International Multicenter Validation Study of the SAGIT® Instrument in Acromegaly.

Abstract Context The SAGIT® instrument (SAGIT) has been developed to enable accurate characterization of acromegaly disease activity. Objective We evaluated the ability of SAGIT to discriminate acromegaly disease control status. Methods This multicenter, noninterventional, prospective and retrospective, longitudinal study, conducted at academic and private clinical practice sites, included patients aged ≥ 18 years with a diagnosis of controlled (n = 109) or non-controlled (n = 105) acromegaly, assessed by clinical global evaluation of disease control (CGE-DC) questionnaire, investigator therapeutic decision, and international guidelines. Control status was not determined at baseline for 13 patients. Since 9 patients were enrolled retrospectively, all presented analyses are based on the prospective population (N = 227). Patients were assessed over a 2-year follow-up period. Classification and regression tree (CART) analyses were performed to investigate how SAGIT components at baseline (signs/symptoms [S], associated comorbidities [A], growth hormone levels [G], insulin-like growth factor 1 levels [I], tumor features [T]) discriminate between controlled and non-controlled acromegaly. Results Baseline mean subscores S, G, I, and T were significantly lower in patients with CGE-DC controlled vs CGE-DC non-controlled acromegaly. SAGIT components I and G for CGE-DC and S, A, G, I, and T for the clinician's therapeutic decision were retained by CART analyses. For international guidelines, only SAGIT component I was retained. The risk for undergoing ≥ 1 treatment change during the study was 3.44 times greater for CGE-DC non-controlled acromegaly relative to CGE-DC controlled acromegaly. Conclusion The SAGIT instrument is a valid and sensitive tool to comprehensively and accurately assess acromegaly severity

Frequency and Predictive Factors of Hypoglycemia in Patients Treated With rhIGF-1: Data From the Eu-IGFD Registry

The European Increlex® Growth Forum Database (Eu-IGFD) is an ongoing surveillance registry (NCT00903110) established to collect long-term safety and effectiveness data on the use of recombinant human insulin-like growth factor-1 (rhIGF-1, mecasermin, Increlex) for the treatment of children/adolescents with severe primary insulin-like growth factor-1 deficiency (SPIGFD). Objective: This analysis of Eu-IGFD data aimed to identify the frequency and predictive factors for hypoglycemia adverse events (AEs) in children treated with rhIGF-1. Methods: Data were collected from December 2008 to May 2021. Logistic regression was performed to identify predictive risk factors for treatment-induced hypoglycemia AEs. Odds ratios (ORs) are presented with 95% CIs for each factor. Results: In total, 306 patients were enrolled in the registry; 84.6% were diagnosed with SPIGFD. Patients who experienced ≥ 1 hypoglycemia AE (n = 80) compared with those with no hypoglycemia AEs (n = 224) had a lower mean age at treatment start (8.7 years vs 9.8 years), a more frequent diagnosis of Laron syndrome (27.5% vs 10.3%), and a history of hypoglycemia (18.8% vs 4.5%). Prior history of hypoglycemia (OR 0.25; 95% CI: [0.11; 0.61]; P = .002) and Laron syndrome diagnosis (OR 0.36; 95% CI: [0.18; 0.72]; P = .004) predicted future hypoglycemia AEs. Total hypoglycemia AEs per patient per treatment year was 0.11 and total serious hypoglycemia AEs per patient per treatment year was 0.01. Conclusion: Hypoglycemia occurs more frequently in patients with prior history of hypoglycemia and/or Laron syndrome compared with patients without these risk factors, and these patients should be carefully monitored for this AE throughout treatment

Effects of lanreotide Autogel primary therapy on symptoms and quality-of-life in acromegaly : data from the PRIMARYS study

To evaluate the effects of lanreotide Autogel on patient-reported outcomes and association with biochemical control, using PRIMARYS data. PRIMARYS was a 1-year, open-label study of lanreotide Autogel (Depot in USA) 120 mg every 4 weeks in 90 treatment-naïve patients with acromegaly. Symptoms were assessed using Patient-assessed Acromegaly Symptom Questionnaire (PASQ) and health-related quality of life (HRQoL) using the AcroQoL questionnaire. Correlations between PASQ and AcroQoL scores, and between PASQ/AcroQoL and growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels were also evaluated (post hoc). Acromegaly symptoms and HRQoL significantly improved from week 12 to week 48, with modest correlations at week 48 between PASQ total score (R = -0.55, p 50 % of baseline standard deviation) in PASQ total score and >40 % achieved a MID in AcroQoL global score (post hoc). Changes in PASQ scores were similar in biochemically controlled (GH levels ≤2.5 μg/L and normal IGF-1 levels) and uncontrolled groups, while changes in global and psychological AcroQoL scores were greater in the controlled group. There was no correlation between changes in PASQ or AcroQoL scores and changes in GH or IGF-1 levels. Primary treatment with lanreotide Autogel over 1 year was associated with rapid and sustained improvements in clinical signs and symptoms and HRQoL in patients with acromegaly. Improvements in HRQoL, but not symptoms, were greater in those achieving biochemical control (ClinicalTrials.gov: NCT00690898; EudraCT: 2007-000155-34). The online version of this article (doi:10.1007/s11102-015-0693-y) contains supplementary material, which is available to authorized users

Lanreotide Autogel 120 mg at extended dosing intervals in patients with acromegaly biochemically controlled with octreotide LAR: The LEAD study

Objective: To evaluate extended dosing intervals (EDIs) with lanreotide Autogel 120 mg in patients with acromegaly previously biochemically controlled with octreotide LAR 10 or 20 mg. Design and methods: Patients with acromegaly had received octreotide LAR 10 or 20 mg/4 weeks for R6 months and had normal IGF1 levels. Lanreotide Autogel 120 mg was administered every 6 weeks for 24 weeks (phase 1); depending on week-24 IGF1 levels, treatment was then administered every 4, 6 or 8 weeks for a further 24 weeks (phase 2). Hormone levels, patient-reported outcomes and adverse events were assessed. Primary endpoint: proportion of patients on 6- or 8-week EDIs with normal IGF1 levels at week 48 (study end). Results: 107/124 patients completed the study (15 withdrew from phase 1 and two from phase 2). Of 124 patients enrolled, 77.4% were allocated to 6- or 8-week EDIs in phase 2 and 75.8% (95% CI: 68.3-83.3) had normal IGF1 levels at week 48 with the EDI (primary analysis). A total of 88.7% (83.1-94.3) had normal IGF1 levels after 24 weeks with 6-weekly dosing. GH levels were ≤2.5 mg/l in >90% of patients after 24 and 48 weeks. Patient preferences for lanreotide Autogel 120 mg every 4, 6 or 8 weeks over octreotide LAR every 4 weeks were high. Conclusions: Patients with acromegaly achieving biochemical control with octreotide LAR 10 or 20 mg/4 weeks are possible candidates for lanreotide Autogel 120 mg EDIs. EDIs are effective and well received among such patients

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe