Context:
Cystic fibrosis-related diabetes (CFRD) is associated with worsening of inflammation and infections, and the beginning of insulin treatment is debated.
Objectives:
To verify high-mobility ...group box 1 protein (HMGB1) levels in CF patients according to glucose tolerance state, and analyze relationships with insulin secretion and resistance. To verify, in an in vitro model, whether HMGB1 gene expression and protein content were affected by insulin administration and whether these changes were dependent on CF transmembrane conductance regulator (CFTR) loss of function.
Patients and Methods:
Forty-three patients in stable clinical conditions and 35 age- and sex-matched controls were enrolled. Glucose tolerance was established in patients based on a 5 point oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FGIR), HOMA-IR index, whole-body insulin sensitivity index (WIBISI), and the areas under the curve for glucose (AUCG) and insulin (AUCI) were calculated. HMGB1 was assayed in serum, in cell lysates and conditioned media using a specific ELISA kit. For the in vitro study we used CFBE41o− cells, homozygous for the F508del mutation, and 16HBE14o− as non-CF control. HMGB1 gene expression was studied by real-time RT-PCR. Cells were stimulated with insulin at 2.5 and 5 ng/mL. The CFTR inhibitor 172 and CFTR gene silencing were used to induce CFTR loss of function in 16HBE14o− cells.
Results:
HMGB1 levels were increased at onset of CFRD (5.04 ± 1.2 vs 2.7 ± 0.3 ng/mL in controls; P < .05) and correlated with FGIR (R = +0.43; P = .038), and AUCI (R = +0.43; P = .013). CFTR loss of function in the 16HBE14o− cells increased HMGB1 and was lowered by insulin.
Conclusion:
HMGB1 was increased in CF patients with deranging glucose metabolism and showed relationships with indexes of glucose metabolism. The increase in HMGB1 was related to CFTR loss of function, and insulin lowered HMGB1. Further research is required to verify whether HMGB1 could potentially be a candidate marker of onset of CFRD and to establish when to start insulin treatment.
•In 2022, newborn bloodspot screening (NBS) for CF is undertaken in 30 European countries, 26 of them are national programmes.•Some programmes are still not achieving ECFS standards. Compared to ...2014, there is an improvement in sensitivity but a deterioration in achieving a sufficient PPV.•There continues to be a wide variety of approaches, but the majority of national programmes are now using DNA analysis as a 2nd tier•This survey demonstrates areas of good practice, but there is considerable scope for improvement in the quality of NBS for CF across Europe.•The framework of the 20 parameters to calculate the 8 key outcomes should be part of any annual report of a CF NBS programme, and thus improve future surveys.
The aim of this study was to record the current status of newborn bloodspot screening (NBS) for CF across Europe and assess performance.
Survey of representatives of NBS for CF programmes across Europe. Performance was assessed through a framework developed in a previous exercise.
In 2022, we identified 22 national and 34 regional programmes in Europe. Barriers to establishing NBS included cost and political inertia. Performance was assessed from 2019 data reported by 21 national and 21 regional programmes. All programmes employed different protocols, with IRT-DNA the most common strategy. Six national and 11 regional programmes did not use DNA analysis.
Integrating DNA analysis into the NBS protocol improves PPV, but at the expense of increased carrier and CFSPID recognition. Some programmes employ strategies to mitigate these outcomes. Programmes should constantly strive to improve performance but large datasets are needed to assess outcomes reliably.
AbstractBackgroundShortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor ...efficiency due to protective biofilm , and short residence in the lung. MethodsEligible patients with forced expiratory volume in 1 s (FEV 1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV 1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). ResultsThe study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV 1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. ConclusionsCyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678
It is now well established that the healthy bronchial tree contains a microbiome distinct from that of the upper respiratory tract and that the lung microbiome may be dysregulated in individuals with ...a chronic respiratory disease, such as asthma. In addition, after birth, gut microbes interact with the host tissue, especially with the lymphatic tissue, thereby guaranteeing efficient immune activation. This review focuses on the available literature on the relationships between the gut microbiome, immune function and asthma in childhood, as well as the therapeutic strategies aimed at acting on the modulation of the microbiome.
My contribution focuses on three books: Female emancipation & urbanism, The metropolitan area & The urban spread. My aim is stressing the intellectual path of Achille Ardigo, who shifted from rural ...Sociology to urban Sociology. Female emancipation is considered in its several elements, & all of them are connected to urbanism; in particular, the movements from rural to urban areas are mentioned. Some elements from the Ecological Chicago School & the Talcott Parsons' theory are used as tools to deal with urbanization & urban spread trends, which were studied by Ardigo since the middle of the 1960s. Some concepts like Dominance & Planning are considered too; Ardigo used them to face the emergencies of the metropolitan area as a social system: in this case, Parsons' functional prerequisites are used as a "compass" to define such concepts, & to combine theory & empirical research. Adapted from the source document.
My contribution focuses on three books: Female emancipation and urbanism, The metropolitan area and The urban spread. My aim is stressing the intellectual path of Achille Ardigò, who shifted from ...rural Sociology to urban Sociology. Female emancipation is considered in its several elements, and all of them are connected to urbanism; in particular, the movements from rural to urban areas are mentioned. Some elements from the Ecological Chicago School and the Talcott Parsons' theory are used as tools to deal with urbanization and urban spread trends, which were studied by Ardigò since the middle of the 1960s. Some concepts like Dominance and Planning are considered too; Ardigò used them to face the emergencies of the metropolitan area as a social system: in this case, Parsons' functional prerequisites are used as a «compass» to define such concepts, and to combine theory and empirical research.
A fixed-dose inhalation of a long-acting β-agonist (LABA) and inhaled corticosteroids (ICS) is commonly recommended for moderate to severe asthmatic patients not adequately controlled by an ICS only. ...In order to improve the patients' adherence and the control of disease there is a noteworthy interest for the next generation inhaled β adrenoreceptor agonists maintaining an over 24 hours bronchodilatation and used once-daily (ultra-LABAs). This review focuses on the currently available evidences on the clinical role of any single ultra-LABAs in the treatment of asthmatic patients. Areas covered: New ultra-LABAs have been developed in recent years for the treatment of asthma. In particular, several evidences in asthmatic patients include indacaterol, vilanterol, olodaterol, and abediterol. Expert opinion: Pharmacologically, all new ultra-LABAs considered have demonstrated a good ability to maintain a true bronchodilatation for over 24 hours and a good safety profile. This aspect could be a key point to improve the patient's perspective, the adherence to the treatment regimens and therefore the control of disease. At this time, however, limited data are available and no ultra-LABA+ICS may be recommended as preferred.
Inhaled therapy is often considered the cornerstone of asthma management and international guidelines recommend combination therapy of inhaled corticosteroids (ICS) and long-acting-beta2-agonists ...(LABA) in a large proportion of asthmatic patients. The effectiveness of ICS/LABA is dependent on the correct choice of device and proper inhalation technique, this influences drug delivery and distribution along the bronchial tree, including the most peripheral airways. The fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/FF) is the only extrafine formulation available in pressurized metered dose inhaler (pMDI) and in dry powder inhaler (DPI). Here, we focus on the recent significant advances regarding BDP/FF fixed combination for the treatment of asthma.
PDF
