The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation

High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low-risk (0–3), medium-risk (4–5), and high-risk (6–10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT.     

Full-left-full-right split liver transplantation for adult recipients: a systematic review and meta-analysis

Full-left-full-right split liver transplantation (FSLT) for adult recipients, may increase the availability of liver grafts, reduce waitlist time, and benefit recipients with below-average body weight. However, FSLT may lead to impaired graft and patient survival. This study aims to assess outcomes after FSLT. Five databases were searched to identify studies concerning FSLT. Incidences of complications, graft- and patient survival were assessed. Discrete data were pooled with random-effect models. Graft and patient survival after FSLT were compared with whole liver transplantation (WLT) according to the inverse variance method. Vascular complications were reported in 25/273 patients after FSLT (Pooled proportion: 6.9%, 95%CI: 3.1–10.7%, I²: 36%). Biliary complications were reported in 84/308 patients after FSLT (Pooled proportion: 25.6%, 95%CI: 19–32%, I²: 44%). Pooled proportions of graft and patient survival after 3 years follow-up were 72.8% (95%CI: 67.2–78.5, n = 231) and 77.3% (95%CI: 66.7–85.8, n = 331), respectively. Compared with WLT, FSLT was associated with increased graft loss (pooled HR: 2.12, 95%CI: 1.24–3.61, P = 0.006, n = 189) and patient mortality (pooled HR: 1.81, 95%CI: 1.17–2.81, P = 0.008, n = 289). FSLT was associated with high incidences of vascular and biliary complications. Nevertheless, long-term patient and graft survival appear acceptable and justify transplant benefit in selected patients.     

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Annals of Surgical Oncology - The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to...     

The pharmacokinetics of high-dose epirubicin and of the cardioprotector ADR-529 given together with cyclophosphamide, 5-fluorouracil,and tamoxifen in metastatic breast-cancer patients

A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-m silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i.v. administration of different doses of ADR-529 (600–1000 mg/m²) together with different doses of epirubicin (E, 60–100 mg/m²), fixed-dose cyclophosphamide (C, 600 mg/m²), fixed-dose 5-fluorouracil (F, 600 mg/m²), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m². We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity.     

Canal geometry changes associated with axial compressive cervical spine fracture

STUDY DESIGN: A laboratory study using isolated ligamentous human cadaveric cervical spines to investigate canal occlusion during (transient) and after (steady-state) axial compressive fracture. OBJECTIVES: To determine whether differences exist between transient and postinjury canal occlusion under axial compressive loading, and to examine the effect of loading rate on canal occlusion. SUMMARY OF BACKGROUND DATA: Prior studies have shown no correlation between neurologic deficit and canal occlusion measurements made on radiographs and computed tomography scans. The authors hypothesized that postinjury radiographic assessment does not provide an appreciation for the transient occlusion that occurs during the traumatic fracture event, which may significantly affect the neurologic outcome. METHODS: Twelve human cervical spines were instrumented with a specially designed canal occlusion transducer, which dynamically monitored canal occlusion during axial compressive impact. Six specimens were subjected to a fast-loading rate (time to peak load, approximately 20 msec), and the other six were subjected to a slow-loading rate (time to peak load, approximately 250 msec). After impact, two different postinjury canal occlusion measurements were performed. RESULTS: Each of the six specimens subjected to the fast-loading rate incurred burst fractures, whereas the slow-loading rate produced six wedge-compression fractures. For the fast-rate group, the postinjury occlusion-measurements were significantly smaller than the transient occlusion. In contrast, transient occlusion was not found to be significantly different from postinjury occlusion in the slow-rate group. All of the comparisons between loading rate groups showed significant differences, with the fast-rate fractures producing larger amounts of canal occlusion in every category. CONCLUSIONS: The findings indicate that even if canal occlusion could be measured immediately after axial compressive trauma, the measurement would underestimate the maximal amount of transient canal occlusion. Therefore, postinjury measurement of canal occlusion may indicate a smaller degree of neurologic deficit than what might be expected if the transient occlusion could be measured.     

3,4,3′-Tri-O-methylellagic acid as an anticancer agent: in vitro and in silico studies

We report a natural product compound isolated from Syzygium polycephalum known as 3,4,3′-tri-O-methylellagic acid (T-EA) as a candidate drug for cancer treatment. The characterization of the isolated T-EA compound was carried out using various spectroscopic methods. The in vitro evaluation showcased the inhibition activity of T-EA towards the T47D and HeLa cell lines with EC₅₀ values of 55.35 ± 6.28 μg mL⁻¹ and 12.57 ± 2.22 μg mL⁻¹, respectively. Meanwhile, the in silico evaluation aimed to understand the interaction of T-EA with enzymes responsible for cancer regulation at the molecular level by targeting the hindrance of cyclin-dependent kinase 9 (CDK9) and sirtuin 1 (SIRT1) enzymes. T-EA showed a binding free energy towards the SIRT1 protein of ΔG_{bind (MM-GBSA)}: −30.98 ± 0.25 kcal mol⁻¹ and ΔG_{bind (MM-PBSA)}: −24.07 ± 0.30 kcal mol⁻¹, while that of CDK9 was ΔG_{bind (MM-GBSA)}: −29.50 ± 0.22 kcal mol⁻¹ and ΔG_{bind (MM-PBSA)}: −25.87 ± 0.40 kcal mol⁻¹. The obtained results from this research could be considered as important information on 3,4,3′-tri-O-methylellagic acid as a drug to treat cervical and breast cancers.

We report a natural product compound isolated from Syzygium polycephalum known as 3,4,3′-tri-O-methylellagic acid (T-EA) as a candidate drug for cancer treatment using in vitro and in silico approaches.