Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients.Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0–24 h).Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0–24 h nor normalized AUCss, 0–24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = −0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0–24 h (r = −0.414, p = 0.049). Patients with AUCss, 0–24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0–24 h < 50 mg·h/L or patients with AUCss, 0–24 h 50–100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose.Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023

Giant thoracic hematoma post-transradial coronary angiography: a case report and review of the literature

Abstract Background Although there are cardiac interventional procedures, certain transradial access complications might be life-threatening. Case presentation A 67-year-old male was admitted for coronary angiography due to chest tightness and shortness of breath on exertion. Hours after the right transradial access angiography, the patients complained the right side of chest pain. Emergent chest X-ray revealed a giant mass in the right chest. The right radial artery was reaccessed and subsequent arteriograms confirmed that the presence of a rupture of the branch of right internal mammary artery. Simultaneously, a microcoil was implanted to seal the perforation. The perforation caused a thoracic hematoma measuring 13.8 cm × 6.7 cm, along with a decrease in hemoglobin concentration from 14.1 g/dL to a minimum of 7.8 g/dL. Additionally, the drainage of the hematoma and red blood cells transfusion were carried out. Further, the patient underwent ascending aortic replacement, aortic valve replacement, mitral valve replacement, and thoracic hematoma removal. Postoperative echocardiography showed that the prosthetic valves were properly positioned and functioning normally. The patient recovered well after the surgery and remained event-free during the latest 14moth follow-up period. Conclusions Vascular perforation and subsequent hematoma might occur due to guidewire maneuvering during transradial approach. Awareness of prevention, early recognition and management of access complications may help reduce the occurrence and severity of complications related to the transradial approach

Alpinia oxyphylla Miq. extract changes miRNA expression profiles in db-/db- mouse kidney

Abstract Background A number of dysregulated miRNAs have been identified and are proposed to have significant roles in the pathogenesis of type 2 diabetes mellitus or renal pathology. Alpinia oxyphylla has shown significant anti-inflammatory properties and play an anti-diabetes role. The objective of this study was to detect the alteration of miRNAs underlying the anti-diabetes effects of A. oxyphylla extract (AOE) in a type II diabetic animal model (C57BIKsj db-/db-). Results Treatment with AOE for 8 weeks led to lower concentrations of blood glucose, urine albumin, and urine creatinine. 17 and 13 miRNAs were statistically identified as differentially regulated in the DB/DB and db-/db- AOE mice, respectively, compared to the untreated db-/db- mice. Of these, 7 miRNAs were identified in both comparison groups, and these 7 miRNAs were verified by quantitative real-time PCR. Functional bioinformatics showed that the putative target genes of 7 miRNAs were associated with several diabetes effects and signaling pathways. Conclusions These founding suggest that the potential of AOE as a medicinal anti-diabetes treatment through changes in the expressions of specific miRNAs. The results provide a useful resource for future investigation of the role of AOE-regulated miRNAs in diabetes mellitus

MOESM1 of Alpinia oxyphylla Miq. extract changes miRNA expression profiles in db-/db- mouse kidney

Additional file 1. Overview of mouse transcriptome sequencing reads

MOESM2 of Alpinia oxyphylla Miq. extract changes miRNA expression profiles in db-/db- mouse kidney

Additional file 2. The sequence length distribution and frequence percentage of small RNA reads of mouse. The x-axis indicates the length of small RNA reads. The y-axis indicates the percentage of small RNA reads with specific length

Challenging the Activity-Durability Tradeoff of Fe-N-C Fuel Cell Catalysts via Controlling thermal Activation Atmosphere

Fe-N-C catalysts, the most promising platinum group metal (PGM)-free oxygen-reduction catalysts, often simultaneously contain pyrrolic N- (S1) and pyridinic N (S2) -coordinated FeN4 sites. These two types of active sites show significantly different intrinsic activity and stability. S1 sites are more active but less stable compared to S2 sites. Designing a Fe-N-C catalyst, which exclusively contains active S1 sites with enhanced intrinsic stability, is highly desirable to break the activity-stability trade-off. Herein, we report a Fe-N-C model catalyst that solely comprises S1 sites prepared by adding H2 in the pyrolysis atmosphere (i.e., 10% H2/Ar). A membrane electrode assembly (MEA) with the Fe-N-C cathode demonstrated compelling activity and generated a current density of 50.8 mA cm−2 at 0.9 ViR-free (H2-O2) and 211 mA cm−2 at 0.8 V (H2-air), which have significantly exceeded the U.S. DOE 2025 targets. The highly active Fe-N-C catalyst also demonstrated improved stability during life tests and accelerated stability tests (ASTs). The knowledge obtained from experimental and theoretical results elucidates that the FeN4 site formation process can be controlled by thermal activation atmospheres, which is essential to breaking activity-stability trade-off and design viable Fe-N-C catalysts with adequate activity and stability for proton exchange membrane fuel cells

Durable and High-Power Iron-Based Cathodes in Competition with Platinum for Proton-Exchange Membrane Fuel Cells

Atomically dispersed and nitrogen-coordinated single iron sites (FeN4) embedded in carbon (Fe-N-C) catalysts are the most promising platinum group metal (PGM)-free catalysts. However, they have yet to match their Pt counterparts for oxygen reduction reaction (ORR) activity and stability in proton exchange membrane fuel cells (PEMFCs). Here, we developed viable Fe-N-C catalysts, which, for the first time, demonstrated competitive activity to that of Pt/C catalysts and dramatically enhanced stability and durability under practical PEMFC operating conditions. The most active Fe-N-C catalyst achieved a record half-wave potential (E1/2 = 0.915 V vs. RHE at 0.6 mgcatcm-2) and an ORR mass activity of 10.5 mA mgcat at 0.9 V in (RDE) tests, exceeding a Pt/C baseline catalyst (60 µgPt cm-2) by 40 mV in acidic electrolytes. This compelling activity of the Fe-N-C catalyst in aqueous acids on rotating disk electrode (RDE) was successfully transferred to a fuel cell membrane electrode assemblies (MEAs), generating an initial current density of 44.2 mA cm-2 exceeding the U.S. DOE 2025 target (i.e., 44 mA cm-2) at 0.9 VIR-free under O2. Under practical hydrogen-air conditions, record 151 mA cm-2 at 0.8 V and peak power density of 601 mW cm-2 were achieved. Importantly, we discovered that depositing nitrogen-carbon species on the catalyst surface via chemical vapor deposition (CVD) dramatically enhanced catalyst stability, evidenced by performance durability after accelerated stress tests (30 000 square-wave voltage cycles under H2/air) and long-term steady-state life tests (> 300 hours at 0.67 V). Innovative identical location-scanning transmission electron microscopy (IL-STEM) experiments confirmed that the CVD process leads to deposition of nitrogen-doped carbon onto the catalyst surfaces. Along with theoretical modeling, a reconstruction of the carbon structure adjacent to FeN4 sites leads to increased robustness against demetallation and carbon oxidation. This work opens new avenues for developing earth-abundant iron-based catalysts with extraordinary activity and stability, thus competing with Pt and addressing the cost barrier of current PEMFCs