Combining Donor and Recipient Age With Preoperative MELD and UKELD Scores for Predicting Survival After Liver Transplantation

Objectives: The end-stage liver disease scoring systems MELD, UKELD, and D-MELD (donor age × MELD) have had mediocre results for survival assessment after orthotopic liver transplant. Here, we introduced new indices based on preoperative MELD and UKELD scores and assessed their predictive ability on survival posttransplant. Materials and Methods: We included 1017 deceased donor orthotopic liver transplants that were performed between 2008 (the year UKELD was introduced) and 2019. Donor and recipient characteristics, liver disease scores, transplant characteristics, and outcomes were collected for analyses. D-MELD, D-UKELD (donor age × UKELD), DR-MELD [(donor age + recipient age) × MELD], and DR-UKELD [(donor age + recipient age) × UKELD] were calculated. Results: No score had predictive value for graft survival. For patient survival, DR-MELD and DR-UKELD provided the best results but with low accuracy. The highest accuracy was observed at 1 year posttransplant (areas under the curve of 0.598 [95% CI, 0.529-0.667] and 0.609 [95% CI, 0.549-0.67] for DR-MELD and DR-UKELD). Addition of donor and recipient age significantly improved the predictive abilities of MELD and UKELD for patient survival, but addition of donor age alone did not. For 1-year mortality (using receiver operating characteristic curves), optimal cut-off points were DR-MELD >2345 and DR-UKELD >5908. Recipients with DR-MELD >2345 (P 5908 (P = .002) had worse patient survival within the first year, but only DR-MELD >2345 remained significant after multiva­riable analysis (P = .007). Conclusions: DR-MELD and DR-UKELD scores provided the best, albeit mediocre, predictive ability among the 6 tested models, especially at 1 year after posttransplant, although only for patient but not for graft survival. A DR-MELD >2345 was considered to be an additional independent risk factor for worse recipient survival within the first postoperative year

Donor-Recipient Body Surface Area Mismatch and the Outcome of Liver Transplantation in the UK

Introduction: Too small or too big liver grafts for recipient's size has detrimental effects on transplant outcomes. Research Questions: The purpose was to correlate donor-recipient body surface area (BSA) ratio or BSA index (BSAi) with recipient survival, graft survival, hepatic artery or portal vein, or vena cava thrombosis. High and low BSAi cut-off points were determined. Design: There were 11,245 adult recipients of first deceased donor whole liver-only grafts performed in the UK from January 2000 until June 2020. The transplants were grouped according to the BSAi and compared to complications, graft and recipient survival. Results: The BSAi ranged from 0.491 to 1.691 with a median of 0.988. The BSAi > 1.3 was associated with a higher rate of portal vein thrombosis within the first 3 months (5.5%). This risk was higher than size-matched transplants (OR: 2.878, 95% CI: 1.292-6.409, P = 0.01). Overall graft survival was worse in transplants with BSAi ≤ 0.85 (HR: 1.254, 95% CI: 1.051-1.497, P = 0.012) or BSAi > 1.4 (HR: 3.704, 95% CI: 2.029-6.762, P 1.4. These findings were confirmed by bootstrap internal validation. No statistically significant differences were detected for hepatic artery thrombosis, occlusion of hepatic veins/inferior vena cava or recipient survival. Conclusions: Donor-recipient size mismatch affects the rates of portal vein thrombosis within the first 3 months and overall graft survival in deceased-donor liver transplants

The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia

Background - Severe preeclampsia is associated with increased neutrophil activation and elevated serum soluble endoglin (sEng) and soluble Flt-1 (sFlt-1) in the maternal circulation. To dissect the contribution of systemic inflammation and anti-angiogenic factors in preeclampsia, we investigated the relationships between the circulating markers of neutrophil activation and anti-angiogenic factors in severe preeclampsia or systemic inflammatory state during pregnancy. Methods and results - Serum sEng, sFlt-1, placenta growth factor, interleukin-6 (IL-6), calprotectin, and plasma a-defensins concentrations were measured by ELISA in 88 women of similar gestational age stratified as: severe preeclampsia (sPE, n = 45), maternal systemic inflammatory response (SIR, n = 16) secondary to chorioamnionitis, pyelonephritis or appendicitis; and normotensive controls (CRL, n = 27). Neutrophil activation occurred in sPE and SIR, as a-defensins and calprotectin concentrations were two-fold higher in both groups compared to CRL (P < 0.05 for each). IL-6 concentrations were highest in SIR (P < 0.001), but were higher in sPE than in CRL (P < 0.01). sFlt-1 (P < 0.001) and sEng (P < 0.001) were ˜20-fold higher in sPE compared to CRL, but were not elevated in SIR. In women with sPE, anti-angiogenic factors were not correlated with markers of neutrophil activation (a-defensins, calprotectin) or inflammation (IL-6). Conclusions - Increased systemic inflammation in sPE and SIR does not correlate with increased anti-angiogenic factors, which were specifically elevated in sPE indicating that excessive systemic inflammation is unlikely to be the main contributor to severe preeclampsia

A comparative randomised study of valacyclovir vs. oral ganciclovir for cytomegalovirus prophylaxis in renal transplant recipients

An open, prospective, randomised study was conducted to compare the safety and efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. Eighty-three renal transplant recipients were assigned randomly to receive valacyclovir (n = 43) or oral ganciclovir (n = 40) for the first 3 months after transplantation. Both groups were similar in terms of demographics, primary renal disease, graft source, HLA matching, immunosuppressive therapy and donor-recipient CMV antibody status. CMV infection was diagnosed by detection of virus DNA in plasma with the Amplicor CMV Test. CMV disease was observed in only one patient belonging to the ganciclovir group, who developed enterocolitis 6 months post-transplantation. No difference was observed between the two treatment groups with respect to detection of CMV DNA, virus infections other than CMV, acute rejection episodes, and serum creatinine levels at 3 and 6 months following transplantation. An increased number of bacterial infections was noted in the ganciclovir group (p 0.003). No adverse reactions with either treatment were reported. The estimated cost of valacyclovir treatment was 20% higher than that of ganciclovir treatment. Overall, both valacyclovir and oral ganciclovir were found to be effective and safe for CMV prophylaxis in renal transplant recipients. Decisions regarding prophylactic regimens should include additional criteria, such as cost or possible development of resistance

Frailty score before admission as risk factor for mortality of renal patients during the first wave of the COVID pandemic in London

BACKGROUND: Frailty is a known predictor of mortality and poor outcomes during hospital admission. In this large renal retrospective cohort study, we investigated whether frailer COVID-19 positive renal patients had worse outcomes. DESIGN: All SARS-Cov-2 positive renal patients aged ≥18 years who presented to the emergency department at the Royal Free Hospital or at the satellite dialysis centres from 10th of March until the 10th of May 2020, with recent data on frailty, were included. The follow up was until 26th of May 2020. Age, gender, ethnicity, body mass index, chronic kidney disease stage, modality of renal replacement therapy, co-morbidities, Rockwood clinical frailty score (CFS), C reactive protein and the neutrophil-to-lymphocyte count were collected at presentation. The primary outcome was the overall mortality rate following COVID-19 diagnosis. Secondary outcomes included the need for hospital admission. RESULTS: A total of 200 renal patients were SARS-Cov-2 positive. In the 174 patients who had a CFS recorded, the age was 65.4 years ± 15.8 (mean ± SD) and 57,5% were male. At the end of follow up, 26% had died. Frail patients (CFS 5-7) were more than three times more likely to die compared to less frail patients (CFS of 1-4) (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.0-10.6). 118 patients (68%) required admission, but there was no difference in hospital admission rates for frail vs non-frail patients (OR 0.6, CI 0.3-1.7). CONCLUSIONS: Frailty is a better predictor of mortality than age and co-morbidities in COVID-19 positive renal patients