Liver Transplantation for Hepatocellular Carcinoma: How Should We Improve the Thresholds?

Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related mortality, and liver transplantation is the ideal treatment for this disease. The Milan criteria provided the opportunity for HCC patients to undergo LT with favorable outcomes and have been the international gold standard and benchmark. With the accumulation of data, however, the Milan criteria are not regarded as too restrictive. After the implementation of the Milan criteria, many extended criteria have been proposed, which increases the limitations regarding the morphological tumor burden, and incorporates the tumor’s biological behavior using surrogate markers. The paradigm for the patient selection for LT appears to be shifting from morphologic criteria to a combination of biologic, histologic, and morphologic criteria, and to the establishment of a model for predicting post-transplant recurrence and outcomes. This review article aims to characterize the various patient selection criteria for LT, with reference to several surrogate markers for the biological behavior of HCC (e.g., AFP, PIVKA-II, NLR, 18F-FDG PET/CT, liquid biopsy), and the response to locoregional therapy. Furthermore, the allocation rules in each country and the present evidence on the role of down-staging large tumors are addressed.

Effect of Dietary Marula Nut Meal on Liver Lipid Content and Surrogate Markers of Liver and Kidney Function of Broiler and Layer Japanese Quail

Marula nut meal (MNM) can substitute soyabean meal (SBM) as a dietary protein source in Japanese quail diets without compromising growth performance and egg production. However, MNM has a high residual oil content which may impact metabolic health. The effects of MNM on hepatic lipid content and general, liver and kidney health have not been determined in both broilers and layers. Accordingly, two studies were run. In the broiler study two hundred 9-days old Japanese quail were randomly allocated to five diets wherein MNM replaced SBM on a crude protein (CP) basis at 0%, 25%, 50%, 75% and 100%, respectively, in both grower and finisher diets. In the layer study, sixty 5-weeks old Japanese maiden hens, individually housed, were randomly allocated to five-layer diets where MNM replaced SBM on a graded CP basis as for the broilers and fed for 8 weeks. At study termination the birds were slaughtered, blood collected and plasma harvested. Livers were excised, weighed and liver lipid content determined. Plasma surrogate markers of general health, liver and kidney function were determined. Dietary MNM had no effect (P > 0.05) on liver lipid content as well plasma surrogate markers of general health, liver and kidney function of the broiler quail. Dietary MNM at 75% of SBM CP significantly increased plasma phosphorus concentration of quail hens compared to that of counterparts fed control. Dietary MNM can be used in broiler and layer Japanese quail diets without risking development of fatty livers and compromising liver and kidney function.

Novel markers to detect HER2 amplification in Breast cancer

Overexpression of HER2 in breast cancer is an important prognostic and predictive biomarker, assessed using immunohistochemistry (IHC) and in situ hybridization (ISH). More than 20% of tumours are graded equivocal on IHC and is send for reflex testing via ISH. In situ hybridization (ISH) is an expensive assay and is not available widely in resource limiting areas. Therefore, we propose that genes found significantly co-expressed with HER2 in breast cancer can be used as surrogate markers for HER2 in breast cancer which can detect HER2 positivity on IHC itself. This hypothesis is based on analysis of publicly available datasets from the Gene Expression Omnibus (GEO) database. The genes found most significantly correlated with HER2 expression were PGAP3 (r = 0.85), GRB7 (r = 0.82), STARD3 (r = 0.78), CDK12 (r= 0.68), PSMD3 (r= 0.67) and GSDMB (r = 0.63). We hypothesize that these identified surrogate markers for HER2 amplification which can be detected on IHC can detect HER2 amplification status in HER2 equivocal tumors based on IHC staining alone and will reduce the number of HER2 2+ (equivocal) category tumours.

TO STUDY THE SIGNIFICANCE OF VARIOUS BIOCHEMICAL AND ND HEMATOLOGICAL PARAMETERS IN COVID CASES IN INDIA IN 2 WAVE OF COVID-19 PANDEMIC: STUDY FROM PUNE, MAHARASHTRA

COVID -19 infection is an ongoing pandemic. The world has already witness two waves and a third one is imminent. Also the COVID 19 infection is now presenting with numerous manifestation besides respiratory symptom. Thus it becomes essential to study surrogate markers or various biochemical and hematological parameters and their signicance in these cases. Data available so far is mostly from other nations with only a limited number of studies from Indian context. Thus the present study was conducted to evaluate the signicance of laboratory parameters in predicting cases infected with COVID 19 and also the correlation of these parameters with gender and course of disease. 557 subjects were included in this study from Pune, Maharashtra. The groups were divided into cases and controls on basis of RT PCR results and clinical manifestations. The control group had 442 subjects and the cases were 135 in number. The inammatory markers (CRP, D-dimer and ferritin) were signicantly high in cases as compared to controls. Among cases 40 % patients belonged to young age (<45 years), 38% to middle age (45 -59 years) and 22 % to elderly group (>60 years). This shows high infectivity rate in st younger group as compared to 1 wave. NLR was higher in cases as compared to controls. CRP, D-dimer and ferritin were signicantly higher in cases as compared to controls

492. Impact of the COVID-19 Pandemic on Diabetes Surrogate Markers in a Population of People Living with HIV

Background COVID-19 has become a worldwide pandemic that brought changes in sociological, economic and health perspectives. The impact of the pandemic on health maintenance is not yet understood, but aspects of the lockdown are being assessed for their impact on society. Diabetes and HIV are diseases that require frequent follow-up to achieve outcomes. Changes to routines during the lockdown, such as physical activity, eating habits, and psychological burden, may result in complications for this patient population. Methods This is a multi-center, retrospective cohort study performed between October 2019 to October 2020 at two medical centers in Brooklyn, NY. All adult patients with diagnoses of diabetes and HIV were screened for inclusion. Exclusion criteria included pregnancy and long-term steroid use. Electronic medical records were reviewed to obtain demographic, laboratory data, and appointment retention data. The primary endpoint was the mean change in HbA1c (A1c) values before and after the pandemic. Endpoints were evaluated using paired T-tests and Wilcoxon Sign-Rank tests, where appropriate, and a repeated measures logistic regression model was used to analyze appointment retention rates. Results Baseline characteristics are summarized in Table 1. No significance was observed between baseline A1c values and those taken either up to 3 months (p= 0.862) or up to 6 months (p= 0.977) after the start of the pandemic, as shown in Table 2. Similarly, no difference was observed in HIV surrogate markers. A1c significantly decreased from between the 3-month and 6-month study dates, after the start of the pandemic (p= 0.022). Table 3 shows patients were more likely to fulfill a scheduled appointment during the pandemic with an odds ratio of 1.455 (95% CI, 1.119-1.891). Conclusion No significance was found in surrogate markers for health maintenance before and after the pandemic. Patients were more likely to keep an appointment after the start of the pandemic and A1c values significantly declined from 3 months to 6 months into the pandemic. Although COVID-19 did not appear to change overall health maintenance of T2DM within our population, our results imply that pandemic measures, such as telehealth appointments, positively affected appointment adherence, which is key to success in this population. Disclosures Jessica E. Yager, MD MPH, Abbott Laboratories (Shareholder)Amgen Inc (Shareholder)Becton Dickenson & Co (Shareholder)Edwards Lifesciences Corp (Shareholder)Gilead Sciences, Inc. (Grant/Research Support, Recipient of FOCUS grant)

P.228 Pre-operative Surrogates Markers of Frailty and Metastatic Spine Disease: Systematic Review

Background: Despite the inherent importance of physical reserve and ability to tolerate surgery, pre-operative patient-specific surrogate markers of frailty that may improve accuracy of outcome prognostication following surgery for SMD are not well described. Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Scopus, EMBASE, Cochrane Registry of Controlled Trials, CINAHL, and Web of Science were searched. Quality of evidence was scored using the Oxford CEBM Scoring Tool. Results: Forty studies accounted for 8,364 patients. Surgical indications included neurological dysfunction, intractable pain, and spinal instability. Tumor histology varied across and within studies. Age, gender, performance status, neurologic function, comorbidities, and biochemical abnormalities were the most frequently analyzed pre-operative surrogate markers of frailty. The most commonly assessed outcomes were overall and progression-free survival; few studies examined health-related quality of life, peri-operative adverse events, and post-operative complications. Conclusions: This study highlights the need for objective measures of frailty in order to improve risk stratification and outcome prognostication among patients receiving surgery for metastatic spinal disease. Future studies should address identified knowledge gaps pertaining to peri-operative adverse events, post-operative complications, and health-related quality of life outcomes.