Outcomes of extracorporeal membrane oxygenation cannulation strategy in lung transplantation: A retrospective cohort study.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) with different cannulation strategies is determined according to surgical position and patient condition. However, no cannulation guidelines have been proposed. This retrospective study assessed the outcomes of diverse ECMO cannulation strategies in patients undergoing lung transplantation (LTx). METHODS: Data of patients undergoing intraoperative veno-arterial ECMO-assisted LTx were retrospectively collected from December 1st, 2015 to October 31st, 2021. Patients were classified into three groups based on the different cannulation strategies: femoral artery-femoral vein (F-F)-ECMO, axillary artery-femoral vein (A-F)-ECMO, and ascending aorta-femoral vein (AAO-F)-ECMO. The F-F-ECMO, A-F-ECMO, and AAO-F-ECMO groups comprised 34, 44, and 30 patients, respectively. MAIN RESULTS: The AAO-F-ECMO group exhibited a significantly shorter duration of postoperative ECMO therapy (3 vs. 2 vs. 0 days, P < 0.01).the level of postoperative proBNP was lower on the third and seventh days (P < 0.001). AAO-F-ECMO patients had a significantly lower incidence of postoperative infections, heart failure, and bleeding (P < 0.05). Similar outcomes were observed in postoperative survival rates among the three groups (P > 0.05). CONCLUSIONS: Ascending aorta-femoral vein ECMO can provide sufficient and effective aerobic blood to perfuse organs with fewer side effects than cannulation in the femoral artery-femoral vein or axillary artery-femoral vein.

Description, clinical impact and early outcome of S. maltophilia respiratory tract infections after lung transplantation, A retrospective observational study.

BACKGROUND AND RESEARCH QUESTION: S. maltophilia infections are associated with significant morbidity and mortality. Little is known regarding its presentation, management, and outcome in lung transplant recipients. STUDY DESIGN AND METHODS: This retrospective case control study reviewed S. maltophilia respiratory tract infection in lung transplant recipients (01/01/2011-31/01/2020) and described the clinical, microbiological and outcome characteristics matched with lung transplant recipients without respiratory tract infection. RESULTS AND INTERPRETATION: We identified 63 S. maltophilia infections in lung transplant recipients. Among them none were colonized before transplantation. Infections occurred a median of 177 (IQR: 45- 681) days post transplantation. Fifty-four (85.7 %) patients received trimethoprim-sulfamethoxazole (400/80 mg three times a week) to prevent Pneumocystis jirovecii pneumonia (PJP). S. maltophilia strains were susceptible to trimethoprim-sulfamethoxazole, levofloxacin, minocycline and ceftazidime in respectively 85.7 %, 82.5 %, 96.8 % and 34.9 % of cases. Median duration of treatment was 9 days (IQR 7-11.5). Clinical and microbiological recurrence were observed in respectively 25.3 % and 39.7 % of cases. Combination therapy was not associated with a decrease in the risk of recurrence and did not prevent the emergence of resistance. S. maltophilia respiratory tract infection was associated with a decline in FEV-1 at one year. CONCLUSION: S. maltophilia is an important cause of lower respiratory tract infection in lung transplant recipients. Trimethoprim-sulfamethoxazole use as prophylaxis for PJP doesn't prevent S. maltophilia infection among lung transplant recipients. Levofloxacin and trimethoprim-sulfamethoxazole appear to be the two molecules of choice for the treatment of these infections and new antibiotic strategies (cefiderocol, aztreonam/avibactam) are currently being evaluated for multi-resistant S. maltophilia infections.

A Case of Single-lung Transplant in a Patient with Mycobacterium avium Pulmonary Disease Successfully Treated with Amikacin Liposome Inhalation Suspension.

A 55-year-old man presented to our hospital with idiopathic pulmonary fibrosis (IPF). He was registered with the Japan Organ Transplant Network the following year due to disease progression. Treatment with clarithromycin, ethambutol, and rifampicin for complications of Mycobacterium avium pulmonary disease was initiated, but sputum conversion could not be achieved. The administration of an amikacin liposome inhalation suspension (ALIS) resulted in sputum conversion, and single-lung transplantation was performed. ALIS therapy was continued after lung transplantation, and no M. avium disease was observed for 15 months. ALIS may cause M. avium pulmonary disease with additional indications for lung transplantation.

Efficacy of tacrolimus versus cyclosporine after lung transplantation: an updated systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials.

BACKGROUND: Little data supports using tacrolimus versus cyclosporin for immunosuppression concerning acute rejection and bronchiolitis obliterans syndrome/Chronic Lung Allograft Dysfunction CLAD complications following lung transplantation (LTx). Our goal was to evaluate the use of tacrolimus versus cyclosporine in preventing these complications after LTx. METHODS: We included randomized controlled trials (RCTs) by searching PubMed, Web of Science, SCOPUS, and Cochrane through January 10th, 2024. We pooled dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD) with a 95% confidence interval (CI). RESULTS: We included Four RCTs with a total of 677 patients. Tacrolimus was significantly associated with decreased risk of acute rejection (RR: 1.21, 95% CI [1.03, 1.42], I2 = 25%, P = 0.02) compared with cyclosporine, bronchiolitis obliterans syndrome/CLAD (RR: 1.87, 95% CI [1.26, 2.77], I2 = 52%, P = 0.002), and treatment withdrawal (RR: 3.11, 95% CI [2.06, 4.70], I2 = 0%, P = < 0.00001). However, tacrolimus significantly increased the risk of new-onset diabetes (RR: 0.33, 95% CI [0.12, 0.91], I2 = 0%, P = 0.03), and kidney dysfunction (RR: 0.79, 95% CI [0.66, 0.93], I2 = 0%, P = 0.006). In contrast, there was no difference in the incidence of all-cause mortality (RR: 91, 95% CI [0.68, 1.22], I2 = 0%, P = 0.53), arterial hypertension (RR: 2.40, 95% CI [0.41, 14.21], I2 = 92%, P = 0.33), and new cancer (RR: 1.57, 95% CI [0.79, 3.10], I2 = 4%, P = 0.20). CONCLUSION: Tacrolimus has decreased acute rejection episodes and CLAD rate than cyclosporine, but it increased the risk of new-onset diabetes and kidney dysfunction.

Clinical features and outcomes of persons with cystic fibrosis and nocardia isolation: a systematic review.

BACKGROUND: Recurrent respiratory infections are a leading cause of morbidity and mortality in persons with Cystic Fibrosis (pwCF). Recently, the emergence of Nocardia species as a potential pathogen in CF has raised questions about its role and management, as its clinical significance and the optimal patient management remain unclear in current clinical practice. This review explores the clinical implications of Nocardia species in patients with Cystic Fibrosis (pwCF) through a comprehensive literature review. Key objectives include assessing its impact on lung function, identifying colonization risk factors, and evaluating an appropriate treatment. METHODS: The literature review, conducted until June 30, 2023, from databases like MEDLINE, PubMed, Embase, and Cochrane, included 16 articles involving 89 pwCF with Nocardia species isolation according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline recommendations. Articles reporting Nocardia prevalence and symptoms based on original data in adult and paediatric pwCF were included. All the retrieved studies were observational ones, thus, they were categorized by study type as case report and case series. RESULTS: Overall 89 pwCF and Nocardia species isolation were included: 42 children and 47 adults. Where reported, we found these main following bacterial species: Nocardia asteroides (35%, 23/64), Nocardia farcinica (21%, 14/64), Nocardia tranvalensis (13%, 8/64) and Nocardia cyriacigeorgica (11%, 7/64). A co-infection was reported in 85% of patients (61/72). Of patients whose lung function was reported before and after Nocardia isolation, 23% (16/68) showed a decline in FEV1. Above all, 82 patients were treated at least once after isolation of Nocardia strain. In 93% (77/82) of cases, treatment was started immediately upon isolation. Antibiotic treatment was performed per os or intravenously depending on the clinical condition of the individual patient. Nocardia eradication was attempted in only 32 cases out of 82, and 78% (25/32) of these patients were successfully eradicated after one or more courses of antibiotics. Death was reported in 3 patients, 2 of which were children. CONCLUSION: In general the isolation of the bacteria does not necessarily imply therapy, but patients need to be monitored closely to assess the possible occurrence of active infection. The treatment seems to be indicated in patients showing lung involvement with the possible appearance of pneumonia, pleural effusion, fever, cough, or a decrease in FEV1, as in the case that we described, or in patients undergoing pulmonary transplantation.

Use of a novel donor lung scoring system as a tool for increasing lung recovery for transplantation.

OBJECTIVE: There is a critical shortage of donor lungs for transplantation. We previously developed a parsimonious, highly discriminatory nine-variable Lung Donor (LUNDON) acceptability score. We assess the utility of this score as a tool to improve lung recovery rates for transplantation. METHODS: We examined all brain-dead donors between 2014-2020 from three US organ procurement organizations and validated the score's predictive performance. We examined the trajectory of donors with low (<40) and high (>60) initial LUNDON scores, their corresponding lung recovery rates, factors contributing to score improvement using multivariable regression models, and one-year post-transplant recipient survival. RESULTS: Overall lung recovery was 32.4% (1410/4351). Validation of the LUNDON score in our cohort revealed a C statistic of 0.904 but required intercept calibration. Low initial LUNDON donors that improved to a high final score had an increase in lung recovery rate from 29.3% (1100/3765) to 86.8% (441/508), associated with lower BMI, management in specialized donor care facilities (SDCF), and more bronchoscopies. Donors with high initial and final LUNDON scores had lung recovery rate of 85.2% (98/115), associated with shorter lengths of stay. One-year survival was similar between recipients of low-to-high versus high-to-high LUNDON score donors (0.89 vs 0.84, p=0.2). CONCLUSIONS: The LUNDON score performs well as a predictor of lung recovery in a contemporary cohort but may require OPO-specific calibration. SDCF use, more bronchoscopies, and expediting time from brain death to organ procurement may improve lung utilization. The LUNDON score can be used to guide donor management to expand the donor pool.

Neutrophil PPIF exacerbates lung ischemia-reperfusion injury after lung transplantation by promoting calcium overload-induced neutrophil extracellular traps formation.

Lung ischemia-reperfusion (I/R) injury is the main risk factor for primary graft dysfunction and patient death after lung transplantation (LTx). It is widely accepted that the main pathological mechanism of lung I/R injury are calcium overload, oxygen free radical explosion and neutrophil-mediated damage, which leading to the lack of effective treatment options. The aim of this study was to further explore the mechanisms of lung I/R injury after LTx and to provide potential therapeutic strategies. Our bioinformatics analysis revealed that the neutrophil extracellular traps (NETs) formation was closely involved in lung I/R injury after LTx, which was accompanied by up-regulation of peptidylprolyl isomerase F (PPIF) and peptidyl arginine deiminase 4 (PADI4). We further established an orthotopic LTx mouse model to simulate lung I/R injury in vivo, and found that PPIF and PADI4 inhibitors effectively reduced neutrophil infiltration, NETs formation, inflammatory response, and lung I/R injury. In the neutrophil model induced by HL-60 cell line in vitro, we found that PPIF inhibitor cyclosporin A (Cys A) better alleviated calcium overload induced inflammatory response, reactive oxygen species content and NETs formation. Further study demonstrated that interfering with neutrophil PPIF protected mitochondrial function by alleviating store-operated calcium entry (SOCE) during calcium overload and played the above positive role. On this basis, we found that the reduction of calcium content in neutrophils was accompanied by the inhibition of calcineurin (CN) and nuclear factor of activated T cells (NFAT). In conclusion, our findings suggested that neutrophil PPIF could serve as a novel biomarker and potential therapeutic target of lung I/R injury after LTx, which provided new clues for its treatment by inhibiting calcium overload-induced NETs formation.

In vitro assessment of the risk of ABCB1-mediated drug-drug interaction between rivaroxaban and tacrolimus in human embryonic kidney 293 recombinant cell lines.

Background: In lung transplant patients, direct oral anticoagulants are often taken in combination with immunosuppressive drugs such as tacrolimus. Since tacrolimus is a substrate and inhibitor of the efflux protein ABCB1, also transporting direct oral anticoagulants, a possible drug-drug interaction mediated by competition for this transporter needs to be investigated. Objectives: To determine the in vitro effect of tacrolimus on ABCB1-mediated rivaroxaban transport in order to support clinician practice. Methods: Recombinant cell line models, based on human embryonic kidney 293 cells, were generated by a stable transfection process to overexpress ABCB1 or not (control cells). The impact of tacrolimus on ABCB1-mediated rivaroxaban transport was assessed by accumulation experiments. Results: ABCB1 expression decreased the cellular accumulation of rivaroxaban and tacrolimus at their respective clinically relevant concentrations when compared with control cells. This confirms the involvement of ABCB1 in the active transport of tacrolimus and rivaroxaban. However, tacrolimus had no significant influence on rivaroxaban disposition at those clinically relevant concentrations. Conclusion: Our study does not provide evidence for a possible interaction between tacrolimus and rivaroxaban when used together in practice.

Mitigating the risk of inflammatory type primary graft dysfunction by applying an integrated approach to assess, modify and match risk factors in lung transplantation.

Long-term outcome following lung transplantation remains one of the poorest of all solid organ transplants with a 1- and 5-year survival of 85% and 59% respectively for adult lung transplant recipients and with 50% of patients developing chronic lung allograft dysfunction (CLAD) in the first 5 years following transplant. Reducing the risk of inflammatory type primary graft dysfunction (PGD) is vital for improving both short-term survival following lung transplantation and long-term outcome due to the association of early inflammatory-mediated damage to the allograft and the risk of CLAD. PGD has a multifactorial aetiology and high-grade inflammatory-type PGD is the result of cumulative insults that may be incurred in one or more of the three variables of the transplantation continuum: the donor lungs, the recipient and intraoperative process. We set out a conceptual framework which uses a fully integrated approach to this transplant continuum to attempt to identify and, where possible, modify specific donor, recipient and intraoperative PGD risk with the goal of reducing inflammatory-type PGD risk for an individual recipient. We also consider the concept and risk-benefit of matching lung allografts and recipients on the basis of donor and recipient PGD-risk compatibility. The use of ex vivo lung perfusion (EVLP) and the extended preservation of lung allografts on EVLP will be explored as safe, non-injurious EVLP may enable extensive inflammatory testing of specific donor lungs and has the potential to provide a platform for targeted therapeutic interventions on lung allografts.

Comparing right- versus left-first implantation in off-pump sequential double-lung transplantation: an observational cohort study.

OBJECTIVES: Historically, the perfusion-guided sequence suggests to first transplant the side with lowest lung perfusion. This sequence is thought to limit right ventricular afterload and prevent acute heart failure after first pneumonectomy. As a paradigm shift, we adopted the right-first implantation sequence, irrespective of lung perfusion. The right donor lung generally accommodates a larger proportion of the cardiac output. We hypothesized that the right-first sequence reduces the likelihood of oedema formation in the firstly transplanted graft during second-lung implantation. Our objective was to compare the perfusion-guided and right-first sequence for intraoperative extracorporeal membrane oxygenation (ECMO) need and primary graft dysfunction (PGD). METHODS: A retrospective single-center cohort study (2008-2021) including double-lung transplant cases (N = 696) started without ECMO was performed. Primary end-points were intraoperative ECMO cannulation and PGD grade 3 (PGD3) at 72 h. Secondary end-points were patient and chronic lung allograft dysfunction (CLAD)-free survival. In cases with native left lung perfusion ≤50% propensity score adjusted comparison of the perfusion-guided and right-first sequence was performed. RESULTS: When left lung perfusion was ≤50%, right-first implantation was done in 219 and left-first in 189 cases. Intraoperative escalation to ECMO support was observed in 10.96% of right-first vs 19.05% of left-first cases (odds ratio 0.448; 95% confidence interval 0.229-0.0.878; p = 0.0193). PGD3 at 72 h was observed in 8.02% of right-first vs 15.64% of left-first cases (0.566; 0.263-1.217; p = 0.1452). Right-first implantation did not affect patient or CLAD-free survival. CONCLUSIONS: The right-first implantation sequence in off-pump double-lung transplantation reduces need for intraoperative ECMO cannulation with a trend towards less PGD grade 3.

Single Versus Double Lung Transplant in Older Adults: A Propensity-Matched Analysis.

BACKGROUND: Single lung transplantation (SLT) is associated with worse long-term outcomes than bilateral lung transplantation (BLT) but is often performed for older adults at risk of not tolerating BLT. RESEARCH QUESTION: How do the outcomes of SLT and BLT compare among older adult recipients? STUDY DESIGN AND METHODS: The Scientific Registry of Transplant Recipients database (2005-2022) was queried for lung transplant recipients aged ≥65 years. Patients were stratified by whether they underwent BLT or SLT, and propensity matched. Baseline characteristics and morbidity were compared with frequentist statistics. Survival was analyzed via Kaplan-Meier estimation. Risk factors for mortality were identified with Cox regression. RESULTS: Of 9,904 included patients, 4,829 (48.8%) underwent SLT. SLT patients had lower lung allocation scores (39.6 v. 40.6, p<0.001), more interstitial lung disease (74.4% v. 64.6%, p<0.001) and lower rates of bridging (0.7% v. 2.4%, p<0.001). Groups did not differ significantly by sex, body mass index, or donor characteristics. Propensity matching resulted in 2,539 patients in each group. On matched analysis, SLT patients had shorter lengths of stay (14 v. 18 d), lower reintubation rates (14.7% v. 19.8%), and less postoperative dialysis use (4.2% v. 6.4%) (all p<0.001). SLT patients had comparable survival at 30-days (97.6% v. 97.3%, p=0.414) and 1-year (85.5% v. 86.3%, p=0.496), but lower survival at 5-years (45.4% v. 53.4%, p<0.001) on matched analysis. SLT was a risk factor for 5-year mortality (adjusted hazard ratio: 1.19, p<0.001). INTERPRETATION: In older adults, SLT is associated with less morbidity and comparable early survival relative to BLT, but lower five-year survival. SLT is reasonable to perform in older adults at high risk for BLT.

Post-lung transplant outcomes of connective tissue disease-related interstitial lung diseases compared with idiopathic interstitial pneumonia: a single-center experience in Japan.

OBJECTIVES: The aim of this study was to investigate the outcomes of lung transplantation for connective tissue disease-related interstitial lung disease (CTD-ILD) conducted at our institution, compared with those for idiopathic interstitial pneumonias (IIPs). METHODS: We retrospectively reviewed patients with CTD-ILD and IIPs who underwent lung transplantation at our hospital from July 2015 to October 2023. We compared patients' backgrounds, early complications within 28 days post-transplant (CTCAE grade 3 or higher), postoperative courses, and prognoses between the two groups. RESULTS: The CTD-ILD group (n = 19) and the IIPs group (n = 56) were compared. The CTD-ILD group had significantly higher preoperative use of corticosteroids and antifibrotic agents, mean pulmonary arterial pressure, anti-human leukocyte antigen antibody positivity, and donor age (p < 0.05). In addition, the CTD-ILD group had significantly longer operation times (579.0 vs 442.5 min), longer stays in the intensive care unit (17.0 vs 9.0 days) and hospital (58.0 vs 44.0 days); required more tracheostomies (57.9 vs 25.0%); and experienced more respiratory (52.6 vs 25.0%) and gastrointestinal (42.1 vs 8.9%) complications (p < 0.05). However, there were no significant differences in overall survival, nor chronic lung allograft dysfunction (CLAD)-free survival between the two groups. CONCLUSION: Perioperative complications, notably respiratory and gastrointestinal complications, were prevalent after lung transplantation among CTD-ILD patients. Despite this, long-term survival rates were comparable to those observed in IIP cases.

Pulmonary Artery Endograft Implantation Using a Parallel Stent Grafting Technique to Enable the Treatment of a Bronchial Anastomosis Complication After Lung Transplantation.

BACKGROUND: Bronchial stenosis associated with bronchial anastomosis dehiscence after lung transplantation is a catastrophic complication following lung transplantation with a paucity of therapeutic solutions. PURPOSE: To describe an adaptation of the parallel stent grafting technique in the pulmonary arterial territory to treat this challenging situation. RESEARCH DESIGN: This is a case report of a 52-year-old patient who presented bronchus stenosis and bronchial anastomosis dehiscence after lung transplantion. Bronchial stenting and lung retransplantation were contraindicated. Therefore, an endovascular approach using pulmonary artery endograft placement to prevent bleeding during repeated right bronchial balloon dilation was propposed. The technique consists of the deployment of an aortic extender endoprosthesis in the right main pulmonary artery and a balloon expandable stent in the upper lobe pulmonary artery (using a parallel graft configuration) through the common femoral and right internal jugular veins, respectively. Intraoperative transesophageal echocardiogram and one-lung ventilatory ventilation are needed. RESULTS: The patient underwent a new bronchoscopy 16 days after the procedure, that showed epithelization at the previous eroded zone, enabling bronchocopic balloon dialtion to be safely performed. A post-operative contrast-enhanced CT scan revealed an adequate positioning of the stent grafts. Despite all eforts, the patient succumbed to ventilator associated pneumonia on postoperative day 108. DATA ANALYSIS: The technique's advantages include its feasibility even in situations in which other techniques may be contraindicated and its potential use in emergencies. Its limitations include the need for experienced interventionists to perform it, and the potential risk of acute tricuspid regurgitation. CONCLUSION: This study illustrates the early feasibility of the parallel stent grafting technique applied to the pulmonary artery territory. However, it's safety profile regarding infectious risk was not demontrated.

The Year in Cardiothoracic Transplant Anesthesia: Selected Highlights From 2022 Part I: Lung Transplantation.

These highlights focus on the research in lung transplantation (LTX) that was published in 2022 and includes the assessment and optimization of candidates for LTX, donor optimization, the use of organs from donation after circulatory death, and outcomes when using marginal or novel donors; recipient factors affecting LTX, including age, disease, the use of extracorporeal life support; and special situations, such as coronavirus disease2019, pediatric LTX, and retransplantation. The remainder of the article focuses on the perioperative management of LTX, including the perioperative risk factors for acute renal failure (acute kidney injury); the incidence and management of phrenic nerve injury, delirium, and pain; and the postoperative management of hyperammonemia, early postoperative infections, and the use of donor-derived cell-free DNA to detect rejection.

Treatment Responses in Histologic Versus Molecular Diagnoses of Lung Rejection.

Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment. 54 TBBs from Prague Lung Transplant Program obtained between December 2015 and January 2020 were included. Patients with acute cellular rejection (ACR) grade ≥ 1 by histology received anti-rejection treatment. Response to therapy was defined as an increase in FEV1 of ≥ 10% 4 weeks post-biopsy compared to the pre-biopsy value. Among the 54 analyzed TBBs, 25 (46%) were concordant with histology, while 29 (54%) showed discrepancies. ACR grade 0 was found in 12 TBBs (22%) and grade A1 ≥ 1 in 42 TBBs (78%). Treatment response was present in 14% in the NR group and in 50% in the TCMR group (p = 0.024). Our findings suggest that low-grade acute cellular rejection is less likely to be associated with molecular TCMR, which might better identify lung transplant recipients who benefit from therapy.

The Impact of Donor-Recipient Human Leukocyte Antigen Matching on Bronchiolitis Obliterans-Free Survival Among Lung Transplant Recipients With Connective Tissue Diseases.

BACKGROUND: The development of connective tissue disease-associated lung diseases (CTD-LD) occurs in association with specific human leukocyte antigens (HLA). For CTD-LD patients who require lung transplant, it is unknown whether utilization of donor organs expressing these same HLA impacts posttransplant outcomes. METHODS: Using the Scientific Registry of Transplant Recipients, we assessed whether CTD-LD lung transplant recipients in the United States have worse bronchiolitis obliterans (BOS)-free survival based on the degree of donor HLA matching. This included overall degree of donor-recipient HLA matching, donor-recipient matching at DR loci, and recipient matching with specific donor HLA antigens associated with the development of pulmonary disease in their condition. RESULTS: Among 1413 patients with CTD-ILD, highly HLA-matched donor-recipients did not have worse adjusted survival (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.58-1.51, p = 0.77). Recipients who were fully matched at HLA DR did not have worse survival (HR = 0.82, 95% CI = 0.56-1.19, p = 0.29). Finally, among individual CTD-LD, including rheumatoid arthritis, systemic sclerosis, the idiopathic inflammatory myopathies, and systemic lupus erythematous, transplant with a donor expressing HLA antigens associated with lung manifestations in these conditions was not associated with worse BOS-free survival. CONCLUSIONS: Among transplant recipients with CTD-LD, HLA donor-recipient matching, including at the DR loci, does not result in worse BOS-free survival. Based on these findings, there is no reason to treat these as unacceptable antigens when considering donor offers for CTD-LD candidates.

Comparison of Prognosis for Lung Transplantation between Older and Younger Donors: A Systematic Review and Meta-Analysis Based on Cohort Studies.

PURPOSE: This meta-analysis aimed to compare the prognosis of lung transplantation recipients based on donor age. METHODS: A detailed search was performed in PubMed, Embase, Web of Science, and the Cochrane Library for cohort studies on lung transplantation. The prognosis of lung transplant recipients was investigated based on the donor age, with the primary outcomes being 1-year overall survival (OS), 3-year OS, 5-year OS, and 5-year chronic lung allograft dysfunction (CLAD)-free survival. RESULTS: This meta-analysis included 10 cohort studies. Among the short-term outcomes, the older donor group demonstrated no significant difference from the young donor group in primary graft dysfunction within 72 hours, use of extracorporeal membrane oxygenation, length of ventilator use, and intensive care unit hours. However, a longer hospital stay was associated with the older donor group. In terms of long-term outcomes, no difference was found between the two groups in 1-year OS, 3-year OS, and 5-year OS. Notably, patients with older donors exhibited a superior 5-year CLAD-free survival. CONCLUSIONS: The results of this meta-analysis indicate that older donors are not inferior to younger donors in terms of long-term and short-term recipient outcomes. Lung transplantation using older donors is a potential therapeutic option after rigorous evaluation.

Hospital- and Ventilator-associated Pneumonia early after Lung Transplantation: a prospective Study on Incidence, Pathogen Origin and Outcome.

BACKGROUND: Hospital- (HAP) and ventilator-associated pneumonia (VAP) are important complications early (<30 days) after lung transplantation (LT). However, current incidence, associated factors and outcomes are not well reported. METHODS: LT recipients transplanted at our institution (07/2019-01/2020 and 10/2021-11/2022) were prospectively included. We assessed incidence and presentation of pneumonia and evaluated the impact of associated factors using regression models. In addition, we evaluated molecular relatedness of respiratory pathogens collected peri-transplant and at pneumonia occurrence using pulsed-field-gel-electrophoresis (PFGE). RESULTS: In the first 30 days post-LT, 25/270 (9.3%) recipients were diagnosed with pneumonia (68% [17/25] VAP; 32% [8/25] HAP). Median time to pneumonia was 11 days (IQR 7-13). 49% (132/270) of donor and 16% (44/270) of recipient respiratory peri-transplant cultures were positive. However, pathogens associated with pneumonia were not genetically related to either donor or recipient cultures at transplant, as determined by PFGE.Diagnosed pulmonary hypertension (HR 4.42, 95% CI 1.62-12.08) and immunosuppression use (HR 2.87, 95% CI 1.30-6.56) were pre-transplant factors associated with pneumonia.Pneumonia occurrence was associated with longer hospital stay (HR 5.44, 95% CI 2.22-13.37) and VAP with longer ICU stay (HR 4.31, 95% CI: 1.73-10.75) within the first 30 days post-transplant; 30- and 90-day mortality were similar. CONCLUSIONS: Prospectively assessed early pneumonia incidence occurred in around 10% of LT. Populations at increased risk for pneumonia occurrence include LT with pre-transplant pulmonary hypertension and pre-transplant immunosuppression. Pneumonia was associated with increased healthcare use, highlighting the need for further improvements by preferentially targeting higher-risk patients.

Contemporary Immunosuppression Management and 1-Year Outcomes in Dual Organ Heart Transplantation.

BACKGROUND: There have been limited reports on immunosuppression strategies and outcomes in dual organ heart transplant populations, primarily from before the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. Recent data suggested that outcomes with heart-lung and heart-liver transplants remained comparable in the new allocation era, yet heart-kidney recipients have worse 1-year survival. METHODS: This single-center retrospective study evaluated adult heart-kidney, heart-liver, and heart-lung transplant recipients from September 2019 to May 2023. Immunosuppression regimen, infectious complications, and graft outcomes were collected for 12 months. RESULTS: A total of 36 patients (kidney n = 20, liver n = 9, and lung n = 7) were included in this study. Basiliximab was the most commonly employed induction strategy across the organ groups (12/20 in kidney, 4/9 in liver, and 7/7 in lung). All patients were on triple immunosuppression at 12 months posttransplant with prednisone wean achieved in one heart-liver recipient. Infection complications were frequently reported (95% kidney, 75% liver, 100% lung group). One patient went back to dialysis due to focal segmental glomerulosclerosis. One chronic lung allograft dysfunction was reported, but no other severe biopsy-proven rejection or retransplant was reported. The 1-year survival was 85% (17/20) in heart-kidney, 78% (7/9) in heart-liver, and 86% (6/7) in heart-lung recipients. CONCLUSION: This study summarized real-world immunosuppression strategies and outcomes in dual organ heart transplant recipients.

Donor Fractions of Cell-Free DNA Are Elevated During CLAD But Not During Infectious Complications After Lung Transplantation.

During the last few years, cell-free DNA (cfDNA) has emerged as a possible non-invasive biomarker for prediction of complications after lung transplantation. We previously published a proof-of-concept study using a digital droplet polymerase chain reaction (ddPCR)-based method for detection of cfDNA. In the current study, we aimed to further evaluate the potential clinical usefulness of detecting chronic lung allograft dysfunction (CLAD) using three different ddPCR applications measuring and calculating the donor fraction (DF) of cfDNA as well as one method using the absolute amount of donor-derived cfDNA. We analyzed 246 serum samples collected from 26 lung transplant recipients. Nine of the patients had ongoing CLAD at some point during follow-up. All four methods showed statistically significant elevation of the measured variable in the CLAD samples compared to the non-CLAD samples. The results support the use of ddPCR-detected cfDNA as a potential biomarker for prediction of CLAD. These findings need to be validated in a subsequent prospective study.