Systemic lupus erythematosus and thyroid disease – Experience in a single medical center in Taiwan

BackgroundTo investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan.MethodsThis is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia.ResultsCompared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p < 0.0001). The average age of SLE patients with thyroid diseases patients were older than those without thyroid diseases (p = 0.002). Those had euthyroid AITD were younger than other patients with thyroid diseases (p = 0.02). Up to 30.3% SLE patients had overlap syndrome and had higher relative risk of thyroid diseases than those without overlap syndrome, in terms of hypothyroidism and AITD, but not hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p < 0.0001).ConclusionSLE patients had significantly higher rate of hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement.     

Mutation spectrum of MMACHC in Chinese pediatric patients with cobalamin C disease: A case series and literature review

Cobalamin (cbl) C disease is a rare autosomal recessive inheritance disease, which is the most common cobalamin metabolic disorder. Its clinical phenotype involves multiple systems with varying degrees of severity, where in mild cases can be asymptomatic for many years, whereas severe cases may cause death during the neonatal period. The disease is caused by mutations in the MMACHC gene located on chromosome 1p34.1 that contains 5 exons; among which, exons 1–4 have an 849 bp coding sequence that encodes a protein containing 282 amino acids. Through clinical physical examination and laboratory tests, especially blood and urine screening, we found 28 cblC pediatric patients with clinical manifestations, such as mental retardation, motor development delay, epilepsy, metabolic acidosis, vomiting and diarrhea. By Sanger sequencing, we found homozygous or compound heterozygous mutations of MMACHC in 27 of the patients, and single heterozygous mutation of MMACHC in one of them. The c.609G > A, c.658-660delAAG, c.80A > G and c.482G > A mutations accounted for 43.64% (24/55), 10.91% (6/55), 9.09% (5/55) and 7.27% (4/55) of all the mutations, respectively. This spectrum finding is basically consistent with the previously reported data in Chinese patients. The most common c.609G > A mutation may likely lead to early-onset cblC disease. In previous literature involving a large sample of Caucasian cblC cases, the mutation spectrum of MMACHC gene is almost completely different from that of the Chinese population. The most common mutations in the Caucasian population were c.271dupA, c.394C > T and c.331C > T, which account for 48.05% (542/1128), 13.65% (154/1128) and 7.36% (83/1128) of all the mutant alleles, respectively. The c.271dupA mutation and c.331C > T mutation were mainly associated with early-onset cblC in children less than 1 year old, whilst the c.394C > T mutation was mainly associated with late-onset cblC patients characterised by isolated acute nervous system abnormalities. We also analysed the cause behind the different mutation spectrum of MMACHC gene between the Chinese and Caucasian populations.     

Clinicoepidemiologic characteristics of scrub typhus and murine typhus: A multi-center study in southern Taiwan

BackgroundThis study aimed to offer key features to differentiate scrub typhus (ST) and murine typhus (MT) at the early stage of the diseases and provide clinicoepidemiologic characteristics of ST and MT in southern Taiwan, a region where both diseases are endemic. Comparison of doxycycline treatment efficacy between the two diseases by matching disease severity and delayed treatment had never been investigated.MethodsWe reviewed the medical records of cases of ST and MT in four hospitals in southern Taiwan. Propensity-score matching was used to analyze the defervescence curves between patients with doxycycline-treated ST and MT by log-rank test.ResultsBetween 2004 and 2016, 265 ST and 63 MT cases were diagnosed. The number of cases of ST was significantly related to temperature (Rs = 0.77) and rainfall (Rs = 0.63). Island area exposure, arthropod bite, eschar, and lymphadenopathy were only recorded in ST patients. Multivariate analysis revealed that mountainous area exposure (odds ratio [OR], 11.0; 95% confidence interval [CI], 4.4–27.2) was an independent predictor for ST, while contact with rats (OR, 8.4; 95% CI, 3.3–21.3) was that for MT. After propensity-score matching, there was no difference in defervescence curves between these two rickettsioses treated with doxycycline (p = 0.24).ConclusionIn the present study, island area exposure, arthropod bite, eschar, and lymphadenopathy were unique manifestations of ST. Mountainous area exposure is a predictive factor for ST, while contact with rats predicted MT. There was no difference in defervescence time between these two rickettsioses after doxycycline treatment.     

带线锚钉在治疗肘关节“恐怖三联征”中的临床应用

目的探讨带线锚钉在手术治疗肘关节"恐怖三联征"中的临床效果。方法回顾性分析2010年1月至2017年6月期间本院手术治疗22例肘关节"恐怖三联征"患者的临床资料,根据桡骨头骨折Mason分型,Ⅰ型2例,Ⅱ型8例,Ⅲ型12例;根据尺骨冠状突骨折Regan-Morrey分型,Ⅰ型5例,Ⅱ型12例,Ⅲ型5例;22例患者均伴有内外侧副韧带损伤,并采用肘部外侧、前内侧联合入路进行手术治疗。15例患者手术后以长臂石膏托外固定1～2周,之后逐步进行肘关节被动、主动康复锻炼。7例使用可活动铰链式外固定架辅助固定的患者早期行肘关节康复锻炼。结果所有患者手术后随访6～18个月,平均12个月。末次随访时肘关节屈曲(110±10)°,伸直受限(10±4)°,前臂旋前(70±6)°,旋后(80±6)°,并对患者进行Mayo肘关节功能评分:优(≥90分)3例,良(75～89分)12例,可(60～74分)7例,优良率为68.2%。手术后2例出现异位骨化,1例出现一过性的正中神经症状,无感染、肘关节不稳定、骨折不愈合、脱位及肘关节僵硬等并发症。结论带线锚钉通过对肘关节内外侧副韧带、关节囊等软组织修复,既增加了肘关节的稳定性,同时也减少了相关并发症的发生,值得临床推广应用。     

Severe aortic valve stenosis in a 14-year-old boy with sitosterolemia

We report a 14-year-old boy finally diagnosed with sitosterolemia, presenting with severe aortic valve stenosis. Genetic analysis revealed homozygous null mutation c.1336 C > T (p.R446X) in ABCG5 gene. His cardiac ultrasound presented aortic valve stenosis and moderate aortic regurgitation. His whole aorta computed tomography angiogram scan revealed aortic stenosis superior to the aortic valve, followed by ascending aorta dilation, whereas his coronary and peripheral arteries appeared normal. His maximum total cholesterol and low-density lipoprotein-cholesterol levels dropped dramatically after diet control, and ezetimibe was prescribed for treatment. The current case indicated that sitosterolemia may be a heterogeneous disease in clinical phenotype.     

Killing Effects of IFN R−/− Mouse NK Cells Activated by HN Protein of NDV on Mouse Hepatoma Cells and Possible Mechanism with Syk and NF-κB

The objective of this article is to evaluate whether the tumoricidal activity of mouse IFN R^−/− nature killer (NK) cells is induced by Newcastle disease virus hemagglutinin-neuraminidase (NDV-HN) stimulation, and to investigate what is the mechanism of the HN-stimulated NK cells to kill mouse hepatoma cell line in vitro. The mouse IFN R^−/− NK cells were stimulated for 16 hr with 500 ng/mL NDV-HN in 1640 medium. Quantify the cytotoxic activities of NK cells against mouse hepatoma cells (Hepa1-6) by flow cytometry. Granzymes B (GrB) and Fas/FasL concentrations in the supernatants of IFN R^−/− NK cells medium were determined by specific ELISA assay. The expression of cell surface GrB and Fas was determined by Western blot. NDV-HN stimulation enhanced tumoricidal activity of IFN R^−/− NK cells toward Hepa1-6 in vitro. Treating with anti-HN neutralizing mAb induced significant decline in the cytotoxicity of IFN R^−/− NK cells toward Hepa1-6 cell line (P < 0.05). After treating with anti-HN protein (1 μL/mL), Syk-specific inhibitor Herbimycin A(250 ng/mL) and NF-κB inhibitor PDTC (500 ng/mL) downregulated the tumoricidal activity of HN-stimulated IFN R^−/− NK cells (P < 0.05). Moreover, significant suppressions in the production of GrB and Fas/FasL were observed in HN-stimulated IFN R^−/− NK cells (P < 0.05). Thus, we concluded that killer activation receptors pathway is involved in the IFN-γ-independent GrB and Fas/FasL expression of NDV-HN-stimulated IFN R^−/− NK cells, and these are activated by Syk and NF-κB. Anat Rec, 302:1718–1725, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association for Anatomy