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.     

Invasive mold infections in acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation

Background/purposePatients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are exposed to high risk of developing invasive fungal infections, and the invasive mold infections (IMIs) are becoming more and more common after transplantation. Here, we conducted a retrospective study to analyze demographics, microbiology, and risk factors for IMIs development in adult acute leukemia patients undergoing allo-HSCT.MethodsWe reviewed 245 adult acute leukemia patients undergoing allo-HSCT from January 2003 to December 2014. Clinical characteristics including age, sex, conditioning regimens, European Group for Blood and Bone marrow Transplantation (EBMT) risk score, and presence of acute graft-versus-host disease (aGVHD) or chronic GVHD (cGVHD) were collected and analyzed. Cox proportional hazard model was adopted to explore the independent risk factors for IMIs developments.ResultsSeventeen of 245 patients developed IMIs during the study period. The cumulative incidence of IMIs in this cohort was 8.7% and 16.8% at 6 and 12 months, respectively, with Aspergillus species being the most common pathogen. The significant risk factors predicting IMIs were unrelated donor transplantation (hazard ratio [HR] 5.11), smoking (HR 3.55), EBMT risk score > 2 (HR 4.22), and moderate to severe cGVHD (HR 3.76).ConclusionsWe identified four risk factors-unrelated donor transplantation, smoking, EBMT risk score >2 and moderate to severe cGVHD to predict IMIs among acute leukemia patients undergoing allo-HSCT. This cohort study suggests early identification of high-risk patients and to provide better prevention strategies would reduce the incidence and severity of IMIs in these patients.     

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。     

G-CSF-Mobilized Blood and Bone Marrow Grafts as the Source of Stem Cells for HLA-Identical Sibling Transplantation in Patients with Thalassemia Major

As an inherited anemia, thalassemia major (TM) is currently only curable with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here we report an allo-HSCT protocol for patients with TM who received a combination of granulocyte colony-stimulating factor-primed bone marrow and peripheral blood stem cells (G-BM & PBSCs) from a matched sibling donor (MSD). The conditioning regimen consisted of i.v. busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin. Chimerism analysis was performed for all patients. Immunosuppressive treatment was terminated if rejection was suspected, and donor lymphocyte infusion was administered once no response was observed. A total of 184 patients with TM were enrolled in the study between July 2007 and July 2018. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 13.1%, and that of moderate or severe chronic GVHD was 5.7%. The cumulative incidence of graft rejection was .6%. In the total cohort, the 3-year overall survival, thalassemia-free survival, and GVHD-free, relapse-free survival were 97.8%, 97.3%, and 89.5%, respectively. Collectively, our results indicate that G-BM & PBSCs from an MSD is be a good stem cell source for patients with TM undergoing allo-HSCT.     

Abnormal neural responses to harmonic syntactic structures in congenital amusia

In music, harmonic syntactic structures are organized hierarchically through local and long‐distance dependencies. This study investigated whether congenital amusia, a neurodevelopmental disorder of pitch perception, is associated with impaired processing of harmonic syntactic structures. For stimuli, we used harmonic sequences containing two phrases, where the first phrase ended with a half cadence and the second with an authentic cadence. In Experiment 1, we manipulated the ending chord of the authentic cadence to be either syntactically regular or irregular based on local dependencies. Sixteen amusics and 16 controls judged the expectedness of these chords while their EEG waveforms were recorded. In comparison to the regular endings, irregular endings elicited an ERAN, an N5, and a late positive component in controls but not in amusics, indicating that amusics were impaired in processing local syntactic dependencies. In Experiment 2, we manipulated the half cadence of the harmonic sequences to either adhere to or violate long‐distance syntactic dependencies. In response to irregular harmonic sequences, an ERAN‐like component and an N5 were elicited in controls but not in amusics, suggesting that amusics were impaired in processing long‐distance syntactic dependencies. Furthermore, for controls, the neural processing of local and long‐distance syntactic dependencies was correlated at the later integration stage but not at the early detection stage. These findings indicate that amusia is associated with impairment in the detection and integration of local and long‐distance syntactic violations. The implications of these findings in terms of hierarchical music‐syntactic processing are discussed.     

Chloride channel 3 (CIC-3) predicts the tumor size in hepatocarcinoma

Chloride channel 3 (CIC-3) has been suggested to be implicated in the carcinogenesis though; it still remains ill understood in hepatocarcinoma, especially in terms of clinicopathological meaning of its expression. Given this, herein, to understand the clinicopathological significance of CIC-3 expression in hepatocarcinoma, Immunohistochemistry was performed to examine the level of CIC-3, followed by statistical analysis of the correlation between expression versus clinicopathological variables, including gender, age, TNM classifications, tumor size, lymph node metastasis and overall prognosis. It was shown that positive staining of CIC-3 can be present in both hepatocarcinoma and its paired normal controls; and that CIC-3 was significantly over-expressed in hepatcarcioma on the whole relative to paired normal controls. Moreover, up-regulation of CIC-3 markedly correlated with tumor size and overall prognosis, suggesting that CIC-3 expression could predict both tumor size and overall prognosis in hepatocarcinoma.     

Molecular characterization of Coxsackievirus A16 strains isolated from children with severe hand,foot, and mouth disease in Yunnan,Southwest China,during 2009-2015

Coxsackievirus A16 (CV-A16) commonly causes mild symptoms, but severe diseases, such as aseptic meningitis, encephalitis, and even fatal cases, have been reported. Thirteen CV-A16 strains were isolated from patients with severe hand, foot, and mouth disease in Yunnan, Southwest China, from 2009 to 2015. Subgenotype B1a and B1b of CV-A16 were predominantly circulating the region with B1b the predominant strain in recent years. The mean rate of nucleotide substitution based on the VP1 gene sequence was 4.545 × 10 ⁻³ substitution per site per year from 2009 to 2015. These results may help in understanding the genetic diversity of CV-A16 and develop a CV-A16 vaccine.     

Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing,China

We assessed the prevalence characteristics of single and multiple high-risk human papillomavirus (HR-HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR-HPV infections exhibited a bimodal age distribution with a peak at ≤25 years, a decline with age and a second peak at ≥55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR-HPV infections in women attending a gynecological outpatient clinic in Beijing.