Effects of insulin therapy optimization with sensor augmented pumps on glycemic control and body composition in people with cystic fibrosis-related diabetes.

Objective: Cystic fibrosis (CF)-related diabetes (CFRD) resulting from partial-to-complete insulin deficiency occurs in 40-50% of adults with CF. In people with CFRD, poor glycemic control leads to a catabolic state that may aggravate CF-induced nutritional impairment and loss of muscle mass. Sensor augmented pump (SAP) therapy may improve glycemic control as compared to multiple daily injection (MDI) therapy. Research design and methods: This non-randomized clinical trial was aimed at evaluating the effects of insulin therapy optimization with SAP therapy, combined with a structured educational program, on glycemic control and body composition in individuals with insulin-requiring CFRD. Of 46 participants who were offered to switch from MDI to SAP therapy, 20 accepted and 26 continued the MDI therapy. Baseline demographic and clinical characteristics were balanced between groups using a propensity score-based overlap weighting procedure and weighted mixed-effects regression models were used to estimate changes in study outcomes. Results: After 24 months changes in HbA1c were: -1.1% (-12.1 mmol/mol) (95% CI: -1.5; -0.8) and -0.1% (-1 mmol/mol) (95% CI: -0.5; 0.3) in the SAP and MDI therapy group, respectively, with a between-group difference of -1.0 (-10 mmol/mol) (-1.5; -0.5). SAP therapy was also associated with a decrease in mean glucose (between group difference: -32 mg/dL; 95% CI: -44; -20) and an increase in TIR (between group difference: 19.3%; 95% CI 13.9; 24.7) and in fat-free mass (between group difference: +5.5 Kg, 95% CI: 3.2; 7.8). Conclusion: Therapy optimization with SAP led to a significant improvement in glycemic control, which was associated with an increase in fat-free mass.

Molecular and clinical features associated with CFTR gene rearrangements in Italian population: identification of a new duplication and recurrent deletions.

Cystic fibrosis (CF) is mainly caused by small deletions or missense mutations in the CFTR gene. The CF mutation database lists more than 35 large rearrangements that may escape detection using polymerase chain reaction-base techniques. The Innogenetics assay, the denaturing high-performance liquid chromatography and sequencing screening showed a mutation detection rate of 92.6% in our population. We report here the results of multiplex ligation-dependent probe amplification (MLPA) screening for CFTR gene rearrangements, performed on the unidentified alleles of our CF patients. Our sample population consists of 692 non-related Italian CF patients (for a total of 1384 alleles), followed at CF Centres in the Lombardia Region. MLPA analysis was performed in 49 patients who still had one or two unidentified alleles (for a total of 52 unidentified alleles) after extensive analysis of CFTR gene. All patients who were studied had the classical form of CF. We characterized nine different deletions and a new duplication. The deletion of exons 22-23 (7/82) was the most frequent in our cohort. The search for deletion/duplications of the CFTR gene has made it possible to reach a 94.1% detection rate, with an improvement (1.6%) of the carrier detection rate in the Italian population.

Plasmatic cytokine network in patients with laryngeal carcinoma after surgical treatment.

Alterations in host immunity, inflammation, angiogenesis and metabolism are all prominent clinical features in patients with laryngeal squamous cell carcinoma (LSCC). Although the origin of the signals and mechanisms underlying these responses are not well understood, their local and systematic nature suggest that squamous cell carcinoma-produced cytokines with proinflammatory and immunoregulatory activity may contribute to the pathogenesis of LSCC. In order to gain a better insight into the roles and relationships of the cytokines, we investigated serum IL-6, IL-10 and IL-12 concentrations in LSCC patients under baseline conditions and after surgery. In comparison with controls, all the patients had higher plasma IL-10 concentrations before surgical treatment (T0), while plasma IL-6 and IL-12 concentrations were higher in 22 (84.6%) and 24 patients (92.3%). The differences in plasma IL-6, IL-10 and IL-12 concentrations at T0 and T1 were statistically significant (p<0.001, p<0.0046 and p<0.011). Our finding suggest that plasma cytokines are overexpressed in LSCC patients. There was an independent increase in plasma IL-6 levels before and after surgical treatment. Furthermore, the up- and down-regulation of plasma IL-10 and IL-12 suggest a regulatory relationship between them.

Reactive oxygen metabolites and prooxidant status in children with Down's syndrome.

Children with Down's syndrome suffer many diseases among which cardiovascular diseases, increased susceptibility to infections, leukemia, endocrine alterations, immune defects, nutritional disturbance and mental retardation have clinical relevance. It has been suggested that the pathogenesis of Down's syndrome involves reactive oxygen species arising from a mutation in gene encoding, which disproportionately elevates superoxide dismutase activity. Reactive oxygen species and total antioxidant capacity were evaluated using two new spectrophotometric methods in a selected group of 40 children with Down's syndrome and in 20 apparently healthy children used as controls. Reactive oxygen species were significantly higher (p <0.05) in children with Down's syndrome than in controls: 452 (+/- 72) U.Carr vs. 270 (+/- 66) U.Carr respectively. Total antioxidant capacity was significantly higher (p <0.05) in controls than in children with Down's syndrome: 380 (+/- 52) micromol hypochlorous acid (HCLO)/ml vs. 281 (+/- 33) micromol HCLO/ml, respectively. In fact, thiol groups (sulfhydryl) were significantly higher (p <0.05) in controls than in children with Down's syndrome: 644 (+/- 78) micromol/l vs. 462 (+/- 54) micromol/l, respectively Our data show how to simply measure chemical indices of oxidative status in serum samples from children with Down's syndrome. We determined the plasmatic activities of reactive oxygen metabolites and oxidative defense molecules. Accumulated macromolecular damage may be one of the causes of some of the abnormalities that are considered part of the syndrome. Therefore, children with Down's syndrome have to cope with a significant prooxidant environment. Oxidative stress causes alterations such as atherosclerosis, early aging, immunological default and neurologic disorders in Down's syndrome patients. The new test available for measuring reactive oxygen species in serum proved to be reliable and useful as an early marker of tissue damage.