Clinical phenotypes and constipation severity in Parkinson’s disease: Relation to Prevotella species

Background: The gut microbiome is speculated to play a crucial role in its pathogenesis of Parkinson’s disease as a triggering factor. Recent hypotheses suggested that Prevotella species regulate gut permeability, exert a neuroprotective effect, and interestingly, has been suspected to be deficient in PD patients, and so may play a role in this disease. Aim: This study was designed to compare between PD patients and their healthy controls as regards relative Prevotella abundance, prevalence of Prevotella-dominant Enterotype, and constipation severity. Also, to correlate Prevotella changes with the clinical phenotypes and  severity of motor and non-motor symptoms of PD. Methods: Twenty-five PD cases were enrolled in this study and cross-matched to 25 healthy subjects representing the control group. Overall NMS severity was assessed using the Non-Motor Symptoms Scale (NMSS). Quantitative SYBR green Real Time PCR was performed for the identification and quantitation of Prevotella in stool. Results: Prevotella relative abundance was 4-fold decreased in cases when compared to controls with PIGD phenotype showing the lowest abundance, however the difference was not statistically significance. Prevotella-dominant Enterotype was less presented in cases compared to controls, the result was statistically significant. Severe and very severe constipation grades presented 64% of cases group Vs 12% of control group. There was statistically significant positive correlation between total constipation score and UPDRS total score and motor symptoms phenotypes. Conclusion: Relative low Prevotella abundance in PD patients appears to be related to severe phenotypes of the disease; PIGD and mixed phenotypes. Severe constipation was more presented in PD cases which may be considered  as a preclinical biomarker for PD

Evaluation of bleeding risk in patients with renal impairment treated with Fondaparinux (Arixtra)

Background: Fondaparinux (Arixtra) a synthetic pentasaccharide that causes an antithrombin III-mediated selective inhibition of factor Xa. The clearance of fondaparinux reduces in patients with renal impairment, and there are no dosage adjustments provided in the manufacturer’s labeling. In patients with creatinine clearance rate (CrCl) >50 ml/min, total clearance is reduced by 25% while in case of CrCl 30–50 ml/min, the total clearance could be 40% lower when compared to patients with normal renal function. Aim of the Study: To evaluate the risk of bleeding in patients with renal impairment treated with fondaparinux. Materials and Methods: We performed a retrospective chart review study of patients 18 years of age and older who received fondaparinux between 11/10/2003 and 30/12/2009 during their hospital stays, and who had a CrCl of ≤80 ml/min. The patients were classified according to their degree of renal dysfunction as either stage A (CrCl: 80–50 ml/min; mild dysfunction) or stage B (CrCl: <50 ml/min; moderate or severe dysfunction). The HAS-BLED scoring system (HAS-BLED mnemonic stands for: hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratios, elderly, drugs or alcohol) was used to categorize the bleeding risk as mild, moderate, or high. Additionally, the bleeding severity was categorized as either major bleeding or minor bleeding. Results: A total of 165 patients were included in the study; of which 87 were men. In that 52.7% of the total were classified as stage A and the remainder as stage B. The patients classified as stage B were more frequently classified at high risk of bleeding than stage A patients (48.7%, n = 38 of stage B patients vs. 23.0%, n = 20 of stage A patients). Twenty-three percent (n = 38) of the patients experienced bleeding, and most of which were stage B patients (55.3%, n = 21). The majority of the patients who bled experienced major bleeding (71.0%, n = 27). Ten percent (n = 16) of the total number of patients, whose fondaparinux doses were adjusted as per the drug monograph, were documented to have had a bleeding event during their hospital stay. By contrast, 13% of the total number of patients (n = 22) who required dose adjustments and received fondaparinux without adjustments had bleeding events. Conclusion: Fondaparinux increases the risk of bleeding in patients with mild-to-moderate renal impairment even with appropriate dose adjustments. The risk of bleeding and the incidence of major bleeding are increased in patients with moderate and severe renal dysfunction