Differentiating early Parkinson's disease and multiple system atrophy with parkinsonism by saccade velocity profiles

ObjectivePatients with Parkinson's disease (PD) and multiple system atrophy both present predominantly with parkinsonism at early stages, whereas cerebellar symptoms are largely masked in multiple system atrophy with parkinsonism (MSAP). We sought to determine whether the velocity profiles of saccades could be used to differentiate between these two disorders, revealing the underlying basal ganglia and/or cerebellar dysfunction and brainstem pathology in these disorders.MethodsSixteen MSA-P patients, 63 PD patients, and 36 age-matched normal subjects performed the visually guided (VGS) and memory-guided saccade (MGS) tasks. Targets were presented at eccentricities of 5, 10, 20, and 30 degrees. The amplitude, peak velocity, and duration of saccades were compared among subject groups. Duration was further subdivided into acceleration and deceleration periods, corresponding to the times before and after peak velocity. These parameters correlated with the severity of Parkinsonism as assessed by the UPDRS motor score.ResultsHypometria predominated in both PD and MSAP patients, whereas hypermetria, frequently noted in cerebellar ataxia, was rarely observed. Saccades in MSAP were characterized both by prolonged acceleration and deceleration periods with reduced peak velocity. In contrast, the velocity profile of PD patients was characterized mainly by the prolonged deceleration period. The changes observed in velocity profiles of MGS deteriorated with advancing severity of parkinsonism in MSAP and PD patients.ConclusionSaccade profiles provide useful information for differentiating between PD and MSAP at early stages. While the changes in velocity profiles may be explained by the cerebellar and brainstem pathology in MSAP, the changes in velocity profile in both PD and MSAP correlated significantly with increasing severity of Parkinsonism in both disorders, suggesting a link with striatonigral pathology.SignificanceThe differential changes in saccade velocity profiles of MSAP and PD may be used as a measure indexing the progression of cerebellar and basal ganglia dysfunction as well as for assessing the functional improvement when clinical treatment becomes available.     

Circulating tumor DNA/circulating tumor cells and the applicability in different causes induced hepatocellular carcinoma

In 2015, liquid biopsy was rated one of the top 10 breakthrough technologies of the year by MIT Technology Review. Liquid biopsy is a type of in vitro diagnostic method involving a noninvasive blood test. It is also a breakthrough technology used to detect tumors and cancers and assist in therapeutic strategies. The most widely used markers are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Primary carcinoma of the liver is a malignancy of hepatocytes or intrahepatic biliary epithelial cells. The most common type of liver cancer is hepatocellular carcinoma (HCC), the causes of which mainly include infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), alcohol abuse, aflatoxicosis, and nonalcoholic fatty liver disease/ nonalcoholic steatohepatitis. As there are few typical clinical characteristics during the early stage of the disease, early diagnosis of HCC is very challenging. However, CTCs and ctDNA carry tumor-specific information. Therefore, the detection and analysis of CTCs and ctDNA can provide evidence for the early diagnosis of HCC and guide treatment. Furthermore, several studies have indicated that different inducers of HCC cause different DNA mutations, and accordingly, detection of specific mutations in ctDNA will facilitate the determination of the HCC type and help physicians provide distinctive therapies.     

Shining a light on posterior cortical atrophy

Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face-to-face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference.     

Rasch analysis of a Spanish language-screening parent survey

The purpose of this study was to evaluate and refine items from a parent survey designed to screen the language skills of Spanish-speaking preschoolers. This investigation applied Rasch modeling to systematically evaluate and identify items that demonstrated favorable qualities.A set of 124 parent survey items was administered to 107 Spanish-speaking parents of preschool age children. Parents completed survey items intended to provide a global measure of preschool language abilities. Rasch analyses of the survey items were conducted using WINSTEPS.Results indicated that 59 items, all vocabulary items, fit the Rasch model. Sufficient unidimensionality was obtained, with the model accounting for 58% of the variance. Item difficulty estimates ranged from −7.43 to 4.12, with a shortage of items at both the lower ability level and at the higher ability level. Analyses of pruned and remaining items identified the type of items that may be most useful for a refined item bank. These results will inform the development of new items for a Spanish language-screening parent survey for preschool age children.     

Potential Overtreatment and Undertreatment of Type 2 Diabetes Mellitus in Long-Term Care Facilities: A Systematic Review

ObjectiveTo investigate the prevalence, outcomes, and factors associated with potential glycemic overtreatment and undertreatment of type 2 diabetes mellitus (T2DM) in long-term care facilities (LTCFs).DesignSystematic review.Setting and ParticipantsResidents with T2DM and aged ≥60 years living in LTCFs.MeasuresArticles published between January 2000 and September 2020 were retrieved following a systematic search of MEDLINE, EMBASE, Cochrane Library, CINAHL plus, and gray literature. Inclusion criteria were the reporting of (1) potential overtreatment and undertreatment quantitatively defined (implicitly or explicitly) based on hemoglobin A1c (HbA1c) and/or blood glucose; (2) prevalence, outcomes, and associated factors of potential glycemic overtreatment and undertreatment; and (3) the study involved residents of LTCFs.ResultsFifteen studies were included. Prevalence of potential overtreatment (5%–86%, n = 15 studies) and undertreatment (1.4%–35%, n = 8 studies) varied widely among facilities and geographical locations, and according to definitions used. Prevalence of potential overtreatment was 16%–74% when defined as treatment with a glucose-lowering medication in a resident with ≥1 hypoglycemia risk factor or serious comorbidity, together with a HbA1c <7% (n = 10 studies). Potential undertreatment was commonly defined as residents on glucose-lowering medication having HbA1c >8.5% and the prevalence 1.4%–14.8% (n = 6 studies). No studies prospectively measured resident health outcomes from overtreatment and undertreatment. Potential overtreatment was positively associated with use of oral glucose-lowering medications, dementia diagnosis or dementia severity, and/or need for assistance with activities of daily living (n = 2 studies). Negative association was found between potential overtreatment and use of insulin/combined insulin and oral glucose-lowering medication. No studies reported factors associated with potential undertreatment.Conclusions and ImplicationsThe prevalence of potential glycemic overtreatment and undertreatment varied widely among residents with T2DM depending on the definition(s) used in each study. Longitudinal studies examining associations between glycemic management and health outcomes, and the use of consensus definitions of overtreatment and undertreatment are required to establish findings about actual glycemic overtreatment and undertreatment in LTCFs.     

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world,multi-center,cohort study

BackgroundThere is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.ObjectiveTo define the characteristics of phenotypic and genetic HoFH probands from mainland China.MethodsWe collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.ResultsA total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.ConclusionsThis report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.