Performance of risk prediction models for post-operative mortality in patients undergoing liver resection

BackgroundLiver resection is commonly performed for hepatic tumors, however preoperative risk stratification remains challenging. We evaluated the performance of contemporary prediction models for short-term mortality after liver resection in patients with and without cirrhosis.MethodsThis retrospective cohort study examined National Surgical Quality Improvement Program data. We included patients who underwent liver resections from 2014 to 2019. VOCAL-Penn, MELD, MELD-Na, ALBI, and Mayo risk scores were evaluated in terms of model discrimination and calibration for 30-day post-operative mortality.ResultsA total 15,198 patients underwent liver resection, of whom 249 (1.6%) experienced 30-day post-operative mortality. The VOCAL-Penn score had the highest discrimination (area under the ROC curve [AUC] 0.74) compared to all other models. The VOCAL-Penn score similarly outperformed other models in patients with (AUC 0.70) and without (AUC 0.74) cirrhosis.ConclusionThe VOCAL-Penn score demonstrated superior predictive performance for 30-day post-operative mortality after liver resection as compared to existing clinical standards.     

Deepm5C: A deep-learning-based hybrid framework for identifying human RNA N5-methylcytosine sites using a stacking strategy

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RESIRT: A Phase 1 Study of Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres in Patients With Primary Renal Cell Carcinoma

IntroductionSelective internal radiation therapy (SIRT) is a potential treatment of primary renal cell carcinoma (RCC) deemed unsuitable for conventional therapy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.Patients and MethodsPatients with RCC, unsuitable for, or who declined conventional therapy, were eligible. A single transfemoral micro-catheter administration of yttrium-90 (Y-90) resin microspheres (SIR-Spheres) was delivered super selectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gy and a final cohort with a procedural endpoint of “imminent stasis,” in a dose-escalation design. Post-SIRT follow-up was 12 months. Study endpoints included safety and toxicity 30-days and 12-months post-SIRT and tumour response (RECIST v1.1).ResultsIn total, 21 patients were enrolled, mean (SD) age was 75 (9.3) years, WHO performance status was 0 in 81%, 12 (57%) had stage 3 chronic kidney disease, and 7 (33%) had prior contralateral nephrectomy. Overall, 71% of patients completed 12 months of follow-up. Intended doses were delivered without any dose-limiting toxicity. Seventeen out of 21 (81%) patients experienced an adverse event (AE) from any cause within 30 days post-SIRT; all SIRT-related AEs were grade 1 to 2. Best overall tumour responses were partial response 1/21 (4.8%), stable disease 19/21 (90.5%) and progressive disease 1/21 (4.8%).ConclusionThis study demonstrated good tolerability of SIRT at all dose levels including “imminent stasis” in treating primary tumours in RCC patients otherwise unsuitable for conventional therapy. SIRT with Y-90 resin microspheres may be a feasible treatment option for RCC.     

Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 2. The biological variability of the murine Local Lymph Node Assay (LLNA) for skin sensitisation

The Local Lymph Node Assay (LLNA) is the most common in vivo regulatory toxicology test for skin sensitisation, quantifying potency as the EC3, the concentration of chemical giving a threefold increase in thymidine uptake in the local lymph node. Existing LLNA data can, along with clinical data, provide useful comparator information on the potency of sensitisers. Understanding of the biological variability of data from LLNA studies is important for those developing non-animal based risk assessment approaches for skin allergy. Here an existing set of 94 EC3 values for 12 chemicals, all tested at least three times in the same vehicle have been analysed by calculating standard deviations (SD) for logEC3 values. The SDs range from 0.08 to 0.22. The overall SD for the 94 logEC3 values is 0.147. Thus the 95% confidence limits (2xSD) for LLNA EC3 values are within a factor of 2, comparable to those for physico-chemical measurements such as partition coefficients and solubility. The residual SDs of Quantitative Mechanistic Models (QMMs) based on physical organic chemistry parameters are similar to the overall SD of the LLNA, indicating that QMMs of this type are unlikely to be bettered for predictive accuracy.     

Pharmacokinetics,safety and metabolite profiling of minesapride,a novel 5-HT4 receptor partial agonist,in healthy elderly and young subjects

Minesapride is a novel 5-hydroxytryptamine 4 (5-HT₄) receptor partial agonist that is expected to show efficacy in patients with irritable bowel syndrome with predominant constipation and functional constipation. An open-label study was conducted to evaluate pharmacokinetics (PK) and safety of minesapride. Japanese subjects, 12 elderly and 12 young, received a single oral dose of minesapride 40 mg/day in the fasted state. Metabolite profiles were also investigated in this clinical study and in an in vitro study using cryopreserved hepatocytes. Clinical results showed that minesapride was rapidly absorbed (C_max: 2302.1 ng/mL in the elderly group, 2117.5 ng/mL in the young group), and the plasma concentration then decreased with half-life of approximately 7 h. There were no notable PK differences between elderly and young groups. No serious adverse events (AEs) were observed. The only AE that occurred in 2 or more subjects was diarrhea. Metabolite profiles in plasma and urine were similar between elderly and young groups. No major metabolites exceeded 10% of unchanged minesapride, and results of the in vitro study suggested that there were no human-specific metabolites. From the viewpoints of PK and metabolite profiling, no dose adjustment of minesapride is warranted in elderly population without renal or hepatic impairment.     

Gynecologic Malignancy-Associated Venous Thromboembolism and Predictive Tool at Thammasat University Hospital

Objectives: Aims were to investigate the prevalence and risk factors of venous thromboembolism (VTE) in gynecologic malignancy cases. Value of screening tool (Caprini) for prediction of VTE was also assessed. Study design: A retrospective study of gynecologic malignancy subjects who underwent major gynecological operation via exploratory laparotomy at Thammasat University Hospital, Pathum Thani, Thailand from January 2015 to December 2020. Participants were categorized into VTE and non-VTE groups. Caprini score, associated laboratory and clinical factors of both groups were evaluated. Results: A total of 392 subjects were recruited into the study. Prevalence of VTE was 7.4 (29/392) percent. VTE was diagnosed in subjects with endometrial, ovarian and cervical cancer at percentage of 7.8 (15/192), 7.9 (11/138) and 5.7 (3/53), respectively. Demographic characters of both groups were comparable. VTE group had significant more Caprini score, platelets count and platelet lymphocyte ratio (PLR) than non-VTE group. Modified Caprini score (2 multiply Caprini score plus 1 multiply PLR) was generated for better VTE prediction. Sensitivity and specificity of Caprini (≥5.5) and modified Caprini scores (≥22.8) were 72.4 vs 39.4, and 79.3 vs 52.1 percent, respectively. Conclusion: Prevalence of VTE among gynecologic malignancy cases was 7.4 percent. The modified Caprini score was an alternative VTE predictive tool. Cut-off point of modified Caprini score at equal or more than 22.8 was proposed.