Regulatory T Cells, IL10 and IL6 in HCV Related Hepatocellular Carcinoma after Transarterial Chemoembolization (TACE).

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Tumors can recruit and promote the expansion of regulatory T cells (Tregs) to suppress antitumor immune responses for survival and progression. Furthermore, there is a strong evidence for the potential roles of cytokines in promoting HCC carcinogenesis and progression. We aimed to evaluate the frequency of Treg cells and serum levels of IL6 and IL10 before and after transarterial chemoembolization (TACE). We carried out a cross-sectional study at Assiut University hospitals that included 34 HCC patients and 10 matched apparently healthy controls. Peripheral Treg frequency was evaluated by Flow cytometry. IL6 and IL10 serum levels were evaluated by ELISA before and after TACE. HCC patients had a significantly higher level of IL6 and IL10 when compared to the control group (P=0.0002, P < 0.0001), respectively. However, after treatment, there was an elevation in the levels of IL6 and IL10 followed by a decrease to the baseline levels. Patients with large tumors (≥5 cm) showed higher levels of both IL 6 and IL 10 than those with smaller tumors. Moreover, HCC patients showed a higher frequency of Treg cells in comparison to the controls (P=0.002). No significant correlation was observed between the frequency of Treg cells and IL10 before and after treatment (r=0.38, P=0.30). In conclusion, HCC patients have significantly higher levels of IL 6, IL 10 and a higher percentage of Tregs than control individuals. Treg levels are altered after chemoembolization. IL 6 have a potential in reflecting the patient's condition after treatment, thus, can help in monitoring therapy.

Efficacy and safety of cholecalciferol-augmented anti-tuberculosis therapy for treatment of naïve patients with pulmonary tuberculosis: A randomized, controlled, clinical study.

BACKGROUND/OBJECTIVE: Vitamin D deficiency may contribute to the therapeutic failure of antituberculosis therapy (ATT). The aim of this study is to explore the role of adding cholecalciferol to the standard ATT in improving the therapeutic outcome among the naïve patients with pulmonary tuberculosis (TB). METHODS: A randomized, controlled, clinical study, which included 496 naïve patients with pulmonary TB, was carried out. The patients were randomly allocated to two groups. Group-A included 247 patients who received ATT, while group-B included 249 patients who received ATT with cholecalciferol. RESULTS: The rate of therapeutic failure among the study population was 29.4%; it was significantly lower among patients of group-B compared to those of group-A (22.1% (95% CI 14.7-26.2) vs 38.1% (95% CI 31.5-46.1), p 0.036). In addition, the rate of early therapeutic response was significantly higher among patients of group-B compared to those of group-A (35.3% (95% CI 29.6-42.3) vs 19.4% (95% CI 15.1-24.6), p 0.041). Incidence rate of adverse effects was 19.3%; it was higher (although not statistically significant) among patients of group-A compared to those of group-B (21.9% vs 16.9%). CONCLUSIONS: In conclusion, cholecalciferol-augmented ATT can be more efficacious in treating naïve patients with pulmonary TB compared to the standard ATT. In addition, adding vitamin D3 to ATT provides extra protection against the hepatic and muscular adverse effects of ATT.

Cholecalciferol for the prophylaxis against recurrent urinary tract infection among patients with benign prostatic hyperplasia: a randomized, comparative study.

PURPOSE: To explore the role of cholecalciferol for the prophylaxis against recurrent urinary tract infection (UTI) in patients with benign prostatic hyperplasia (BPH). METHODS: Our randomized, uncontrolled prospective study included 389 naïve BPH patients with moderate/severe symptoms, consecutively. The patients were randomly allocated to two groups; group-A included 193 patients who received tamsulosin, while group-B included another 196 patients who received tamsulosin with cholecalciferol. The study population was followed up for 2 years after the start of the treatment. For all the patients enrolled, clinical evaluation, imaging studies (abdominal and trans-rectal ultrasonography), and laboratory investigations [including urinalysis, urine culture with antibiotic susceptibility testing for positive cultures and estimation of prostate-specific antigen (PSA) level] were provided. RESULTS: The incidence rate of recurrent UTI was 9% among the study population; it was significantly higher among group-A patients compared to those of group-B (13.5% vs. 4.6%, p 0.003, OR 2.7, 95% CI 1.5-4.3). Compared to patients of group-A, those of group-B developed a significantly lower level of PSA at the end of treatment period (0.16 ± 0.03 ng/mL vs. 0.27 ± 0.08 ng/mL, p 0.043, OR 1.9, 95% CI 1.2-6.8). CONCLUSIONS: Adjuvant cholecalciferol supplementation may be protective against recurrent UTI among patients with BPH receiving tamsulosin therapy without extra adverse effects.

Predictors of therapeutic failure among patients with acute brucellosis treated by dual therapy with doxycycline-rifampin.

OBJECTIVE: To determine the frequency of therapeutic failure among patients with acute and subacute brucellosis and to explore the predictors of failure. METHODS: The study included 213 consecutive, naïve patients with acute and subacute brucellosis. All participants underwent clinical evaluation, chest radiography, stool microscopic examination and interferon-gamma release assay. Patients received the WHO-recommended therapy of doxycycline 200 mg/day and rifampin 900 mg/day, for 6 weeks. RESULTS: Mean age of the study population was 39.8 ± 12.2 years; 64.8% of them were males. The therapeutic failure rate was 16.4%. Adverse effects were reported by 13.1%. Multivariate analysis of factors associated with therapeutic failure revealed latent tuberculosis infection (LTBI) (OR 3.1, 95% CI, 1.9-24.6, P: 0.009), ascariasis (OR 2.6, 95% CI 1.5-17.9, P: 0.012), and the use of acid suppressive therapy (OR 2.1, 95% CI 1.2-19.5, P: 0.037) as the predictors of therapeutic failure. CONCLUSIONS: The prevalence of therapeutic failure among the Egyptian patients with acute/subacute brucellosis is increasing. Predictors of therapeutic failure are LTBI, ascariasis, and the use of acid suppressive therapy.

The adipokine Chemerin and Fetuin-A Serum Levels in Type 2 Diabetes Mellitus: Relation to Obesity and Inflammatory Markers.

Chemerin and fetuin-A are recently discovered as metabolic regulator hormone in obesity and type 2 diabetes mellitus. However, elevated levels of chemerin and fetuin-A have been associated with insulin resistance and systemic inflammation. The present study aimed to investigate the significance of serum chemerin and fetuin-A levels in obese diabetic patients. Also, to determine whether, chemerin and fetuin-A along with markers of inflammation (IL6 and CRP) and obesity-related parameters in T2DM patients. Serum levels of chemerin and fetuin-A were evaluated using ELISA in 71 T2DM patients and 14 apparently healthy controls. Both groups were subdivided into obese and lean. Serum chemerin and fetuin-A levels were significantly higher in T2DM patients compared to controls (P < 0.001, for both) and significantly higher in obese T2DM in comparison to obese control group (P < 0.01 & P < 0.05, respectively). Serum chemerin and fetuin-A levels correlated positively with HbA1c, HOMA-IR, FBG, IL6 and CRP. In obese patients, serum chemerin and fetuin-A levels correlated positively with BMI and waist circumference. In conclusion, the strong association of chemerin and fetuin-A with insulin resistance and some inflammatory markers may provide an interesting link between obesity, inflammation and diabetes mellitus in human.

Erectile dysfunction among patients with chronic brucellosis.

OBJECTIVE: Only a single study investigated erectile dysfunction (ED) among patients with chronic brucellosis without including a control group. Our study objective was to determine the prevalence of ED among patients with chronic brucellosis compared to normal subjects, and to explore the predictors of ED. MATERIALS AND METHODS: We included 93 chronic brucellosis patients and 92 subjects as a control, from June 2013 to August 2017. Chronic brucellosis was diagnosed based on persistent symptoms for ≥1 year with positive immunoglobulin G antibody titer (≥1:160) by standard tube agglutination test; the mean duration was 21 ± 6.2 months. Clinical evaluation (including an Arabic validated version of the five-item International Index of Erectile Function to diagnose ED; score of 5-21 was diagnostic), imaging studies (including scrotal ultrasonography) and laboratory investigations (including estimation of fasting serum level of glucose (after fasting for 8 h), lipids profile (after fasting for 14 h), and serum level of testosterone) were conducted. A fasting serum glucose level of ≥ 7 mmol/L defined diabetes mellitus (DM). Predictors of ED were identified using multivariate analysis (binary logistic regression). RESULTS: The mean age of patients was 35.4 ± 13.7 years; 24.7% of them had DM, while low serum level of testosterone was detected among 54.8%. Among the patients, ED was significantly more frequent compared to the control subjects (69.9% vs. 19.6%, p < 0.001). Low serum level of testosterone (OR 4.8, 95% CI 1.7-29.3, p 0.008), and DM (OR 3.5, 95% CI 1.2-34.6, p 0.011) were the predictors of ED among the patients. CONCLUSIONS: The prevalence of ED among patients with chronic brucellosis is high. Low serum level of testosterone and DM are associated with ED among such patients.

Latent tuberculosis infection among patients with coronary artery stenosis: A case-Control study.

Background: The activation of the cell-mediated immune responses by Mycobacterium tuberculosis can promote atherogenesis. Aims: The aim of this study is to determine the frequency of latent tuberculosis infection (LTBI) among patients with coronary artery stenosis (CAS) and to explore the association between LTBI and development of CAS. We conducted a case-control study which included 183 patients' who underwent percutaneous coronary angiography (121 patients with CAS and 62 patients without as a control group). Methods: For all the study population, clinical evaluation, tuberculin skin test (TST), imaging studies (including chest radiography and echocardiography), laboratory investigations, and electrocardiography were carried out. Only for the patients with positive TST, QuantiFERON-TB Gold test was performed. Predictors of CAS were identified using univariate analyses (Yates' corrected Chi-square test or Fischer's exact test) followed by multivariate analysis (binary logistic regression). Results: Among 29.5% of the study population, LTBI was detected, and among patients with CAS, 56.2% of patients had advanced CAS. After multivariate analysis, it was found that metabolic syndrome (MS) (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.5-22.6, P = 0.022) and LTBI (OR 2.5, 95% CI 1.2-17.3, P = 0.018) were the predictors of CAS among the study population, while only diabetes mellitus (DM) (OR 1.9, 95% CI 1.1-11.7, P = 0.031) was the predictor of advanced CAS. Conclusion: LTBI is associated with the development of CAS. In addition, MS is associated with CAS, while its related disorder, DM, is associated with advanced CAS.

Latent tuberculosis infection among patients with erectile dysfunction.

No previous studies have investigated the prevalence of latent tuberculosis infection (LTBI) among patients with erectile dysfunction (ED) or its contribution to the development of high-grade ED through a process of chronic inflammation-induced atherosclerosis. The aim of this study was to determine the frequency of LTBI among patients with erectile dysfunction and to explore the contribution of LTBI to high-grade ED. For all the study sample, clinical evaluation, imaging studies, and laboratory investigations were provided. Evaluation included, but was not confined to, scrotal ultrasonography, tuberculin skin test, and QuantiFERON-TB Gold test. The study sample mean ± SD age was 47.9 ± 13.6 years. Approximately 30% of the patients had LTBI and 43% had high-grade ED. After a multivariate analysis, it was found that older age (≥40 years) (OR, 5.2; 95% CI, 1.9-54.6; p 0.004), metabolic syndrome (MS) (OR, 3.4; 95% CI, 1.3-48.2; p 0.016), and LTBI (OR, 4.1; 95% CI, 1.7-61.3; p 0.021) were significantly, independently associated with high-grade ED as opposed to low-grade ED. In conclusion, the prevalence of LTBI among patients with high-grade ED is higher than among those with low-grade ED. In addition to LTBI, older age and MS are associated with high-grade ED as opposed to low-grade ED.

Visfatin Serum Levels in Obese Type 2 Diabetic Patients: Relation to Proinflammatory Cytokines and Insulin Resistance.

Visfatin, an adipocytokine with insulin-mimetic activity, has been previously reported to associate with obesity. Herein, we aimed to investigate the serum level of visfatin and association with proinflammatory markers and insulin resistance in obese type 2 diabetic patients. A case control study was carried out among 80 diabetics and 40 non-diabetic healthy controls, after obtaining Anthropometric measurements and blood pressure. Serum level of visfatin and C-reactive protein (CRP) were measured by Enzyme Immunoassay. Interleukin 6 (IL6), tumor necrosis factor α (TNF-) were measured by ELISA and the homeostasis model assessment for insulin resistance was calculated as a marker of insulin resistance. Compared to healthy controls, diabetic patients showed a significant high serum levels of visfatin (40.33±9.98 vs 19.03±8.22), (P= 0.001), IL6 (12.06±2.69 vs 6.02±3.03), (P < 0.0001), TNF- (13.53±2.54 vs 8.70±3.40), P < 0.0001) and CRP (7.77±1.61 vs 6.01±1.99), (P=0.003). Also there was a strong positive correlation between serum level of visfatin, IL6, TNF- and CRP and some anthropometric characteristics including (WC,BMI and insulin resistance). Furthermore, among 80 diabetic patients, serum level of visfatin was positively correlated with IL6 (r=0.47, P < 0.0001), TNF- (r=0.62, P < 0.0001), CRP (r=0.4, P=0.002) respectively. In conclusion, there is a strong positive correlation between visfatin serum level and the inflammatory markers IL6, TNF- and CRP in type 2 diabetic patients. There is also a positive correlation with insulin resistance and BMI which indicates association of visfatin with obesity and type 2 diabetes mellitus.

Cholecalciferol for prophylaxis against antituberculosis therapy-induced liver disorders among naïve patients with pulmonary tuberculosis: A randomized, comparative study.

BACKGROUND: Patients in countries endemic for chronic viral hepatitis are more vulnerable to antituberculosis therapy-induced liver disorders (ATT-LDs). The aim of this study was to explore the role of cholecalciferol in prophylaxis against ATT-LD among patients with pulmonary tuberculosis (TB) receiving ATT. MATERIAL AND METHODS: We conducted a hospital-based, prospective, randomized, comparative study which included 300 consecutive, naïve patients with pulmonary TB eligible for ATT. The patients were randomly allocated to Group A (150 patients who received ATT) and Group B (150 patients who received ATT with cholecalciferol) who had clinical evaluation, laboratory investigations, and imaging studies. Statistical analysis used student's t-test and Chi-square test were used as appropriate to compare the variables between the study groups. RESULTS: The study population mean age was 35.6 ± 15.3 years. The overall incidence rate of ATT-LD among the study population was 9.3%; the incidence rate was significantly higher among Group A patients compared to those of Group B (13.3 vs. 5.3%;P = 0.001). The onset of ATT-LD was significantly earlier among patients of Group A compared to those of Group B (31.4 vs. 58.7 days,P = 0.027), while the duration of ATT-LD was significantly longer among patients of Group A compared to those of Group B (34.8 vs. 16.9 days,P = 0.009). No adverse effects related to cholecalciferol use were observed. CONCLUSIONS: Adjuvant cholecalciferol supplementation may be protective against ATT-LD without extra adverse effects. Before recommending the routine use of cholecalciferol supplementation for prevention of ATT-LD, larger scale studies are recommended.

Effect of IL6 and IL23 on double negative T cells and anti ds-DNA in systemic lupus erythematosus patients.

Several evidences suggest that DN T cells, IL23 and IL6 play a role in the pathogenesis of SLE. This study aimed to evaluate the frequency of DN T cells in SLE patients and the relation to their activity also to assess the possible role of IL6 and IL23 on DN T cells. Thirty patients with SLE and sixteen healthy blood donor females were enrolled. There was a significant increase in DN T cells in patients than controls (P=0.001). These cells had a significant positive correlation with SLEDAI (r=0.486, P=0.006). DN T cells from SLE patient samples were expanded when stimulated in vitro with RhIL6 or RhIL23 in patients than controls. Furthermore, anti ds-DNA level was found to be increased in supernatant of PBMCs when stimulated by these cytokines in different concentrations. Our findings suggest that IL6 and IL23 may play role in SLE pathogenesis through their effect on DN T cells and anti ds-DNA.

Hookworm infection among patients with pulmonary tuberculosis: Impact of co-infection on the therapeutic failure of pulmonary tuberculosis.

OBJECTIVE/BACKGROUND: The aim of this study is to determine the rate of hookworm infection among patients with pulmonary tuberculosis (TB) and to find out if there is a relation between hookworm infection and the therapeutic failure of pulmonary TB. METHODS: We carried out a prospective, hospital-based study. The study included 231 naïve patients with pulmonary TB, consecutively. Patients were evaluated at the 4th month of therapy for persistence of Mycobacterium tuberculosis infection. All patients had clinical evaluation, laboratory investigations (including sputum culture and stool microscopic examination), and imaging studies (abdominal ultrasonography and chest radiography). RESULTS: The study population mean age was 42.7±13.9 years old with 26.8% of them 40 years old or more. Out of 231 patients, 133 (57.6%) were men. Therapeutic failure rate of pulmonary TB was 29.4%. Hookworm infection was diagnosed among 16.5% of patients and 27.7% had diabetes mellitus (DM). Using multivariate analysis, it was found that age of 40 years or more (odds ratio [OR] 8.4; 95% confidence interval [CI] 1.7-41.3; p=.009), hookworm infection (OR 7.6; 95% CI 1.2-49.9; p=.034), and DM (OR 5.9; 1.2-28; p=.027) were independently associated with therapeutic failure of pulmonary TB among the study population with pulmonary TB. CONCLUSION: In conclusion, the rate of therapeutic failure of pulmonary TB is high. Besides older age and DM, hookworm infection can reduce the therapeutic response of pulmonary TB. Screening for and control of DM and hookworm infection among patients with pulmonary TB may improve their therapeutic response.