LTx Patients Research Articles

Factors associated with quality of life in patients receiving lung transplantation: a cross-sectional study

BackgroundWith improved prognosis after lung transplantation (LTx), improving health-related quality of life (HRQL) in patients who have undergone LTx is a key goal. Although HRQL is improved significantly after transplantation, it is poorer than that in ordinary healthy people. However, the factors associated with poor HRQL remain unclear. This cross-sectional study aimed to identify the factors associated with poor HRQL in patients who have undergone LTx.MethodsBetween December 2018 and May 2022, 80 patients who had undergone LTx completed St. George’s Respiratory Questionnaire (SGRQ) as a disease-specific quality of life measure, the Short Form-12 (SF-12) as a generic quality of life measure, and modified Medical Research Council (mMRC) scale of dyspnea. The groups were assigned according to the median SGRQ-total score and the Japanese population standard for SF-12, and those with good HRQL were compared with those with poor HRQL. Independent factors were evaluated using multivariate analysis.ResultsWith regard to the SGRQ, there were significant differences in the forced expiratory volume in 1 s (FEV1) (P = 0.041), use of bronchodilators (P = 0.026), 6-min walk distance (6MWD) (P < 0.001), and Mmrc (P < 0.001) between better and poorer HRQL. For the SF-12 physical component summary score (PCS), age (P = 0.017), sex (P = 0.011), FEV1 (P < 0.001), forced vital capacity (FVC) (P < 0.001), diagnosis (P = 0.011), handgrip force (P = 0.003), 6MWD (P < 0.001), and Mmrc (P < 0.001) varied. Multivariate analyses revealed that Mmrc was the only independent factor in the SGRQ (P < 0.001, odds ratio [OR] = 6.65, 95% confidence interval [CI]: 2.49–17.74) and SF-12 PCS (P = 0.001, OR = 0.185, 95% CI: 0.07–0.52). There were significant correlations between the SGRQ-Total score and SF-12 PCS (correlation coefficient = -0.612, P < 0.001).ConclusionsDyspnea may be an independent factor of poor disease-specific and generic HRQL in LTx patients. The management of dyspnea may improve the HRQL in patients who have undergone LTx.

Increasing Antibody Responses to Five Doses of SARS-CoV-2 mRNA Vaccine in Lung Transplant Patients.

COVID-19 causes high mortality in Lung Transplant (LTx) patients, therefore vaccination in this population is potentially life-saving. However, the antibody response is impaired after three vaccinations in LTx patients. We questioned whether this response might be increased, and therefore studied the serological IgG antibody response across up to five doses of the SARS-CoV-2 vaccine. In addition, risk factors for non-response were investigated. In this large retrospective cohort study, antibody responses were assessed after 1-5 mRNA-based SARS-CoV-2 vaccines in all LTx patients between February 2021 and September 2022. A positive vaccine response was defined as an IgG level ≥ 300 BAU/mL. Positive antibody responses due to COVID-19 infection were excluded from the analysis. Outcome and clinical parameters were compared between responders and non-responders, and multivariable logistic regression analysis was performed to determine the risk factors for vaccine-response failure. The antibody responses of 292 LTx patients were analyzed. Positive antibody response to 1-5 SARS-CoV-2 vaccinations occurred in 0%, 15%, 36%, 46%, and 51%, respectively. During the study period, 146/292 (50%) of the vaccinated individuals tested positive for SARS-CoV-2 infection. The COVID-19-related mortality was 2.7% (4/146), and all four patients were non-responders. Risk factors associated with non-response to SARS-CoV-2 vaccines in univariable analyses were age (p = 0.004), chronic kidney disease (CKD) (p = 0.006), and shorter time since transplantation (p = 0.047). In the multivariable analysis, they were CKD (p = 0.043), and shorter time since transplantation (p = 0.028). A two- to five-dose regime of SARS-CoV-2 vaccines in LTx patients increases the probability of vaccine response and results in a cumulative vaccine response in 51% of the LTx population. LTx patient antibody response to SARS-CoV-2 vaccinations is therefore impaired, especially in patients shortly after LTx, patients with CKD, and the elderly.

WS10.02 Pharmacological effects of CFTR-modulation in cystic fibrosis patients after lung transplantation: interim results of the multicenter KOALA study

Objectives: Cystic Fibrosis leads to dysfunction of multiple organ systems, lung transplant (LTx) patients experience extrapulmonary symptoms even after lung transplantation, and might benefit from CFTR modulator therapy. The multicenter KOALA study aims to assess the extrapulmonary effect of CFTR modulators in LTx patients with CF. Here, we report the short-term interim results of a single site.

TOP6: Ambulatory Extra Corporeal Membrane Oxygenation as a Bridge to Lung Transplant

Background: Mechanical circulatory support, including both veno-venous (VV) and veno-arterial (VA) extra corporeal membrane oxygenation (ECMO), is being used more frequently to bridge critically ill patients to lung transplant (LTX). This study evaluates post LTX survival outcomes of patients bridged by ECMO. Methods: The United Network for Organ Sharing (UNOS) thoracic organ transplant database was queried for patients aged >/= 18 years between year 2016 and 2021 to identify pre-transplant patients supported by ECMO. Patients supported by both VA and VV-ECMO were excluded. The patients initially classified in VA-ECMO and VV-ECMO cohorts and further classified as ambulatory (AMB) and non-ambulatory (nAMB) within their respective ECMO cohorts. Each cohort was controlled against the non-ECMO patients. Univariate statistical tests as well as Kaplan-Meier survival curves were used for analysis. Results: Of total 14,369 LTX patients, 13,470 were non-ECMO, 702 were VV-ECMO (44% AMB, 56% nAMB) and 197 were VA-ECMO (47% AMB, 53% nAMB). Table 1A (non-ECMO v. AMB VV-ECMO v. nAMB VV-ECMO at time of LTX) and 1B (non-ECMO v. AMB VA-ECMO v. nAMB VA-ECMO at time of LTX) shows higher age (62 v. 52 v. 50) lower O2 requirement (4 v. 15 v. 10), LAS (44 v. 88 v. 89) and lesser likelihood of COVID etiology (1% v. 22% v. 6%) in non-ECMO group compared to VV-ECMO and VA-ECMO. Within the ECMO groups AMB and nAMB patients were comparable except idiopathic fibrosis was more common in nAMB. The 1-year post LTX survival between non-ECMO and AMB VV-ECMO was comparable (88% v. 88%, p=0.66) which was better than nAMB VV-ECMO patients (88% v. 88% v. 81% (nAMB VV-ECMO), p<.01, F1A). The 1-year (71% v. 78% v. 88%) survival was better for AMB VA-ECMO patients than nAMB VA-ECMO patients, and better for non-ECMO patients than AMB VA-ECMO patients (p<.01, F1B). A Cox proportional hazard model showed that compared to non-ECMO patients, the nAMB VV-ECMO patients (HR = 1.25, p=0.02) had higher risk of post LTX mortality whereas post LTX risk for AMB VV-ECMO patients (HR = 0.95, p=0.71) was similar. Conclusion: Although ambulatory VV-ECMO patients have higher LAS and O2 requirements at time of transplant, their post LTX survival is comparable to the non-ECMO patients. Survival amongst the VA-ECMO patients continued to be poor compared to the non-ECMO patients irrespective of their ambulatory status. Strategies to ambulate ECMO patients could be associated better post LTX outcomes. Figure 1. Survival by ECMO ambulationTable 1. Patient Characteristics at time of LTX

Development and validation of a nomogram model to predict primary graft dysfunction in patients after lung transplantation based on the clinical factors.

Primary graft dysfunction (PGD), a significant complication that can affect patients' prognosis and quality of life, develops within 72 h post lung transplantation (LTx). Early detection and prevention of PGD should be given special consideration. The purpose of this study was to create a clinical prediction model to forecast the occurrence of PGD. We collected information on 622 LTx patients from Wuxi People's Hospital from 2016 to 2020 and used the data to construct the prediction model. Information on 224 patients from 2021 to June 2022 was used for external validation. We used LASSO regression for variable screening. A nomogram was developed for model presentation. Distinctness, fit, and calibration were used to evaluate the performance of the model. Subjects with respiratory failure, who received fresh frozen plasma, donor age, donor gender, donor mechanism of death, donor smoking, donor ventilator use time, and donor PaO 2/FiO 2 ratio were independent predictor variables for the occurrence of PGD. The area under the curve of the nomogram was .779. The Hosmer-Lemeshow test showed a good model fit (P= .158). The calibration curve of the nomogram is fairly close to the ideal diagonal. Moreover, the decision curve analysis revealed a positive net benefit of the model. External validation also confirmed the reliability of the model. The nomogram of PGD based on clinical risk factors in postoperative LTx patients was established with high reliability. It provides clinicians and nurses with a new and effective tool for early prediction of PGD and early intervention.

Lung transplantation for lung cancer: A systematic review of the literature

Lung transplant (LTx) is an accepted treatment for end-stage pulmonary failure. A small proportion of explanted lungs harbor incidentally identified nonsmall cell lung cancers (NSCLC). We review the literature on studies assessing LTx patients found to have NSCLC lung cancer in their explanted lungs, and perform a pooled analysis of outcomes. MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. We included studies assessing outcomes of patients with incidentally identified NSCLC following LTx, or following LTx for diffuse lepidic adenocarcinoma as a primary indication. A total of 1404 articles were reviewed. 17 eligible studies were identified: 14 studies on incidental NSCLC (N=169), 4 on diffuse lepidic adenocarcinoma (N=70). Overall survival (OS) for patients with incidentally identified lung cancer at 1-year, 3-year, and 5-year was 60.8% (95%CI 43.7%-77.9%, I2 =81.8%), 25.5% (95%CI 1.6%-49.5%, I2 =93.6%), and 23.0% (95%CI 2.0%-44.0%, I2 =92.0%) respectively. When restricted to those with earlier stage disease, those with stage I or II NSCLC had better 1-year, 3-year, and 5-year OS at 72.7% (95%CI 57.2%-88.2%, I2 =67.3%), 41.6% (95%CI 14.0%-69.1%, I2 =89.1%), and 34.5% (95%CI 8.1%-61.0%, I2 =89.8%), respectively. A sensitivity analysis limited to stage I showed 1-year, 3-year, and 5-year survival of 73.0% (95%CI 56.3%-89.7%), 40.4% (95%CI 110.3%-70.6%), and 35.4% (95%CI 6.2%-64.5%), respectively. The 4 studies on diffuse lepidic adenocarcinoma were too heterogeneous for pooled analysis. We present a review and pooled analysis examining survival following LTx with incidentally identified NSCLC. Patients with earlier stage incidentally explanted NSCLC had better survival outcomes. OS in the stage I population approximates that of LTx without incidental NSCLC.

Calcineurin-inhibitor free immunosuppression after lung transplantation - a single center case-control study in 51 patients converted to Mechanistic Target of Rapamycin (mTOR) inhibitors.

Data on calcineurin-inhibitor (CNI) free immunosuppression after lung transplantation (LTx) are limited. Aim of this study was to investigate CNI-free immunosuppression using mechanistic target of rapamycin (mTOR) inhibitors. This retrospective analysis was performed at a single center. Adult patients after LTx without CNI during the follow-up period were included. Outcome was compared to those LTx patients with malignancy who continued CNI. Among 2,099 patients in follow-up, fifty-one (2.4%) were converted median 6.2 years after LTx to a CNI-free regimen combining mTOR inhibitors with prednisolone and an antimetabolite, two patients were switched to mTOR inhibitors with prednisolone only. In 25 patients, malignancies without curative treatment options were the reason of the conversion, with a 1-year survival of 36%. The remaining patients had a 1-year survival of 100%. Most common non-malignant indication was neurological complications (n = 9). Fifteen patients were re-converted to a CNI-based regimen. The median duration of CNI-free immunosuppression was 338 days. No acute rejections were detected in 7 patients with follow-up biopsies. In multivariate analysis, CNI-free immunosuppression were not associated with improved survival after malignancy. The majority of patients with neurological diseases improved 12 months after conversion. Glomerular filtration rate increased by median 5 (25 and 75% percentiles -6; +18) ml/min/1.73 m2. mTOR inhibitor based CNI-free immunosuppression may be safely performed in selected patients after LTx. This approach was not associated with improved survival in patients with malignancy. Significant functional improvements were observed in patients with neurological diseases.

Acute transcutaneous electrical stimulation (TES) augments esophageal contractility in patients with weak peristalsis.

Lung transplantation (LTx) remains controversial in patients with absent peristalsis (AP) given the increased risk for gastroesophageal reflux (GER), and chronic lung allograft dysfunction. Furthermore, specific treatments to facilitate LTx in those with AP have not been widely described. Transcutaneous Electrical Stimulation (TES) has been reported to improve foregut contractility in LTx patients and therefore we hypothesize that TES may augment the esophageal motility of patients with ineffective esophageal motility (IEM). We included 49 patients, 14 with IEM, 5 with AP, and 30 with normal motility. All subjects underwent standard high-resolution manometry and intraluminal impedance (HRIM) with additional swallows as TES was delivered. TES induced a universal impedance change observable in real-time by a characteristic spike activity. TES significantly augmented the contractile vigor of the esophagus measured by the distal contractile integral (DCI) in patients with IEM [median DCI (IQR) 0 (238) mmHg-cm-s off TES vs. 333 (858) mmHg-cm-s on TES; p=.01] and normal peristalsis [median DCI (IQR) 1545 (1840) mmHg-cm-s off TES vs. 2109 (2082) mmHg-cm-s on TES; p=.01]. Interestingly, TES induced measurable contractile activity (DCI>100mmHg-cm-s)in three out of five patients with AP [median DCI (IQR) 0 (0) mmHg-cm-s off TES vs. 0 (182) mmHg-cm-s on TES; p<.001]. TES acutely augmented contractile vigor in patients with normal and weak/ AP. The use of TES may positively impact LTx candidacy, and outcomes for patients with IEM/AP. Nevertheless, further studies are needed to determine the long-term effects of TES in this patient population.

Application of the Balance of Risk Score to Liver Transplantation

BackgroundTo evaluate the capacity of BARS to predict 90-day, 1-year, 3-year, and 5-year survival after liver transplantation (LTx). The Balance of Risk Score (BARS), proposed by the Swiss Hepato-pancreato-biliary and Transplant Center, University Hospital Zurich, Switzerland, was conceptualized to determine survival after LTx preemptively. Sample and MethodsThis was a retrospective observational study on 866 cases of LTx among adults (>18 years) performed within the transplantation program at Hospital Israelita Albert Einstein between January 1, 2010, and December 31, 2015. Cases of loss from follow-up, split-liver transplantation, transplantation from a live donor, and combinations of LTx with transplantation of other organs were excluded. BARS was calculated for each transplantation performed. The survival estimates were accompanied by 95% CIs, and the associations between the variables of interest and the patients’ overall survival were evaluated using Cox proportional risk models. Receiver operating characteristic curves and the estimated area under the curve were used with 95% CIs and P values for the equality test on the area at .5. ResultsThe area under the curve for the 90-day period was 0.725, with a 95% CI from 0.670 to 0.81 and a P value < .001 for the equality test at 0.5. In the stratified analysis, the score of 18 presented the highest sensitivity, taking a minimum specificity of 90%. The BARS >18 gave rise to a significant decline in survival, from 89.7% to 60.4% over the first 90 days, from 83.3% to 56.2% over a 1-year period, from 75.7% to 49.5% over 3 years, and from 72.2% to 43.4% over 5 years. ConclusionThe BARS was shown to be reproducible and can be used as a tool for estimating survival among LTx patients. LTx performed on patients with BARS >18 significantly predicts lower survival for such patients.

Predictive value of molecular matching tools for the development of donor specific HLA-antibodies in patients undergoing lung transplantation.

Molecular matching is a new approach for virtual histocompatibility testing in organ transplantation. The aim of our study was to analyze whether the risk for de novo donor-specific HLA antibodies (dnDSA) after lung transplantation (LTX) can be predicted by molecular matching algorithms (MMA) and their combination. In this retrospective study we included 183 patients undergoing LTX at our center from 2012-2020. We monitored dnDSA development for 1 year. Eplet mismatches (epMM) using HLAMatchmaker were calculated and highly immunogenic eplets based on their ElliPro scores were identified. PIRCHE-II scores were calculated using PIRCHE-II algorithm (5- and 11-loci). We compared epMM and PIRCHE-II scores between patients with and without dnDSA using t-test and used ROC-curves to determine optimal cut-off values to categorize patients into four groups. We used logistic regression with AIC to compare the predictive value of PIRCHE-II, epMM, and their combination. In total 28.4% of patients developed dnDSA (n = 52), 12.5% class I dnDSA (n = 23), 24.6% class II dnDSA (n = 45), and 8.7% both class II and II dnDSA (n = 16). Mean epMMs (p-value = 0.005), mean highly immunogenic epMMs (p-value = 0.003), and PIRCHE-II (11-loci) (p = 0.01) were higher in patients with compared to without class II dnDSA. Patients with highly immunogenic epMMs above 30.5 and PIRCHE-II 11-loci above 560.0 were more likely to develop dnDSA (31.1% vs. 14.8%, p-value = 0.03). The logistic regression model including the grouping variable showed the best predictive value. MMA can support clinicians to identify patients at higher or lower risk for developing class II dnDSA and might be helpful tools for immunological risk assessment in LTX patients.

Reduced Community-acquired Respiratory Virus Infection, but Not Non-virus Infection, in Lung Transplant Recipients During Government-mandated Public Health Measures to Reduce COVID-19 Transmission.

A single-center, retrospective cohort analysis comparing CARV infection before a statewide stay-at-home order, during the stay-at-home order and subsequent statewide mask mandate, and during 5 mo following the elimination of NPI was performed. All LTx recipients followed by and tested at our center were included. Data (multiplex respiratory viral panels; SARS-CoV-2 reverse transcription polymerase chain reaction; blood cytomegalovirus and Epstein Barr virus polymerase chain reaction; blood and bronchoalveolar lavage bacterial and fungal cultures) were collected from the medical record. Chi-square or Fisher exact tests were utilized for categorical variables. A mixed-effect model was used for continuous variables. Incidence of non-COVID CARV infection was significantly lower during the MASK period than during the PRE period. No difference was noted in airway or bloodstream bacterial or fungal infections, but cytomegalovirus bloodborne viral infections increased. Reductions in respiratory viral infections, but not bloodborne viral infections nor nonviral respiratory, bloodborne, or urinary infections, were observed in the setting of public health COVID-19 mitigation strategies, suggesting the effectiveness of NPI in preventing general respiratory virus transmission.

Esophageal Inlet Patch: A Clinically Significant Entity in Advanced Pulmonary Disease and Lung Transplant Rejection

Background: Esophageal inlet patch (IP) refers to heterotopic gastric mucosa in the cervical esophagus. Secretions from IP may produce symptoms of laryngopharyngeal reflux (LPR) and accelerate progression of lung disease. We aimed to characterize the significance of IP among patients with advanced pulmonary disease, including lung transplant (LTx) recipients, and to assess outcomes following IP ablation. Methods: We established and reviewed a prospective database of all patients with advanced pulmonary disease referred for GI motility evaluation for presence of IP over 7 years. Total IP size, results of pH testing, incidence of transplant rejection and mortality, and effects of IP ablation on symptoms were analyzed. Results: Twenty-seven (13 LTx recipients) of 440 pulmonary patients referred for upper endoscopy were found to have IPs, and 14 completed IP ablation (mean number of 1.7 sessions to ablate IP). Total IP size correlated with total acid exposure time ( P = .01) and symptoms of cough ( P &lt; .00001), heartburn ( P = .0001), and globus ( P &lt; .00001). Symptom severity of heartburn and dysphagia improved following IP ablation ( P = .04 and 0.008). Eight of 13 LTx patient with IP developed either acute or chronic rejection, with 3 cases of post-LTx mortality occurring in patients who did not undergo IP ablation. Conclusions: IP should be given careful consideration in patients with advanced pulmonary disease and lung transplant recipients, particularly if symptoms of cough, heartburn, or globus are present. Total IP size may be predictive of severity of LPR, and symptom recurrence should prompt re-examination for residual IP.

Textbook Outcome: Definition and Analysis of a Novel Quality Measure in Lung Transplantation.

To define textbook outcome (TO) for lung transplantation (LTx) using a contemporary cohort from a high-volume institution. TO is a standardized, composite quality measure based on multiple postoperative endpoints representing the ideal "textbook" hospitalization. Adult patients who underwent LTx at our institution between 2016 and 2019 were included. TO was defined as freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay >75th percentile of LTx patients, 90 day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, postoperative extracorporeal membrane oxygenation, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Recipient, operative, financial characteristics, and post-transplant outcomes were recorded from institutional data and compared between TO and non-TO groups. Of 401 LTx recipients, 97 (24.2%) achieved TO. The most common reason for TO failure was extubation >48 hours post-transplant (N = 119, 39.1%); the least common was mortality (N = 15, 4.9%). Patient and graft survival were improved among patients who achieved versus failed TO (patient survival: log-rank P < 0.01; graft survival: log-rank P < 0.01). Rejection-free and chronic lung allograft dysfunction-free survival were similar between TO and non-TO groups (rejection-free survival: log-rank P = 0.07; chronic lung allograft dysfunction-free survival: log-rank P = 0.3). On average, patients who achieved TO incurred approximately $638,000 less in total inpatient charges compared to those who failed TO. TO in LTx was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer providers and patients new insight into transplant center quality of care and highlight areas for improvement.

Lung Transplantation for Bronchopulmonary Dysplasia

Patients with bronchopulmonary dysplasia (BPD) have poor respiratory trajectories and are at increased risk of lung function decline with age. Lung transplant (LTx) is a possible treatment option for this growing patient population, but little has been published on LTx in this patient group. What are the characteristics of patients with BPD who are listed for LTx? How do waitlist and post-LTx outcomes for BPD compare with LTx for other diagnoses? The United Network for Organ Sharing (UNOS) registry was queried for patients of all ages listed for or who underwent LTx (2000-2020). Descriptive analysis, waitlist outcomes, and post-LTx survival at 1, 5, and 10 years were assessed comparing patients with BPD vsLTx patients with other diagnoses. Post-LTx survival for patients with BPD born in the pre-surfactant era (pre-SE, before 1990) and those born in the post-surfactant era (post-SE) was compared. Propensity score matching was performed to control for the risk factors and match patients with BPD with other LTx patients on a 1:1 ratio. BPD was reported in 65 patients, of whom 32 (49.2%) underwent LTx. Patients with BPD at listing were younger than those with other diagnoses (median age, 21 [interquartile range, 5-31] years vs57 [45-63] years; P< .001), and more were likely to receive mechanical ventilation at listing (23%vs3.7%; P< .001). Patients with BPD had an FEV1 of 17%compared with 34%predicted in other patients (P= .002). Patients with BPD had an overall similar post-LTx survival compared with patients with other diagnoses (P= .106), even following propensity score matching (P= .41). LTx for BPD has increased over the last 20 years. Patients with BPD have similar post-LTx outcomes compared with those of other patient populations in the modern era. Thus, LTx could be considered for patients with BPD experiencing progressive respiratory deterioration.

Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective.

Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40-70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.

COVID-19 in pediatric lung transplant recipients: Clinical course and outcome

COVID-19 causes high morbidity and mortality in adult lung transplant (LTX) recipients. Data on COVID-19 in children after LTX is limited. We report the clinical presentation and outcome of SARS-CoV-2 infection in 19 pediatric LTX recipients. Between March 2020 and June 2022, SARS-CoV-2 testing was performed on all pediatric LTX patients with COVID-19 symptoms or contact with a SARS-CoV-2 infected person. Positive patients were prospectively evaluated for symptoms, treatment and outcome. Vaccination status and immune response were recorded. Nineteen out of 51 pediatric LTX recipients had a SARS-CoV-2 infection. Mean age was 12.3 years (IQR 9-17), 68% were female, 84% had preexisting comorbidities. Mean time between LTX and SARS-CoV-2 infection was 4.8 years (IQR 2-6). No patients experienced severe COVID-19: 11% were asymptomatic, and 89% had mild symptoms, primarily rhinitis (74%), fever (47%), and cough (37%). One SARS-CoV-2 positive patient was hospitalized due to combined fungal and bacterial infection. Mean duration of symptoms was 10.5 days (IQR 3-16), whereas mean period of positivity by antigen test was 21 days (IQR 9-27, p=0.013). Preventive antiviral therapy was initiated in 3 patients. After a mean follow-up of 2.5 months (IQR 1.1-2.4), no patient reported persistent complaints related to COVID-19. Lung function tests remained stable. Unlike adult LTX recipients, children and adolescents are at low risk for severe COVID-19, even with risk factors beyond immunosuppression. Our findings cast doubt on the necessity of excessive isolation for these patients and should reassure clinicians and caregivers of LTX patients.

Laparoscopic Toupet Fundoplication for Lung Transplant Recipients: Outcomes and Effects on Symptoms

INTRODUCTION: Lung transplant (LTx) recipients often experience GERD, which predisposes them to bronchiolitis obliterans syndrome and obstructive chronic lung allograft dysfunction, ultimately resulting in early rejection and death. Laparoscopic Nissen fundoplication (LNF) has historically been the procedure of choice for LTx-related GERD. However, LNF is associated with high rate of postoperative dysphagia and bloating in the general population. Hence, we evaluate laparoscopic Toupet fundoplication (LTF) as an option for antireflux surgery in LTx recipients, investigating the effects of LTF on DeMeester score, gastric emptying, esophageal manometry, and patient symptoms. METHODS: A retrospective review of LTx patients who underwent LTF at a single center by 1 surgeon (n = 59) between September 2018 and November 2020 was performed, excluding a patient who had a revision of their fundoplication. Preoperative and postoperative esophageal manometry, gastric emptying studies, and patient-reported GERD symptoms were collected. Statistical analyses were performed using Prism 9 Version 9.3.1 for macOS, GraphPad Software. RESULTS: After LTF, DeMeester score and relative risk of abnormal esophageal function and gastroparesis were significantly decreased, with most patients having lower gastroparesis severity score. Reports of heartburn, regurgitation, and bloating were also reduced. However, the rates of dysphagia were similar. There was no decline in pulmonary function. CONCLUSION: LTF, in addition to providing antireflux control in LTx recipients, has low rate of complication and trends with overall improvement of gastrointestinal issues. LTF ultimately has the potential to be the antireflux operation of choice in LTx recipients, protecting against early rejection and death.

Sirolimus Attenuates Calcineurin Inhibitor-Induced Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

Calcineurin inhibitors (CNIs), which are potent immunosuppressants (ISs), increase the risk for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LTx). Epithelial-mesenchymal transition (EMT) is a key process in which epithelial cancer cells lose their polarity, resulting in cancer progression and metastasis. The aim of this study was to evaluate the effect of sirolimus (SRL) individually and in combination with other ISs to reduce EMT. HCC SK-Hep1 cells were used and various ISs (SRL, tacrolimus, cyclosporine A, or mycophenolate mofetil) were administered at 2 dosages and in combination therapies. Mice were transplanted with SK-Hep1 cells (in the liver) and were monitored after 2 weeks. The in vitro treatment with SRL showed a dose-dependent attenuation of cell proliferation and migration in case of the individual and IS combination treatments; further, decreased levels of pro-EMT proteins, namely, N-cadherin, transforming growth factor-β, ZEB1, Slug, and Snail were observed. In contrast, E-cadherin expression was upregulated after both the individual and IS combination treatments. These results were also observed in the samples from mice transplanted with the SK-Hep1 cells. The present study demonstrated that SRL reduced HCC metastasis by inhibiting EMT. Thus, our findings provide a rationale for the use of SRL in combination with ISs in HCC LTx patients.

Extracorporeal membrane oxygenation support for lung transplantation: Initial experience in a single center in China and a literature review.

BackgroundExtracorporeal membrane oxygenation (ECMO) is a versatile tool associated with favorable outcomes in the field of lung transplantation (LTx). Here, the clinical outcomes and complications of patients who underwent LTx with ECMO support, mainly prophylactically both intraoperatively and post-operatively, in a single center in China are reviewed.MethodsThe study cohort included all consecutive patients who underwent LTx between January 2020 and January 2022. Demographics and LTx data were retrospectively reviewed. Perioperative results, including complications and survival outcomes, were assessed.ResultsOf 86 patients included in the study, 32 received ECMO support, including 21 who received prophylactic intraoperative use of ECMO with or without prolonged post-operative use (pro-ECMO group), while the remaining 54 (62.8%) received no external support (non-ECMO group). There were no significant differences in the incidence of grade 3 primary graft dysfunction (PGD), short-term survival, or perioperative outcomes and complications between the non-ECMO and pro-ECMO groups. However, the estimated 1- and 2-year survival were superior in the pro-ECMO group, although this difference was not statistically significant (64.1% vs. 82.4%, log-rank P = 0.152; 46.5% vs. 72.1%, log-rank P = 0.182, respectively). After regrouping based on the reason for ECMO support, 30-day survival was satisfactory, while 90-day survival was poor in patients who received ECMO as a bridge to transplantation. However, prophylactic intraoperative use of ECMO and post-operative ECMO prolongation demonstrated promising survival and acceptable complication rates. In particular, patients who initially received venovenous (VV) ECMO intraoperatively with the same configuration post-operatively achieved excellent outcomes. The use of ECMO to salvage a graft affected by severe PGD also achieved acceptable survival in the rescue group.ConclusionsProphylactic intraoperative ECMO support and post-operative ECMO prolongation demonstrated promising survival outcomes and acceptable complications in LTx patients. Particularly, VV ECMO provided safe and effective support intraoperatively and prophylactic prolongation reduced the incidence of PGD in selected patients. However, since this study was conducted in a relatively low-volume transplant center, further studies are needed to validate the results.

Concurrent Change in Serum Cholinesterase Activity and Midregional-Proadrennomedullin Level Could Predict Patient Outcome following Liver Transplantation.

Background: After liver transplantation (LTX), patients are susceptible to opportunistic infections resulting in reduced outcomes within the early post-transplantation period. The postoperative monitoring of LTX patients has gained much importance in recent years. However, reliable plasmatic markers predicting 90-day outcomes are still lacking. Methods: In the post hoc analysis of a prospective, observational study, butyrylcholinesterase (BChE), mid-regional proadrenomedullin (MR-proADM), as well as conventional inflammatory markers (procalcitonin, C-reactive protein) were evaluated in 93 patients at seven consecutive timepoints within the first 28 days following LTX. Results: Persistently reduced activity of BChE and elevated MR-proADM levels indicated reduced 90-day survival following LTX. Furthermore, reduced BChE and increased MR-proADM activity could indicate early post-transplantation bacterial infections, whereas conventional inflammatory biomarkers showed no diagnostic efficacy within the observation period. Conclusion: Concurrent assessment of BChE and MR-proADM activity might serve as a bedside diagnostic tool for early bacterial infections following liver transplantation. Thus, a combined utilization of the two biomarkers may be a useful tool in the risk evaluation of patients following liver transplantation.