Secondary Analysis of Fluids and Catheters Treatment Trial (FACTT) data reveal poor clinical outcomes in acute respiratory distress syndrome patients with diabetes.

OBJECTIVES: Conflicting reports exist about the link between diabetes mellitus (DM) and acute respiratory distress syndrome (ARDS). Our study examines the impact of pre-existing DM on ARDS patients within the Fluid and Catheter Treatment Trial (FACTT). DESIGN: Conducting a secondary analysis of FACTT data, we incorporated 967 participants with identified DM status (173 with DM, 794 without DM) and examined outcomes like 90-day mortality, hospital and ICU stays, and ventilator days until unassisted breathing. The primary outcome of hospital mortality at day 90 was evaluated through logistic regression using IBM SPSS software. Additionally, we assessed plasma cytokines and chemokines utilizing a human magnetic bead-based multiplex assay. RESULTS: Patients with pre-existing DM exhibited a lower survival rate compared to non-DM patients (61.3 vs. 72.3 %, p = 0.006). Subjects with DM experienced significantly longer hospital lengths of stay (24.5 vs. 19.7 days; p = 0.008) and prolonged ICU stays (14.8 vs. 12.4 days; p = 0.029). No significant difference was found in ventilator days until unassisted breathing between the two groups (11.7 vs. 10; p = 0.1). Cytokine/chemokine analyses indicated a non-significant trend toward heightened levels of cytokines (TNF-α, IL-10, and IL-6) and chemokines (CRP, MCP-1) in DM patients compared to non-DM on both days 0 and 1. Notably, lipopolysaccharide-binding protein (LBP) exhibited significantly higher levels in DM compared to non-DM individuals. CONCLUSIONS: ARDS patients with DM suffered worse clinical outcomes compared to non-DM patients, indicating that DM may negatively affect the respiratory functions in these subjects. Further comprehensive clinical and pre-clinical studies will strengthen this relationship.

A multi-arm, parallel, preclinical study investigating the potential benefits of acetazolamide, candesartan, and triciribine in combination with fluconazole for the treatment of cryptococcal meningoencephalitis.

Cryptococcus neoformans, an opportunistic fungal pathogen, primarily infects immunodeficient patients frequently causing cryptococcal meningoencephalitis (CM). Increased intracranial pressure (ICP) is a serious complication responsible for increased morbidity and mortality in CM patients. Non-invasive pharmacological agents that mitigate ICP could be beneficial in treating CM patients. The objective of the study was to investigate the efficacy of acetazolamide (AZA), candesartan (CAN), and triciribine (TCBN), in combination with the antifungal fluconazole, on C. neoformans-induced endothelial, brain, and lung injury in an experimental mouse model of CM. Our study shows that C. neoformans increases the expression of brain endothelial cell (BEC) junction proteins Claudin-5 (Cldn5) and VE-Cadherin to induce pathological cell-barrier remodeling and gap formation associated with increased Akt and p38 MAPK activation. All three agents inhibited C. neoformans-induced endothelial gap formation, only CAN and TCBN significantly reduced C. neoformans-induced Cldn5 expression, and only TCBN was effective in inhibiting Akt and p38MAPK. Interestingly, although C. neoformans did not cause brain or lung edema in mice, it induced lung and brain injuries, which were significantly reversed by AZA, CAN, or TCBN. Our study provides novel insights into the direct effects of C. neoformans on BECs in vitro, and the potential benefits of using AZA, CAN, or TCBN in the management of CM patients.

Elevated Intracranial Pressure in Cryptococcal Meningoencephalitis: Examining Old, New, and Promising Drug Therapies.

Despite the availability of effective antifungal therapy, cryptococcal meningoencephalitis (CM) remains associated with elevated mortality. The spectrum of symptoms associated with the central nervous system (CNS) cryptococcosis is directly caused by the high fungal burden in the subarachnoid space and the peri-endothelial space of the CNS vasculature, which results in intracranial hypertension (ICH). Management of intracranial pressure (ICP) through aggressive drainage of cerebrospinal fluid by lumbar puncture is associated with increased survival. Unfortunately, these procedures are invasive and require specialized skills and supplies that are not readily available in resource-limited settings that carry the highest burden of CM. The institution of pharmacologic therapies to reduce the production or increase the resorption of cerebrospinal fluid would likely improve clinical outcomes associated with ICH in patients with CM. Here, we discuss the potential role of multiple pharmacologic drug classes such as diuretics, corticosteroids, and antiepileptic agents used to decrease ICP in various neurological conditions as potential future therapies for CM.

Off-the-shelf thermoluminescent silica glass media for use in medical diagnostic dosimetry applications.

In respect of radiation exposure assessments, thermoluminescent dosimeters (TLD) represent a notable and important subset of passive detector technology, gaining widespread use over a period of many decades, not least for medical applications. TLDs are available in a range of physical and chemical forms, in particular the popularity of phosphor-based commercial products arising from features that include availability down to low mm dimensions, soft-tissue equivalence in some cases, and relatively low TL fading. Novel doped silica glass TL material fabricated as fibres also offer favourable responses, recent developments in co-doping leading to their ability to also provide for diagnostic radiology applications, adding to the attractive features of being impervious to water, of good sensitivity, and generally offering wide dynamic range. Thus said, doping and fibre fabrication involve relatively high costs. Accordingly, herein exploratory investigations are made of the cost-effective colourless silica-based glass medium from which marbles are made, reduced into chip form for ease of application, examining sensitivity to dose. In particular, the study focuses on the computerised tomography clinical application regime, 80- to 140 kVp, with excellent response being shown for doses within the range 2- to 50 mGy.