Relationship between Glucose-6-Phosphate Dehydrogenase Deficiency, X-Chromosome Inactivation and Inflammatory Markers.

Recent studies suggest that X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency entails a proinflammatory state that may increase the risk of several disease conditions. However, it is not clear how this relates to the degree of enzyme insufficiency and, in heterozygous females, to skewed inactivation of the X chromosome. This study aimed to (i) investigate the enzyme activity in a cohort of 232 subjects (54.3% females) from Northern Sardinia, Italy, further stratified into three subgroups (G6PD normal, partial deficiency and total deficiency); (ii) measure the levels of some non-specific inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and those derived from cell counts, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR), in relation to the underlying molecular defect and X inactivation. G6PD activity was measured in red blood cells according to G6PD/6PGD ratio, and X-chromosome inactivation was assessed by the HUMARA method. Overall, ESR was increased in males with total deficiency compared with normal males (15.0 ± 7.2 vs. 11.9 ± 6.2, p = 0.002, Tukey's test), albeit not in males with partial deficiency. High-sensitivity CRP was slightly increased in males with total deficiency, compared to males with normal G6PD activity (5.96 ± 3.39 vs. 3.95 ± 2.96, p = 0.048). In females, neither marker showed significant differences across the subgroups. MLR was significantly and progressively increased from normal to totally deficient subjects with intermediate values in partially deficient subjects (0.18, 0.31 and 0.37, ANOVA p = 0.008). The NLR and PLR were not different in the three subgroups. Our findings show that G6PD deficiency may be associated with a proinflammatory profile, especially in elderly females, and worsened by the concomitant asymmetric inactivation of the X chromosome.

The Rise and Fall of the Secular Trend in Body Height in Sardinia: An Age-Period-Cohort Analysis.

OBJECTIVE: Over the last century, a progressive rise in stature, known as the 'secular trend', was documented worldwide, and especially in Sardinia, it has reached a peak in Europe. However, this situation recently ceased in several populations. In this study, we tested the hypothesis that the stature secular trend has significantly leveled off in the Sardinian younger generations. METHODS: Height measurements were retrieved from a database of patients undergoing digestive endoscopy, spanning generations between 1920 and 1990. Sex-specific principal component regression models were fitted to decompose stature variation into the contribution of age, period, and birth cohort. RESULTS: A steady increase in stature was observed in generations born after 1920, with an upward surge in those born after 1950. However, a significant leveling off was observed among cohorts born after 1970 among both sexes, as mean heights stabilized at 171.1 cm with a standard error (SE) of 0.9 cm among men and a mean of 160.1 cm (SE = 0.9 cm) among women. CONCLUSION: Our findings support a significant slowdown in the secular trend of stature among the latest Sardinian generations. Several factors, including the consumption of low-quality food, lack of physical activity, and late motherhood, among others, may explain the decline in the secular trend.

Overweight: A Protective Factor against Comorbidity in the Elderly.

The aim of this study was to investigate the relationship between body mass index (BMI) categories and comorbidity in 9067 patients (age range 18‒94 years) who underwent upper digestive endoscopy in Northern Sardinia, Italy. The majority of participants (62.2%) had a BMI under 25 kg/m2, overweight was detected in 30.4%, and obesity (BMI ≥ 30 kg/m2) in 7.4% of patients. The most frequent illness recorded was hypertension followed by cardiovascular and liver disease. The multivariate analysis, after adjusting for sex, residence, marital status, smoking habits, occupation and hospitalization detected an association between comorbidity and aging that was statistically significant and progressive. Among patients younger than 60 years (n = 5612) the comorbidity risk was higher for BMI ranging 27.5‒29.9 kg/m2 compared with BMI 25.0‒27.4 kg/m2 (RR = 1.38; 95% CI 1.27‒1.50 vs. RR = 0.86; 95% CI 0.81‒0.90). In patients older than 60 years (n= 3455) the risk was lower for a BMI in the range 27.5-29.9 kg/m2 compared with a BMI in the range 25.0-27.4 kg/m2 (RR = 1.11; 95% CI 1.05‒1.18 vs. RR = 1.28; 95% CI 1.21‒1.35). These results suggest that being moderately overweight is a marker of a healthy aging process and might protect, at least in part, against comorbidity. However, further research is needed to better understand this unexpected finding.

Twice-a-day PPI, tetracycline, metronidazole quadruple therapy with Pylera® or Lactobacillus reuteri for treatment naïve or for retreatment of Helicobacter pylori. Two randomized pilot studies.

BACKGROUND: Bismuth is no longer available in Europe except as part of combination therapy. Lactobacillus reuteri has also been used as an adjuvant for Helicobacter pylori therapy. We aimed to investigate the efficacy of a b.i.d. quadruple therapy containing Pylera® or L reuteri for H pylori infection. MATERIALS AND METHODS: We performed two open-label randomized pilot studies. Adult patients positive for H pylori were randomly assigned to b.i.d therapy with quadruple therapy containing bismuth (2 capsules of Pylera® plus 250 mg each of tetracycline and metronidazole for a total of 500 mg of each), or the same dose of antibiotics plus 2 × 108  CFU L reuteri DSM 17 938 plus 2 × 108  CFU L reuteri ATCC PTA 6475 (Gastrus®) once daily and pantoprazole 20 mg b.i.d. Regimens were given with meals for 10 days. Cure was defined by negative 13C-UBT or stool antigen test. RESULTS: A total of 99 subjects (29% men) were enrolled; 92 completed the study. In the Pylera® group, H pylori infection was cured in 95.7%; 95% CI = 85%-99% (44/46) PP and 88%; 95% CI = 75%-95% (44/50) ITT vs. 84.8%; 95% CI = 71%-95% (39/46) PP and 79.6%; 95% CI = 65%-89% (39/49) ITT in the Gastrus® group, respectively. Cure rates in naїve patients were 100%; 95% CI = 85%-100% (25/25) PP with Pylera®, and 89.7%; 95% CI = 72%-97% (26/29) with Gastrus®. Compliance was excellent and side effects mild with both regimens. CONCLUSIONS: B.i.d. bismuth quadruple therapy was highly effective for H pylori eradication in treatment of naïve patients in Sardinia. Replacement of bismuth with Gastrus® might be considered when bismuth is contraindicated or unavailable.

Helicobacter pylori infection and occurrence of celiac disease in subjects HLA-DQ2/DQ8 positive: A prospective study.

BACKGROUND: Celiac disease (CD) occurs in subjects positive for HLA-DQ2 and/or DQ8 gene loci at any age following ingestion of gluten-containing food. An increased permeability of the mucosa allows interactions between gliadin macromolecules and genetic factors. It has been observed that Helicobacter pylori has the ability to modulate the integrity of the duodenal epithelium. We aimed to determine whether H. pylori infection may enhance the occurrence of CD in genetically susceptible subjects. MATERIALS AND METHODS: This was a prospective observational study. Patients undergoing upper endoscopy for any reason and positive for HLA-DQ2 and/or DQ8 haplotypes with or without CD were included. H. pylori infection was defined as a positive gastric histopathology and/or 13C-urea breath test. Prevalence of infection was compared between enrolled subjects with and without CD. Multiple logistic regression analysis, adjusting odds ratios for patient age, gender, smoking habit, residency, body mass index, and assumption of nonsteroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPIs) were performed. RESULTS: A total of 397 genetically susceptible individuals (mean age: 37.7 ± 15.3 years; 86% women) were enrolled between October 2014 and October 2017. There were 265 (68%) patients with a diagnosis of CD. Overall, the prevalence of H. pylori infection was 33% and was similar in patients with and without CD (32% vs 36%). Adjustment for all covariates did not reveal any significant association, although adjusted odds ratio (OR) for CD was higher in female (OR = 1.302), in patients H. pylori positive (OR = 1.277), followed by use of NSAIDs (OR = 1.126), respectively. The use of PPIs appeared to be mildly protective against CD (OR = 0.644). CONCLUSION: Our study did not reveal any significant relationship between H. pylori and CD risk, even taking into account other confounders. More importantly, our findings do not support a "protective" role of H. pylori infection against CD, as previously reported. Therefore, there are no reasons to avoid eradication of H. pylori also in subject genetically susceptible for CD.

Chronic autoimmune disorders are increased in coeliac disease: A case-control study.

Coeliac disease (CD) is an autoimmune disorder of the small bowel associated with increased risk of additional autoimmune diseases (ADs).To investigate the prevalence of ADs in a population of adult coeliac patients.This was a retrospective case-control study. Data from coeliac patients and controls referred to a tertiary center between 2013 and 2016 were collected. The frequency of ADs and the unadjusted and adjusted odds ratios (ORs) for age, gender, disease duration, and body mass index with their 95% confidence intervals (CIs) were evaluated.Two hundred fifty-five patients with CD (median age 37.1 years; 206 women) were matched with 250 controls. ADs were more frequent (35.3%) in coeliac patients than in controls (15.2%). Adjusted ORs for the presence of only 1, at least 1, and more than 1 AD were 3.13 (95% CI 1.81-5.42, P < .0001), 3.31 (95% CI 2.00-5.46, P < .0001), and 3.93 (95% CI 1.49-10.36, P = .006), respectively. Hashimoto thyroiditis was the most prevalent AD (24.3% vs. 10%) OR = 2.55 (95% CI 1.39-4.70, P < .0001), followed by psoriasis (4.3% vs. 1.6%), type 1 diabetes (2.7% vs. 0.4%), and Sjögren syndrome (2.4% vs. 0.4%).These findings suggest a need for a careful surveillance of autoimmune status, especially for Hashimoto thyroiditis in patients with celiac disease.