Abstract
Introduction: Patisiran is approved for the treatment of hATTR amyloidosis with polyneuropathy and its long-term efficacy/safety is being studied in a Global OLE. Plasma biomarkers are being investigated for utility in facilitating earlier diagnosis and monitoring disease /treatment response. Objective: Evaluate long-term change in neurofilament light chain (NfL) levels in response to patisiran in patients enrolled in the Global Open-Label Extension (OLE) study. Methods: NfL plasma levels were measured in duplicate in healthy controls and patients with ATTRv amyloidosis with polyneuropathy using the Quanterix Simoa platform. Patient samples were analyzed from the APOLLO study at baseline and 18 months, and also measured at 12 and 24 months following APOLLO in patients who rolled into the Global OLE. Results: NfL levels at APOLLO baseline were 63.2 (placebo) and 72.1 pg/ mL (patisiran). NfL increased during APOLLO in the placebo group (99.5 pg/mL), whereas a significant decrease was observed at 18 months following patisiran (48.8 pg/mL). Reduced NfL levels were maintained in the APOLLO-patisiran group through 24 months of additional patisiran treatment in the Global OLE (44.0 pg/mL), consistent with maintained improvement in mNIS+7. Upon initiation of patisiran in the Global OLE, the APOLLO-placebo group experienced a reduction in NfL levels through 24 months (44.2 pg/mL), reaching a similar level to the APOLLO-patisiran group. Conclusions: NfL may serve as a biomarker of active nerve damage and polyneuropathy, making it useful as a potential biomarker of disease progression, treatment response and for earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and monitoring disease.
Highlights
Capsaicin is able to induce mast cell degranulation, an event probably related to the pathophysiology of a migraine attack
Objectives: The present review study aimed to address the mechanisms of action of capsaicin and other chemical inducers in mast cell degranulation and an interaction of nerves and events that happen in the dura mater with the activation of mast cells
The analyses showed significantly higher frequency of the genotype VV in those who had depression, compared with the allele A
Summary
Capsaicin is able to induce mast cell degranulation, an event probably related to the pathophysiology of a migraine attack. Neuroinfections are pathologies that affect the CNS, for example, we have Murcomycosis, a progressive infection caused by opportunistic fungi of the order Mucorales, with high frequency in Immunodepressed patients, Diabetes Mellitus (DM) is the main underlying pathology associated with the development of Rhinocerebral Murcomycosis, which represents 50% of the cases, with a mortality rate of 70% (Sidrim, 2012, p.168). The COVID-19 pandemic has been alarming the world since its first outbreak in December 2019 In this scenario, the presence of aggravating factors such as the elevation of the D-dimer and the reduction of the angiotensin-converting enzyme 2 (ACE2) during the clinical course of the disease, collaborated in the appearance of thromboembolic events derived from inflammatory processes and extensive intravascular coagulation, contributing to the emergence of diseases such as Hemorrhagic Stroke (ICH), leading the patient to have a worse clinical prognosis and a consecutive worsening of their health. Despite being classically associated with this etiology, the finding may be present in other diseases, especially infiltrative ones
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