查看更多>>摘要：Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of 1∶6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and skin.Importantly,TSC is also associated with significant neurological manifestations including epilepsy,TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum disorder.Mutations in the TSC1 or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling pathway.Animal models have been widely used to study the effect of TSC 1/2 genes on the development and function of the brain.Despite considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSC1/2 mutations that are unique to human neurodevelopment.Data sources Literature reviews and research articles were published in PubMed-indexed journals.Results Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human brain.Conclusions In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.
查看更多>>摘要：Introduction Antibiotic use for acute otitis media(AOM)is one of the major sources of antimicrobial resistance.However,the effective minimal antibiotic duration for AOM remains unclear.Moreover,guidelines often recommend broad ranges(5-10 days)of antibiotic use,yet the clinical impact of such a wide window has not been assessed.Methods We systematically searched PubMed/MEDLINE,Embase,Scopus,Web of Science,and Cochrane Library from database inception to 6 October 2021.Network meta-analysis was conducted on randomized controlled trials that assessed antibiotic treatment for AOM in children(PROSPERO CRD42020196107).Results For amoxicillin and amoxicillin-clavulanate,7-day regimens were noninferior to 10-day regimens in clinical responses[amoxicillin:risk ratio(RR)0.919(95％CI 0.820-1.031),amoxicillin-clavulanate:RR 1.108(0.957-1.282)],except for ≤ 2 years.For the third-generation cephalosporins,7-day and 10-day regimens had similar clinical responses compared to placebo[7-day:RR 1.420(1.190-1.694),10-day:RR 1.238(1.125-1.362)compared to placebo].However,5-day regimens of amoxicillin-clavulanate and third-generation cephalosporins were inferior to 10-day regimens.Compared to amoxicillin,a shorter treatment duration was tolerable with amoxicillin-clavulanate.Conclusions Our findings indicated that 10 days of antibiotic use may be unnecessarily long,while the treatment duration should be longer than 5 days.Otherwise,5-day regimens would be sufficient for a modest treatment goal.Our findings revealed that the current wide range of recommended antibiotic durations may have influenced the clinical outcome of AOM,and a narrower antibiotic duration window should be re-established.
查看更多>>摘要：Background Since 2010,most tertiary care hospitals in Australia have changed how they care for extremely premature infants.However,in-hospital and longer-term outcome data have suggested unchanged or even worse health outcomes in later epochs,especially respiratory outcomes.This study examined the trend in outcomes since these changes were introduced,particularly the prevalence of chronic neonatal lung disease(CLD).Methods This is a retrospective cross-sectional analysis of data from the Neonatal Intensive Care Units'(NICUS)database of all perinatal intensive care units in New South Wales and the Australian Capital Territory,including infants born at ≥24 and≤28 weeks of gestational age in tertiary perinatal units between January 1,2010,and December 31,2020.Temporal trends and changes in primary outcome were examined by linear and adjusted multivariable logistic regression models.Results This study included 3258 infants.We saw significant changes in antenatal magnesium sulfate(75％increase),delayed cord clamping(66％increase),delivery room intubations(30％decrease),any time(20％decrease),duration on mechanical ventilation(100-hour decrease),and hours on noninvasive ventilation(200-hour increase).Mortality decreased from 17％to 6％.The incidence of CLD increased significantly even when adjusted for confounders(15％increase).Any time and mean hours spent on mechanical ventilation significantly increased the odds of CLD.This study could not find a significant association of any of the protective antenatal treatments on CLD.Conclusions The last decade saw a significant improvement in survival and survival to discharge without major morbidity.There was increased use of magnesium sulfate,delayed cord clamping,and less invasive respiratory management of extremely preterm infants.The avoidance of mechanical ventilation may impact the incidence of CLD.
查看更多>>摘要：Background Liver transplantation is the main treatment for cholestatic liver disease and some metabolic liver diseases in children.However,no accurate prediction model to determine the survival probability of grafts prior to surgery exists.This study aimed to develop an effective prognostic model for allograft survival after pediatric liver transplantation.Methods This retrospective cohort study included 2032 patients who underwent pediatric liver transplantation between January 1,2006,and January 1,2020.A nomogram was developed using Cox regression and validated based on bootstrap sampling.Predictive and discriminatory accuracies were determined using the concordance index and visualized using calibration curves;net benefits were calculated for model comparison.An online Shiny application was developed for easy access to the model.Results Multivariable analysis demonstrated that preoperative diagnosis,recipient age,body weight,graft type,preoperative total bilirubin,interleukin-1β,portal venous blood flow direction,spleen thickness,and the presence of heart disease and cholangitis were independent factors for survival,all of which were selected in the nomogram.Calibration of the nomogram indicated that the 1-,3-,and 5-year predicted survival rates agreed with the actual survival rate.The concordance indices for graft survival at 1,3,and 5 years were 0.776,0.757,and 0.753,respectively,which were significantly higher than those of the Pediatric End-Stage Liver Disease and Child-Pugh scoring systems.The allograft dysfunction risk of a recipient could be easily predicted using the following URL:https://aspelt.shinyapps.io/ASPELT//Conclusion The allograft survival after pediatric liver transplantation(ASPELT)score model can effectively predict the graft survival rate after liver transplantation in children,providing a simple and convenient evaluation method for clinicians and patients.
查看更多>>摘要：Background Surgery plays an important role in the treatment of neuroblastoma.Perioperative complications may impact the course of neuroblastoma treatment.To date,comprehensive analyses of complications and risk factors have been lacking.Methods Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021.The data collected included clinical characteristics,operative details,operative complications and postopera-tive outcomes.Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed.Results A total of 571 patients were enrolled in this study.Perioperative complications were observed in 255(44.7％)patients.Lymphatic leakage(28.4％),diarrhea(13.5％),and injury(vascular,nerve and organ;7.5％)were the most frequent compli-cations.There were three operation-related deaths(0.53％):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P＜0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative complications.Conclusions Despite the high incidence of perioperative complications,the associated mortality rate was quite low.Perio-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular encasement.Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.
查看更多>>摘要：Background Myelin oligodendrocyte glycoprotein(MOG)antibody-associated disease(MOGAD)is an autoimmune demy-elinating disorder of the central nervous system.Methods Extracted proteins from 34 cerebrospinal fluid(CSF)samples[patients with MOGAD(MOG group,n=12);healthy controls(HC group,n=12);patients with MOG seronegative and metagenomics next-generation sequencing-negative inflammatory neurological diseases(IND group,n=10)]were processed and subjected to label-free quantitative proteomics.Supervised partial least squares-discriminant analysis(PLS-DA)and orthogonal PLS-DA(O-PLS-DA)models were also performed based on proteomics data.Functional analysis of differentially expressed proteins(DEPs)was performed using Gene Ontology,InterPro,and Kyoto Encyclopedia Genes and Genomes.An enzyme-linked immunosorbent assay was used to determine the complement levels in serum from patients with MOGAD.Results Four hundred and twenty-nine DEPs(149 upregulated and 280 downregulated proteins)were identified in the MOG group compared to the HC group according to the P value and fold change(FC).Using the O-PLS-DA model,872 differentially abundant proteins were identified with variable importance projection(VIP)scores＞1.Five proteins(gamma-glutamyl hydrolase,cathepsin F,interalpha-trypsin inhibitor heavy chain 5,latent transforming growth factor beta-binding protein 4 and leukocyte-associated immunoglobulin-like receptor 1)overlapping between the top 30 DEPs with top-ranked P value and FC and top 30 proteins in PLS-DA VIP lists were acquired.Functional analysis revealed that the dysregulated proteins in the MOG group were primarily involved in complement and coagulation cascades,cell adhesion,axon guidance,and glycosphingolipid biosynthesis compared to the HC group.Conclusion The proteomic alterations in CSF samples from children with MOGAD identified in the current study might provide opportunities for developing novel biomarker candidates.
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