Dopamine receptor and dopamine transporter in obesity: A meta-analysis.

The brain plays a major role in controlling the desire to eat. This meta-analysis aimed to assess the association between dopamine receptor (DR) availability and dopamine transporter (DAT) availability, measured using positron emission tomography, and obesity. We performed a systematic search of MEDLINE (from inception to November 2020) and EMBASE (from inception to November 2020) for articles published in English using the keywords "dopamine receptor," "dopamine transporter," "obesity," and "neuroimaging." Body mass index (BMI) and the corresponding binding potential (BPND ) were extracted from figures in each study using Engauge Digitizer, version 12.1, and plotted for radiopharmaceuticals and regions of interest (ROIs). Five studies involving 119 subjects with DR and five studies including 421 subjects with DAT were eligible for inclusion in this study. In overweight or obese subjects with BMI of 25 kg/m2 or higher, DR availability from 11 C-Racloprie was negatively associated with BMI. However, DR availability from 11 C-PHNO was positively associated with BMI. DAT ratio was calculated after dividing DAT availabilities of overweight/obese BMI with mean DAT availabilities of normal BMI. The association between DAT ratio and BMI was not significant regardless of radiopharmaceuticals. In conclusion, dopamine plays a main role in the reward system with regard to obesity. Overweight and obese subjects had negative association between DR availability from 11 C-Raclopride and BMI. However, the association of DR availability with BMI was dependent on radiopharmaceuticals. DAT availability did not show the significant relationship with BMI regardless of radiopharmaceuticals.

Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80-85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas. METHODS: We used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients' tissues. RESULTS: We identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC. CONCLUSIONS: Both TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC.

SLC6A3 gene polymorphisms are associated with striatal dopamine transporter changes after glucose loading.

We investigated the association between SLC6A3 gene polymorphisms and changes in dopamine transporter (DAT) availability after glucose loading in humans. An intravenous injection of 18 F-FP-CIT was administered after infusion of glucose or placebo, and the emission data were acquired over 90 min in 38 healthy male participants. DAT availability expressed in terms of binding potential (BPND ) was recorded. The 40-bp variable number of tandem repeats (VNTR) in the 3' untranslated region and two single nucleotide polymorphisms (SNPs), rs2652511 and rs2937639, in the SLC6A3 gene were genotyped. Among the 38 participants, those with a VNTR other than 10R/10R (n = 7) were excluded. The alleles of the two SNPs (rs2652511 and rs2937639) appeared to be inherited together in two fixed combinations (C-G or T-A) in 29 of 31 individuals. The BPND in the ventral striatum (VST), caudate nucleus, and putamen was not significantly different after glucose or placebo loading according to genotype. However, BPND s from the caudate nucleus and putamen of all participants with rs2652511 CT/rs2937639 AG (n = 6) were higher after glucose loading. In conclusion, the SLC6A3 gene polymorphism is associated with the changes in DAT availability after glucose loading. DAT availability after glucose or placebo loading in the VST, caudate nucleus, and putamen did not differ according to the SLC6A3 genotype.

Limited power of dopamine transporter mRNA mapping for predicting dopamine transporter availability.

Dopamine transporters (DAT) are transmembrane proteins that translocate dopamine from the extracellular space into presynaptic neurons. We aimed to investigate the predictive power of DAT mRNA for DAT protein expression, measured using positron emission tomography (PET). We performed 18 F-FP-CIT PET scans in 35 healthy individuals. Binding potentials (BPND ) from the ventral striatum, caudate nucleus, putamen, and middle frontal, orbitofrontal, cingulate, parietal, and temporal cortices were measured. DAT gene expression data were obtained from the freely available Allen Human Brain Atlas derived from six healthy donors. The auto-correlation of PET-derived BPND s for DAT was intermediate (mean ρ2  = .66) with ρ2 ranging from .0811 to 1. However, the auto-correlation of mRNA expression was weak across the probes with a mean ρ2 of .09-.23. Cross-correlations between PET-derived BPND s and mRNA expression were weak with a mean ρ2 ranging from 0 to .22 across the probes. In conclusion, we observed weak associations between DAT mRNA expression and DAT availability in human brains. Therefore, DAT mRNA mapping may have only limited predictive power for DAT availability in humans. However, the difference in distribution of DAT mRNA and DAT protein may influence this limitation.

Hedonic Rating of Sucrose Is Sub-Regionally Associated with Striatal Dopamine Transporter in Humans.

BACKGROUND: Eating behavior is determined by both homeostatic and hedonic values. OBJECTIVE: We investigated the association of hedonic value with striatal dopamine transporter (DAT) availability sub-regionally. METHOD: An intravenous bolus injection of 18F-FP-CIT was administered after the infusion of glucose or placebo, and the emission data were acquired over 90 min. DAT availability and binding potential (BPND) were measured via the simplified reference tissue method. Subjects were assessed with sensory taste test of sucrose solutions. The "most liked" sucrose concentration (%) was determined as the hedonic rating for sucrose. RESULTS: Twenty healthy males participated in this study. After glucose loading, BPNDs of putamen significantly increased, and those of caudate nucleus showed the increasing trend, while those of ventral striatum were not significantly different. After glucose loading, the "most liked" sucrose concentration (%) was negatively associated with BPNDs of caudate nucleus and showed the trend of positive association with those from ventral striatum. Slopes of regression lines were significantly different according to the sub-regions of striatum. CONCLUSION: We have highlighted that striatal DAT increased after glucose loading in dorsal striatum, not in ventral striatum. These changes of striatal DAT were sub-regionally associated with the hedonic rating of sucrose from each subject.

A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study.

AIMS: To compare the efficacy and safety of adding low-dose lobeglitazone (0.25 mg/day) or standard-dose lobeglitazone (0.5 mg/day) to patients with type 2 diabetes mellitus (T2DM) with inadequate glucose control on metformin and dipeptidyl peptidase (DPP4) inhibitor therapy. MATERIALS AND METHODS: In this phase 4, multicentre, double-blind, randomized controlled, non-inferiority trial, patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor combination therapy were randomized to receive either low-dose or standard-dose lobeglitazone. The primary endpoint was non-inferiority of low-dose lobeglitazone in terms of glycaemic control, expressed as the difference in mean glycated haemoglobin levels at week 24 relative to baseline values and compared with standard-dose lobeglitazone, using 0.5% non-inferiority margin. RESULTS: At week 24, the mean glycated haemoglobin levels were 6.87 ± 0.54% and 6.68 ± 0.46% in low-dose and standard-dose lobeglitazone groups, respectively (p = .031). The between-group difference was 0.18% (95% confidence interval 0.017-0.345), showing non-inferiority of the low-dose lobeglitazone. Mean body weight changes were significantly greater in the standard-dose group (1.36 ± 2.23 kg) than in the low-dose group (0.50 ± 1.85 kg) at week 24. The changes in HOMA-IR, lipid profile and liver enzyme levels showed no significant difference between the groups. Overall treatment-emergent adverse events (including weight gain, oedema and hypoglycaemia) occurred more frequently in the standard-dose group. CONCLUSIONS: Adding low-dose lobeglitazone to metformin and DPP4 inhibitor combination resulted in a non-inferior glucose-lowering outcome and fewer adverse events compared with standard-dose lobeglitazone. Therefore, low-dose lobeglitazone might be one option for individualized strategy in patients with T2DM.

Hepatic Fat Quantification with the Multi-Material Decomposition Algorithm by Using Low-Dose Non-Contrast Material-Enhanced Dual-Energy Computed Tomography in a Prospectively Enrolled Cohort.

The early diagnosis of hepatic steatosis is important. No study has assessed hepatic fat quantification by using low-dose dual-energy computed tomography (CT). We assessed the accuracy of hepatic fat quantification using the multi-material decomposition (MMD) algorithm with low-dose non-contrast material-enhanced dual-energy CT. We retrospectively reviewed 33 prospectively enrolled patients who had undergone low-dose non-contrast material-enhanced dual-energy CT and magnetic resonance image (MRI) proton density fat fraction (PDFF) on the same day. Percentage fat volume fraction (FVF) images were generated using the MMD algorithm on the low-dose dual-energy CT data. We assessed the correlation between FVFs and MRI-PDFFs by using Spearman's rank correlation. With a 5% cutoff value of MRI-PDFF for fatty liver, a receiver operating characteristic (ROC) curve analysis was performed to identify the optimal criteria of FVF for diagnosing fatty liver. CTDIvol of CT was 2.94 mGy. FVF showed a strong correlation with MRI-PDFF (r = 0.756). The ROC curve analysis demonstrated that FVF ≥ 4.61% was the optimal cutoff for fatty liver. With this cutoff value for diagnosing the fatty liver on low-dose dual-energy CT, the sensitivity, specificity, and area under the curve were 90%, 100%, and 0.987, respectively. The MMD algorithm using low-dose non-contrast material-enhanced dual-energy CT is feasible for quantifying hepatic fat.

Prognostic value of metabolic activity of the psoas muscle evaluated by preoperative 18F-FDG PET-CT in breast cancer: a retrospective cross-sectional study.

BACKGROUND: This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by 18F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer. METHODS: The medical records of 288 patients who had undergone surgical resection for stages I-III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the mean SUV of the bilateral psoas muscle to the mean SUV of the liver. RESULTS: Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for disease-free survival (DFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter DFS. CONCLUSIONS: A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.

Spine-Hip Discordance and FRAX assessment Fracture Risk in Postmenopausal Women with Osteopenia from Concordant Diagnosis Between Lumbar Spine and Femoral Neck.

The diagnostic criteria proposed by the World Health Organization did not consider the discrepancy in diagnosis between lumbar spine (LS) and femoral neck (FN) and the clinical implications is unclear. Therefore, this retrospective study evaluated the probability of fracture risk in postmenopausal women with lumbar spine (LS)-femoral neck (FN) bone mineral density (BMD) discordance or not Patients included 1066 healthy postmenopausal women (median age 55.5 years) who visited our hospital for a health check-up between May 2013 and April 2017. Discordance was defined as a difference of one or two degrees between LS BMD and FN BMD. TBS was calculated from dual energy absorptiometry (DXA) images. Fracture risk was assessed using the Fracture Risk Assessment Tool (FRAX), including TBS-adjusted FRAX Seven hundred and two patients (65.9%) showed concordant LS and FN results, whereas 364 patients (34.1%) exhibited discordance. Normal BMD was found in 519 concordant patients (73.9%). Concordant patients showed significantly higher FRAX scores, including TBS-adjusted FRAX results, than discordant patients with low LS or FN. Furthermore, FRAX results in concordant osteopenia patients were similar to that of osteoporosis patients with osteopenia or a normal result at one site. FRAX and TBS-adjusted FRAX results in concordant osteopenia patients were comparable to that of discordant osteoporosis patients We concluded that patients with colncordant osteopenia in both the FN and LS should be managed in a similar way to patients with discordant osteoporosis.

Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study.

BACKGROUND: This study aimed to evaluate the benefit of brachial-ankle pulse wave velocity (baPWV) as a noninvasive marker of arterial stiffness for the prediction of all-cause and cause-specific mortality in patients with type 2 diabetes. METHODS: This multicenter prospective observational study analyzed 2308 patients with type 2 diabetes between 2008 and 2018. The patients were categorized according to the quartiles of baPWV. Cause of mortality was determined using death certificates and patient clinical records. We estimated proportional mortality rates from all causes, cardiovascular, cancer, and other causes among adults with diabetic status according to their baPWV. Cox regression models were used to estimate hazard ratios (HRs). RESULTS: There were 199 deaths (8.6%) in the study population during a median follow-up duration of 8.6 years. When baPWV was assessed as quartiles, a significantly higher risk of all-cause mortality (HR = 5.39, P < 0.001), cardiovascular-mortality (HR = 14.89, P < 0.001), cancer-mortality (HR = 5.42, P < 0.001), and other-cause mortality (HR = 4.12, P < 0.001) was found in quartile 4 (Q4, ≥ 1830 cm/s) than in quartiles 1-3 (Q1-3). Adding baPWV to baseline model containing conventional risk factors such as age, sex, diabetes duration, body mass index, glycated hemoglobin, systolic blood pressure, glomerular filtration rate, smoking, and insulin improved the risk prediction for all-cause (net reclassification index (NRI) = 49%, P < 0.001) and cause-specific (cardiovascular NRI = 28%, P = 0.030; cancer NRI = 55%, P < 0.001; other-cause NRI 51%, P < 0.001) mortality. CONCLUSION: This long-term, large-scale, multicenter prospective observational cohort study provide evidence that increased arterial stiffness, as measured by baPWV, predicts the risk of all-cause and cause-specific mortality in type 2 diabetes, supporting the prognostic utility of baPWV. Trial registration Clinical Research Information Service (CRIS), KCT 0005010. Retrospectively Registered May 12, 2020. https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=16677.

The feasibility of quantitative parameters of lymphoscintigraphy without significant dermal backflow for the evaluation of lymphedema in post-operative patients with breast cancer.

PURPOSE: We aimed to evaluate the potential role of quantitative methods associated with lymphoscintigraphy for the assessment of severity of lymphedema post-operatively in patients with breast cancer who did not show definite dermal backflow activity on the lymphoscintigraphy. METHODS: We evaluated 47 lymphoscintigraphies without dermal backflow in patients with lymphedema who received a mastectomy and axillary dissection or sentinel lymph node dissection for invasive ductal carcinoma of the breast. The quantitative asymmetry indices (QAIs) of both arms were calculated for each axilla, upper arm, forearm, and the whole arm. The QAI was defined as the radiopharmaceutical uptake ratio of the affected side to the unaffected side. Arm circumference was measured at four locations per arm to identify the maximal circumference difference (MCD) between affected and unaffected sides. RESULTS: The total and forearm QAIs of each side arm were significantly higher in the group with above moderate stage lymphedema compared with the mild stage group. Previous radiotherapy also had a significant effect on radiotracer retention expressed as QAI. The MCD was significantly correlated with QAI values of the forearm and the whole arm. The QAI of axillary areas was not significantly correlated with circumferential measurements of the arm. CONCLUSIONS: The QAIs have significant value for the diagnosis and severity of lymphedema and may therefore potentially be used as an objective tool for the assessment of lymphedema.

Striatal dopamine transporter changes after glucose loading in humans.

AIMS: The dopamine transporter (DAT) actively translocates dopamine that is released from the presynaptic neurons across the membranes of nerve terminals into the extracellular space. We hypothesized that glucose loading-induced changes in striatal DAT levels could be associated with food intake in humans. MATERIALS AND METHODS: An intravenous bolus injection of 18 F-FP-CIT was administered after infusion of glucose or placebo (normal saline), and emission data were acquired over 90 minutes in 33 healthy males. For a volume-of-interest-based analysis, an atlas involving sub-striatal regions of ventral striatum (VST), caudate nucleus and putamen was applied. DAT availability and binding potential (BPND ) were measured using a simplified reference tissue method with cerebellum as the reference. RESULTS: The glucose-loaded BPND from the VST negatively correlated with body mass index (BMI), whereas the placebo-loaded BPND from the VST did not. After loading with glucose, there were substantial increases in BPND s: 18.3%, 71.7% and 34.0% on average in the VST, caudate nucleus and putamen, respectively. CONCLUSION: Striatal DAT changes after glucose loading, and BMI is associated with glucose-loaded DAT availability, not with placebo-loaded DAT availability. DAT might have a role in the reward system of eating behavior.

Prediction of Response to Tumor Necrosis Value-α Blocker Is Suggested by 18F-NaF SUVmax But Not by Quantitative Pharmacokinetic Analysis in Patients With Ankylosing Spondylitis.

OBJECTIVE. We aimed to evaluate the pharmacokinetics and maximum standardized uptake value (SUVmax) of 18F-NaF PET/CT for assessment of disease activity and prediction of response in patients with ankylosing spondylitis (AS). MATERIALS AND METHODS. Twenty-seven patients (age, interquartile range, 30.25-49.75 years) with AS who were receiving a tumor necrosis factor-α (TNF-α) blocker were included. All patients underwent dynamic PET of the pelvis followed by whole-body PET/CT. Quantitative analysis of kinetic data of the sacroiliac joints (SIJs) was performed, and the SUVmax of the SIJs and SUVmax of the spine were calculated. Clinical indexes related to AS disease activity (serum C-reactive protein level, Bath ankylosing spondylitis disease activity index [ BASDAI], and Bath ankylosing spondylitis functional index) were evaluated. Clinical response was defined as an improvement from the initial BASDAI score of 50% or more (BASDAI 50) within 2 years after baseline 18F-NaF PET/CT. RESULTS. The BASDAI score at 18F-NaF PET/CT was significantly different between the responders and nonresponders: 18F-NaF uptake at the spine was significantly higher in the responders than in the nonresponders. Only SUVmax of the spine had a significant positive correlation with BASDAI score at PET/CT (r = 0.38, p = 0.048). The BASDAI score at PET/CT (odds ratio [OR], 35.32; 95% CI, 2.09-57.84; p = 0.014) and SUVmax of the spine (OR, 14.69; 95% CI, 0.79-27.27; p = 0.027) were significantly associated with BASDAI 50 response prediction. CONCLUSION. The results of our study suggest that the SUVmax of the spine on whole-body 18F-NaF PET/CT is a reliable and noninvasive biomarker for predicting therapeutic response to TNF-α blocker and shows better performance for predicting response than quantitative pharmacokinetic parameters. Fluorine-18-labeled NaF PET/CT showed axial bone lesions with bone formation and can be used as a monitoring tool in patients with AS receiving anti-TNF-α drugs. However, these results need to be validated in a larger cohort.

Short-term bone marrow suppression in differentiated thyroid cancer patients after radioactive iodine treatment.

After thyroidectomy in differentiated thyroid cancer (DTC), radioactive iodine (RAI) treatment is often used for remnant ablation. However, RAI treatment has been associated with bone marrow suppression, and leukopenia, anemia, and thrombocytopenia may occur after a single RAI administration. In this study, we examined the change in complete blood counts at 1 week after RAI administration; this is less well studied. A group of 189 DTC patients who received RAI treatment and underwent blood tests before and after treatment, were included. Peripheral blood counts at baseline were compared to those obtained at 1 week, 1-6 months, and 6-12 months after RAI treatment in order to test for bone marrow suppression. At 1 week after RAI treatment, there was a significant decrease in the white blood cell count (WBC, 5.8 ± 1.6 × 109/L vs. 5.4 ± 1.5 × 109/L, p < 0.001) and hemoglobin level (Hb, 13.5 ± 1.7 g/dL vs. 13.3 ± 1.4 g/dL, p = 0.001). The WBC decrease was mostly due to lymphocyte counts (2.2 ± 0.6 × 109/L vs. 1.6 ± 0.5 × 109/L, p < 0.001), with no decrease in the neutrophil count. Although not significantly changed at 1 week, platelets counts were altered within 6 months (265 ± 69 × 109/L vs. 239 ± 53 × 109/L, p < 0.001). The decline in the WBC count recovered within 6 months; lymphocyte and platelet counts recovered within 12 months. In conclusion, RAI treatment after a thyroidectomy was associated with a statistically significant but temporary decline in WBC counts and Hb levels at 1 week. Physicians treating DTC patients should not decrease usage of moderate dose RAI treatments.

Differential Urinary Proteome Analysis for Predicting Prognosis in Type 2 Diabetes Patients with and without Renal Dysfunction.

Renal dysfunction, a major complication of type 2 diabetes, can be predicted from estimated glomerular filtration rate (eGFR) and protein markers such as albumin concentration. Urinary protein biomarkers may be used to monitor or predict patient status. Urine samples were selected from patients enrolled in the retrospective diabetic kidney disease (DKD) study, including 35 with good and 19 with poor prognosis. After removal of albumin and immunoglobulin, the remaining proteins were reduced, alkylated, digested, and analyzed qualitatively and quantitatively with a nano LC-MS platform. Each protein was identified, and its concentration normalized to that of creatinine. A prognostic model of DKD was formulated based on the adjusted quantities of each protein in the two groups. Of 1296 proteins identified in the 54 urine samples, 66 were differentially abundant in the two groups (area under the curve (AUC): p-value < 0.05), but none showed significantly better performance than albumin. To improve the predictive power by multivariate analysis, five proteins (ACP2, CTSA, GM2A, MUC1, and SPARCL1) were selected as significant by an AUC-based random forest method. The application of two classifiers-support vector machine and random forest-showed that the multivariate model performed better than univariate analysis of mucin-1 (AUC: 0.935 vs. 0.791) and albumin (AUC: 1.0 vs. 0.722). The urinary proteome can reflect kidney function directly and can predict the prognosis of patients with chronic kidney dysfunction. Classification based on five urinary proteins may better predict the prognosis of DKD patients than urinary albumin concentration or eGFR.

Development of a risk scoring system for patients with papillary thyroid cancer.

As the importance of personalized therapeutics in aggressive papillary thyroid cancer (PTC) increases, accurate risk stratification is required. To develop a novel prognostic scoring system for patients with PTC (n = 455), we used mRNA expression and clinical data from The Cancer Genome Atlas. We performed variable selection using Network-Regularized high-dimensional Cox-regression with gene network from pathway databases. The risk score was calculated using a linear combination of regression coefficients and mRNA expressions. The risk score and clinical variables were assessed by several survival analyses. The risk score showed high discriminatory power for the prediction of event-free survival as well as the presence of metastasis. In multivariate analysis, the risk score and presence of metastasis were significant risk factors among the clinical variables that were examined together. In the current study, we developed a risk scoring system that will help to identify suitable therapeutic options for PTC.

Concordance in postsurgical radioactive iodine therapy recommendations between Watson for Oncology and clinical practice in patients with differentiated thyroid carcinoma.

BACKGROUND: To the authors' knowledge, the indications for radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC) are unclear; treatment decisions are based on physician judgment. The objective of the current study was to identify the degree of concordance between postsurgical RAI therapy recommended by Watson for Oncology (WFO), a clinical decision support system for oncological therapy, and that recommended by physicians for patients with DTC. METHODS: The current retrospective cohort study included 207 patients with DTC who underwent thyroidectomy between 2017 and 2018. Treatment recommendations were considered concordant if WFO rendered recommendations consistent with those of the physicians. RESULTS: Treatment recommendations were concordant for 160 patients (77%). The concordance rate significantly differed according to the American Thyroid Association (ATA) risk category (P < .001) and American Joint Committee on Cancer TNM stage (seventh edition; P = .004). Logistic regression analysis demonstrated that treatment recommendations were significantly less likely to be concordant in patients with ATA intermediate-risk and stage III disease compared with those with ATA low-risk and stage I disease (odds ratio, 0.16 [P < .001] and OR, 0.35 [P = .004], respectively). CONCLUSIONS: The authors believe the concordance rate between postsurgical RAI therapy recommendations rendered by WFO and those rendered by physicians was too low to justify adopting WFO for the comprehensive screening of patients with DTC. This is particularly true among patients with ATA intermediate-risk and stage III disease, reflecting differences in practice patterns between the United States (where WFO was calibrated) and Korea. Hence, WFO is not a substitute for physicians, and also may require regional customization to improve its assistive capability.

Impact of delayed radioiodine therapy in intermediate-/high-risk papillary thyroid carcinoma.

OBJECTIVE: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine therapy (RAIT) affects clinical outcomes in papillary thyroid carcinoma (PTC). Therefore, we evaluated the impact of timing of the first post-thyroidectomy RAIT in intermediate-to-high-risk PTC. DESIGN AND PATIENTS: This retrospective propensity score-matched cohort study included 720 PTC patients who received RAIT for <90 or 90-180 days (early and delayed groups, n = 360 each) after thyroidectomy. Responses to therapy, disease-free survival (DFS) and overall survival (OS) were compared between the two groups. RESULTS: After matching, the baseline characteristics of the 360 patients in each group were similarly adjusted. Within the first 2 years after initial therapy, the number of patients classified into excellent, indeterminate, biochemical incomplete and structural incomplete response categories were 221 (61%), 74 (21%), 39 (11%) and 26 (7%) in the early group, and 204 (57%), 73 (20%), 59 (16%) and 24 (7%) in the delayed group, respectively. There was no significant difference in response to therapy between the two groups (P = 0.183). During the median follow-up of 8.6 years, there was no significant difference in DFS (P = 0.060) and OS (P = 0.400) curves between the two groups. Delayed RAIT was not significantly associated with worse DFS (HR = 1.3, 95% CI 0.9-1.8, P = 0.061) or OS (HR = 1.5, 95% CI 0.6-3.4, P = 0.388). CONCLUSIONS: Delaying the first RAIT until 180 days after total thyroidectomy had no impact on restaging, recurrence and mortality in intermediate-to-high-risk PTC.

BRAF-positive multifocal and unifocal papillary thyroid cancer show different messenger RNA expressions.

OBJECTIVE: Thyroid cancer is the most common malignant endocrine tumour, and its incidence has continuously increased worldwide over the past three decades. We focused on the association of multifocal papillary thyroid carcinoma (PTC) with messenger RNA (mRNA) expression to characterize how molecular and histopathologic features relate to multifocality. DESIGN: A retrospective cohort study. PATIENTS: The primary and processed data were downloaded from The Cancer Genome Atlas. A total of 490 patients were included in this study. METHODS: The statistical significance of differences in sex, age, histology, LN metastasis and recurrence were analysed using chi-squared test. To identify differentially expressed genes between BRAF (+) multifocal and unifocal PTCs and between BRAF (-) multifocal and unifocal PTCs, we used the Significance Analysis of Microarray. Over-representation analysis is conducted using CPDB. RESULTS: A total of 237 patients had BRAF (+) PTCs, whereas 253 had BRAF (-) PTCs. There were 110 patients with multifocal PTCs and 127 with unifocal PTCs in the BRAF (+) group and 116 patients with multifocal PTCs and 137 with unifocal PTCs in the BRAF (-) group. In BRAF (+) group, multifocal PTCs had increased expression of 158 mRNAs as compared to that in unifocal PTCs. Ten mRNAs were involved in Wnt-related pathways, and seven mRNAs were included in pluripotency-related pathways. CONCLUSION: Multifocal PTCs have higher expression of mRNAs in Wnt- and pluripotency-related pathways when BRAF mutation is present. This might be the mechanism that accounts for the difference between multifocal and unifocal PTCs.

Prediction of future weight change with dopamine transporter in patients with Parkinson's disease.

Fluctuating body weight is a commonly reported nonmotor feature in patients with Parkinson's disease (PD). We hypothesised that striatal dopamine transporter (DAT) density at the time of diagnosis might play an important role in weight regulation in patients with PD. DAT density was measured from 123I-FP-CIT single-photon emission computed tomography. Region-of-interest analyses were performed to measure the specific binding of 123I-FP-CIT to DAT, and the putamen-to-caudate nucleus ratio (PCR) was calculated. Body weight was measured at baseline (W0) and at 48 months (W48). We classified subjects into three groups: weight loss, stable, and weight gain. In final analyses, 163 patients (106 men, 57 women) were included. PCR significantly differed by group in men, but not in women or across all patients. In men, PCR was slightly negatively associated with the percentage change in weight. No such correlation was found across all patients or in women. In univariate and multivariate logistic regression analyses, low PCR was associated with future weight gain in men with PD but not in women. In conclusion, striatal DAT availability at the time of diagnosis could predict subsequent weight change in men with PD.