Synthesis, Characterization, and Potential Usefulness in Liver Function Assessment of Novel Bile Acid Derivatives with Near-Infrared Fluorescence (NIRBAD).

Conventional serum markers often fail to accurately detect cholestasis accompanying many liver diseases. Although elevation in serum bile acid (BA) levels sensitively reflects impaired hepatobiliary function, other factors altering BA pool size and enterohepatic circulation can affect these levels. To develop fluorescent probes for extracorporeal noninvasive hepatobiliary function assessment by real-time monitoring methods, 1,3-dipolar cycloaddition reactions were used to conjugate near-infrared (NIR) fluorochromes with azide-functionalized BA derivatives (BAD). The resulting compounds (NIRBADs) were chromatographically (FC and PTLC) purified (>95%) and characterized by fluorimetry, 1H NMR, and HRMS using ESI ionization coupled to quadrupole TOF mass analysis. Transport studies using CHO cells stably expressing the BA carrier NTCP were performed by flow cytometry. Extracorporeal fluorescence was detected in anesthetized rats by high-resolution imaging analysis. Three NIRBADs were synthesized by conjugating alkynocyanine 718 with cholic acid (CA) at the COOH group via an ester (NIRBAD-1) or amide (NIRBAD-3) spacer, or at the 3α-position by a triazole link (NIRBAD-2). NIRBADs were efficiently taken up by cells expressing NTCP, which was inhibited by taurocholic acid (TCA). Following i.v. administration of NIRBAD-3 to rats, liver uptake and consequent release of NIR fluorescence could be extracorporeally monitored. This transient organ-specific handling contrasted with the absence of release to the intestine of alkynocyanine 718 and the lack of hepatotropism observed with other probes, such as indocyanine green. NIRBAD-3 administration did not alter serum biomarkers of hepatic and renal toxicity. NIRBADs can serve as probes to evaluate hepatobiliary function by noninvasive extracorporeal methods.

Recurrence of Hypoglycemia in Hospitalized Adult Patients in Non-Critical Areas: An Opportunity to Improve Patient Care Using Electronic Health Records.

Electronic Health Records offer an opportunity to improve patient care (in terms of quality and/or safety) by making available patient health information stored in a single Clinical Data Repository. We aimed to estimate the frequency of hypoglycemic recurrences in hospitalized adult patients in non-critical areas. We designed a cross sectional study with hospitalizations between 2017 and 2018, which included patients with at least one hypoglycemia health record (defined as a value <70 mg/dL, either by capillary glycemic monitoring or serum measurement). Recurrence was defined as those who presented a second event, with at least 2 hours of difference. We included 1884 patients, and 573 presented recurrences, yielding a global prevalence of 30.41% (95%CI 28.34-32.54). Due to the high frequency, it is important to identify vulnerable populations, to implement preventive measures to assist clinicians for decision-making tasks, as a clinical decision support system.