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.

Humoral and cell-mediated immune responses to BNT162b2 vaccine against SARS-CoV-2 in people with cystic fibrosis.

People with cystic fibrosis (pwCF) were considered to be clinically vulnerable to COVID-19 and were therefore given priority in the vaccination campaign. Vaccines induced a humoral response in these patients that was comparable to the response observed among the general population. However, the role of the cell-mediated immune response in providing long-term protection against SARS-CoV-2 in pwCF has not yet been defined. In this study, humoral (antibody titre) and cell-mediated immune responses (interferon-γ release) to the BNT162b2 vaccine were measured at different time points, from around 6-8 months after the 2nd dose and up to 8 months after the 3rd dose, in 118 CF patients and 26 non-CF subjects. Subjects were sampled between November 2021 and September 2022 and followed-up for breakthrough infection through October 2022. pwCF mounted a cell-mediated response that was similar to that observed in non-CF subjects. Low antibody titres (<1st quartile) were associated with a higher risk of breakthrough infection (HR: 2.39, 95 % CI: 1.17-4.88), while there was no significant association with low INF-γ levels (<0.3 IU/mL) (HR: 1.38, 95 % CI: 0.64-2.99). Further studies are needed in subgroup of pwCF receiving immunosuppressive therapy, such as organ transplant recipients. This data is important for tailoring vaccination strategies for this clinically vulnerable population.

Cancer mortality in Europe in 2015 and an overview of trends since 1990.

BACKGROUND: Cancer mortality in Europe has been decreasing since the late 1980s or 1990s in some countries with different patterns in many areas. In this study, we updated trends in cancer mortality in Europe. MATERIALS AND METHODS: We extracted data from the World Health Organization mortality database for 24 cancer sites, 36 European countries and the European Union (EU) as a whole over the 1990-2017 period. We computed age-standardized death rates per 100 000 person-years, and we carried out a joinpoint regression analysis of mortality trends from all cancers and selected major neoplasms. The estimated annual percent change (APC) for each identified linear segment, and the weighted average APC (AAPC) over the entire study period were provided as summary measures of the changes in rates over the time period. RESULTS: In 2015, the age-standardized mortality rates from all cancers in the EU were 137.5 deaths per 100 000 in men and 85.7 in women. Eastern European countries showed the highest rates with values over 150 deaths per 100 000 in men and over 100 deaths per 100 000 in women. Mortality from all cancers in the EU declined annually by 1.5% in men since 2006 and by 0.8% in women since 2007. Most cancer sites showed decreasing trends, with steady declines over the whole period for cancers of stomach, intestines, lung in men, breast and prostate. Unfavourable mortality trends persisted for cancers of liver, lung in women, pancreas, besides skin and kidney in men. CONCLUSIONS: The downward trends in total cancer mortality in Europe still continue over the last decade. However, the trends were less favourable in most eastern European countries. Tobacco control in men (but not in women), improvements in diagnosis and therapy were the main underlying factors of these trends.

The main causes of death contributing to absolute and relative socio-economic inequality in Italy.

OBJECTIVES: Monitoring socio-economic inequality has become a priority for many governments, especially after the socio-economic changes that followed the 2008 financial crisis. This study aimed at detecting the causes of death with the largest socio-economic inequality in relative and absolute terms in Italy. STUDY DESIGN: This is a historical cohort study. METHODS: We used two regression-based measures of socio-economic inequality, the relative index of inequality (RII) and the slope index of inequality (SII), to rank the causes of death with the highest relative and absolute socio-economic inequality. We obtained these measures on a large census-based cohort study with more than 35 million individuals and 452,273 deaths registered in the period 2012-2014. RESULTS: The causes with the highest relative socio-economic inequality were the following: laryngeal cancer (RII: 6.1, 95% confidence interval [CI]: 4.8-7.78), AIDS/HIV (RII: 4.8, 95% CI: 3.1-7.4), chronic liver disease (RII: 4.8, 95% CI: 3.2-7.3), and chronic lower respiratory diseases (RII: 4.8, 95% CI: 3.5-6.5) in men, and diabetes (RII: 6.2, 95% CI: 4.8-7.9), AIDS/HIV (RII: 4.5, 95% CI: 2.7-7.7), genitourinary system (RII: 3.8, 95% CI: 2.6-5.4) and chronic liver diseases (RII: 3.6, 95% CI: 2.9-4.5) in women. In absolute terms, lung cancer and ischemic heart diseases contributed more to the overall socio-economic inequality in men, whereas diabetes and ischemic heart diseases accounted for most of the socio-economic inequality in women. CONCLUSIONS: Our findings call for effective policies to reduce the disparities in mortality from ischemic heart diseases, lung cancer, and diabetes taking into account the sex-specific pattern of inequality.

Psoriasis and the risk of acute coronary syndrome in the elderly.

BACKGROUND: Psoriasis has been associated with a higher prevalence of cardiovascular disease risk factors. However, there is inadequate quantification on the association between psoriasis and acute coronary syndrome (ACS), particularly in the elderly. Therefore, the aim of the present study was to assess the risk of ACS according to history of psoriasis in subjects aged 75 years and older. METHODS: We carried out a case control study based on 1455 cases and 1108 controls. Cases were all the patients admitted in the randomized Elderly ACS 2 trial. Controls were selected from subjects aged ≥75 years included in the Prevalence of Actinic Keratoses in the Italian Population Study (PraKtis), based on a representative sample of the general Italian population. Odds ratios (OR) of ACS according to history of psoriasis were obtained using a multiple logistic regression model including terms for age, sex and smoking. RESULTS: The prevalence of psoriasis was lower among cases (12/1455, 0.8%) than among controls (18/1108, 1.6%). The multivariate OR of ACS according to history of psoriasis was 0.51 (95% confidence interval: 0.23-1.09). CONCLUSIONS: Our data does not support an association between psoriasis and risk of ACS in the elderly.

A randomized placebo-controlled study on high-dose oral algal docosahexaenoic acid supplementation in children with cystic fibrosis.

Low plasma concentrations of docosahexaenoic acid (DHA) are reported in unsupplemented cystic fibrosis (CF) patients. Forty-one CF patients aged from 6 to 12 years were randomized to receive high-dose DHA (100 mg/kg/day in the first month and 1g per day thereafter through a 12-month supplementation) or placebo (germ oil). Primary outcome was percentage change in plasma AA:DHA ratio. Secondary outcomes were changes in the number of pulmonary exacerbations compared to previous year, lung function, BMI, skinfold thicknesses, and body composition assessed by DXA and in serum concentrations of C-reactive protein, cytokines and vitamin (α-tocopherol and retinol). Compared to the control group plasma AA:DHA ratio decreased in the intervention group after 6 months (median percentage changes: -73% in the intervention group vs. -10% in the control group, P=0.001). No differences were detected between groups for secondary outcomes. Despite a decrease of the AA/DHA ratio, DHA supplementation for one year did not induce any significant biochemical and clinical improvement in CF patients.

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance. AIM: To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population. METHODS: A total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas ß-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration. RESULTS: Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. ß-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6  pmol/min per m(2) per mM, P<0.001) and decreased significantly with age by -2.7  pmol/min per m(2) per mM per year (confidence interval (CI) -4.5 to -0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower ß-cell function and higher insulin sensitivity. CONCLUSION: The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining ß-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.