A Decline in Overutilization of Transfusion after Total Knee Arthroplasty Using Pharmacological Agents for Patient Blood Management in South Korea: An Analysis Based on the Korean National Health Insurance Claims Database from 2008 to 2019.

Background: This study aimed to evaluate the annual trends of transfusion rates and utilization of blood management agents in total knee arthroplasty (TKA) based on the operation type and to analyze the risk factors of transfusion after TKA. Methods: Using the Korean National Insurance claims database of 797,106 primary and revision TKAs between January 2008 and October 2019, data on the patients' characteristics, comorbidities, utilization of transfusion, and blood management agents were collected. The patients were categorized into three groups based on the operation type: primary, revision, and simultaneous bilateral TKA. The transfusion rate and utilization of blood management agents (intraoperative tranexamic acid [TXA] and preoperative iron supplements) were compared, and the risk factors for transfusion were evaluated. Results: After excluding the inaccurate data, 730,554 arthroplasties (636,292 primary, 10,540 revision, and 41,861 simultaneous bilateral TKAs) were identified. The transfusion rates of primary, revision, and simultaneous bilateral TKAs in 2019 were 64.0%, 67.7%, and 68.9%, respectively, which were significantly decreased compared with 83.2%, 88.0%, and 92.5% in 2008, respectively (p < 0.001). Conversely, the utilization of intraoperative TXA and preoperative iron supplements was significantly increased from 4.6% and 13.8%, respectively, in 2008 to 52.4% and 27.0%, respectively, in 2019 (p < 0.001). The utilization of intraoperative TXA and preoperative iron supplements significantly lowered the risk of transfusion after TKA (odds ratio [OR], 0.20; p < 0.001 and OR, 0.71; p < 0.001). Conclusions: The transfusion rate after TKA decreased gradually from 83.5% to 64.5% between 2008 and 2019 in South Korea corresponding with the increased utilization of blood management agents. Therefore, consistent attention to patient blood management should be emphasized to reduce the transfusion rate after TKA.

Gastrectomy, vitamin B12 supplementation and the risk of Parkinson's disease: A nationwide cohort study.

INTRODUCTION: Previous evidence has suggested roles for α-synuclein propagation and vitamin B12 (VitB12) deficiency in the pathogenesis of Parkinson's disease (PD). We investigated whether gastric cancer (GC) patients who underwent gastrectomy had a lower risk of PD and whether VitB12 supplementation modified the risk. METHODS: GC patients aged ≥50 years who underwent curative gastrectomy between 2007 and 2012 (n = 72,216) and matched comparison groups (n = 211,389) were identified from the Korean National Health Insurance database. The risks of PD were analyzed by Cox regression. RESULTS: Compared to their matched comparison groups, GC patients who underwent gastrectomy showed a decreased risk of PD (adjusted HR [aHR] 0.86; 95% confidence interval [CI] 0.75-0.98), but the significance disappeared after further adjustment with smoking and body mass index (BMI). To elaborate, subtotal gastrectomy (STG) was associated with decreased risk of PD (aHR 0.85; 95% CI 0.74-0.99) while total gastrectomy (TG) was not (aHR 0.89; 95% CI 0.66-1.19), although the risk reduction was not significant when further adjusted for smoking and BMI. Among the patients who underwent TG, their risk of PD was markedly lower when they had VitB12 supplementation after surgery (aHR 0.36; 95% CI 0.17-0.76), while the risk was higher when they did not have any (aHR 1.55; 95% CI 1.03-2.32). CONCLUSIONS: GC patients who underwent gastrectomy and received uninterrupted VitB12 supplementation had a decreased incidence of PD. This study provides indirect epidemiological evidence for the potential roles of gastrectomy and VitB12 in the pathogenesis of PD.

Risk of Dementia in Gastric Cancer Survivors Who Underwent Gastrectomy: A Nationwide Study in Korea.

PURPOSE: This study was designed to compare the risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD), between gastric cancer patients who underwent gastrectomy and the general population. METHODS: All patients (n = 63,998) aged ≥ 50 years who received a diagnosis of gastric cancer and underwent curative gastrectomy between 2007 and 2012 and a noncancer control population (n = 203,276), matched by age and sex, were identified from the Korean National Health Insurance Services and traced until 2017. Hazard ratios and 95% confidence intervals for dementia were calculated with a Cox regression analysis. RESULTS: Gastric cancer patients who received a gastrectomy showed an increased risk of AD [adjusted hazard ration (aHR) 1.08, 95% confidence interval (CI) 1.03-1.14], and the risk was especially marked for those who received a total gastrectomy (aHR 1.39, 95% CI 1.25-1.54). Gastric cancer survivors showed a decreased risk for VaD (aHR 0.85; 95% CI 0.73-0.98) regardless of operation type. Those who received continual vitamin B12 supplementation after a total gastrectomy were less likely than controls to develop AD (aHR 0.71; 95% CI 0.54-0.92). CONCLUSIONS: Compared with controls, gastric cancer patients who received a total gastrectomy had an increased incidence of AD and a decreased risk of VaD. Our results suggest that vitamin B12 deficiency might play a role in the development of AD and highlight the need for vitamin B12 supplementation after total gastrectomy.

Association of statin use with Parkinson's disease: Dose-response relationship.

BACKGROUND: There have been conflicting results on the association between statin use and Parkinson's disease (PD) incidence. OBJECTIVES: This study investigated the association between time-varying status of statin use and incidence of PD while considering the dose-response relationship and total cholesterol level. METHODS: Using the database of the Korean National Health Insurance Service from 2002 to 2015, we examined 76,043 subjects (≥60 years old) free of PD, dementia, and stroke at baseline. The dose of statin use was classified into the following four 6-month categories (<180, 180-365, 365-540, and ≥540 days) for each 2-year interval. The incidence of PD was identified by the prescription records for any anti-PD medication with a diagnosis of PD. RESULTS: During 10 years of follow-up, 1,427 PD cases occurred. Statin "ever use" was significantly associated with a high risk of PD incidence (adjusted hazard ratio = 1.28; 95% confidence interval = 1.12-1.46) when compared with statin nonuse. In terms of a dose-response relationship, although a duration of statin use <365 days was associated with a higher risk of PD, the duration of statin use ≥365 days was not significantly associated with an increased risk of PD. CONCLUSIONS: Statin use was associated with an elevated PD risk of PD, but long-term and adherent statin use was not significantly associated with elevated PD risk. However, there was no evidence of benefit with any statin treatment related to PD risk. Our study suggests that there is a complex relationship among cholesterol level, statin use, and PD risk that warrants further studies. © 2019 International Parkinson and Movement Disorder Society.

SILAC Expands its Territory to the Pathogenic Yeast, Candida albicans.

Quantitative proteomic analysis using stable isotope labeling with amino acids in cell culture (SILAC), as metabolic labeling with MS, has been used as an excellent technique to measure relative abundance change in proteins and post-transitional modifications. Since its development in 2002, SILAC has proven to have unique and specific advantage compared to other labeling methods such as Isobaric tags for relative and absolute quantitation (iTRAQ) and Tandem Mass Tag (TMT). However, SILAC has limitations in its application to human tissue/organ samples and some types of unicellular organisms that convert supplemented heavy amino acids to others. In this issue, Kaneva et al. (Proteomics 2018, 18, 1700278) introduces a new application of SILAC to a pathogen, which allows quantitative proteomics analysis to be performed without the need of arginine auxotrophs for SILAC experiment. In fungal pathogens, such as Candida albicans and other yeast family, arginine metabolism is one of the factors that helps pathogen escape host's defenses. This prevents arginine auxotrophs from being used in C. albicans research and limits SILAC-based MS method as a choice of quantitation. However, possibilities for quantitative proteomic analysis of a pathogenic yeast C. albicans using SILAC has now opened by Kaneva et al.

Hypovitaminosis D and orthostatic hypotension: a systematic review and meta-analysis.

OBJECTIVES: Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes. Recently, interest has developed in hypovitaminosis D (defined as low 25 hydroxiyvitamin D levels) as a potential risk factor for orthostatic hypotension. We conducted a systematic review and meta-analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D, including the adjustment of potential confounders (age, sex, BMI, renal function, comorbidities, seasonality, use of antihypertensive medications, and supplementation with cholecalciferol). METHODS: A systematic literature search of major electronic databases from inception until 09/2015 was made for articles providing data on orthostatic hypotension and hypovitaminosis D. A random effects meta-analysis of cross-sectional studies investigating orthostatic hypotension prevalence comparing participants with vs. those without hypovitaminosis D was undertaken, calculating the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 317 initial hits, five cross-sectional studies were meta-analysed including 3646 participants (1270 with hypovitaminosis D and 2376 without). The participants with hypovitaminosis D had a higher prevalence of orthostatic hypotension (OR = 1.88; 95% CI: 1.25-2.84; I = 68%) that was not affected by adjusting for a median of five potential confounders (OR = 2.03; 95% CI: 1.13-3.68; I = 73%). People with orthostatic hypotension had significantly reduced serum vitamin D concentrations (standardized mean difference = -0.42; 95% CI: -0.72 to -0.12). One longitudinal study confirmed the association between hypovitaminosis D and orthostatic hypotension. CONCLUSION: Our meta-analysis highlights that hypovitaminosis D is associated with orthostatic hypotension, independent of potential confounders. Further longitudinal studies and clinical trials are required to confirm these findings.

Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration.