Perioperative Pleural Drainage in Liver Transplantation: A Retrospective Analysis from a High-Volume Liver Transplant Center

BACKGROUND Pleural effusions represent a common complication after liver transplantation (LT) and chest drain (CD) placement is frequently necessary. MATERIAL AND METHODS In this retrospective cohort study, adult LT recipients between 2009 and 2016 were analyzed for pleural effusion formation and its treatment within the first 10 postoperative days. The aim of the study was to compare different settings of CD placement with regard to intervention-related complications. RESULTS Overall, 597 patients met the inclusion criteria, of which 361 patients (60.5%) received at least 1 CD within the study period. Patients with a MELD >25 were more frequently affected (75.7% versus 56.0%, P<0.001). Typically, CDs were placed in the intensive care unit (ICU) (66.8%) or in the operating room (14.1% during LT, 11.5% in the context of reoperations). In total, 97.0% of the patients received a right-sided CD, presumably caused by local irritations. Approximately one-third (35.4%) of ICU-patients required pre-interventional optimization of coagulation. Of the 361 patients receiving a CD, 15 patients (4.2%) suffered a post-interventional hemorrhage and 6 patients (1.4%) had a pneumothorax requiring further treatment. Less complications were observed when the CD was performed in the operating room compared to the ICU: 1 out 127 patients (0.8%) versus 20 out of 332 patients (6.0%); P=0.016. CONCLUSIONS CD placement occurring in the operating room was associated with fewer complications in contrast to placement occurring in the ICU. Planned CD placement in the course of surgery might be favorable in high-risk patients

Chlamydia pneumoniae infection acts as an endothelial stressor with the potential to initiate the earliest heat shock protein 60-dependent inflammatory stage of atherosclerosis

We identified increased expression and redistribution of the intracellular protein 60-kDa human heat shock protein (hHSP60) (HSPD1) to the cell surface in human endothelial cells subjected to classical atherosclerosis risk factors and subsequent immunologic cross-reactivity against this highly conserved molecule, as key events occurring early in the process of atherosclerosis. The present study aimed at investigating the role of infectious pathogens as stress factors for vascular endothelial cells and, as such, contributors to early atherosclerotic lesion formation. Using primary donor-matched arterial and venous human endothelial cells, we show that infection with Chlamydia pneumoniae leads to marked upregulation and surface expression of hHSP60 and adhesion molecules. Moreover, we provide evidence for an increased susceptibility of arterial endothelial cells for redistribution of hHSP60 to the cellular membrane in response to C. pneumoniae infection as compared to autologous venous endothelial cells. We also show that oxidative stress has a central role to play in endothelial cell activation in response to chlamydial infection. These data provide evidence for a role of C. pneumoniae as a potent primary endothelial stressor for arterial endothelial cells leading to enrichment of hHSP60 on the cellular membrane and, as such, a potential initiator of atherosclerosi

Hepatitis B Immunoglobulin discontinuation in long‐term liver transplant patients

Background: Hepatitis B immunoglobulin (HBIG)-as a monotherapy or combined with nucleos(t)ide analogs (NUCs)-has effectively lowered Hepatitis B virus (HBV) reinfection after liver transplantation. However, it is associated with high costs and viral resistance. HBIG-free prophylaxis with novel NUCs (tenofovir, entecavir) composes a viable alternative. We evaluated reinfection rate, histological changes, and outcome associated with HBIG discontinuation. Methods: A retrospective analysis was performed of patients undergoing liver transplantation due to HBV-induced liver disease at our center since 1988. A controlled HBIG discontinuation was conducted between 2015 and 2017 in 65 patients. Recurrent infection was determined by HbsAg values. Fibrosis and inflammation were evaluated by routine biopsy. The survival of patients after HBIG discontinuation was compared to a control population on HBIG for prophylaxis. Results: From 1988 to 2013, 352 patients underwent liver transplantation due to HBV-induced liver disease. 169 patients could be included for analysis. 104 (51.5%) patients continued a prophylaxis containing HBIG. HBIG was discontinued in 65 (38.5%) patients in a controlled manner, maintaining an oral NUC. None of those patients showed HBV reinfection or graft dysfunction. No significant changes of inflammation grades (P = .067) or fibrosis stages (P = .051) were detected. The survival of patients after HBIG discontinuation was comparable to the control (P = .95). Conclusion: HBIG withdrawal under continuation of oral NUC therapy is safe and not related to graft dysfunction, based on blood tests and histology. HBIG-free prophylaxis is not associated with a worse outcome and displays a financial relief as well as a logistic simplification during long-term follow-up

Validation of a new prognostic model to predict short and medium-term survival in patients with liver cirrhosis

Background: MELD score and MELD score derivates are used to objectify and grade the risk of liver-related death in patients with liver cirrhosis. We recently proposed a new predictive model that combines serum creatinine levels and maximum liver function capacity (LiMAx®), namely the CreLiMAx risk score. In this validation study we have aimed to reproduce its diagnostic accuracy in patients with end-stage liver disease. Methods: Liver function of 113 patients with liver cirrhosis was prospectively investigated. Primary end-point of the study was liver-related death within 12 months of follow-up. Results: Alcoholic liver disease was the main cause of liver disease (n = 51; 45%). Within 12 months of follow-up 11 patients (9.7%) underwent liver transplantation and 17 (15.1%) died (13 deaths were related to liver disease, two not). Measures of diagnostic accuracy were comparable for MELD, MELD-Na and the CreLiMAx risk score as to power in predicting short and medium-term mortality risk in the overall cohort: AUROCS for liver related risk of death were for MELD [6 months 0.89 (95% CI 0.80–0.98) p < 0.001; 12 months 0.89 (95% CI 0.81–0.96) p < 0.001]; MELD-Na [6 months 0.93 (95% CI 0.85–1.00) p < 0.001 and 12 months 0.89 (95% CI 0.80–0.98) p < 0.001]; CPS 6 months 0.91 (95% CI 0.85–0.97) p < 0.01 and 12 months 0.88 (95% CI 0.80–0.96) p < 0.001] and CreLiMAx score [6 months 0.80 (95% CI 0.67–0.96) p < 0.01 and 12 months 0.79 (95% CI 0.64–0.94) p = 0.001]. In a subgroup analysis of patients with Child-Pugh Class B cirrhosis, the CreLiMAx risk score remained the only parameter significantly differing in non-survivors and survivors. Furthermore, in these patients the proposed score had a good predictive performance. Conclusion: The CreLiMAx risk score appears to be a competitive and valid tool for estimating not only short- but also medium-term survival of patients with end-stage liver disease. Particularly in patients with Child-Pugh Class B cirrhosis the new score showed a good ability to identify patients not at risk of death

Effects of Artificial Intelligence-Derived Body Composition on Kidney Graft and Patient Survival in the Eurotransplant Senior Program

The Eurotransplant Senior Program allocates kidneys to elderly transplant patients. The aim of this retrospective study is to investigate the use of computed tomography (CT) body composition using artificial intelligence (AI)-based tissue segmentation to predict patient and kidney transplant survival. Body composition at the third lumbar vertebra level was analyzed in 42 kidney transplant recipients. Cox regression analysis of 1-year, 3-year and 5-year patient survival, 1-year, 3-year and 5-year censored kidney transplant survival, and 1-year, 3-year and 5-year uncensored kidney transplant survival was performed. First, the body mass index (BMI), psoas muscle index (PMI), skeletal muscle index (SMI), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) served as independent variates. Second, the cut-off values for sarcopenia and obesity served as independent variates. The 1-year uncensored and censored kidney transplant survival was influenced by reduced PMI (p = 0.02 and p = 0.03, respectively) and reduced SMI (p = 0.01 and p = 0.03, respectively); 3-year uncensored kidney transplant survival was influenced by increased VAT (p = 0.04); and 3-year censored kidney transplant survival was influenced by reduced SMI (p = 0.05). Additionally, sarcopenia influenced 1-year uncensored kidney transplant survival (p = 0.05), whereas obesity influenced 3-year and 5-year uncensored kidney transplant survival. In summary, AI-based body composition analysis may aid in predicting short- and long-term kidney transplant survival

Effects of Artificial Intelligence-Derived Body Composition on Kidney Graft and Patient Survival in the Eurotransplant Senior Program

The Eurotransplant Senior Program allocates kidneys to elderly transplant patients. The aim of this retrospective study is to investigate the use of computed tomography (CT) body composition using artificial intelligence (AI)-based tissue segmentation to predict patient and kidney transplant survival. Body composition at the third lumbar vertebra level was analyzed in 42 kidney transplant recipients. Cox regression analysis of 1-year, 3-year and 5-year patient survival, 1-year, 3-year and 5-year censored kidney transplant survival, and 1-year, 3-year and 5-year uncensored kidney transplant survival was performed. First, the body mass index (BMI), psoas muscle index (PMI), skeletal muscle index (SMI), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) served as independent variates. Second, the cut-off values for sarcopenia and obesity served as independent variates. The 1-year uncensored and censored kidney transplant survival was influenced by reduced PMI (p = 0.02 and p = 0.03, respectively) and reduced SMI (p = 0.01 and p = 0.03, respectively); 3-year uncensored kidney transplant survival was influenced by increased VAT (p = 0.04); and 3-year censored kidney transplant survival was influenced by reduced SMI (p = 0.05). Additionally, sarcopenia influenced 1-year uncensored kidney transplant survival (p = 0.05), whereas obesity influenced 3-year and 5-year uncensored kidney transplant survival. In summary, AI-based body composition analysis may aid in predicting short- and long-term kidney transplant survival

Humoral Immune Response following SARS-CoV-2 Vaccination in Liver Transplant Recipients

As COVID-19 remains an issue in transplantation medicine, a successful vaccination can prevent infections and life-threatening courses. The probability of poor immune response in liver transplant recipients gained attention and insecurity among those patients, leading us to investigate the humoral immune response alongside the influence of underlying diseases and immunosuppressive regimen on seroconversion rates. We included 118 patients undergoing anti-spike-protein-IgG testing at least 21 days after completed SARS-CoV-2 vaccination. Ninety-seven patients also underwent anti-spike-protein-IgA testing. The influence of baseline demographics, immunosuppressive regimen and underlying disease on seroconversion was analyzed, and 92 of 118 patients (78.0%) developed anti-spike-protein-IgG antibodies. Patients with a history of alcoholic liver disease before transplantation showed significantly lower seroconversion rates (p = 0.006). Immunosuppression also significantly influenced antibody development (p < 0.001). Patients run on a mycophenolate mofetil (MMF)-based regimen were more likely not to develop antibodies compared to patients run on a non-MMF regimen (p < 0.001). All patients weaned off immunosuppression were seropositive. The seroconversion rate of 78.0% in our cohort of liver transplant recipients is promising. The identification of alcohol-induced cirrhosis as underlying disease and MMF for immunosuppression as risk factors for seronegativity may serve to identify vaccination non-responder after liver transplantation

The role of neoadjuvant radiochemotherapy in the management of localized high-grade soft tissue sarcoma

Background: Standard treatment of soft tissue sarcoma (STS) of the extremities includes limb-sparing surgery combined with pre- or postoperative radiotherapy (RT). The role of perioperative chemotherapy (CTX) remains uncertain. STS patients with high-risk features for local recurrence, distant metastases, and increased mortality may require additional systemic therapy. The objective of this study was to evaluate predictors of outcome regarding local control (LC), overall survival (OS), and freedom from distant metastases (FFDM) in a large single-center cohort of patients suffering from localized high-grade STS (grade 2/3, G2/G3). Special emphasis was put on a subgroup of patients who received combined neoadjuvant radiochemotherapy (RCT). Methods: Overall, 115 adult STS patients were included in this retrospective study. The median follow-up was 34 months. Twenty-three patients (20.0%) were treated with neoadjuvant RCT, 92 (80.0%) received other therapies (adjuvant RT alone (n = 58); neoadjuvant CTX + adjuvant RT (n = 17); adjuvant RCT (n = 10), neoadjuvant RT alone (n = 7)). To assess potential prognostic factors on LC, OS, and FFDM, univariate (UVA) and multivariable (MVA) Cox proportional hazards models were applied. Results: UVA showed significantly better LC rates in the neoadjuvant RCT group (p = 0.025), with trends in MVA (p = 0.057). The 3-year LC rate was 89.7% in the neoadjuvant RCT group vs. 75.6% in the "other therapies" group. UVA also showed significantly better OS rates in the neoadjuvant RCT group (p = 0.049), however, this was not confirmed in MVA (p = 0.205), the 3-year OS rate was 85.8% for patients treated with neoadjuvant RCT compared to 73.5% in the "other therapies" group. UVA showed significantly better FFDM rates in (p = 0.018) and a trend towards better FFDM rates in MVA (p = 0.059). The 3-year FFDM rate was 89.7% for patients treated with neoadjuvant RCT compared to 65.9% in the "other therapies" group. In the subgroup of patients with G3 STS, neoadjuvant RCT was a significant positive predictor of LC and FFDM in MVA (p = 0.047, p = 0.027) but not for OS. Overall grade 3 and 4 toxicities were significantly higher (p = 0.019) in the neoadjuvant RCT group and occurred in 73.9% vs. 38.0% in patients receiving other therapies. Conclusions: The results suggest that neoadjuvant RCT might improve LC and FFDM in patients with localized G3 STS while also being associated with increased acute complication rates. Further prospective research is warranted to confirm these findings

Reducing the Pill Burden: Immunosuppressant Adherence and Safety after Conversion from a Twice-Daily (IR-Tac) to a Novel Once-Daily (LCP-Tac) Tacrolimus Formulation in 161 Liver Transplant Patients

Non-adherence to immunosuppressant therapy reduces long-term graft and patient survival after solid organ transplantation. The objective of this 24-month prospective study was to determine adherence, efficacy and safety after conversion of stable liver transplant (LT) recipients from a standard twice-daily immediate release Tacrolimus (IR-Tac) to a novel once-daily life cycle pharma Tacrolimus (LCP-Tac) formulation. We converted a total of 161 LT patients at baseline, collecting Tacrolimus trough levels, laboratories, physical examination data and the BAASIS(C) questionnaire for self-reported adherence to immunosuppression at regular intervals. With 134 participants completing the study period (17% dropouts), the overall adherence to the BAASIS(C) increased by 57% until month 24 compared to baseline (51% vs. 80%). Patients who required only a morning dose of their concomitant medications reported the largest improvement in adherence after conversion. The intra-patient variability (IPV) of consecutive Tacrolimus trough levels after conversion did not change significantly compared to pre-conversion levels. Despite reducing the daily dose by 30% at baseline as recommended by the manufacturer, Tac-trough levels remained stable, reflected by an increase in the concentration-dose (C/D) ratio. No episodes of graft rejection or loss occurred. Our data suggest that the use of LCP-Tac in liver transplant patients is safe and can increase adherence to immunosuppression compared to conventional IR-Tac