19 research outputs found
Adrenarche in patients with central precocious puberty: Influence on growth parameters before and during GnRH-Analog therapy
No full textObjective: the aims of this study were to evaluate the relationship between
adrenarche and central precocious puberty (CPP) and the influence of the
adrenarche upon skeletal maturation and growth parameters of patients with
CPP during GnRH-A therapy.
Patients and methods: 40 patients (37 F, 3M) with CPP were studied before
and during 2-4 years of GnRH-A therapy. Mean age at onset of CPP and at
the start of GnRH-A therapy were 6.35±1.78 yrs and 7.7±1.6 yrs, respectively.
The plasma DHEA-S levels at a concentration > 0.60 mcg/ml were used as a
hormonal marker of adrenarche.
Results: Before GnRH-A therapy 30 out of 40 patients aged 7.33±1.7 yrs had
a preadrenarcheal DHEA-S levels that were similar to those of prepubertal
age-matched controls, the remaining 10 patients older than 7 yrs (8.27±0.84
yrs) showed adrenarcheal DHEA-S levels that were similar to those of normal
pubertal children. Before therapy the adrenarcheal children didn’t show significant
differences in growth parameters and bone age (BA) compared with
preadrenarcheal patients, in the former the BMI SDS tended to be higher than
in the latter but not significantly (1.92±1.84 vs 1.35±1.81). During gonadal
suppression, the improvement in predicted adult height and in CA /BA ratio
induced by GnRH-A therapy was not significantly different in adrenarcheal
and preadrenarcheal patients.
Conclusion: The results of this study show that adrenarche was present only
in patients with onset of CPP after 7 years of age. This finding may suggest
that the onset of CPP was independent of activation of adrenal androgens in
young patients. The adrenarcheal children didn‘t show growth parameters and
bone age maturation different from those without adrenarche. Moreover, the
increased adrenal DHEA-S production at the diagnosis of CPP didn‘t restrain
the beneficial effects of GnRH-A therapy on bone age and predicted adult
height of our CPP patients
Influenza dell’adrenarca sui parametri auxologici e sull’età ossea in pazienti con pubertà precoce centrale prima e durante terapia con analoghi dl GnRH.
No full textThe influence of adrenarche on bone age and final height prediction of patients with central precocious puberty before and during GnRH analog therapy
No full textThe aim of this study was to evaluate the onset or adrenarche in patients with central precocious puberty (CPP) and to determine whether adrenarche may counteract the effect on growth and skeletal maturation of GnRH analog (GnRHa) therapy in patients with CPP. Forty patients (39 F, 1 M) with CPP were studied before and during GnRHa therapy. Mean age at the initial evaluation and at the start of GnRHa therapy were 7.57 +/- 1.58 and 7.73 +/- 1.60 years, respectively. DHEA-S serum levels >0.60 mu g/ml were used as a hormonal marker of adrenarche. Before GnRHa therapy, 30 out of 40 patients had pre-adrenarcheal DHEA-S levels that were similar to those of prepubertal age-matched controls; the other 10 patients older than 7 years (8.27 +/- 0.84 years) showed adrenarcheal DHEA-S levels that were similar to those of normal pubertal children. Before GnRHa therapy, the children with adrenarche did not show significant differences in height SDS, bone age (BA) advance and predicted adult height compared with pre-adrenarcheal patients; in the former BMI SDS tended to be higher than in the latter, but not significantly. During GnRHa therapy, the improvement in predicted adult height and in CA/BA ratio was not significantly different in drenarcheal and pre-adrenarcheal patients. However, in two girls who manifested exaggerated adrenarche (DHEA-S values >1.2 mu g/ml) during GnRHa therapy, the BA progressed more rapidly the year after the elevation of DHEA-S, and the predicted adult height was reduced in both patients, by 4 cm and 6 cm, respectively. In conclusion, this study shows that young patients with CPP do not exhibit adrenarche; DHEA-S elevation was found only in patients with onset of CPP after 7 years of age. Patients with CPP and adrenarche did not show any difference in clinical characteristics and BA advance from the pre-adrenarcheal patients before and during GnRHa therapy. On the contrary, exaggerated adrenarche, with DHEA-S values higher than is typical, may reduce the efficacy of GnRHa therapy on growth and skeletal maturation
National Institute for the Infectious Diseases “L. Spallanzani” IRCCS. Recommendations for COVID-19 Clinical Management
No full textOn January 9th, 2020, the “World Health Organization” (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a diseases (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9th, 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The “L. Spallanzani” National Institute for the Infectious Diseases, IRCCS has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; these recomendations should be considered as expert opinions, which may be modified according to newly produced literature data. *for the INMI COVID-19 Treatment Group – ICOTREG Abdeddaim A, Agrati C, Albarello F, Antinori A, Ascoli Bartoli T, Baldini F, Bellagamba R, Bevilacqua N, Bibas M, Biava G, Boumis E, Busso D, Camici M, Capobianchi MR, Capone A, Caravella I, Cataldo A, Cerilli S, Chinello G, Cicalini S, Corpolongo A, Cristofaro M, D’Abramo A, Dantimi C, De Angelis G, De Palo MG, D’Offizi G, De Zottis F, Di Lorenzo R, Di Stefano F, Fusetti M, Galati V, Gagliardini R, Garotto G, Gebremeskel Tekle Saba, Giancola ML, Giansante F, Girardi E, Goletti D, Granata G, Greci MC, Grilli E, Grisetti S, Gualano G, Iacomi F, Iannicelli G, Ippolito G, Lepore L, Libertone R, Lionetti R, Liuzzi G, Loiacono L, Macchione M, Marchioni L, Mariano A, Marini MC, Maritti M, Mastrobattista A, Mazzotta V, Mencarini P, Migliorisi-Ramazzini P, Mondi A, Montalbano M, Mosti S, Murachelli S, Musso M, Nicastri E, Noto P, Oliva A, Palazzolo C, Palmieri F, Pareo C, Petrone A, Pianura E, Pinnetti C, Pontarelli A, Puro V, Rianda A, Rosati S, Sampaolesi A, Santagata C, Scarcia D’Aprano S, Scarabello A, Schininà V, Scorzolini L, Stazi GV, Taibi C, Taglietti F, Tonnarini R, Topino S, Vergori A, Vincenzi L, Visco-Comandini U, Vittozzi P, Zaccarelli M, Zaccaro G
The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex
No full textImpact of new DAA therapy on real clinical practice: A multicenter region-wide cohort study
No full textBackground: Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. Methods: The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient's level and random slope at the level of the time; i.e. either before or after therapy. Results: Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient's baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. Conclusion: Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis
Profiling BRCA1-BRCT interactions and their functional relevance at amino acid resolution
No full textBRCA1 (breast cancer-associated protein 1) plays a central role in homologous recombination (HR) through interactions with multiple proteins across its various domains. The C-terminal BRCT domains bind HR regulators such as ABRAXAS1, CtIP, and BRIP1, each contributing to distinct, sometimes opposing, functions. While pathogenic mutations frequently cluster within the canonical BRCT phospho-binding pocket, the broader mutational landscape and its functional consequences remain poorly understood. Here, we used a site-saturation mutagenesis library of the BRCT domains to test >4,000 single-residue variants for their ability to bind ABRAXAS1 and CtIP. Using a yeast two-hybrid screen, we systematically assessed these interactions and validated key findings in mammalian cells. The resulting interaction map identified previously uncharacterized residues critical for partner binding and demonstrated their detrimental impact on HR. Importantly, we identified separation-of-function mutations that selectively disrupt individual protein interactions, enabling a more detailed analysis of each partner's contribution to HR. Functional assays suggested that disruption of CtIP binding had the most pronounced impact on HR. Furthermore, integration of our data with clinical variant data revealed a strong correlation between loss of protein binding and pathogenicity, highlighting the potential utility of our interaction map for clinical variant interpretation.[GRAPHICS]Genome Instability and CancerMolecular Technology and Informatics for Personalised Medicine and Healt
