Lipid accumulation product and visceral adiposity index: two indices to predict metabolic syndrome and insulin resistance in chronic kidney disease patients.

Objective. Chronic kidney disease (CKD), metabolic syndrome (MetS) and insulin resistance (IR) are the major health problems associated with the increasing risk of cardiovascular and cerebrovascular complications. Methods. This cross-sectional study included 209 CKD patients of stage (3-5) on conservative treatment to assess the usage of lipid accumulation product (LAP) and visceral adiposity index (VAI) to predict both MetS and IR in CKD patients. Results. In males, from the anthropometric measurements, LAP was the best predictor of MetS with 94.4% sensitivity and 77.8% specificity. VAI was the next one with 83.3% sensitivity and 69.4% specificity. The same results were obtained in females. The receiver operating characteristic (ROC) curve showed LAP as the best predictor of MetS with the highest 92.6% sensitivity and 60.6% specificity followed by VAI with 83.6% sensitivity and 83.6% specificity. In addition, LAP was a good predictor of IR with more than 70% sensitivity in both males and females. VAI as a predictor of IR showed 62.2% sensitivity in males and 69.9% in females. Conclusion. The present data indicate that both LAP and VAI can serve as predictors of MetS and IR in CKD patients, whereas LAP is the best anthropometric measure to predict MetS and LAP is more sensitive and specific than VAI in IR predicting in both males and females.

The Impact of SKP2 Gene Expression in Chronic Myeloid Leukemia.

Introduction: The prognosis of chronic myeloid leukemia (CML) patients has been dramatically improved with the introduction of imatinib (IM), the first tyrosine kinase inhibitor (TKI). TKI resistance is a serious problem in IM-based therapy. The human S-phase kinase-associated protein 2 (SKP2) gene may play an essential role in the genesis and progression of CML. Aim of the study: We try to explore the diagnostic/prognostic impact of SKP2 gene expression to predict treatment response in first-line IM-treated CML patients at an early response stage. Patients and methods: The gene expression and protein levels of SKP2 were determined using quantitative RT-PCR and ELISA in 100 newly diagnosed CML patients and 100 healthy subjects. Results: SKP2 gene expression and SKP2 protein levels were significantly upregulated in CML patients compared to the control group. The receiver operating characteristic (ROC) analysis for the SKP2 gene expression level, which that differentiated the CML patients from the healthy subjects, yielded a sensitivity of 86.0% and a specificity of 82.0%, with an area under the curve (AUC) of 0.958 (p < 0.001). The ROC analysis for the SKP2 gene expression level, which differentiated optimally from the warning/failure responses, yielded a sensitivity of 70.59% and a specificity of 71.21%, with an AUC of 0.815 (p < 0.001). Conclusion: The SKP2 gene could be an additional diagnostic and an independent prognostic marker for predicting treatment responses in first-line IM-treated CML patients at an early time point (3 months).

The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway.

BACKGROUND: Diabetic retinopathy (DR) signifies a frequent serious diabetic complication influencing retinal structure and function. Dysregulation of lncRNAs drives a wide array of human diseases especially diabetes; thus, we aimed to study lncRNA HIF1A-AS2 role and its interplay with hypoxia, oxidative stress (OS), and angiogenesis in DR. MATERIALS AND METHODS: 60 DM patients in addition to 15 healthy subjects. were enrolled. LncRNA HIF1A-AS2 mRNA relative gene expression was assessed. Hypoxia inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), mitogen activated protein kinase (MAPK), and endoglin levels were assessed. Detection of DNA damage using comet assay, and Redox status parameters were also detected. RESULTS: LncRNA HIF1A-AS2 expression was significantly increased in diabetic patients with the highest levels in proliferative DR patients. Moreover, HIFα, VEGF, MAPK, and Endogolin levels were significantly higher in the diabetic patients compared to control group with the highest levels in in proliferative DR patients. Significant DNA damage in comet assay was observed to be the highest in this group. CONCLUSION: We observed for the first time the imminent role of long noncoding RNA HIF1A-AS2 in DR throughout its stages and its interplay with hypoxia, OS, and angiogenesis via MAPK/VEGF-dependent pathway.

CCL2 rs1024611Gene Polymorphism in Philadelphia-Negative Myeloproliferative Neoplasms.

Introduction: The onset of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) is caused by acquired somatic mutations in target myeloid genes "driver mutations". The CCL2 gene is overexpressed by non-Hodgkin lymphomas and multiple solid tumors. Aim of the study: to evaluate the possible association of CCL2 rs1024611 SNP and its expression level and the risk of developing Philadelphia-negative MPNs. Patients and methods: A total of 128 newly diagnosed Philadelphia-negative MPN patient and 141 healthy subjects were evaluated for the genotype distribution of CCL2 rs1024611 and CCL2 expression levels. Results: The CCL2 rs1024611 G/G genotype was more frequent and significantly frequent among PMF and Post-PV/ET-MF patients and the mean CCL2 expression levels were significantly higher in PMF and Post-PV/ET-MF compared to the healthy subjects. The CCL2 rs1024611 SNP was significantly correlated to the CCL2 gene expression level and fibrosis grade. ROC analysis for the CCL2 gene expression level that discriminates MF patients from PV + ET patients revealed a sensitivity of 80.43% and a specificity of 73.17% with an AUC of 0.919 (p < 0.001). Conclusion: The CCL2 rs1024611 polymorphism could be an independent risk factor for developing MF (PMF and Post-PV/ET-MF). Moreover, CCL2 gene expression could be potential genetic biomarker of fibrotic progression.

Genetic Risk Profiling Associated with Recurrent Unprovoked Venous Thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and/or pulmonary embolism (PE), is a common, acute, multifactorial disease with a five-years cumulative incidence of recurrence of approximately 25%. Actually, no single genetic defect can predict the risk of recurrence of VTE. Therefore, individual genetic risk profiling could be useful for the prediction of VTE recurrence. AIM OF THE STUDY: To assess the combined effect of the common prothrombotic genotypes on the risk of recurrence of VTE in recently diagnosed unprovoked VTE patients. PATIENTS AND METHODS: This population based, prospective follow-up study was carried out from January 2015 to December 2020 in (internal medicine, cardiovascular medicine and anesthesia and ICU departments, Tanta University Hospital, Egypt) on 224 recently diagnosed unprovoked VTE patients. Whole blood was collected by standard venipuncture at the time of admission prior to the beginning of anticoagulant therapy. Genomic DNA was extracted and was genotyped for the 5-SNPs Genetic risk score (GRS), previously validated for first venous thrombosis (FVL rs6025, PTM rs1799963, ABO rs8176719, FGG rs2066865 and FXI rs2036914). RESULTS: The main important finding in the present study was that patients having ≥3 risk alleles were associated with higher risk of VTE recurrence compared to those having ≤2 risk alleles (the reference group) (HR 2.5, 95% CI 1.48-4.21) (p = 0.001). Patients with GRS ≥ 3 had a significantly shorter time recurrence free survival (43.07 months) compared to the low risk group of patients with GRS (0-2) (p < 0.001). CONCLUSION: GRS model could be an effective and useful model in risk stratification of VTE patients, and genetic risk profiling of VTE patients could be used for the prediction of recurrence of VTE.

Predictors for Fibrosis Regression in Chronic HCV Patients after the Treatment with DAAS: Results of a Real-world Cohort Study.

INTRODUCTION: The goal of treatment of chronic hepatitis C (HCV) is viral eradication. However, obtaining histological regression is even more important, because it will reduce the overall morbidity and mortality related to cirrhosis. Introduction of direct-acting antivirals (DAAs) in HCV improves rates of sustained virologic response (SVR). However, fibrosis regression has not been extensively assessed. The aim of this study was to detect the factors affecting fibrosis regression in chronic HCV patients treated with interferon containing regimens versus interferon-free DAA regimens. METHODS: This prospective observational cohort study was conducted at the Tropical Medicine and Infectious Diseases Department, Tanta University, Egypt, between October 2015 and December 2017. Transient elastography (FibroScan®) examination was performed before therapy, at SVR12, 6 months and 1 year after completing therapy for cured patients. RESULTS: Reduction in fibrosis was reported in; 46.7% and 49.3% of patients with moderate fibrosis, and 89% and 78.7% of patients with advanced fibrosis after one year of interferon containing and interferon free DAAs regimens respectively. Using multiple regression analysis; it was found that BMI, degrees of hepatic stiffness and steatosis were related to regression of hepatic fibrosis after therapy. CONCLUSION: DAAs with or without interferon resulted in a significant reduction of liver fibrosis. BMI, steatosis and liver stiffness were independent factors for fibrosis regression in chronic HCV patients treated with DAAs. Further studies are needed to explore the mechanism by which steatosis affects HCV related fibrosis regression after treatment with DAAs.

Galectin-3 as a prognostic biomarker for diabetic nephropathy.

INTRODUCTION: Diabetic nephropathy (DN) represents one of the main causes of end-stage renal disease in type 2 diabetes mellitus (DM) patients. Galectin-3 has been implicated in pathogenesis of many pathological conditions. To date, there are limited data regarding the relationship between galectin-3 and DN. AIM OF THE STUDY: Evaluation of serum galectin-3 as a novel prognostic biomarker in patients with DN. PATIENTS AND METHODS: This prospective study was carried out in the Internal Medicine and Clinical Pathology Departments, Tanta University Hospital, Egypt, from March 2015 to March 2018 on 300 patients with type 2 DM. Patients were divided into three groups: group I included 100 patients with albumin/creatinine ratio (ACR) <30 mg/g (normoalbuminuria), group II included 100 patients with ACR within 30-300 mg/g (microalbuminuria), and group III included 100 patients with ACR >300 mg/g (macroalbuminuria). All patients were subjected to the following: full history taking, clinical examination, and laboratory evaluation (HbA1c, creatinine, estimated glomerular filtration rate, ACR, and serum galectin-3). RESULTS: The mean levels of galectin-3 were significantly higher in patients with macroalbuminuria than in those with microalbuminuria and normoalbuminuria. Galectin-3 was a significant predictor for progression to microalbuminuria, macroalbuminuria, dialysis, and death among patients with type 2 DM. CONCLUSION: Based on this single center prospective study, serum galectin-3 is considered a significant predictor for DN progression among patients with type 2 DM.

Endoscopic injection sclerotherapy versus N-Butyl-2 Cyanoacrylate injection in the management of actively bleeding esophageal varices: a randomized controlled trial.

BACKGROUND: The management of acute esophageal variceal bleeding remains a clinical challenge. Band ligation is the main therapeutic option, but it may be technically difficult to perform in active bleeders. This may necessitate an alternative therapy for this group of patients. This study was conducted to assess the safety and efficacy of sclerotherapy versus cyanoacrylate injection for management of actively bleeding esophageal varices in cirrhotic patients. METHODS: This prospective study included 113 cirrhotic patients with actively bleeding esophageal varices. They were randomly treated by endoscopic sclerotherapy or cyanoacrylate injection as banding was not suitable for those patients due to profuse bleeding making unclear endoscopic visual field. Primary outcome was incidence of active bleeding control and secondary outcomes were incidence of six weeks rebleeding, complications, and mortality among the studied patients. RESULTS: Initial bleeding control was significantly higher in cyanoacrylate versus sclerotherapy groups (98.25, 83.93% respectively, P = 0.007). No significant differences between sclerotherapy and cyanoacrylate groups regarding rebleeding (26.79, 19.30% respectively, P = 0.344), complications, hospital stay or mortality rate were observed. CONCLUSIONS: Based on this single-center prospective study, both of these therapies appear to have relatively favorable outcomes, although cyanoacrylate injection may be superior to sclerotherapy for initial control of active bleeding. TRIAL REGISTRATION: [ClinicalTrials.gov Identifier: NCT03388125 ]-Date of registration: January 2, 2018 "Retrospectively registered".

Sofosbuvir, Pegylated Interferon and Ribavirin in the Treatment of an Egyptian Cohort with Hepatitis C Virus Infection in Real-Life Clinical Practice.

BACKGROUND & AIMS: Hepatitis C virus infection is a major public health problem in Egypt with a risk for morbidity and mortality due to chronic liver disease complications. Worldwide, Egypt has the highest prevalence of HCV infection with the overall prevalence of about 14.7%. The aim of this study was to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) plus Pegylated Interferon (Peg- IFNa) and Ribavirin (RBV) in Egyptian patients with chronic hepatitis C virus (HCV) infection. METHODS: This study was carried out in 1200 patients with chronic hepatitis C virus infection who were eligible for interferon therapy. They were treated with the triple therapy of sofosbuvir 400 mg once daily, Peg-INF subcutaneous injection weekly for 12 weeks in combination with oral weight-based ribavirin. The primary outcome measures were the number of patients with successful eradication of the virus evidenced by the sustained virologic response (SVR) at 12 Weeks. After discontinuation of Therapy (SVR12), the secondary outcome measures were the incidence of adverse effects associated with the tested HCV therapy. RESULT: The mean age of the patients was 49.32 ± 6.97 years. 45.9% of them were males and 54.1% were females.70 patients (5.8%) had a history of previous HCV treatment. ''1077 (89.8%)'' of patients achieved successful eradication of virus while ''106 (8.8%)'' were resistant to treatment and ''17 (1.4%)'' stopped treatment. Good predictors of response to the triple therapy were female gender, treatment naive and non-cirrhotic patients. CONCLUSION: The triple regimen of Pegylated interferon, sofosbuvir plus ribavirin is safe and effective in the treatment of Egyptian patients with hepatitis C virus and is associated with real-life SVR12 rates of 89.8%.

A novel scoring system for prediction of esophageal varices in critically ill patients.

BACKGROUND AND AIMS: Patients with advanced systemic illness or critically ill patients may present with upper gastrointestinal tract (GIT) bleeding which may need endoscopic intervention; however, this may expose them to unnecessary endoscopy. The aim was to validate a novel scoring system for risk stratification for urgency of GIT endoscopy in critically ill patients. METHODS: This is an observational study conducted from January 2013 to January 2016 to analyze 300 patients with critical medical conditions and presenting with upper gastrointestinal bleeding. Meticulous clinical, laboratory, and sonographic evaluations were performed to calculate Glasgow Blatchford score (GBS) and variceal metric score for risk stratification and prediction of the presence of esophageal varices (OV). Finally, this score was applied on a validation group (n=100). RESULTS: The use of GBS and variceal metric scores in critically ill patients revealed that patients who showed a low risk score value for OV (0-4 points) and GBS <2 can be treated conservatively and discharged safely without urgent endoscopy. In patients with a low risk for varices but GBS >2, none of them had OV on endoscopy. In patients with intermediate risk score value for OV (5-8 points) and with GBS >2, 33.33% of them had varices on endoscopy. In patients with high risk score value for varices (9-13) and GBS >2, endoscopy revealed varices in 94.4% of them. Finally, in patients with very high risk score for varices (14-17), endoscopy revealed varices in 100% of them. CONCLUSION: GBS and variceal metric score were highly efficacious in identifying critically ill patients who will benefit from therapeutic endoscopic intervention.

Serum Midkine and Osteopontin Levels as Diagnostic Biomarkers of Hepatocellular Carcinoma.

INTRODUCTION: Hepatocellular Carcinoma (HCC) is a primary tumor of the liver; it is one of the most common cancers worldwide. Osteopontin (OPN) is a phosphorylated glycoprotein which is implicated in enhancing invasive and metastatic progression of many tumors. Midkine (MDK) is a 13-kDa small heparin-binding growth factor which plays a significant role in carcinogenesis related activities. The aim of this study was to assess the efficacy of serum Midkine and Osteopontin levels as diagnostic biomarkers of Hepatocellular Carcinoma. METHODS: This study was carried out from January 2014 to January 2016 in Internal Medicine, Clinical Oncology and Tropical Medicine Departments of Tanta University Hospital (Egypt). One hundred forty subjects were enrolled in our study, they were divided into four groups: Group I included 35 patients presented with HCV without cirrhosis; Group II included 35 patients presented with HCV with liver cirrhosis; Group III included 35 patients presented with HCC on top of cirrhosis; and Group IV included 35 apparently healthy subjects as a control group. The studied groups were age and sex matched. Routine and specific (OPN and MDK) laboratory investigations were performed in all included subjects. RESULTS: The main finding of the present work was that the mean serum levels of OPN and MDK were significantly elevated in HCC patients either by comparing HCC patients vs. HCV patients without cirrhosis, HCC patients vs. HCV patients with cirrhosis or HCC patients vs. healthy subjects. Interestingly, by performing a ROC analysis, serum MDK levels had better sensitivity and specificity than OPN and AFP levels in the diagnosis of HCC (98.4 %, 97.1% and 97%) and (96.2%, 95.3% and 95%) for MDK, OPN and AFP respectively. CONCLUSION: Serum MDK and OPN levels are comparable to AFP levels and could be used as potential diagnostic biomarkers of HCC in HCV patients with liver cirrhosis and in the prediction of liver cirrhosis in HCV patients without cirrhosis.

Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease.

OBJECTIVES: We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. METHODS: A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia), time needed for complete recovery, and time needed for discharge. RESULTS: There was no statistical significant difference between the studied groups regarding age, sex, weight, Child-Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (P = 0.001). CONCLUSION: The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with ClinicalTrials.gov Identifier: NCT03063866.

Impact of iron deficiency anemia on the function of the immune system in children.

The importance of iron deficiency as a public health problem is based ultimately on the seriousness of its consequences on health. The most extensively investigated consequences of iron deficiency involve work performance and immune function. The significance of the effects on work performance is generally accepted. In contrast, data on the influence of iron deficiency on immune function are often perceived as being confusing and contradictory.We aimed to evaluate the effect of iron deficiency anemia on humoral, cellular, nonspecific immunity, and also the effect on the cytokines that are the key factors of many immunologic steps.Forty children with iron deficiency anemia and 20 age and sex-matched healthy children were included. All children were subjected to full medical history, thorough clinical examination, complete blood count, iron indices (serum iron, serum total iron-binding capacity, serum ferritin, and transferrin saturation), immunoglobulin assay (IgA, IgG, and IgM), interleukin (IL)-6 serum level, study of T-lymphocyte subsets, and evaluation of phagocytic function of macrophages and oxidative burst activity of neutrophils.Patients had significantly lower IgG levels, IL-6, phagocytic activity, and oxidative burst of neutrophils than controls, although there was no significant difference between patients and controls with regard to other immunoglobulins and CD4/CD8 ratio. There was significantly positive correlation between serum iron and IL-6 serum level.We concluded that humoral, nonspecific immunity (phagocytic activity and oxidative burst), and the IL-6 are influenced in patients with iron deficiency anemia. Study of these abnormalities after correction of iron deficiency is strongly needed.

Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: A single center study.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) has an increasing incidence worldwide. In this study we aimed to assess the prevalence of HCC among HCV patients in our center in Mid Delta, Egypt. PATIENTS AND METHODS: During the period between April 2013 and January 2015, we screened sequentially chronic HCV patients attending inpatient wards or outpatient Clinic of Tropical Medicine Department in Tanta University Hospital for HCC. Individuals with focal lesion in Ultrasound (US) and/or serum α-fetoprotein (AFP) level >200ng/ml were examined by triphasic computed tomography scanning (CT), and/or magnetic resonance imaging (MRI). RESULTS: Among 514 HCV patients interviewed and accepted sharing in this study, 90 (17.5%), 144 (28%), and 280 (54.5%) were Child A, B, and C, respectively. We found that 108/514 patients (21%) had focal lesion detected by US. Also, 89/514 (17.3%) had elevated AFP >200, 13 of them (14.6%) had no focal lesion on US, but further work up showed HCC in 2 of them. Overall HCC diagnosis was confirmed in 103 cases, 94 of them (91.3%) were Child B or C. Occurrence of HCC was significantly higher in smokers, diabetics, patients with decompensated liver and those with positive family history of HCC. Only 20/103 (19.4%) were candidates to curative treatments, 8 of them were Child A asymptomatic and discovered accidentally during screening. CONCLUSION: The high prevalence of HCC in our HCV patients (22%) was mainly associated with decompensated cirrhosis. A national surveillance program for the detection of HCC in cirrhotic HCV Egyptian patients by combining ultrasound examination and AFP is highly recommended.

Correction of hemodialysis anemia is associated with significant increase in serum concentration of IGF-I in patients treated with erythropoietin: a randomized controlled study.

BACKGROUND: The effect of erythropoietin (EPO) therapy on the serum level of IGF-I among hemodialysis patients is debated. The aim of this study is to study the effect of EPO on the erythropoiesis and the change of serum level of IGF-I among adequately hemodialyzed patients. PATIENTS AND METHODS: Forty patients (25 males and 15 females) who had an adequate level of both hemodialysis and nutrition were randomly allocated into two equal groups. Besides parenteral iron, the first group of patients received a conventional EPO dose regimen of 2000 U subcutaneously (SC) thrice weekly, the second group of patients remained on parenteral iron and ranked as a control group. The patients were subjected to thorough laboratory investigations. IGF-I concentration was measured before and at the end of the study. RESULTS: Both groups were comparable in their demographic, laboratory, dialysis level, and nutritional status. There was no statistical differences in hemoglobin, hematocrit %, iron store indices and serum level of IGF-I at the study entry. We found a significant rise of both hemoglobin and hematocrit as well as IGF-I serum level in the EPO group at the end of the study in comparison to their values at the starting points in comparison to the control group (P< 0.001). CONCLUSION: Erythropoietin therapy enhances erythropoiesis and modulates the serum concentration of IGF-I.

Use of nandrolone decanoate as an adjuvant for erythropoietin dose reduction in treating anemia in patients on hemodialysis.

BACKGROUND/AIMS: Use of androgen as an adjuvant therapy to treat anemia in patients on hemodialysis is debated. Our target is to assess the safety and the efficacy of nandrolone decanoate (ND) as an effective adjunctive therapy to treat such anemia. METHODS: This study included 32 anemic adult hemodialysis patients who had adequate iron stores. They were randomized into two equal groups: the first group received subcutaneously a low dose of erythropoietin (EPO) 1,000 U three times weekly combined with ND, 50 mg intramuscularly twice weekly, and the second group received only the same low dose of EPO for the 6-month study period. All patients were subjected to a serial follow-up of hemoglobin (Hb), hematocrit % (Hct%), iron store indices, serum insulin-like growth factor-1 (IGF-1) concentration and liver function tests. RESULTS: A significant rise of both Hb and Hct in both groups was found at the end of the study (p < 0.001). Although the rise of both Hb and Hct was higher in the androgen group, it was not rated as being statistically significant. Both groups showed a significant rise of serum IGF-1 concentration at the end of the study in comparison to its initial value. Moreover, the androgen group attained a more statistically significant rise of IGF-1 serum concentration. Four female patients discontinued ND because of related adverse effects, principally distressing hirsutism and hepatic dysfunction. CONCLUSION: Addition of ND to a low-dose EPO regimen does not offer a significant benefit. Androgen-related side effects limit its use in female patients.