Therapeutic Drug monitoring (TDM) is a multidisciplinary endeavor encompassing skills of the laboratory, clinical pharmacologists and physicians aimed at providing the best possible patient care via ...the individualization of drug therapy. The expanding role of liquid chromatography - tandem mass spectrometry (LC–MS/MS) in TDM is based on dramatic improvements in analytical instrumentation, thereby enabling unique specificity, extreme sensitivity, high throughput, the simultaneous analysis of multiple drugs and metabolites in a drop of blood within several minutes and the use of multiplexed platforms for the rapid determination of single analytes. However, analysis by LC–MS/MS does not automatically ensure reliable results and superiority over other assays. The aim of this article is to provide an overview of the current use, advantages, and challenges of LC–MS/MS methods in TDM services, to summarize ongoing issues, and to provide an outlook on new perspectives.
•This article provides an overview of the current use of LC–MS/MS methods for TDM services.•It discuss both the advantages and challenges when using LC–MS/MS for TDM.•It summarizes ongoing issues of LC–MS/MS for TDM.•It provides an outlook on new perspectives of the application of LC-MS/MS in the field of TDM.
There is an extraordinary flood of new technologies in medicine nowadays. Sophisticated diagnostics based on genome assays, mass spectrometry and cell sorting platforms are driving the technological ...transfer and promote the entrance of individualized patient management in clinical practice. Mass spectrometry (MS) could be viewed as one of the major tools that promote the development of precision medicine (PM), which employs a patient's genotype and phenotype investigation to establish individually tailored drug treatment. While genetic testing allows the physician to choose appropriate medicine, MS assays provide the patient's actual phenotype, with all of the environmental, pharmacological and pathological variables. Therefore, MS is an essential technology for personalized patient management, and high-resolution MS systems are employed to resolve challenging analytical demands. The great technological advance of MS resulted in the introduction of methods with unprecedented identification power, extreme sensitivity, specificity and extended linearity range, which are simpler to use in the medical laboratories, and are based on the current reference analytical principles. Further, the ability to perform panel profiling with simultaneous measurement of bioactive compounds, their precursors and metabolites in a single sample, enormously amplifies the informative value of results, with ultimate improvement of patient care. Typical examples include newborn screening, therapeutic drug management, toxicology, endocrinology, microbiology, clinical omics assays and others. It should be specially emphasized that clinical MS integrates chemical and anatomical pathology: MS imaging and iKnife-MS guidance in surgery, although still in the research phase, open new horizons for personalized treatment and individualized patient care.
In this prospective study, we assessed biomarkers of inflammation (IL-6 and SAA) from the serum of 120 COVID-19 patients, of whom 70 had chronic kidney disease. All the samples were taken at ...emergency-department (ED) admission. Our goal was to relate the biomarkers to the results of death and acute kidney injury. All the patients underwent chest computer tomography to estimate the severity score (0-5), which was performed at hospital admission. Finally, biomarkers were also evaluated in a healthy control group and in non-COVID-19-CKD patients. IL-6 and SAA were statistically different between the subgroups, i.e., they were significantly increased in patients with COVID-19. Both of the biomarkers (IL-6 and SAA) were independently associated with mortality, AKI and a higher grade of pathological changes in the lung's parenchyma. Both high baseline levels of IL-6 and SAA on hospital admission were highly correlated with a later ventilatory requirement and mortality, independent of hospital stay. Mortality was found to be significantly higher when the chest CT severity score was 3-4, compared with a severity score of 0-2 (
< 0.0001). Conclusions: at the admission stage, IL-6 and SAA are useful markers for COVID-19 patients with CKD.
: Stroke is a disease with high mortality and morbidity. Currently, there are no specific laboratory markers that can replace or improve clinical and radiological diagnosis and prognosis. We ...evaluated the role of C-reactive protein (CRP), fibrinogen and D-dimer in predicting short-term outcomes in acute ischemic stroke.
: We included 118 acute ischemic stroke patients, admitted within 24 h of onset, mean age 72.73±10.08 years. The severity of the stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS), and for poor outcome (PO) we accepted a severe functional deficit at the end of the hospital stay with NIHSS ≥15, and for good outcome (GO) – NIHSS ≤ 14. In all patients, we monitored the dynamics of CRP, fibrinogen and D-dimer and evaluated their predictive value regarding to the PO and GO of the stroke.
: D-dimer had the strongest poor predictive value at admission (p<0.001). Six hours after admission, CRP, D-dimer or both were higher in PO patients (p=0.046, p=0.022 and p=0.006, respectively). At the 24.h, only CRP could be used to predict PO (p<0.001). Elevated CRP, D-dimer or both have been determined as strong indicators of PO with 72 hours of admission (p<0.001, p=0.032 and p=0.001, respectively). Fibrinogen levels were higher 72 hours after admission without a significant relationship with the NIHSS.
: Changes in routine biomarkers CRP and D-dimer, but not fibrinogen, can predict short-term stroke prognosis and may be associated with the risk of early neurological deterioration or death during hospital stay.
European Union (EU) Directive 2013/55/EC (The Recognition of Professional Qualifications) allows Member States to decide on a common set of minimum knowledge, skills and competences that are needed ...to pursue a given profession through a Common Training Framework. To be adopted the framework must combine the knowledge, skills and competences of at least one third of the Member States. Professionals who have gained their qualifications under a Common Training Framework will be able to have these recognised automatically within the Union. The backbone of the European Federation of Clinical Chemistry and Laboratory Medicine’s (EFLM) proposed Common Training Framework for non-medical
is outlined here. It is based on an Equivalence of Standards in education, training, qualifications, knowledge, skills, competences and the professional conduct associated with specialist practice. In proposing the recognition of specialist practice EFLM has identified 15 EU Member States able to meet Equivalence and in whom the profession and/or its training is regulated (an additional EU Commission requirement). The framework supports and contributes to the Directive’s enabling goals for increasing professional mobility, safeguarding consumers and ensuring a more equitable distribution of skills and expertise across the Member States. It represents EFLM’s position statement and provides a template for professional societies and/or competent authorities to engage with the EU Commission.
The skin manifestations in hypothyroidism are common but their advanced forms do not have adequate therapy. Along with achievement of euthyroidism, thyroid-associated dermatopathy (TAD) needs an ...inhibition of the proliferation and activation of fibroblasts, and of the glycosaminoglycans synthesis. Pentoxifylline (PTX) exerts multifaceted effects and has shown properties to inhibit certain constitutive activities of dermal fibroblasts. The aim of this study was to determine the histopathological changes and to establish the amount and distribution of mucin in hypothyroid skin, with or without treatment with PTX. Hypothyroid skin showed abundant diffuse mucin deposition in all dermal compartments in comparison with euthyroid skin. After administration of PTX in dose 100 mg/kg daily, there was a significant decreased amount of mucin in the dermis. The improvement of the dermal histological manifestations, in general demonstrated by narrowing between the dermal collagen fibers and by a decrease in mucin deposition, might be explained with dose-dependent PTX inhibition of the synthesis and accumulation of glycosaminoglycans. The histological results of this study confirmed several clinical observations about the beneficial effect of PTX on clinical skin manifestations in hypothyroid state. Therefore, we may propose PTX as a new potential therapeutic agent for TAD treatment. Further studies are needed to fully establish the effect of PTX on dermal fibroblasts after continuous administration.
The human microbiome plays a very important role in the normal functioning of both metabolic and immune systems. Changes in gut microbiota (dysbiosis) possibly contribute to the development of ...metabolic and autoimmune diseases. There is close association between the human gut microbiome and Vitamin D metabolism. The objective of our study was to characterize the composition of the gut microbiome in patients with type 2 diabetes mellitus (T2DM) in comparison to controls with normal glucose tolerance, and to correlate the Vitamin D status with the changes in the gut microbiome. Totally, 15 patients with T2DM and 16 controls were enrolled in the study. The complex gut microbiome was analysed by next generation sequencing (NGS) in both groups, additionally divided into subgroups according to serum 25-hydroxyVitamin D (25OHD) levels. We found a significant decrease in butyrate-producing bacteria Eubacterium spp. and an increase in lipopolysaccharide (LPS) - positive bacteria Enterobacter spp., Escherichia spp. and Pseudomonas spp. in T2DM patients compared to controls. Control individuals with 25OHD levels of over 80 nmol/L were characterized with significantly decreased amount of Escherichia spp. and Pseudomonas spp. and increased Eubacterium spp. On the other hand, 25OHD < 80nmol/L levels in diabetic patients were related with lower content of butyrate-producing bacteria and higher levels of LPS-positive bacteria. The results showed an influence of gut microbiome on the glucose homeostasis and a relationship between Vitamin D levels and the gut microbiome.
There is a growing body of evidence for the protective role of vitamin D in diabetes mellitus (DM), infection, cancer, cardiovascular disease, immune disorders and kidney function. Considering the ...reported high prevalence of vitamin D insufficiency among kidney transplant recipients (KTRs), the aim of this study was to assess the influence of immunosuppressive therapy and other factors on vitamin D status in such patients. The study included 289 KTRs (189 males and 100 females) who consented to participate. The first test for 25-hydrohyvitamin D 25(OH)D was performed by a validated liquid chromatography-tandem mass spectrometry method. Influence of immunosuppressive drugs and previously reported predictors on vitamin D status was assessed by descriptive statistics, univariate and multivariate regression. Our results showed that only 53 patients (18.34%) of the studied KTRs were vitamin D sufficient. In addition to a well expected positive association between serum 25(OH)D and summer blood sampling (p < 0.05) and inverse relationship between vitamin D status and DM, gender (female) and body mass index, serum 25(OH)D was found to be inversely associated with calcineurin inhibitors (CNI) (p < 0.05) and unaffected by other immunosuppressive agents. Our study demonstrated high prevalence of vitamin D insufficiency after kidney transplantation in the studied cohort of patients. Apart from female gender, winter months, DM and overweight, the use of CNI could be considered an additional significant predictor of lower 25(OH)D in Bulgarian KTRs.
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