Association between FGFR1OP2/wit3.0 polymorphisms and residual ridge resorption of mandible in Korean population

BACKGROUND: A previous study on the genetic association between single nucleotide polymorphisms in FGFR1OP2/wit3.0 and the long term atrophy of edentulous mandible hypothesized that the excessive jawbone atrophy after dental extraction may be associated with abnormal oral mucosa contraction induced by the FGFR1OP2/wit 3.0 gene. It was reported that the minor allele of rs840869 or rs859024 in FGFR1OP2/wit3.0 was associated with the excessive atrophy of edentulous mandible. The present study represents an attempt to replicate the results of this previous study and to examine the genetic association between polymorphisms in FGFR1OP2 and residual ridge resorption of mandible in a Korean population. METHODOLOGY/PRINCIPAL FINDINGS: 134 subjects (70.46 ± 9.02 years) with partially or completely edentulous mandible were recruited. The mandibular bone height was measured following the protocol of the American College of Prosthodontists (ACP). From 24 subjects, seven variants in FGFR1OP2 were discovered and four of them were novel. Selected SNPs that are not in high LD at r2 threshold of 0.8 were genotyped for the remaining population. There was no frequency of the minor allele of SNP rs859024 in Korean population. SNP rs840869 was not associated with residual ridge resorption (p = 0.479). The bone height of the subject with the ss518063493 minor allele (8.52 mm) was shorter than that of those subjects with major alleles (18.96 ± 5.33 mm, p = 0.053). CONCLUSIONS/SIGNIFICANCE: The patient with minor allele of ss518063493 may be associated with excessive atrophy of edentulous mandible whereas the patients with that of rs840869 are not associated in Korean population. The result from this study may assist in developing a novel genetic diagnostic test and be useful in identifying Koreans susceptible to developing excessive jawbone atrophy after dental extraction.ope

Comparison of empagliflozin and sitagliptin therapy on myocardial perfusion reserve in diabetic patients with coronary artery disease

Background Sodium-glucose co-transporter 2 inhibitors reduce the risk of cardiovascular events in type 2 diabetic patients with coronary artery disease (CAD); however, the underlying mechanisms remain unclear. Objectives We compared the effects of empagliflozin vs. sitagliptin therapy on myocardial perfusion reserve (MPR) using dynamic single-photon emission computed tomography (SPECT) imaging. Methods In total, 100 patients with type 2 diabetes, CAD and an MPR <2.5 were randomized to receive either empagliflozin (10 mg once daily) or sitagliptin (100 mg once daily). Dynamic SPECT examinations were performed at baseline and at 6 months. The primary endpoint was the percent change of global MPR. Evaluable SPECT data were available for 98 patients. Results Baseline clinical characteristics and SPECT data were well balanced between the two groups. At a 6-month follow-up, the fasting glucose and glycated hemoglobin levels significantly decreased in both groups. Hematocrit and hemoglobin levels significantly increased in the empagliflozin group but not in the sitagliptin group. The global MPR significantly improved after treatment in both groups (34.5 +/- 70.6%; P = 0.005 for empagliflozin vs. 22.4 +/- 45.7%; P = 0.024 for sitagliptin). However, there was no significant difference in the global MPR between the two groups (P = 0.934). Similar findings were detected with regard to the regional MPR. Conclusion Among patients with type 2 diabetes and CAD, both empagliflozin and sitagliptin significantly improved the global MPR with no significant difference between the groups

Statin/ezetimibe combination therapy vs statin monotherapy for carotid atherosclerotic plaque inflammation

It remains uncertain whether statin/ezetimibe combination therapy serves as a useful and equivalent alternative to statin monotherapy for reducing atherosclerotic plaque inflammation. The aim of the present study was to compare the effects of statin/ezetimibe combination therapy and statin monotherapy on carotid atherosclerotic plaque inflammation using F-18-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET)/computed tomography (CT) imaging. Data were pooled from 2 clinical trials that used serial (18)FDG PET/CT examination to investigate the effects of cholesterol-lowering therapy on carotid atherosclerotic plaque inflammation. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS) at 6-month follow-up. Baseline characteristics were largely similar between the 2 groups. At the 6-month follow-up, the MDS TBR of the index vessel significantly decreased in both groups. The percent change in the MDS TBR of the index vessel (primary outcome) did not differ significantly between the 2 groups (-8.41 +/- 15.9% vs -8.08 +/- 17.0%, respectively, P = .936). Likewise, the percent change in the whole vessel TBR of the index vessel did not differ significantly between the 2 groups. There were significant decreases in total and LDL cholesterol levels in both groups at follow-up (P < .001). There were no significant correlations between the percent changes in MDS TBR of the index vessel, changes in the lipid, and high-sensitive C-reactive protein levels. The reduction in carotid atherosclerotic plaque inflammation by statin/ezetimibe combination therapy was equivalent to that by the statin monotherapy

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome

Introduction: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. Methods: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. Results: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia Conclusion: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS

Combination of automated brain volumetry on MRI and quantitative tau deposition on THK-5351 PET to support diagnosis of Alzheimer's disease

Imaging biomarkers support the diagnosis of Alzheimer's disease (AD). We aimed to determine whether combining automated brain volumetry on MRI and quantitative measurement of tau deposition on [18F] THK-5351 PET can aid discrimination of AD spectrum. From a prospective database in an IRB-approved multicenter study (NCT02656498), 113 subjects (32 healthy control, 55 mild cognitive impairment, and 26 Alzheimer disease) with baseline structural MRI and [18F] THK-5351 PET were included. Cortical volumes were quantified from FDA-approved software for automated volumetric MRI analysis (NeuroQuant). Standardized uptake value ratio (SUVR) was calculated from tau PET images for 6 composite FreeSurfer-derived regions-of-interests approximating in vivo Braak stage (Braak ROIs). On volumetric MRI analysis, stepwise logistic regression analyses identified the cingulate isthmus and inferior parietal lobule as significant regions in discriminating AD from HC and MCI. The combined model incorporating automated volumes of selected brain regions on MRI (cingulate isthmus, inferior parietal lobule, hippocampus) and SUVRs of Braak ROIs on [18F] THK-5351 PET showed higher performance than SUVRs of Braak ROIs on [18F] THK-5351 PET in discriminating AD from HC (0.98 vs 0.88, P=0.033) but not in discriminating AD from MCI (0.85 vs 0.79, P=0.178). The combined model showed comparable performance to automated volumes of selected brain regions on MRI in discriminating AD from HC (0.98 vs 0.94, P=0.094) and MCI (0.85 vs 0.78; P=0.065)

Metabolic activity by FDG-PET/CT after neoadjuvant chemotherapy in borderline resectable and locally advanced pancreatic cancer and association with survival

Background: The optimal prognostic markers for neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer are not yet established. Method: Patients who received neoadjuvant chemotherapy prior to surgery and underwent FDG-PET/CT between July 2012 and December 2017 were included. Metabolic parameters including standardised uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) on PET/CT, and response evaluations using PERCIST criteria, were investigated for its impact on survival and recurrence. Cox proportional hazards model was performed. Differences in risk were expressed as hazard ratio [HR] with 95% confidence interval [c.i.]. Results: The patients with borderline resectable (N = 106) or locally advanced pancreatic cancer (N = 82) were identified. The median survival was 33.6 months. Decreased metabolic parameters of PET/CT after neoadjuvant chemotherapy were associated with positive impacts on survival and recurrence such as SUVmax (HR 1.16, 95% c.i. 1.01 to 1.32, P = 0.025), SUVpeak (HR 1.26, 95% c.i. 1.05 to 1.51, P = 0.011), and MTV (HR 1.15, 95% c.i. 1.04 to 1.26, P = 0.005). Large delta values were related to a positive impact on recurrence such as SUVmax (HR 1.21, 95% c.i. 1.06 to 1.38, P = 0.005). Post-neoadjuvant chemotherapy SUVmax ≥3 (HR 3.46, 95% c.i. 1.21 to 9.91; P = 0.036) was an independent prognostic factor for negative impact on survival. Patients with post-neoadjuvant chemotherapy SUVmax <3 showed more chemotherapy cycles (8.7 versus 6.2, P = 0.001), more frequent complete metabolic response (25 vs 2.2%, P = 0.002), smaller tumour size (2.1 vs 3.1 cm, P = 0.002), and less frequent lymphovascular invasion (23.7 vs 51.1%, P = 0.020) than patients with SUVmax ≥3. Conclusion: Reduction in metabolic tumour parameters of FDG- PET/CT after neoadjuvant chemotherapy indicates improved overall survival and recurrence-free survival