LTx Patients Research Articles

Postoperative Fluid Accumulation is Associated With Underestimation of AKI Severity in Lung Transplant Recipients.

Post-lung transplantation (LTx) fluid accumulation can lead to dilution of serum creatinine (SCr). We hypothesized that fluid accumulation might impact the diagnosis, staging, and outcome of posttransplant acute kidney injury (AKI). In this retrospective study, we analyzed data from 131 adult LTx patients at a single German lung center between 2005 and 2018. We assessed the occurrence of AKI within 7 days posttransplant, both before and after SCr-adjustment for fluid balance (FB), and investigated its impact on all-cause mortality. Transient and persistent AKIs were defined as return to baseline kidney function or continuation of AKI beyond 72h of onset, respectively. AKI was diagnosed in 58.8% of patients according to crude SCr values. When considering FB-adjusted SCr values, AKI severity was underestimated in 20.6% of patients, that is, AKI was detected in an additional 6.9% of patients and led to AKI upstaging in 23.4% of cases. Patients initially underestimated but detected with AKI only after FB adjustment had higher mortality compared to those who did not meet AKI criteria (hazard ratio [HR] 2.98; 95% confidence interval [CI] 1.06, 8.36; p=0.038). Persistent AKI was associated with higher mortality than transient AKI, regardless of using crude or adjusted SCr values (p < 0.05). Persistent AKI emerged as an independent risk factor for mortality (HR 2.35; 95% CI 1.29, 4.30; p=0.005). Adjusting for FB and evaluating renal recovery patterns post-AKI may enhance the sensitivity of AKI detection. This approach could help identify patients with poor prognosis and potentially improve outcomes in lung transplant recipients. ClinicalTrials.gov identifier: NCT03039959, NCT03046277.

Initial experience with transcatheter aortic valve replacement before and after lung transplant

ObjectivesPatients with end-stage lung disease and lung transplant (LTx) recipients are high-risk candidates for surgical aortic valve replacement (AVR). Transcatheter AVR (TAVR) is an established treatment for aortic stenosis. Experience with TAVR in the LTx population is limited. We sought to report our experience in patients who underwent TAVR before or after LTx. MethodsSingle-center, retrospective analysis, including all patients who underwent TAVR pre- or post-LTx from 2000 to 2020. Indications, mode of anesthesia, timing of TAVR, and procedural outcomes were reviewed. ResultsIn total, 10 LTx patients underwent TAVR. Aortic stenosis was the indication for TAVR in all patients: 5 had TAVR pre-LTx, and 5 post-LTx. All 10 TAVRs were performed with transfemoral access, and 9 out of 10 with intravenous sedation and monitored anesthesia care; only 1 required general anesthesia. In the TAVR pre-LTx group, mean age was 62 years and 4 patients were men. Four TAVR valves were balloon-expandable and 1 self-expanding. Median time from TAVR to transplant was 7.4 months (range, 1.7-36 months), and median length of stay after TAVR 4 days (range, 2-36 days). The only TAVR-related complication was a pacemaker for heart block (1 out of 5). All 5 subsequently underwent successful double LTx (1 with concurrent liver transplant). In the TAVR post-LTx group, mean age was 66 years and 2 patients were men. Four TAVR valves were balloon-expandable and 1 was self-expanding. Median time from LTx to TAVR was 5 years (range, 2.6-7.6 years), and median length of stay post-TAVR was 2 days (range, 1-17 days). The only TAVR-related complication in this group was heart block requiring pacemaker (1 out of 5). In both groups, there were no intraprocedural mortality or conversion to surgical AVR. No patients required post-TAVR surgical intervention during study follow-up. ConclusionsOur initial experience suggests that TAVR is safe and feasible for treatment of aortic stenosis in patients with end-stage lung disease awaiting LTx, and in patients who have undergone LTx. Overall TAVR-related complications included need for pacemaker. TAVR should be considered for treatment of aortic stenosis in patients with end-stage lung disease awaiting transplant, and for post-LTx patients as an alternative to surgical aortic valve replacement.

Machine learning model predicts airway stenosis requiring clinical intervention in patients after lung transplantation: a retrospective case-controlled study

BackgroundPatients with airway stenosis (AS) are associated with considerable morbidity and mortality after lung transplantation (LTx). This study aims to develop and validate machine learning (ML) models to predict AS requiring clinical intervention in patients after LTx.MethodsPatients who underwent LTx between January 2017 and December 2019 were reviewed. The conventional logistic regression (LR) model was fitted by the independent risk factors which were determined by multivariate LR. The optimal ML model was determined based on 7 feature selection methods and 8 ML algorithms. Model performance was assessed by the area under the curve (AUC) and brier score, which were internally validated by the bootstrap method.ResultsA total of 381 LTx patients were included, and 40 (10.5%) patients developed AS. Multivariate analysis indicated that male, pulmonary arterial hypertension, and postoperative 6-min walking test were significantly associated with AS (all P < 0.001). The conventional LR model showed performance with an AUC of 0.689 and brier score of 0.091. In total, 56 ML models were developed and the optimal ML model was the model fitted using a random forest algorithm with a determination coefficient feature selection method. The optimal model exhibited the highest AUC and brier score values of 0.760 (95% confidence interval [CI], 0.666–0.864) and 0.085 (95% CI, 0.058–0.117) among all ML models, which was superior to the conventional LR model.ConclusionsThe optimal ML model, which was developed by clinical characteristics, allows for the satisfactory prediction of AS in patients after LTx.

Early extracorporeal photopheresis treatment is associated with better survival in patients with chronic or recurrent acute lung allograft dysfunction.

Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid organ transplant recipients. Treatment options for slowing down CLAD progression are scarce with extracorporeal photopheresis (ECP) as an established rescue therapy. The aim of the study was to identify characteristics of responders and non-responders to ECP treatment, assess their survival, lung function development and by that define the subset of patients who should receive early ECP treatment. We performed a retrospective study of all LTx patients receiving ECP treatment at the University Hospital Zurich between January 2010 and March 2020. Patients were followed-up for a maximum period of 5 years. Mortality and lung function development were assessed by CLAD stage and by CLAD subtype before initiation of ECP treatment. Overall, 105 patients received at least one ECP following LTx. A total of 57 patients (61.3%) died within the study period with a median survival of 15 months. Mortality was 57% for patients who started ECP at CLAD1, 39% for CLAD2, 93% for CLAD3, and 90% for CLAD4 (p < 0.001). Survival and lung function development was best in young patients at early CLAD stages 1 and 2. Response to ECP treatment was worst in patients with CLAD-RAS/mixed subtype (14.3%) and patients with ECP initiation in CLAD stages 3 (7.1%) and 4 (11.1%). Survival was significantly better in a subset of patients with recurrent acute allograft dysfunction and earlier start of ECP treatment (105 vs 15 months). In this retrospective analysis of a large group of CLAD patients treated with ECP after LTx, early initiation of ECP was associated with better long-term survival. Besides a subset of patients suffering of recurrent allograft dysfunction, especially a subset of patients defined as responders showed an improved response rate and survival, suggesting that ECP should be initiated in early CLAD stages and young patients. ECP might therefore prevent long-term disease progression even in patients with CLAD refractory to other treatment options and thus prevent or delay re-transplantation.

Magnetic sphincter augmentation: A promising alternative to fundoplication for preserving lung function and protecting against chronic lung transplant rejection

BackgroundEarly laparoscopic fundoplication (LF) has been shown to slow lung function decline in chronic lung disease (CLD) patients and lung transplant (LTx) recipients. Magnetic sphincter augmentation (MSA) has emerged as an effective minimally invasive alternative to LF for the treatment of GERD. We evaluate the safety and efficacy of MSA compared to LF for GERD in CLD and LTx. MethodsA retrospective review identified CLD and LTx patients undergoing LF or MSA for GERD. Primary outcome was change in percent predicted FEV1. Secondary outcomes were 30d morbidity, mortality, operative time, and length of stay (LOS). Results77 patients met inclusion criteria, 45 (58.5 %) were LTx recipients. 35 (45.5 %) underwent Nissen, 23 (29.9 %) underwent Toupet, and 19 (24.7 %) underwent MSA. Average age was 54.2 years, 54.5 % were female, and average BMI at ARS was 24.9 kg/m2. Median FEV1 % change between pre-ARS and post-ARS was 0 % with no significant differences between groups. MSA had faster operative times at 50.5 min than Nissen (83.5 min, p = 0.002) and Toupet (72.6 min, p = 0.003) and shorter LOS at 0.8 days than Nissen (3.7 days, p = 0.002) and Toupet (2.1 days, p = 0.0008). MSA and Nissen had higher reintervention rates than Toupet, though this was not statistically significant. There were no differences in 30-day morbidities or 30-day ED visits between groups. There were no mortalities. ConclusionMSA is an advantageous alternative to LF in the CLD and LTx population with stabilization of percent predicted FEV1, equivalent safety profile, shorter operative times, and shorter length of hospital stay.

Evaluation of liver transplantation services in Kazakhstan from 2012 to 2023

There is a scarcity of publications evaluating the performance of the national liver transplantation (LTx) program in Kazakhstan. Spanning from 2012 to 2023, it delves into historical trends in LTx surgeries, liver transplant centers, and the national cohort of patients awaiting LTx. Survival analysis for those awaiting LTx, using life tables and Kaplan–Meier, is complemented by time series analysis projecting developments until 2030. The overall per million population (pmp) LTx rate varied from 0.35 to 3.77, predominantly favoring living donor LTx. Liver transplant center rates ranged from 0.06 to 0.40. Of 474 LTx patients, 364 on the waiting list did not receive transplantation. The 30-day and 1-year survival rates on the waiting list were 87.0% and 68.0%, respectively. Viral hepatitis and cirrhosis prevalence steadily rose from 2015 to 2023, with projections indicating a persistent trend until 2030. Absent targeted interventions, stable pmp rates of LTx and liver transplant centers may exacerbate the backlog of unoperated patients. This study sheds light on critical aspects of the LTx landscape in Kazakhstan, emphasizing the urgency of strategic interventions to alleviate the burden on patients awaiting transplantation.

Effect of a 12-week nutritional intervention in the food intake of patients on the waiting list for liver transplantation: A secondary analysis of a randomized controlled trial

BackgroundInadequate food intake contributes to malnutrition in patients with cirrhosis on the waiting list for liver transplantation (LTx). ObjectiveTo evaluate food intake during 12 weeks of nutritional follow-up and assess factors independently associated with the difference between caloric and protein intake in LTx patients. MethodsA secondary analysis of data from a randomized controlled trial that evaluated the effects of HMB supplementation in patients on a liver transplant waiting list. Dietary guidelines for patients with cirrhosis were used to prescribe the nutritional plan (35kcal/kg; 1.5g/kg dry weight for protein) and to evaluate the nutritional goals (30kcal/kg; 1.2g/kg dry weight for protein). Food intake was assessed in six moments: Baseline, week 0(W0), week 2(W2), week 4(W4), week 8(W8), and week 12(W12). ResultsForty-seven patients (55.0±10.6y;72.3% male) were evaluated. Only 25.5% (n=12) of patients achieve nutritional goals at the end of the study. The mean energy intake in baseline was 1782±784kcal (27.6±13.2kcal/kg) without difference between times. The protein intake increased between week W0 [63.4±29.8g; 0.8(0.2-2.2g/kg)] and W8 [72.0±28.0g; 1.0(0.4–2.6g/kg); p=0.03; p=0.03, respectively]. The consumption of cholesterol, calcium, phosphorus, magnesium, iron, and niacin increased (p<0.05), as well as the consumption of the leguminous; roots and tubers; dairy; and meat, poultry, and fish groups through the time (p<0.05). The presence of ascites, patients nourished, frailty index classification, short physical performance battery score, systemic symptoms, and emotional function were independently associated with the caloric intake difference W12-Baseline (p<0.05). Diabetes mellitus, patients with moderately malnourishment, poor performance, fatigue, systemic symptoms, and emotional function were independently associated with the difference in protein intake between W12-Baseline (p<0.05). ConclusionPatients on the liver transplant waiting list showed slight food intake improvement during the follow-up, but few met nutritional guidelines. Various clinical and nutritional factors independently affected energy and protein intake from W12 to baseline.

A Single-Center Analysis of How HLA Mismatch and Donor-Specific Antibodies Affect Short-Term Outcome After Lung Transplantation: A Pilot Study Before a Country-Wide Histocompatibility Study in Japan

Analyzing HLA polymorphism in lung transplantation (LTx) is important, given its impact on LTx recipient survival and graft function. Accordingly, we conducted a retrospective study to examine the influence of HLA mismatch and donor-specific antibodies (DSA) on short-term outcomes and early-phase post-LTx complications. HLA antigen or eplet mismatch in LTx patients at Tohoku University Hospital from 2018 to 2023 was determined, and DSA was measured on admission for surgery to identify preformed DSA and at weeks 4 to 12 post-LTx for de novo DSA, respectively. The participants were 45 LTx recipients, HLA-A/B/DR antigen mismatch (5-6 of 6) being identified in 57%, HLA-A/B/Cw/DR/DQ mismatch (8-10 of 10) in 57%, and HLA eplet mismatch (>61) in 46%. The prevalence of preformed DSA was 24%, and persistence (uncleared) was 16%. The incidence of de novo DSA was 16% after LTx. During the study,16 recipients experienced grade 3 primary graft dysfunction (PGD), 8 developed acute rejection, and 5 died. No HLA-related variables were significantly associated with post-LTx mortality and were not risk factors for high-grade PGD or acute rejection. Despite limitations in sample size, resulting in tentative findings, the study serves as a crucial pilot study for an ongoing multicenter prospective trial in Japan.

Impact of minimally invasive lung transplantation on early outcomes and analgesia use: A matched cohort study

IntroductionMinimally invasive (MI) approaches to lung transplantation (LTx) offer the prospect of faster recovery compared to traditional incisions, however, little data exist describing the impact of surgical technique on early outcomes and analgesia use. MethodsA prospectively maintained institutional registry identified 170 patients who underwent LTx between 01/2017 and 06/2022. Post-COVID acute respiratory distress syndrome, repeat, and multiorgan transplants were excluded (n=27) leaving 37 MILTx and 106 traditional LTx patients. Propensity score matching by age, sex, body mass index, diagnosis, lung allocation score, double vs. single lung, hypertension, diabetes, and hospitalization status created 37 pairs. ResultsBefore matching, MILTx patients were more often male (70% vs 43%) and more likely to receive grafts from younger (31 vs 42 years), circulatory death donors (19% vs 6%) compared with traditional LTx patients (all p<0.05). After matching, there were no differences in graft warm ischemia or operative duration (both p>0.05). Postoperatively, MILTx experienced shorter ICU (4.3 [IQR 3.1-5.5] vs 8.2 [IQR 3.7-10.8] days) and hospital lengths of stay (LOS) (13 [IQR 11-15] vs 17 [IQR 12-25] days) (both p<0.05). Among patients surviving to discharge, MILTx patients required fewer opioid prescriptions at discharge (38% vs 66%, p=0.008) and had improved pulmonary function at 3-months (FEV1 82 [IQR 72-102] vs 77 [IQR 52-88] % predicted; FVC 78 [IQR 65-92] vs 70 [IQR 62-80] % predicted] (both p<0.05). ConclusionMinimally invasive LTx techniques demonstrate potential advantages over traditional approaches, including reduced ICU and hospital LOS, lower opioid use on discharge, and improved early pulmonary function. Word count: 250/250

Perceptions of barriers to and facilitators of exercise rehabilitation in adults with lung transplantation: a qualitative study in China

BackgroundExercise is crucial for pulmonary rehabilitation and improving the prognosis of lung transplantation (LTx) patients. However, many LTx patients in China have low exercise tolerance and compliance, and the reasons behind these challenges have not been fully elucidated. Therefore, this qualitative research aims to identify the barriers to and facilitators of exercise rehabilitation in LTx patients.MethodsFrom January to July 2023, 15 stable LTx patients were recruited and participated in in-depth, semi-structured, face-to-face interviews at Henan Provincial People’s Hospital. The interview transcripts were analyzed using the COM-B model and the Theoretical Domains Framework (TDF).ResultsSix general themes including 19 barriers and 14 facilitators for the exercise rehabilitation of LTx patients were identified based on the COM-B model and TDF. The barriers to exercise included physical limitations, insufficient exercise endurance, lack of knowledge, and lack of motivation. The facilitators of exercise included motivation, self-efficacy, perceived significance of exercise rehabilitation, and social support.ConclusionThe study offers detailed insight into the development and implementation of exercise rehabilitation intervention strategies for LTx patients. By combining COM-B model and TDF, the study provides strong evidence that active behavior change strategies are required for LTx patients to promote their participation in exercise rehabilitation. Professional support, pulmonary rehabilitation training, behavior change technology, and digital health tools are essential for strengthening the evidence system for reporting exercise efficacy and effectiveness.

Lung Transplantation for Pulmonary Vascular Disease in Children: A United Network for Organ Sharing Analysis.

Pulmonary vascular disease (PVD) represents an important clinical indication for lung transplant (LTx) in infants, children, and adolescents. There is limited information on LTx outcomes in these patients. We explored LTx volumes and post-LTx survival in children with PVD compared to other diagnoses. The UNOS Registry was queried from 1989 to 2020 to identify first-time pediatric LTx recipients (< 18 yo). PVD was categorized as idiopathic pulmonary arterial hypertension (IPAH) and non-idiopathic arterial hypertension (non-IPAH) and compared to all other patients as other diagnoses. Univariate and multivariate regression models were performed. 984 pediatric LTx patients (593 before 2010 and 391 during/after 2010) were identified, of which 145 (14.7%) had PVD. There has been no significant change in annual rate of all LTxs over comparative eras. However, there has been a decrease in rate of LTxs for PVD patients. Children with PVD had similar survival to other LTx groups in the early era (p = 0.2) and the latter era (p = 0.9). Univariate Cox models, showed that LTx in patients with PVD was associated with a significantly less risk of mortality for children aged 6-11years compared to younger and older cohorts (HR = 0.4 [0.17-0.98]; p = 0.045), whereas multivariate analysis showed a trend toward higher mortality in 11-17-year-olds (HR = 1.54 [0.97-2.45]; p = 0.06). For PVD patients, oxygen supplementation and ventilator support at LTx were associated with worse post-transplant survival (p = 0.029 and p = 0.01). There has been a decrease in LTx volume for pediatric patients with PVD in the modern era. Post-LTx outcomes for children with PVD are similar to those of other diagnoses in both eras, with children aged 6-11years having the best survival. Given these findings, LTx should be considered for this patient population.

Gut microbiota dynamics in a 1-year follow-up after adult liver transplantation in Northeast China.

Background: Liver transplantation (LTx) is the most effective treatment for end-stage liver diseases. Gut microorganisms influence the host physiology. We aim to profile the dynamics of gut microbiota in the perioperative period and a 1-year follow-up of LTx recipients in Northeast China. Methods: A total of 257 fecal samples were longitudinally collected from 85 LTx patients using anal swabs from pre-LTx to 1-year post-LTx. A total of 48 fecal samples from end-stage liver disease patients without LTx served as the control. 16S rRNA sequencing was used to analyze gut microbiota diversity, bacterial genera, phenotype classification, and metabolic pathways. Results: The diversity of gut microbiota decreased significantly after transplantation, accompanied by a profound change in the microbial structure, which is characterized by increased abundance of facultative anaerobic bacteria dominated by g_Enterococcus and reduced anaerobic bacteria composition. Predicted functional analysis also revealed disturbances in the metabolic pathway of the gut microbiota. After LTx, the diversity of microbiota gradually recovered but to a less preoperative level after 1 year of recovery. Compared with pre-transplantation, the microbiome structure was characterized by an increase in Acidaminococcus and Acidithiobacillus after 1 year of transplantation. Conclusion: LTx and perioperative treatment triggered gut microbial dysbiosis. The gut microbiota was restructured after LTx to near to but significantly differed from that of pre-LTx.

Design and Rationale of Cytokine Filtration in Lung Transplantation (GLUSorb): Protocol for a Multicenter Clinical Randomized Controlled Trial.

Lung transplantation (LTx) is the only treatment option for end-stage lung disease. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the main factor in late mortality after LTx. PGD develops within the first 72 hours and impairs the oxygenation capacity of the lung, measured as partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2). Increasing the PaO2/FiO2 ratio is thus critical and has an impact on survival. There is a general lack of effective treatments for PGD. When a transplanted lung is not accepted by the immune system in the recipient, a systemic inflammatory response starts where cytokines play a critical role in initiating, amplifying, and maintaining the inflammation leading to PGD. Cytokine filtration can remove these cytokines from the circulation, thus reducing inflammation. In a proof-of-concept preclinical porcine model of LTx, cytokine filtration improved oxygenation and decreased PGD. In a feasibility study, we successfully treated patients undergoing LTx with cytokine filtration (ClinicalTrials.gov; NCT05242289). The purpose of this clinical trial is to demonstrate the superiority of cytokine filtration in improving LTx outcome, based on its effects on oxygenation ratio, plasma levels of inflammatory markers, PGD incidence and severity, lung function, kidney function, survival, and quality of life compared with standard treatment with no cytokine filtration. This study is a Swedish national interventional randomized controlled trial involving 116 patients. Its primary objective is to investigate the potential benefits of cytokine filtration when used in conjunction with LTx. Specifically, this study aims to determine whether the application of cytokine filtration, administered for a duration of 12 hours within the initial 24 hours following a LTx procedure, can lead to improved patient outcomes. This study seeks to assess various aspects of patient recovery and overall health to ascertain the potential positive impact of this intervention on the posttransplantation course. The process of patient recruitment for this study is scheduled to commence subsequent to a site initiation visit, which was slated to take place on August 28, 2023. The primary outcome measure that will be assessed in this research endeavor is the oxygenation ratio, a metric denoted as the highest PaO2/FiO2 ratio achieved by patients within a 72-hour timeframe following their LTx procedure. We propose that cytokine filtration could enhance the overall outcomes of LTx. Our hypothesis suggests potential improvements in LTx outcome and patient care. ClinicalTrials.gov NCT05526950; https://www.clinicaltrials.gov/study/NCT05526950. PRR1-10.2196/52553.

THU441 Teriparatide As Treatment For Severe Osteoporosis In Lung Transplant Recipients

Abstract Disclosure: C.A. Muir: None. L.M. Raven: None. L. Goodall: None. J.R. Center: None. Background: Lung transplantation (LTx) is a life-saving treatment for end-stage pulmonary disease. With improvements in immunosuppression, LTx survival continues to improve with current 5-year survival rates of over 70%. Consequently, management of long-term transplant-related complications is increasingly important. Osteoporosis is one such complication, with the incidence of osteoporosis and osteoporotic fracture highest in LTx patients compared to other solid organ transplant recipients. Despite high fracture rates, including in patients treated with anti-resorptive medications, no data has been published using anabolic treatments for the management of osteoporosis in LTx recipients. Study design: Clinical case series. We present clinical, biochemical and bone mineral density data for four patients with severe osteoporosis post LTx treated with teriparatide. Results: Four LTx patients were treated with teriparatide 20 mcg daily for 18 months. Prednisone dose ranged between 5-10 mg daily throughout the treatment period. All patients had been previously treated for osteoporosis using zolendronate (last dose 12-24 months prior to teriparatide initiation). Bone turnover was monitored repeatedly during treatment in two patients. Following completion of teriparatide treatment, all patients received consolidation treatment with zolendronate (3 patients) or denosumab (1 patient). Bone density was measured prior and within 6-12 months after completion of teriparatide. All four patients experienced an increase in bone density at the spine (median 13%; range 2-14%) and total proximal femur (median 8%, range 6-10%) related to teriparatide treatment. No adverse effects were observed. Conclusion: Given that severe osteoporosis is highly prevalent in LTx patients and that fractures often continue to occur after treatment with anti-resorptive medication, teriparatide should be further studied as an alternative treatment in this clinical setting. Our experience in four patients suggest it is safe and effective. Presentation: Thursday, June 15, 2023

Liver transplant in patients with primary sclerosing cholangitis: A retrospective cohort from Northeastern Brazil.

Primary sclerosing cholangitis (PSC) manifests within a broad ethnic and racial spectrum, reflecting different levels of access to health care. To evaluate the clinical profile, complications and survival rates of patients with PSC undergoing liver transplantation (LTx) at a Brazilian reference center. All patients diagnosed with PSC before or after LTx were included. The medical records were reviewed for demographic and clinical variables, including outcomes and survival. The level of statistical significance was set at P < 0.05. Our cohort represented 1.6% (n = 34) of the 2113 patients receiving liver grafts at our service over the past two decades. Most were male (n = 19; 56%). The average age (40 ± 14 years) was similar for men and women (P = 0.347). The mean follow-up time from diagnosis to LTx was 68 mo. Most patients had the classic form of PSC. Three women had PSC/autoimmune hepatitis overlap syndrome, and one patient had small-duct PSC. Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease. scores were significantly higher in males. Inflammatory bowel research (IBD) was investigated by colonoscopy in 26/34 (76%) and was present in most cases (18/26; 69%). IBD was less common in women than in men (44.4% vs. 55.6%) (P = 0.692). Cholangiocarcinoma (CCA) was diagnosed in 2/34 (5.9%) patients by histopathology of the explant (survival: 3 years 6 mo, and 4 years 11 mo). Two patients had complications requiring a second LTx (one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction). Five patients (14.7%) developed biliary stricture. The overall median post-LTx survival was 66 mo. Most deaths occurred in the first year (infection n = 2, primary liver graft dysfunction n = 3, unknown cause n = 1). The 1-year and 5-year survival rates of this cohort were 82.3% and 70.6%, respectively, matching the mean overall survival rates of LTx patients at our center (87.1% and 69.43%, respectively) (P = 0.83). Survival after 1 and 5 years was similar to that of other LTx indications. The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.

Early chest CT abnormalities to predict the subsequent occurrence of chronic lung allograft dysfunction

IntroductionChronic lung allograft dysfunction (CLAD) can take two forms: bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). The aim was to determine if chest-CT abnormalities after lung transplantation (LTx) could predict CLAD before respiratory functional deterioration.Materials and methodsThis monocentric retrospective study analyzed consecutive patients who underwent LTx from January 2015 to December 2018. Initial CT post-LTx (CTi) and a follow-up CT at least 9 months post-LTx (CTf) were reviewed. CLAD was defined as a persistent respiratory functional decline (> 20% of basal FEV1) outside acute episode. A Cox regression was performed in univariate, then in multivariate analysis (including features with p < 0.01 in univariate or of clinical importance) to determine risk factors for CLAD. Subgroup analyses were made for BOS, RAS, and death.ResultsAmong 118 LTx patients (median (min–max) 47 (18–68) years), 25 developed CLAD during follow-up (19 BOS). The median time to CLAD since LTx was 570 days [150–1770]. Moderate pulmonary artery stenosis (30–50%) was associated with the occurrence of CLAD on CTi (hazard ratio HR = 4.6, CI [1.6–13.2]) and consolidations and pleural effusion on CTf (HR = 2.6, CI [1.3–4.9] and HR = 4.5, CI [1.5–13.6] respectively). The presence of mosaic attenuation (HR = 4.1, CI [1.4–12.5]), consolidations (HR = 2.6, CI [1.3–5.4]), and pleural effusions (p = 0.01, HR = 5.7, CI [1.4–22.3]) were risk factors for BOS on CTf. The consolidations (p = 0.029) and pleural effusions (p = 0.001) were risk factors for death on CTf.ConclusionsCTi and CTf in the monitoring of LTx patients could predict CLAD. Moderate pulmonary artery stenosis, mosaic pattern, parenchyma condensations, and pleural effusions were risk factors for CLAD.Critical relevance statementThere is a potential predictive role of chest CT in the follow-up of LTx patients for chronic lung allograft dysfunction (CLAD). Early chest CT should focus on pulmonary artery stenosis (risk factor for CLAD in this study). During the follow-up (at least 9 months post-LTx), parenchymal consolidations and pleural effusions were shown to be risk factors for CLAD, and death in subgroup analyses.Key points• Pulmonary artery stenosis (30–50%) on initial chest-CT following lung transplantation predicts CLAD HR = 4.5; CI [1.6–13.2].• Pleural effusion and consolidations 1 year after lung transplantation predict CLAD and death.• Early evaluation of lung transplanted patients should evaluate pulmonary artery anastomosis.Graphical

Favorable effect of CD26/DPP-4 inhibitors on postoperative outcomes after lung transplantation: A propensity-weighted analysis

We have shown the efficacy of CD26/dipeptidyl peptidase 4 (CD26/DPP-4) inhibitors, antidiabetic agents, in allograft protection after experimental lung transplantation (LTx). We aimed to elucidate whether CD26/DPP-4 inhibitors effectively improve postoperative outcomes after clinical LTx. We retrospectively reviewed the records of patients undergoing LTx at our institution between 2010 and 2021 and extracted records of patients with diabetes mellitus (DM) at 6months post-LTx. The patient characteristics and postoperative outcomes were analyzed. We established 6months post-LTx as the landmark point for predicting overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. Hazard ratios were estimated by Cox regression after propensity score weighting, using CD26/DPP-4 inhibitor treatment up to 6months post-LTx as the exposure variable. We evaluated CLAD samples pathologically, including for CD26/DPP-4 immunohistochemistry. Of 102 LTx patients with DM, 29 and 73 were treated with and without CD26/DPP-4 inhibitors, respectively. Based on propensity score adjustment using standardized mortality ratio weighting, the 5-year OS rates were 77.0% and 44.3%, and the 5-year CLAD-free survival rates 77.8% and 49.1%, in patients treated with and without CD26/DPP-4 inhibitors, respectively. The hazard ratio for CD26/DPP-4 inhibitor use was 0.34 (95% confidence interval (CI) 0.14-0.82, p=0.017) for OS and 0.47 (95% CI 0.22-1.01, p=0.054) for CLAD-free survival. We detected CD26/DPP-4 expression in the CLAD grafts of patients without CD26/DPP-4 inhibitors. Analysis using propensity score weighting showed that CD26/DPP-4 inhibitors positively affected the postoperative prognosis of LTx patients with DM.

Cultivation-based characterization of biliary microbiota in bile samples collected during routine endoscopic retrograde cholangiography: 10 years of experience at a tertiary center.

Bile has long been considered sterile. Recent studies show that bacteria can frequently be detected in bile and certain bacterial species are associated with bile duct-associated liver disease. To detect bacterial species and antibiotic resistance in bile in bile duct-associated liver disease. To evaluate microbiological findings of bile samples obtained during ERCP at a tertiary center from 2009 to 2019. There were 1885 bile samples from 992 patients examined by cultural microbiological analysis. Germs were detected in 91% of the samples. Most bile samples (n) were obtained from patients who had undergone liver transplantation (LTX; n = 556), followed by patients with primary sclerosing cholangitis (PSC; n = 287). Enterococci were detected in 67% of samples, followed by E. coli (32.2%) and Klebsiella (28.2%). Of 1151 enterococci detected, 13.1% were vancomycin (VRE)s and of 216 staphylococci detected, 10% were ORSA. The proportion of VRE increased with the number of tests performed during ERCPs ( P < 0.01; chi-square) and increased 2.5-fold over 10 years, whereas the detection of ORSA remained stable. Patients with cholecystolithiasis were significantly more likely to have evidence of VRE in bile compared to LTX and PSC patients ( P = 0.02, P < 0.01; chi-square). The most abundant bacterial genera showed highly statistically significant differences in their levels of liver enzymes and c-reactive protein ( P < 0.001). Knowledge of the bacterial composition of bile in various bile duct-associated liver diseases may allow more targeted antibiotic use in the future.

Tolerability and Feasibility of the Upper Esophageal Sphincter Assist Device in Preventing Acute and Chronic Allograft Rejection Among Lung Transplant Recipients.

We aimed to evaluate a novel upper esophageal sphincter (UES) assist device loaner program for the prevention of acute cellular rejection and chronic lung allograft dysfunction among lung transplant (LTx) recipients. Laryngopharyngeal reflux can lead to chronic microaspiration and LTx rejection. The UES assist device applies external pressure at the level of UES to decrease reflux. We prospectively enrolled and issued UES assist devices to consecutive transplant patients referred for gastrointestinal motility testing from 2016 to 2020. Device tolerability was defined by successful utilization as a bridge to ambulatory pH monitoring and/or antireflux procedure, or as permanent therapy. Incidence of rejection was analyzed before, during, and after device implementation. Twenty-six participants were issued devices (15 pathologic, 5 physiological, 6 unknown reflux status), none of whom developed acute rejection episodes or chronic lung allograft dysfunction while using the device. Thirteen adopted the device promptly after transplantation (mean 1.7 mo) and remained free of rejection episodes over a mean 24.7 months of follow-up. Among those with pathologic reflux, lag time to device adoption strongly correlated with the development of rejection (r=0.8, P=0.0006). There was no such correlation among those with physiological reflux. Five developed acute rejection after device return. The device was tolerated by a majority of LTx patients and appears feasible as a barrier measure in the prevention of rejection. Delayed treatment of laryngopharyngeal reflux may lead to early allograft failure; therefore, the UES assist device should be given important consideration in transplant protection.

A Combination of Cytological Biomarkers as a Guide in the Diagnosis of Acute Rejection in Lung Transplant Recipients

The usefulness of bronchoalveolar lavage fluid (BALF) to support the diagnosis of acute cellular (ACR) rejection in lung transplant (LTX) recipients remains controversial. ACR has been associated with blood eosinophil counts (EOS) in other solid organ recipients, but there are few studies in relation to lung transplants. Our aim was to assess the usefulness of the combined analysis of BALF cellularity and EOS for the diagnosis of ACR in lung transplant recipients. This is a retrospective study of findings observed simultaneously in 887 transbronchial biopsies (TBB), BALF, and blood samples obtained from 363 LTx patients transplanted between 2014 and 2020. The variables collected were: demographics, ACR degree, BALF cellularity, and simultaneous blood EOS counts. The lymphocyte count in BALF was significantly higher in patients with ACR than in those without (11.35% vs. 6.11%; p &lt; 0.001). In parallel, EOS counts were also significantly higher in patients with ACR than in the non-ACR group (EOS 213 ± 206/mm3 vs. 83 ± 129/mm3; p &lt; 0.001). Increases in both parameters were associated with an increased risk of ACR (lymphocytes OR 1.100; 95% CI 1.080–1.131; EOS OR 1.460; 95% CI 1.350–1.580). The diagnostic specificity of ACR for a lymphocyte count &gt; 12% was 71.1%, which increased to 95.8% when taking into account a simultaneous blood EOS count &gt; 200/mm3. Simultaneous assessment of BALF lymphocyte counts and blood eosinophil counts may be useful for diagnosing ACR in patients with risk factors for TBB or in the presence of inconclusive histological samples.