Summary Fulminant type 1 diabetes (FT1D) is a subset of type 1 diabetes characterized by extremely rapid pancreatic β‐cell destruction with aggressive progression of hyperglycaemia and ketoacidosis. It was initially classified as idiopathic type 1 diabetes due to the absence of autoimmune markers. However, subsequent studies provide evidences supporting the involvement of autoimmunity in rapid β‐cell loss in FT1D pathogenesis, which are crucial for FT1D being an autoimmune disease. This article highlights the role of immunological aspects in FT1D according to the autoimmune‐associated genetic background, viral infection, innate immunity, adaptive immunity, and pancreas histology.
The precise stage of lymph node (LN) metastasis is a strong prognostic factor in breast cancers, and sentinel lymph node (SLN) is the first station of nodal metastasis. A number of patients have extranodal extension (ENE) in SLN, whereas the clinical values of ENE in SLN in breast cancers are still in exploration. The aim of our study was to evaluate the predictive and prognostic values of ENE in SLN in breast cancers, and to investigate the feasibility of ENE to predict non-SLN metastasis, nodal burden, disease free survival (DFS) and overall survival (OS) in clinical practice. 266 cases of primary invasive breast cancer (cT1-2N0 breast cancer) underwent SLN biopsy and axillary lymph node dissection (ALND) between 2008 and 2015 were extracted from the pathology database of Fudan University Shanghai Cancer Center. ENE in SLN was defined as extension of neoplastic cells through the lymph-nodal capsule into the peri-nodal adipose tissue, and was classified as no larger than 2 mm and larger than 2 mm group. The associations between ENE and clinicopathological features, non-SLN metastasis, nodal burden, DFS, and OS were analyzed. In the 266 patients with involved SLN, 100(37.6%) were positive for ENE in SLN. 67 (25.2%) cases had ENE no larger than 2 mm in diameter, and 33(12.4%) had ENE larger than 2 mm. Among the clinicopathological characteristics, the presence of ENE in SLN was associated with higher pT and pN stages, PR status, lympho-vascular invasion. Logistic regression analysis indicated that patients with ENE in SLN had higher rate of non-SLN metastasis (OR4.80, 95% CI 2.47–9.34, P < 0.001). Meanwhile, in patients with SLN micrometastasis or 1–2 SLNs involvement, ENE positive patients had higher rate of non-SLN metastasis, comparing with ENE negative patients (P < 0.001, P = 0.004 respectively). The presence of ENE in SLN was correlated with nodal burden, including the pattern and number of involved SLN (P < 0.001, P < 0.001 respectively), the number of involved non-SLN and total positive LNs (P < 0.001, P < 0.001 respectively). Patients with ENE had significantly higher frequency of pN2 disease (P < 0.001). For the disease recurrence and survival status, Cox regression analysis showed that patients with ENE in SLN had significantly reduced DFS (HR 3.05, 95%CI 1.13–10.48, P = 0.008) and OS (HR 3.34, 95%CI 0.74–14.52, P = 0.092) in multivariate analysis. Kaplan–Meier curves and log-rank test showed that patients with ENE in SLN had lower DFS and OS (for DFS: P < 0.001; and for OS: P < 0.001 respectively). Whereas no significant difference was found in nodal burden between ENE ≤ 2 mm and > 2 mm groups, except the number of SLN metastasis was higher in patients with ENE > 2 mm. Cox regression analysis, Kaplan–Meier curves and log-rank test indicated that the size of ENE was not an independent factor of DFS and OS. Our study indicated that ENE in SLN was a predictor for non-SLN metastasis, nodal burden and prognosis in breast cancers. Patients with ENE in SLN had a higher rate of non-SLN metastasis, higher frequency of pN2 disease, and poorer prognosis. Patients with ENE in SLN may benefit from additional ALND, even in SLN micrometastasis or 1–2 SLNs involvement patients. The presence of ENE in SLN should be evaluated in clinical practice. Size of ENE which was classified by a 2 mm cutoff value had no significant predictive and prognostic values in this study. The cutoff values of ENE in SLN need further investigation.
Background Studies on organ-specific autoimmune endocrine disorders showed correlations between disease risks and vitamin D pathways gene variants, such as CYP27B1 rs10877012 and rs4646536, or CYP2R1 rs10741657 single nucleotide polymorphisms. However, previous works presented inconsistent conclusions. Our study aimed at assessing the association of CYP27B1 and CYP2R1 polymorphisms with autoimmune endocrine disorder susceptibility using the meta-analysis method. Methods Case-control studies of the interested subject were identified from databases Pubmed, Embase, Cochran Library, and China National Knowledge Infrastructure. Studies met inclusion and quality criteria were pooled. Observational outcomes were diagnosis of autoimmune Addison’s disease, Graves disease, Hashimoto thyroiditis, or type 1 diabetes mellitus. Statistical analysis was performed using software STATA 16.0. Results 14 studies involving 12929 patients (2243 autoimmune Addison disease, 1253 Graves disease, 612 Hashimoto thyroiditis, 8821 type 1 diabetes), and 12907 healthy control subjects were pooled for meta-analysis. Rs10877012 minor allele A and its homozygote and heterozygote conferred to low overall disease risk [OR (odd ratio)=0.748, 95% CI (confidence interval) 0.620-0.902 in dominant model; OR=0.709, 95% CI 0.571-0.879 in recessive model; OR=0.777, 95% CI 0.674-0.895 in the allele model]. Population carrying rs4646536 minor allele C and its homozygote and heterozygote showed decreased overall autoimmune endocrine disorders risk (OR=0.849, 95% CI 0.748-0.963; OR=0.868, 95% CI 0.790-0.955; OR=0.915, 95% CI 0.875-0.957 in dominant, recessive, and allele model, respectively). No significant genetic association was found for rs10741657. Conclusion Our study suggested CYP27B1 polymorphisms rs10877012 minor allele A and rs4646536 minor allele C were negatively related to susceptibilities of organ-specific autoimmune endocrine diseases.
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