Health-Related Quality of Life in Patients with CVID Under Different Schedules of Immunoglobulin Administration: Prospective Multicenter Study

We assessed the health-related quality of life (HRQoL) in CVID adults receiving different schedules of immunoglobulin replacement therapy (IgRT) by intravenous (IVIG), subcutaneous (SCIG), and facilitated (fSCIG) preparations. For these patients, IgRT schedule was chosen after a period focused on identifying the most suitable individual option

Combined use of serum (1,3)-\u3b2-D-glucan and procalcitonin for the early differential diagnosis between candidaemia and bacteraemia in intensive care units

BACKGROUND: This study aimed to assess the combined performance of serum (1,3)-\u3b2-D-glucan (BDG) and procalcitonin (PCT) for the differential diagnosis between candidaemia and bacteraemia in three intensive care units (ICUs) in two large teaching hospitals in Italy. METHODS: From June 2014 to December 2015, all adult patients admitted to the ICU who had a culture-proven candidaemia or bacteraemia, as well as BDG and PCT measured closely to the time of the index culture, were included in the study. The diagnostic performance of BDG and PCT, used either separately or in combination, was assessed by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LR+ and LR-). Changes from pre-test probabilities to post-test probabilities of candidaemia and bacteraemia were inferred from Fagan's nomograms. RESULTS: One hundred and sixty-six patients were included, 73 with candidaemia (44%) and 93 with bacteraemia (56%). When both markers indicated candidaemia (BDG 6580 pg/ml and PCT <2 ng/ml) they showed higher PPV (96%) compared to 79% and 66% for BDG or PCT alone, respectively. When both markers indicated bacteraemia (BDG <80 pg/ml and PCT 652 ng/ml), their NPV for candidaemia was similar to that of BDG used alone (95% vs. 93%). Discordant BDG and PCT results (i.e. one indicating candidaemia and the other bacteraemia) only slightly altered the pre-test probabilities of the two diseases. CONCLUSIONS: The combined use of PCT and BDG could be helpful in the diagnostic workflow for critically ill patients with suspected candidaemia

Glucokinase Gene Mutations: Structural and Genotype-Phenotype Analyses in MODY Children from South Italy

BACKGROUND: Maturity onset diabetes of the young type 2 (or GCK MODY) is a genetic form of diabetes mellitus provoked by mutations in the glucokinase gene (GCK). METHODOLOGY/PRINCIPAL FINDINGS: We screened the GCK gene by direct sequencing in 30 patients from South Italy with suspected MODY. The mutation-induced structural alterations in the protein were analyzed by molecular modeling. The patients' biochemical, clinical and anamnestic data were obtained. Mutations were detected in 16/30 patients (53%); 9 of the 12 mutations identified were novel (p.Glu70Asp, p.Phe123Leu, p.Asp132Asn, p.His137Asp, p.Gly162Asp, p.Thr168Ala, p.Arg392Ser, p.Glu290X, p.Gln106_Met107delinsLeu) and are in regions involved in structural rearrangements required for catalysis. The prevalence of mutation sites was higher in the small domain (7/12: approximately 59%) than in the large (4/12: 33%) domain or in the connection (1/12: 8%) region of the protein. Mild diabetic phenotypes were detected in almost all patients [mean (SD) OGTT = 7.8 mMol/L (1.8)] and mean triglyceride levels were lower in mutated than in unmutated GCK patients (p = 0.04). CONCLUSIONS: The prevalence of GCK MODY is high in southern Italy, and the GCK small domain is a hot spot for MODY mutations. Both the severity of the GCK mutation and the genetic background seem to play a relevant role in the GCK MODY phenotype. Indeed, a partial genotype-phenotype correlation was identified in related patients (3 pairs of siblings) but not in two unrelated children bearing the same mutation. Thus, the molecular approach allows the physician to confirm the diagnosis and to predict severity of the mutation

Direct and indirect costs of immunoglobulin replacement therapy in patients with common variable immunodeficiency (CVID) and X-Linked agammaglobulinemia (XLA) in Italy

In Italy, there is scarce evidence on the epidemiological and economic burden induced by primary antibody deficiencies

Asthma, atopy and airway inflammation in obese children.

The concurrent increased prevalence of asthma and obesity in adults as well in children has led investigators to consider a possible correlation between the 2 conditions. However, mechanisms underlying this association have not been completely explained.1 A recent study of a large population-based cohort assessed at age 32 years showed that adiposity is associated with asthma and airflow obstruction in women but not in men.2 The authors also demonstrated the absence of a significant association between body fat and airway inflammation in both sexes. Results suggested that being overweight or obese might cause asthma symptoms and airflow limitation in women. Nevertheless, this was not likely originated by an increase in airway inflammation. These findings encouraged us to develop a pilot study aimed at exploring the association among adiposity and asthma symptoms, lung function, atopy, and airway inflammation, as indicated by exhaled nitric oxide (eNO) levels in a group of obese children. Patients were recruited from those attending the Obesity Unit, Department of Pediatrics, Federico II University, Naples, Italy. The patients consisted of 50 children with a body mass index (BMI) >95th percentile for age and sex reference values [28 males; median age, 12.2 years (range, 8-16.8); 34 showing signs of initial or advanced pubertal stage]. A questionnaire was administered to patients and their families to obtain information about any physiciandiagnosed respiratory disease. Atopy was defined as a positive response to 1 or more aeroallergens during skin prick testing. Median FEV1 (% predicted), and percent change in FEV1 after albuterol were obtained. We measured eNO by the single-breath on-line method (NIOX, Aerocrine, Sweden). Patients had not had asthma or rhinitis symptoms or signs, nor did they take inhaled or nasal steroids in the 4 weeks prior to the study. No patient was an active smoker. We also measured eNO levels in 50 age- and sex-matched healthy nonatopic controls. The BMI z score was computed in both obese and healthy children. Because eNO distribution was skewed, analyses were performed with log-transformed data. Comparisons were made using the Student t test. A stepwise regression analysis evaluated the contribution to eNO of all subjectspecific variables in obese children, including age, sex, BMI, BMI z score, FEV1, atopy, and asthma. The level of significance was determined asP<.05. The Institutional Review Board approved the study, and informed consent was obtained from the parent or legal guardian of each child. In obese children, median BMI and BMI z scores were 34.5 kg/m2 (range, 23-54.7) and 2.51 (range, 1.81-4.08), respectively. Fifty-four percent and 42% of the cases were classified as severely or moderately obese because they had a BMI z score 2.5 or 2, respectively.3 Eighteen (36%) and 11 (22%) children had previously received a diagnosis of asthma or seasonal rhinitis, respectively. Among subjects with asthma, 6 (12% of the whole population) had current asthma defined as physician-diagnosed asthma in the previous year. Skin prick test results were positive in 29 cases (58%). Thirteen atopic children had asthma. In all obese children, median FEV1 and percent change in FEV1 after albuterol were 114% predicted (range, 81-168) and 4% (range, 28.8-13.1), respectively. In healthy controls, median BMI and BMI z scores were 18.9 kg/m2 (range, 14.6-24.6) and 0.46 (21.58-1.61), respectively. In obese children, eNO geometric mean (95% CI) was 12.5 ppb (10.4-15.1) and did not appear significantly different from eNO levels of healthy controls [10.8 ppb (9.6-12.2); P 5 .2; 95% CI of the difference, 20.03-0.2]. No significant difference in eNO was found in obese children with a BMI z score <2.5 or 2.5 [12.8 ppb (9.4- 17.3) vs 12.3 ppb (9.7-15.8); P 5 .8; 95% CI of the difference, 0.7-1.5]. In obese children,eNOwas not significantly different between boys and girls [13 ppb (10.2-16.7) vs 11.9 ppb (8.8-16.2); P 5 .6; 95% CI of the difference, 0.7-1.6], between asthmatics and nonasthmatics [11.6 ppb (7.8-17.2) vs 13.1 ppb (10.7-16.1); P 5 .5; 95% CI of the difference, 0.6-1.3], and between atopic and nonatopic subjects [12.3 ppb (9.6-15.9) vs 12.8 ppb (9.5-17.3); P5.8;95%CI of the difference, 0.7-1.4], respectively (Fig 1). In the 13 children with atopic asthma, eNO was not significantly different from the remaining 37 subjects [14.8 ppb (9.3-23.5) vs 11.8 (9.7-14.5);P5.3;95%CI of the difference, 0.8-1.9]. No differences in BMI were found between asthmatics and nonasthmatics [35.2 kg/m2 (range, 24.1-42.1) vs 33.2 kg/m2 (range, 23-54.7); P 5 .6; 95% CI of the difference, 24.8-2.6], and between atopic and nonatopic subjects [34.4 kg/m2 (range, 23-54.7) vs 34.9 kg/m2 (range, 25.5-42.3); P5.6; 95% CI of the difference, 22.7-4.8]. The BMI z score was not different between asthmatics and nonasthmatics [2.49 (range, 1.81-2.83) vs 2.52 (range, 2.05-4.08); P 5 .1; 95% CI of the difference, 20.4-0.05] and between atopic and nonatopic patients [2.53 (range, 1.81-4.08) vs 2.5 (range, 2.09-2.95); P 5 .7;95%CI of the difference,20.2-0.2]. In the linear regression model, none of the subject-specific variables (age, sex, BMI, BMI z score, FEV1, atopy, and asthma) showed a significant association with eNO (P > .05)

RB137 recognizes LL37 in neutrophil-extracellular trap-like (NET) structures in systemic lupus erythematosus and rheumatoid arthritis inflamed tissues by immunofluorescence in histological sections

Besides being a natural antibiotic, the human cathelicidin LL37, produced by epithelial cells and neutrophils, is an important immune-modulator. LL37 alone, or in complex with DNA, can activate inflammatory pathways in psoriasis, Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). In this work, we describe the capacity of the recombinant monoclonal antibody RB137, previously shown to specifically recognize LL37 in its native form by ELISA, to detect LL37 by immunofluorescence in human tissues derived from SLE and RA patients. In these tissues, LL37 decorates DNA filaments resembling neutrophil-extracellular-trap (NET) structures. This antibody represents a valuable tool to detect the presence, the native state and the exact localization of LL37 in human tissues in health and disease