Lung Transplantation Research Articles

Identification of immune patterns in idiopathic pulmonary fibrosis patients driven by PLA2G7-positive macrophages using an integrated machine learning survival framework

Patients with advanced idiopathic pulmonary fibrosis (IPF), a complex and incurable lung disease with an elusive pathology, are nearly exclusive candidates for lung transplantation. Improved identification of patient subtypes can enhance early diagnosis and intervention, ultimately leading to better prognostic outcomes for patients. The goal of this study is to identify new immune patterns and biomarkers in patients. Immune subtypes in IPF patients were identified using single-sample gene set enrichment analysis, and immune subtype-related genes were explored using the weighted correlation network analysis algorithm. A machine learning integration framework was used to establish the optimal prognostic model, known as the immune-related risk score (IRS). Single-cell sequencing was conducted to investigate the major role of macrophage-derived PLA2G7 in the immune microenvironment. We assessed the stability of celecoxib in targeting PLA2G7 through molecular docking and surface plasmon resonance. IPF patients present two distinct immune subtypes, one characterized by immune activation and inflammation, and the other by immune suppression. IRS can predict the immune status and prognosis of IPF patients. Furthermore, multi-cohort analysis and single-cell sequencing analysis demonstrated the diagnostic and prognostic value of PLA2G7 derived from macrophages and its role in shaping the inflammatory immune microenvironment in IPF patients. Celecoxib could effectively and stably bind with PLA2G7. PLA2G7, as identified through IRS, demonstrates marked stability in diagnosing and predicting the prognosis of IPF patients as well as predicting their immune status. It can serve as a novel biomarker for IPF patients.

Impact of Functional Status at the Time of Transplant on Short-Term Pediatric Lung Transplant Outcomes in the USA.

Poor functional status is associated with pediatric lung transplant (LTx) waitlist mortality. We investigate how pre-transplant functional status affects post-LTx survival. A retrospective analysis was performed using The United Network for Organ Sharing (UNOS) Registry data. Pediatric first-time lung transplant candidates between ages 1 and 18years with reported Lansky Play-Performance Scores (LPPS) at the time of waitlist and/or transplant were included from 2005 and 2021. Functional status by the LPPS scores is defined as severe limitation for LPPS score 10-40, mild limitation for LPPS score 50-70, and normal activity for LPPS score 80-100. Univariate analyses, multivariable Cox regression, and Kaplan-Meier plots were used to assess the impact of functional status on 1-year post-LTx survival. There were 913 and 610 patients at the time of LTx listing and transplant with LPPS scores, respectively. Poor functional status as determined by the LPPS score at the time of LTx, but not at the time of waitlist, was associated with worse 1-year post-LTx outcome (p value 0.0025 vs. 0.071). Multivariable survival analysis using Cox proportional hazards regression identified that a severely limited functional status at the time of LTx was the most profound risk factor for worse 1-year post-LTx survival outcomes when compared to a normal functional status (HR 2.16; 95% CI 1.15-4.07, p value 0.017). Children with severely limited functional status at the time of LTx have worse 1-year post-LTx outcome. It is important to develop strategies to optimize the functional status of children for improved post-LTx outcomes.

Population pharmacokinetic analysis and dosing optimization of colistin sulphate in lung transplant recipients with pneumonia: A prospective study

ObjectiveCurrently, there is a lack of information on the clinical pharmacokinetics (PK), effectiveness, and safety of colistin sulphate (CS) in lung transplant recipients. This study aims to improve CS dosing regimens and evaluate its population PK in lung transplant recipients. MethodsThis study evaluated the clinical efficacy, microbiological efficacy, and adverse events of CS in lung transplant recipients. The NONMEM program was employed to construct the population PK model, and Monte Carlo simulations were executed to establish dosing regimens according to the probability of target attainment (PTA). ResultsThe study included 146 CS concentrations, spanning from 0.05 to 4.18 mg/L from 39 lung transplant recipients with multidrug-resistant Gram-negative bacteria. 26 (66.67%) patients successfully eradicated bacteria, and 30 (76.92%) patients had clinical cure or improvement. Additionally, only 2 (5.13%) patients developed CS-related nephrotoxicity. The PK profile was effectively represented by a one-compartmental model with linear elimination. Creatinine clearance and concomitant furosemide use were recognized as covariates influencing the clearance of CS. Based on the PTA results, a daily dosage of 1.5 million IU, divided into 2–3 administrations, could attain a PTA exceeding 90% for MIC ≤ 1 µg/mL at creatinine clearance of about 110 mL/min. However, this regimen would lead to insufficient exposure for MIC ≥ 2 µg/mL. ConclusionsThe clearance of CS is significantly influenced by concomitant furosemide use and renal function. The currently recommended dosing regimens by label sheet may result in subtherapeutic exposure for MIC exceeding 1 mg/L in lung transplant recipients.

Comprehensive Risk Assessment in Patients With Pulmonary Arterial Hypertension Referred for Lung Transplantation.

Whether comprehensive risk assessment predicts post-referral outcome in patients with pulmonary arterial hypertension (PAH) referred for lung transplantation (LT) in Japan is unknown. We retrospectively analyzed 52 PAH patients referred for LT. Risk status at referral was assessed using 3- and 4-strata models from the 2022 European Society of Cardiology and European Respiratory Society guidelines. The 3-strata model intermediate-risk group was further divided into 2 groups based on the median proportion of low-risk variables (modified risk assessment [MRA]). The primary outcome was post-referral mortality. During follow-up, 9 patients died and 13 patients underwent LT. There was no survival difference among 3-strata model groups. The 4-strata model classified 33, 16, and 3 patients as low intermediate, high intermediate, and high risk, respectively. The 4-strata model identified high-risk patients with a 1-year survival rate of 33%, but did not discriminate survival between the intermediate-risk groups. The MRA classified 15, 28, 8, and 1 patients as low, low intermediate, high intermediate, and high risk, respectively. High intermediate- or high-risk patients had worse survival (P<0.001), with 1- and 3-year survival rates of 64% and 34%, respectively. MRA high intermediate- or high-risk classification was associated with mortality (hazard ratio 12.780; 95% confidence interval 2.583-63.221; P=0.002). Patients classified as high intermediate or high risk by the MRA after treatment should be referred for LT.

A Case of Lautropia mirabilis Infection in a Lung Transplant Patient and a Review of the Literature

Lautropia mirabilis is an opportunistic pathogen that typically causes intestinal and oral infections when the body’s immune system is compromised or the microbial flora is imbalanced. Respiratory infections caused by Lautropia mirabilis are extremely rare. The symptoms and severity of Lautropia mirabilis infection may vary depending on individual differences and the site of infection. Through a review of relevant literature and this case study, it has been observed that Lautropia mirabilis may also cause pulmonary infectious diseases, and in immunocompromised patients, it can lead to severe infections, potentially resulting in death.

The management of Familial Pulmonary Fibrosis in different medical settings: Where does that leave us? An Italian nationwide survey.

Familial Pulmonary Fibrosis (FPF) is an emerging group of interstitial lung diseases (ILDs) caused by mutations mainly involving "telomere-related genes" and "surfactant-related genes". Although, in 2023, European Respiratory Society proposed a statement for FPFs management, these still remain a burden. Our work aimed to evaluate the management and impact of FPF in three Italian different medical settings: University Hospitals (UHs), non-University Hospitals (N-UHs) and outpatient clinics. This survey was created by ILDs Study Group Società Italiana di Pneumologia/ Italian Respiratory Society (SIP-IRS) and diffused via email to all SIP-IRS members. The descriptive statistical analysis was conducted through GraphPad Prism software (version 8.0). Results: Twenty participants replied to the survey, of which 65% (13/20) worked at UH while the remaining 25% (6/20) and 5% (1/20) worked at N-UH and outpatient clinics, respectively. Centers with, at least, 150 ILD patients visits/year followed a higher number of FPF patients, regardless of University affiliation (p=0.0046). Despite significant discrepancies in genetic testing and availability of counselling were registered, no statistically significant differences in patients' anamnesis assessment were observed between UHs and N-UHs (p=0.4192 and p=0.6525). However, there were relevant differences in the number of FPF patients undergoing genetic assessment in the Centers with Genetics Lab or Unit inside the Hospital (p=0.0253). There was no consensus regarding the impact of FPF diagnosis on lung transplantation and screening of asymptomatic relatives. Similarly, no differences were reported in antifibrotic prescriptions between UHs and N-UHs. Although the typical UIP pattern was the most common radiological pattern observed in FPF patients, there were no differences in the prevalence of histopathological patterns between UH and N-UH. Improving pulmonologists' knowledge of the approach, diagnosis and management of FPF is a global medical topic. Scientific societies can provide significant support in raising physicians' awareness of this issue.

Predicting Primary Graft Dysfunction in Lung Transplantation: Machine Learning-Guided Biomarker Discovery.

There is an urgent need to better understand the pathophysiology of primary graft dysfunction (PGD) so that point-of-care methods can be developed to predict those at risk. Here we utilize a multiplex multivariable approach to define cytokine, chemokines, and growth factors in patient-matched biospecimens from multiple biological sites to identify factors predictive of PGD. Biospecimens were collected from patients undergoing bilateral LTx from three distinct sites: donor lung perfusate, post-transplant bronchoalveolar lavage (BAL) fluid (2h), and plasma (2h and 24h). A 71-multiplex panel was performed on each biospecimen. Cross-validated logistic regression (LR) and random forest (RF) machine learning models were used to determine whether analytes in each site or from combination of sites, with or without clinical data, could discriminate between PGD grade 0 ( n = 9) and 3 ( n = 8). Using optimal AUROC, BAL fluid at 2h was the most predictive of PGD (LR, 0.825; RF, 0.919), followed by multi-timepoint plasma (LR, 0.841; RF, 0.653), then perfusate (LR, 0.565; RF, 0.448). Combined clinical, BAL, and plasma data yielded strongest performance (LR, 1.000; RF, 1.000). Using a LASSO of the predictors obtained using LR, we selected IL-1RA, BCA-1, and Fractalkine, as most predictive of severe PGD. BAL samples collected 2h post-transplant were the strongest predictors of severe PGD. Our machine learning approach not only identified novel cytokines not previously associated with PGD, but identified analytes that could be used as a point-of-care cytokine panel aimed at identifying those at risk for developing severe PGD.

Takotsubo Syndrome-Induced Cardiogenic Shock in Lung Transplantation: Importance of Early Diagnosis and ECMO Implantation

Takotsubo Syndrome-Induced Cardiogenic Shock in Lung Transplantation: Importance of Early Diagnosis and ECMO Implantation

Pulmonary rehabilitation in lung transplant candidates with pulmonary arterial hypertension

BackgroundPulmonary rehabilitation (PR) guidelines support the efficacy and safety of supervised exercise training in mild-moderate pulmonary arterial hypertension (PAH). However, the exercise training response and safety of PR in PAH lung transplant (LTx) candidates has not been described. Objectives: (1) characterize the clinical characteristics and illness trajectory of adult patients with severe PAH listed for LTx and participating in PR; (2) evaluate the change in exercise capacity, aerobic and resistance training volumes; (3) assess PR safety. MethodsSingle-centre retrospective cohort study of PAH LTx candidates listed January 2014–December 2018 attending a supervised, facility-based outpatient program three times per week. Functional capacity was evaluated using 6-min walk distance (6MWD). Aerobic and muscle training volumes were evaluated with paired comparisons. Results40 PAH LTx candidates (age 50 ± 12 years, 73% females, mean pulmonary artery pressure 53 ± 16 mmHg) were included. The median listing duration was 91 [IQR 43–232] days. Sixteen patients (40%) had ≥1 admission pre-transplant. Nine patients (56%) were discharged home and resumed outpatient PR. Baseline 6MWD was 330 ± 119 metres (n = 40) with the final 6MWD pre-LTx increasing by 18 metres 95% CI (−18 to 56), p-value = 0.31, n = 25) over a median duration of 225 [IQR 70–311] days. Modest gains were observed in aerobic and resistance training volumes in PR with no adverse safety events. ConclusionDespite progressive and severe disease in PAH LTx candidates, patients safely participated in PR and maintained exercise capacity. Given frequent admissions, physiotherapy during hospitalization should focus on preserving functional capacity and facilitating re-integration into outpatient PR post-discharge.

Enhancing Lung Recellularization with Mesenchymal Stem Cells via Photobiomodulation Therapy: Insights into Cytokine Modulation and Sterilization.

Several lung diseases can cause structural damage, making lung transplantation the only therapeutic option for advanced disease stages. However, the transplantation success rate remains limited. Lung bioengineering using the natural extracellular matrix (ECM) of decellularized lungs is a potential alternative. The use of undifferentiated cells to seed the ECM is practical; however, sterilizing the organ for recellularization is challenging. Photobiomodulation therapy (PBMT) may offer a solution, in which the wavelength is crucial for tissue penetration. This study aimed to explore the potential of optimizing lung recellularization with mesenchymal stem cells using PBMT (660 nm) after sterilization with PBMT (880 nm). The lungs from C57BL/6 mice were decellularized using 1% SDS and sterilized using PBMT (880 nm, 100 mW, 30 s). Recellularization was performed in two groups: (1) recellularized lung and (2) recellularized lung + 660 nm PBMT (660 nm, 100 mW, 30 s). Both were seeded with mesenchymal stem cells from human tooth pulp (DPSc) and incubated for 24 h at 37 °C and 5% CO2 in bioreactor-like conditions with continuous positive airway pressure (CPAP) at 20 cmH2O and 90% O2. The culture medium was analyzed after 24 h. H&E, immunostaining, SEM, and ELISA assays were performed. Viable biological scaffolds were produced, which were free of cell DNA and preserved the glycosaminoglycans; collagens I, III, and IV; fibronectin; laminin; elastin; and the lung structure (SEM). The IL-6 and IL-8 levels were stable during the 24 h culture, but the IFN-γ levels showed significant differences in the recellularized lung and recellularized lung + 660 nm PBMT groups. Greater immunological modulation was observed in the recellularized groups regarding pro-inflammatory cytokines (IL-6, IFN-γ, and IL-8). These findings suggest that PBMT plays a role in cytokine regulation and antimicrobial activity, thus offering promise for enhanced therapeutic strategies in lung bioengineering.

High-Risk HLA-DQ Mismatches Are Associated With Adverse Outcomes After Lung Transplantation.

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

Circulating Vesicular-bound HLA-G as Noninvasive Predictive Biomarker of CLAD After Lung Transplantation.

Circulating extracellular vesicles (EVs) have shown promising results as noninvasive biomarkers for predicting disease outcomes in solid organ transplantation. Because in situ graft cell expression of the tolerogenic molecule HLA-G is associated with acceptance after lung transplantation (LTx), we hypothesized that plasma EV-bound HLA-G (HLA-GEV) levels could predict chronic lung allograft dysfunction (CLAD) development. We analyzed 78 LTx recipients from the Cohort-for-Lung-Transplantation cohort, all in a stable (STA) state within the first year post-LTx. At 3 y, 41 patients remained STA, and 37 had CLAD (bronchiolitis obliterans syndrome, BOS, [n = 32] or restrictive allograft syndrome [n = 5]). HLA-GEV plasma levels were measured at month 6 (M6) and M12 in 78 patients. CLAD occurrence and graft failure at 3 y post-LTx were assessed according to early HLA-GEV plasma levels. In patients with subsequent BOS, (1) HLA-GEV levels at M12 were significantly lower than those in STA patients (P = 0.013) and (2) also significantly lower than their previous levels at M6 (P = 0.04).A lower incidence of CLAD and BOS and higher graft survival at 3 y were observed in patients with high HLA-GEV plasma levels at M12 (high versus low HLA-GEVs patients [cutoff 21.3 ng/mL]: freedom from CLAD, P = 0.002; freedom from BOS, P < 0.001; and graft survival, P = 0.04, [log-rank]). Furthermore, in multivariate analyses, low HLA-GEV levels at M12 were independently associated with a subsequent risk of CLAD, BOS, and graft failure at 3 y (P = 0.015, P = 0.036, and P = 0.026, respectively [Cox models]). This exploratory study suggests the potential of EV-bound HLA-G plasma levels as a liquid biopsy in predicting CLAD/BOS onset and subsequent graft failure.

Pulmonary and extra-pulmonary effects of lung transplantation in an Italian cohort of patients with systemic sclerosis

Abstract Objectives Lung transplantation (LuTx) is a life-saving intervention for SSc patients with end-stage lung disease. The aim of this study was to evaluate patients’ survival and LuTx outcomes on systemic disease manifestations. Methods A retrospective evaluation was conducted on SSc patients who underwent LuTx between 2010 and 2021. Outcomes assessed at baseline, 6, 12 and 24 months post-LuTx included skin involvement by modified Rodnan skin score (mRSS), and global disease activity using a modified EUSTAR index (0–9 scale). Lung function rescue was evaluated by forced vital capacity (FVC). Patient survival was assessed by Kaplan–Meier analysis. Results Thirteen SSc patients were included, with a male/female ratio 9/4 and a median age of 48.7 years. Nine patients were affected by diffuse cutaneous scleroderma (dcSSc) and four by limited cutaneous scleroderma (lcSSc). FVC significantly increased from 56% of the predicted value at baseline to 78% at 2 years (P = 0.003). mRSS decreased from 7.4 ± 3.8 to 3.3 ± 2.5 in patients with dcSSc (P = 0.02). The modified EUSTAR index score decreased from 2.54 ± 1.8 at baseline to 0.49 ± 0.5 at 2 years (P = 0.02). Survival rate was 92.3% at 2 years, and 76.9% at 5 years. No unexpected adverse events were observed. Conclusions In SSc patients undergoing LuTx, an excellent 2-year survival was observed, without any disease-related adverse events. Our study supports LuTx as a viable option in SSc patients with end-stage lung disease. Apart from expected recovery of lung function, LuTx was associated with improvement of mRSS and global systemic disease activity.

Forty-year single-center experience of Burkholderia cystic fibrosis airway infections

ObjectivesTo resolve the epidemiology of airway infections with Burkholderia cepacia complex (Bcc) in patients with cystic fibrosis (pwCFs) over 40 years at a single treatment center. MethodsAll Bcc and Burkholderia gladioli airway isolates were collected from pwCFs who presented at the cystic fibrosis outpatient and the lung transplantation clinics from 1983 to 2022. ResultsThe collection of 1205 strains is dominated by B. multivorans (56%), followed by B. cenocepacia (16%), B. stabilis (10%), and B. orbicola (9%). A total of 27 pwCFs experienced a single self-limiting episode of airway infection with Bcc. A total of 13 pwCFs were harboring Bcc for 1.7-13.6 years and 15 pwCFs were persistently infected with Bcc. A total of 16 Bcc-positive pwCFs received a lung transplant. Fatal post-transplant sepsis happened in one patient with B. multivorans, two with B. cenocepacia, and two with B. orbicola. ConclusionsAfter the first acquisition of Bcc, transient carriage was 2.7 times more frequent than persistent colonization. Infections with B. cenocepacia or B. orbicola confer a higher risk for post-transplant sepsis than an infection with B. multivorans.

Pushing the Survival Bar Higher: Two Decades of Innovation in Lung Transplantation.

Survival after lung transplantation has significantly improved during the last two decades. The refinement of the already existing extracorporeal life support (ECLS) systems, such as extracorporeal membrane oxygenation (ECMO), and the introduction of new techniques for donor lung optimization, such as ex vivo lung perfusion (EVLP), have allowed the extension of transplant indication to patients with end-stage lung failure after acute respiratory distress syndrome (ARDS) and the expansion of the donor organ pool, due to the better evaluation and optimization of extended-criteria donor (ECD) lungs and of donors after circulatory death (DCD). The close monitoring of anti-HLA donor-specific antibodies (DSAs) has allowed the early recognition of pulmonary antibody-mediated rejection (AMR), which requires a completely different treatment and has a worse prognosis than acute cellular rejection (ACR). As such, the standardization of patient selection and post-transplant management has significantly contributed to this positive trend, especially at high-volume centers. This review focuses on lung transplantation after ARDS, on the role of EVLP in lung donor expansion, on ECMO as a principal cardiopulmonary support system in lung transplantation, and on the diagnosis and therapy of pulmonary AMR.

Continuous serratus anterior plane block for postoperative analgesia following lung transplantation via anterolateral incision: a pilot study.

Unilateral or bilateral anterolateral thoracotomy May lead to severe acute pain in lung transplantation (LTx). Although serratus anterior plane block (SAPB) is apparently effective for pain control after open thoracic surgery, there remains a lack of evidence for the application of SAPB for postoperative analgesia after LTx. In this case series pilot study, we describe the feasibility of continuous SAPB after lung transplantation and provide a preliminary investigation of its safety and efficacy. After chest incisions closure was complete, all patients underwent ultrasound-guided SAPB with catheter insertion. Numerical rating scale (NRS), additional opioid consumption, time to endotracheal tube removal, ICU length of stay, and catheter-related adverse events were followed up and recorded for each patient within 1 week after the procedure. A total of 14 patients who received LTx at this center from August 2023 to November 2023 were included. All patients received anterolateral approaches, and 10 (71.4%) of them underwent bilateral LTx. The duration of catheter placement was 2 (2-3) days, and the Resting NRS during catheter placement was equal to or less than 4. A total of 11 patients (78.6%) were supported by extracorporeal membrane oxygenation (ECMO) in LTx, whereas 8 patients (57.1%) removed the tracheal tube on the first day after LTx. Intensive care unit (ICU) stay was 5 (3-6) days, with tracheal intubation retained for 1 (1-2) days, and only one patient was reintubated. The morphine equivalent dose (MED) in the first week after LTx was 11.95 mg, and no catheter-related adverse events were detected. We did not assess the sensory loss plane due to the retrospective design. In addition, differences in catheter placement time May lead to bias in pain assessment. Although continuous SAPB May be a safe and effective fascial block technique for relieving acute pain after LTx, it should be confirmed by high-quality clinical studies.

Paediatric donor lung preservation using Paragonix BAROguard.

Paediatric lung transplantation is a lifesaving option in selected patients with end-stage lung disease. Favourable long-term outcomes are limited by impaired mucus clearance, increased risk of infection resulting from immunosuppression, and chronic lung allograft dysfunction. Organ preservation techniques play an important role in the quality of donated organs. Barotrauma to donated lungs may arise from a combination of excessive recruitment manoeuvres and altitude change during air transportation. The Paragonix BAROguard Donor Lung Preservation System is an FDA-approved advanced organ recovery system that maintains continuous airway pressure of 15 cm of water during transportation of the donated lung(s) to the recipient. The Paragonix LUNGguard monitors temperature during transportation of donor lung(s), while the new BAROguard monitors both temperature and pressure during transportation of donor lung(s). In this publication, we present technical aspects of advanced preservation of paediatric donor lungs using the Paragonix BAROguard Donor Lung Preservation System.

Predicting post-lung transplant survival in systemic sclerosis using CT-derived features from preoperative chest CT scans.

The current understanding of survival prediction of lung transplant (LTx) patients with systemic sclerosis (SSc) is limited. This study aims to identify novel image features from preoperative chest CT scans associated with post-LTx survival in SSc patients and integrate them into comprehensive prediction models. We conducted a retrospective study based on a cohort of SSc patients with demographic information, clinical data, and preoperative chest CT scans who underwent LTx between 2004 and 2020. This cohort consists of 102 patients (mean age, 50 years ± 10, 61% (62/102) females). Five CT-derived body composition features (bone, skeletal muscle, visceral, subcutaneous, and intramuscular adipose tissues) and three CT-derived cardiopulmonary features (heart, arteries, and veins) were automatically computed using 3-D convolutional neural networks. Cox regression was used to identify post-LTx survival factors, generate composite prediction models, and stratify patients based on mortality risk. Model performance was assessed using the area under the receiver operating characteristics curve (ROC-AUC). Muscle mass ratio, bone density, artery-vein volume ratio, muscle volume, and heart volume ratio computed from CT images were significantly associated with post-LTx survival. Models using only CT-derived features outperformed all state-of-the-art clinical models in predicting post-LTx survival. The addition of CT-derived features improved the performance of traditional models at 1-year, 3-year, and 5-year survival prediction with maximum AUC scores of 0.77 (0.67-0.86), 0.85 (0.77-0.93), and 0.90 (95% CI: 0.83-0.97), respectively. The integration of CT-derived features with demographic and clinical features can significantly improve t post-LTx survival prediction and identify high-risk SSc patients. Question What CT features can predict post-lung-transplant survival for SSc patients? Finding CT body composition features such as muscle mass, bone density, and cardiopulmonary volumes significantly predict survival. Clinical relevance Our individualized risk assessment tool can better guide clinicians in choosing and managing patients requiring lung transplant for systemic sclerosis.

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Textbook Outcomes in Solid Transplantation: A Systematic Review.

The concept of TO is expanding across various surgical disciplines to establish a standardized, comprehensive quality benchmark. Traditional metrics such as 1-y patient and graft survival have been key for evaluating transplant program performance but are now deemed inadequate because of significant field advancements. This systematic review aims to provide a comprehensive understanding of the applicability and validity of textbook outcome (TO) in the setting of solid organ transplantation. A structured search, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, was conducted across PubMed, Embase, and Scopus databases on March 10, 2024. Fourteen articles were identified for inclusion in this review. Of these, 2 studies addressed TO in heart transplantation, 3 in lung transplantation, 2 in kidney transplantation, and 7 in liver transplantation. A subgroup analysis was conducted to categorize the different definitions of TOs and identify the most common reasons for TO failure. Our systematic review highlights the ongoing efforts in the field of solid organ transplantation to define TO and emphasizes the importance of developing a universally recognized set of TO criteria for each type of transplant. TO provides a valuable framework for transplant centers to benchmark their performance against similar institutions on a risk-adjusted basis and to pinpoint specific areas for enhancing patient outcomes. Even the most successful programs may discover aspects within the composite outcome with scope for improvement.