Gamma-interferon activates a nuclear protein that binds to the gamma-interferon activation site of the thyroglobulin gene

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Characterization of thyroid-stimulating blocking antibodies that appeared during transient hypothyroidism after radioactive iodine therapy

Hypothyroidism after radioactive iodine (RAI) therapy for Graves' disease can be transient or permanent. The cause for early transient hypothyroidism is unknown. We evaluated 11 patients who developed transient hypothyroidism within 6 months of RAI and 12 who remained euthyroid after RAI. Approximately equal numbers of patients in each group had thyroid-stimulating antibody (TSAb) that increased cyclic adenosine monophosphate (cAMP) levels in Chinese hamster ovary (CHO) cells transfected with the recombinant human thyrotropin receptor (TSHR) (WT cells). Approximately equal numbers of patients from both groups had an increase in TSAb activity post-RAI. All TSAbs had their dominant functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity because they, but not TSH, completely lost stimulating activity in a receptor chimera, wherein TSHR residues 90-165 were substituted by equivalent residues of the lutropin/choriogonadotropin receptor (LH/CGR). Although equal numbers of patients in both groups had thyrotropin-binding inhibiting immunoglobulin activity (TBII), as measured by radioreceptor assay before RAI, patients with transient hypothyroidism had a surge in TBII activity and all except one became positive for thyroid-stimulating blocking antibodies (TSBAb), as measured by inhibition of TSH-stimulated cAMP from WT cells. When immunoglobulin G (IgGs) were epitope-mapped using TSHR/LH-CGR chimeras with different substitutions, 8 hypothyroid subjects had TSBAbs directed against residues 90-165 of the TSHR, as well as TSHR residues 261-370. Two had functional epitopes directed at residues 9-89 as well as TSHR residues 261-370. None of the euthyroid control patients developed TSBAbs and their TBII activity decreased post-RAI. When patients with transient hypothyroidism reverted to a euthyroid state, TSAb was still detectable in 5; however, TBII was present in all and TSBAb, although decreased, was still positive in 9. In summary, RAI therapy was associated with a change in thyroid antibody characteristics in most patients. Additionally, patients with a surge in TBII and the appearance of TSBAb developed transient hypothyroidism after RAI.published_or_final_versio

The prevalence of diabetes mellitus and its effect in elderly subjects in Hong Kong

The prevalence of non-insulin-dependent diabetes mellitus in 1467 ambulatory elderly subjects aged from 60 to 90 years was determined using fasting plasma glucose as a screening test. A questionnaire survey on the history of diabetes and related complications was performed. The results showed that 10.7% had already been diagnosed as having diabetes mellitus. Screening revealed a further 5% who had diabetes mellitus but were asymptomatic. The prevalence of non-insulin-dependent diabetes mellitus was 15% (95% confidence interval 9-21) among the 60- to 80-year-old age group and 17% confidence interval (3 to 30) in those older than 80 years. Obesity and advancing age were adverse risk factors associated with diabetes. The diabetic subjects had significantly more coronary and cerebrovascular atherosclerosis, hypertension, and adverse lipid profiles. Even in the non-diabetic elderly subjects, fasting blood glucose was positively correlated with body weight and body mass index, confirming the importance in the aetiology of non-insulin-dependent diabetes mellitus. This is a common disease in the elderly and is associated with significant cardiovascular morbidity.published_or_final_versio

Transforming growth factor-betal gene polymorphisms and bone turnover, bone mineral density and fracture risk in Southern Chinese Women

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Does timing of surgery matter in fragility hip fractures?

The effect of delay of surgery on the geriatric hip fractures has been a subject of interest in the past two decades. While the elderly patients will not tolerate long periods of immobilization, it is still unclear how soon these surgeries need to be performed. A review of existing literature was performed to examine the effect of timing of surgery on the different outcome parameters of these patients. Although there is conflicting evidence that early surgery would improve mortality, there is widespread evidence in the literature that other outcomes including morbidity, the incidence of pressure sores, and the length of hospital stay could be improved by shortening the waiting time of hip fracture surgery. We concluded that it is beneficial to the elderly patients to receive surgical treatment as an urgent procedure as soon as the body meets the basic anesthetic requirements. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Genetic mapping for thyrotoxic periodic paralysis

Symposium on Endocrine SurgeryTPP is a complication of thyrotoxicosis affecting 25% of thyrotoxic southern Chinese male but not female patients. Paralysis due to hypokalemia typically occurs after a high carbohydrate meal. This episodic paralysis will remit with the control of thyrotoxicosis but may recur with relapse of the disease. Shifting of potassium into intracellular space results in hypokalemia and paralysis. Increased Na, K-ATPase activity has been observed in TPP patients when compared to thyrotoxic Graves’ disease (GD) patients and normal controls. To study the association of Na, K-ATPase genotype with TPP, we evaluated TPP patients (n = 100) and compared them to male GD patients without TPP (n = 60) and normal male subjects (n = 70). A set of polymorphic microsatellite markers with a genetic distance < 10 cM was used to study the allelic distribution. Our results showed that there was no significant difference between the 3 groups in the allelic distribution for all markers associated with the Na, K-ATPase α1 (1p13), α2 (1q21-23), α3 (19q13.2) and β1 (1q22-25), β2 (17p13.1), β3 (3q22-23) genes. There was also no association of CACNL1A3 (dihydropyridine sensitive calcium channel receptor gene, located at chromosome 1q32) with TPP. Mutation of CACNL1A3 gene is linked to Familial Hypokalemia Periodic Paralysis in Caucasians. On screening the X-chromosome, one of the alleles (size 289) of the marker DXS1214 in the region of Xp11.3-21 was observed to be more frequent in TPP subjects when compared to GD patients and normal subjects (p < 0.05), suggesting that this locus may be linked to TPP.published_or_final_versio

Nitrogen-containing bisphosphonates are associated with reduced risk of pneumonia in patients with hip fracture

The objective of this work was to study the risk of pneumonia and pneumonia mortality among patients receiving nitrogen‐containing bisphosphonates (N‐BPs), non‐N‐BP anti‐osteoporosis medications, and no anti‐osteoporosis medications after hip fracture. We studied a historical cohort using a population‐wide database. Patients with first hip fracture during 2005–2015 were identified and matched by time‐dependent propensity score. The cohort was followed until December 31, 2016, to capture any pneumonia and pneumonia mortality. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox‐proportional hazards regression. Absolute risk difference (ARD) and number needed to treat (NNT) were calculated. We identified 54,047 patients with hip fracture. Of these, 4041 patients who received N‐BPs and 11,802 without anti‐osteoporosis medication were propensity score–matched. N‐BPs were associated with a significantly lower risk of pneumonia compared with no treatment (6.9 versus 9.0 per 100 person‐years; HR 0.76; 95% CI, 0.70 to 0.83), resulting in an ARD of 0.02 and NNT of 46. A similar association was observed with pneumonia mortality (HR 0.65; 95% CI, 0.56 to 0.75). When N‐BPs were compared with non‐N‐BP anti‐osteoporosis medications, the association remained significant. N‐BPs were associated with lower risks of pneumonia and pneumonia mortality. Randomized controlled trials are now required to determine whether N‐BPs, non–vaccine‐based medications, can reduce pneumonia incidence in high risk groups

Surgical site abscess caused by Lactobacillus fermentum identified by 16S ribosomal RNA gene sequencing

We report the first case of surgical site abscess caused by Lactobacillus fermentum from a 53-year-old woman with squamous cell carcinoma of the esophagus after transthoracic esophagectomy and neoadjuvant chemoirradiation. 16S rRNA gene sequencing is a useful tool to better characterize the epidemiology and clinical significance of L. fermentum. © 2007 Elsevier Inc. All rights reserved.postprin

Development and validation of sex-specific hip fracture prediction models using electronic health records: a retrospective, population-based cohort study

Background: Hip fracture is associated with immobility, morbidity, mortality, and high medical cost. Due to limited availability of dual-energy X-ray absorptiometry (DXA), hip fracture prediction models without using bone mineral density (BMD) data are essential. We aimed to develop and validate 10-year sex-specific hip fracture prediction models using electronic health records (EHR) without BMD. Methods: In this retrospective, population-based cohort study, anonymized medical records were retrieved from the Clinical Data Analysis and Reporting System for public healthcare service users in Hong Kong aged ≥60 years as of 31 December 2005. A total of 161,051 individuals (91,926 female; 69,125 male) with complete follow-up from 1 January 2006 till the study end date on 31 December 2015 were included in the derivation cohort. The sex-stratified derivation cohort was randomly divided into 80% training and 20% internal testing datasets. An independent validation cohort comprised 3046 community-dwelling participants aged ≥60 years as of 31 December 2005 from the Hong Kong Osteoporosis Study, a prospective cohort which recruited participants between 1995 and 2010. With 395 potential predictors (age, diagnosis, and drug prescription records from EHR), 10-year sex-specific hip fracture prediction models were developed using stepwise selection by logistic regression (LR) and four machine learning (ML) algorithms (gradient boosting machine, random forest, eXtreme gradient boosting, and single-layer neural networks) in the training cohort. Model performance was evaluated in both internal and independent validation cohorts. Findings: In female, the LR model had the highest AUC (0.815; 95% Confidence Interval [CI]: 0.805–0.825) and adequate calibration in internal validation. Reclassification metrics showed the LR model had better discrimination and classification performance than the ML algorithms. Similar performance was attained by the LR model in independent validation, with high AUC (0.841; 95% CI: 0.807–0.87) comparable to other ML algorithms. In internal validation for male, LR model had high AUC (0.818; 95% CI: 0.801–0.834) and it outperformed all ML models as indicated by reclassification metrics, with adequate calibration. In independent validation, the LR model had high AUC (0.898; 95% CI: 0.857–0.939) comparable to ML algorithms. Reclassification metrics demonstrated that LR model had the best discrimination performance. Interpretation: Even without using BMD data, the 10-year hip fracture prediction models developed by conventional LR had better discrimination performance than the models developed by ML algorithms. Upon further validation in independent cohorts, the LR models could be integrated into the routine clinical workflow, aiding the identification of people at high risk for DXA scan. Funding: Health and Medical Research Fund, Health Bureau, Hong Kong SAR Government (reference: 17181381)

Clinical management guidelines for osteoporosis in Hong Kong

The following guidelines provide a basis for the management of osteoporosis for the practising physician in Hong Kong. The guidelines have been complied by a working group that represents the specialties concerned with osteoporosis and summarise the current management of osteoporosis based on available published evidence and relevant local experience.published_or_final_versio