Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years' follow-up

Objective Sarilumab is a human monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor-alpha. We assessed the long-term safety of sarilumab in patients from eight clinical trials and their open-label extensions.Methods Data were pooled from patients with rheumatoid arthritis who received at least one dose of sarilumab in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; combination group) or as monotherapy (monotherapy group). Treatment-emergent adverse events (AEs) and AEs and laboratory values of special interest were assessed.Results 2887 patients received sarilumab in combination with csDMARDs and 471 patients received sarilumab monotherapy, with mean exposure of 2.8 years and 1.7 years, maximum exposure 7.3 and 3.5 years, and cumulative AE observation period of 8188 and 812 patient-years, respectively. Incidence rates per 100 patient-years in the combination and monotherapy groups, respectively, were 9.4 and 6.7 for serious AEs, 3.7 and 1.0 for serious infections, 0.6 and 0.5 for herpes zoster (no cases were disseminated), 0.1 and 0 for gastrointestinal perforations, 0.5 and 0.2 for major adverse cardiovascular events, and 0.7 and 0.6 for malignancy. Absolute neutrophil counts <1000 cells/mm(3) were recorded in 13% and 15% of patients, respectively. Neutropenia was not associated with increased risk of infection or serious infection. Analysis by 6-month interval showed no signal for increased rate of any AE over time.Conclusion The long-term safety profile of sarilumab, either in combination with csDMARDs or as monotherapy, remained stable and consistent with the anticipated profile of a molecule that inhibits IL6 signalling.Pathophysiology and treatment of rheumatic disease

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Spectrum of pheochromocytoma in the 131 I-MIBG era

131 I-metaiodobenzylguanidine ( 131 I-MIBG) scintigraphy allows for both functional diagnosis and anatomical localization of pheochromocytoma. The spectrum of pheochromocytoma since the routine use of preoperative 131 I-MIBG scan was studied. From 1980 to 1986, a total of 34 patients were primarily diagnosed and treated at the University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A. There were 16 males and 18 females. The mean age was 38 years and 4 patients (11.8%) were under 18 years of age. Six patients (17.6%) had family history of pheochromocytoma or multiple endocrine neoplasia (MEN) II syndrome. The presenting symptoms were hypertension in 29 patients (85.3%); attacks of headache, palpitation, sweating, and flushing in 4 (11.8%), and 1 patient presented with a neck mass. Plasma catecholamines were elevated in 97% of patients while urinary catecholamines and metabolites were elevated in 93.5%. 131 I-MIBG was accurate in 82.3%, partly positive in 11.8%, and false-negative in 5.9% of patients. CT scan was accurate in 80%, partly positive in 10%, but failed to show the tumor in another 10% of patients. At operation, extraadrenal lesions were found in 38.2% of the patients and among these, one-third were extraabdominal. Multiple tumors occurred in 5 (14.7%), and bilateral adrenal lesions occurred in 4 patients (11.8%). Malignancy was diagnosed in 3 patients (8.8%) after an average follow-up period of 2 years. We conclude that the use of routine preoperative 131 I-MIBG scanning improves localization of pheochromocytoma and earlier diagnosis is possible in patients with MEN II syndrome. Multiple tumors, extraadrenal and extraabdominal lesions occur more often than commonly believed. The low rate of confirmed malignancy is probably related to the short period of follow-up. La scintigraphie à l' 131 I-MIBG permet de diagnostiquer et de localiser les phéochromocytomes. Toute la gamme de types de phéochromocytomes reconnu depuis l'utilisation préopératoire systématique de la scintigraphie à l' 131 I-MIBG est présentée. Entre 1980 et 1986, 34 patients ont été explorés et traités au Centre Médical de l'Université de Michigan, Ann Arbor, Michigan. Il y avait 16 hommes et 18 femmes. L'âge moyen était de 38 ans, et 4 patients (11.8%) avaient moins de 18 ans. Six patients (17.6%) avaient des antécédents familiaux de phéochromocytome ou de néoplasmes endocrines multiples (MEN) du type II. Les symptômes amenant à consulter étaient l'hypertension chez 29 patients (85.3%), des crises de céphalées, des palpitations et un flush chez 4 patients (11.8%); un patient présentait une masse cervicale. Les catécholamines plasmatiques étaient élevées chez 97% des patients alors que les catécholamines et leurs métabolites étaient en quantité élevée chez 93.5% des patients. La scintigraphie à l' 131 I-MIBG était positive chez 82.3%, partiellement positive chez 11.8%, et faussement négative chez 5.9% des patients. La tomodensitométrie était positive chez 80%, partiellement positive chez 10%, et faussement négative chez 10% des patients. A l'intervention, des lésions extra-surrénales étaient présentes dans 38.2% des cas, et parmi celles-ci, un tiers étaient extra-abdominales. Les tumeurs étaient multiples dans 5 cas (14.7%), et bilatérales surrénales dans 4 cas (11.8%). Une tumeur maligne était diagnostiquée chez 3 patients (8.8%), après une période de suivi de 2 ans en moyenne. Nous concluons que l'utilisation systématique de la scintigraphie à l' 131 I-MIBG améliore la localisation des phéochromocytomes, permettant un diagnostic plus précoce chez les patients présentant un syndrome MEN II. La multiplicité tumorale et les localisations extra-médullosurrénales ou extra-abdominales se voient beaucoup plus fréquemment qu'on le pensait auparavant. Le taux de malignité peu élevé était probablement en rapport avec la courte période de suivi. La escintigrafía con 131 I-MIBG permite tanto la localización anatómica como el diagnóstico funcional del feocromocitoma. Las características o espectro del feocromocitoma a partir del uso rutinario de 131 I-MIBG han sido estudiadas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41282/1/268_2005_Article_BF01655447.pd

Measurement of the mass difference between top quark and antiquark in pp collisions at root s=8 TeV

Peer reviewe

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Measurement of the charge ratio of atmospheric muons with the CMS detector

This is the pre-print version of this Article. The official published version can be accessed from the link below - Copyright @ 2010 ElsevierWe present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/c to 1 TeV/c. The surface flux ratio is measured to be 1.2766 \pm 0.0032(stat.) \pm 0.0032 (syst.), independent of the muon momentum, below 100 GeV/c. This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experiments

Observation of a new Xi(b) baryon

The first observation of a new b baryon via its strong decay into Xi(b)^- pi^+ (plus charge conjugates) is reported. The measurement uses a data sample of pp collisions at sqrt(s) = 7 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 5.3 inverse femtobarns. The known Xi(b)^- baryon is reconstructed via the decay chain Xi(b)^- to J/psi Xi^- to mu^+ mu^- Lambda^0 pi^-, with Lambda^0 to p pi^-. A peak is observed in the distribution of the difference between the mass of the Xi(b)^- pi^+ system and the sum of the masses of the Xi(b)^- and pi^+, with a significance exceeding five standard deviations. The mass difference of the peak is 14.84 +/- 0.74 (stat.) +/- 0.28 (syst.) MeV. The new state most likely corresponds to the J^P=3/2^+ companion of the Xi(b).Comment: Submitted to Physical Review Letter