Vol 69, No 1 (2024)

In modern medicine, the problem of the toxic effect of drugs on the human body persists. Cardiotoxicity is damage to the heart muscle by drugs and biologically active additives is one of the most common negative consequences. The task of doctors is to identify the presence of cardiotoxicity in the early stages before the appearance of clinical symptoms, timely adjust therapy and add cardioprotectors if necessary. Today, the main methods of diagnosing cardiotoxicity are imaging methods — echocardiography and magnetic resonance imaging. These methods show structural changes in the myocardium that have already occurred and a decrease in the working indicators of the heart. The active implementation and development of an algorithm for the use of troponin tests before and during therapy by drugs with cardiotoxic effects makes it possible to identify high-risk patients, diagnose damage to the heart muscle earlier and reduce the number of studies. The review analyzes trials in which cardiac troponins were used as cardiotoxicity markers of various drugs, shows the technical limitations of laboratory methods for troponin T and I tests, and the prospects for predictive use of determining highly sensitive tests for cardiac troponins.

BACKGROUND: Migraine is a disease with a complex pathogenesis and a significant frequency of treatment resistance. In the development of migraine attacks, the leading role is assigned to trigeminovascular system, associated with the release of proinflammatory cytokines and vasoactive molecules in the vessels of the dura mater.

AIM: To evaluate the circulating markers of inflammation and vasodilation in patients with frequent episodic and chronic migraine and their importance in predicting resistance to preventive treatment.

MATERIALS AND METHODS: 88 patients (average age is 35.05±0.95 years, women — 81%) with frequent episodic and chronic migraine were examined. At the beginning of the study, all subjects had vasodilating and inflammatory profile indicators in their blood once: calcitonin gene-related peptide (CGRP), vascular endothelial growth factor A (VEGF-A), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta-1 (TGF-β1), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-18 (IL-18), gasdermin D, caspase 1. For three months, patients kept a headache diary and took preventive therapy in accordance with recommendations. The effect of therapy was evaluated based on the headache diary provided by patients in the end of the third month. ROC-analysis was used to analyze the prognostic value of the laboratory parameters used in relation to resistance to treatment of patients with migraine.

RESULTS: The prediction of treatment resistance in patients with migraine is possible by the level of IL-6 (area under the ROC-curve 0.716, p =0.028) and CGRP (area under the ROC-curve 0.695; p =0.047). The threshold value of IL-6 in the blood was 2.58 pg/mL (Sensitivity — 73%, Specificity — 70%), CGRP — 64.58 pg/mL (Sensitivity — 95%, Specificity — 58%).

CONCLUSION: The data obtained indicate the role of proinflammatory cytokines and vasoactive molecules in the development of resistance to preventive treatment of migraine. Subsequent studies on a larger sample are necessary to confirm the possibility of using IL-6 and CGRP levels to explain cases of migraine resistance to treatment and, potentially, the choice of therapy to correct the mechanisms associated with an increase in these indicators.

BACKGROUND: The timing of samples collection of blood for neonatal screening is a critical mean for the results accuracy. Changing the timing of samples of blood collection can affect the concentrations of amino acids and acylcarnitines, which requires clarifying the reference intervals to minimize false positive and false negative results.

AIM: To evaluate the effect of samples collection of blood time (on the 1 ^st –2 ^nd and 4 ^th –5 ^th days of life) on the concentrations of amino acids and acylcarnitines in dry blood spots of full-term newborns and verify the appropriate reference intervals for use in extended neonatal screening.

MATERIALS AND METHODS: A retrospective observational study was conducted, which included 83 087 newborn blood samples collected at the Morozov Children’s City Clinical Hospital in 2022–2023. Concentrations of 11 amino acids, 31 acylcarnitine and succinylacetone were determined by tandem mass spectrometry. Nonparametric methods with a significance level of p <0.05 were used to calculate the reference intervals and analyze the differences between the groups.

RESULTS: The analysis showed significant differences in concentrations for all 43 analytes between the groups (Day 1–2, n =61,996; Day 4–5, n =21,091). Concentrations of many amino acids were higher at later sampling periods, while methionine levels decreased. 99% reference intervals have been established for all analytes, which allows the threshold values to be adapted depending on the time of samples collection of blood.

CONCLUSION: The obtained data emphasize the need to adjust the reference intervals for amino acids and acylcarnitines depending on the timing of blood collection. This will ensure a more accurate diagnosis of hereditary diseases in newborns and increase the effectiveness of neonatal screening.