Synucleinopathies are a set of devastating neurodegenerative diseases that share a pathologic accumulation of the protein α-synuclein (α-syn). This accumulation causes neuronal death resulting in irreversible dementia, deteriorating motor symptoms, and devastating cognitive decline. While the etiology of these conditions remains largely unknown, microglia, the resident immune cells of the central nervous system (CNS), have been consistently implicated in the pathogenesis of synucleinopathies. Microglia are generally believed to be neuroprotective in the early stages of α-syn accumulation and contribute to further neurodegeneration in chronic disease states. While the molecular mechanisms by which microglia achieve this role are still being investigated, here we highlight the major findings to date. In this review, we describe how structural varieties of inherently disordered α-syn result in varied microglial receptor-mediated interactions. We also summarize which microglial receptors enable cellular recognition and uptake of α-syn. Lastly, we review the downstream effects of α-syn processing within microglia, including spread to other brain regions resulting in neuroinflammation and neurodegeneration in chronic disease states. Understanding the mechanism of microglial interactions with α-syn is vital to conceptualizing molecular targets for novel therapeutic interventions. In addition, given the significant diversity in the pathophysiology of synucleinopathies, such molecular interactions are vital in gauging all potential pathways of neurodegeneration in the disease state.
As cholesterol fraction increases, ligand-bound receptor occupies more vesicle surface area, demonstrating co-localization with the cholesterol-rich phase.
Background Catheter associated urinary tract infections (CAUTIs) are the most common hospital acquired infections in the United States. External urinary collection devices (EUCDs) may serve as an alternative to indwelling urethral catheters (IUCs) and decrease the rate of CAUTIs. PureWick® is a novel female EUCD, with early case reports suggesting safe and efficacious use. However, no study has definitively proven benefit of PureWick® regarding reduction of CAUTIs. We sought to compare the CAUTI rate and median indwelling catheter days before and after availability of PureWick® at a single academic institution, as well as provide a descriptive analysis on female medical patients receiving an EUCD. Methods We performed a retrospective review of adult female patients admitted to our institution on a medical service who received an IUC and/or an EUCD. Patients admitted in the 3 months before (PRE) and 12 months after (POST) PureWick® availability were included. Two groups were compared: PRE patients who received an IUC vs. POST patients who received an IUC and/or EUCD. Results Out of 866 female patients, 296 received an EUCD in the POST cohort and overall, 673 received an IUC (261 (100%) PRE vs. 412 (68.1%) POST). There were no differences in the cohorts regarding age and comorbidities (all p >0.05). Compared to the PRE cohort, the POST cohort had a higher number of IUC days (median, 3 vs. 2 days, p< 0.001) and a higher rate of CAUTI (infections per 1,000 catheter days, 11.8 vs. 4.1, p=0.003) while overall UTI rate was similar (infections per 1,000 patient days, 19.1 vs. 14.12, p=0.410). In the POST cohort, the rate of UTI associated with EUCD use was 11.6 infections per 1,000 device days. Measurement of strict ins and outs (56.8%) was the most common indication for use of EUCD. Table 1. Characteristics and comorbidities of female catheterized patients admitted to a medical service before (PRE) and after (POST) PureWick implementation. Table 2. Urinary tract infection rates of female catheterized patients PRE and POST PureWick implementation. Table 3. Characteristics of hospitalized female patients admitted to a medical service who received a PureWick catheter. Conclusion While EUCDs might appear to be a promising alternative to IUCs for female patients, this single center pre/post analysis found that both the median number of IUC days and the CAUTI rate increased after introduction of a single EUCD. This may be related to selection bias, with EUCDs being ordered for patients who would not have otherwise received an IUC. Further research is needed to clarify if female EUCDs can be effective in decreasing IUC days and/or CAUTI rates prior to any widespread adoption. Disclosures All Authors: No reported disclosures
Background External urinary collection devices (EUCDs) may serve as an alternative to indwelling urinary catheters (IUCs) and decrease the rate of catheter associated urinary tract infections (CAUTIs). PureWick® is a novel female EUCD; however, no study has definitively proven benefit regarding reduction of CAUTIs. Aim We sought to compare the CAUTI rate and IUC days before and after availability of the PureWick® EUCD at a single institution. We provide a descriptive analysis of female medical patients receiving an EUCD. Methods A retrospective review of adult female patients admitted to a single institution on a medical service who received an IUC and/or an EUCD was performed. Patients who received an IUC in the 3 months before EUCD availability (PRE) were compared to patients who received an IUC and/or EUCD in the 12 months after (POST). Results Out of 848 female patients, 292 received an EUCD in the POST cohort and overall, 656 received an IUC (259 (100%) PRE vs. 397 (67.4%) POST). Compared to the PRE cohort, the POST cohort had a higher number of IUC days (median, 3 vs 2 days, p = 0.001) and a higher rate of CAUTI (infections per 1000 catheter days, 9.3 vs 2.3, p = 0.001). The rate of UTI associated with EUCD use was 9.8 infections per 1000 device days. Discussion While EUCDs might appear to be a promising alternative to IUCs for female patients, this single center pre-/post-analysis found that both the number of IUC days and the CAUTI rate increased after introduction of a female EUCD.
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