Congenital analbuminemia associated with compound heterozygous novel nucleotide variations in a young adult with coronary thrombosis.

Congenital analbuminemia (CAA) is a very rare genetic disorder characterized by a significant reduced or even complete absence of human serum albumin. Our data describe the clinical features and laboratory results of a case confirmed by mutation analysis of the albumin gene in a 35-year-old man presenting recurrent acute coronary syndrome. To the best of our knowledge, only two cases of coronary artery disease have been reported worldwide without recurrence. Our findings contribute to shed light on the clinical characteristics and biochemical parameters of this disease and confirm that cardiovascular complications must be taken seriously in this pathology. Mutational screening disclosed two novel compound heterozygous nucleotide variations located in intron 12 and in 3'UTR. The prediction of the functional and structural impact of the reported variations using different bioinformatics tools demonstrates that these genetics variations affect RNA transcription and mRNA folding.

sCXCL16 as a prognostic biomarker for COVID-19 outcome.

As elevated levels of the soluble CXCL16 (sCXCL16) chemokine have been reported in severe coronavirus disease 2019 (COVID-19) patients, this study examined whether sCXCL16 concentration on the first day of hospitalization predicted death in COVID-19 patients. A total of 76 patients with COVID-19 were admitted to the Military Hospital of Tunis, Tunisia, between October 2020 and April 2021, and later classified as survivors or nonsurvivors based on their outcomes. At admission, the groups were matched by age, gender, comorbidities, and the percentage of patients with moderate conditions. On the first day of admission, serum's sCXCL16 concentrations were measured using a magnetic-bead assay. There was an eightfold increase in serum sCXCL16 levels in the nonsurvivors' group (3661.51 ± 2464.87 pg/mL vs. 454.3 ± 338.07 pg/mL, p < 0.0001). For the optimal cutoff value of sCXCL16 at 2095 pg/mL, we found a 94.6% sensitivity and a 97.4% specificity, with an area under curve of 0.981 (p = 5.03E-08; 95% confidence interval [95% CI]: 0.951-1.0114). Considering the risk of death at a concentration above the threshold, the unadjusted odds ratio was 36 (p < 0.0001). The adjusted odd ratio was estimated at 1.003 (p < 0.0001; 95% CI: 1.002-1.004). Finally, there was a significant difference between survival and nonsurvival groups in leukocyte numbers (p = 0.006), lymphocytes (p = 0.001), polymorphonuclear neutrophils (p = 0.001), and C-reactive protein levels (p = 0.007), except for monocytes (p = 0.881). Based on these results, sCXCL16 level could be used for detecting nonsurvival COVID-19 patients. Therefore, we recommend assessing this marker in hospitalized COVID-19 patients.

Neuromeningeal cryptoccocosis revealing IgA-λ multiple myeloma.

Cryptococcosis is an opportunistic fungal infection that is commonly associated with an immune-compromised state. Cases of cryptococcosis have rarely been reported in patients with multiple myeloma (MM). However, cryptococcosis as a presenting symptom of MM has never been reported. We presented here a case of neuromeningeal cryptococcosis in a patient without underlying diseases, who has revealed IgA-λ MM. Early detection and treatment of cryptococcosis are essential to reduce morbidity.

The Association of IL-6, TNFα and CRP Gene Polymorphisms with Coronary Artery Disease in a Tunisian Population: A Case-Control study.

Coronary artery disease is an inflammatory disease. Systemic markers of inflammation such as Interleukin-6, Tumor Necrosis Factor alpha and C-reactive protein have previously been shown to be associated with increased risk of cardiovascular events. The aim of the present study is to assess the role of variants in the IL-6 (- 174 G/C), TNFα (- 308 A/G) and CRP (+ 1059G/C) genes as susceptibility markers for CAD in a Tunisian population. The investigation was conducted as a case-control study involving 204 patients and 400 age-gender matched controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. There are significant differences between CAD patients and the control group with regard to BMI (p < 10-3) and family history of CAD (p < 10-3). The CAD patients are more likely to have a history of smoking (p < 10-3), have a higher value of TC (p = 0.003), LDLc (p = 0.016), hs-CRP (p = 0.01), IL6 (p < 10-3) and TNFα (p = 0.038). Our analysis showed significant differences between cases and controls in genotypic distribution of IL6-174CC (p = 0.003; OR = 7.71 CI (1.58-37.56)), TNFα - 308 AA (p = 0.004; OR = 2.95 (1.57-5.51)) and CRP + 1059 CC (p < 10-3; OR = 5.40 (2.30-12.68)). However, we failed to find an association between the different genotypes and the inflammatory markers levels. Our results suggest that the presence of IL-6 (- 174 G/C), TNFα (-308 A/G) and CRP (+ 1059G/C) polymorphisms, may be considered to be a risk factor for CAD in Tunisian population.

Association of methylenetetrahydrofolate reductase A1298C polymorphism but not of C677T with multiple sclerosis in Tunisian patients.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic neurological disease characterized by central nervous system (CNS) inflammation and demyelination of nerve axons. The aim of this study was to investigate a possible association between the methylenetetrahydrofolate reductase (MTHFR) gene and multiple sclerosis in Tunisian patients. PATIENTS AND METHODS: The genotyping of two missense variants of the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C was performed in 80 multiple sclerosis patients and 200 healthy controls. RESULTS: No significant differences were found in the frequency of the MTHFR C677T polymorphism between MS patients and healthy controls. However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p<10(-3); C/C: 13.75% versus 0%, p<10(-3), respectively). CONCLUSION: Although our preliminary findings suggest no association between the MTHFR C677T variants and MS, there is evidence to suggest a significant association between the MTHFR A1298C polymorphisms and MS.

Homocysteine and inflammatory biomarkers plasma levels, and severity of acute coronary syndrome.

Recently, homocysteine and new inflamatory biomarkers are demonstrated to be involved in cardiovascular diseases. These risk factors are not well studied in acute coronary syndrome. We investigated the distribution of homocysteine and inflammatory markers in patients with acute coronary syndrome and evaluated the association between these parameters and severity of the disease. One hundred and twenty-two patients with acute coronary syndrome were recruited in the cardiac intensive unit care of military hospital of Tunis. Classic risk factors, lipid parameters, total homocysteine, HsCRP, IL-6 and TNFα were determined for all participants. We investigated the distribution of these parameters according to the number of diseased vessels in patients with acute coronary syndrome. Patients with three affected vessels showed significant elevated homocysteine, HsCRP, IL-6, TNF-α, total cholesterol, LDL-cholesterol and Lp (a) compared to those with one and those with two affected vessels. Homocysteine (OR = 1.14; 95%IC: 1.04-1.25; P = 0.006), TNF-α (OR = 1.27; 95%IC: 1.13-1.44; P = 10(-3)), HsCRP (OR = 1.09; 95%IC:1.03-1.16; P = 0.005) and IL-6 (OR = 1.15; 95%IC: 1.06-1.25; P = 0.001) were significant predictors of severity of the disease. We conclude that homocysteine and inflammatory biomarkers appear to enhance the degree of affected arteries and so the severity of coronary artery disease.

Hyperhomocysteinemia, C677T MTHFR polymorphism and ischemic stroke in Tunisian patients.

BACKGROUND: Hyperhomocysteinaemia has been identified as a strong risk factor for ischemic stroke (IS). A point mutation in methylene tetrahydrofolate reductase (MTHFR C677T) has been associated with increased plasma homocysteine (Hcy) levels. AIM: This preliminary study aimed to investigate whether hyperhomocysteinaemia and/or MTHFR C677T mutation are associated with ischemic stroke. METHODS: A case-control study including 50 consecutive patients with confirmed IS and 97 controls was performed. Fasting plasma homocysteine levels, MTHFR C677T genotypes were assessed. Other factors such as hypertension, obesity, dyslipidemia, diabetes mellitus, recurrent stroke tobacco and alcohol were investigated. RESULTS: Mean plasma homocysteine levels were significantly higher in IS patients than in controls (15.83+/-10.60) µmol/L vs 13.78+/-6.29 µmol/L, p=0.04), while no association of MTHFR C677T variant was observed even with homocysteine. The risk to develop ischemic stroke in hyperhomocysteinemic subjects was 2.4 times more than in subjects with normal Hcy levels (OR= 2.4; 95% CI: 1.13-5.06; p<0.05). CONCLUSION: Our findings suggest that high levels of homocysteine but not MTHFR C677T polymorphism represent risk factors for arterial ischemic stroke in Tunisian subjects.

Homocysteine and markers of inflammation in acute coronary syndrome.

BACKGROUND: An elevated level of homocysteine (Hcy) has been shown to be a cardiovascular risk factor in the majority of research studies. Recently, it was found to be associated with new risk factors such as inflammatory markers. OBJECTIVES: To investigate the distribution of plasma total Hcy (tHcy) and the levels of inflammatory markers in patients with acute coronary syndrome (ACS), and to evaluate the association between these parameters and the severity of the disease. METHODS: A total of 122 patients with ACS and 80 control subjects were recruited from the cardiac intensive care unit of the Military Hospital of Tunis, Tunisia. Lipid profile and the levels of tHcy, high-sensitivity C-reactive protein (HsCRP), interleukin (IL)-6, IL-8, IL-1beta and tumour necrosis factor-alpha (TNFalpha) were determined for all participants. The distribution of these parameters were compared between groups and according to the number of diseased vessels in patients with ACS. RESULTS: ACS patients had significantly elevated levels of tHcy (P<0.01), HsCRP (P<0.001), IL-6 (P<0.001), TNFalpha (P<0.001), folates (P<0.05) and vitamin B(12) (P<0.001), but lower high-density lipoprotein cholesterol (P<0.05) levels. The analysis of the association between these parameters and the number of diseased vessels showed significant differences in tHcy, HsCRP, IL-6 and TNFalpha, with positive correlations. Significantly negative correlations were found between the number of diseased vessels and folate (r=-0.34; P<0.01), and vitamin B(12) (r=-0.22; P<0.01). CONCLUSION: Elevated levels of tHcy, IL-6, TNFalpha and HsCRP appear to be associated with a greater number of diseased arteries and, consequently, the severity of coronary artery disease.

Effect of lipopenic and hypotensive treatment on homocysteine levels in type 2 diabetics.

AIM: Evaluate the effect of lipopenic and hypotensive treatment on homocysteine levels. METHODS: We recruited 145 type 2 diabetics and 130 control subjects. Thirty-seven diabetics had no complications, 54 had microvascular complications and 54 had macrovascular complications. We determined the parameters homocysteine of lipid, vitamin B12, triglycerides, and folates for all subjects. Associated treatments used one or more of the following drugs, statin, fibrate, angiotensin-converting enzyme inhibitor and beta-blockers. RESULTS: Hyperhomocysteinemia was present in 35.6% of patients. Diabetics had elevated serum levels of triglycerides (P < 0.001), homocysteine (P < 0.01), folates (P < 0.01) and vitamin B12 (P < 0.001). A strong association was found between type 2 diabetes and hyperhomocysteinemia (P < 0.001). Diabetics with associated treatment had elevated homocysteine, vitamin B12 and folate levels when compared to diabetes-free controls. For diabetics with macrovascular complications, we found significant differences in homocysteine (P = 0.010) and folate (P = 0.014) between those taking associated drugs and those who did not. For diabetics with microvascular complications, a significant difference was found in folate only (P = 0.012). CONCLUSION: Drugs used for hypertension and hyperlipidemia may have an effect on homocysteine levels, for this reason the interaction between drug action and homocysteine levels should be taken into consideration.

Variability of acid-base status in acetate-free biofiltration 84% versus bicarbonate dialysis.

The ultimate goal of hemodialysis (HD) treatment is to achieve the highest level of efficacy in the presence of maximal clinical tolerance. With an aim to offer good hemodynamic stability, as observed during the acetate-free biofiltration 14% (AFB 14%) to patients who are intolerant to bicarbonate dialysis (BD) and with less cost, we have developed since June 1994, a new HD technique, namely AFB 84%. This study was carried out to analyze acid-base variations during the AFB 84% in comparison to BD in hemodynamically stable patients on regular HD. This was a prospective randomized crossover study carried out on 12 patients (6 males and 6 females) for a total of 144 HD sessions (72 BD and 72 AFB 84%). Patients with decompensated cardiomyopathy, respiratory diseases or uncontrolled hypertension were not included in the trial. All the patients were treated with BD or AFB 84%; the latter is characterized by the absence of acetate in the dialysate and a complete correction of buffer balance by post-dilutional infusion of bicarbonate-based replacement solution. The comparison of pre-dialysis arterial acid-base and blood-gas parameters revealed no significant differences of pH, HCO(3)(-) and paCO(2) levels between the two techniques. Analysis of post-dialysis parameters showed that, among patients dialyzed with BD, there was over correction of metabolic acidosis with a tendency towards metabolic alkalosis. In contrast, in patients dialyzed with AFB 84%, we observed a significant improvement in pH and HCO(3)(-) levels but the increase in paCO(2) level was not significant. A comparison of these parameters between the two techniques showed statistically significant difference in pH, HCO(3)(-) and paCO(2) levels, but not for paO(2) level. AFB 84% can offer some important advantages with the complete absence of acetate from the substitution fluids, and permits a better correction of metabolic acidosis than BD, without causing alkalosis.