National strategic advocacy to manage patients with inherited bleeding disorders in low and lower-middle income countries.

INTRODUCTION: Inherited bleeding disorders (IBDs) including hemophilia, von Willebrand disease, platelet disorders, mucocutaneous bleeding disorders and coagulation factor deficiencies are rarely found and under-recognized in low and lower-middle-income countries. Some patients succumbed to serious bleeding without diagnosis and treatment during childhood. AREA COVERED: Diagnosis, management, and prevention should be integrated into the existing health care system. Although some countries have not implemented appropriate health care infrastructure, an initiative plan should be set up by cooperation of experienced experts and health care providers. Identification of patients with IBDs should be started in the antenatal setting to search for females at risk of carrier state. The investigations include bleeding assessment, mixing venous clotting time, coagulogram, coagulation factor assay and mutation detection. Genotypic analysis is helpful for confirming the definite diagnosis, carrier detection as well as prenatal diagnosis for females at risk of bearing an offspring with severe bleeding manifestations. Management involves replacement therapy ranging from blood component to virus-inactivated factor concentrate. Appropriate research is an essential backbone for improving patients' care. EXPERT OPINION: Effective national strategic advocacy to manage patients with IBDs requires intensive collaboration among policy makers, health care providers, patients, and family members.

Risk-stratified papillary thyroid microcarcinoma: post-operative management and treatment outcome in a single center.

PURPOSE: This article aims to review and assess the post-operative management and treatment outcomes of papillary thyroid microcarcinoma (PTMC) in risk-stratified patients. METHODS: We retrospectively analyzed the data of PTMC patients who underwent thyroid surgery with or without radioactive iodine treatment (RAI) in a single center between January 2011 and December 2017. Demographic and clinicopathologic data were collected. Risk stratification according to the 2015 American Thyroid Association guideline was applied. RESULTS: Three hundred forty PTMC patients were included. Post-operative RAI was performed in 216/340 (63.53%) patients. In the non-RAI scenario, there were 122 low-risk and two intermediate-risk patients. In total, 261 (76.77%), 57 (16.76%), and 22 (6.47%) patients were classified as low, intermediate, and high risk, respectively. With a median follow-up time of 36 months (interquartile range: 23, 52), we found unfavorable outcomes (evidenced by imaging or out-of-range serum tumor marker levels: high thyroglobulin [Tg] or rising Tg antibody [TgAb] levels) in 8/340 (2.35%) patients, all of which received RAI. PTMC patients with unfavorable outcomes were stratified as low risk (4/261 [1.53%]), intermediate risk (1/57 [1.75%]), or high risk (3/22 [13.64%]). One death occurred in a patient with initial distant metastasis in the high-risk group. Initial high-risk stratification and initial stimulated Tg (of at least 10 ng/mL) were demonstrated as independent predictors for PTMC unfavorable outcomes (persistent or recurrent disease). Five patients with unfavorable outcomes (four with persistent disease and one with recurrent disease) had abnormal Tg or TgAb values despite unremarkable imaging findings. Moreover, 79/124 (63.71%) patients in the non-RAI scenario were only followed up with neck ultrasound. CONCLUSIONS: In general, at least 98% of low-risk and intermediate-risk PTMC patients showed favorable outcomes without persistent or recurrent disease, defined by either imaging or serum tumor markers. Nevertheless, aggressive disease could occur in few PTMC patients. Decisions on post-operative management and follow-up may be guided by initial high-risk stratification and initial stimulated Tg levels (≥10 ng/mL) as independent predictors for PTMC unfavorable outcomes. Monitoring using both imaging and serum tumor markers is crucial and should be implemented for patients with PTMC.

Precision and Effects of a Small Meal on DXA-Derived Visceral Adipose Tissue, Appendicular Lean Mass, and Other Body Composition Estimates In Nonobese Elderly Men.

BACKGROUND: Information on precision errors and the least significant change (LSC) of dual energy X-ray absorptiometry (DXA)-derived body composition estimates is scarce, particularly for the appendicular lean mass (ALM) and appendicular lean mass index (ALMI). Overnight fasting is recommended for body composition measurements but has not been well tolerated by some elderly patients. This study aimed to establish precision errors and LSC values of body composition estimates in all regions-including visceral adipose tissue (VAT) and ALM-and the ALMI to assess the effect of a small meal on body composition and to estimate the changes it incurred. METHODOLOGY: Our institutional review board approved the study protocol. Altogether, 36 non-obese men aged ≥60 years, having given written informed consent, underwent body composition assessment after fasting overnight except for water. They underwent DXA scans three times, each time with repositioning (to simulate the clinical setting), the last after consuming a standardized meal (210-250 g and 200 cc of water). RESULTS: Precision errors and LSC values of DXA-derived body composition estimates in these elderly men tended to be higher than those in reports on younger subjects. Coefficients of variation (CVs (%)) of total bone mass (Tb.BMC) and total lean mass (Tb.LM) were <1%, whereas those of total fat mass (Tb.FM) and total %fat mass (Tb.%FM) were <2%, with LSCs of 45.8 g, 706.52 g, 731.4 g, and 1.15%, respectively. The CVs (LSC) of VAT, ALM, and ALMI were 8.9% (150.65 g), 0.93% (501 g), and 0.94% (0.19), respectively. After meal consumption, the mean changes in Tb.FM, Tb.BMC, and Tb.LM were -100, -8.2, and 440 g, respectively. CONCLUSIONS: Effects of a small meal on most parameters were trivial, including those for VAT, ALM, and ALMI, where changes were not statistically significant. None exceeded the LSC of ALM and ALMI, suggesting that a small meal is allowable before these measurements.

Iodine-131 metaiodobenzylguanidine (131I-mIBG) treatment in relapsed/refractory neuroblastoma.

BACKGROUND: I-meta-iodo-benzylguanidine (I-mIBG) therapy has been used in treatment of for advanced neuroblastoma for many years with promising results. There are several studies regarding predictors and outcomes of I-mIBG therapies in relapsed/refractory neuroblastoma patients. OBJECTIVE: To identify the predictors and outcomes of I-mIBG treatment in relapsed/refractory neuroblastoma. METHODS: This study was a retrospective review of 22 patients with high risk stage IV relapsed/refractory neuroblastoma who received at least one cycle of I-mIBG therapy. Patient' characteristics, hematologic toxicity, scintigraphic semi-quantitative scoring, and overall survival were recorded. Factors predicting survival were analyzed. RESULTS: Twenty-two patients (50% male) with mean age of 3.7 years (4.8 months to 8.3 years) received I-mIBG therapies at an average of 3.8 and mean dose of 136 mCi (5032 MBq) per treatment. Most common acute hematologic toxicity was thrombocytopenia. Overall 5-year survival rate was 37% (95% confidence interval: 16.3-58.0) and median survival time was 2.8 year (95% confidence interval: 1.38-6.34). Patients with rising Curie score of ≥25% upon the second therapy were major determinants of overall survival with poorer response to treatment. At least three treatments of I-mIBG were needed to identify some degrees of survival prolongation (crude hazard ratio: P-value = 0.003). Age, sex, metastatic status, and baseline Curie scoring system were good predictors associated with survival. Seven patients (32%) demonstrated objective responses. CONCLUSION: Despite multimodality therapy, high risk neuroblastoma had a propensity of treatment failure in terms of relapsed or refractory, with some objective responses after I-mIBG treatments. The declined or non-rising Curie score upon second post-treatment total body scan was an important predictor of survival and aided a decision whether or not to proceed with bone marrow transplantation.

Errors in Patient Positioning for Bone Mineral Density Assessment by Dual X-Ray Absorptiometry: Effect of Technologist Retraining.

Improper positioning is one of the factors that can lead to incorrect bone mineral density (BMD) results. This study aimed to assess the frequencies of erroneous positioning during three periods: before retraining of the technologists (BR), after retraining (AR), and at the current timepoint 8 years after retraining (C). The BMD images of the first 150 consecutive patients who underwent DXA of the lumbar spine and hip during each of the three periods were retrospectively reviewed. Patients were excluded if they had severe scoliosis, rendering proper positioning impossible. Each BMD image was assessed by an International Society of Clinical Densitometry certified clinical densitometrist who was blinded to the date of the initial examination. For the lumbar spine in the BR group, the criteria frequently not met were inclusion of both iliac crests (33.8%), straightness (30.3%), and midline positioning (20.4%); the respective frequencies were significantly reduced to 0.8%-5.6%, 2.1%-3.0%, and 0%-2.8% in the AR and C groups (p < 0.05). For the hip in the BR group, the criteria frequently not met were straightness (52.8%) and internal rotation (21.8%); the respective frequencies were significantly reduced to 0%-4.2% and 8.3%-8.4% in the AR and C groups (p < 0.05). Overall improper positioning in the BR group was 49.3% and 57.3% at the lumbar spine and the hip, respectively; the respective frequencies were reduced to 9.3% and 12.7% in the AR group, and to 2.7% and 7.3% in the C group. The least significant change values for the lumbar spine, femoral neck, and total hip also became smaller after retraining. Retraining the technologists improved patient positioning, as evidenced by the decreased frequencies of erroneous positioning and the improved least significant change values after the retraining.

Simulated increased soft tissue thickness artefactually decreases trabecular bone score: a phantom study.

BACKGROUND: Trabecular bone score (TBS), which has been proposed to be used in complementary with bone mineral density (BMD) to improve the assessment of fracture risk, is negatively associated with body mass index (BMI). The effect of soft tissue, which is expected to be thicker in subjects with high BMI, on TBS was studied using three scan types: Hologic with fast array mode (Hfa), Hologic with high definition mode (Hhd), and GE-Lunar iDXA. METHODS: A spine phantom provided by Hologic for routine quality control procedure was scanned using three scan types: Hfa, Hhd, and iDXA. The phantom was scanned with an overlying soft tissue equivalent material (bolus used in radiotherapy) of 0 (without), 1, 2.5, 3.5, 5 and 7.5 cm thick. For each setting, 30 acquisitions were performed in the same way as for the quality control procedure. TBS was calculated using TBS iNsight® software version 2.1 on the same regions of interest as those used for lumbar spine BMD. RESULTS: Mean ± SD TBS of the phantom (without overlying soft tissue) were 1.379 ± 0.018, 1.430 ± 0.009, and 1.423 ± 0.005 using Hfa, Hhd, and iDXA, respectively. A one-way repeated measures ANOVA showed that there were statistically differences in TBS due to different thicknesses of soft tissue equivalent materials for all three scan types (p < 0.001). A Tukey post-hoc test revealed that the decrease in TBS was statistically significant (p < 0.001) when the soft tissue thickness was 1 cm (-0.0246 ± 0.0044, -0.0319 ± 0.0036, and -0.0552 ± 0.0015 for Hfa, Hhd, and iDXA, respectively). Although to a lesser degree, the effects were also statistically significant for BMD (p < 0.05): an increase for Hfa and Hhd but a decrease for iDXA. However, these changes did not exceed the least significant change (LSC) derived from patients. CONCLUSIONS: Increased soft tissue thickness results in lower TBS value. Although BMD is also affected, it is unlikely to pose a clinical problem because the change is unlikely to exceed the patient-derived LSC.

Incidental Gallbladder Cancer Visualized From Posttreatment 131I Whole-Body Scan.

A 72-year-old woman with papillary thyroid cancer post-total thyroidectomy was referred for post-I treatment whole-body scan. Images revealed focal uptake within the gallbladder. Cholecystectomy was subsequently performed, and the pathology report showed well-differentiated adenocarcinoma. Given a history of papillary thyroid cancer, the iodine uptake was reasonably explained as metastasis; however, gallbladder metastasis was extremely infrequent. Literature described the incidental radioiodine retention in the gallbladder as false-positive findings, which can be normal variants or benign hepatobiliary conditions. Primary gallbladder malignancy could be counted for another possibility despite controversial mechanism of uptake.

Age-Adjusted Dual X-ray Absorptiometry-Derived Trabecular Bone Score Curve for the Lumbar Spine in Thai Females and Males.

Trabecular bone score (TBS), which has been shown to discriminate patients with fractures from healthy individuals, decreases with age. This study was conducted to derive an age-adjusted normative TBS curve for each gender aged 30-80 + years to serve as reference data for Thai males and females. A cross-sectional study was conducted among employees from the Electricity Generating Authority of Thailand cohorts, after excluding those with conditions potentially affecting bone metabolism and analysis. The values of TBS at L1-L4 vertebrae were analyzed using a commercial software. Age-adjusted TBS curves were constructed using segmental linear regression analysis for each gender. Additional analysis was also performed on TBS with age, body mass index, and body mineral density (BMD) at L1-L4 vertebrae as covariates. A database of 848 healthy subjects (341 females and 507 males) aged 30-80+ years was created. The BMDs of both male and female subjects in the youngest decade were not statistically different from previous reports (p = 0.31 and 0.22 for females and males, respectively). In this age group, the mean TBS was higher in females, albeit not statistically significant (p = 0.12). Between the ages of 30-80+ years, female and male TBS dropped by 19.8% (0.40% per year) and 10.1% (0.20% per year), respectively. The association with TBS was weak for body mass index and moderate for BMD (coefficients of about -0.01 and 0.4-0.5, respectively). The age-adjusted reference curves for healthy Thai females and males aged 30-80+ years have been established.

Factors affecting disease-free status of differentiated thyroid carcinoma patients.

PURPOSE: The study aim was to assess factors that impact on the outcome of radioiodine therapy in patients diagnosed with differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: We performed a retrospective cohort study on 256 patients with DTC who underwent thyroidectomy and received radioiodine therapy during December 2003 to January 2012. All patients were followed up for at least 1 year. They were considered disease- free by the criteria of the revised American Thyroid Association Management Guideline for Patients with Thyroid nodules and DTC (ATA guideline 2009). RESULTS: On Cox univariate analysis, factors associated with disease-free status were age<45, stage I tumor, low risk group by histopathology, unifocal tumor involvement, stimulated serum Tg level at 1st dose of radioiodine therapy and no distant metastasis from 1st post-treatment WBS (post RxWBS). On multivariate analysis, stage I tumor and stimulated serum Tg level at 1st dose of radioiodine therapy<30 ng/mL were the significant prognostic factors that increased disease-free rate by 1.73 times and 2.60 times, respectively (P-value<0.05). CONCLUSIONS: Factors affecting the outcome of radioiodine therapy in our study were age, stage, risk of recurrence by histopathology, unifocal tumor involvement and 1st postRxWBS findings. From these factors, stage I tumor and stimulated serum Tg level at 1st dose of radioiodine therapy were independent prognostic factors that substantial increase the disease-free rate.

Unexpectedly expected fetal thyroid function on posttreated radioiodine (131I) SPECT/CT of a patient with differentiated thyroid cancer.

We present a 25-year-old woman who has a diagnosis of differentiated thyroid cancer, a 2.5-cm papillary carcinoma in the right lobe, and presence of minimal extrathyroid invasion. 131I ablation and/or treatment of 150 mCi was given orally 3 months after total thyroidectomy. A fetus with radioiodine uptake in the fetal thyroid was unsuspectedly detected by SPECT/CT after 131I treatment.

131I-rituximab treatment in patient with relapsed non-Hodgkin's lymphoma: the first case report in Thailand.

Radioimmunotherapy (RIT) with 131-rituximab is a safe and effective treatment in patients with relapsed, refractory follicular lymphoma. The authors demonstrated the first case of 131-rituximab treatment in the patient with relapsed non-Hodgkin's lymphoma (NHL) in Thailand. There was no immediate complication after treatment. Impressive treatment response occurred.

Serum oncofetal fibronectin (onfFN) mRNA in differentiated thyroid carcinoma (DTC): large overlap between disease-free and metastatic patients.

AIM: This study assessed if onfFN mRNA in the peripheral blood of patients with DTC can identify individuals with metastatic disease. METHODS: Comparison of onfFN mRNA was made among 3 groups: disease-free, lymph node metastasis, and distant metastasis using real-time RT-PCR on 5 ml blood samples from each DTC patient. RESULTS: Fifty-one patients were included: 30 (59%) were disease-free; 7 (13.7%) had lymph node metastasis; and 14 (27.5%) had distant metastasis. OnfFN mRNA levels in the 3 groups were significantly different (P=0.001) but with a large overlap and the expression being highest in the disease-free group. Subgroup analysis of the metastatic groups did not show any effect of age, cell type, and serum TSH, Tg, and antiTg on onfFN mRNA. The within-run and between-run root mean square coefficients of variations were <2%. CONCLUSION: OnfFN mRNA in patients with DTC cannot identify those with metastatic disease.