Prognostic Significance of VEGF and HIF-1 α in Hepatocellular Carcinoma Patients Receiving Sorafenib Versus Metformin Sorafenib Combination.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem. HCC burden has been increasing in Egypt in the past 10 years. Most HCC cases are diagnosed at an advanced stage with limited treatment options. Sorafenib is the standard therapy for advanced HCC, but the effectiveness is not satisfied. Metformin may decrease the risk of HCC development in diabetic patients, reduces tumor invasion, and augments sensitivity to sorafenib; however, safety and efficacy of combined treatment are still unclear. As HCC is characterized by high vascularity, and vascular endothelial growth factor (VEGF) plays an important role in vascularization, many studies questioned if VEGF and HIF-1 α could offer information about HCC response to sorafenib. We conducted this study to assess the benefits from adding metformin to HCC treatment, and appraise the role of VEGF and HIF-1 α in HCC prognosis. METHOD: This was a prospective, randomized study in which 80 advanced measurable patients consecutively treated with sorafenib plus metformin (arm A) or sorafenib alone (arm B), prognostic value of plasma, and tissue levels of VEGF and HIF-1 α were evaluated. RESULTS: We enrolled 61 men and 19 women with a median age of 60 years (range 49-68 years). Fifty-seven patients had Child-Pugh A while 23 had early B, the most common etiology of liver disease was hepatitis C (86%). Sixty percent of patients were diabetic. No significant difference was detected between arm A and arm B regarding response to treatment (p = 0.5), time to disease progression (p = 0.3), or overall survival (p = 0.6). Low VEGF and HIF-1 α plasma levels were significantly associated with better treatment response (p < 0.001 for both), and higher OS (p < 0.001). Patients with high expressions of VEGF and HIF in HCC tissue had significantly poor treatment outcome (p < 0.001, p = 0.03, respectively), and poor OS (p < 0.001, p < 0.001, respectively). CONCLUSIONS: No superior efficacy of adding metformin to sorafenib in HCC treatment. VEGF and HIF-1 α had promising prognostic value in HCC.

Serum Pentraxin 3 level as a recent biomarker of diabetic retinopathy in Egyptian patients with diabetes.

INTRODUCTION: Serum Pentraxin3 Level As A recent Biomarker Of Diabetic Retinopathy In Egyptian patients with diabetes. OBJECTIVE: To evaluate the association between elevated levels of plasma pentraxin 3 and the development and/or progression of diabetic retinopathy. SUBJECTS: and methods: This case control study was carried out in internal medicine department, outpatient clinic of internal medicine and outpatient clinic of ophthalmology, at Zagazig university Hospital, 2018. Serum PTX3 level, HsCRP, HbA1c, lipid profile, serum creatinine were determined in 20 normal subjects, 20 patients with prediabetes, 20 patients with diabetes without diabetic retinopathy (DR), 20 patients with non-proliferative diabetic retinopathy (NPDR) and 20 patients with proliferative diabetic retinopathy (PDR). RESULTS: Serum PTX3 level significantly increased in patients with DR more than patients without DR with cut off point 1150 pg/ml, sensitivity 93.3%and specificity 72%. Serum HsCRP level significantly increased in patients with DR more than patients without DR with cut off point of 7.60 pg/ml has sensitivity 93.3% and specificity 68%.. Combined use of PTX3 and HsCRP decreases sensitivity to 76.7%, but combined use increases specificity to 90%.Significant relation between poor glycemic control and development of DR and its severity as showed by HbA1c. CONCLUSION: Serum PTX3 levels mayt have significant role in the development of DR and its severity. Serum HsCRP increased with DR progression. Poor glycemic control significantly associated with high incidence of diabetic retinopathy and its severity. Longer diabetes duration is associated with progression of DR.

Proinsulin/insulin ratio as a predictor of insulin resistance and B-cell dysfunction in obese Egyptians ((insulin resistance & B-cell dysfunction in obese Egyptians)).

Insulin resistance (IR) and ß-cell dysfunction are key pathological features of type 2 diabetes mellitus, the aim of this study was to investigate the role of proinsulin level and proinsulin/insulin ratio in early prediction of beta cell dysfunction and insulin resistance in obese Egyptian adolescent. PATIENTS AND METHODS: This Case control study was conducted from June 2017 to March 2018. Total of 60 patients were divided into 2 groups after exclusion of patients with diabetes: normal body weight group and Obese group. Demographic, clinical data were collected. Laboratory investigation included fasting insulin, proinsulin, and estimation of HOMA IR and HOMA-B were done. RESULTS: There are highly statistically significant increase in obese group regarding insulin, proinsulin, proinsulin/insulin ratio and HOMA-IR while there is significant decrease in HOMA-B in this group. The best cutoff value of Proinsulin in prediction of beta cell function was ≥7.829 pmol/L with sensitivity 95.8, specificity 72.2. The best cutoff value of Proinsulin/insulin ratio in prediction of insulin resistance was ≥0.1545 with sensitivity 87.5, specificity 61.1. CONCLUSION: both beta cell dysfunction and insulin resistance increased in obese group and so increased risk of type 2 diabetes. We found that Pro insulin/insulin ratio is a significant predictor for insulin resistance and Proinsulin is good predictor for beta cell dysfunction.