Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China

Since December 2019,COVID-19 has occurred unexpectedly and emerged as a health problem worldw ide.Despite the rapidly increasing number of cases in subsequent weeks,the clinical characteristics of pediatric cases are rarely described.A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province.A total of 25 confirmed pediatric cases of COVID-19 were collected.The demographic data,epidemiological history,underlying discascs,clinical mani festations,laboratory and radiological data,treatments,and outcomes were analyzcd.Of 25 hospitalized patients with COVID-19,the boy to girl ratio was 1.27:1.The median age was 3 years.COVID-19 cases in children aged<3 years,3-6 years,and≥6-years patients were 10(40%),6(24%),and 9(36%),respectively.The most common symptoms at onset of ilness were fever(13[52%]),and dry cough(11[44%]).Chest CT images showed essential normal in 8 cases(33.3%),unilateral involvement of lungs in 5 cases(20.8%),and bilateral involvement in 11 cases(45.8%).Clinical diagnoses included upper respiratory tract infection(n=8),mild pneumonia(n=15),and critical cases(n=2).Two critical cases(8%)were given invasive mechanical ventilation,corticosteroids,and immunoglobulin.The symptoms in 24(96%)of 25 patients were alleviated and one patient had been discharged.It was concluded that children were susceptible to COVID-19 like adults,while the clinical presentations and outcomes were more favorable in children.However,children less than 3 years old accounted for majority cases and critical cases lied in this age group,which demanded extra attentions during home caring and hospitalization treatment.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

Huai Qi Huang-induced Apoptosis via Down-regulating PRKCH and Inhibiting RAF/MEK/ERK Pathway in Ph+ Leukemia Cells

Imatinib mesylate(IM)is the first-line treatment for Philadelphia(Ph)chromosomal positive leukemia by inhibiting phosphorylation of substrates via binding to the ABL kinase domain.Because of the drug resistance,side effects and the high cost of IM,it is necessary to find anti-cancer drugs with relatively low toxicity and cost,and enhanced efficacy,such as traditional Chinese medicines(TCMs).As one of TCMs,Huai Qi Huang(HQH)was chosen to treat BV173 and K562 cells.Various concentrations of HQH were added to cells for 24-72 h.Co-treatment of HQH and trametinib,an MEK inhibitor,was used to verify the synergistic effects on cell viability and apoptosis.Knockdown and overexpression of mitogen-activated protein kinase kinase 4(MEK4)were implemented to demonstrate the role of MEK in cell apoptosis.Cell viability and apoptosis were measured by cell counting kit-8 assay(CCK8)and flow cytometry,respectively.Western blotting and real-time quantitative PCR(RT-qPCR)were used to assess protein and mRNA expression levels,respectively.The results showed that HQH inhibited survival and promoted apoptosis of BV173 and K562 cells in a dose-dependent manner,accompanied with down-regulation of PRKCH mRNA as well as CRAF,MEK4,phospho-ERK(pERK)and BCL2 proteins,and up-regulation of cleaved caspase3 protein.Co-treatment of HQH and trametinib had.a synergistic effect on inhibiting survival and promoting apoptosis.MEK4 knockdown increased apoptosis,and had a synergistic effeet with HQH.In contrast,MEK4 overexpression decreased.apoptosis,and had the opposite efect with HQH.Collectively,the results of this study may identify a therapeutic mechanism of HQH on promoting apoptosis,and provide a potential option for treatment of Pht leukemia.

A New Immunosuppressive Therapy for Very Severe Aplastic Anemia in Children with Autoantibodies

Objective At present,a number of very severe aplastic anemia(VSAA)patients cannot receive hematopoietic stem cell transplantation(HSCT)or standard immunosuppressive therapy(IST)due to the high cost of therapy,shortage of sibling donors,and lack of resources to support the HSCT.In addition,some VSAA patients with autoantibodies have no life-threatening infections or bleeding at the time of initial diagnosis.Considering the disease condition,economics and other factors,the present study designed a new and relatively mild treatment strategy:cyclosporine A plus pulsed high-dose prednisone(CsA+HDP).Methods The present study retrospectively analyzed 11 VSAA patients,who were treated with CsA+HDP in our hospital from August 2017 to August 2019.Results The median follow-up time for these patients was 24.9 months.The overall response rate was 54.5%(6/11)at six months after the initiation of IST and 81.8%(9/11)at deadline.Five patients achieved complete remission and four patients met the criteria for partial response at the last follow-up.The median time to response for responders was 110 days.Three patients underwent HSCT due to the poor effect of CsA+HDP or to find a suitable transplant donor.Recurrence and clonal evolution were not found in any of these patients.The estimated 3-year overall survival rate and 3-year failure-free survival rate were 100.0%and 72.7%,respectively.In addition,the results revealed that the cyclosporine-prednisone-associated toxicity was mild and well-tolerated by most patients.Conclusion The novel CsA+HDP regimen has good therapeutic effect and safety for VSAA patients with autoantibodies,who have no serious life-threatening infections or bleeding at the time of initial diagnosis.

Behavioral Intervention Reduces Unhealthy Eating Behaviors in Preschool Children via a Behavior Card Approach

Many eating behaviors form in childhood,and some unhealthy behaviors may persist into adulthood and have potential impacts on people＇s health.This study evaluated the effectiveness of behavioral intervention in reducing consumption of Western fast food,sweetened beverages,fried food in preschool children,and changing parents＇ rewarding behaviors that encourage the consumption of the unhealthy foods.The research was a cluster randomized trial of seven kindergartens,involving 1138 children aged 3–6 years and their parents in Beijing,China.Parents and children allocated to the intervention group received two lectures and printed resources,including behavior cards,educational sheets.Children＇s behavior cards,applied with behavior-changing techniques,were used to intervene,and monitor behavior changes over time.Children in the control group just followed their usual health education curriculum in kindergartens.Intervention effects on food consumption behaviors were assessed by examining pre-and post-questionnaires.Of the 1138 children screened at baseline,880（77.3%） were measured at the end of the intervention period.The intervention lasted from March to June in 2010.The results showed that consumption of Western fast food,sweetened beverages,and fried food was decreased among the intervention group（P〈0.001）.Proportions of parents using Western fast food as rewards for their children were decreased（P=0.002）.From March to June 2010,the frequency of each target behavior in children tended to decrease over the intervention period（P〈0.001）.Most parents favored regularly-delivered behavior cards or materials for behavioral intervention.In conclusion,the behavioral intervention encourages the healthier eating behaviors of children and reduces the parents＇ practice of using unhealthy foods as reward.

Diagnosis,treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children:experts'consensus statement updatedforthe Omicron variant

It has been more than 3 years since the novel coronavirus(SARS-CoV-2)pandemic raged globally.The coronavirus disease 2019(COVID-19)has greatly influenced human society.According to data from the World Health Organization(WHO),there were over 656 million confirmed cases of COVID-19 in the world as of January 1,2023,including over 6.6 million deaths[1].

Diagnosis,treatment,and prevention of monkeypox in children:an experts'consensus statement

Monkeypox is a zoonotic disease.Since the first human monkeypox case was detected in 1970,it has been prevalent in some countries in central and western Africa.Since May 2022,monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide.As of September 14,2022,there have been more than 58,200 human monkeypox cases,and there is community transmission.The cessation of smallpox vaccination in 1980,which had some cross-protection with monkeypox,resulted in a general lack of immunity to monkeypox,which caused global concern and vigilance.As of Sep-tember 14,2022,there are four monkeypox cases in China,including three in Taiwan province and one in Hong Kong city.Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians'understanding of monkeypox and achieve early detection,early diagno-sis,early treatment,and early disposal,we have organized national authoritative experts in pediatric infection,respiratory,dermatology,critical care medicine,infectious diseases,and public health and others to formulate this expert consensus,on the basis of the latest"Clinical management and infection prevention and control for monkeypox"released by The World Health Organization,the"guidelines for diagnosis and treatment of monkeypox(version 2022)"issued by National Health Commission of the People's Republic of China and other relevant documents.During the development of this consensus,multidisciplinary experts have repeatedly demonstrated the etiology,epidemiology,transmission,clinical manifestations,laboratory examinations,diagnosis,differential diagnosis,treatment,discharge criteria,prevention,disposal process,and key points of prevention and control of suspected and confirmed cases.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition)

In the early February,2020,we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis,treatment and prevention of coronavirus disease 2019 (COVID-19) in children,which has been published in this journal.With accumulated experiences in the diagnosis and treatment of COVID-19 in children,we have updated the consensus statement and released the second edition recently.The current version in English is a condensed version of the second edition of consensus statement on diagnosis,treatment and prevention of COVID-19 in children.In the current version,diagnosis and treatement criteria have been optimized,and early identification of severe and critical cases is highlighted.The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice.This version of experts consensus will be valuable for better prevention,diagnosis and treatment of COVID-19 in children worldwide.

Expert consensus on COVID-19 vaccination in children

Coronavirus disease 2019(COVID-19)is a public health disaster that has not been encountered for a hundred years.On January 12,2020,the World Health Organization(WHO)confirmed and named the coronavirus which caused unexplained pneumonia as 2019 novel coronavirus(2019-nCoV).Since then,the disease caused by this virus had been named as coronavirus disease 2019(COVID-19).On February 11,2020,the International Committee on Taxonomy of Viruses announced that the English name of the novel coronavirus was severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)[1].At present,SARS-CoV-2 infection is still rampant worldwide.As of September 10,2021,there were about 222 million confirmed cases of COVID-19 and more than 4.5 million deaths worldwide[2].According to the American Centers for Disease Control and Prevention,by July 29,2021,4.19 million pediatric COVID-19 cases had been reported in the United States。

Neutropenia:diagnosis and management

Neutropenia is definedas an absolute neutrophil count(ANC)of less than 1500/μL.According to the number of circulating neutrophils,neutropenia is divided into mild(1000/μL≤ANC<1500/μL),mode rate(500/μL≤ANC<1000/μL),and severe(ANC<500/μL)[1].