Association of epistatic effects of MTHFR, ACE, APOB, and APOE gene polymorphisms with the risk of myocardial infarction and unstable angina in Egyptian patients.

Despite remarkable discoveries in the genetic susceptibility of coronary artery disease (CAD), a large part of heritability awaits identification. Epistasis or gene-gene interaction has a profound influence on CAD and might contribute to its missed genetic variability; however, this impact was largely unexplored. Here, we appraised the associations of gene-gene interactions and haplotypes of five polymorphisms, namely methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE) insertion/deletion (I/D), apolipoprotein B (APOB) R3500Q, and apolipoprotein E (APOE) ε4 with the risk of myocardial infarction (MI) and unstable angina (UA). Gene-environment interactions with traditional risk factors and clinical data were also scrutinized. This study recruited 100 MI, 50 UA patients, and 100 apparently healthy controls. Logistic regression models were employed in association analyses. We remarked that the single locus effect of individual polymorphisms was relatively weak; however, a magnified effect of their combination via gene-gene interaction may predict MI risk after adjustment for multiple comparisons. Only MTHFR C677T, ACE I/D, and APOB R5300Q were associated with the risk of UA, and the ACE I/D-R3500Q interaction posed a decreased UA risk. APOB R3500Q was in strong linkage disequilibrium with MTHFR C677T, ACE I/D, and APE ε4 polymorphisms. The TCDGε3, CADGε4, and TADGε4-C677T-A1298C-ACE I/D-R3500Q-APOE haplotypes were associated with escalating MI risk, while the CDG or CIG-C677T-ACE I/D-R3500Q haplotype was highly protective against UA risk compared to controls. Interestingly, the CADGε4 and CAIGε3 haplotypes were strongly associated with the presence of diabetes and hypertension, respectively in MI patients; both haplotypes stratified patients according to the ECHO results. In UA, the CDG haplotype was negatively associated with the presence of diabetes or dilated heart. Conclusively, our results advocate that a stronger combined effect of polymorphisms in MTHFR, ACE, APOB, and APOE genes via gene-gene and gene-environment interactions might help in risk stratification of MI and UA patients.

Role of elastography strain ratio and TIRADS score in predicting malignant thyroid nodule.

OBJECTIVE: Ultrasonography (US) is the most accurate and cost-effective imaging method in diagnosis of thyroid nodules. A practical thyroid imaging reporting and data system (TIRADS) for thyroid nodules has been proposed to classify nodules of the thyroid gland to solve the problem of nodule selection for fine needle aspiration cytology (FNAC). Real-time elastography and strain ratio (SR) is a method used to assess the stiffness and predict the malignancy of thyroid nodules. The objective of this study was to assess the role of elastography and SR and the TIRADS scoring system in discriminating malignant from benign thyroid nodules. METHODS: From 2015 to 2018 at Cairo University Hospital, a series of 409 patients with thyroid nodules was referred to undergo thyroid ultrasound. Categorization of each nodule according to the TIRADS ranged from 1 to 5. The qualitative elastography score and semiquantitative SR of the nodules were evaluated. Final diagnosis was done by either post-thyroidectomy histopathological examination or US-guided FNAC. RESULTS: Our study included 409 patients with thyroid nodules. Their mean age was 39 ± 10 SD; 36 were males and 373 were females. There were 22 malignant nodules and 387 benign nodules. There were statistical differences between benign and malignant nodules regarding TIRADS classification, SR, anteroposterior/transverse ratio, degree of echogenicity, border, presence of calcification, and absence of halo sign (P < 0.001). The elastic properties of thyroid nodules proved to be a good discriminator between malignant and benign nodules (P- < 0.001) at a cut off value of > 2.32 with 95.2% sensitivity and 86.5% specificity. For every unit increase in SR, the risk of malignancy increased by nearly 2 times. Patients with irregular borders had nearly 17 times increased risk of malignancy than those with regular borders. CONCLUSION: Elastography and SR proved to be of high significant value in discriminating benign from malignant nodules, so we recommend adding it to the TIRADS classification.

Role of elastography strain ratio and TIRADS score in predicting malignant thyroid nodule

ABSTRACT Objective: Ultrasonography (US) is the most accurate and cost-effective imaging method in diagnosis of thyroid nodules. A practical thyroid imaging reporting and data system (TIRADS) for thyroid nodules has been proposed to classify nodules of the thyroid gland to solve the problem of nodule selection for fine needle aspiration cytology (FNAC). Real-time elastography and strain ratio (SR) is a method used to assess the stiffness and predict the malignancy of thyroid nodules. The objective of this study was to assess the role of elastography and SR and the TIRADS scoring system in discriminating malignant from benign thyroid nodules. Materials and methods: From 2015 to 2018 at Cairo University Hospital, a series of 409 patients with thyroid nodules was referred to undergo thyroid ultrasound. Categorization of each nodule according to the TIRADS ranged from 1 to 5. The qualitative elastography score and semiquantitative SR of the nodules were evaluated. Final diagnosis was done by either post-thyroidectomy histopathological examination or US-guided FNAC. Results: Our study included 409 patients with thyroid nodules. Their mean age was 39 ± 10 SD; 36 were males and 373 were females. There were 22 malignant nodules and 387 benign nodules. There were statistical differences between benign and malignant nodules regarding TIRADS classification, SR, anteroposterior/transverse ratio, degree of echogenicity, border, presence of calcification, and absence of halo sign (P < 0.001). The elastic properties of thyroid nodules proved to be a good discriminator between malignant and benign nodules (P- < 0.001) at a cut off value of > 2.32 with 95.2% sensitivity and 86.5% specificity. For every unit increase in SR, the risk of malignancy increased by nearly 2 times. Patients with irregular borders had nearly 17 times increased risk of malignancy than those with regular borders. Conclusion: Elastography and SR proved to be of high significant value in discriminating benign from malignant nodules, so we recommend adding it to the TIRADS classification.

Effect of carvedilol versus nebivolol on insulin resistance among non-diabetic, non-ischemic cardiomyopathy with heart failure.

BACKGROUND: Although B-blockers provide unequivocal benefits in heart failure (HF) management, some B-blockers worsen insulin resistance. It will be a promising strategy to recruit such a B blocker that did not worsen or can even improve insulin resistance (IR). So, this study aimed to assess the effect of two of the third-generation B-blockers (carvedilol versus nebivolol) on insulin sensitivity state in non-diabetic patients with non-ischemic cardiomyopathy with heart failure. RESULTS: Out of 43 patients enrolled, 58.1% represented the carvedilol group while 41.9% represented the nebivolol group. Nebivolol improves insulin resistance-related variables (fasting glucose, fasting insulin, and HOMA-IR; P < 0.001, 0.01, and 0.01 respectively). The percentage of change at homeostasis model of assessment (HOMA-IR), indicative of insulin sensitivity status, between baseline versus at 3-months follow-up level of intra-group comparison was increased by 4.58% in the carvedilol arm whereas it was decreased by 11.67% in the nebivolol arm, and the difference on the intragroup level of comparison was significant (P < 0.001 and 0.01 respectively). CONCLUSION: Nebivolol improves insulin resistance-related variables .Nebivolol may be recommended as the B blocker of the first choice for those with non-ischemic cardiomyopathy heart failure with evident insulin resistance; however, larger scaled prospective multicenter randomized trials are needed for confirming our favorable results.

Managing diabetes and liver disease association.

There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.

Association of genetic variants of hemostatic genes with myocardial infarction in Egyptian patients.

Hemostatic genes polymorphisms are well known to be associated with venous thrombosis, but their association with arterial thrombosis especially myocardial infarction (MI) remains to be clarified. We investigated the role of three hemostatic gene polymorphisms, prothrombin G20210A, factor XIII (FXIII) Val34Leu (G/T), and fibrinogen-ß-455G/A and their coexistence in Egyptian patients with MI. The possible correlation of these polymorphisms with plasma fibrinogen level was also evaluated. The study included 120 patients with MI and 60 healthy volunteers. Gene polymorphisms were tested using multiplex polymerase chain reaction and reverse-hybridization technique. Plasma fibrinogen level was determined by ELISA. Our study showed an increased risk of MI with fibrinogen ß-455G/A heterozygosity as well as FXIII Val34Leu homo and heterozygosity. In addition, the FXIII T allele (Leu34) and fibrinogen ß-455A allele were significantly associated with MI. Conversely, the prevalence of prothrombin mutation did not differ between patients with MI and controls. Combined carriers of FXIII Leu34 and fibrinogen-ß455A alleles were at higher risk of MI, whereas combined FXIII Val34Leu and prothrombin 20210A polymorphisms did not show increased risk for MI compared with controls. Plasma fibrinogen levels were significantly higher in patients with MI than controls. In MI patients, plasma fibrinogen levels were significantly higher in those with FXIII GT/TT or fibrinogen ß-455 GA, while were significantly lower in those with prothrombin 20210 GA compared with patients with wild type genotypes. In conclusion, our results suggest a possible thrombotic predisposition of FXIII Val34Leu, fibrinogen ß-455G/A polymorphisms and their coexistence for MI. These polymorphisms may add complexity to disease pathology by increasing plasma fibrinogen level. Extended studies are needed to confirm our results; nevertheless, these data may be implicated in genetic counseling and screening of high-risk individuals.

Vascular endothelial growth factor before and after locoregional treatment and its relation to treatment response in hepatocelluar carcinoma patients

Objective: To evaluate vascular endothelial growth factor (VEGF) levels in hepatocel-lular carcinoma patients before and after transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) and its relation to treatment response. Methods: A total of 40 patients with unrespectable hepatocelluar carcinoma were assessed clinically. Twenty patients were suitable to be treated by TACE, while other 20 patients were treated with PEI. Serum VEGF levels were measured before and 1 month after each procedure by ELISA. Response was assessed after 1 month according to Union Internationale Contre le Cancer evaluation criteria based on change in tumor size as measured by ultrasound. Results: There was no significant difference between TACE and PEI groups with regard to age, sex, tumor size, response to local therapy, or VEGF and alpha-fetoprotein before and after therapy. VEGF levels after TACE were significantly higher than before TACE [(298.1 ± 123.6) pg/mL vs. (205.8 ± 307.3) pg/mL;P=0.001]. Also, VEGF levels were significantly higher after PEI than before PEI [(333.8 ± 365.6) pg/mL vs. (245.3 ± 301.8) pg/mL;P=0.000]. Non-responders of both groups had significantly high VEGF levels than responder's, both before [(985.0 ± 113.2) pg/mL vs. (117.1 ± 75.3) pg/mL;P Conclusions: Both TACE and PEI were associated with an increase in serum VEGF in hepatocelluar carcinoma patients. Higher levels of VEGF before and after therapy were found in non-responders, suggesting that VEGF is a useful marker in predicting treatment response.

Association of E-selectin gene polymorphism and serum PAPP-A with carotid atherosclerosis in end-stage renal disease.

BACKGROUND: Atherosclerotic vascular disease represents a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD). The endothelium plays a crucial role in vascular inflammation. E-selectin is exclusively expressed on activated endothelial cells and is upregulated following an inflammatory response and oxidative stress, while serum pregnancy-associated plasma protein-A (PAPP-A) concentrations are related to the presence and stability of carotid atherosclerotic plaques. OBJECTIVE: The aim of this study was to investigate whether there is an association between SELE rs5355C>T gene polymorphism, serum PAPP-A level and the presence of carotid atherosclerosis in ESRD patients. SUBJECTS AND METHODS: Seventy subjects were recruited into this study; 40 ESRD patients [age (mean ± SD) 43.42 ± 13.94 years] and 30 age- and gender-matched healthy individuals assigned to the control group. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of SELE rs5355C>T gene polymorphism, while serum PAPP-A concentrations were measured using electro-chemiluminescence immunoassay. Routine laboratory tests were measured on an automated chemistry analyzer. Carotid ultrasonographic studies were performed by a bilateral high-resolution B-mode ultrasound. RESULTS: There was no significant relationship between the SELE rs5355C>T gene polymorphism and ESRD incidence. Serum PAPP-A levels were significantly higher in ESRD patients compared with controls [median (interquartile range) 5.8 (5.1-11.6) and 5.1 (4.1-6.7), respectively; p = 0.005]. Serum PAPP-A correlated positively with urea, creatinine, systolic and diastolic blood pressure (DBP). Serum PAPP-A showed a statistically significant increase in SELE rs5355TT versus CC in both patients and controls. There was no association on comparing right intima-media thickness (IMT), left IMT, right cross-sectional area (CSA) and left CSA with the CC, CT and TT genotypes of SELE rs5355C>T. No correlation between serum PAPP-A with each of the above-mentioned carotid doppler findings was observed. There was a statistically significant increase in DBP in TT genotype carriers when compared with CC genotype carriers (p = 0.009). Serum PAPP-A levels were higher in hypertensive ESRD patients when compared with normotensive ESRD patients. There was a statistically significant decrease in high-density lipoprotein cholesterol (HDL-C) in TT genotype carriers when compared with CT genotype carriers in the whole study group (p = 0.003). Serum PAPP-A correlated negatively with HDL-C. CONCLUSION: The lack of a direct association between SELE rs5355C>T gene polymorphism, serum PAPP-A level and IMT suggests that their hypothesized association with carotid atherosclerosis might reflect an indirect mechanism of SELE rs5355C>T gene polymorphism and serum PAPP-A with cardiovascular risk factors such as blood pressure and HDL-C rather than a direct effect on the vasculature.

Long-term effect of argon plasma coagulation (APC) in the treatment of gastric antral vascular ectasia (GAVE).

BACKGROUND AND STUDY AIMS: Gastric antral vascular ectasia (GAVE) is a distinct vascular abnormality, mainly involving the gastric antrum. It is a rare but well-known cause of occult gastrointestinal bleeding. Various endoscopic treatment modalities have been tried in this condition. The aim of the study is to show the long-term effect of argon plasma coagulation (APC) on GAVE. PATIENTS AND METHODS: Twenty-nine patients with endoscopically proved GAVE were enrolled in the study. Clinical assessment of GAVE patients, haemoglobin (Hb) level and transfused blood units were recorded after APC using 60-80-W power setting. A second session was done 1month after the therapeutic procedure to ensure complete ablation of all lesions. RESULTS: The documented Hb levels and number of blood units transfused 3months after APC were recorded. At endoscopy, all patients had the classic type of GAVE. The mean Hb level increased from 7.5±1.7gdl(-1) before APC to 10.2±0.8gdl(-1) after APC (p value <0.001). The transfusion requirements significantly decreased to 0.2±0.5units/patient (p value <0.001). CONCLUSION: Endoscopic APC is a safe, effective and inexpensive modality in treating GAVE and could be an alternative to the currently available endoscopic methods.

Endothelial nitric oxide synthase and angiotensinogen gene polymorphism in coronary artery diseases in Egypt.

Genetic factors contribute to the pathogenesis of coronary artery disease (CAD). We studied 100 patients with CAD and 50 healthy individuals to assess the association of endothelial nitric oxide (eNOS) polymorphism (Glu298Asp) and angiotensinogen polymorphisms (M235T) and CAD in an Egyptian population. Serum nitric oxide (NO) and angiotensin I levels were also measured. The frequency of Glu298Asp and M235T polymorphisms were higher in the CAD group compared with controls. The mean level of NO was significantly lower (P < .05) while angiotensin I was significantly higher (P < .05) in patients CAD than in controls. The frequency of eNOS TT allele of M235T variant was significantly higher in patients with CAD (20% vs 6%). The frequency of angiotensinogen (AGT) TT and T allele in patients with CAD was significantly higher (P < .05) than in controls (22% vs 6%and 47% vs23%, respectively). Homozygosity for Glu298Asp and M235T polymorphisms may predispose to CAD.

Periodontitis and cardiovascular disease: Floss and reduce a potential risk factor for CVD.

There is evidence supporting an association between cardiovascular disease (CVD) and periodontitis. We determined whether patients with chronic periodontitis, who are otherwise healthy individuals, have higher serum concentrations of emerging risk markers of CVD such as C-reactive protein (CRP) and interleukin 6 (IL-6) and investigated the effect of subsequent periodontal treatment on the levels of these markers. A total of 40 individuals were included in the study. Serum levels of CRP and IL-6 were estimated twice, once on the initial visits and the other 3 months after periodontal therapy. The mean CRP and IL-6 levels were significantly higher (P < .001) in the patients compared with controls and significantly decreased (P < .001) following periodontal treatment. This study suggests that periodontitis is a potential modifiable risk factor for CVD.