence interval 1.1–11.5; p = 0.046). Organ specific utilisation of heart, liver, and kidney, and total organ yield per donor, did not differ significantly between CPR and non-CPR donors. CONCLUSION: Our study reveals that a substantial proprotion of deceased organ donors in Switzerland underwent CPR in context of their hospitalisation. CPR donors are different from non-CPR donors with respect to age, cause of death and donation type. However, when carefully selected according to their haemodynamic condition, CPR donors are comparable to non-CPR donors in terms of donor and organ utilisation, as well as the average organ yield. Thus, all patients who are resuscitated from cardiac arrest but who subsequently progress to death should be evaluated for organ donation. How CPR donors compare with non-CPR donors regarding transplant outcomes should be studied further.


Subject(s)
Cardiopulmonary Resuscitation , Organ Transplantation , Tissue and Organ Procurement , Adult , Child , Humans , Middle Aged , Switzerland , Tissue Donors
19.
J Clin Apher ; 36(1): 186-188, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32838480

ABSTRACT

Extra-corporeal photopheresis (ECP) is known as safe ultimate treatment option for chronic lung allograft dysfunction (CLAD). Here, we report the first case of ECP as "second-line" immunomodulatory therapy early post-transplant in an adult patient undergoing lung transplantation for severe chronic thromboembolic pulmonary hypertension, complicated by impaired consciousness due to idiopathic hyperammonemia resulting in recurrent hypercapnic respiratory failure. ECP was initiated twice weekly on post-transplant day 25 and standard triple immunosuppression reduced. Within 2 weeks, the clinical status improved. ECP has been continued every 4 weeks after discharge. At 1 year post-transplant, ECP was stopped as maintenance immunosuppression was reached. We recommend to consider the immunomodulatory effect of ECP as "second line" immunomodulatory therapy in cases where standard immunosuppression causes severe collateral damage. ECP is able to assist prevention of allograft rejection in conjunction with reduced levels of standard immunosuppression, even in the early period following lung transplantation.


Subject(s)
Hyperammonemia/therapy , Immunomodulation , Lung Transplantation/adverse effects , Photopheresis/methods , Respiratory Insufficiency/therapy , Adult , Female , Humans , Immunosuppression Therapy , Recurrence
20.
Pediatr Pulmonol ; 56(3): 587-592, 2021 03.
Article in English | MEDLINE | ID: mdl-33210834

ABSTRACT

Lung transplantation is a treatment option for selected children with end-stage lung disease and pulmonary vascular disorders. Overall, pulmonary hypertension (PH) is the second most frequent indication for infants and children requiring lung transplants. In pediatric PH patients, timing for listing remains a difficult decision due to patient heterogeneity and varying allocation policies across different countries. Furthermore, perioperative management can be challenging, making interdisciplinary collaboration among surgical, anesthesiology, critical care, and lung transplant teams essential. Because pediatric PH patients typically have preserved cardiac index and exercise tolerance even with advanced disease, they should be referred early even if they do not meet the criteria for listing of primarily adults by International Society for Heart and Lung Transplantation (ISHLT) published in 2015: New York Heart Association (NYHA) functional class III or IV without improvement, cardiac index < 2 L/min/m2 , mean right atrial pressure of >15 mmHg. Bridging strategies with extracorporeal support should be determined at the time of listing in anticipation of possible clinical deterioration. Bilateral lung transplantation using cardiopulmonary bypass to provide hemodynamic stability is nowadays the standard surgical approach in pediatric centers. The immediate post-transplant period is characterized by dramatic changes in the right ventricle (RV) and and left ventricle (LV) anatomy and physiology, which can be life-threatening. Induction, immunosuppression, prophylaxis, and surveillance are not different from patients without PH. Overall, outcomes in pediatric lung and heart-lung transplant patients for PH are not different from those children undergoing transplantation for other indications. In fact, long-term survival is superior in children with idiopathic PH compared to other diseases, providing most recipients with improved quality of life.


Subject(s)
Familial Primary Pulmonary Hypertension/surgery , Lung Diseases/surgery , Lung Transplantation/methods , Adolescent , Child , Child, Preschool , Echocardiography , Exercise Test , Heart Transplantation/adverse effects , Heart Transplantation/methods , Heart Ventricles , Humans , Immunosuppression Therapy , Infant , Lung/surgery , Lung Transplantation/adverse effects , Magnetic Resonance Imaging , Postoperative Period , Quality of Life , Symptom Assessment , Treatment Outcome , Ventricular Function , Waiting Lists
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