CSF α-Synuclein Seed Amplification Assay in Patients With Atypical Parkinsonian Disorders.

BACKGROUND AND OBJECTIVES: There is no disease-modifying treatment of corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), 2 disorders characterized by their striking phenotypic, and, in CBS, pathologic heterogeneity. Seed amplification assays (SAAs) could enable the detection of neuropathologic processes, such as α-synuclein (αSyn) copathology, that affect the success of future disease-modifying treatment strategies. The primary objective was to assess possible αSyn copathology in CBS and PSP, as detected in CSF using an αSyn SAA (αSyn-SAA). Secondary objectives were to evaluate the association of αSyn-SAA positivity with other biomarkers including of Alzheimer disease (AD), and with clinical presentation. We hypothesized that αSyn-SAA positivity would be detectable in CBS and PSP and that it would be associated with AD biomarker positivity and ß-amyloid (Aß) 42 levels, neurodegeneration as assessed by neurofilament light chain (NfL) levels, and symptoms associated with synucleinopathies. METHODS: This cross-sectional observational study included patients clinically diagnosed with CBS and PSP who underwent a lumbar puncture between 2012 and 2021 (Toronto Western Hospital, Canada). CSF was tested for αSyn-SAA positivity, AD biomarkers, and NfL levels. Clinical data were derived from medical records. RESULTS: We tested the CSF of 40 patients with CBS (19 female patients, 65.9 ± 8.6 years) and 28 with PSP (13 female patients, 72.5 ± 8.7 years old), mostly White (n = 50) or Asian (n = 14). αSyn-SAA positivity was observed in 35.9% patients with CBS and 28.6% with PSP. In young-onset, but not late-onset patients, αSyn-SAA positivity and AD positivity were associated (odds ratio [OR] 8.8, 95% CI 1.2-82.6, p < 0.05). A multivariable linear regression analysis showed a significant interaction of αSyn-SAA status by age at onset on CSF Aß42 levels (ß = 0.3 ± 0.1, p < 0.05). Indeed, age at onset was positively related to Aß42 levels only in αSyn-SAA-positive patients, as shown by slope comparison. A logistic regression analysis also suggested that REM sleep behavior disorder was associated with αSyn-SAA positivity (OR 60.2, 95% CI 5.2-1,965.8; p < 0.01). DISCUSSION: We detected a frequency of αSyn-SAA positivity in CBS and PSP in line with pathologic studies, highlighting the usefulness of SAAs for in vivo detection of otherwise undetectable neuropathologic processes. Our results also suggest that AD status (specifically low Aß42) and older age at onset may contribute to αSyn-SAA positivity. This opens new perspectives for the stratification of patients in clinical trials.

Influence of peritoneal dialysis catheter type on dislocations and laxative use: a retrospective observational study.

BACKGROUND: There is currently no consensus regarding the optimal type of peritoneal dialysis (PD) catheter. Although few studies showed that weighted catheters result in lower complication rates and superior long-term outcomes than non-weighted catheters, there are no studies on the use of laxatives linked to catheter malfunction, a patient-related outcome potentially affecting the quality of life. Thus, we compared the burden of acute and chronic laxative use in a cohort of PD patients having either weighted or non-weighted catheters. METHODS: We performed a single-center, retrospective, observational study in two renal units, comparing acute and chronic laxative therapy related to catheter drainage failure in a cohort of 74 PD patient,s divided by peritoneal dialysis catheter type. In addition, we evaluated the number of patients who experienced minor and major dislocations, catheter-related infection rate, hospitalization for catheter malfunctioning, episodes of catheter repositioning, and dropout from PD. RESULTS: Laxative use was significantly more common among patients in the non-weighted catheter group (acute: 30.3% vs. 9.8%, p = 0.03; chronic: 36.4% vs. 12.2%; p≤0.02). Furthermore, weighted catheters were superior to non-weighted catheters for all the secondary outcomes (dislocations: 12.2% vs. 45.5%; p = 0.001). CONCLUSIONS: Weighted self-locating catheters have lower drainage failure, thus reducing the need and burden of acute and chronic laxative use among PD patients.

Continuous glucose monitoring in patients with type 2 diabetes on hemodialysis.

Diabetic kidney disease is the leading cause of end-stage kidney disease in high-income countries. The strict control of glycemic oscillations is the principal therapeutic target, but this could be hard to achieve in uremic patients due to their unpredictable insulin sensitivity. Currently, the evaluation of the glycemic profile relies on serum markers (glycated hemoglobin HbA1c, glycated albumin, and fructosamine), capillary glucose blood control (self-monitoring of blood glucose), and interstitial glucose control (continue glucose monitoring). We conducted a systematic review of published articles on continue glucose monitoring in hemodialysis patients with type 2 diabetes, which included 12 major articles. Four studies found significant fluctuations in glucose levels during hemodialysis sessions. All studies reported a higher mean amplitude of glucose variations on the hemodialysis day. Three studies agreed that continue glucose monitoring is better than glycated hemoglobin in detecting these abnormalities. Moreover, continue glucose monitoring was more accurate and perceived as easier to use by patients and their caregivers. In patients with type 2 diabetes on hemodialysis, glucose levels show different variation patterns than the patients on hemodialysis without diabetes. Considering manageability, accuracy, and cost-effectiveness, continue glucose monitoring could be the ideal diagnostic tool for the patient with diabetes on hemodialysis.

Human immunodeficiency virus and tuberculosis in Argentina: prevalence, genotypes and risk factors.

The objective of this study was to determine the prevalence and genetic variability of human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted infections (STIs) among 205 patients with clinical diagnosis of tuberculosis (TB) in Buenos Aires in 2001. Infections with hepatitis B virus (HBV), HIV-1, hepatitis C virus (HCV), Treponema pallidum and human T-cell lymphotropic virus types I/II were diagnosed in 37/187 (19.8 %), 35/205 (17.1 %), 22/187 (11.8 %), 13/187 (7.0 %) and 4/181 (2.2 %) patients, respectively. Almost one in three participants (33.1 %) presented at least one infection in addition to TB. Multiresistance to TB drugs (isoniazid plus rifampicin) was detected in the isolates recovered from three patients. Injecting drug use was detected as the main risk factor for HIV, HBV and HCV infections. Of ten patients who died, eight were infected with HIV. HIV genetic characterization showed the presence of two different subtypes. Env subtype F was found in 13/24 samples (54.2 %) and subtype B in 11/24 samples (45.8 %) by heteroduplex mobility assay. Sequencing of the protease/RT region was performed in ten samples: three were characterized as subtype B and seven as B/F recombinants by bootscanning analysis. Phylogenetic analysis of four full-length sequences showed that three were the circulating recombinant form CRF12_BF. The results of this study suggest an urgent need to detect HIV infection in high-risk groups to prevent future HIV transmission as well as morbidity and mortality associated with TB by providing highly active antiretroviral therapy (HAART) and/or TB treatment. Collaboration between TB and HIV programmes seems to be the best approach to decrease the incidence of these diseases, especially in high-prevalence HIV settings.