Beijing Children’s Hospital

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
\nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198,
\nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544,
\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
\nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007,
\nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591,
\nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930,
\nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794,
\nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727,
\nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986,
\nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409,
\nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368,
\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
\nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997,
\nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798,
\nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909,
\nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336,
\nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419,
\nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490,
\nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401,
\nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880,
\nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913,
\nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381,
\nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112,
\nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812,
\nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287,
\nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308,
\nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901,
\nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141,
\nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374,
\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
\nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217,
\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
\nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318,
\nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462,
\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

TO THE EDITOR:
\nAs of March 10, 2020, the 2019 novel coronavirus (SARS-CoV-2) has been responsible for more than 110,000 infections and 4000 deaths worldwide, but data regarding the epidemiologic characteristics and clinical features of infected children are limited.1-3 A recent review of 72,314 cases by the Chinese Center for Disease Control and Prevention showed that less than 1% of the cases were in children younger than 10 years of age.2 In order to determine the spectrum of disease in children, we evaluated children infected with SARS-CoV-2 and treated at the Wuhan Children’s Hospital, the only center assigned by the central government for treating infected children under 16 years of age in Wuhan. Both symptomatic and asymptomatic children with known contact with persons having confirmed or suspected SARS-CoV-2 infection were evaluated. Nasopharyngeal or throat swabs were obtained for detection of SARS-CoV-2 RNA by established methods.4 The clinical outcomes were monitored up to March 8, 2020.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

Primary erythermalgia is a rare autosomal dominant disease characterised by intermittent burning pain with redness and heat in the extremities. A previous study established the linkage of primary erythermalgia to a 7.94 cM interval on chromosome 2q, but the causative gene was not identified. We performed linkage analysis in a Chinese family with primary erythermalgia, and screened the mutations in the two candidate genes, SCN9A and GCA, in the family and a sporadic patient. Linkage analysis yielded a maximum lod score of 2.11 for both markers D2S2370 and D2S2330. Based on critical recombination events in two patients in the family, we further limited the genetic region to 5.98 cM between D2S2370 and D2S2345. We then identified two missense mutations in SCN9A in the family (T2573A) and the sporadic patient (T2543C). Our data suggest that mutations in SCN9A cause primary erythermalgia. SCN9A, encoding a voltage-gated sodium channel alpha subunit predominantly expressed in sensory and sympathetic neurones, may play an important role in nociception and vasomotor regulation.

Flexible wearable sweat sensors allow continuous, real-time, noninvasive detection of sweat analytes, provide insight into human physiology at the molecular level, and have received significant attention for their promising applications in personalized health monitoring. Electrochemical sensors are the best choice for wearable sweat sensors due to their high performance, low cost, miniaturization, and wide applicability. Recent developments in soft microfluidics, multiplexed biosensing, energy harvesting devices, and materials have advanced the compatibility of wearable electrochemical sweat-sensing platforms. In this review, we summarize the potential of sweat for medical detection and methods for sweat stimulation and collection. This paper provides an overview of the components of wearable sweat sensors and recent developments in materials and power supply technologies and highlights some typical sensing platforms for different types of analytes. Finally, the paper ends with a discussion of the challenges and a view of the prospective development of this exciting field.

Elucidating the mechanisms by which short chain fatty acids (SCFA) reduce body weight may assist in the development of an effective weight control strategy. Dietary supplementation of acetate, propionate, butyrate or their admixture was shown to significantly inhibit the body weight gain induced by high-fat diet feeding. Supplementation of SCFAs caused significant changes in the expressions of G-protein coupled receptor 43 (GPR43) and GPR41 characterized by increases in the adipose tissue and reductions in the colon. Additionally, they influenced the bacterial community structure in feces, with a reduction in the proportion of Firmicutes and an increase in the proportion of Bacteroidetes. The effects of dietary SCFAs on the GPR expression and gut microbiota composition may further result in body weight reduction by enhancing triglyceride hydrolysis and FFA oxidation in the adipose tissue, promoting beige adipogenesis and mitochondrial biogenesis, and inhibiting chronic inflammation.

In northern China, annual epidemics of acute-onset flaccid paralysis diagnosed clinically as Guillain-Barré syndrome have been recognized for at least 20 years. On the basis of an historical analysis of more than 3,200 patients, distinctive features include most cases occurring during the summer months among children and young adults, most of whom reside in rural areas. Of 90 patients with acute flaccid paralysis, 88 had a distinctive pattern that shares clinical and cerebrospinal fluid findings with demyelinating Guillain-Barré syndrome, but that differs from Guillain-Barré syndrome physiologically and pathologically. The clinical course is marked by rapidly progressive ascending tetraparesis, often with respiratory failure, but without fever, systemic illness, or sensory involvement. Cerebrospinal fluid is acellular, and elevations of protein content occur in the second or third week of illness. Electrodiagnostic studies show normal motor distal latencies and limb conduction velocities, but reduced compound muscle action potential amplitudes. Sensory nerve action potentials and, when elicitable, F waves are within the range of normal. Recovery is usually good. Autopsy studies have shown Wallerian-like degeneration of motor fibers. These studies establish that this is a distinctive syndrome, distinguishable from poliomyelitis and demyelinating Guillain-Barré syndrome.

The Codex Alimentarius Commission of the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) develops food standards, guidelines and related texts for protecting consumer health and ensuring fair trade practices globally. The major part of the world's population lives in more than 160 countries that are members of the Codex Alimentarius. The Codex Standard on Infant Formula was adopted in 1981 based on scientific knowledge available in the 1970s and is currently being revised. As part of this process, the Codex Committee on Nutrition and Foods for Special Dietary Uses asked the ESPGHAN Committee on Nutrition to initiate a consultation process with the international scientific community to provide a proposal on nutrient levels in infant formulae, based on scientific analysis and taking into account existing scientific reports on the subject. ESPGHAN accepted the request and, in collaboration with its sister societies in the Federation of International Societies on Pediatric Gastroenterology, Hepatology and Nutrition, invited highly qualified experts in the area of infant nutrition to form an International Expert Group (IEG) to review the issues raised. The group arrived at recommendations on the compositional requirements for a global infant formula standard which are reported here.

Thierry Wirth, Philip Supply, Stefan Niemann and colleagues analyze 4,987 Mycobacterium tuberculosis strains of the Beijing lineage isolated from 99 countries. They report whole-genome sequencing of 110 representative strains, characterize global population structure and reconstruct the evolutionary history of this lineage. Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

Background To date, no national‐scale psychiatric epidemiological survey for children and adolescents has been conducted in China. In order to inform government officials and policymakers and to develop a comprehensive plan for service providers, there was a clear need to conduct an up‐to‐date systematic nationwide psychiatric epidemiological survey. Methods We conducted a two‐stage large‐scale psychiatric point prevalence survey. Multistage cluster stratified random sampling was used as the sampling strategy. Five provinces were selected by comprehensively considering geographical partition, economic development, and rural/urban factors. In Stage 1, the Child Behavior Checklist was used as the screening tool. In Stage 2, Mini‐International Neuropsychiatric Interview for Children and Adolescents and a diagnostic process based on the Diagnostic and Statistical Manual were used to make the diagnoses. Sampling weights and poststratification weights were employed to match the population distributions. Exploratory analyses were also performed using socio‐demographic factors. Prevalence in socio‐demographic factor subgroups and overall were estimated. Rao‐Scott adjusted chi‐square tests were utilized to determine if between‐group differences were present. Factor interactions were checked by logistic regression analyses. Results A total of 73,992 participants aged 6–16 years of age were selected in Stage 1. In Stage 2, 17,524 individuals were screened and diagnosed. The weighted prevalence of any disorder was 17.5% (95% CI: 17.2–18.0). Statistically significant differences in prevalence of any psychiatric disorder were observed between sexes [χ 2 (1, N = 71,929) = 223.0, p < .001], age groups [χ 2 (1, N = 71,929) = 18.6, p < .001] and developed vs. developing areas [χ 2 (1, N = 71,929) = 2,129.6, p < .001], while no difference was found between rural and urban areas [χ 2 (1, N = 71,929) = 1.4, p = .239]. Male, younger individuals, children, and adolescents from developed areas had higher prevalence of any psychiatric disorder. The prevalence of any psychiatric disorder was found to decrease with the age in the male group, while the female group increased with the age. Individuals diagnosed with attention‐deficit hyperactivity disorder, oppositional defiant disorder, a tic disorder, conduct disorder, and major depression disorder had the highest rates of comorbidity. Conclusions The prevalence of any psychiatric disorder we found is the highest ever reported in China. These results urgently need to be addressed by public mental health service providers and policymakers in order to provide access to the necessary treatments and to reduce the long‐term negative impact of these conditions on families and the society as a whole.

OBJECTIVE: To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA). METHODS: In this multinational, multicenter study, pediatric rheumatologists and hemato-oncologists entered patient data collected retrospectively into a web-based database. RESULTS: A total of 362 patients, 22% of whom had MAS at the onset of systemic JIA, were included in the study by 95 investigators from 33 countries. The most frequent clinical manifestations were fever (96%), hepatomegaly (70%), and splenomegaly (58%). Central nervous system dysfunction and hemorrhages were recorded in 35% and 20% of the patients, respectively. Platelet count and liver transaminase, ferritin, lactate dehydrogenase, triglyceride, and d-dimer levels were the sole laboratory biomarkers showing a percentage change of >50% between the pre-MAS visit and MAS onset. Evidence of macrophage hemophagocytosis was found in 60% of the patients who underwent bone marrow aspiration. MAS occurred most frequently in the setting of active underlying disease, in the absence of a specific trigger. Nearly all patients were given corticosteroids, and 61% received cyclosporine. Biologic medications and etoposide were given to 15% and 12% of the patients, respectively. Approximately one-third of the patients required admission to the intensive care unit (ICU), and the mortality rate was 8%. CONCLUSION: This study provides information on the clinical spectrum and current management of systemic JIA-associated MAS through the analysis of a very large patient sample. MAS remains a serious condition, as a sizeable proportion of patients required admission to the ICU or died.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals in many Asian countries. Recent emergence of community-associated (CA) MRSA worldwide has added another serious concern to the epidemiology of S. aureus infections. To understand the changing epidemiology of S. aureus infections in Asian countries, we performed a prospective, multinational surveillance study with molecular typing analysis. METHODS: We evaluated the prevalence of methicillin resistance in S. aureus isolates in CA and healthcare-associated (HA) infections, and performed molecular characterization and antimicrobial susceptibility tests of MRSA isolates. RESULTS: MRSA accounted for 25.5% of CA S. aureus infections and 67.4% of HA infections. Predominant clones of CA-MRSA isolates were ST59-MRSA-SCCmec type IV-spa type t437, ST30-MRSA-SCCmec type IV-spa type t019 and ST72-MRSA-SCCmec type IV-spa type t324. Previously established nosocomial MRSA strains including sequence type (ST) 239 and ST5 clones were found among CA-MRSA isolates from patients without any risk factors for HA-MRSA infection. CA-MRSA clones such as ST59, ST30 and ST72 were also isolated from patients with HA infections. CONCLUSIONS: Our findings confirmed that MRSA infections in the community have been increasing in Asian countries. Data also suggest that various MRSA clones have spread between the community and hospitals as well as between countries.

Direct sequencing of exons 3 to 35 and the exon-intron boundaries of the CACNA1H gene was conducted in 118 childhood absence epilepsy patients of Han ethnicity recruited from North China. Sixty-eight variations have been detected in the CACNA1H gene, and, among the variations identified, 12 were missense mutations and only found in 14 of the 118 patients in a heterozygous state, but not in any of 230 unrelated controls. The identified missense mutations occurred in the highly conserved residues of the T-type calcium channel gene. Our results suggest that CACNA1H might be an important susceptibility gene involved in the pathogenesis of childhood absence epilepsy.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

A total of 685 clinical Streptococcus pneumoniae isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate, and 29.4% were penicillin resistant (MICs >/= 2 mg/liter). Isolates from Vietnam showed the highest prevalence of penicillin resistance (71.4%), followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The penicillin MICs at which 90% of isolates are inhibited (MIC(90)s) were 4 mg/liter among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%), Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC(90)s of erythromycin were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore, Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan(19F) clone and the Spain(23F) clone could be one of the major reasons for the rapid increases in antimicrobial resistance among S. pneumoniae isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among S. pneumoniae isolates in many Asian countries, which are among the highest in the world published to date.

BACKGROUND: Improving the quality of hospital antibiotic use is a major goal of WHO's global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally. We aimed to present data on patterns of paediatric AWaRe antibiotic use that could be used for local and national stewardship interventions. METHODS: 1-day point prevalence survey antibiotic prescription data were combined from two independent global networks: the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children and the Global Point Prevalence Survey on Antimicrobial Consumption and Resistance networks. We included hospital inpatients aged younger than 19 years receiving at least one antibiotic on the day of the survey. The WHO AWaRe classification was used to describe overall antibiotic use as assessed by the variation between use of Access, Watch, and Reserve antibiotics, for neonates and children and for the commonest clinical indications. FINDINGS: Of the 23 572 patients included from 56 countries, 18 305 were children (77·7%) and 5267 were neonates (22·3%). Access antibiotic use in children ranged from 7·8% (China) to 61·2% (Slovenia) of all antibiotic prescriptions. The use of Watch antibiotics in children was highest in Iran (77·3%) and lowest in Finland (23·0%). In neonates, Access antibiotic use was highest in Singapore (100·0%) and lowest in China (24·2%). Reserve antibiotic use was low in all countries. Major differences in clinical syndrome-specific patterns of AWaRe antibiotic use in lower respiratory tract infection and neonatal sepsis were observed between WHO regions and countries. INTERPRETATION: There is substantial global variation in the proportion of AWaRe antibiotics used in hospitalised neonates and children. The AWaRe classification could potentially be used as a simple traffic light metric of appropriate antibiotic use. Future efforts should focus on developing and evaluating paediatric antibiotic stewardship programmes on the basis of the AWaRe index. FUNDING: GARPEC was funded by the PENTA Foundation. GARPEC-China data collection was funded by the Sanming Project of Medicine in Shenzhen (SZSM2015120330). bioMérieux provided unrestricted funding support for the Global-PPS.

Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.

Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among nonmeningeal isolates, the prevalence rate of penicillin-nonsusceptible pneumococci (MIC, ≥ 4 μg/ml) was 4.6% and penicillin resistance (MIC, ≥ 8 μg/ml) was extremely rare (0.7%). Resistance to erythromycin was very prevalent in the region (72.7%); the highest rates were in China (96.4%), Taiwan (84.9%), and Vietnam (80.7%). Multidrug resistance (MDR) was observed in 59.3% of isolates from Asian countries. Major serotypes were 19F (23.5%), 23F (10.0%), 19A (8.2%), 14 (7.3%), and 6B (7.3%). Overall, 52.5% of isolates showed PCV7 serotypes, ranging from 16.1% in Philippines to 75.1% in Vietnam. Serotypes 19A (8.2%), 3 (6.2%), and 6A (4.2%) were the most prominent non-PCV7 serotypes in the Asian region. Among isolates with serotype 19A, 86.0% and 79.8% showed erythromycin resistance and MDR, respectively. The most remarkable findings about the epidemiology of S. pneumoniae in Asian countries after the introduction of PCV7 were the high prevalence of macrolide resistance and MDR and distinctive increases in serotype 19A.

OBJECTIVES: Our aims were to assess the relationship between workplace violence, job satisfaction, burnout, organisational support and turnover intention, and to explore factors associated with turnover intention among nurses in Chinese tertiary hospitals. METHODS: The purposive sampling method was used to collect data from August 2016 through January 2017. A total of 1761 nurses from 9 public tertiary hospitals in 4 provinces (municipalities) located in eastern (Beijing), central (Heilongjiang, Anhui) and western (Shaanxi) regions of China completed the questionnaires (effective response rate=85.20%). A cross-sectional study was conducted using the Workplace Violence Scale, Chinese Maslach Burnout Inventory General Survey, Minnesota Job Satisfaction Questionnaire Revised Short Version, Perceived Organizational Support-Simplified Version Scale and Turnover Intention Scale. RESULTS: A total of 1216 of 1706 (69.1%) participants had high turnover intention. During the previous 12 months, the prevalence of physical violence and psychological violence towards nurses was 9.60% and 59.64%, respectively. As expected, the level of turnover intention was negatively correlated with participants' scores on job satisfaction (r=-0.367, p<0.001) and perceived organisational support (r=-0.379, p<0.001), respectively. Burnout was positively associated with turnover intention (r=0.444, p<0.001). Workplace violence was positively associated with turnover intention (β=0.035, p<0.001) in linear regression analysis. The total effect (β=0.53) of workplace violence on turnover intention comprised its direct effect (β=0.36) and its indirect effect (β=0.17). CONCLUSIONS: Perceived organisational support served as a mediator between workplace violence, job satisfaction, burnout and turnover intention, and it had a significantly negative impact on turnover intention. Therefore, nursing managers should understand the importance of the organisation's support and establish a reasonable incentive system to decrease turnover intention.