Impact of Ramadan intermittent fasting on metabolic and inflammatory profiles in type 2 diabetic patients.

Purpose: The aim of this study was to assess the impact of Ramadan intermittent fasting on metabolic and inflammatory profiles in type 2 diabetic patients (T2D). Methods: It was a prospective study including 55 T2D patients treated with oral hypoglycemic drugs, who intended to observe Ramadan fasting in 2019. All participants underwent a questionnaire, a physical examination, laboratory investigations, and a cardiovascular risk assessment using the Framingham score before Ramadan (T0), immediately after Ramadan (T1), and two months after Ramadan (T2). Results: The mean age of participants was 54.5 ± 10.1 years. The number of fasted days was 29.3 ± 2.3 days. The mean total daily calorie intake decreased significantly by 19% during Ramadan (p < 10-3). A significant decrease in weight (79.8 ± 12.9 vs 78.4 ± 13.3 kg, p = 0.003), body mass index (29.8 ± 5.4 vs 29.2 ± 5.4 kg/m2, p = 0.004), waist circumference (98.2 ± 9.6 vs 96.3 ± 10.2 cm, p = 0.015), fat body mass (24.3 ± 9.4 vs 23.5 ± 9.7 kg, p = 0.043) was observed at T1. The weight loss was significantly correlated with the number of fasting days (r = 0.348, p = 0.009) and was maintained at T2. Serum fructosamine increased at T1 (303.6 ± 46 vs 333.49 ± 59.49 µmol/L, p < 10-3) and returned to its baseline levels at T2. A significant decrease in insulin (9.7 ± 5.5 vs 7.98 ± 5.05 mIU/L, p = 0.043), fibrinogen (3.7 ± 0.8 vs 3.4 ± 0.6 g/L, p = 0.003), and hs-CRP (4.8 ± 5.7 vs 3.7 ± 4.5 mg/L, p = 0.058) levels was observed at T1. Homocysteine level was significantly higher after Ramadan (12.2 ± 6.2 vs 13.5 ± 6.4 µmol/L, p = 0.001). However, no significant changes were found in blood pressure, fasting blood glucose, HOMA-IR, uric acid, lipids, and white blood cells count. The mean Framingham score decreased insignificantly after Ramadan. Conclusions: Ramadan fasting in T2D patients seems to have a favorable impact on anthropometric parameters and inflammatory profile. However, it may cause a transient worsening of glycemic control.

Contribution of the ACE (rs1799752) and CYP11B2 (rs1799998) Gene Polymorphisms to Atrial Fibrillation in the Tunisian Population.

BACKGROUND: This study investigated the association of angiotensin-converting enzyme (ACE I/D) and aldosterone synthase (CYP11B2-344C/T) gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) with atrial fibrillation (AF) in the Tunisian population. MATERIALS AND METHODS: The study population included 120 patients with AF and 123 age-matched controls. Genotyping of the I/D polymorphism in the ACE gene and the -344C/T polymorphism in the CYP11B2 gene was performed by polymerase chain reaction (PCR) and PCR-RFLP methods, respectively. RESULTS: The genotype distribution of the ACE I/D and CYP11B2-344C/T polymorphisms was significantly different between AF patients and control participants (p < 0.01 and p < 0.006 respectively). In addition, ACE I/D increased the risk of AF significantly by 3.41-fold for the DD genotype (OR = 3.41; 95% CI [1.39-8.34]; p < 0.007), and after adjusting for confounding factors (age, diabetes, hypertension, and dyslipidemia), the risk was higher (OR = 5.71; 95% CI [1.48-21.98]; p < 0.01). Likewise, the CYP11B2-344C/T polymorphism increased the incidence of AF for the TT genotype (OR = 3.66; 95% CI [1.62-8.27]; p < 0.002) and the CT genotype (OR = 2.68; 95% CI [1.22-5.86]; p < 0.01). After adjusting for confounding factors (age, diabetes, hypertension and dyslipidemia), the risk remained higher for the TT genotype (OR = 3.58; 95% CI [1.08-11.77]; p < 0.03). Furthermore, the haplotype-based association of the ACE I/D and CYP11B2-344C/T polymorphisms showed that the D-T haplotype increased the risk for AF. CONCLUSION: Our study suggests a significant association of the ACE (I/D) and CYP11B2-344C/T polymorphisms with AF in the Tunisian population.

ImpaCt of aspirin regimen on THrombin generation in diabEtic patients with acute coronary syndrome: CARTHaGE-ACS trial.

BACKGROUND: Diabetes is associated with a high rate of events after acute coronary syndrome. It was recently reported that once-daily aspirin might not provide stable biological efficacy in patients with diabetes. AIMS: We sought to compare the biological efficacy of aspirin given once a day versus aspirin divided twice per day in a population of diabetic patients with non-ST elevation acute coronary syndrome (NSTE-ACS) as assessed by the thrombin generation test. METHODS: We performed an open-label single-blind randomized study including 59 consecutive diabetic patients admitted for NSTE-ACS. Patients were randomly treated with aspirin 100 mg once a day (GA100; n = 20), aspirin 160 mg once a day (GA160; n = 19) or aspirin 100 mg twice a day (G2A100; n = 20). The primary endpoint was endogenous thrombin potential (ETP) at discharge and after 6 months. RESULTS: The mean age of our patients was 61.5 ± 9 years, and 73% were male. The baseline characteristics were comparable between the three groups. In the GA100 group, there was no significant effect on ETP variation at 6 months (1150.46 ± 504.84 vs. 1087.63 ± 454.18; p = 0.794). An increase in aspirin dose with a second daily administration of 100 mg was associated with a significant reduction in ETP at 6 months (1004.87 ± 196.2 vs. 1233.63 ± 333.5; p = 0.003). A nonsignificant decrease in ETP was seen in the GA160 group (from 1173.8 ± 388.07 to 1053.64 ± 269.93 at 6 months, p = 0.117). CONCLUSION: Only the twice-daily aspirin regimen led to better control of hypercoagulability in NSTE-ACS diabetic patients. However, no thrombin generation normalization was reported.

hOCT1 gene expression predict for optimal response to Imatinib in Tunisian patients with chronic myeloid leukemia.

PURPOSE: Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression changes may influence IM response. In this study, we aimed to investigate the impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the clinical outcome in CML patients. METHODS: hOCT1 expression profile was determined using the quantitative real-time polymerase chain reaction in 69 CML patients treated with IM (35 responders to IM patients and 34 IM-resistant patients), while genotyping of 69 cases and 51 controls for hOCT1 polymorphisms was performed by direct sequencing after amplification of exon7. RESULTS: Our results showed that the hOCT1 gene was significantly downregulated in the samples of the IM-resistant group when compared with the IM-responder group (p = 0.0211). Moreover, sequencing data show an association in all cases between the SNP 408V>M (g.1222G>A) and an intronic 8 bp (base pairs) insertion of GTAAGTTG (rs36056065) at the 3' end of exon 7. The genotype and allele distribution of the different SNPs did not differ significantly between the two groups of patients. CONCLUSIONS: hOCT1 mRNA expression may serve as a clinical biomarker of response to imatinib and could be useful to predict IM therapy outcome of CML patients.

Cerebral Venous Thrombosis: A Tunisian Monocenter Study on 160 Patients.

OBJECTIVE: Data regarding cerebral venous thrombosis in North Africa are scarce. This study aims to identify the clinical features, risk factors, outcome, and prognosis of cerebral venous thrombosis in Tunisia. METHODS: Data of 160 patients with radiologically confirmed cerebral venous thrombosis, hospitalized in Mongi Ben Hmida National Institute of Neurology (Tunis, Tunisia), were retrospectively collected and analyzed. RESULTS: The mean age was 37.3 years with a female predominance (83.1%). The mode of onset was subacute in most cases (56.2%). Headache was the most common symptom (71.3%), and focal neurologic symptoms were the main clinical presentation (41.8%). The most common sites of thrombosis were the superior sagittal sinus (65%) and the lateral sinus (60.6%). More than 1 sinus was involved in 114 (71.2%) patients. Parenchymal lesions observed in 85 (53.1%) patients did not correlate with cerebral venous thrombosis extent. Major risk factors were obstetric causes (pregnancy and puerperium) found in 46 (38.6% of women aged <50 years) patients, followed by anemia (28.1%) and congenital or acquired thrombophilia (16.2%). Mortality rate was of 6.6%. Good outcome at 6 months (modified Rankin Scale ≤2) was observed in 105 (87.5%)of 120 patients available for follow-up. Predictors of poor outcome were altered consciousness and elevated plasma C-reactive protein levels. CONCLUSION: Clinical and radiologic presentation of cerebral venous thrombosis in Tunisia was quite similar to other parts of the world with, however, a particularly high frequency of obstetric causes. Plasma C-reactive protein level should be considered as a prognostic factor in CVT.

Pleural myelomatous involvement in multiple myeloma: five cases.

Pleural myelomatous involvement in multiple myeloma (MM) is rare, occurring in less than 1% of cases. We retrospectively studied five cases of patients with MM who developed myelomatous pleural effusions. Three men and 2 women with a mean age of 61 years presented with myelomatous pleural effusion. The pleural fluid electrophoresis revealed a peak of IgG in three cases, of IgA in one case, and of lambda light chains in one case, which were identical to that in the sera of the patients. Detection of typical plasma cells in pleural fluid cytology was contributive, and histologic confirmation by pleural biopsy was positive in four cases. Treatment consisted of chemotherapy. The clinical outcome was initially good, but relapses occurred in all cases early and were complicated by fatal infections. Myelomatous pleural effusion is a rare affection. It is usually a late complication associated with poor prognosis.

Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial.

From April 2003 to December 2006, 195 patients with de novo symptomatic myeloma and younger than 60 years of age were randomly assigned to receive either tandem transplantation up front (arm A, n = 97) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide (day + 90, 100 mg per day during 6 months) (arm B, n = 98). Patients included in arm B received a second transplant at disease progression. In both arms, autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m(2)) and granulocyte colony stimulating factor. Data were analyzed on an intent-to-treat basis. With a median follow-up of 33 months (range, 6-46 months), the 3-year overall survival was 65% in arm A and 85% in arm B (P = .04). The 3-year progression-free survival was 57% in arm A and 85% in arm B (P = .02). Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide (with second transplant in reserve for relapse or progression) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to tandem transplant in this setting. This study was registered at www.ClinicalTrials.gov as (NCT 00207805).

Prevention of central venous line-related thrombosis by continuous infusion of low-dose unfractionated heparin, in patients with haemato-oncological disease. A randomized controlled trial.

We have conducted a prospective randomized controlled trial to evaluate the role of low-dose unfractionated heparin prophylaxis in preventing central venous line-related thrombosis in patients with haemato-oncological disease. Patients were randomly assigned to receive either prophylactic intravenous unfractionated heparin (continuous infusion of 100 IU/kg/daily) or 50 ml/daily of normal saline solution as a continuous infusion. CVLs were externalized, non tunneled, double lumen catheters. All CVLs were placed percutaneously by the same physician in the subclavian vein. Upper limb veins were systematically examined by ultrasonography just before, or <24 hours after, catheter removal, and in case of clinical signs of thrombosis. One hundred and twenty-eight CVLs were inserted. Catheter-related thrombosis occurred in 1.5% of the catheters inserted in patients of the heparin group, and in 12.6% in the control group (p = 0.03). No other risk factors were found for the development of catheter-related thrombosis. Two and three patients experienced severe bleeding in the heparin group, and in the control group, respectively (p = 0.18). There were no other side-effects clearly ascribable to the use of unfractionated heparin. This is the first prospective, randomized study, which shows that low-dose of unfractionated heparin is safe and effective to prevent catheter-related thrombosis in patients with haemato-oncological disease.