Obesità e carcinoma differenziato della tiroide: relazione tra indice di massa corporea e presentazione di malattia

Nelle ultime tre decadi si è registrato un aumento parallelo dell’incidenza dell’obesità e del carcinoma differenziato della tiroide (CDT). Questa osservazione ha suscitato interesse nella comunità scientifica, e sono stati condotti diversi studi che hanno dimostrato l’esistenza di una associazione positiva, modesta ma significativa, tra indice di massa corporea (IMC) e rischio di CDT. Il nostro studio si propone di indagare la relazione tra obesità e aggressività alla presentazione del CDT. A tal fine abbiamo condotto un’analisi retrospettiva su una serie consecutiva di 619 pazienti affetti da CDT valutati presso l’U.O. di Endocrinologia 1 dell’Azienda Ospedaliera Universitaria Pisana nel biennio 2010-2011. Abbiamo suddiviso i pazienti del nostro gruppo di studio in tre categorie secondo il loro IMC (normopeso, sovrappeso e obesi) e abbiamo esaminato diversi parametri clinico-patologici di presentazione del tumore, quali l’istologia, le dimensioni, la focalità, le metastasi linfonodali all’istologia, lo stadio TNM, il rischio istologico secondo la classificazione ATA 2009, l’ecografia post-chirurgica, la dose di radioiodio somministrato e la scintigrafia totale corporea post I131. I risultati delle nostre analisi non hanno mostrato alcuna differenza significativa di queste caratteristiche di presentazione tra le categorie di peso. In conclusione, nel nostro gruppo di studio un più alto indice di massa corporea non correla con una maggiore aggressività di presentazione

Poor adherence during adolescence is a risk factor for becoming lost-to-follow-up in patients with phenylketonuria

Purpose: A high rate of lost to follow-up (LTFU) in patients with phenylketonuria (PKU) represents a main challenge. In this study, we investigated potential risk factors for becoming LTFU related to adolescence as a critical period of life. Methods: We retrospectively analyzed longitudinal data collected from 1993 to 2019 of patients diagnosed with classic PKU that were followed at our center during adolescence (14–18 y) and at least once in adulthood (>18 y). Patients who interrupted their contact with our center after the 18th birthday for at least 2 years were classified as LTFU. We performed a multivariate regression analysis to investigate following potential risk factors for becoming LTFU in adult life: sex, dietary compliance during adolescence assessed through the mean of the annual medians of phenylalanine plasma values, average number of contacts with the center during adolescence and age at first visit after the 18th birthday. Results: 93 patients (52 males, 41 females) were included in the study. 58% became LTFU during adulthood. The mean age at the last visit before becoming LTFU was 26.2 ± 5.1 years. In the multivariate Cox regression analysis we found that poor dietary compliance during adolescence was significantly associated with a higher risk of becoming LTFU during adulthood (p-value = 0.028). Discussion: Adult patients who displayed poor treatment adherence during adolescence should be identified and carefully monitored to prevent loss of contact

Potential impact of BMI on the aggressiveness of presentation and clinical outcome of Differentiated Thyroid Cancer

BACKGROUND: Obesity is a risk factor for several cancers, including differentiated thyroid cancer (DTC). Moreover, it has also been investigated as a potential risk factor for aggressiveness of DTC, but the data gathered so far are conflicting. The aim of our study was to evaluate the relationship between body mass index (BMI), aggressiveness of DTC at diagnosis, and clinical outcome. METHODS: We evaluated 1058 consecutive DTC patients treated with total thyroidectomy and enrolled at the time of first radioactive iodine (131I) treatment. Patients were divided into 4 groups based on their BMI: underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2). Histological aggressiveness of DTC at the time of diagnosis and clinical outcome according to 2015 American Thyroid Association (ATA) guidelines were evaluated. RESULTS: No differences in histological features, ATA risk of recurrence, activity of 131I administered and prevalence of 131I avid metastatic disease after first131I treatment, have been demonstrated among the groups. Furthermore, at the end of follow up (median = 5.7 years), no differences were evident in the number of further treatments performed as well as in the clinical response. CONCLUSIONS: In our study group of Caucasian subjects, we could not demonstrate any association between BMI and aggressiveness of DTC, neither at the time of diagnosis nor during follow-up. These data indicate that postsurgical assessment and therapeutic attitude for treatment and follow-up of DTC should be based on the class of risk applied to the general population, with no concern for BMI

Serum IGF1 and linear growth in children with congenital leptin deficiency before and after leptin substitution

Background!#!Evidence from in vitro and rodent studies suggests that leptin, a key signal of long-term energy reserves, promotes IGF1 synthesis and linear growth. This effect of leptin has not been fully investigated in humans. The aim of our study was to investigate the effect of leptin substitution on growth factors and linear growth in children with congenital leptin deficiency (CLD).!##!Methods!#!In this cohort study we included eight pediatric patients (six males), age 0.9-14.8 years, who were diagnosed with CLD and received leptin substitution at our University Medical Center. We calculated standard deviation scores (SDS) for serum levels of IGF1 and IGFBP3, IGF1/IGFBP3 molar ratio, and height at baseline (T0) and 12 months (T12) after the initiation of substitution with metreleptin.!##!Results!#!All patients had severe obesity (BMI-SDS mean ± SD: 4.14 ± 1.51) at T0 and significant BMI-SDS reduction to 2.47 ± 1.05 at T12. At T0, all patients were taller than the mid-parental median, yet had low IGF1 and IGF1/IGFBP3 molar ratios (IGF1-SDS[Formula: see text]!##!Conclusions!#!These results in CLD patients are contrary to observations in children with idiopathic obesity who typically have above-mean IGF1 levels that decrease with weight loss, and therefore suggest that leptin increases IGF1 levels and promotes linear growth

2024 update in heart failure

In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article

Proceedings of the annual meeting of the European Consortium of Lipodystrophies (ECLip), Pisa, Italy, 28–29 September 2023

Lipodystrophy syndromes are rare diseases primarily affecting the development or maintenance of the adipose tissue but are also distressing indirectly multiple organs and tissues, often leading to reduced life expectancy and quality of life. Lipodystrophy syndromes are multifaceted disorders caused by genetic mutations or autoimmunity in the vast majority of cases. While many subtypes are now recognized and classified, the disease remains remarkably underdiagnosed. The European Consortium of Lipodystrophies (ECLip) was founded in 2014 as a non-profit network of European centers of excellence working in the field of lipodystrophies aiming at promoting international collaborations to increase basic scientific understanding and clinical management of these syndromes. The network has developed a European Patient Registry as a collaborative research platform for consortium members. ECLip and ECLip registry activities involve patient advocacy groups to increase public awareness and to seek advice on research activities relevant from the patients perspective. The annual ECLip congress provides updates on the research results of various network groups members

Metabolic and other morbid complications in congenital generalized lipodystrophy type 4

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346–3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias