Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature.

Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of nuclear factor kappa B ligand (RANKL), involved in bone resorption. Continued use of denosumab results in a potent and sustained decrease in bone turnover, an increase in bone mineral density (BMD), and a reduction in vertebral and hip fractures. The anti-resorptive effects of denosumab are reversible upon cessation, and this reversal is accompanied by a transient marked increase in bone turnover that is associated with bone loss, and of concern, an increased risk of multiple vertebral fractures. In this review, we outline the effects of denosumab withdrawal on bone turnover markers, BMD, histomorphometry, and fracture risk. We provide an update on recent clinical trials that sought to answer how clinicians can transition away from denosumab safely with follow-on therapy to mitigate bone loss and summarise the recommendations of various international guidelines.

Severe radiation thyroiditis after radioactive iodine for treatment of Graves' disease.

Radiation thyroiditis resulting from radioactive iodine-131 treatment for Graves' disease is an uncommon complication. Although a majority of patients are asymptomatic or manifest mild symptoms that can be managed conservatively, published literature describing severe radiation thyroiditis resulting in significant morbidity is lacking. We herein report on six patients with severe radiation thyroiditis that resulted in hospitalisation, including an unusual complication of myopericarditis.

High Thyroid Stimulating Receptor Antibody Titre and Large Goitre Size at First-Time Radioactive Iodine Treatment are Associated with Treatment Failure in Graves' Disease.

INTRODUCTION: Our study aimed to identify the factors associated with successful first-time radioactive iodine (RAI) treatment in patients with Graves' disease (GD). MATERIALS AND METHODS: This is a restrospective study of patients with GD who were treated with RAI. Treatment success was defined as onset of permanent hypothyroidism or euthyroidism after 1 dose of RAI at 1-year follow-up. RESULTS: There were 388 GD patients who underwent RAI treatment between January 2014 and December 2015. Of these, 74% achieved treatment success. Median time to achieve permanent hypothyroidism was 2 months. Male gender, smoking, higher antithyroid drug dosage, lower thyroid stimulating hormone (TSH) level, large goitre size and TSH receptor antibody (TRAb) titre at time of RAI were significantly associated with treatment failure. Multivariate analysis showed that larger goitre size and higher TRAb titre were associated with lower first-time RAI success. CONCLUSION: Larger goitre size and higher TRAb titre predict lower success of RAI therapy in GD patients. Treatment decisions and strategies should be customised for patients who present with these characteristics.

Beyond HbA1c: Comparing Glycemic Variability and Glycemic Indices in Predicting Hypoglycemia in Type 1 and Type 2 Diabetes.

BACKGROUND: Hypoglycemia is the major impediment to therapy intensification in diabetes. Although higher individualized HbA1c targets are perceived to reduce the risk of hypoglycemia in those at risk of hypoglycemia, HbA1c itself is a poor predictor of hypoglycemia. We assessed the use of glycemic variability (GV) and glycemic indices as independent predictors of hypoglycemia. METHODS: A retrospective observational study of 60 type 1 and 100 type 2 diabetes subjects. All underwent professional continuous glucose monitoring (CGM) for 3-6 days and recorded self-monitored blood glucose (SMBG). Indices were calculated from both CGM and SMBG. Statistical analyses included regression and area under receiver operator curve (AUC) analyses. RESULTS: Hypoglycemia frequency (53.3% vs. 24%, P < 0.05) and %CV (40.1% ± 10% vs. 29.4% ± 7.8%, P < 0.001) were significantly higher in type 1 diabetes compared with type 2 diabetes. HbA1c was, at best, a weak predictor of hypoglycemia. %CVCGM, Low Blood Glucose Index (LBGI)CGM, Glycemic Risk Assessment Diabetes Equation (GRADE)HypoglycemiaCGM, and Hypoglycemia IndexCGM predicted hypoglycemia well. %CVCGM and %CVSMBG consistently remained a robust discriminator of hypoglycemia in type 1 diabetes (AUC 0.88). In type 2 diabetes, a combination of HbA1c and %CVSMBG or LBGISMBG could help discriminate hypoglycemia. CONCLUSION: Assessment of glycemia should go beyond HbA1c and incorporate measures of GV and glycemic indices. %CVSMBG in type 1 diabetes and LBGISMBG or a combination of HbA1c and %CVSMBG in type 2 diabetes discriminated hypoglycemia well. In defining hypoglycemia risk using GV and glycemic indices, diabetes subtypes and data source (CGM vs. SMBG) must be considered.

Radioiodine associated de novo Graves' opthalmopathy in an Asian cohort.

Radioactive iodine in the treatment of Graves' disease has been associated with the development of de novo Graves' ophthalmopathy (GO). In this report, we describe five individuals who required extensive ophthalmic treatment for post-RAI de novo GO.

Persistent hyperthyroidism and de novo Graves' ophthalmopathy after total thyroidectomy.

We report a patient with Graves' disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves' ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion. LEARNING POINTS: It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves' ophthalmopathy.

Risk of Major Abdominal Surgery in an Asian Population-based Crohn's Disease Cohort.

BACKGROUND: Crohn's disease (CD) is increasing in incidence and prevalence in Asia, but there is a paucity of population-based studies on risk factors for surgery in Asian patients with CD. This will be useful to identify patients who may benefit from top-down treatment. This study describes the rates of abdominal surgery and identifies associated risk factors in Singaporean patients with CD. METHODS: This was a retrospective observational study. The medical records of Singaporeans diagnosed with CD from 1970 to 2013 were reviewed from 8 different hospitals in Singapore. The cumulative probability of CD-related abdominal surgery was estimated using the Kaplan-Meier method. The logistic regression model was used to assess associations between independent risk factors and surgery. RESULTS: The cohort of 430 Singaporean patients with CD included 63.5% Chinese, 11.9% Malay, and 24.7% Indians, with a male to female ratio of 1.6; median follow-up was 7.3 years (range, 2.9-13.0 yr) and median age at diagnosis 30.5 years (range, 19.5-43.7 yr). One hundred twelve patients (26.0%) required major abdominal surgery: the cumulative risk of surgery was 14.9% at 90 days, 21.2% at 5 years, 28.8% at 10 years, 38.3% at 20 years, and 50.6% at 30 years from diagnosis. Of the surgical patients, 75.0% were Chinese, 10.7% Malays, and 14.3% Indians; 21.4% underwent surgery for inflammatory disease, 40.2% for stricturing disease, and 38.4% for penetrating disease. Age at diagnosis (A2 17-40 yr, OR: 2.75, 95% confidence interval [CI], 1.14-7.76), ileal disease (L1 location, OR: 2.35, 95% CI, 1.14-5.0), stricturing (B2 OR: 6.09, 95% CI, 3.20-11.8), and penetrating behavior (B3 OR: 21.6, 95% CI, 9.0-58.8) were independent risk factors for CD-related abdominal surgery. Indian patients were less likely to require surgery (OR: 0.40, 95% CI, 0.19-0.78). CONCLUSIONS: Age at diagnosis, L1 location, B2, and B3 disease behavior are independent risk factors for abdominal surgery. Interestingly, despite a higher prevalence of CD in Indians, a smaller proportion of Indian patients required surgery. These findings suggest that both environmental and genetic factors contribute to the risk of surgery in Asian patients with CD.

Y-Box-binding protein-1 is a promising predictive marker of radioresistance and chemoradioresistance in nasopharyngeal cancer.

The Y-Box-binding protein-1, a member of the cold-shock domain DNA- and RNA-binding protein superfamily, is known to mediate chemoresistance. The aim of this study was to determine the expression of Y-Box-binding protein-1 in nasopharyngeal cancer in vitro and in tumor tissue samples as well as analyze the clinicopathological significance of Y-Box-binding protein-1 expression in nasopharyngeal cancer, in particular as a predictor of outcome after treatment. The Y-Box-binding protein-1 expression profile was evaluated at the mRNA and protein levels in poorly differentiated CNE-2 nasopharyngeal cancer cells by real-time RT-PCR, western blot analysis and immunohistochemistry. Y-Box-binding protein-1 expression in 143 nasopharyngeal cancer specimens was examined by immunohistochemistry and correlated with clinicopathologic parameters. Y-Box-binding protein-1 mRNA and protein were found to be expressed in CNE-2 nasopharyngeal cancer cells in vitro. Of 143 patient tissue sections, 137 (96%) were stained positive for the Y-Box-binding protein-1 protein. Y-Box-binding protein-1 immunostaining was observed to be predominantly cytoplasmic. A higher recurrence of nasopharyngeal cancer was found in patients whose tissues had increased Y-Box-binding protein-1 expression (P<0.001). The Cox proportionate hazard regression model also established that high Y-Box-binding protein-1 immunoreactivity was significantly correlated with increased risk (2.13 times) of recurrence as compared to low Y-Box-binding protein-1 immunoreactivity (P=0.01). Within groups of patients treated by radiotherapy or chemoradiotherapy, recurrent cases had significantly higher Y-Box-binding protein-1 expression than nonrecurrent cases (P<0.001 and P=0.0035, respectively). These data suggest that Y-Box-binding protein-1 expression has clinicopathological significance with potential as a predictive marker of recurrence in nasopharyngeal cancer patients who undergo radiotherapy or chemoradiotherapy.