Journal of Clinical Practice

BACKGROUND: Asymptomatic development and untimely diagnostics of lung cancer are the main reasons of high mortality caused by this disease. The development of tests based on “fluid biopsy”, which analyze circulating nucleic acids in blood, including the microRNA (miRNA) derived from the microvesicles, can be implemented as an effective screening test for lung cancer assuring the timely detection of the disease. AIM: To analyze the relative expression of 17 miRNAs in the microvesicles fraction from blood plasma samples from patients with non-small-cell lung cancer (NSCLC) and healthy donors. METHODS: The blood plasma microvesicles were isolated by aggregation-precipitation. miRNA was then isolated from the obtained blood microvesicles fraction using the glass fiber filters. Using the method of reverse transcription polymerаse chain reaction, an evaluation was carried out for the diagnostic efficiency of previously proposed miRNA pairs. This analysis was also used to select the most effective diagnostic pairs and panels. RESULTS: The obtained data have confirmed the diagnostic efficiency of four miRNA pairs (-31/-125b; -133b/-374a; -133b/-425; -133b/-222). The sensitivity and the specificity of distinguishing NSCLC patients from donors were 79% and 100%, respectively. Further analysis using paired normalization, compiling the regression models and multiple sample generations yielded three independent minimal panels of miRNA pairs, capable of diagnosing NSCLC with 100% accuracy: (1) -19b/-425, -125b/-378a, -205/-660; (2) -324/-374a, -30e/-92a, -125b/-378a; (3) -324/-374a, -125b/-378a, -205/-660. CONCLUSION: The diagnostic performance of the proposed miRNA panel across independent cohorts, along with the observed inter-cohort variability, supports its promising potential for NSCLC screening test development. These data demonstrate the necessity to identify additional multi-purpose miRNA markers and to validate the panel in further independent patient groups. Such research is essential to establish a reliable and timely miRNA-based screening tool for NSCLC.

BACKGROUND: The suppurative lung disease accompanied by destruction of lung tissueinclude the pleural empyema with or without fistula, the lung abscess with or without sequestration, the gangrenous abscess and several other less frequent conditions. The mortality among patients with this profile, considered as critical illness, remains high due to the development of life-threatening complications. The early stratification of patients by the risk of such complications can be useful for the physician when choosing the strategy for personalized treatment. The genetic variability of the AQP4 gene, the expression of which on the surface of cells in the lungs and in the immune system may have the pathogenetic meaning for the development of lung diseases and their complications, is the source of early markers for predicting the course of suppurative lung diseases. Previously we have demonstrated that the polymorphic gene variants of AQP4 rs1058427 are associated with the septic shock development and the outcome of sepsis. The contribution of AQP4 into the development of pulmonary hypertension was not investigated previously. AIM: To clarify the contribution of the AQP4 gene polymorphic variants and pathogenically relevant immune cells levels to the development of pulmonary hypertension in patients with the suppurative lung disease. METHODS: The research included the patients aged 18–87 years with suppurative lung diseases developed after the previous community-acquired pneumonia. Pulmonary hypertension was detected using the echocardiography (as demonstrated by the parameters of systolic pressure in the pulmonary artery ≥36 mm.Hg. and regurgitation rate of the tricuspid valve ≥2.9 m/sec). In all patients, the genotypes of AQP4 rs1058427 were determined. RESULTS: The presence of the AQP4 rs1058427 minor allele Т in patients with the suppurative lung disease was associated with the development of pulmonary hypertension and with the increase in blood monocytes count, with the presence of minor genotypes GT or TT of AQP4 rs1058427 indicating the high risk of developing the pulmonary hypertension. In cases of separately analyzing the subgroups of patients with or without the previous episodes of laboratory confirmed COVID-19, the statistical significance of the association remained only for the carriers of the allele Т and with no documented history of COVID-19 episode. CONCLUSION: The presence of the minor allele AQP4 rs1058427 (genotypes GT or TT) in the genotype of patients with the suppurative disease of the lungs has determined the increased risk of developing the pulmonary hypertension and the increased blood monocytes count.

BACKGROUND: Invasive aspergillosis is a threatening fungal infection with high mortality rates. One of the key factors for timely diagnostics of the disease is an approach based on detection of galactomannan, a polysaccharide from the pathogen’s cell wall. The existing galactomannan enzyme-linked immunosorbent assays (ELISA) employ the colorimetric detection. The emergence of the new highly sensitive techniques for the measurement of peroxidase label in ELISA, e.g., based on the effect of surface-enhanced Raman scattering (SERS), facilitates the development of a next generation assays with improved sensitivity and with potentially broader range of biological fluids applicable for analysis. An important step of developing the new test-system is the demonstration of its applicability to real clinical samples and comparability of the results with reference method. AIM: To evaluate the applicability of the previously developed highly sensitive and selective SERS-based ELISA protocol for the measurement of Aspergillus galactomannan in bronchoalveolar lavage fluid samples. METHODS: Ten bronchoalveolar lavage fluid samples were analyzed using both the GalMAg-EIA ELISA kit (XEMA LLC, Russia) and the previously developed SERS-based ELISA, which employs o-phenylenediamine substrate and silver nanoparticles colloid. RESULTS: Using standard samples prepared with in vitro cultivated galactomannan, the limit of detection for the SERS-based ELISA was estimated as 53 pg/mL with the working range spanning up to 10.8 ng/mL and the mean coefficient of variation within this range being 4%. Using the GalMAg-EIA kit, 6 out of 10 bronchoalveolar lavage fluid samples were identified as positive and 4 — as negative. The comparison of the results for these two methods demonstrates the non-linear dependence with the Spearman coefficient of correlation being 0.93–0.95 (p=2.3×10^-5–1.1×10^-4). CONCLUSION: For the bronchoalveolar lavage fluid samples, the comparability of the results was demonstrated when detecting the galactomannan using the commercially available GalMAg-EIA kit and the previously developed SERS-based ELISA. The results confirm the high sensitivity of the SERS-based Aspergillus galactomannan ELISA and its prospectiveness for practical laboratory applications. Compared to chromogenic detection, the advantages of surface-enhanced Raman scattering readout include a lower limit of detection for galactomannan and increased sensitivity at the lower end of the galactomannan-positivity index (<2). These findings could enable more accurate determination of the threshold for discriminating the positive and the negative samples. Thus, the research provides the basis for future larger scale trials of the SERS-based galactomannan ELISA in order to evaluate its applicability for clinical-laboratory diagnostics.

Stroke is often accompanied by psychoemotional and cognitive disorders, such as depression, anxiety, decreased memory and attention focusing, decreased executive functions and emotion regulation. These disorders significantly decrease the quality of life in the patients and complicate the rehabilitation processes. For their elimination, the actively implemented methods include the one employing the biological feedback (neurofeedback). Our review includes the clinical research works conducted during the period from 2010 until 2025 and devoted to investigating the role of neurofeedback in restoring the cognitive and the psychoemotional functions in stroke patients; various types of biological feedback were taken into account with analyzing the data on their efficiency in correcting the mental disorders after a cerebrovascular stroke. The main protocols of neurofeedback were described, such as the training of the sensory-motor rhythm (SMR-training, alpha and beta training) along with providing the results of their clinical application in the cognitive and the psychoemotional rehabilitation. It was shown that the methods of neurofeedback show high potential in the rehabilitation treatment of stroke consequences. The efficiency of therapy largely depends on the choice of the optimal treatment protocol, on the course duration, on the individual adaptivity of the approaches and on the thorough monitoring of changes in the brain functional parameters.

BACKGROUND: Left ventricular noncompaction cardiomyopathy is one of the rare forms of primary cardiomyopathy with an unfavorable prognosis and disease course. The mortality among the adult population is approximately 50%. The clinical signs are not specific and the diagnostics in some cases takes a long period of time. In this article, based on an example of one of the variants of cardiomyopathy development, a path of setting the diagnosis and adjusting the treatment in real-life clinical practice is described. CLINICAL CASE DESCRIPTION: In the patient with a noncompaction cardiomyopathy in the left ventricle, the leading clinical symptoms were the complex cardiac rhythm disorders (ventricular extrasystoles of high grade, paroxysmal-persistent form of atrial fibrillation and flutter), the development and the progression of cardiac failure with the decreased ejection fraction down to 22%. The adjustment of the antiarrhythmic and the pulse-decreasing therapy was done, as well as the attempts of medicinal stabilization of the course of cardiac failure. Due to the inefficiency of conservative therapy with the development of uncontrolled rhythm disorders and the terminal cardiac failure, the orthotopic heart transplantation was carried out. CONCLUSION: The presented clinical case demonstrates a variation of the progressive course of the left ventricular noncompaction cardiomyopathy with the development of terminal cardiac failure within 4 years after the onset of the disease, requiring the heart transplantation. The clinicists and the functional and ultrasonic diagnostics specialists need to be aware of the rare forms of cardiomyopathies, including the asymptomatic variants, for the timely diagnostics and for adequate treatment.

BACKGROUND: Rehabilitation of patients who have suffered from intraventricular hemorrhage is often complicated by respiratory dysfunction due to prolonged immobilization, intensive care consequences syndrome, and disturbances in physiological, anatomical, and topographic relationships. CLINICAL CASE DESCRIPTION: The patient, a 20-year-old man, suffered from cryptogenic non-traumatic intracranial hemorrhage. He was hospitalized with functional disorders in the form of central tetraparesis and bulbar syndrome. He suffered from nosocomial lower lobe pneumonia during his stay in the specialized department. According to visualization data, lower lobe pneumonia is in the resolution stage, lower lobe fibro atelectasis. Upon admission to the rehabilitation center, severe respiratory dysfunction was diagnosed. Visualization by the electrical impedance tomography of the lungs suggested the presence of hypoventilation zones in the dorsal parts of the right lung, uneven, acyclic ventilation, uneven ventilation in all regions of the lungs during spontaneous breathing, hyper perfusion of the dorsal part of the left lung, tachypnea; instrumental and laboratory diagnostic data revealed serous-purulent sputum and hypercapnia. Rehabilitated with positive dynamics. By the end of the course, uniform bilateral ventilation and normalization of clinical indicators were recorded. Pulmonary rehabilitation program: physical training, verticalization, positioning, extrapulmonary and intrapulmonary percussion, inhalation therapy, hardware physiotherapy, respiratory support with positive pressure at the end of exhalation. CONCLUSION: The examination revealed the presence of pronounced functional respiratory disorders that directly affect the plan and possibility of rehabilitation measures. Visualization allowed to clearly demonstrate the state of the impaired function and its dynamics during therapy. The result of successful restoration of the impaired function was obtained not only by visual representation using the electrical impedance tomography method, but also according to laboratory, instrumental diagnostics, and clinical examination. A multidisciplinary approach to managing a patient with pronounced impaired functions due to concomitant pathology is important. It is proposed for discussion to visualize using the electrical impedance tomography method in managing a patient with intensive care consequences syndrome with respiratory complications, as well as patients of a specialized pulmonology hospital.