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Objective: This study aimed to investigate the efficacy and tolerability of Lacosamide (LCM) in a pediatric population with epilepsy using LCM serum concentration and its correlation to the age of the participants and the dosage of the drug. Methods: Demographic and clinical data were collected from the medical records of children with epilepsy treated with LCM at Shamir Medical Center between February 2019 to September 2021, in whom medication blood levels were measured. Trough serum LCM concentration was measured in the biochemical laboratory using High-Performance Liquid Chromatography (HPLC) and correlated with the administered weight-based medication dosing and clinical report. Results: Forty-two children aged 10.43 ± 5.13 years (range: 1–18) were included in the study. The average daily dose of LCM was 306.62 ± 133.20 mg (range: 100–600). The average number of seizures per day was 3.53 ± 7.25 compared to 0.87 ± 1.40 before and after LCM treatment, respectively. The mean LCM serum concentration was 6.74 ± 3.27 mg/L. No statistically significant association was found between LCM serum levels and the clinical response ( p = 0.58), as well as the correlation between LCM dosage and the change in seizure rate ( p = 0.30). Our study did not find a correlation between LCM serum concentration and LCM dosage and the gender of the participants: males (n = 17) females (n = 23) ( p = 0.31 and p = 0.94, respectively). A positive trend was found between age and LCM serum concentrations (r = 0.26, p = 0.09). Conclusion: Based on the data that has been obtained from our study, it appears that therapeutic drug monitoring for LCM may not be necessary. Nonetheless, further research in this area is needed in the light of the relatively small sample size of the study.

Multiple myeloma (MM) accounts for 13% to 15% of all blood cancers1 and is characterized by the proliferation of malignant cells within the bone marrow (BM). Despite important advances in treatment, most patients become refractory and relapse with the disease. As MM tumors grow in the BM, they disrupt hematopoiesis, create monoclonal protein spikes in the blood, initiate systemic organ and immune system shutdown,2 and induce painful osteolytic lesions caused by overactive osteoclasts and inhibited osteoblasts.3, 4 MM cells are also extremely dependent on the BM niche, and targeting the BM niche has been clinically transformative for inhibiting the positive-feedback \"vicious cycle\" between MM cells and osteoclasts that leads to bone resorption and tumor proliferation.5, 6, 7, 8 Bone marrow adipocytes (BMAs) are dynamic, secretory cells that have complex effects on osteoblasts and tumor cells, but their role in modifying the MM cell phenotype is relatively unexplored.9, 10, 11, 12, 13 Given their active endocrine function, capacity for direct cell-cell communication, correlation with aging and obesity (both MM risk factors), potential roles in bone disease, and physical proximity to MM cells, it appears that BMAs support MM cells.14, 15, 16, 17 This supposition is based on research from many laboratories, including our own. Therapeutically targeting the BMA may prove to be equally transformative in the clinic if the pathways through which BMAs affect MM cells can be determined. In this review, we discuss the potential for BMAs to provide free fatty acids to myeloma cells to support their growth and evolution. We highlight certain proteins in MM cells responsible for fatty acid uptake and oxidation and discuss the potential for therapeutically targeting fatty acid metabolism or BMAs from where they may be derived. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

The aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague–Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins – casein or whey. In terms of body weight, CU growth was incomplete in all study groups. Despite their similar food consumption, casein-re-fed rats had a significantly higher body weight and longer humerus than whey-re-fed rats in the long term. The height of the epiphyseal growth plate (EGP) in both casein and whey groups was greater than that of rats re-fed normal chow. Microcomputed tomography yielded significant differences in bone microstructure between the casein and whey groups, with the casein-re-fed animals having greater cortical thickness in both the short and long term in addition to a higher trabecular bone fraction in the short term, although this difference disappeared in the long term. Mechanical testing confirmed the greater bone strength in rats re-fed casein. Bone quality during CU growth significantly depends on the type of protein ingested. The higher EGP in the casein- and whey-re-fed rats suggests a better growth potential with milk-based diets. These results suggest that whey may lead to slower bone growth with reduced weight gain and, as such, may serve to circumvent long-term complications of CU growth.

The incidence of community-onset (CO) symptomatic urinary tract infection (SUTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales is increasing worldwide. Our study aims were to explore the independent predictors for CO-ESBL SUTI and to compare the effectiveness of several oral therapeutics, which are used for this indication in community health settings. Retrospective matched case-case-control and case-case studies, among insurers of Maccabi health maintenance organization, Shfella district, Israel (10-11/2019). Patients with CO-ESBL ( ) SUTI were matched to patients with CO-non-ESBL SUTI and to uninfected controls (1:1:1). Matched analyses (logistic regressions) were used to model predictors for CO-ESBL SUTI. A composite parameter for worse SUTI outcomes was compared among patients who were managed with a single, supposedly effective (ie, in vitro), oral agent. The study consisted of 1,455 patients (ie, three matched groups of 485 patients). The independent predictors for CO-ESBL SUTI were certain recent exposures: (1) hospitalization (3 months), (2) past carriage of multidrug-resistant organisms (2 years), (3) exposure to any antimicrobial (3 months), and (4) prior SUTI (6 months). Among 331 patients with CO-ESBL SUTI, resistance rates were lowest for fosfomycin (4.9%), while outcomes were worst for patients managed with oral amoxicillin-clavulanate. CO-ESBL SUTI independent predictors in this community region were recent hospitalization, known MDRO carriage, exposure to antimicrobials and prior SUTI. Amoxicillin-clavulanate should be avoided, even for ESBL susceptible isolates.

The use of protein- and peptide-based drugs in the treatment of disease has significantly increased in recent years. However, their chemical and physical properties make them unsuitable for simple oral delivery. The objective of this proof-of-concept study was to examine the feasibility of protein administered via intraosseous (IO) injection. Human growth hormone (GH), a 22-kd protein, served as the model protein. An indwelling IO needle and intravenous (IV) line were placed in four New Zealand white male rabbits, and 50, 100, 200, or 400 μg/kg of GH were injected. Blood samples were taken at different time points and analyzed for GH concentration. There were no significant pharmacokinetic differences between the IO and IV routes. For the 400 μg/kg dose, the area under the serum GH concentration time curve was 100.55 ± 46.7 μg/min*mL with IV administration and 84.6 ± 34 μg/min*mL for IO (P = .73 compared to the IV route), Cmax measured 11.2 ± 5 μg/L and Tmax 0.9 ± 0.7 minutes. For the 200 μg/kg dose, the area under the curve was 68.5 ± 16.7 μg/min*mL with IV administration, and 85.1 ± 1.5 μg/min*mL (P = .39) for IO, Cmax measured 8.13 ± 2.44 μg/L and Tmax 1.92 ± 1.06 minutes. The findings confirm that a large protein (22 kd) can be administered via IO injection, reaching blood levels comparable to IV injection. Further studies with a larger number of animals are required to evaluate the pharmacokinetics and pharmacodynamics of high-molecular-weight proteins injected by the IO route.

ObjectiveThis study aimed to investigate the efficacy and tolerability of Lacosamide (LCM) in a pediatric population with refractory epilepsy in relation to serum concentration, age, and dosage. MethodsDemographic and clinical data were collected from the medical records of children with refractory epilepsy treated with LCM at Shamir Medical Center between February 2019 to September 2021, in whom medication blood levels were measured. Trough serum LCM concentration was measured in the biochemical laboratory using High-Performance Liquid Chromatography (HPLC) and correlated with the administered dose and clinical report. ResultsForty-two children aged 10.43 ± 5.13 (range: 1–18) years old were included in the study. The average daily dose of LCM was 306.62 ± 133.20 mg (range: 100–600). The average number of seizures per day was 3.53±7.25 compared to 0.87±1.40 before and after LCM treatment, respectively. The mean LCM serum concentration was 6.74±3.27 mg/l. No statistically significant association was found between LCM serum levels and the clinical response (p=0.58), as well as the correlation between LCM dosage and the change in seizure rate (p=0.30). Our study did not find a correlation between LCM serum concentration and LCM dosage and the gender of the participants: males (n=17,) females (n=23) (p=0.31 and p=0.94, respectively). A positive trend was found between age and LCM serum concentrations (r=0.26, p=0.09).ConclusionDetermination of serum concentrations is not needed in all children treated with LCM. Serum concentrations may be valuable in patients with refractory epilepsy for compliance evaluation or in patients with satisfactory control of seizures to determine their therapeutic baseline.