BRAF mutation in papillary thyroid cancer-Prevalence and clinical correlation in a South-East Asian cohort.

OBJECTIVE: BRAF mutation is the commonest mutation seen in papillary thyroid cancer (PTC), but its prevalence and clinical significance vary across countries. We aim to evaluate the prevalence and clinico-pathological correlation of BRAF mutation in PTC patients at our centre. STUDY DESIGN: Retrospective cohort study of 75 consecutive archival thyroid specimens, whereby BRAF mutation was detected using a polymerase chain reaction (PCR) technique and correlated with clinical and pathological features and outcomes. SETTING: Tertiary university hospital in Singapore. PARTICIPANTS: A total of 75 consecutive histologically proven archival thyroid specimens from patients who underwent thyroidectomy for PTC were accrued for this study. MAIN OUTCOME MEASURES: Main outcome is to determine the prevalence of the BRAF mutation in our South-East Asian population. Secondary aim is to correlate the mutational status with adverse pathological features like histological variants, multi-focality, lymphovascular invasion and extra-thyroidal extension, clinical features like demographics, TNM stage, recurrence and survival, as well as treatment details like type of surgery performed and radioiodine doses. RESULTS: BRAF mutation was detected in 56% (42/75) of PTC. All but one BRAF-mutated PTC had the BRAFV600E mutation. BRAF-mutated tumours were associated with an advanced T-stage (P = 0.049) and were more likely to have a central neck dissection (P = 0.036). There was no significant correlation between BRAF mutation status and clinical outcomes. CONCLUSION: The prevalence of BRAF mutation is 56%. BRAF mutation-positive tumours were associated with locally advanced disease, but not poorer survival.

Consensus of official position of IOF/ISCD FRAX initiatives in Asia-Pacific region.

The fracture risk assessment tool (FRAX(®)) has been developed for the identification of individuals with high risk of fracture in whom treatment to prevent fractures would be appropriate. FRAX models are not yet available for all countries or ethnicities, but surrogate models can be used within regions with similar fracture risk. The International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) are nonprofit multidisciplinary international professional organizations. Their visions are to advance the awareness, education, prevention, and treatment of osteoporosis. In November 2010, the IOF/ISCD FRAX initiative was held in Bucharest, bringing together international experts to review and create evidence-based official positions guiding clinicians for the practical use of FRAX. A consensus meeting of the Asia-Pacific (AP) Panel of the ISCD recently reviewed the most current Official Positions of the Joint Official Positions of ISCD and IOF on FRAX in view of the different population characteristics and health standards in the AP regions. The reviewed position statements included not only the key spectrum of positions but also unique concerns in AP regions.

Official Positions for FRAX® clinical regarding international differences from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Osteoporosis is a serious worldwide epidemic. Increased risk of fractures is the hallmark of the disease and is associated with increased morbidity, mortality and economic burden. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors, femoral neck BMD, country specific mortality and fracture data and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator at the time paper was accepted for publication. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. In order to provide additional guidance to clinicians, a FRAX® International Task Force was formed to address specific questions raised by physicians in countries without FRAX® calculators and seeking to integrate FRAX® into their clinical practice. The main questions that the task force tried to answer were the following: The Task Force members conducted appropriate literature reviews and developed preliminary statements that were discussed and graded by a panel of experts at the ISCD-IOF joint conference. The statements approved by the panel of experts are discussed in the current paper.

Use of age-dependent FRAX-based intervention thresholds for Singapore.

Assessment and treatment pathways based on age-specific intervention thresholds in Singapore using FRAX paths can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low risk. PURPOSE: Intervention thresholds for the treatment of osteoporosis have been based historically on the measurement of bone mineral density. The development of FRAX® has permitted a more accurate assessment of fracture risk. The aim of the present study was to explore treatment paths and characteristics of women selected for treatment in Singapore based on FRAX. METHODS: The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Singapore. The methodology was applied to women age 50 years or more drawn from the population-based Singapore Chinese Health Study (SCHS) cohort. Missing data for the calculation of FRAX was simulated using data from Chinese cohorts from Hong Kong. RESULTS: Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.9% at the age of 50 years increasing to 32% at the age of 90 years. A total of 1927 of 29,323 women (7%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 3019 women (10.3%) would be eligible for treatment on the basis of age-dependent thresholds. The mean BMD T-score of women so selected was -2.94. CONCLUSION: Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Singapore to help guide decisions about treatment.

Assessment of sensory neuropathy in diabetic patients without diabetic foot problems.

OBJECTIVES: To study the incidence and extent of peripheral sensory neuropathy in diabetic patients without diabetic foot problems (DFPs) with <5, 5-10 and >10 years duration of diabetes using three different modalities of testing: Pin-Prick Testing, 5.07 Semmes-Weinstein Monofilament Testing (SWMT) and Rapid-Current Perception Threshold (R-CPT) measurements using the Neurometer. METHODS: Our study population consisted of 60 patients (120 feet) treated for diabetes mellitus in the Division of Endocrinology at the National University Hospital. No patient had any DFPs. Twenty-two, 21 and 17 patients had duration of diabetes of <5, 5-10 and >10 years, respectively. All patients were tested for sensory neuropathy using Pin-Prick Testing using a standardized protocol, SWMT and the Neurometer. RESULTS: There was a significantly higher incidence of sensory neuropathy detected by both the Pin-Prick Test and the Neurometer as compared to the SWMT. Also, in all three modalities, there was a significant increase in incidence of sensory neuropathy detected in diabetics with >5 years duration of diabetes. In addition, the Pin-Prick Test showed an increase in extent of sensory neuropathy with a longer duration of diabetes. CONCLUSIONS: The Pin-Prick Test was found to be a simple, cheap and useful diagnostic tool for detection of sensory neuropathy in diabetics without DFPs. In addition, it could accurately delineate the extent of neuropathy in the lower limb - additional useful information not obtainable with SWMT or Neurometer. Even for patients with <5 years duration of diabetes, the incidence of sensory neuropathy detected was considerable. The incidence of neuropathy detected continued to increase with length of duration of diabetes. Hence, we recommend screening of patients for neuropathy as soon as they are diagnosed with diabetes.

Laparoscopic partial adrenalectomy for bilateral cortisol-secreting adenomas.

Bilateral cortisol-secreting adenomas are a rare cause of Cushing's syndrome. We report a case of a 35-year-old woman who presented with ACTH-independent Cushing's syndrome and bilateral adrenal adenomas. Adrenal venous sampling confirmed both adenomas to be hyper-secreting cortisol. She underwent bilateral laparoscopic adrenalectomy; total right and partial left adrenalectomies. At 2-year follow-up, she is maintained on low-dose fludrocortisone and hydrocortisone, and without recurrence of hypercorticolism. Laparoscopic partial adrenalectomy is a feasible option for this rare condition; however, long-term follow-up is needed to determine her total independence from steroid usage.

Measuring the quality of care of diabetic patients at the specialist outpatient clinics in public hospitals in Singapore.

INTRODUCTION: This study aims to measure the quality of care for patients with diabetes mellitus at selected Specialist Outpatient Clinics (SOCs) in the National Healthcare Group. MATERIALS AND METHODS: The cross-sectional study reviewed case-records of patients from 6 medical specialties who were on continuous care for a minimum of 15 months from October 2003 to April 2005. Disproportionate sampling of 60 patients from each specialty, excluding those co-managed by Diabetes Centres or primary care clinics for diabetes, was carried out. Information on demographic characteristics, process indicators and intermediate outcomes were collected and the adherence rate for each process indicator compared across specialties. Data analysis was carried out using SPSS version 13.0. RESULTS: A total of 575 cases were studied. The average rate for 9 process indicators by specialty ranged from 47.8% to 70.0%, with blood pressure measurement consistently high across all specialties (98.4%). There was significant variation (P <0.001) in rates across the specialties for 8 process indicators; HbA1c, serum creatinine and lipid profile tests were over 75%, while the rest were below 50%. The mean HbA1c was 7.3% +/- 1.5%. "Optimal" control of HbA1c was achieved in 51.2% of patients, while 50.6% of the patients achieved "optimal" low-density lipoprotein (LDL)-cholesterol control. However, 47.3% of patients had "poor" blood pressure control. Adherence to process indicators was not associated with good intermediate outcomes. CONCLUSIONS: There was large variance in the adherence rate of process and clinical outcome indicators across specialties, which could be improved further.

Hereditary paraganglioma due to the SDHD M1I mutation in a second Chinese family: a founder effect?

OBJECTIVES/HYPOTHESIS: Hereditary paraganglioma is a rare condition that is inherited in an autosomal-dominant fashion. Four distinct loci have been associated with hereditary paraganglioma, including the SDHD, SDHC, and SDHB genes and a locus at 11q13. The SDHD, SDHC, and SDHB genes code for subunits of succinate dehydrogenase, which forms part of the mitochondrial respiratory chain. SDHD mutations are widely distributed along the gene with no apparent hot spots, although a founder effect has been described in the Dutch population. METHODS: Following a prior report of the SDHD M1I mutation in an Australian Chinese family, a second Chinese family with the same mutation is reported. The proband developed bilateral head and neck paragangliomas at age 34 years and a functioning adrenal pheochromocytoma and two extra-adrenal abdominal paragangliomas 7 years later. His brother had unilateral head and neck paraganglioma at age 39 years. Given the multicentricity of the proband's tumor and the familial clustering of paragangliomas, a clinical diagnosis of hereditary paraganglioma was made, and the proband was tested for a mutation in the SDHD gene. RESULTS: The proband was found to be heterozygous for the SDHD MII mutation that removes the start codon, and his brother subsequently tested positive for the same mutation. The family is not related to the Australian Chinese family. CONCLUSION: The finding suggests the possibility of a founder effect in the Chinese population and warrants further investigation.

Effectiveness of vacuum-assisted closure (VAC) therapy in the healing of chronic diabetic foot ulcers.

INTRODUCTION: This is the fi rst prospective study done locally to determine the effectiveness of vacuum-assisted closure (VAC) therapy in the healing of chronic diabetic foot ulcers. MATERIALS AND METHODS: An electronic vacuum pump was used to apply controlled negative pressure evenly across the wound surface. Changes in wound dimension, presence of wound granulation and infection status of diabetic foot ulcers in 11 consecutive patients with diabetes were followed over the course of VAC therapy. RESULTS: Healing was achieved in all wounds. Nine wounds were closed by split-skin grafting and 2 by secondary closure. The average length of treatment with VAC therapy was 23.3 days. Ten wounds showed reduction in wound size. All wounds were satisfactorily granulated and cleared of bacterial infection at the end of VAC therapy. CONCLUSIONS: VAC therapy was useful in the treatment of diabetic foot infection and ulcers, which after debridement, may present with exposed tendon, fascia and/or bone. These included ray amputation wounds, wounds post-debridement for necrotising fasciitis, wounds post-drainage for abscess, a heel ulcer and a sole ulcer. It was able to prepare ulcers well for closure via split-skin grafting or secondary closure in good time. This reduced cost of VAC therapy, as therapy was not prolonged to attain greater reduction in wound area. VAC therapy also provides a sterile, more controlled resting environment to large, exudating wound surfaces. Large diabetic foot ulcers were thus made more manageable.

Foot screening for diabetics.

INTRODUCTION: This study aims to evaluate the results of foot screening performed in a study population of 2137 diabetics (3926 feet) screened from 2006 to 2008 by the National University Hospital (NUH) multi-disciplinary team for diabetic foot problems. MATERIALS AND METHODS: A standardised protocol was designed. Foot screening consisted of detailed history taking and clinical examination including assessment for sensory neuropathy by Semmes Weinstein monofilament (SWMF) and neurothesiometer and assessment of vasculopathy by ankle-brachial index (ABI) and total body irradiation (TBI). The foot screening was performed by a trained staff nurse. All patients were classified according to King's College Classification. RESULTS: Majority of the patients were in the fifth (27.9%) and sixth (30.0%) decades of life. Two thousand sixty-four had type II diabetes, and only 73 had type I diabetes. Neuropathy was found in 1307 (33.3%) feet based on 5.07 SWMF. Vasculopathy was recorded in 510 (13.0%) and 546 (13.9%) feet based on ABI <0.8 and TBI <0.7. According to King's Classification, 1069 (50.0%) were Stage 1: Normal and 615 (28.8%) were Stage 2: At-Risk. CONCLUSION: Foot screening should be performed as early as possible to detect "At-Risk" feet and prevent the development of diabetic foot complications, thereby further reducing the risk of major amputations.

SECONDARY CAUSES OF OSTEOPOROSIS

Osteoporosis is primarily caused by menopause andageing. However, secondary causes of bone loss can befound in up to 64 percent of patients with osteoporosis.Common medical causes identified have included VitaminD deficiency, glucocorticoid excess, hyperthyroidism,hyperparathyroidism, malabsorption, hypercalciuria,rheumatoid arthritis, and myeloma, while other lifestylerelated causes, such as smoking and excessive alcoholconsumption can also result in bone loss. Addressing all ofthese factors are required to optimise the management ofosteoporosis.