Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Search for the X(5568) State Decaying into B-s(0)pi(+/-) in Proton-Proton Collisions at root s=8 TeV

A search for resonancelike structures in the B-s(0)pi(+/-) invariant mass spectrum is performed using proton-proton collision data collected by the CMS experiment at the LHC at root s = 8 TeV, corresponding to an integrated luminosity of 19.7 fb(-1). The B-s(0) mesons are reconstructed in the decay chain B-s(0) -> J/Psi phi, with J/Psi -> mu(+) mu(-) and phi -> K+K-. The B-s(0)pi(+/-) invariant mass distribution shows no statistically significant peaks for different selection requirements on the reconstructed B-s(0) and pi(+/-) candidates. Upper limits are set on the relative production rates of the X(5568) and B-s(0) states times the branching fraction of the decay X(5568)(+/-) -> B-s(0)pi(+/-). In addition, upper limits are obtained as a function of the mass and the natural width of possible exotic states decaying into B-s(0)pi(+/-).Peer reviewe

Measurements of the Upsilon(1S), Upsilon(2S), and Upsilon(3S) differential cross sections in pp collisions at root s=7 TeV

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Search for supersymmetry in the multijet and missing transverse momentum final state in pp collisions at 13 TeV

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Evidence for collectivity in pp collisions at the LHC

Measurements of two- and multi-particle angular correlations in pp collisions at s=5,7, and 13TeV are presented as a function of charged-particle multiplicity. The data, corresponding to integrated luminosities of 1.0pb−1 (5 TeV), 6.2pb−1 (7 TeV), and 0.7pb−1 (13 TeV), were collected using the CMS detector at the LHC. The second-order (v2) and third-order (v3) azimuthal anisotropy harmonics of unidentified charged particles, as well as v2 of KS0 and Λ/Λ‾ particles, are extracted from long-range two-particle correlations as functions of particle multiplicity and transverse momentum. For high-multiplicity pp events, a mass ordering is observed for the v2 values of charged hadrons (mostly pions), KS0, and Λ/Λ‾, with lighter particle species exhibiting a stronger azimuthal anisotropy signal below pT≈2GeV/c. For 13 TeV data, the v2 signals are also extracted from four- and six-particle correlations for the first time in pp collisions, with comparable magnitude to those from two-particle correlations. These observations are similar to those seen in pPb and PbPb collisions, and support the interpretation of a collective origin for the observed long-range correlations in high-multiplicity pp collisions.BMWFW and FWF (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MOST, and NSFC (China); COLCIEN-CIAS (Colombia); MSES and CSF (Croatia); RPF (Cyprus); SENESCYT (Ecuador); MoER, ERC IUT and ERDF (Estonia); Academy of Fin-land, MEC, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NIH (Hun-gary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); MSIP and NRF (Republic of Korea); LAS (Lithuania); MOE and UM (Malaysia); BUAP, CINVESTAV, CONACYT, LNS, SEP, and UASLP-FAI (Mexico); MBIE (New Zealand); PAEC (Pakistan); MSHE and NSC (Poland); FCT (Portugal); JINR (Dubna); MON, RosAtom, RAS and RFBR (Russia); MESTD (Serbia); SEIDI and CPAN (Spain); Swiss Funding Agencies (Switzerland); MST (Taipei); ThEPCenter, IPST, STAR and NSTDA (Thailand); TUBITAK and TAEK (Turkey); NASU and SFFR (Ukraine); STFC (United Kingdom); DOE and NSF (USA)

Measurement of the mass of the top quark in decays with a J/ψ meson in pp collisions at 8 TeV

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Search for neutral resonances decaying into a Z boson and a pair of b jets or tau leptons

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