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Abstract Dopamine is one of the significant neurotransmitters and its monitoring in biological fluids is a critical issue in healthcare and modern biomedical technology. Here, we have developed a dopamine biosensor based on surface plasmon resonance (SPR). For this purpose, the carboxymethyl dextran SPR chip was used as a surface to immobilize laccase as a bioaffinity recognition element. Data analysis exhibited that the acidic pH value is the optimal condition for dopamine interaction. Calculated kinetic affinity (KD) (48,545 nM), obtained from a molecular docking study, showed strong association of dopamine with the active site of laccase. The biosensor exhibited a linearity from 0.01 to 189 μg/ml and a lower detection limit of 0.1 ng/ml (signal-to-noise ratio (S/N) = 3) that is significantly higher than the most direct dopamine detecting sensors reported so far. Experiments for specificity in the presence of compounds that can co-exist with dopamine detection such as ascorbic acid, urea and l-dopa showed no significant interference. The current dopamine biosensor with high sensitivity and specificity, represent a novel detection tool that offers a label-free, simple procedure and cost effective monitoring system.

Advancements in psychotropic therapy for pregnant women are pivotal for addressing maternal mental health during the perinatal period. Screening for mood and anxiety symptoms during pregnancy is recommended to enable early intervention. Psychotropic medications, including antidepressants, benzodiazepines, antipsychotics, and mood stabilizers, are commonly used, but challenges remain regarding their safety and efficacy during pregnancy. Pregnancy induces significant changes in pharmacokinetics, necessitating personalized dosing strategies and careful monitoring. Real-time monitoring technologies, such as smartphone-integrated platforms and home-based monitoring, enhance accessibility and accuracy. Prospective studies and collaboration among healthcare providers are essential for evidence-based guidelines and optimal treatment strategies. Reducing stigma around mental health during pregnancy is crucial to ensure women seek help and discuss treatment options, promoting understanding and acceptance within the community. [ABSTRACT FROM AUTHOR]

This study presents an in-depth analysis of mitochondrial enzyme activities in Friedreich's ataxia (FA) patients, focusing on the Electron Transport Chain complexes I, II, and IV, the Krebs Cycle enzyme Citrate Synthase, and Coenzyme Q10 levels. It examines a cohort of 34 FA patients, comparing their mitochondrial enzyme activities and clinical parameters, including disease duration and cardiac markers, with those of 17 healthy controls. The findings reveal marked reductions in complexes II and, specifically, IV, highlighting mitochondrial impairment in FA. Additionally, elevated Neurofilament Light Chain levels and cardiomarkers were observed in FA patients. This research enhances our understanding of FA pathophysiology and suggests potential biomarkers for monitoring disease progression. The study underscores the need for further clinical trials to validate these findings, emphasizing the critical role of mitochondrial dysfunction in FA assessment and treatment. [ABSTRACT FROM AUTHOR]

Four sample preparation techniques, namely direct protein precipitation through a) trichloroacetic acid addition (PPA) or b) acetonitrile addition (PPO), c) liquid-liquid extraction in n-octanol followed by the direct injection of the organic layer, and d) supramolecular solvent extraction in a tetrahydrofuran/n-octanol/water coacervate (SUPRAS) were evaluated to be used for the RPLC/DAD assay of carbamazepine in human plasma samples, targeting therapeutic monitoring (TM) purposes. The chromatographic approach to separating carbamazepine from human plasma matrices was designed to be a simple gradient elution with an octadecyl chemically modified silica gel stationary phase, and a mobile phase composed of acetonitrile (organic) and HPLC grade water (aqueous), both with 0.1% formic acid. Monitoring at 290 nm allowed for the detection of carbamazepine. After optimizing both sample preparation procedures and chromatographic separation parameters, LOQ values of 3 µg/mL (PPA), 0.6 µg/mL (PPO), 12 ng/mL (LLE) and 50 ng/mL (SUPRAS) were determined. Detector response functions were studied over an interval up to 20 µg/mL (ULOQ). [ABSTRACT FROM AUTHOR]

Abstract Background Immune cells and cytokines have been linked to viremia dynamic and immune status during HIV infection. They may serve as useful biomarkers in the monitoring of people living with HIV-1 (PLHIV-1). The present work was aimed to assess whether cytokines and immune cell profiles may help in the therapeutic follow-up of PLHIV-1. Methods Forty PLHIV-1 in treatment success (PLHIV-1s) and fifty PLHIV-1 in treatment failure (PLHIV-1f) followed at the University Hospital of Abomey-Calavi/Sô-Ava in Benin were enrolled. Twenty healthy persons were also recruited as control group. Circulating cytokines and immune cells were quantified respectively by ELISA and flow cytometry. Results PLHIV-1 exhibited low proportions of CD4 + T cells, NK, NKT, granulocytes, classical and non-classical monocytes, and high proportions of CD8 + T cells, particularly in the PLHIV-1f group, compared to control subjects. Eosinophils, neutrophils and B cell frequencies did not change between the study groups. Circulating IFN-γ decreased whereas IL-4 significantly increased in PLHIV-1s compared to PLHIV-1f and control subjects even though the HIV infection in PLHIV-1s downregulated the high Th1 phenotype observed in control subjects. However, Th1/Th2 ratio remained biased to a Th1 phenotype in PLHIV-1f, suggesting that high viral load may have maintained a potential pro-inflammatory status in these patients. Data on inflammatory cytokines showed that IL-6 and TNF-α concentrations were significantly higher in PLHIV-1s and PLHIV-1f groups than in control subjects. Significant high levels of IL-5 and IL-7 were observed in PLHIV-1f compared to controls whereas PLHIV-1s presented only a high level of IL-5. No change was observed in IL-13 levels between the study groups. Conclusion Our study shows that, in addition to CD4/CD8 T cell ratio, NK and NKT cells along with IL-6, TNF-α, IL-5 and IL-7 cytokines could serve as valuable immunological biomarkers in the therapeutic monitoring of PLHIV-1 although a larger number of patients would be necessary to confirm these results.

INTRODUCTION: The antiplatelet effect of clopidogrel can vary between patients. A modified thromboelastography (TEG) protocol (TEG-Platelet Mapping assay® [TEG-PM]) can be used for clopidogrel monitoring but is not widely available. Thrombin generation (TG) assays could offer a novel alternative. The main objective of this pilot study was to assess TG assay variables (lag time, peak, endogenous thrombin potential [ETP]) in dogs before and after 7 days of clopidogrel administration and compare with TEG-PM variables (maximum amplitude [MA]-ADP and percentage (%) inhibition). METHODS: Six healthy mix-breed dogs were enrolled in this pilot study. Blood samples for platelet count, TG assays, and TEG-PM were obtained at two time points, corresponding to baseline, and after 7 days of clopidogrel administration (mean 2.3 +/- 0.3 mg/kg PO q24 hours). Data were then compared with a Students t-test. RESULTS: There was no significant change in TG assay variables performed on platelet poor plasma after 7 days of clopidogrel administration: lag time (Day 1: 1.8 +/- 0.2 min, Day 7: 1.8 +/- 0.2 min, p = 0.42); peak (Day 1: 76 +/- 7 nM, Day 7: 72 +/- 10 nM, p = 0.49); and ETP (Day 1: 399 +/- 27 nM*min, Day 7: 392 +/- 32 nM*min; p = 0.49). There were significant changes in TEG MA-ADP (Day 1: 19 +/- 8 mm, Day 7: 9 +/- 6 mm, p = 0.04) and % inhibition (Day 1: 58 +/- 27, Day 7: 99 +/- 0.3, p = 0.02). DISCUSSION: Clopidogrel administration did not lead to changes in TG assay variables performed on platelet poor plasma samples, despite concomitant changes in TEG-PM variables consistent with platelet inhibition. Based on this pilot study, thrombin generation performed on platelet poor plasma may not be a useful antiplatelet monitoring tool in dogs.

Background: Immune cells and cytokines have been linked to viremia dynamic and immune status during HIV infection. They may serve as useful biomarkers in the monitoring of people living with HIV-1 (PLHIV-1). The present work was aimed to assess whether cytokines and immune cell profiles may help in the therapeutic follow-up of PLHIV-1. Methods: Forty PLHIV-1 in treatment success (PLHIV-1s) and fifty PLHIV-1 in treatment failure (PLHIV-1f) followed at the University Hospital of Abomey-Calavi/Sô-Ava in Benin were enrolled. Twenty healthy persons were also recruited as control group. Circulating cytokines and immune cells were quantified respectively by ELISA and flow cytometry. Results: PLHIV-1 exhibited low proportions of CD4 + T cells, NK, NKT, granulocytes, classical and non-classical monocytes, and high proportions of CD8 + T cells, particularly in the PLHIV-1f group, compared to control subjects. Eosinophils, neutrophils and B cell frequencies did not change between the study groups. Circulating IFN-γ decreased whereas IL-4 significantly increased in PLHIV-1s compared to PLHIV-1f and control subjects even though the HIV infection in PLHIV-1s downregulated the high Th1 phenotype observed in control subjects. However, Th1/Th2 ratio remained biased to a Th1 phenotype in PLHIV-1f, suggesting that high viral load may have maintained a potential pro-inflammatory status in these patients. Data on inflammatory cytokines showed that IL-6 and TNF-α concentrations were significantly higher in PLHIV-1s and PLHIV-1f groups than in control subjects. Significant high levels of IL-5 and IL-7 were observed in PLHIV-1f compared to controls whereas PLHIV-1s presented only a high level of IL-5. No change was observed in IL-13 levels between the study groups. Conclusion: Our study shows that, in addition to CD4/CD8 T cell ratio, NK and NKT cells along with IL-6, TNF-α, IL-5 and IL-7 cytokines could serve as valuable immunological biomarkers in the therapeutic monitoring of PLHIV-1 although a larger number of patients would be necessary to confirm these results. [ABSTRACT FROM AUTHOR]

AbstractIt is essential to monitor the blood level of flutamide (FLT) during prostate cancer treatment since the abnormal renal elimination due to pathophysiological factors hinders attaining steady-state drug concentration. This study reports a systematic investigation of aggregation of silver nanoparticles (AgNPs) based on Hofmeister effect and eventual change in surface-enhanced Raman spectroscopy (SERS) enhancement for the determination of FLT. Among the aggregants, MgSO4 showed the maximum enhancement. The concentration of MgSO4, pH, and duration of aggregation were optimized for FLT detection. The aggregated AgNPs (a-AgNPs) SERS substrate enhanced the Raman signal of FLT by up to five-orders of magnitude under optimized conditions. The developed technique was able to determine FLT from 0.25 × 10−3 μM to 250 μM with a limit of detection (LoD) of 1 pM. The application of the SERS substrate in practical analysis has been demonstrated using FLT-spiked human serum from 0 nM to 1000 nM with a detection limit of 0.3 nM. The reported Hofmeister series of AgNPs aggregation will assist in the development of SERS substrates for other analytes. [ABSTRACT FROM AUTHOR]

Objectives Quantification of direct oral anticoagulant (DOAC) plasma levels can guide clinical management, but insight into clinical scenarios surrounding DOAC-calibrated anti-FXa assays is limited. Methods Apixaban- and rivaroxaban-calibrated chromogenic anti-Xa assays performed over a 1-year period were retrospectively analyzed. Patient demographics, DOAC history, concomitant medications, and renal/liver comorbidities were obtained. Indications for testing and associated clinical actions were reviewed. Machine learning (ML) models predicting clinical actions were evaluated. Results In total, 371 anti-FXa apixaban and 89 anti-FXa rivaroxaban tests were performed for 259 and 67 patients in recurring urgent (acute bleeding, unplanned procedures) and nonurgent situations, including several scenarios not captured by existing testing recommendations (eg, drug monitoring, recurrent thromboembolic events, bleeding tendency). In urgent settings, andexanet reversal was guided by radiologic and clinical findings over DOAC levels in 14 of 32 instances, while 51% of apixaban patients qualified for nonreversal strategies through the availability of levels. Levels also informed procedure/intervention timing and supported management decisions when DOAC clearance or DOAC target levels were in question. The importance of clinical context was emphasized by exploratory ML models predicting particular clinical actions. Conclusions Although clinical situations are complex, DOAC testing facilitates clinical decision-making, including reversal, justifying more widespread implementation of these assays. [ABSTRACT FROM AUTHOR]

Simple Summary: This comprehensive systematic review provides valuable insights into the landscape of biomarkers in clear cell renal cell carcinoma (ccRCC) and their potential applications in the prediction of treatment response, prognosis, and therapeutic monitoring. One of the major challenges in ccRCC is determining the most effective treatment strategies and identifying patients who would benefit from adjuvant or neoadjuvant therapy. This review aims to provide a comprehensive overview of biomarkers in ccRCC and their utility in the prediction of treatment response, prognosis, and therapeutic monitoring in patients receiving systemic therapy for metastatic disease. The findings underscore the importance of incorporating biomarker assessment into clinical practice to guide treatment decisions and improve patient outcomes in ccRCC. Background: Challenges remain in determining the most effective treatment strategies and identifying patients who would benefit from adjuvant or neoadjuvant therapy in renal cell carcinoma. The objective of this review is to provide a comprehensive overview of biomarkers in metastatic renal cell carcinoma (mRCC) and their utility in prediction of treatment response, prognosis, and therapeutic monitoring in patients receiving systemic therapy for metastatic disease. Methods: A systematic literature search was conducted using the PubMed database for relevant studies published between January 2017 and December 2022. The search focused on biomarkers associated with mRCC and their relationship to immune checkpoint inhibitors, targeted therapy, and VEGF inhibitors in the adjuvant, neoadjuvant, and metastatic settings. Results: The review identified various biomarkers with predictive, prognostic, and therapeutic monitoring potential in mRCC. The review also discussed the challenges associated with anti-angiogenic and immune-checkpoint monotherapy trials and highlighted the need for personalized therapy based on molecular signatures. Conclusion: This comprehensive review provides valuable insights into the landscape of biomarkers in mRCC and their potential applications in prediction of treatment response, prognosis, and therapeutic monitoring. The findings underscore the importance of incorporating biomarker assessment into clinical practice to guide treatment decisions and improve patient outcomes in mRCC. [ABSTRACT FROM AUTHOR]

Introduction: 18F-FDG-PET/CT is recommended to improve the diagnosis of prosthetic valve infective endocarditis (PVIE) and is a major criterion in the ESC-2015 classification. However, there is little evidence for its usefulness in the follow-up of medically treated PVIE patients. Methods: A monocentric retrospective analysis of patients hospitalized for PVIE between January 2013 and December 2019 who were not treated with surgery and who had at least two 18F-FDG-PET/CT examinations during their medical management. Results: Among 170 patients with PVIE, 117 were treated with antibiotic therapy but no surgery. Of these, 36 (31%) had at least two 18F-FDG-PET/CT examinations. At initial imaging, 28 patients had heterogeneous FDG uptake on their prosthetic valve and eight on their associated aortic graft. Hypermetabolism of spleen and bone marrow (HSBM) was observed in 18 and 19 patients, respectively. At the first follow-up 18F-FDG-PET/CT, 21 (58%) patients still had heterogeneous uptake, indicating persistent active endocarditis. HSBM was still present at the last follow-up imaging in four of the six patients with recurrent PVIE. Conclusion: 18F-FDG-PET/CT monitoring of medically treated patients with PVIE provides valuable additional information and prospective multicentric study should be conducted to assess its usefulness. [ABSTRACT FROM AUTHOR]

Background: Vancomycin area-under-the-curve (AUC) monitoring is associated with reduced nephrotoxicity but may increase cost and workload for personnel compared to trough monitoring. Objective: The purpose of this study was to compare the accuracy of vancomycin AUC calculated by open-access, online, trough-only calculators to AUCs calculated by the trapezoidal method (TM) using peak and trough concentrations. Methods: This retrospective, multi-center study included adults ≥18 years old with stable renal function who received vancomycin with steady-state peak and trough concentrations. Areas under the curve calculated by TM were compared to AUCs calculated by 3 online calculators using trough-only options for calculation: ClinCalc, VancoVanco, and VancoPK. The primary outcome was actual difference in AUC between TM and the online calculators. Secondary outcomes were percent difference in AUC and clinical alignment in dose adjustments between methods. Results: Seventy patients were included for analysis. There was a statistically significant difference in AUC between TM and ClinCalc (median actual difference: −52, P < 0.001) and VancoVanco (median actual difference: 95, P < 0.001), whereas there was no significant difference between TM and VancoPK (median actual difference: −0.8, P = 0.827). Discordant dose adjustments were indicated when comparing ClinCalc, VancoVanco, and VancoPK to TM in 28%, 36%, and 12% of cases, respectively. Conclusion: The AUC calculator most closely aligned with TM was VancoPK, whereas other included calculators were statistically different. Owing to the cost and complexity of obtaining multiple levels, our findings support using a single steady-state trough using VancoPK as an alternative to TM for calculation of vancomycin AUC. [ABSTRACT FROM AUTHOR]

Although phage therapy has been in existence for a century, a recent resurgence in interest has occurred because of the continued emergence of antimicrobial resistance and the rising use of indwelling medical devices, resulting in biofilm-associated infections, for which conventional antibiotics are of limited use. Despite this, the clinical successes have been inconsistent because of multiple reasons, including (1) the narrow host range of phages, (2) challenges with concentrating phages at the site of infection, (3) development of resistance of bacteria to phages and (4) immune neutralization. Microbiologic assays have the potential to help guide the course of clinical therapy and improve outcomes. Methods developed decades ago remain the mainstay of phage diagnostics and recently, newer diagnostics are closing the gap needed to further advance clinical phage therapy. To review the current state of clinical phage microbiology and identify gaps. A PubMed search was performed using the terms "phage microbiology", "phage susceptibility test", "phage host range", "phage biofilm", and "phage therapeutic monitoring". Phage susceptibility testing, biofilm assays, phage-antibiotic combination testing, therapeutic drug monitoring, and immune monitoring assays are the current foundation for clinical phage diagnostics. Standardization of these assays and better understanding as to if and how they should be used in terms of clinical management of patients receiving phage therapy is needed. A substantial gap between in vitro studies and in vivo outcomes indicates that further work is needed in phage pharmacokinetics to accurately assay phage particles at the site of infection; recapitulate in vivo biofilm; capture the complex interactions between phages and antibiotics, phages and their target bacteria, among phages in a cocktail, and with the superhost immune system. [ABSTRACT FROM AUTHOR]

Context: Therapeutic drug monitoring (TDM) allows personalizing the dose of valproic acid in patients with epilepsy to optimize drug therapy, minimize adverse effects and detect interactions. Aims: To determine valproic acid concentrations in serum samples from people with epilepsy and to analyze its clinical implications. Methods: Cloned donor enzyme immunoassay; descriptive, cross-sectional, non-randomized, convenience recruitment study of 57 voluntary patients with epilepsy (n = 39 male, 68.42%; n = 18 female, 31.58%) aged between 19 and 62 years. After three months of treatment with valproic acid, a single blood sample was collected from each volunteer at a minimal concentration. Results: Serum drug concentrations 51.30-100.10 mg/L (SD 5.94) and level/dose 2.17-5.31 (SD 1.14) were observed. Association was shown between the dose ratio/dose of valproic acid (R2 = 0.8693; p α = 0.05). Conclusions: Serum valproic acid concentrations are within the therapeutic range, and there is a significant inverse linear correlation between dose ratio/dose, which must be considered to personalize the dose and optimize the pharmacotherapeutic result.

IntroductionThe antiplatelet effect of clopidogrel can vary between patients. A modified thromboelastography (TEG) protocol (TEG-Platelet Mapping assay® [TEG-PM]) can be used for clopidogrel monitoring but is not widely available. Thrombin generation (TG) assays could offer a novel alternative. The main objective of this pilot study was to assess TG assay variables (lag time, peak, endogenous thrombin potential [ETP]) in dogs before and after 7 days of clopidogrel administration and compare with TEG-PM variables (maximum amplitude [MA]-ADP and percentage (%) inhibition).MethodsSix healthy mix-breed dogs were enrolled in this pilot study. Blood samples for platelet count, TG assays, and TEG-PM were obtained at two time points, corresponding to baseline, and after 7 days of clopidogrel administration (mean 2.3 +/− 0.3 mg/kg PO q24 hours). Data were then compared with a Student’s t-test.ResultsThere was no significant change in TG assay variables performed on platelet poor plasma after 7 days of clopidogrel administration: lag time (Day 1: 1.8 +/− 0.2 min, Day 7: 1.8 +/− 0.2 min, p = 0.42); peak (Day 1: 76 +/− 7 nM, Day 7: 72 +/− 10 nM, p = 0.49); and ETP (Day 1: 399 +/− 27 nM*min, Day 7: 392 +/− 32 nM*min; p = 0.49). There were significant changes in TEG MA-ADP (Day 1: 19 +/− 8 mm, Day 7: 9 +/− 6 mm, p = 0.04) and % inhibition (Day 1: 58 +/− 27, Day 7: 99 +/− 0.3, p = 0.02).DiscussionClopidogrel administration did not lead to changes in TG assay variables performed on platelet poor plasma samples, despite concomitant changes in TEG-PM variables consistent with platelet inhibition. Based on this pilot study, thrombin generation performed on platelet poor plasma may not be a useful antiplatelet monitoring tool in dogs.

Diagnosis and therapeutic management in ulcerative colitis (UC) relies on a combination of endoscopic and histological scorings which are difficult to objectively quantify. Artificial intelligence (AI) might overcome the current issues of inter-observer variability, repetitive need for biopsies and estimation of disease activity medicine currently encourages. With this narrative literature review we aim to provide a clear and critical overview of the recent evolutions in the field of AI and UC, based on a literature search performed on Pubmed, Embase and Cochrane Library. The major focus of this review is the use of AI for endoscopic assessment of disease activity and the correlation with histology and long-term outcome. Moreover, we elucidate on the more recent developments in the field of AI as support in histological disease assessment, surveillance, therapy monitoring and natural language processing. UC management is evolving with AI impacting nearly every aspect of it. The immediate future influence of AI in UC management will be focussed on the collection, extraction and organization of particular clinical information. Expect is the transformation toward a real-time standardized, reproducible, objective and high-reliable disease grading, especially in endoscopy, histology and eventually radiology applications for UC. [ABSTRACT FROM AUTHOR]

Background: Vulvar lichen sclerosus (VLS) in girls presents with itching, dysuria, and constipation and may result in the loss of vulvar architecture. In patients with an ambiguous clinical presentation, reflectance confocal microscopy (RCM) could be a helpful noninvasive diagnostic tool. The aim of this study was to describe the RCM characteristics of VLS and explore the clinical application value of RCM in therapeutic monitoring. Methods: Sixteen patients with VLS were included in the study. All patients were periodically evaluated clinically with RCM, and different treatment regimens were given based on the patient's clinical appearances and RCM features. Results: Some major key diagnostic features of VLS can be observed by RCM, including round to oval cyst‐like structures with medium‐to‐low‐refractive keratinoid substances (75%), thinning of the epidermal thickness (100%), destruction of the ring‐like structures around dermal papillae (100%), disorderly distributed coarse medium‐refractive fibrous material (100%),polygonal, plump, high‐refractive cellular structures and linear low‐refractive canalicular structures (100%). All of these characteristics had a high correspondence with histopathological features. The clinical manifestations improved after individualized treatment regimens based on the clinical appearances and RCM features. Conclusion: RCM allows the visualization of major key diagnostic features of VLS and represents a valid option for objective therapeutic monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory bowel diseases (IBDs) are idiopathic inflammations of the colon, which can often undergo remission with the use of specific anti-TNF antibodies such as the infliximab. Although that the therapeutic monitoring can provide valuable insight into the possible etiology of unfavorable outcomes and allow for an appropriate management strategy for these patients, currently none technique or biomarker have proved ideal for the evaluation of therapeutic benefices of anti-TNF antibodies in IBDs. Aim: To summarise current knowledge on the role of serum adipokines as potential biomarkers for the therapeutic monitoring of patients with IBDs under infliximab. Methods: A systematic review was carried out in the PubMed/MEDLINE, Cochrane Library, Scopus and Biblioteca Virtual em Saúde databases. Next, the meta-analysis was performed with the mean values of serum adipokine levels in patients with IBDs before and after the use of infliximab using the Review Manager (RevMan) ® 5.3 software. Results: Three studies that together included 58 patients diagnosed with IBDs and treated with infliximab at 5 mg/kg were selected. According to the quantitative analysis, serum leptin levels were significantly increased after the use of infliximab (p-value=0.01; Heterogeneity: I²=61%), which is correlated with the clinical remission of the disease. In addition, the circulating adiponectin (p-value=0.006; Heterogeneity: I²=0%) and resistin (p-value=0.009; Heterogeneity: I²=93%) concentrations were both reduced after the clinical remission of IBD with the use of infliximab. Conclusion: Serum leptin levels are significantly increased, while circulating adiponectin and resistin is reduced among IBD patients after the use of infliximab. [ABSTRACT FROM AUTHOR]

Early diagnosis and effective therapy are essential for improving the overall prognosis and quality of life of patients with nephropathic cystinosis. The severity of kidney dysfunction and the multi-organ involvement as a consequence of the increased intracellular concentration of cystine highlight the necessity of accurate monitoring of intracellular cystine to guarantee effective treatment of the disease. Cystine depletion is the only available treatment, which should begin immediately after diagnosis, and not discontinued, to significantly slow progression of renal and extra-renal organ damage. This review aims to discuss the importance of the close monitoring of intracellular cystine concentration to optimize cystine depletion therapy. In addition, the role of new biomarkers in the management of the disease, from timely diagnosis to implementing treatment during follow-up, is overviewed. [ABSTRACT FROM AUTHOR]

The α-glucosidase inhibitor is regarded as one of the most important drugs for the treatment of diabetes, which can control postprandial blood glucose levels via prolonging the carbohydrate digestion time and retarding the carbohydrates' absorption. The present work aims to establish a facile bioanalytical method, based on α-glucosidase catalyzing the hydrolysis of 2-O-alpha-D-Glucopyranosyl-L-ascorbic acid (AA-2G), for the quantification of acarbose and migliol using a personal glucose meter (PGM). The hydrolysis products (ascorbic acid and glucose) can trigger the reduction of K3[Fe(CN)6] to K4[Fe(CN)6] in the glucose test strips, which results in the formation of the electron, which can be measured by PGM. Thus, ascorbic acid and glucose can be simultaneously measured by a simplified and miniaturized PGM method. However, the products produced by the hydrolysis of AA-2G will be decreased after the addition of acarbose or migliol to inhibit the activity of α-glucosidase, thereby resulting in a decreased PGM readout. After being incubated with α-glucosidase for 3.0 min and enzymatic reaction for 5.0 min, the quantitative detection of acarbose and migliol can be achieved within the ranges of 1.0–30.0 μM with the limit of detection of 0.33 μM and 3.0–33.3 μM with the limit of detection of 1.0 μM, respectively. IC50 values for acarbose and migliol are calculated to be 10.0 μM and 16.0 μM, respectively. The recoveries of the acarbose and migliol spiked with three different concentrations (final concentrations of 10.0, 20.0, and 30.0 μM) in human serum sample are in the ranges of 89.6–114.5% and 93.9–106.5%, respectively. These results demonstrate that the developed PGM method may be useful in future studies on therapeutic monitoring of acarbose and migliol. [ABSTRACT FROM AUTHOR]

Objective: To analyse the concentrations of lamotrigine in maternal serum, colostrum, and serum of breastfed newborns, and to evaluate the effect of comedication with enzyme-inducing antiseizure medication and valproic acid. Methods: This cohort study collected data from 158 women and 143 breastfed newborns. Maternal serum, milk (i.e., colostrum), and newborn serum samples were collected between the 2nd and 5th postnatal days, and lamotrigine concentrations were measured by high-performance liquid chromatography. Results: The median lamotrigine concentrations were 2.7 mg/L in maternal serum, 1.4 mg/L in milk, and 1.7 mg/L in newborn serum. The median milk/maternal serum concentration ratio was 0.60, the median newborn/maternal serum concentration ratio was also 0.60, and the median newborn serum/milk concentration ratio was 1.00. A significant correlation was observed between milk and maternal serum concentrations and between newborn serum and milk concentrations, maternal serum concentrations, maternal daily dose, and dose related to maternal body weight. Conclusions: Exposure to lamotrigine in breastfed newborns is lower than exposure during pregnancy. However, by the same dose by the same mother, lamotrigine concentrations in both maternal serum and milk increase significantly after delivery. This finding, together with the immature function of eliminating enzymes in newborns, may be the reason for reaching concentrations in the reference range used for the general epileptic population in breastfed newborns. Therapeutic monitoring of breastfed newborns serum concentrations of lamotrigine is not mandatory; however, if signs of possible adverse events are noted, newborn serum concentrations should be analysed.

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Background: Therapeutic drug monitoring is commonly performed to confirm the safe and effective use of the vancomycin; however, the facility for it is not available in many hospitals. Many clinicians use conventional fixed dose of 1000 mg every 12 h irrespective of the body weight. Aim: The aim of the study was to assess the appropriateness of vancomycin initial dose in adult patients with normal renal function. Setting and Design: This was a retrospective observational study involving medical records of patients treated with intravenous vancomycin during January 1, 2016–December 30, 2016, at a major tertiary care hospital in southern region of Saudi Arabia. Materials and Methods: The study was conducted based on electronic medical records of the patients who received intravenous vancomycin, aged ≥ 18 years, weighing more than 50 kg, and with normal renal functions during the period of the study. Chi-square tests were used for categorical variables. Multivariable logistic regressions were computed to examine the relationships between the explanatory variables and the appropriateness of vancomycin dose. Results: The study evaluated records of 456 adult patients, of which 63.8% were male. As per vancomycin dose received, 229 patients received suboptimal dosing of vancomycin when the dose was recalculated using actual body weight. The majority of the prescriptions of junior residents (68.5%) were using an optimal initial dose of vancomycin as compared to 43.6% of the senior residents or 48% of the consultants. Conclusions: A significant number of patients were receiving suboptimal initial dose of vancomycin. Junior residents were more meticulous with the initial vancomycin dosing.

Background: Neuroblastoma (NBL), is the most common, non-CNS solid tumor of childhood. This disease presents with unique biological and clinical challenges necessitating accurate diagnosis, prognosis assessment, treatment, and vigilant monitoring. Liquid biopsy is an upcoming, innovative, and non-invasive diagnostic modality. It has the potential to detect tumors and perform therapeutic monitoring through the analysis of circulating biomarkers in blood, urine, saliva, and other bodily fluids., Methodology: This scoping review offers an in-depth exploration, of the current landscape of liquid biopsy-based biomarkers in NBL. The review looks at the clinical implications, prevalent challenges, and future outlook of their clinical applications in NBL. The scoping review adhered to the guidelines of the PRISMA extension for scoping reviews, known as PRISMA-ScR, as the skeletal framework. The review involved comprehensive searches for liquid biopsy-based biomarkers in NBL across multiple databases, including PUBMED, EMBASE, SCOPUS, and WEB of Science, without restrictions., Results: The scoping review process uncovered a significant body of literature (n = 201) that underwent meticulous scrutiny, ultimately leading to the final selection of studies (n = 15). The liquid biopsy biomarkers included circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and other entities in bodily fluids. Their evaluation focused on associations with clinical outcomes such as overall survival, event-free survival, and risk stratification in NBL., Conclusion: Our findings highlight the potential of liquid biopsy biomarkers to revolutionize NBL diagnosis and therapeutic monitoring. This rapidly evolving frontier in pediatric oncology suggests significant advancements in precision medicine for the management of NBL., Competing Interests: Conflict of interest All authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In high-dose methotrexate (HD-MTX) therapy, delayed elimination of MTX from plasma leads to severe adverse effects. However, the risk factors for the delayed elimination of plasma MTX are still unclear. Objective: The purpose of this study was to investigate the factors related to the delayed MTX elimination in HD-MTX monotherapy. Methods: This retrospective study was performed on patients who received HD-MTX monotherapy between April 2009 and March 2019 at the Hiroshima University Hospital. Patients were divided into a "Normal" and a "Delayed" group according to their MTX plasma concentration at 48 or 72 hours after administration. Patient characteristics, dose of HD-MTX, MTX plasma concentration, and adverse effects were analyzed and compared between the 2 groups. Results: A total of 74 patients were included in this study. Logistic analysis of patient baseline characteristics was performed to identify risk factors for delayed MTX elimination. Serum albumin (ALB) was detected as a risk factor. Univariate and multivariate analysis revealed that low ALB level (<3.7 g/dL) and type of cancer were associated with delayed MTX elimination (univariate analysis: odds ratio [OR] = 6.00, P = 0.004, and OR = 4.33, P = 0.039, respectively; multivariate analysis: adjusted OR [AOR] = 6.45, P = 0.006, and AOR = 8.11, P = 0.018, respectively). Adverse effects were not significantly different between the 2 groups, excluding renal impairment. Conclusions and Relevance: Our study showed that low ALB is a risk factor for delayed MTX elimination in HD-MTX monotherapy. Pharmacokinetic analysis is needed to establish the dose of HD-MTX in patients with a low ALB level. [ABSTRACT FROM AUTHOR]

Cystine-depleting therapy in nephropathic cystinosis is currently monitored via the white blood cell cystine assay, although its application and usefulness are limited by practical and technical issues. Therefore, alternative biomarkers that are widely available, more economical and less technically demanding, while reliably reflecting long-term adherence to cysteamine treatment, are desirable. Recently, we proposed chitotriosidase enzyme activity as a potential novel biomarker for the therapeutic monitoring of cysteamine treatment in cystinosis. In this study, we aimed to validate our previous findings and to confirm the value of chitotriosidase in the management of cystinosis therapy. A retrospective study was conducted on 12 patients treated at the National Institutes of Health Clinical Center and followed up for at least 2 years. Plasma chitotriosidase enzyme activity was correlated with corresponding clinical and biochemical data. Plasma chitotriosidase enzyme activity significantly correlated with WBC cystine levels, cysteamine total daily dosage and a Composite compliance score. Moreover, plasma chitotriosidase was a significant independent predictor for WBC cystine levels, and cut-off values were established in both non-kidney transplanted and kidney transplanted cystinosis patients to distinguish patients with a good versus poor compliance with cysteamine treatment. Our observations are consistent with those of our previous study and validate our findings. Chitotriosidase enzyme activity is a valid potential alternative biomarker for monitoring cysteamine treatment in nephropathic cystinosis patients. Chitotriosidase enzyme activity is a valid potential alternative biomarker for monitoring cysteamine treatment in nephropathic cystinosis patients. [ABSTRACT FROM AUTHOR]

• We classified ALK -positive NSCLC into three subgroups with distinct biological and clinical features by proteomic data. • A novel plasma-based prognostic model was developed for predicting response to ALK-TKI therapy. • Longitudinal changes in acute-phase proteins during treatment reflect the treatment status of ALK -positive NSCLC patients. Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) has demonstrated remarkable therapeutic effects in ALK -positive non-small cell lung cancer (NSCLC) patients. Identifying prognostic biomarkers can enhance the clinical efficacy of relapsed or refractory patients. We profiled 737 plasma proteins from 159 pre-treatment and on-treatment plasma samples of 63 ALK -positive NSCLC patients using data-independent acquisition-mass spectrometry (DIA-MS). The consensus clustering algorithm was used to identify subtypes with distinct biological features. A plasma-based prognostic model was constructed using the LASSO-Cox method. We performed the Mfuzz analysis to classify the patterns of longitudinal changes in plasma proteins during treatment. 52 baseline plasma samples from another independent ALK-TKI treatment cohort were collected to validate the potential prognostic markers using ELISA. We identified three subtypes of ALK -positive NSCLC with distinct biological features and clinical efficacy. Patients in subgroup 1 exhibited activated humoral immunity and inflammatory responses, increased expression of positive acute-phase response proteins, and the worst prognosis. Then we constructed and verified a prognostic model that predicts the efficacy of ALK-TKI therapy using the expression levels of five plasma proteins (SERPINA4, ATRN, APOA4, TF, and MYOC) at baseline. Next, we explored the longitudinal changes in plasma protein expression during treatment and identified four distinct change patterns (Clusters 1–4). The longitudinal changes of acute-phase proteins during treatment can reflect the treatment status and tumor progression of patients. Finally, we validated the prognostic efficacy of baseline plasma CRP, SAA1, AHSG, SERPINA4, and TF in another independent NSCLC cohort undergoing ALK-TKI treatment. This study contributes to the search for prognostic and drug-resistance biomarkers in plasma samples for ALK-TKI therapy and provides new insights into the mechanism of drug resistance and the selection of follow-up treatment. [ABSTRACT FROM AUTHOR]

Early diagnosis and effective therapy are essential for improving the overall prognosis and quality of life of patients with nephropathic cystinosis. The severity of kidney dysfunction and the multi-organ involvement as a consequence of the increased intracellular concentration of cystine highlight the necessity of accurate monitoring of intracellular cystine to guarantee effective treatment of the disease. Cystine depletion is the only available treatment, which should begin immediately after diagnosis, and not discontinued, to significantly slow progression of renal and extra-renal organ damage. This review aims to discuss the importance of the close monitoring of intracellular cystine concentration to optimize cystine depletion therapy. In addition, the role of new biomarkers in the management of the disease, from timely diagnosis to implementing treatment during follow-up, is overviewed.

Introduction Efficacy of lithium is well documented in the literature, making it the gold standard treatment. However, its use declines with the advent of anticonvulsants. This raises the question about monitoring of mood stabilizers in practice. Objectives The aims of this study were to determine the prophylactic lithium response in patients followed for bipolar disorder and compared to those of anticonvulsants and assess the mood stabilizers monitoring procedures in clinical practice. Methods A retrospective study was conducted, over a period of six months, with patients followed for bipolar disorder stabilized under the same mood stabilizer (lithium or anticonvulsant) for at least one year. The participants were divided into two groups according to the mood stabilizing treatment. The two groups were compared according to socio-demographic, clinical and evolutionary profiles as well as the prophylactic response to treatment. Results Patients included were 64 in the study, 28 received lithium and 36 received anticonvulsants. The socio-demographic profile and clinical characteristics were similar in two groups, except for the average total number of mood episodes. Retrospective evaluation of the prophylactic response by ALDA scale showed a significantly higher mean total score in patients receiving lithium (5.9 ± 2.8 versus 2.58 ± 2.4, p = 0.025).). Ten of them were in compliance with the recommendations; while 19.44% received anticonvulsants had all the monitoring parameters within the recommended time frame. Conclusions Thymoregulators significantly modify the disease’s prognosis. Practitioners will attach particular special attention to distinguish the therapeutic efficacy of the side effects which are numerous and sometimes serious.

La prise en charge d'un patient transplanté requiert une surveillance clinique et biologique parfois complexe. L'adaptation de la posologie des immunosuppresseurs est fréquente, en particulier en début de greffe. Elle s'appuie notamment sur le suivi thérapeutique pharmacologique, nécessaire pour apprécier la variabilité pharmacocinétique des immunosuppresseurs, mais qui peut s'avérer contraignant pour le patient. The management of a transplanted patient requires clinical and biological monitoring, which is sometimes complex. Dose adjustment is based on therapeutic drug monitoring, which allows compensating for the wide pharmacokinetic variability of immunosuppressive drugs, but represents constraints for the patient. [ABSTRACT FROM AUTHOR]

Amikacin (AMK) is an important member of aminoglycoside class, and its determination has therapeutic importance due to its matchless potency against gram –ve pathogens. Due to narrow therapeutic window, its monitoring in clinical samples is inevitable. Direct determination of AMK using HPLC with UV–visible detection is not possible because of its limited absorbance. Herein, Hantzsch reagent (mixture of acetylacetone, formaldehyde and acetate buffer) was used as pre-column derivatization for AMK. UV–visible detection was performed at 340 nm. Separation and identification of derivatized drug (amikacin) were carried out using C-18 column Kromasil 100 (15 cm × 0.46 mm, 5 μm) with isocratic mobile phase elution of pH 5 (acetate buffer 0.01 M):acetonitrile (30:70 v/v) with flow rate of 1 ml/min. The procedure was able to resolve AMK from endogenous compounds and from cephalosporin drug (most prescribed combination) with run time of 10 min. Under optimized conditions; calibration curve was linear in the range 0.10–25.0 µg/mL with LOD and LOQ values of 0.024 and 0.071 µg/mL. Method was also validated for reproducibility, ruggedness and accuracy. The procedure was found sensitive, robust and precise for the comprehensive analysis (qualitative and quantitative) that was applied for determination of AMK in pharmaceuticals, urine and blood samples. [ABSTRACT FROM AUTHOR]

The α-glucosidase inhibitor is regarded as one of the most important drugs for the treatment of diabetes, which can control postprandial blood glucose levels via prolonging the carbohydrate digestion time and retarding the carbohydrates’ absorption. The present work aims to establish a facile bioanalytical method, based on α-glucosidase catalyzing the hydrolysis of 2-O-alpha-D-Glucopyranosyl-L-ascorbic acid (AA-2G), for the quantification of acarbose and migliol using a personal glucose meter (PGM). The hydrolysis products (ascorbic acid and glucose) can trigger the reduction of K3[Fe(CN)6] to K4[Fe(CN)6] in the glucose test strips, which results in the formation of the electron, which can be measured by PGM. Thus, ascorbic acid and glucose can be simultaneously measured by a simplified and miniaturized PGM method. However, the products produced by the hydrolysis of AA-2G will be decreased after the addition of acarbose or migliol to inhibit the activity of α-glucosidase, thereby resulting in a decreased PGM readout. After being incubated with α-glucosidase for 3.0 min and enzymatic reaction for 5.0 min, the quantitative detection of acarbose and migliol can be achieved within the ranges of 1.0–30.0 μM with the limit of detection of 0.33 μM and 3.0–33.3 μM with the limit of detection of 1.0 μM, respectively. IC50 values for acarbose and migliol are calculated to be 10.0 μM and 16.0 μM, respectively. The recoveries of the acarbose and migliol spiked with three different concentrations (final concentrations of 10.0, 20.0, and 30.0 μM) in human serum sample are in the ranges of 89.6–114.5% and 93.9–106.5%, respectively. These results demonstrate that the developed PGM method may be useful in future studies on therapeutic monitoring of acarbose and migliol.

Recent analyses demonstrate roughly 16–24% of patients taking direct-acting oral anticoagulants (DOACs) are prescribed an inappropriate dose, exposing patients to increased risk of thrombosis or bleeding. The use of reporting systems in the outpatient setting can efficiently identify potential medication errors and safety concerns. The purpose of this study was to evaluate the effect of a novel pharmacist-driven reporting system on appropriate prescribing of DOACs in the outpatient setting. This single-center qualitative study was conducted within a patient-centered medical home (PCMH). Reports were generated monthly to include all new DOAC prescriptions. Branching logic and filters were utilized within a secure web application to make the reporting process more efficient and identify regimens needing an intervention. Pharmacists reviewed the regimens populated by filters and made recommendations to prescribers as appropriate. The number of interventions proposed was captured as the primary outcome. Secondary outcomes include the nature of drug therapy problems identified and number of interventions accepted by prescribers. A total of 107 patients were analyzed for appropriateness from November 2017 to February 2019. Of the regimens included for review, 15 regimens were identified as potentially inappropriate. The nature of drug therapy problems identified include under dosing (4.25%), overdosing (2.13%), correction of documentation (2.13%), clarification of indication (3.19%), and ordering laboratory studies (3.19%). Of the interventions recommended, fourteen (93%) were accepted. Pharmacists integrated in a PCMH are well positioned to monitor and resolve DOAC drug therapy problems using local clinical reports. [ABSTRACT FROM AUTHOR]

Chemoimmunotherapy has evolved as a standard treatment for advanced non-small cell lung cancer (aNSCLC). However, inevitable drug resistance has limited its efficacy, highlighting the urgent need for biomarkers of chemoimmunotherapy. A three-phase strategy to discover, verify, and validate longitudinal predictive autoantibodies (AAbs) for aNSCLC before and after chemoimmunotherapy was employed. A total of 528 plasma samples from 267 aNSCLC patients before and after anti-PD1 immunotherapy were collected, plus 30 independent formalin-fixed paraffin-embedded samples. Candidate AAbs were firstly selected using a HuProt high-density microarray containing 21,000 proteins in the discovery phase, followed by validation using an aNSCLC-focused microarray. Longitudinal predictive AAbs were chosen for ELISA based on responders versus non-responders comparison and progression-free survival (PFS) survival analysis. Prognostic markers were also validated using immunohistochemistry and publicly available immunotherapy datasets. We identified and validated a panel of two AAbs (MAX and DHX29) as pre-treatment biomarkers and another panel of two AAbs (MAX and TAPBP) as on-treatment predictive markers in aNSCLC patients undergoing chemoimmunotherapy. All three AAbs exhibited a positive correlation with early responses and PFS (p < 0.05). The kinetics of MAX AAb showed an increasing trend in responders (p < 0.05) and a tendency to initially increase and then decrease in non-responders (p < 0.05). Importantly, MAX protein and mRNA levels effectively discriminated PFS (p < 0.05) in aNSCLC patients treated with immunotherapy. Our results present a longitudinal analysis of changes in prognostic AAbs in aNSCLC patients undergoing chemoimmunotherapy., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Approximately 8-20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.

Background. Monitoring of serum digoxin concentration (SDC) is one of the approaches for controlling the safety of the long-term digoxin treatment, however, the benefits from SDC monitoring in paroxysmal arrhythmias have not been studied.Aim. To evaluate the potential benefits of digoxin laboratory monitoring at the initiation of digoxin therapy in patients with paroxysmal atrial fibrillation (AF).Material and methods. A retrospective analysis of SDC was performed in patients with paroxysmal or persistent (n=142) and permanent AF (n=48) who received digoxin therapy. Anthropometric features, comorbidity, anamnesis of the underlying disease, concomitant therapy, severity of signs of myocardial remodeling and the presence of cardiac rhythm and/or conduction disorders before and after the treatment were considered to analyze the results of treatment. SDC was measured in 20 hours after digoxin treatment initiation and after restoration of sinus rhythm, or in 1 week after the start of therapy if arrhythmia persisted.Results. During the first week after digoxin therapy initiation the rate of non-specific ECG repolarization abnormalities was 54%, the incidence of clinically significant conductivity disturbances – 28%. We found a relationship between SDC in the first week of treatment and the risk of high grade AVor SA-conduction abnormalities after the restoration of sinus rhythm (mean SDC 0.98Ѓ}0.72 ng/dL in the group of patients with complications and 0.45Ѓ}0.42 – in the group without them, p=0.015); these complications did not correlate with clinical signs of digitalization or intensity of digoxin therapy. The intake of digoxin was not an independent factor for the occurrence of cardiac rhythm disturbances. Comparison of the direct SDC measurements and the calculated values obtained with the valid calculators developed for the long-term digoxin use did not show reliable reproducibility of the calculated data.Conclusion. SDC monitoring may be used during the first week of therapy (before the establishment of a steady-state SDС) to minimize the risks of clinically significant adverse effects of digoxin on intracardiac conduction at the start of therapy. The existing empiric SDC calculators are not suitable as an alternative to the direct measurement. Further studies are needed to determine the clinically valid borderline values of the safe SDC in the condition of rapid digitalization.

• New therapies are emerging for lysosomal storage disorders (LSDs). • Novel biomarkers are required to satisfy the need for more representation of disease severity and response to therapy. • Metabolomic and proteomic approaches are the way to the discovery of new biomarkers for LSDs. • Validation and clinical value of novel biomarkers for LSDs is extremely important. Lysosomal storage disorders (LSDs) are characterized by the accumulation of specific disease substrates inside the lysosomes of various cells, eventually leading to the deterioration of cellular function and multisystem organ damage. With the continuous discovery and validation of novel and advanced therapies for most LSDs, there is an urgent need to discover more versatile and clinically relevant biomarkers. The utility of these biomarkers should ideally extend beyond the screening and diagnosis of LSDs to the evaluation of disease severity and monitoring of therapy. Metabolomic and proteomic approaches provide the means to the discovery and validation of such novel biomarkers. This is achieved mainly through the application of various mass spectrometric techniques to common and easily accessible biological samples, such as plasma, urine and dried blood spots. In this review, we tried to summarize the complexity of the lysosomal disorders phenotypes, their current diagnostic and therapeutic approaches, the various techniques supporting metabolomic and proteomic studies and finally we tried to explore the newly discovered biomarkers for most LSDs and their reported clinical values. [ABSTRACT FROM AUTHOR]

Purpose: Though previous studies have shown benefit with pharmacist-managed dosing of antibiotics, many institutions still do not offer such services. Our objective was to determine and report novel outcomes associated with the implementation of a pharmacist-managed pharmacokinetic/pharmacodynamic consult service and to assess the impact of direct pharmacist involvement in therapeutic drug monitoring. Methods: Retrospective cohort study of patients who received vancomycin or an aminoglycoside in the medical intensive care unit from January 5, 2013, to January 6, 2015, divided into 2 groups: before/after implementation of the consult service on January 6, 2014. Results: Nine-hundred sixty-two patients were included. Groups were similar at baseline. There were fewer critical values after implementation of the consult service (40.8% vs 27.3%, P <.001). The intervention group had significantly more vancomycin troughs within therapeutic range (15.4% vs 32.8%, P =.019). Time from order entry to medication administration was shorter when pharmacists entered the medication order, although this difference was nonsignificant (103 minutes vs 77 minutes, P =.054). Conclusion: Implementation of a pharmacist-managed dosing and monitoring program led to significantly decreased rates of critical value drug concentrations and increased rates of therapeutic concentrations, with a 25% (NS) decreased time-to-antibiotic administration, therefore demonstrating the additive value of the pharmacist-managed over pharmacist-monitored approach. [ABSTRACT FROM AUTHOR]

Background: Therapeutic drug monitoring is commonly performed to confirm the safe and effective use of the vancomycin; however, the facility for it is not available in many hospitals. Many clinicians use conventional fixed dose of 1000 mg every 12 h irrespective of the body weight. Aim: The aim of the study was to assess the appropriateness of vancomycin initial dose in adult patients with normal renal function. Setting and Design: This was a retrospective observational study involving medical records of patients treated with intravenous vancomycin during January 1, 2016–December 30, 2016, at a major tertiary care hospital in southern region of Saudi Arabia. Materials and Methods: The study was conducted based on electronic medical records of the patients who received intravenous vancomycin, aged ≥ 18 years, weighing more than 50 kg, and with normal renal functions during the period of the study. Chi-square tests were used for categorical variables. Multivariable logistic regressions were computed to examine the relationships between the explanatory variables and the appropriateness of vancomycin dose. Results: The study evaluated records of 456 adult patients, of which 63.8% were male. As per vancomycin dose received, 229 patients received suboptimal dosing of vancomycin when the dose was recalculated using actual body weight. The majority of the prescriptions of junior residents (68.5%) were using an optimal initial dose of vancomycin as compared to 43.6% of the senior residents or 48% of the consultants. Conclusions: A significant number of patients were receiving suboptimal initial dose of vancomycin. Junior residents were more meticulous with the initial vancomycin dosing. [ABSTRACT FROM AUTHOR]

There is limited guidance on intravenous dosing of unfractionated heparin in obese patients. The purpose of this study was to determine the efficacy and safety of a standard unfractionated heparin (UFH) protocol in obese patients based on total body weight (TBW) or adjusted body weight (ABW) to reach two consecutive therapeutic anti-Xa levels. This was a retrospective observational cohort study conducted in a large academic medical center. Adults received a standard UFH protocol between January 1, 2013 to December 31, 2015. Inclusion criteria included age ≥ 18 years of age, weight ≥ 100 kg with a BMI ≥ 30 kg/m2, and received intravenous UFH. Patients were excluded if they received an alternative UFH protocol, received < 24 h of the standard UFH protocol, or had inadequate compliance to protocol. Out of the 131 patients included, 109 patients reached two consecutive therapeutic UFH levels within 96 h. The average time to two consecutive therapeutic UFH levels was 29.4 h and 27.6 h in patients dosed by TBW and ABW, respectively (95% CI − 4.63 to 8.11; P = 0.93). Safety outcomes included major bleeding, overt bleeding, or death events between patients dosed by TBW compared to ABW, (p = 0.61, p = 1.0, p = 1.0, respectively). Dosing intravenous UFH based on TBW or ABW resulted in similar times to therapeutic anti-Xa levels and safety outcomes. The data provided suggests using either TBW or ABW in obese patients is as effective and safe to use. [ABSTRACT FROM AUTHOR]

Therapeutic monitoring of drugs, particularly those with multiple metabolites, can be time-consuming and labor-intensive due to the need for different analytical methods depending on the specific metabolite or matrix of interest. In this study, we employed a heart-cutting 2D-LC separation method based on the coupling of reversed-phase and mixed-mode mechanisms to determine Favipiravir and surrogates of five main metabolites. This approach was applied to serum, plasma, urine, and human peripheral blood mononuclear cells. The method underwent validation to ensure its reliability. The findings highlight the potential of 2D-LC as a practical and efficient approach for therapeutic drug monitoring. [Display omitted] • First time determination, in a single LC run, of Favipiravir and its 5 metabolites. • 2D-LC combination of reversed-phase and mixed-mode retention mechanisms. • 2D-LC method fully validated and applied to human serum, plasma, urine, and cells. [ABSTRACT FROM AUTHOR]