Comparison of Endothelial Progenitor Cells in Parkinson's Disease Patients Treated with Levodopa and Levodopa/COMT Inhibitor

BACKGROUND: Levodopa treatment in Parkinson's disease (PD) increases in serum homocysteine levels due to its metabolism via catechol O-methyltransferase. Endothelial progenitor cells (EPCs) have the capacity to differentiate into mature endothelial cells and are markers for endothelial functions and cardiovascular risks. Along with traditional vascular risk factors, hyperhomocysteinemia is known to decrease the level of EPCs. In the present study, we hypothesized that that levodopa-induced hyperhomocysteinemia leads to a change in EPC levels. METHODOLOGY/PRINCIPAL FINDINGS: We prospectively enrolled PD patients who had been prescribed either levodopa/carbidopa (PD-L group, n = 28) or levodopa/carbidopa/COMT inhibitor (PD-LC group, n = 25) for more than 1 year. The number of circulating EPCs was measured by flow cytometry using dual staining of anti-CD34 and anti-KDR antibodies. The EPCs were divided into tertiles based on their distributions and a logistic regression analysis was used to estimate independent predictors of the highest tertile of EPCs. The number of endothelial progenitor cells was significantly decreased in PD-L patients (118±99/mL) compared with either PD-LC patients (269±258/mL, p = 0.007) or controls (206±204/mL, p = 0.012). The level of homocysteine was significantly increased in PD-L patients (14.9±5.3 µmol/L) compared with either PD-LC patients (11.9±3.0 µmol/L, p = 0.028) or controls (11.1±2.5 µmol/L, p = 0.012). The level of homocysteine was negatively correlated with endothelial progenitor cell levels (r = -0.252, p = 0.028) and was an independent predictor of the highest tertile of endothelial progenitor cell levels (OR; 0.749 [95% CI: 0.584-0.961]). CONCLUSIONS/SIGNIFICANCE: These data indicate that a higher consumption of EPC for restoration of endothelial damage may be associated with chronic levodopa treatment in PD patients

Stochastic Particle Flow for Nonlinear High-Dimensional Filtering Problems

A series of novel filters for probabilistic inference that propose an alternative way of performing Bayesian updates, called particle flow filters, have been attracting recent interest. These filters provide approximate solutions to nonlinear filtering problems. They do so by defining a continuum of densities between the prior probability density and the posterior, i.e. the filtering density. Building on these methods' successes, we propose a novel filter. The new filter aims to address the shortcomings of sequential Monte Carlo methods when applied to important nonlinear high-dimensional filtering problems. The novel filter uses equally weighted samples, each of which is associated with a local solution of the Fokker-Planck equation. This hybrid of Monte Carlo and local parametric approximation gives rise to a global approximation of the filtering density of interest. We show that, when compared with state-of-the-art methods, the Gaussian-mixture implementation of the new filtering technique, which we call Stochastic Particle Flow, has utility in the context of benchmark nonlinear high-dimensional filtering problems. In addition, we extend the original particle flow filters for tackling multi-target multi-sensor tracking problems to enable a comparison with the new filter

The Paradoxical Protective Effect of Liver Steatosis on Severity and Functional Outcome of Ischemic Stroke

Background: There is very limited information on the relationship between non-alcoholic fatty liver disease (NAFLD) and the severity or functional outcomes of ischemic stroke or transient ischemic stroke (TIA). We investigated the correlation between NAFLD and stroke outcomes.Methods: NAFLD was assessed in 321 patients with first-ever acute ischemic stroke or TIA, who underwent transient elastography from January 2014 to December 2014. The association of liver steatosis with stroke severity, assessed using the National Institute of Health Stroke Scale (NIHSS), was investigated using robust regression analysis. We also compared the functional outcome at 90 days according to the presence or burden of liver steatosis.Results: NAFLD was observed in 206 (64.2%) patients. Patients with NAFLD had less severe stroke (median NIHSS score 2 vs. 3, P = 0.012) and more favorable functional outcome at 90 days (85.3 vs. 70.5, P = 0.004). Patients with NAFLD were likely to have a 23.3% lower [95% confidence interval (CI), −39.2 to −3.2%, P = 0.026] NIHSS score and a 2.5-fold higher (95% CI, 1.08–5.67, P = 0.033) possibility of favorable functional outcome in multivariate analysis.Conclusions: Our study shows that a higher burden of liver steatosis seems to be associated with less severe stroke and better functional outcome after ischemic stroke or TIA

Clinical outcomes of spontaneous bacterial peritonitis due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species: A retrospective matched case-control study

<p>Abstract</p> <p>Background</p> <p>Clinical outcomes of spontaneous bacterial peritonitis (SBP) due to extended-spectrum β-lactamase-producing <it>Escherichia coli </it>and <it>Klebsiella </it>species (ESBL-EK) have not been adequately investigated.</p> <p>Methods</p> <p>We conducted a retrospective matched case-control study to evaluate the outcomes of SBP due to ESBL-EK compared with those due to non-ESBL-EK. Cases were defined as patients with liver cirrhosis and SBP due to ESBL-EK isolated from ascites. Control patients with liver cirrhosis and SBP due to non-ESBL-EK were matched in a 3:1 ratio to cases according to the following five variables: age (± 5 years); gender; species of infecting organism; Child-Pugh score (± 2); Acute Physiological and Chronic Health Evaluation II score (± 2). 'Effective initial therapy' was defined as less than 72 hours elapsing between the time of obtaining a sample for culture and the start of treatment with an antimicrobial agent to which the EK was susceptible. Cephalosporin use for ESBL-EK was considered 'ineffective', irrespective of the minimum inhibitory concentration. ESBL production was determined according to the Clinical and Laboratory Standards Institute guidelines on stored isolates.</p> <p>Results</p> <p>Of 1026 episodes of SBP in 958 patients from Jan 2000 through Dec 2006, 368 (35.9%) episodes in 346 patients were caused by SBP due to EK, isolated from ascites. Of these 346 patients, twenty-six (7.5%) patients with SBP due to ESBL-EK were compared with 78 matched controls. Treatment failure, evaluated at 72 hours after initial antimicrobial therapy, was greater among the cases (15/26, 58% <it>vs</it>. 10/78, 13%, <it>P </it>= .006); 30-day mortality rate was also higher than in the controls (12/26, 46% <it>vs</it>. 11/78, 15%, <it>P </it>= .001). When the case were classified according to the effectiveness of the initial therapy, 'ineffective initial therapy' was associated with higher 30-day mortality rate (11/18, 61% <it>vs</it>. 1/8, 13%, <it>P </it>= .036).</p> <p>Conclusion</p> <p>SBP due to ESBL-EK had poorer outcomes than SBP due to non-ESBL-EK. Ineffective initial therapy seems to be responsible for the higher rate of treatment failure and mortality in SBP due to ESBL-EK.</p

Endovascular and Clinical Outcomes of Vertebrobasilar Intracranial Atherosclerosis-Related Large Vessel Occlusion

Background and Purpose: Endovascular treatment (EVT) for acute vertebrobasilar intracranial atherosclerosis-related large vessel occlusion (ICAS-LVO) and its outcomes are not well known. We aimed to evaluate endovascular and clinical outcomes of vertebrobasilar ICAS-LVO patients who underwent EVT.Methods: Consecutive acute stroke patients who underwent EVT for vertebrobasilar LVO were retrospectively reviewed. Patients were assigned to the ICAS (+) or the ICAS (–) group based on angiographical findings. Procedural details and clinical outcomes were compared between the ICAS (+) and ICAS (–) groups.Results: This study included 77 patients with acute vertebrobasilar LVO who underwent EVT. Among the study subjects, 24 (31.2%) had an ICAS-LVO. Recanalization was achieved in 19 patients in the ICAS (+) group (79.2%), which was comparable with the ICAS (–) group (84.9%; p = 0.529). However, recanalization using conventional endovascular modalities (stent retriever thrombectomy, contact aspiration thrombectomy, or intra-arterial urokinase infusion) was less successful in the ICAS (+) group (36.8%) than the ICAS (–) group (100.0%; p &lt; 0.001). All the remaining patients in the ICAS (+) group required specific rescue treatments appropriate for ICAS, including balloon angioplasty, stenting, or intra-arterial glycoprotein IIb/IIIa inhibitor infusion to obtain a successful recanalization. Procedural time was not significantly longer in the ICAS (+) group. The rates of favorable outcomes (37.5% vs. 41.5%; p = 0.740), death, and symptomatic intracerebral hemorrhage were not significantly different between the groups.Conclusion: ICAS-LVO was common in patients who underwent EVT for acute vertebrobasilar LVO. Although conventional modalities were often ineffective for vertebrobasilar ICAS-LVO, a comparable recanalization rate could be obtained with ICAS-specific modalities. Recanalization rate and procedural time were comparable, and clinical outcomes did not differ between patients with or without ICAS-LVO

Impact of Non-vitamin K Antagonist Oral Anticoagulant Withdrawal on Stroke Outcomes

Introduction: Discontinuation of oral anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) may induce a hypercoagulable state, leading to severe stroke and poor outcomes. This study aimed to compare stroke outcomes between NOACs withdrawal and other prior medication statuses in patients with non-valvular atrial fibrillation (NVAF).Methods: Consecutive patients who had pre-existing NVAF and were admitted for an acute ischemic stroke or transient ischemic attack- at five hospitals between January 2013 and December 2016 were included. Prior medication status was categorized into seven groups such as no antithrombotics, antiplatelet-only, warfarin with subtherapeutic intensity, warfarin with therapeutic intensity, NOAC, warfarin withdrawal, and NOAC withdrawal. We compared initial National Institute of Health Stroke Scale (NIHSS) scores between groupsResults: Among 719 patients with NVAF, The median NIHSS score at admission was 5 (IQR 1-13). The NOAC withdrawal group had the highest median NIHSS scores at stroke onset [16, interquartile range, IQR (1–17)], followed by the warfarin withdrawal group [11, IQR (1–14, 18)], the no antithrombotic group [5, IQR (1–13, 18, 19)], and the warfarin with subtherapeutic intensity group [5, IQR (1–10, 18, 19)]. A Multivariable analysis demonstrated that NOAC withdrawal was independently associated with higher NIHSS scores at stroke onset (B 4.645, 95% confidence interval 0.384–8.906, P = 0.033). The median interval from drug withdrawal to ischemic stroke or TIA was 7 days (IQR 4-15) in the NOAC group.Conclusions: Stroke that occurred after stopping oral anticoagulants, especially NOAC, and was more severe at presentation and associated with poorer outcomes

High Dose Vitamin D3 Attenuates the Hypocalciuric Effect of Thiazide in Hypercalciuric Rats

Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D28K, and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D3. Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D

Effects of Thiazide on the Expression of TRPV5, Calbindin-D28K, and Sodium Transporters in Hypercalciuric Rats

TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague-Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin-D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats