AIM To study the type and frequency of adverse events associated with anti-tumor necrosis factor(TNF)therapy and evaluate for any serologic and genetic associations.METHODS This study was a retrospective review of pat...AIM To study the type and frequency of adverse events associated with anti-tumor necrosis factor(TNF)therapy and evaluate for any serologic and genetic associations.METHODS This study was a retrospective review of patients attending the inflammatory bowel disease(IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure.RESULTS Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients(21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the antiTNF agent. In total: n = 66(5%) infusion reactions; n = 49(4%) allergic/serum sickness reactions; n = 19(1.5%) lupus-like reactions, n = 52(4%) rash, n = 18(1.4%) infections. In Crohn's disease, Ig A ASCA(P = 0.04) and Ig G-ASCA(P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions(P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT(Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. CONCLUSION Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic, and pathways associations.展开更多
BACKGROUND Epidemiological studies of chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC)are limited.Understanding demographic and ethno-racial factors may help identify patients at...BACKGROUND Epidemiological studies of chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC)are limited.Understanding demographic and ethno-racial factors may help identify patients at the highest risk for CP and PDAC.AIM To evaluate the ethno-racial risk factors for CP and its association with PDAC.The secondary aim was to evaluate hospitalization outcomes in patients admitted with CP and PDAC.METHODS This retrospective cohort study used the 2016 and 2017 National Inpatient Sample databases.Patients included in the study had ICD-10 codes for CP and PDAC.The ethnic,socioeconomic,and racial backgrounds of patients with CP and PDAC were analyzed.RESULTS Hospital admissions for CP was 29 per 100000,and 2890(0.78%)had PDAC.Blacks[adjusted odds ratio(aOR)1.13],men(aOR 1.35),age 40 to 59(aOR 2.60),and being overweight(aOR 1.34)were significantly associated with CP(all with P<0.01).In patients with CP,Whites(aOR 1.23),higher income,older age(aOR 1.05),and being overweight(aOR 2.40)were all significantly associated with PDAC(all with P<0.01).Men(aOR 1.81)and Asians(aOR 15.19)had significantly increased mortality(P<0.05).Hispanics had significantly increased hospital length of stay(aOR 5.24)(P<0.05).CONCLUSION Based on this large,nationwide analysis,black men between 40-59 years old and overweight are at significantly increased risk for admission with CP.White men older than 40 years old and overweight with higher income were found to have significant associations with CP and PDAC.This discrepancy may reflect underlying differences in healthcare access and utilization among different socioeconomic and ethno-racial groups.展开更多
文摘AIM To study the type and frequency of adverse events associated with anti-tumor necrosis factor(TNF)therapy and evaluate for any serologic and genetic associations.METHODS This study was a retrospective review of patients attending the inflammatory bowel disease(IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure.RESULTS Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients(21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the antiTNF agent. In total: n = 66(5%) infusion reactions; n = 49(4%) allergic/serum sickness reactions; n = 19(1.5%) lupus-like reactions, n = 52(4%) rash, n = 18(1.4%) infections. In Crohn's disease, Ig A ASCA(P = 0.04) and Ig G-ASCA(P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions(P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT(Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. CONCLUSION Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic, and pathways associations.
文摘BACKGROUND Epidemiological studies of chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC)are limited.Understanding demographic and ethno-racial factors may help identify patients at the highest risk for CP and PDAC.AIM To evaluate the ethno-racial risk factors for CP and its association with PDAC.The secondary aim was to evaluate hospitalization outcomes in patients admitted with CP and PDAC.METHODS This retrospective cohort study used the 2016 and 2017 National Inpatient Sample databases.Patients included in the study had ICD-10 codes for CP and PDAC.The ethnic,socioeconomic,and racial backgrounds of patients with CP and PDAC were analyzed.RESULTS Hospital admissions for CP was 29 per 100000,and 2890(0.78%)had PDAC.Blacks[adjusted odds ratio(aOR)1.13],men(aOR 1.35),age 40 to 59(aOR 2.60),and being overweight(aOR 1.34)were significantly associated with CP(all with P<0.01).In patients with CP,Whites(aOR 1.23),higher income,older age(aOR 1.05),and being overweight(aOR 2.40)were all significantly associated with PDAC(all with P<0.01).Men(aOR 1.81)and Asians(aOR 15.19)had significantly increased mortality(P<0.05).Hispanics had significantly increased hospital length of stay(aOR 5.24)(P<0.05).CONCLUSION Based on this large,nationwide analysis,black men between 40-59 years old and overweight are at significantly increased risk for admission with CP.White men older than 40 years old and overweight with higher income were found to have significant associations with CP and PDAC.This discrepancy may reflect underlying differences in healthcare access and utilization among different socioeconomic and ethno-racial groups.
