Validity Assessment of an Automated Brain Morphometry Tool for Patients with De Novo Memory Symptoms.

BACKGROUND AND PURPOSE: Automated volumetric analysis of structural MR imaging allows quantitative assessment of brain atrophy in neurodegenerative disorders. We compared the brain segmentation performance of the AI-Rad Companion brain MR imaging software against an in-house FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. MATERIALS AND METHODS: T1-weighted images of 45 participants with de novo memory symptoms were selected from the OASIS-4 database and analyzed through the AI-Rad Companion brain MR imaging tool and the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. Correlation, agreement, and consistency between the 2 tools were compared among the absolute, normalized, and standardized volumes. Final reports generated by each tool were used to compare the rates of detection of abnormality and the compatibility of radiologic impressions made using each tool, compared with the clinical diagnoses. RESULTS: We observed strong correlation, moderate consistency, and poor agreement between absolute volumes of the main cortical lobes and subcortical structures measured by the AI-Rad Companion brain MR imaging tool compared with FreeSurfer. The strength of the correlations increased after normalizing the measurements to the total intracranial volume. Standardized measurements differed significantly between the 2 tools, likely owing to differences in the normative data sets used to calibrate each tool. When considering the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline as a reference standard, the AI-Rad Companion brain MR imaging tool had a specificity of 90.6%-100% and a sensitivity of 64.3%-100% in detecting volumetric abnormalities. There was no difference between the rate of compatibility of radiologic and clinical impressions when using the 2 tools. CONCLUSIONS: The AI-Rad Companion brain MR imaging tool reliably detects atrophy in cortical and subcortical regions implicated in the differential diagnosis of dementia.

Borosilicate glass 60Co high dose rate brachytherapy thermoluminescence dosimetry.

Brachytherapy is commonly used in treatment of cervical, prostate, breast and skin cancers, also for oral cancers, typically via the application of sealed radioactive sources that are inserted within or alongside the area to be treated. A particular aim of the various brachytherapy techniques is to accurately transfer to the targeted tumour the largest possible dose, at the same time minimizing dose to the surrounding normal tissue, including organs at risk. The dose fall-off with distance from the sources is steep, the dose gradient representing a prime factor in determining the dose distribution, also representing a challenge to the conduct of measurements around sources. Amorphous borosilicate glass (B2O3) in the form of microscope cover slips is recognized to offer a practicable system for such thermoluminescence dosimetry (TLD), providing for high-spatial resolution (down to < 1 mm), wide dynamic dose range, good reproducibility and reusability, minimal fading, resistance to water and low cost. Herein, investigation is made of the proposed dosimeter using a 1.25 MeV High Dose Rate (HDR) 60Co brachytherapy source, characterizing dose response, sensitivity, linearity index and fading. Analysis of the TL glow curves were obtained using the Tmax-Tstop method and first-order kinetics using GlowFit software, detailing the frequency factors and activation energy.

Genome-wide interaction study of brain beta-amyloid burden and cognitive impairment in Alzheimer's disease.

The lack of strong association between brain beta-amyloid deposition and cognitive impairment has been a challenge for the Alzheimer's disease (AD) field. Although beta-amyloid is necessary for the pathologic diagnosis of AD, it is not sufficient to make the pathologic diagnosis or cause dementia. We sought to identify the genetic modifiers of the relation between cortical beta-amyloid burden (measured using [18F]Florbetapir-PET) and cognitive dysfunction (measured using ADAS-cog) by conducting a genome-wide interaction study on baseline data from participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) phases GO/2 (n=678). Near genome-wide significant interaction effect was observed for rs73069071 within the IAPP (amylin) and SLCO1A2 genes (P=6.2 × 10-8). Congruent results were found using data from participants followed up from ADNI-1 (Pone-tailed=0.028, n=165). Meta-analysis across ADNI-GO/2 and ADNI-1 revealed a genome-wide significant interaction effect (P=1.1 × 10-8). Our results were further supported by similar interaction effects on temporal lobe cortical thickness (whole-brain voxelwise analysis: familywise error corrected P=0.013) and longitudinal changes in ADAS-cog score and left middle temporal thickness and amygdalar volume (Pone-tailed=0.026, 0.019 and 0.003, respectively). Using postmortem beta-amyloid immunohistochemistry data from 243 AD participants in the Religious Orders Study and Memory and Aging Project, we also observed similar rs73069071-by-beta-amyloid deposition interaction effect on global cognitive function (Pone-tailed=0.005). Our findings provide insight into the complexity of the relationship between beta-amyloid burden and AD-related cognitive impairment. Although functional studies are required to elucidate the role of rs73069071 in AD pathophysiology, our results support the recently growing evidence on the role of amylin in AD.

DiabCare 2013: A cross-sectional study of hospital based diabetes care delivery and prevention of diabetes related complications in Malaysia.

AIMS: The aim of the study was to re-evaluate the relationship between hospital based diabetes care delivery and prevention of complications. METHODS: DiabCare is an observational, non-interventional, cross-sectional study of hospital-based outpatient diabetes care. RESULTS: A total of 1668 patients participated in the study: mean age 57.8 ± 11.0 years, duration of diabetes 13.0 ± 8.6 years, and duration of insulin treatment 5.6 ± 5.5 years. Mean weight was 74.3 ± 16.6 kg (BMI 29.1 ± 5.8 kg/m2). The majority of patients were female (53.6%) and the largest ethnic group was Malay (51.3%), followed by Indian (21.9%) and Chinese (20.1%). The percentage of patients with HbA1c < 6.5% (< 42 mmol/mol) and < 7.0% (< 53 mmol/mol) was 12.2% and 23.8%, respectively (mean HbA1c 8.52 ± 2.01% [70 ± 22 mmol/mol]). The proportion of patients using insulin was 65% at a total daily dose of 60 ± 37 IU. One or more episodes of hypoglycaemia were reported by 39% (n=658) of patients within the previous three months. The risk of any hypoglycaemia was associated with the use of insulin (odds ratio [OR 3.26, 95% CI 2.59-4.09]), and total daily insulin dose (OR 1.04, 95% CI 1.01-1.07 per 10 IU increase). Mean HbA1c had not changed significantly between DiabCare cohorts 2008 and 2013 (p=0.08). CONCLUSIONS: Despite evidence of improving processes of diabetes care, glycaemic control and the prevalence of many diabetes related complications were unchanged.

Expression of insulin-like growth factor II mRNA binding protein 3 (IMP3) in enchondroma and chondrosarcoma.

Atypical cartilaginous tumor and enchondroma are similar in histopathologic aspects. Although the clinical course, radiologic and pathologic examinations enable distinction in most cases, difficulties are still encountered by the pathologists. There is no known biomarker to help make a distinction between benign and malignant cartilaginous tumors. Insulin-like growth factor II mRNA binding protein (IMP3) is a member of an oncofetal family of proteins that is expressed in different human malignancies and rapidly emerging as a prognostic and diagnostic marker in surgical pathology. In this study, IMP3 expression was examined by immunohistochemistry in 36 enchondromas and 42 chondrosarcomas of different histologic grades. The results showed that all 36 cases of enchondroma were negative for IMP3, while it was overexpressed in 15 of 42 chondrosarcomas (36%) (P<0.01). Significant higher levels of IMP3 were detected in grade III chondrosarcomas (6 of 7; 85.7%) when compared to low-grade tumors (6 of 19; 31.5% in grade II and 3 of 16; 18.7% in Atypical Cartilaginous Tumor). We proved statistically significant difference in IMP3 expression between enchondromas and ACTs (P=0.025). Our study clearly demonstrated differentiation-dependent expression of IMP3 in chondrosarcoma, and suggests IMP3 as a novel marker for differentiating problematic cases of enchondroma from well-differentiated chondrosarcomas. To our knowledge, this study is the first study to clarify expression of IMP-3 in chondromas and chondrosarcomas.

Once-daily initiation of basal insulin as add-on to metformin: a 26-week, randomized, treat-to-target trial comparing insulin detemir with insulin glargine in patients with type 2 diabetes.

AIMS: This study assessed the efficacy and safety of once-daily insulin initiation using insulin detemir (detemir) or insulin glargine (glargine) added to existing metformin in type 2 diabetes (T2D). METHODS: This 26-week, multinational, randomized, treat-to-target trial involved 457 insulin-naïve adults with T2D (HbA1c 7-9%). Detemir or glargine was added to current metformin therapy [any second oral antidiabetic drug (OAD) discontinued] and titrated to a target fasting plasma glucose (FPG) ≤90 mg/dl (≤5.0 mmol/l). Primary efficacy endpoint was change in HbA1c. RESULTS: Mean (s.d.) HbA1c decreased with detemir and glargine by 0.48 and 0.74%-points, respectively, to 7.48% (0.91%) and 7.13% (0.72%) [estimated between-treatment difference, 0.30 (95% CI: 0.14-0.46)]. Non-inferiority for detemir at the a priori level of 0.4%-points was not established. The proportions of patients reaching HbA1c ≤ 7% at 26 weeks were 38% and 53% (p = 0.026) with detemir and glargine, respectively. FPG decreased ∼43.2 mg/dl (∼2.4 mmol/l) in both groups [non-significant (NS)]. Treatment satisfaction was good for both insulins. Hypoglycaemia, which occurred infrequently, was observed less with detemir than glargine [rate ratio 0.73 (95% CI 0.54-0.98)]. The proportions of patients reaching HbA1c ≤ 7% without hypoglycaemia in the detemir and glargine groups were 32% and 38% (NS), respectively. Weight decreased with detemir [-0.49 (3.3) kg] and increased with glargine [+1.0 (3.1) kg] (95% CI for difference: -2.17 to -0.89 kg). CONCLUSION: While both detemir and glargine, when added to metformin therapy, improved glycaemic control, glargine resulted in greater reductions in HbA1c, while detemir demonstrated less weight gain and hypoglycaemia.

The safety and efficacy of adding once-daily insulin detemir to oral hypoglycaemic agents in patients with type 2 diabetes in a clinical practice setting in 10 countries.

AIMS: Evaluate the safety and efficacy of once-daily insulin detemir initiated in routine clinical practice in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycaemic agents (OHAs). METHODS: This large observational study was conducted in 10 countries. Adverse event data (including hypoglycaemia) and glycaemic control were recorded before and 24 weeks following insulin initiation while patients continued routine clinical management. RESULTS: In this study, 17 374 patients (53% male) were included. Mean pre-insulin values (±s.d.) were: age 62 ± 12 years; body mass index (BMI) 29.3 ± 5.4 kg/m(2); diabetes duration 10 ± 7 years; haemoglobin A1c (HbA1c) 8.9 ± 1.6%. During the study, 27 patients experienced serious adverse drug reaction, severe hypoglycaemic events or both; and there were 31 episodes of severe hypoglycaemia in 21 patients. After 24 weeks, HbA1c was 7.5 ± 1.2% (change of -1.3%; p < 0.001) and mean weight change was -0.6 kg (confidence interval -0.7, -0.5 kg, p < 0.001). Daily insulin dose increased from 13 ± 6 U (0.16 ± 0.09 U/kg) to 22 ± 16 U (0.27 ± 0.17U/kg) by 24 weeks. Multivariate regression analysis identified several independent demographic and treatment predictors of end of study HbA1c. CONCLUSIONS: Addition of once-daily insulin detemir to patients with type 2 diabetes mellitus on OHA therapy resulted in few adverse events, significant improvements in glycaemic control, small reductions in weight and low rates of hypoglycaemia. On the basis of this study, concerns about hypoglycaemia or weight gain should not preclude initiation of basal insulin analogues in patients with poor glycaemic control on OHAs.

A late complication of percutaneous radial artery cannulation.

Radial artery pseudoaneurysms occurring as a late complication of percutaneous radial artery cannulation are rare, while those which are infected are exceptional. Known risk factors are age-related with patients being in their seventies and onwards, the duration of the radial artery catheter and staphylococcal catheter-related infections. We report the case of an 82-year-old patient who developed a mycotic radial artery pseudoaneurysm as a late complication of arterial catheterization.

Type 2 diabetes care and insulin intensification: is a more multidisciplinary approach needed? Results from the MODIFY survey.

PURPOSE: The purpose of this study was to investigate the opinions of primary care physicians (PCPs) and diabetes specialists on their perceived role in tackling type 2 diabetes (T2D) and the challenges they face, particularly regarding insulin intensification. METHODS: Six hundred physicians from Germany, Japan, Spain, Turkey, the United Kingdom, and the United States were recruited to complete an online survey. Screening criteria included T2D patients seen per week (Europe/Japan: all ≥ 2; United States: PCPs ≥ 5; specialists ≥ 10) and years in practice (3-30 years). RESULTS: Most physicians had seen an increase in TD2 patients in the past 5 years, and almost all agreed that the burden of diabetes is increasing. Notable proportions of PCPs never initiate/modify insulin and never/rarely intensify insulin. Main barriers to insulin intensification cited were lack of experience and lack of time to educate patients. Better collaboration between primary and secondary care was considered one of the most important factors in improving insulin treatment of T2D. CONCLUSIONS: PCPs are less involved in the initiation and intensification of insulin than specialists; however, all physicians appreciate the need for increased PCP involvement. A multidisciplinary approach that includes using the skills of diabetes educators will assist physicians in improving management of T2D.

The effect of HCO3- on anion-stimulated ATPase from rat parotid granules.

ATPase from isolated secretory granules was stimulated in a concentration-dependent manner by HCO3- above 0.9 mM. Maximal stimulation was found at about 16 mM HCO3- and was about half of that with sulphite (SO3(2-)). The activation site(s) appeared to be similar to at least one class of SO3(2-) sites, HCO3(-)-stimulate ATPase was inhibited by SITS. Furthermore, maximal stimulation with SO3(2-) was not enhanced with HCO3-. At low Mg2+ concentrations, Ca2+ stimulated granule ATPase. At higher concentrations of Mg2+ (0.5 mM and above), Ca2+ at 0.1 mM or less had little effect on HCO3(-)-ATPase, and Ca2+ at 4 mM inhibited HCO3(-)-ATPase. At concentrations of Ca2+ above 0.44 mM, the enzyme was partially stimulated in the absence of Mg2+ and presence of HCO3-. Mitochondrial contamination did not account for the presence of ATPase in the isolated granule fraction. The granule ATPase may be regulated by HCO3- and calcium and this could be related to changes in the granule environment during exocytosis.