Can Small Molecules Provide Clues on Disease Progression in Cerebrospinal Fluid from Mild Cognitive Impairment and Alzheimer's Disease Patients?

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease, which is currently diagnosed via clinical symptoms and nonspecific biomarkers (such as Aß1-42, t-Tau, and p-Tau) measured in cerebrospinal fluid (CSF), which alone do not provide sufficient insights into disease progression. In this pilot study, these biomarkers were complemented with small-molecule analysis using non-target high-resolution mass spectrometry coupled with liquid chromatography (LC) on the CSF of three groups: AD, mild cognitive impairment (MCI) due to AD, and a non-demented (ND) control group. An open-source cheminformatics pipeline based on MS-DIAL and patRoon was enhanced using CSF- and AD-specific suspect lists to assist in data interpretation. Chemical Similarity Enrichment Analysis revealed a significant increase of hydroxybutyrates in AD, including 3-hydroxybutanoic acid, which was found at higher levels in AD compared to MCI and ND. Furthermore, a highly sensitive target LC-MS method was used to quantify 35 bile acids (BAs) in the CSF, revealing several statistically significant differences including higher dehydrolithocholic acid levels and decreased conjugated BA levels in AD. This work provides several promising small-molecule hypotheses that could be used to help track the progression of AD in CSF samples.

Phase-Resolved Functional Lung (PREFUL) MRI to Quantify Ventilation: Feasibility and Physiological Relevance in Severe Asthma.

RATIONALE AND OBJECTIVES: Emergent evidence in several respiratory diseases supports translational potential for Phase-Resolved Functional Lung (PREFUL) MRI to spatially quantify ventilation but its feasibility and physiological relevance have not been demonstrated in patients with asthma. This study compares PREFUL-derived ventilation defect percent (VDP) in severe asthma patients to healthy controls and measures its responsiveness to bronchodilator therapy and relation to established measures of airways disease. MATERIALS AND METHODS: Forty-one adults with severe asthma and seven healthy controls performed same-day free-breathing 1H MRI, 129Xe MRI, spirometry, and oscillometry. A subset of participants (n = 23) performed chest CT and another subset of participants with asthma (n = 19) repeated 1H MRI following the administration of a bronchodilator. VDP was calculated for both PREFUL and 129Xe MRI. Additionally, the percent of functional small airways disease was determined from CT parametric response maps (PRMfSAD). RESULTS: PREFUL VDP measured pre-bronchodilator (19.1% [7.4-43.3], p = 0.0002) and post-bronchodilator (16.9% [6.1-38.4], p = 0.0007) were significantly greater than that of healthy controls (7.5% [3.7-15.5]) and was significantly decreased post-bronchodilator (from 21.9% [10.1-36.9] to 16.9% [6.1-38.4], p = 0.0053). PREFUL VDP was correlated with spirometry (FEV1%pred: r = -0.46, p = 0.0023; FVC%pred: r = -0.35, p = 0.024, FEV1/FVC: r = -0.46, p = 0.0028), 129Xe MRI VDP (r = 0.39, p = 0.013), and metrics of small airway disease (CT PRMfSAD: r = 0.55, p = 0.021; Xrs5 Hz: r = -0.44, p = 0.0046, and AX: r = 0.32, p = 0.044). CONCLUSION: PREFUL-derived VDP is responsive to bronchodilator therapy in asthma and is associated with measures of airflow obstruction and small airway dysfunction. These findings validate PREFUL VDP as a physiologically relevant and accessible ventilation imaging outcome measure in asthma.

Aspergilosis traqueobronquial necrotizante en paciente crítico / Necrotizing tracheobronchial aspergillosis in an immunosuppressed patient. Report of one case

Necrotizing tracheobronchitis due to Aspergillus spp is a rare form of invasive aspergillosis. This infection is limited to or predominant in the bronchial tree. The clinical evolution is gradual: from mild non-specific manifestations of acute tracheobronchitis to severe acute respiratory insufficiency determined by a bronchial obstruction syndrome. We report a 38 years old female with systemic lupus erythematosus treated with methylprednisolone and cyclophosphamide. She developed an invasive aspergillosis, severe respiratory failure with predominant tracheobronchial damage and upper respiratory complications.