Effectiveness and Safety of Flexible Therapeutic Schemes Including First- and Secondgeneration Basal Insulins during a Pediatric Summer Diabetes Camp

Outcomes of insulin analogues in pediatric diabetes camps are poorly investigated; no data is available about insulin degludec (IDeg).Our aim was to assess impact of insulin therapy adopted by the participants to a 4-day diabetes camp held in 2017, hypothesizing a possible excess risk of hypoglycemia in patients treated with IDeg. Overall, 40 children with type 1 diabetes (mean age 13.4±3.0 years; 62.5% males) attended the camp (20.0% on continuous subcutaneous insulin infusion and 80.0% on multiple daily injections - MDI). Among children in MDI regimen, 71.9% were treated with IDeg as basal insulin and 28.1% with glargine U100 (IGlar). All patients used Lispro or Aspart as short-acting insulin. Daily plan of the camp included educational sessions, physical exercise, 3 main meals and 2 snacks. At the arrival, IGlar and short-acting insulin doses were revised according to existing guidelines, while IDeg dose was revised based on an empirical individualized approach. At the arrival, insulin doses were reduced in 22 participants (-19.4±10.5%), while doses were increased in 17 children (+17.8±12.7%), based on individual needs. No statistically significant between-group difference emerged in mean blood glucose and glucose variability. No excess risk of hypoglycemia was found in the IDeg group. The study suggests similar effectiveness and safety of different insulin schemes when associated with appropriate diabetes education and management, and flexible dose adjustments. Despite its longer halflife and the lack of a validated algorithm, IDeg was not associated with an excess risk of hypoglycemia

Novel tricyclic pyrrolo-quinolines as pharmacological correctors of the mutant CFTR chloride channel

Abstract F508del, the most frequent mutation in cystic fibrosis (CF), impairs the stability and folding of the CFTR chloride channel, thus resulting in intracellular retention and CFTR degradation. The F508del defect can be targeted with pharmacological correctors, such as VX-809 and VX-445, that stabilize CFTR and improve its trafficking to plasma membrane. Using a functional test to evaluate a panel of chemical compounds, we have identified tricyclic pyrrolo-quinolines as novel F508del correctors with high efficacy on primary airway epithelial cells from CF patients. The most effective compound, PP028, showed synergy when combined with VX-809 and VX-661 but not with VX-445. By testing the ability of correctors to stabilize CFTR fragments of different length, we found that VX-809 is effective on the amino-terminal portion of the protein that includes the first membrane-spanning domain (amino acids 1–387). Instead, PP028 and VX-445 only show a stabilizing effect when the second membrane-spanning domain is included (amino acids 1–1181). Our results indicate that tricyclic pyrrolo-quinolines are a novel class of CFTR correctors that, similarly to VX-445, interact with CFTR at a site different from that of VX-809. Tricyclic pirrolo-quinolines may represent novel CFTR correctors suitable for combinatorial pharmacological treatments to treat the basic defect in CF

Is growth-discordance in twins a substantial risk factor in adverse neonatal outcomes?

To evaluate whether growth discordance is an independent risk factor in the neonatal outcome of the smaller twin, all medical records of twin pregnancies delivered between 26 and 41 weeks during a 5-year period (January 2004-December 2008) were reviewed. Among the 49 selected twins, weight discordance was 15-20% in 7 infants, 21-30% in 16 infants, 31-40% in 16 infants and > 40% in 10 infants. No significant differences between the four groups were found with regards to obstetric complications and neonatal disease. Occurrence of birthweight below the 10th percentile and rate of admission to the neonatal intensive care unit significantly increased as intra-pair birthweight difference increased (p = .03). The > 40% discordant group had a significantly lower gestational age (p = .03), lower birthweight (p = .007) and a significantly higher mortality rate (4/10 versus 3/39 p = .04) in comparison with the other discordant groups. Multiple logistic regression analysis showed that birthweight was the single independent and consistent factor associated with elevated risks of mortality. For every 250 g increase in birthweight, the risk for mortality decreased by about 84% [RR 0.16(CI 0.00-0.70)]. Gestational age was the most reliable predictor for major neonatal complications. For every 1-week increase in gestational age a significant decreased risk for all outcomes was found. Discordance alone should not be considered as a predictor for adverse neonatal outcome. Neonatal outcome in discordant twins appears to be related to gestational age and birthweight rather than to the degree of discordance

SICOB-endorsed national Delphi consensus on obesity treatment optimization: focus on diagnosis, pre-operative management, and weight regain/insufficient weight loss approach

PurposeOverweight and obesity affects 60% of adults causing more than 1.2 million deaths across world every year. Fight against involved different specialist figures and multiple are the approved weapons. Aim of the present survey endorsed by the Italian Society of Bariatric Surgery (SICOB) is to reach a national consensus on obesity treatment optimization through a Delphi process.MethodsEleven key opinion leaders (KOLs) identified 22 statements with a major need of clarification and debate. The explored pathways were: (1) Management of patient candidate to bariatric/metabolic surgery (BMS); (2) Management of patient not eligible for BMS; (3) Management of patient with short-term (2 years) weight regain (WR) or insufficient weight loss (IWL); (4) Management of the patient with medium-term (5 years) WR; and (5) Association between drugs and BMS as WR prevention. The questionnaire was distributed to 65 national experts via an online platform with anonymized results.Results54 out of 65 invited panelists (83%) respond. Positive consensus was reached for 18/22 statements (82%); while, negative consensus (s20.4; s21.5) and no consensus (s11.5, s17) were reached for 2 statements, respectively (9%).ConclusionThe Delphi results underline the importance of first-line interdisciplinary management, with large pre-treatment examination, and establish a common opinion on how to properly manage post-operative IWL/WR

Gamma-glutamyltransferase, arterial remodeling and prehypertension in a healthy population at low cardiometabolic risk

International audiencePlasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and <0.05). In the view of previous evidence linking plasma GGT concentration to the level of systemic oxidative stress, our findings suggest a role of oxidative stress in subclinical arterial damage and in prehypertension, even in healthy subjects free of cardiometabolic risk. Arterial organ damage may represent the link between GGT and hypertension

Asthma in patients admitted to emergency department for COVID-19: prevalence and risk of hospitalization

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