Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

Rheumatic immune- and nonimmune-related adverse events in phase 3 clinical trials assessing PD-(L)1 checkpoint inhibitors for lung cancer: a systematic review and meta-analysis

International audienceWe aimed to analyze rheumatic immune-related (ir) and nonimmune-related adverse events (AEs) due to immune-checkpoint inhibitors (ICIs) targeting programmed cell death-1 or its ligand PD-(L)1 in lung cancer patients from the available literature

Organisational models supported by technology for the management of diabetic disease and its complications in a diabetic clinic setting: study protocol for a randomised controlled trial targeting type 2 diabetes individuals with non-ideal glycaemic values (Telemechron study)

Introduction: Type 2 diabetes mellitus (T2DM) is a non-communicable disease representing one of the most serious public health challenges of the twenty-first century. Its incidence continues to rise in both developed and developing countries, causing the death of 1.5 million people every year. The use of technology (e.g. smartphone application-App) in the health field has progressively increased as it has been proved to be effective in helping individuals manage their long-term diseases. Therefore, it has the potential to reduce the use of health service and its related costs. The objective of this study is to evaluate the impact of using a digital platform called "TreC Diabete" embedded into a novel organisational asset targeting poorly controlled T2DM individuals in the Autonomous Province of Trento (PAT), Italy. Methods: This trial was designed as a multi-centre, open-label, randomised, superiority study with two parallel groups and a 1:1 allocation ratio. Individuals regularly attending outpatient diabetes clinics, providing informed consent, are randomised to be prescribed TreC Diabete platform as part of their personalised care plan. Healthcare staff members will remotely assess the data shared by the participants through the App by using a dedicated online medical dashboard. The primary end-point is the evaluation of the Hb1Ac level at 12-month post-randomisation. Data will be analysed on an intention-to-treat (ITT) basis. Discussion: This trial is the first conducted in the PAT area for the use of an App specifically designed for individuals with poorly controlled T2DM. If the effects of introducing this specific App within a new organisational asset are positive, the digital platform will represent a possible way for people diagnosed with T2DM to better manage their health in the future. Results will be disseminated through conferences and peer-reviewed journals once the study is completed. Trial registration: ClinicalTrials.gov NCT05629221. Registered on November 29, 2022, prior start of inclusion