Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study).

BACKGROUND & AIM: We aimed to assess long-term outcome after transplantation of HOPE-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of a HOPE-treated liver transplanted between January 2012 and December 2021. Analyses were stratified for brain-dead (DBD) and circulatory-dead (DCD) donor livers, sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischemic cholangiopathy (IC). RESULTS: We report on 1202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low-risk (10%), 186 as high-risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival for DBD and DCD was 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (logrank p=0.003). Within DBD and DCD-strata, death-censored graft survival was similar among risk groups (logrank p=0.26, p=0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE-treatment has now reached IDEAL-D stage 4, which further supports the implementation of HOPE in routine clinical practice. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of HOPE-treatment of DCD and DBD liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomized controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE-treatment has now reached the final IDEAL-D Stage 4, which further supports the implementation of HOPE in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320.

Improved outcomes after hypothermic oxygenated machine perfusion in liver transplantation-Long-term follow-up of a multicenter randomized controlled trial.

BACKGROUND: While 4 randomized controlled clinical trials confirmed the early benefits of hypothermic oxygenated machine perfusion (HOPE), high-level evidence regarding long-term clinical outcomes is lacking. The aim of this follow-up study from the HOPE-ECD-DBD trial was to compare long-term outcomes in patients who underwent liver transplantation using extended criteria donor allografts from donation after brain death (ECD-DBD), randomized to either HOPE or static cold storage (SCS). METHODS: Between September 2017 and September 2020, recipients of liver transplantation from 4 European centers receiving extended criteria donor-donation after brain death allografts were randomly assigned to HOPE or SCS (1:1). Follow-up data were available for all patients. Analyzed endpoints included the incidence of late-onset complications (occurring later than 6 months and graded according to the Clavien-Dindo Classification and the Comprehensive Complication Index) and long-term graft survival and patient survival. RESULTS: A total of 46 patients were randomized, 23 in both arms. The median follow-up was 48 months (95% CI: 41-55). After excluding early perioperative morbidity, a significant reduction in late-onset morbidity was observed in the HOPE group (median reduction of 23 Comprehensive Complication Index-points [p=0.003] and lower incidence of major complications [Clavien-Dindo ≥3, 43% vs. 85%, p=0.009]). Primary graft loss occurred in 13 patients (HOPE n=3 vs. SCS n=10), resulting in a significantly lower overall graft survival (p=0.029) and adverse 1-, 3-, and 5-year survival probabilities in the SCS group, which did not reach the level of significance (HOPE 0.913, 0.869, 0.869 vs. SCS 0.783, 0.606, 0.519, respectively). CONCLUSIONS: Our exploratory findings indicate that HOPE reduces late-onset morbidity and improves long-term graft survival providing clinical evidence to further support the broad implementation of HOPE in human liver transplantation.

Clinical Research in Renal Transplantation: A Bibliometric Perspective on a Half-century of Innovation and Progress.

BACKGROUND: Groundbreaking biomedical research has transformed renal transplantation (RT) into a widespread clinical procedure that represents the mainstay of treatment for end-stage kidney failure today. Here, we aimed to provide a comprehensive bibliometric perspective on the last half-century of innovation in clinical RT. METHODS: The Web of Science Core Collection was used for a comprehensive screening yielding 123 303 research items during a 50-y period (January 1973-October 2022). The final data set of the 200 most-cited articles was selected on the basis of a citation-based strategy aiming to minimize bias. RESULTS: Studies on clinical and immunological outcomes (n = 63 and 48), registry-based epi research (n = 38), and randomized controlled trials (n = 35) dominated the data set. Lead US authors have signed 110 of 200 articles. The overall level of evidence was high, with 84% of level1 and -2 reports. Highest numbers of these articles were published in New England Journal of Medicine , Transplantation , and American Journal of Transplantation. Increasing trend was observed in the number of female authors in the postmillennial era (26% versus 7%). CONCLUSIONS: This study highlights important trends in RT research of the past half-century. This bibliometric perspective identifies the most intensively researched areas and shift of research interests over time; however, it also describes important imbalances in distribution of academic prolificacy based on topic, geographical aspects, and gender.

Detrimental impact of immunosuppressive burden on clinical course in patients with Cytomegalovirus infection after liver transplantation.

INTRODUCTION: Cytomegalovirus (CMV)-infection and reactivation remain a relevant complication after liver transplantation (LT). The recipient and donor serum CMV-IgG-status has been established for risk stratification when choosing various pharmaceutical regimens for CMV-prophylaxis in the last two decades. However, factors influencing course of CMV-infection in LT remain largely unknown. In this study, the impact of immunosuppressive regimen was examined in a large cohort of patients. METHODS: All patients that underwent primary LT between 2006 and 2018 at the Charité-Universitaetsmedizin, Berlin, were included. Clinical course as well as histological and laboratory findings of patients were analyzed our prospectively maintained database. Univariate and multivariate regression analysis for impact of variables on CMV-occurrence was conducted, and survival was examined using Kaplan-Meier analysis. RESULTS: Overall, 867 patients were included in the final analysis. CMV-infection was diagnosed in 325 (37.5%) patients after transplantation. Significantly improved overall survival was observed in these patients (Log rank = 0.03). As shown by correlation and regression tree classification and regression tree analysis, the recipient/donor CMV-IgG-status with either positivity had the largest influence on CMV-occurrence. Analysis of immunosuppressive burden did not reveal statistical impact on CMV-infection, but statistically significant inverse correlation of cumulative tacrolimus trough levels and survival was found (Log rank < .001). Multivariate analysis confirmed these findings (p = .02). DISCUSSION: CMV-infection remains of clinical importance after LT. Undergone CMV-infection of either recipient or donor requires prophylactic treatment. Additionally, we found a highly significant, dosage-dependent impact of immunosuppression (IS) on long-term outcomes for these patients, underlying the importance of minimization of IS in liver transplant recipients.

How to Estimate the Probability of Tolerance Long-Term in Liver Transplant Recipients.

BACKGROUND: Operational tolerance as the ability to accept the liver transplant without pharmacological immunosuppression is a common phenomenon in the long-term course. However, it is currently underutilized due to a lack of simple diagnostic support and fear of rejection despite its recognized benefits. In the present work, we present a simple score based on clinical parameters to estimate the probability of tolerance. PATIENTS AND METHODS: In order to estimate the probability of tolerance, clinical parameters from 82 patients after LT who underwent weaning from the IS for various reasons at our transplant center were extracted from a prospectively organized database and analyzed retrospectively. Univariate testing as well as multivariable logistic regression analysis were performed to assess the association of clinical variables with tolerance in the real-world setting. RESULTS: The most important factors associated with tolerance after multivariable logistic regression were IS monotherapy, male sex, history of hepatocellular carcinoma pretransplant, time since LT, and lack of rejection. These five predictors were retained in an approximate model that could be presented as a simple scoring system to estimate the clinical probability of tolerance or IS dispensability with good predictive performance (AUC = 0.89). CONCLUSION: In parallel with the existence of a tremendous need for further research on tolerance mechanisms, the presented score, after validation in a larger collective preferably in a multicenter setting, could be easily and safely applied in the real world and already now address all three levels of prevention in LT patients over the long-term course.

Body composition is associated with disease aetiology and prognosis in patients undergoing resection of intrahepatic cholangiocarcinoma.

BACKGROUND: Body composition alterations are frequent in patients with cancer or chronic liver disease, but their prognostic value remains unclear in many cancer entities. OBJECTIVE: We investigated the impact of disease aetiology and body composition after surgery for intrahepatic cholangiocarcinoma (iCCA), a rare and understudied cancer entity in European and North American cohorts. METHODS: Computer tomography-based assessment of body composition at the level of the third lumbar vertebra was performed in 173 patients undergoing curative-intent liver resection for iCCA at the Department of Surgery, Charité - Universitätsmedizin Berlin. Muscle mass and -composition as well as subcutaneous and visceral adipose tissue quantity were determined semi-automatically. (Secondary) sarcopenia, sarcopenic obesity, myosteatosis, visceral and subcutaneous obesity were correlated to clinicopathological data. RESULTS: Sarcopenia was associated with post-operative morbidity (intraoperative transfusions [p = 0.027], Clavien-Dindo ≥ IIIb complications [p = 0.030], post-operative comprehensive complication index, CCI [p < 0.001]). Inferior overall survival was noted in patients with myosteatosis (33 vs. 23 months, p = 0.020). Fifty-eight patients (34%) had metabolic (dysfunction)-associated fatty liver disease (MAFLD) and had a significantly higher incidence of sarcopenic (p = 0.006), visceral (p < 0.001) and subcutaneous obesity (p < 0.001). Patients with MAFLD had longer time-to-recurrence (median: 38 vs. 12 months, p = 0.025, log-rank test). Multivariable cox regression analysis confirmed only clinical, and not body, composition parameters (age > 65, fresh frozen plasma transfusions) as independently prognostic for overall survival. CONCLUSION: This study evidenced a high prevalence of MAFLD in iCCA, suggesting its potential contribution to disease aetiology. Alterations of muscle mass and adipose tissue were more frequent in patients with MAFLD.

A Reduction of Calcineurin Inhibitors May Improve Survival in Patients with De Novo Colorectal Cancer after Liver Transplantation.

Background and Objectives: After liver transplantation (LT), long-term immunosuppression (IS) is essential. IS is associated with de novo malignancies, and the incidence of colorectal cancer (CRC) is increased in LT patients. We assessed course of disease in patients with de novo CRC after LT with focus of IS and impact on survival in a retrospective, single-center study. Materials and Methods: All patients diagnosed with CRC after LT between 1988 and 2019 were included. The management of IS regimen following diagnosis and the oncological treatment approach were analyzed: Kaplan−Meier analysis as well as univariate and multivariate analysis were performed. Results: A total of 33 out of 2744 patients were diagnosed with CRC after LT. Two groups were identified: patients with restrictive IS management undergoing dose reduction (RIM group, n = 20) and those with unaltered regimen (maintenance group, n = 13). The groups did not differ in clinical and oncological characteristics. Statistically significant improved survival was found in Kaplan−Meier analysis for patients in the RIM group with 83.46 (8.4−193.1) months in RIM and 24.8 (0.5−298.9) months in the maintenance group (log rank = 0.02) and showed a trend in multivariate cox regression (p = 0.054, HR = 14.3, CI = 0.96−213.67). Conclusions: Immunosuppressive therapy should be reduced further in patients suffering from CRC after LT in an individualized manner to enable optimal oncological therapy and enable improved survival.

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

Reducing Immunosuppression in Patients with De Novo Lung Carcinoma after Liver Transplantation Could Significantly Prolong Survival.

(1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised. (2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution's register of liver allograft recipients (Charité-Universitätsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach. (3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7-27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0-196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function. (4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.

Diagnostic value of contrast-enhanced ultrasound (CEUS) in kidney allografts - 12 years of experience in a tertiary referral center.

BACKGROUND: B-Mode and Doppler ultrasound are standard diagnostic techniques for early postoperative monitoring and long-term follow-up of kidney transplants. In certain cases, contrast-enhanced ultrasound (CEUS) is used to clarify unclear Doppler findings. OBJECTIVE: To investigate the diagnostic performance of CEUS in the workup of renal allograft pathologies. METHODS: A systematic search for CEUS examinations of renal transplants conducted in our department between 2008 and 2020 was performed using the following inclusion criteria: i) patient age ≥18 years and ii) confirmation of diagnosis by biopsy and histopathology, imaging follow-up by CEUS, contrast-enhanced computed tomography (ceCT), contrast-enhanced magnetic resonance imaging (ceMRI), or angiography, or intraoperative findings. Exclusion criteria were: i) CEUS performed in the setting of a study and ii) CEUS for other indications than dedicated renal transplant examination. Statistical analysis was performed separately for subgroups with different indications (focal vs non-focal). RESULTS: Overall, 78 patients were included in the statistical analysis, which revealed high sensitivity (92.2%, 95% -confidence interval [CI] 81.5-96.9%) and high specificity (88.9%, 95% -CI 71.9-96.1%) of CEUS. CONCLUSIONS: The high diagnostic performance demonstrated here and the superficial location of kidney allografts advocate the additional use of CEUS in the follow-up of renal transplant recipients.

The Role of Immunosuppression for Recurrent Cholangiocellular Carcinoma after Liver Transplantation.

Liver transplantation (LT) for cholangiocarcinoma (CCA), or biliary tract cancer (BTC), remains controversial regarding high recurrence rates and poor prognosis. Oncological follow-up may benefit from tumor-inhibiting properties of mTOR inhibitors (mTORI), shown with improved survival for recurrent hepatocellular carcinoma (HCC) patients after LT. The aim of this study was to investigate the recurrence and survival in relation to tumor type and type of immunosuppression (IS). LT patients with CCA or mixed HCC/CCA (mHCC/CCA) (n = 67) were retrospectively analyzed. Endpoints were the time from LT to recurrence (n = 44) and survival after recurrence. Statistically significant impairment in survival for recurrent CCA (rCCA) was shown in patients not eligible for surgical resection (HR 2.46 (CI: 1.2−5.1; p = 0.02). Histological proven grading >1 and N1 status at initial transplantation were associated with impaired survival (HR 0.13 (CI: 0.03−0.58); p < 0.01 and HR 3.4 (CI: 1.0−11.65); p = 0.05). Reduced IS after tumor recurrence improved survival (HR 4.2/CI: 1.3−13.6; p = 0.02). MTORI initiation before recurrence or after had no significant impact on survival. Our data thereby indicate, similar to findings in recurrent HCC after LT, that patients with rCCA after LT benefit from a reduction in IS upon recurrence.

Prognostic and Predictive Molecular Markers in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the second most common primary liver cancer and subsumes a heterogeneous group of malignant tumors arising from the intra- or extrahepatic biliary tract epithelium. A rising mortality from CCA has been reported worldwide during the last decade, despite significant improvement of surgical and palliative treatment. Over 50% of CCAs originate from proximal extrahepatic bile ducts and constitute the most common CCA entity in the Western world. Clinicopathological characteristics such as lymph node status and poor differentiation remain the best-studied, but imperfect prognostic factors. The identification of prognostic molecular markers as an adjunct to traditional staging systems may not only facilitate the selection of patients who would benefit the most from surgical, adjuvant or palliative treatment strategies, but may also be helpful in defining the aggressiveness of the disease and identifying patients at high-risk for tumor recurrence. The purpose of this review is to provide an overview of currently known molecular prognostic and predictive markers and their role in CCA.

Hyperkalemia Following Parathyroidectomy in Patients with Renal Hyperparathyroidism-New Thresholds for Urgent Perioperative Dialysis.

Parathyroidectomy (PTX) is a mainstay of treating secondary hyperparathyroidism (SHPT) in patients with kidney failure in order to reduce the incidence of cardiovascular events (CVE), increase overall survival and improve quality of life. Perioperative hyperkalemia may lead to devastating cardiac complications. Distinct preoperative thresholds for serum potassium levels (SPL) were defined, but neither their usefulness nor consecutive risks are understood. This study compared the results and efficacy of different clinical procedures in preventing or treating perioperative hyperkalemia, including postoperative urgent hemodialysis (UHD). Methods: Patients from Charité-Universitätsmedizin Berlin and Rheinland Klinikum Lukaskrankenhaus, Neuss, undergoing PTX due to SHPT between 2008 and 2018 were analyzed retrospectively with regard to demographic parameters, surgery specific conditions and perioperative laboratory results. Comparisons of patient values from both centers with focus on perioperative hyperkalemia and the need for UHD were performed. Results: A total of 251 patients undergoing PTX for SHPT were included (Neuss: n = 121 (48%); Berlin: n = 130 (52%)). Perioperative hyperkalemia (SPL ≥ 5.5 mmol/L) was noted in 134 patients (53%). UHD on the day of surgery was performed especially in patients with intraoperative hyperkalemia, in females (n = 40 (16%) vs. n = 27 (11%); p = 0.023), in obese patients (n = 27 (40%) vs. n = 50 (28%), p = 0.040) and more often in patients treated in Neuss (n = 42 (35%) vs. 25 (19%); p = 0.006). For patients treated in Neuss, the intraoperative hyperkalemia cut-off level above 5.75 mmol/L was the most predictive factor for UHD (n = 30 (71%) vs. n = 8 (10%); p < 0.001). Concerning secondary effects of hyperkalemia or UHD, no patient died within the postoperative period, and only three patients suffered from acute CVE, with SPL > 5.5 mmol/L measured in only one patient. Conclusion: Perioperative values could not predict postoperative hyperkalemia with the need for UHD. Previously defined cut-off levels for SPL should be reconsidered, especially for patients undergoing PTX. Early postoperative dialysis in patients with postoperative hyperkalemia can be performed with a low risk for complications and may be indicated for all patients with increased perioperative SPL.

E-scooter incidents in Berlin: an evaluation of risk factors and injury patterns.

BACKGROUND: E-scooters have emerged as a frequently used vehicle in German cities due to their high availability and easy access. However, investigations about the causes and mechanisms of E-scooter incidents and their trauma-specific consequences are rare. METHODS: We analysed all patients involved in E-scooter incidents from June to December 2019 who presented to four inner-city EDs in Berlin. The prospective data included patient-related and incident-related data, information on injury patterns and therapy, responses in a voluntary questionnaire concerning E-scooter use and general traffic experience. RESULTS: 248 patients (129 males; median age 29 years (5-81)) were included: 41% were tourists and 4% were children. Most incidents (71%) occurred between July and September 2019, the majority occurring at weekends (58%). The injury pattern was mostly multifocal, affecting the lower (42%) and upper limbs (37%) and the head (40%). Traumatic brain injury was associated with alcohol consumption. Inpatient admission was recorded in 25%, surgery in 23%. CONCLUSION: This study has defined the incidence of injury related to E-scooter use in a major European city. Stricter laws governing the use of E-scooters, the wearing of helmets and technical modifications to the E-scooter platforms might decrease E-scooter-associated incidents and resulting injuries in the future. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS00018061).

Hypothermic oxygenated machine perfusion for extended criteria donor allografts: Preliminary experience with extended organ preservation times in the setting of organ reallocation.

BACKGROUND: In times of critical organ shortage, poor organ pool utilization and increased use of extended-criteria donor (ECD) allografts remain a major problem. Hypothermic oxygenated machine perfusion (HOPE) has emerged as a promising and feasible strategy in ECD liver transplantation (LT). However, potential safety limits regarding the duration of perfusion are yet to be explored. Besides marginal allograft quality (steatosis), prolonged cold ischemia time remains the most important factor for a high number of liver allografts being declined for transplantation. PATIENTS AND METHODS: Two ECD-allografts were each allocated to two recipients, who proved to be unsuitable to receive the assigned allograft upon arrival at the transplant center. The organs were reallocated by Eurotransplant and accepted by our center for two different backup patients. During that time, HOPE was commenced and continued until the recipient hepatectomy was completed. Postoperative allograft function was assessed by serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and International Normalized Ratio. Incidence of early allograft dysfunction (EAD), postoperative complications, and length of hospital stay were analyzed. RESULTS: HOPE was applied for 4 h 35 min and 4 h 20 min, resulting in a total cold preservation time of 17 h 29 min and 15 h 20 min, respectively. Both recipients displayed decreasing serum transaminases and bilirubin levels postoperatively. No EAD or major postoperative complications occurred in either patient. Serum ALT and AST levels were within the normal range at discharge. CONCLUSIONS: Extended HOPE enables the safe extension of preservation time for up to 18 h in human LT. End-ischemic HOPE may significantly improve organ pool utilization, while simultaneously facilitating operating room logistics and preventing organ injury.

Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation From Donation After Brain Death: Results From a Multicenter Randomized Controlled Trial (HOPE ECD-DBD).

OBJECTIVE: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD). BACKGROUND: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT). METHODS: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD). RESULTS: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59-78) years, recipient age: 62 (IQR: 55-65) years, labMELD: 15 (IQR: 9-25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221-828) vs 796 (IQR: 477-1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12-56) vs 52 (IQR: 35-98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4-8) vs 8 (IQR: 5-18) days, P = 0.045; 20 (IQR: 16-27) vs 36 (IQR: 23-62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314). CONCLUSION: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.

Is There a Gender Difference in Clinical Presentation of Renal Hyperparathyroidism and Outcome after Parathyroidectomy?

INTRODUCTION: Gender has been proven to influence the pathophysiology and treatment of numerous diseases, including kidney diseases and hormonal dysfunction like hyperparathyroidism. Thus, higher parathormone levels have been demonstrated in women with end-stage kidney disease, when compared to men. OBJECTIVES: We questioned whether female gender is associated with an increased risk for parathyroid nodular hyperplasia and necessary parathyroidectomy in dialysis patients and assessed demographics as well as outcome data for women and men undergoing parathyroidectomy for renal hyperparathyroidism. PATIENTS AND METHODS: One hundred and thirty patients (men = 75, female = 55) with end-stage renal disease on chronic dialysis and advanced secondary hyperparathyroidism who underwent parathyroidectomy between 2008 and 2014 at our center were analyzed retrospectively. Perioperative characteristics and short-term outcome were evaluated with respect to biological gender. RESULTS: No differences could be demonstrated for patient demography, comorbidities and the perioperative course between males and females. Only preoperative calcium levels were lower in female than in male patients (2.3 ± 0.19 vs. 2.3 ± 0.26, p = 0.04). There were more women, however, with cerebrovascular complications during follow-up (p = 0.04). There was no postoperative mortality, and all complications and comorbidities with exception of cerebrovascular diseases were equally distributed between female and male patients. CONCLUSION: Overall, we could not demonstrate many significant differences between male and female patients with end-stage renal diseases, chronic dialysis and operated secondary hyperparathyroidism. Only preoperative electrolyte levels were higher in male than in female patients, and cerebrovascular complications developed more often in females than in males during long-term follow-up.

Thymectomy in ocular myasthenia gravis before generalization results in a higher remission rate.

OBJECTIVES: This study aimed to compare the outcomes of patients with ocular myasthenia gravis (OMG) who underwent thymectomy before generalization with the outcomes of those who underwent thymectomy after generalization. METHODS: We retrospectively reviewed patients who underwent robotic thymectomy for myasthenia gravis between January 2003 and February 2018. Patients who presented with purely ocular symptoms at myasthenia gravis onset were eligible for inclusion. Exclusion criteria were patients who were lost to follow-up and patients who underwent re-thymectomy. Patients with OMG who developed generalization before thymectomy were categorized into gOMG group and those who did not were categorized into OMG group. The primary outcome was complete stable remission according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS). RESULTS: One hundred and sixty-five (66 males and 99 females) out of 596 patients with myasthenia gravis were eligible for inclusion. Of these, there were 73 and 92 patients undergoing thymectomy before and after the generalization of OMG, respectively. After propensity score matching, a data set of 130 patients (65 per group) was formed and evaluating results showed no statistical differences between the 2 groups. The estimated cumulative probabilities of complete stable remission at 5 years were 49.5% [95% confidence interval (CI) 0.345-0.611] in the OMG group and 33.4% (95% CI 0.176-0.462) in the gOMG group (P = 0.0053). Similar results were also found in patients with non-thymomatous subgroup [55 patients per group, OMG vs gOMG, 53.5% (95% CI 0.370-0.656) vs 28.9% (95% CI 0.131-0.419), P = 0.0041]. CONCLUSIONS: Thymectomy in OMG before generalization might result in a higher rate of complete stable remission than thymectomy after generalization.