The New Diagnosis-Related Group Reimbursement System and Laboratory Test Quality in Korea: Analysis of External Quality Assessment Results.

Korea introduced a new diagnosis-related group (NDRG), which is a mixed-bundle reimbursement system. We evaluated the effects of NDRGs on laboratory test quality by analyzing data over three years (2016-2018) from the Korean Association of External Quality Assessment Service (KEQAS). A total of 42 NDRG-participating hospitals (CASE), 84 non-participating similar size-hospitals (CON-1), and 42 tertiary hospitals (CON-2) were included. We assumed the proportion of KEQAS results with a larger than 2 standard deviation index (SDI) to be a bad laboratory quality marker (BLQM). CASE BLQMs were lower than CON-1 BLQMs for more than 2 years in alkaline phosphatase (ALP), alanine aminotransferase (ALT), chloride, glucose, sodium, and total protein, and higher in creatinine. CASE BLQMs were higher than CON-2 BLQMs for more than 2 years in ALP, chloride, creatinine, glucose, lactate dehydrogenase (LDH), phosphorus, potassium, sodium, total calcium, total cholesterol, triglyceride, and uric acid. Mean SDIs for general chemistry tests were not significantly different depending on NDRG participation. However, the NDRG is currently a pilot program that compensates the amount of each institution's reimbursement based on the fee-for-service system, and most participants were public hospitals. Thus, the effects of NDRGs on laboratory test quality should be re-evaluated after the NDRG program has stabilized and more private hospitals are participating.

Relationships between [¹8F]-THK5351 Retention and Language Functions in Primary Progressive Aphasia.

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹8F]-THK5351 retention across all three subtypes and determine the topography of [¹8F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹8F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹8F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹8F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹8F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹8F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹8F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹8F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹8F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹8F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.

Topical anti-inflammatory and anti-oxidative effects of porcine placenta extracts on 2,4-dinitrochlorobenzene-induced contact dermatitis.

BACKGROUND: The placenta is a reservoir enriched with growth factors, hormones, cytokines and minerals. While several beneficial effects of placenta extracts on wound healing, anti-aging and anti-inflammatory responses have been reported, relatively limited mechanistic exploration has been conducted to date. Here, we provide compelling evidence of anti-inflammatory and anti-oxidative activities of porcine placenta extracts (PPE) against contact dermatitis in vivo. METHODS: A contact dermatitis mouse model was established by sensitizing the dorsal skin of BALB/c mice using the contact allergen, 2,4-dinitrochlorobenzene (DNCB), and molecular consequences of topical application of PPE were investigated. PPEs were pre-sterilized via γ-irradiation, which is a milder but more effective way of sterilizing biomolecules relative to the conventional autoclaving method. RESULTS: DNCB-induced skin lesions displayed clear contact dermatitis-like symptoms and topical application of PPE dramatically alleviated both local and systemic inflammatory responses. Inflammatory epidermal thickening was completely abrogated and allergen-specific serum IgE levels significantly reduced in the presence of PPE. Moreover, anti-oxidative activities of PPE were observed both in vitro and in vivo, which may lead to attenuation of inflammatory responses. Prolonged treatment with PPE strongly inhibited production of DNCB-induced reactive oxygen species (ROS) and subsequently prevented oxidative degradation of hyaluronic acid (HA), which triggers innate inflammatory responses. CONCLUSION: Our findings supply valuable insights into the mechanisms underlying the anti-inflammatory effects of PPE and provide a functional basis for the clinical application of PPE in inflammatory diseases.

18F-THK5351 PET Imaging in Nonfluent-Agrammatic Variant Primary Progressive Aphasia.

BACKGROUND AND PURPOSE: To analyze 18F-THK5351 positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). METHODS: Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, 18F-THK5351 PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of 18F-THK5351 in navPPA patients. RESULTS: In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. CONCLUSIONS: In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.

[18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive Aphasia.

BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and ß-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS: Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for ß-amyloid. CONCLUSIONS: These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

Neurological Complications during Treatment of Middle East Respiratory Syndrome.

BACKGROUND AND PURPOSE: Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012. METHODS: We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described. RESULTS: Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2-3 weeks. CONCLUSIONS: Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.

The clinical significance of brain microbleeds in patients with Alzheimer's disease: Preliminary study.

BACKGROUND: Microbleeds (MBs) are observed frequently in Alzheimer's disease (AD) and suggested to play a crucial role in the pathophysiology, but their clinical significance remains unclear. MATERIALS AND METHODS: The study recruited 100 patients with AD who were diagnosed at the memory clinic in Seoul Medical Center in 2014. For each patient, baseline characteristics, neuropsychological tests, cerebrovascular risk factors, medial temporal lobe atrophy (MTLA), and severity of small vessel disease (SVD) according to the existence of MBs were evaluated. RESULTS: The prevalence of MBs in patients with AD was 33%. The percentage of male gender, the severity of SVD and MTLA were significantly increased in MB(+) group. The MB(+) group showed more severe MTLA and SVD than MB(-) group. CONCLUSIONS: These results suggested that MBs might reflect the burden of amyloid and ischemic vascular pathology.

Effect of Korean Red Ginseng on Cognitive Function and Quantitative EEG in Patients with Alzheimer's Disease: A Preliminary Study.

BACKGROUND: Korean red ginseng (KRG) has a nootropic effect. This study assessed the efficacy of KRG on cognitive function and quantitative electroencephalography (EEG) in patients with Alzheimer's disease (AD). METHODS: Fourteen patients with AD (mean age, 74.93 years; 11 women and 3 men) were recruited and treated with KRG (4.5 g per day) for 12 weeks. Cognitive function was assessed by the Korean Mini-Mental State Examination (K-MMSE) and the Frontal Assessment Battery (FAB). EEG performed before and after treatment were analyzed with quantitative spectral analysis. RESULTS: The FAB score improved significantly after 12 weeks of treatment. In the relative power spectrum analysis performed according to responsiveness, alpha power increased significantly in the right temporal area of the responders. The increments of relative alpha power in the right temporal, parietal, and occipital areas were significantly higher in the responders than the nonresponders. CONCLUSIONS: This study indicates the efficacy of KRG on frontal lobe function in AD, related to increasing relative alpha power.

Quantitative EEG and medial temporal lobe atrophy in Alzheimer's dementia: Preliminary study.

BACKGROUNDS: The electroencephalogram (EEG) abnormalities in Alzheimer's disease (AD) have been widely reported, and medial temporal lobe atrophy (MTLA) is one of the hallmarks in early stage of AD. We aimed to assess the relationship between EEG abnormalities and MTLA and its clinical validity. MATERIALS AND METHODS: A total of 18 patients with AD were recruited (the mean age: 77.83 years). Baseline EEGs were analyzed with quantitative spectral analysis. MTLA was assessed by a T1-axial visual rating scale (VRS). RESULTS: In relative power spectrum analysis according to the right MTLA severity, the power of theta waves in C4, T4, F4, F8, and T5 increased significantly and the power of beta waves in T6, C4, T4, F8, T5, P3, T3, and F7 decreased significantly in severe atrophy group. In relative power spectrum analysis according to the left MTLA severity, the power of theta waves in T3 increased significantly and that of beta waves in P4, T6, C4, F4, F8, T5, P3, C3, T3, F3, and F7 decreased significantly in severe atrophy group. CONCLUSION: The severe MTLA group, regardless of laterality, showed more severe quantitative EEG alterations. These results suggest that quantitative EEG abnormalities are correlated with the MTLA, which may play an important role in AD process.

Air Quality, Biomarker Levels, and Health Effects on Staff in Korean Restaurants and Pubs Before and After a Smoking Ban.

INTRODUCTION: The Korean government implemented a smoking ban at square floor area of ≥150 m(2), rather than <150 m(2), restaurants and pubs from July 2013. This study examined the effects of the smoking regulations in restaurants and pubs in terms of the air quality, biomarker levels and health effects on staff. METHODS: Particulate matter smaller than 2.5 µm (PM2.5) was measured in 146 facilities before and 1 month after the ban. The urinary cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanol (NNAL) levels were measured in 101 staff members at 77 facilities before and 1 month after the ban. We also measured self-reported respiratory and sensory symptoms on both phases. RESULTS: Of the 146 facilities, 121 facilities were included in the PM2.5 analysis. In ≥150 m(2) pubs, the indoor PM2.5 concentration was significantly reduced after the ban (p < .05). While the urinary cotinine concentrations of the staff in all facilities were not changed after the ban, the total NNAL concentrations of the staff in ≥150 m(2) pubs were significantly reduced after the ban (p < .05). The health effects on staff show that only sensory symptoms significantly improved in ≥150 m(2) facilities after the ban (p < .05). CONCLUSIONS: The smoking ban significantly reduced the levels of PM2.5 and total NNAL concentrations in ≥150 m(2) pubs and improved sensory health among staff in ≥150 m(2) facilities. The results of this study can be useful in supporting an expansion of the smoking ban in all indoor places, including <150 m(2) restaurants and pubs.

Enhanced Anti-inflammatory Effects of γ-irradiated Pig Placenta Extracts.

Porcine placenta extract (PPE) is known to possess anti-inflammatory properties owing to its high concentration of bioactive substances. However, the need to eliminate blood-borne infectious agents while maintaining biological efficacy raises concerns about the optimal method for sterilizing PPE. Therefore, the objective of this study was to compare the effects of the standard pressurized heat (autoclaving) method of sterilization with γ-irradiation on the anti-inflammatory effects of PPE. The anti-inflammatory actions of these two preparations of PPE were evaluated by measuring their inhibitory effects on the production of NO, the expression of iNOS protein, and the expression of iNOS, COX2, TNF-α, IL-1ß, and IL-6 mRNA in lipopolysaccharide-stimulated RAW 264.7 cells. Compared with autoclaved PPE, γ-irradiated PPE showed significantly greater inhibition of NO production and iNOS protein expression, and produced a greater reduction in the expression of iNOS, COX2, TNF-α, IL-1ß, and IL-6 mRNA. These results provide evidence that the sterilization process is crucial in determining the biological activity of PPE, especially its anti-inflammatory activity. Collectively, our data suggest that γ-irradiated PPE acts at the transcriptional level to effectively and potently suppresses the production of NO and the expression of pro-inflammatory cytokines.

Usefulness of medial temporal lobe atrophy visual rating scale in detecting Alzheimer's disease: Preliminary study.

BACKGROUND: The Korean version of Mini-Mental Status Examination (K-MMSE) and the Korean version of Addenbrooke Cognitive Examination (K-ACE) have been validated as quick neuropsychological tests for screening dementia in various clinical settings. Medial temporal atrophy (MTA) is an early pathological characteristic of Alzheimer's disease (AD). We aimed to assess the diagnostic validity of the fusion of the neuropsychological test and visual rating scale (VRS) of MTA in AD. MATERIALS AND METHODS: A total of fifty subjects (25 AD, 25 controls) were included. The neuropsychological tests used were the K-MMSE and the K-ACE. T1 axial imaging visual rating scale (VRS) was applied for assessing the grade of MTA. We calculated the fusion score with the difference of neuropsychological test and VRS of MTA. The receiver operating characteristics (ROC) curve was used to determine optimal cut-off score, sensitivity and specificity of the fusion scores in screening AD. RESULTS: No significant differences in age, gender and education were found between AD and control group. The values of K-MMSE, K-ACE, CDR, VRS and cognitive function test minus VRS were significantly lower in the AD group than control group. The AUC (Area under the curve), sensitivity and specificity for K-MMSE minus VRS were 0.857, 84% and 80% and for K-ACE minus VRS were 0.884, 80% and 88%, respectively. Those for K-MMSE only were 0.842, 76% and 72% and for K-ACE only were 0.868, 80% and 88%, respectively. CONCLUSIONS: The fusion of the neuropsychological test and VRS suggested clinical usefulness in their easy and superiority over neuropsychological test only. However, this study failed to find any difference. This may be because of small numbers in the study or because there is no true difference.

The possible role of antioxidant vitamin C in Alzheimer's disease treatment and prevention.

Oxidative stress is suggested to play a major role in the pathogenesis of Alzheimer's disease (AD). Among the antioxidants, vitamin C has been regarded as the most important one in neural tissue. It also decreases ß-amyloid generation and acetylcholinesterase activity and prevents endothelial dysfunction by regulating nitric oxide, a newly discovered factor in the pathogenesis and progression of AD. However, clinical trials using antioxidants, including vitamin C, in patients with AD yielded equivocal results. The current article discusses the relevance of vitamin C in the cellular and molecular pathogenesis of AD and explores its therapeutic potential against this neurodegenerative disorder.

Response to rivastigmine transdermal patch or memantine plus rivastigmine patch is affected by apolipoprotein E genotype in Alzheimer patients.

BACKGROUND/AIMS: The apolipoprotein E (APOE) genotype in response to pharmacological treatments in patients with Alzheimer's disease (AD) remains a matter of controversy. This analysis investigated the effect of the APOE genotype on the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine patch in patients with mild to moderate AD. METHODS: Two hundred and six (n = 206) patients with probable AD and Mini-Mental State Examination (MMSE) scores of 10-20 were randomized to rivastigmine patch monotherapy or memantine plus rivastigmine patch for 24 weeks. Of the 206 patients with probable AD, 146 patients who consented to genetic testing for APOE were included and assessed for this subgroup study. RESULTS: There were no significant differences on MMSE, NPI, ADAS-cog, ADCS-ADL, CDR-SB, NPI and FAB between rivastigmine patch monotherapy and memantine plus rivastigmine patch according to the APOE genotype. However, patients with moderately severe AD (MMSE ≤15) who were APOE ε4 carriers showed higher responder rates on ADCS-ADL with memantine plus rivastigmine patch compared to rivastigmine patch monotherapy. CONCLUSION: Moderately severe AD patients with the APOE ε4 allele may respond more favorably to memantine plus rivastigmine patch than ε4 noncarriers.

Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer's disease.

OBJECTIVES: Ginseng has been reported to improve cognitive function in animals and in healthy and cognitively impaired individuals. In this study, we investigated the efficacy of a heat-processed form of ginseng that contains more potent ginsenosides than raw ginseng in the treatment of cognitive impairment in patients with moderately severe Alzheimer's disease (AD). METHODS: Forty patients with AD were randomized into one of three different dose groups or the control group as follows: 1.5 g/day (n = 10), 3 g/day (n = 10), and 4.5 g/day (n = 10) groups, or control (n = 10). The Alzheimer's Disease Assessment Scale (ADAS) and Mini-Mental State Examination (MMSE) were used to assess cognitive function for 24 weeks. RESULTS: The treatment groups showed significant improvement on the MMSE and ADAS. Patients with higher dose group (4.5 g/day) showed improvements in ADAS cognitive, ADAS non-cognitive, and MMSE score as early as at 12 weeks, which sustained for 24-week follow-up. DISCUSSION: These results demonstrate the potential efficacy of a heat-processed form of ginseng on cognitive function and behavioral symptoms in patients with moderately severe AD.

Validation of the Korean Addenbrooke's Cognitive Examination for diagnosing Alzheimer's dementia and mild cognitive impairment in the Korean elderly.

The Addenbrooke's Cognitive Examination (ACE) is a valid dementia-screening test that is a simple and effective instrument. We aimed to assess the diagnostic accuracy of the Korean version of the ACE (K-ACE) in a Korean population. A total of 115 subjects (50 with Alzheimer's dementia [AD], 26 with mild cognitive impairment [MCI], and 39 controls) who visited the Neurology Outpatient Clinic of Seoul Medical Center were included. The ACE was translated and modified to create the K-ACE. The sensitivity, specificity, area under the curve, reliability, and Verbal-Language/Orientation-Memory ratio were evaluated. The receiver-operating characteristic (ROC) curve was used to determine the optimal cutoff score in screening for dementia. The ROC curves showed the superiority of the K-ACE over the Korean Mini-Mental Status Examination in the diagnosis of AD and MCI. The optimal cutoff of the K-ACE for the identification of AD was 68/69, which had a sensitivity of 90% and a specificity of 84%. The K-ACE is a short, reliable, and valid neuropsychological test battery used to screen for dementia in the Korean elderly.