Filter

Refine by Access

Refine by Date

—
  • Print
  • Save

Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Xuefeng Chen x
  • Refine by Access: All content x
Clear All Modify Search
Free access

Immune checkpoint inhibitor-associated thyroid dysfunction: a disproportionality analysis using the WHO Adverse Drug Reaction Database, VigiBase

Xuefeng Bai, Xiaoyu Chen, Xiaohong Wu, Yinqiong Huang, Yong Zhuang, and Xiahong Lin

Objective

Our study aimed to identify and characterize thyroid dysfunctions associated with immune checkpoint inhibitors (ICIs).

Design

Data were obtained from VigiBase, between January 1, 2011 to March 6, 2019.

Methods

All thyroid drug-adverse events are classified by group queries according to the Medical Dictionary for Regulatory Activities. Information component (IC) and reporting odds ratio (ROR) were considered as measures of disproportionality for the assessment of association between ICIs and thyroid dysfunctions. We used IC to identify meaningful drug-adverse events while using ROR to compare differences in the reporting of drug-adverse events caused by different ICI subgroups. Positive IC values are deemed significant.

Results

Compared with the full database, the following ICI-associated thyroid dysfunctions were over-reported: hypothyroidism (1125 reports for ICIs vs 12495 for all drugs; Information Component 4.28 (95% CI: 4.18–4.35)), hyperthyroidism (926 vs 7538; 4.66 (95% CI: 4.55–4.74)), thyroiditis (294 vs 1237; 5.40 (95% CI: 5.21–5.54)), thyrotoxic crisis (11 vs 288; 3.55 (95% CI: 2.61–4.20)). Hypothyroidism was over-reported for patients treated with ICI combination therapy versus those treated with ICI monotherapy (ROR 1.3 (95% CI: 1.1–1.7)), and the same was observed for hyperthyroidism (ROR: 1.9 (95% CI: 1.5–2.4)), thyroiditis (ROR: 3.3 (95% CI: 2.3–4.8)), thyrotoxic crisis (ROR: 11.5 (95% CI: 2.4–53.8)). All 11 thyrotoxic crisis cases were malignant melanoma patients, of which seven occurred under ICI combination therapy.

Conclusions

Thyroid dysfunction may occur after ICI therapies, and severe thyrotoxic crisis may even occur. Raising awareness of ICI-associated thyroid dysfunction can improve the detection and treatment of these diseases.

Free access

Prevalence and phenotypic features of diabetes due to recessive, non-syndromic WFS1 mutations

Mingqiang Zhu, Yangxi Li, Guanping Dong, Xuefeng Chen, Ke Huang, Wei Wu, Yangli Dai, Li Zhang, Hu Lin, Sihua Wang, Constantin Polychronakos, and Junfen Fu

Objective

Recessive WFS1 mutations are known to cause Wolfram syndrome, a very rare systemic disorder. However, they were also found in non-syndromic diabetes in Han Chinese misdiagnosed with type 1 diabetes (T1D), a molecular cause that appears to be considerably more common than the fully expressed syndrome. We aimed to better define the incidence and clinical features of non-syndromic diabetes due to recessive WFS1 mutation.

Design

We analyzed the genotype and phenotype of 320 consecutive incident Chinese pediatric diabetic patients diagnosed from 2016 to 2019 to search for non-syndromic diabetic cases due to recessive WFS1 mutation.

Methods

A cohort of 105 pancreatic autoantibody-negative patients were recruited for exome sequencing. All patients tested positive for pathogenic diallelic WFS1 mutations were examined for phenotypic features (fundoscopy, audiogram, and urine density).

Results

We found three cases of non-syndromic diabetes due to recessive WFS1 mutations (incidence = 0.94% (95% CI: 0.25–2.7%)). All three cases only had mild diabetes when diagnosed. All patients had well-conserved fasting C-peptide when diagnosed but one of them progressed to T1D-like insulin deficiency. In addition, we found a fourth case with previously undetected features of Wolfram syndrome.

Conclusions

Non-syndromic diabetes due to WFS1 mutation may be common among Chinese pediatric patients with diabetes. It is important to differentiate it from other maturity-onset diabetes in the young subtypes with similar phenotype by molecular diagnosis because of different prognosis and, potentially, therapy.