Evaluation of the appropriateness of vancomycin therapeutic drug monitoring in the intensive care unit with a clinical pharmacy approach, a cross-sectional study.

OBJECTIVES: Vancomycin, a glycopeptide antibiotic has antibacterial activity against Gram-positive bacteria and is frequently used in the intensive care unit (ICU). Inappropriate therapeutic drug monitoring (TDM) of vancomycin is a common problem encountered in hospital daily practice. The aim of this study was to evaluate the appropriateness of vancomycin trough-guided TDM in patients treated in the ICU using a clinical pharmacy approach. METHODS: The study was conducted retrospectively in patients over 18 years old who had at least one vancomycin trough level and who had received intravenous (IV) vancomycin for ≥3 days between 1 November 2020 and 1 April 2022. The study included 137 patients. Patient demographics and relevant vancomycin TDM data were collected from medical records. The appropriateness of TDM was evaluated according to the criteria established based on the monitoring recommendations specified in consensus guidelines for therapeutic drug monitoring of vancomycin published by the American Society of Health-System Pharmacists (ASHP) in 2009 and 2020. RESULTS: Of a total of 238 vancomycin trough levels measured in patients, 32.4% were collected at an inappropriate time. When patients were evaluated in terms of TDM appropriateness according to vancomycin level ranges (<10 µg/mL, 10-20 µg/mL and >20 µg/mL), we found the appropriate TDM was significantly higher in the therapeutic range (10-20 µg/mL) (p <0.001). Of the total 238 vancomycin trough concentrations taken from patients, 77 (32.4%) were measured at an inappropriate time. This caused dose withholding, wrong adjustments and therapy failure. The total TDM appropriateness of vancomycin was significantly higher in the therapeutic range defined as 10-20 µg/mL when evaluated based on 'TDM appropriateness criteria' (p <0.001). CONCLUSION: Our study shows that appropriate vancomycin TDM increases the likelihood of achieving target trough concentrations. Involvement of clinical pharmacists in TDM management may prevent the development of adverse reactions by ensuring appropriate sampling time and appropriate interpretation of vancomycin levels.

The Wound-Healing Potential of the Endemic Plant Helianthemum canum (L.) Baumg: Preclinical Studies Supported with Phytochemical Profiling.

The study's objective is to clarify the probable mechanisms underlying the wound-healing properties of Helianthemum canum L. (Cistaceae), a traditional anti-inflammatory and wound-healing medicine. LC/MS-MS was used to perform phytochemical analyses on a 70 % methanol extract of the plant's aerial parts. In vivo, linear incision and circular excision models were used to evaluate the wound healing activity. For anti-inflammatory effect, in vivo acetic acid capillary permeability assay and in vitro Interleukin 1, Interleukin 6, and Interferon É£ levels in LPS-induced FR skin fibroblast cell line were also evaluated. The extract significantly improved wound healing in experimental models, with tensile strength values of 27.8 % and a contraction value of 35.09 %. Histopathological examinations, hydroxyproline estimation, hyaluronidase, collagenase, and elastase enzyme inhibitory assays confirmed wound healing potential. Inflammatory cytokines were significantly inhibited in the LPS-induced FR cell line, with the highest effect seen on IL-6 (34.5±2.12 pg/mL). This study offered the first concrete proof that H. canum can be used to treat wounds by suggesting that the myricetin and quinic acid content identified by LCMS-MS analysis may be accountable for the effect of H. canum on wound contraction and hydroxyproline production.

Risk factors for early onset acute kidney injury after allogeneic haematopoietic stem cell transplantation and the role of drug-drug interactions.

INTRODUCTION: Acute kidney injury (AKI) is an important and life-threatening complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT). This is therefore an active research area with studies aiming to understand the factors that cause this complication. MATERIALS AND METHODS: We conducted a retrospective study to identify the factors that caused AKI in 100 patients who underwent allo-HSCT in the first 100 days after transplantation using logistic regression analysis. RESULTS: The mean time of onset of AKI was 45.58 days (range 13-97) and the mean±SD maximum serum creatinine value was 1.53±0.78 mg/dL. In 47 patients, level 1 or higher AKI occurred in the first month of transplantation and 38 of these patients were diagnosed with a higher level of AKI 31-100 days after transplantation. According to multivariate analysis, use of cyclophosphamide (adjusted odds ratio (AOR) 4.01, p=0.012), mean ciclosporin blood levels ≥250 ng/mL (AOR 2.81, p=0.022) and ciclosporin blood levels ≥450 ng/mL in the first month of transplantation (AOR 3.30, p=0.007) were found to be potential factors for early onset AKI. Ciclosporin blood levels exceeded 450 ng/mL in 35% of those using posaconazole and voriconazole during administration route change of ciclosporin. Use of ≥2 nephrotoxic anti-infective drugs (AOR 3, p=0.026) and developing AKI in the first month of transplantation (AOR 4.14, p=0.002) were found to be potential factors in the development of advanced AKI. CONCLUSION: Nephrotoxic drugs, cyclophosphamide use and ciclosporin blood levels are factors to be considered to prevent the development of AKI in patients undergoing allo-HSCT.

Assessment of clinical, biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study.

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 108 WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1ß, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid. Level of evidence: IV.

A comparison of four drug-drug interaction databases for patients undergoing haematopoietic stem cell transplantation.

WHAT IS KNOWN AND OBJECTIVE: Patients who have undergone haematopoietic stem cell transplantation are prone to drug-drug interactions due to polypharmacy. Drug-drug interaction databases are essential tools for identifying interactions in this patient group. However, drug-drug interaction checkers, which help manage interactions, may have disagreements about assessing the existence or severance of the interactions. The study aimed to determine differences among popular drug-drug interaction databases from several angles for patients who underwent haematopoietic stem cell transplantation. METHODS: The 21-day treatment sheets of one hundred patients who underwent haematopoietic stem cell transplantation were examined in two subscription-based (Uptodate and Micromedex) and two open-access databases (Drugs.com and Epocrates) in terms of several categories two years in a row. Statistical analysis was utilized to understand the compatibility of databases in terms of severity scores, evidence levels, given references, and word counts in interaction reports. Fleiss' and Cohen's kappa statistics were used to analyse the databases' agreement levels. RESULTS AND DISCUSSION: A total of 1393 and 1382 different drug-drug interactions were detected in subsequent versions of the databases, namely the 2021 and 2022 versions. The Fleiss kappa overall agreement among databases was slight. Uptodate and Micromedex showed fair agreement, and other database pairs showed slight agreement in severity ratings. CONCLUSION: There was a poor agreement among databases for interactions seen in bone marrow transplantation patients. Therefore, it would be safer to use more than one database in daily practice. Further work needs to be done to understand the agreement level of databases for different types of interactions.

Effect of kirenol on the interaction between the WNT/ß-Catenin and RUNX2/TCF/LEF1 pathways in fracture healing in vivo.

OBJECTIVE: This study aimed to determine the effects of a natural diterpenoid, kirenol, on fracture healing in vivo in an experimental rat model of femur fracture and investigate its potential mechanism of action via the Wnt/ß-catenin pathway. METHODS: In this study, 64 male Wistar albino rats aged 5-7 weeks and weighing 261-348 g were randomly divided into 8 groups from A to L, with eight rats in each group. Standardized fractures were created in the right femurs of the rats and then fixed with an intramedullary Kirschner wire. Four experimental groups were administered 2 mg/kg/day kirenol (Groups C and G) and 4 mg/kg/day (Groups D and H) kirenol by oral gavage.Thereafter, the animals were sacrificed at two time points as follows: on the 10th day (Groups B, C and D) and on the 21st day (Groups F, G and H) after the surgery; fracture healing in each group was assessed radiologically and histopathologically. The Radiographic Union scale of tibia fracture scoring system was used in the radiological examination; callus volume and density were measured using computed tomography. In the histopathologic examination, the scoring system described by Huo et al. was used. Additionally, the mechanism of action was evaluated based on the analyses of protein expression of Wnt3a, LRP5, TCF-LEF1, ß-catenin, and Runx-2 proteins using western blot analysis. RESULTS: Among the animals sacrificed on the 10th day after the surgery, the highest histopathological and radiological scores were observed in Group D (p<0.05). Furthermore, the callus density (p<0.05) was highest in Group D. Among the animals sacrificed on the 21st day, the highest histopathological and radiological scores were found in Group H, although the differences among the groups were not significant (p>0.05). The callus volume and density were the highest in Groups G and H, respectively, although the differences among groups were not significant. CONCLUSION: Kirenol may improve fracture healing in a dose-dependent manner with the early activation of the Wnt/ß-catenin pathway and the activation of the Runx-2 pathway.