Background The early prediction of intravenous corticosteroid(IVCS)resistance in acute severe ulcerative colitis(ASUC)patients remains an unresolved challenge.This study aims to construct and validate a model that acc...Background The early prediction of intravenous corticosteroid(IVCS)resistance in acute severe ulcerative colitis(ASUC)patients remains an unresolved challenge.This study aims to construct and validate a model that accurately predicts IVCS resistance.Methods A retrospective cohort was established,with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020.The primary outcome was IVCS resistance.Classification models,including logistic regression and machine learning-based models,were constructed.External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University.Results A total of 129 patients were included in the derivation cohort.During index hospitalization,102(79.1%)patients responded to IVCS and 27(20.9%)failed;18(14.0%)patients underwent colectomy in 3 months;6 received cyclosporin as rescue therapy,and 2 eventually escalated to colectomy;5 succeeded with infliximab as rescue therapy.The Ulcerative Colitis Endoscopic Index of Severity(UCEIS)and C-reactive protein(CRP)level at Day 3 are independent predictors of IVCS resistance.The areas under the receiver-operating characteristic curves(AUROCs)of the logistic regression,decision tree,random forest,and extreme-gradient boosting models were 0.873(95%confidence interval[CI],0.704–1.000),0.648(95%CI,0.463–0.833),0.650(95%CI,0.441–0.859),and 0.604(95%CI,0.416–0.792),respectively.The logistic regression model achieved the highest AUROC value of 0.703(95%CI,0.473–0.934)in the external validation.Conclusions In patients with ASUC,UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance.We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC.A nomogrambased on the logistic regression model might aid in the management of ASUC patients.展开更多
Objective This study aimed to investigate the long-term outcomes in children with steroid-resistant nephrotic syndrome （SRNS）, who received methylprednisolone pulse therapy （MPT）-based sequential steroid therapy. ...Objective This study aimed to investigate the long-term outcomes in children with steroid-resistant nephrotic syndrome （SRNS）, who received methylprednisolone pulse therapy （MPT）-based sequential steroid therapy. In particular, we aimed to observe whether these patients had a high risk of adverse events. Methods We conducted a retrospective study over a 5-year period. The long-term outcomes for children with SRNS receiving sequential therapy were observed. Results Sixty-three children were diagnosed with SRNS and underwent MPT-based sequential steroid therapy. Thirty-five （55.6%） achieved complete or partial remission, 19 （30.2%） of whom were in remission even after treatment cessation at last review. The mean time to initial remission after MPT was 24.3±13.1 days. Forty-nine children （77.8%） experienced relapses, of whom 31 （49.2%） demonstrated a frequent relapsing course. Adverse effects relevant to MPT were generally mild and infrequent. Five patients （7.9%） complained of vomiting or nausea during MPT infusion; 25 （39.7%） experienced excessive weight gain and developed an obvious Cushingoid appearance; and 26 （41.3%） had poor growth associated with long-term steroid use. Twenty-eight patients （44.4%） failed to respond to MPT, of whom 21 （33.3%） achieved complete or partial remission with immunosuppressive agents. Conclusion MPT-based sequential steroid therapy appears to be a safe and effective method for inducing rapid remission in childhood SRNS. Further clinical studies are needed to comprehensively evaluate this therapy.展开更多
Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevert...Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.展开更多
基金supported by the Beijing Municipal Natural Science Foundation[grant number 7212078]the CAMS Innovation Fund for Medical Sciences(CIFMS)[grant number 2020-I2 M-C&T-B-005].
文摘Background The early prediction of intravenous corticosteroid(IVCS)resistance in acute severe ulcerative colitis(ASUC)patients remains an unresolved challenge.This study aims to construct and validate a model that accurately predicts IVCS resistance.Methods A retrospective cohort was established,with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020.The primary outcome was IVCS resistance.Classification models,including logistic regression and machine learning-based models,were constructed.External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University.Results A total of 129 patients were included in the derivation cohort.During index hospitalization,102(79.1%)patients responded to IVCS and 27(20.9%)failed;18(14.0%)patients underwent colectomy in 3 months;6 received cyclosporin as rescue therapy,and 2 eventually escalated to colectomy;5 succeeded with infliximab as rescue therapy.The Ulcerative Colitis Endoscopic Index of Severity(UCEIS)and C-reactive protein(CRP)level at Day 3 are independent predictors of IVCS resistance.The areas under the receiver-operating characteristic curves(AUROCs)of the logistic regression,decision tree,random forest,and extreme-gradient boosting models were 0.873(95%confidence interval[CI],0.704–1.000),0.648(95%CI,0.463–0.833),0.650(95%CI,0.441–0.859),and 0.604(95%CI,0.416–0.792),respectively.The logistic regression model achieved the highest AUROC value of 0.703(95%CI,0.473–0.934)in the external validation.Conclusions In patients with ASUC,UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance.We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC.A nomogrambased on the logistic regression model might aid in the management of ASUC patients.
文摘Objective This study aimed to investigate the long-term outcomes in children with steroid-resistant nephrotic syndrome （SRNS）, who received methylprednisolone pulse therapy （MPT）-based sequential steroid therapy. In particular, we aimed to observe whether these patients had a high risk of adverse events. Methods We conducted a retrospective study over a 5-year period. The long-term outcomes for children with SRNS receiving sequential therapy were observed. Results Sixty-three children were diagnosed with SRNS and underwent MPT-based sequential steroid therapy. Thirty-five （55.6%） achieved complete or partial remission, 19 （30.2%） of whom were in remission even after treatment cessation at last review. The mean time to initial remission after MPT was 24.3±13.1 days. Forty-nine children （77.8%） experienced relapses, of whom 31 （49.2%） demonstrated a frequent relapsing course. Adverse effects relevant to MPT were generally mild and infrequent. Five patients （7.9%） complained of vomiting or nausea during MPT infusion; 25 （39.7%） experienced excessive weight gain and developed an obvious Cushingoid appearance; and 26 （41.3%） had poor growth associated with long-term steroid use. Twenty-eight patients （44.4%） failed to respond to MPT, of whom 21 （33.3%） achieved complete or partial remission with immunosuppressive agents. Conclusion MPT-based sequential steroid therapy appears to be a safe and effective method for inducing rapid remission in childhood SRNS. Further clinical studies are needed to comprehensively evaluate this therapy.
基金This study was funded by the Science and Technology Projects of Zhejiang Province(No.LGC21H200004)the Key Research and Development Plan of Zhejiang Province(No.2019C03028)the Medical Scientific Projects from Health Department of Zhejiang Province(No.2018KY455)。
文摘Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.
