[The effect of non-invasive brain stimulation on neuroplasticity in the early recovery period after ischemic stroke]. / Vliyanie neinvazivnoi stimulyatsii golovnogo mozga na neiroplastichnost' v rannem vosstanovitel'nom periode ishemicheskogo insul'ta.

The post-stroke cognitive impairment syndrome (PSCI) develops in 10-80% cases of ischemic stroke and leads to a significant patients' quality of life impairment. The standard program of cognitive rehabilitation includes nootropic agents therapy and neuro-cognitive training. The additional various methods of non-invasive brain stimulation (NIBS) application can improve the results of PSCI rehabilitation. PURPOSE OF THE STUDY: Studying the different variants of NIBS influence on synaptic neuroplasticity in the early recovery period after ischemic stroke. MATERIAL AND METHODS: The rehabilitation of 62 patients with PSCI syndrome after ischemic stroke outcomes were studied. The patients were assigned to 5 groups. Patients from the control group underwent standardized nootropic therapy and course sessions with a neuropsychologist. The rest of the patients were divided into 4 groups, in which, in addition to the basic program of cognitive rehabilitation, different options for the course use of NIBS were used: photochromotherapy (PCT) with narrow-band optical radiation (NOR) with a wavelength of 530 nm (green light); rhythmic transcranial magnetic stimulation (rTMS) with a low-intensity high-frequency running pulsed magnetic field; infrared radiation with a wavelength of 1-56 microns, modulated by terahertz frequencies (IRMT); bioacoustic correction (BAC). We analyzed the dynamics of changes in scores of MMSE scales, FAB, Roshchina. In order to assess the effect of NIBS on neuroplasticity, the concentrations of BDNF and antibodies to the NR2 fragment of the NMDA receptor were evaluated before and after the completion of the rehabilitation course. RESULTS: Concentration values of antibodies to the NR2 subunit of the NMDA receptor in all groups remained consistently above the norm (more than 2 ng/ml) throughout the entire course of rehabilitation. Differences between groups in the dynamics of BDNF concentration in the peripheral blood were revealed. There was a significant (p<0.05) decrease in its concentration by almost 2 times by the end of rehabilitation course in control group. In the rTMS and IRMT groups, a decrease in the BDNF concentration was also recorded in dynamics, which, however, did not reach a significant level. There was no decrease in BDNF levels in the BAC group. There was an increase of this level in the PCT group. CONCLUSION: The use of different types of NIBS in the program of cognitive rehabilitation of patients with PSCI syndrome contributes to an increase in the rehabilitation potential due to the activation of neurotrophin-mediated synaptic neuroplasticity. Green light PCT and BAC have the greatest effect on increasing neuroplasticity after ischemic stroke.

[Detection of paraprotein in plasma cell tumors].

Paraprotein is a laboratory biomarker of plasma cell tumors and other lymphoproliferative diseases. Its determination is necessary for diagnosing, monitoring and assessment of therapy effectiveness. The lecture presents the main methods of qualitative and quantative analysis of monoclonal proteins: gel electrophoresis, capillary electrophoresis, immunofixation and nephelometry features, possibilities and limitations are reviewed. The main sources of errors and artifacts during these studies are considered. Also the difficulties in the diagnosis and interpretation of the results of serum and urine tests are highlighted.

Validation of the infrared spectroscopy method for analysis of the composition of urine concretes.

The aim of this study was to validate the method for analyzing the composition of calculus using infrared (IR) spectroscopy by studying model mixtures of salts. Study was made with an ALPHA-P IR Fourier spectrometer with OPUS software (Bruker, Germany). The samples of pure chemical salts manufactured by Sigma-Aldrich USA were used to validate the method. Salt mixtures were prepared in ratios of 10/90, 50/50 and 90/10. To assess the effect of the fraction size on the calculus component results, were used calculi of patients with urolithiasis. For each mixture were used 10 repeated measurements. Analysis of the composition of model salts showed that in the study of pure cystine salt CV(%) was 0,79%, calcium carbonate - 0,92%, sodium urate - 0,97%, calcium oxalate monohydrate - 4,94%, magnesium ammonium phosphate - 5,59%. And the most common components were analyzed in the composition of complex mixtures, including 90%, 50% and 10% of the investigated component. Calcium oxalate monohydrate has CV(%) 5.70% in mixture 9 part of it to one part of impurities, in mixture 50/50 - 21.57% and in 10/90 - 5.70%. For uric acid in 90/10 - 2.20%, in 50/50 - 10.09%, in 10/90 - 31.94%. For calcium carbonate in 90/10 - 9.02%, in 50/50 - 11.98%, in 10/90 - 24.70%. The dispersion analysis showed that the weighed portions of salts with a particle diameter of more than 0.8 mm provide reproducibility with a CV - 11.48%, with a diameter of 0.2-0.8 mm - 5.35%, and finally less than 0.1 mm - 2.28%. The accuracy of the method is high, but the reproducibility of the IR-spectroscopy method is relatively low in the analysis of stones of mixed composition, due to the greater error in the determination of impurities. Laboratories should pay special attention to optimizing sample preparation to ensure particle fineness less than 0.1 mm.

Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III-IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57-89%) in acute GVHD and 81% (95% CI 67-92%) in chronic. Overall survival was 59% (95% CI 49-74%) in acute group and 85% (95% CI 70-93%). The major risk factors for lower survival were grade III-IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III-IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

[The role of fraction analysis of ferritin in diagnostic of secondary hemophagocyte syndrome].

The secondary hemophagocytic syndrome is a life-threatening condition characterized by non-specifc manifestations: systemic inflammatory reaction, cytopenia, liver affection, high content of ferritin in blood serum. One of manifestations of secondary hemophagocytic syndrome is decreasing of level of glycated ferritin in blood serum expressed in percentage of total level. The detection of glycated ferritin can be applied for a differentiated diagnosis with cli9nically similar conditions, including septic process. The purpose of study was to determine clinical value of easurement of glycated ferritin for diagnostic and differentiated diagnostic of secondary hemophagocytic syndrome. The analysis was applied to samples of blood serum and clinical data of patients with diagnoses of secondary hemophagocytic syndrome (n=40), severe sepsis (n=24), cytolitic syndrome (n=36) and healthy donors (n=40). The total content of ferritin is established using rbidimetric technique ("BioSystems", Spain). The glycated ferritin was calculated. To determine level of of glycated ferritin the glycated fraction of ferritin was precipitated using concanavalin A, polymerized with sepharose 4B ("GE Healthcare", USA). The normal values of glycated ferritin made up to 78.3%-87.1%. Under secondary hemophagocytic syndrome decreasing of content of glycated ferritin made up to 25.0 ± 18.7% and was signifcantly lower than under sepsis (47.0 ±17.7%, p<0.001) and cytolytic syndrome(63.5% ±18.7%, p<0.001). According the results of ROC-analysis, the area under curve was maximal as compared with other markers of secondary hemophagocytic syndrome, including total ferritin, triglycerides, fbrinogen. At decreasing of level of glycated ferritin lower than 30.4% the applied technique provides clinical sensitivity 69%, specifcity 94.3%, accuracy 86.9% in applying differentiating diagnosis of secondary hemophagocytic syndrome. At calculation of absolute content of non-glycated ferritin it was discovered that its values correlate with concentration of triglycerides, international normalized ratio, aspartataminotransferase, alaninaminotransferase and total bilirubin in patients with secondary hemophagocytic syndrome (p<0.05). Therefore, decreasing of level of glycated ferritin permits to diagnose secondary hemophagocytic syndrome with higher accuracy.

Profiles of pro-inflammatory cytokines in allogenic stem cell transplantation with post-transplant cyclophosphamide.

Large number of studies was published about predictive value of cytokines for graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Recently, there has been a growing interest in GVHD prophylaxis with post-transplant cyclophosphamide (PTCy). Clinical data on the dynamics of proinflammatory cytokines with this prophylaxis is lacking. In this study, we have measured the levels of IL-17, IL-6, IL-8, IFN-γ and TNF-α in plasma on days -7, 0, +7, +14 and after engraftment in 20 patients with acute GVHD and 40 matched control patients with PTCy-based prophylaxis. Low levels of IL-8 (p=0.04) on day +7 and IFN-γ (p=0.03) after engraftment were associated with grade II-IV acute GVHD. The same pattern was observed for severe acute GVHD. Low IFN-γ after engraftment was also associated with increased non-relapse mortality (p=0.014). No impact of cytokine levels on overall survival and relapse incidence was observed (p>0.05). In conclusion, the dynamics of IL-8 and IFN-γ in GVHD patients after PTCy was different from previously reported after conventional prophylaxis.

Immunogenicity of Human Interferon-Beta-Containing Pharmaceuticals.

Multiple sclerosis is a severe autoimmune disease with inflammatory component that continues to be resistant to treatment. One of the approaches retarding its progression is based on using nonspecific therapy with human interferon-beta (IFN-ß)-containing pharmaceuticals. Neutralizing antibodies (NAbs) against genetically engineered pharmaceuticals developed by the patient's immune system, which reduce their therapeutic and biological activity, pose a serious problem. Cell lines sensitive to IFN-ß activity also quantifying NAb level are applied because direct measurement of IFN-ß antiviral activity is complicated. This study was aimed at standardization and validation of a reporter cell system for measuring anti-human IFN-ß NAb titers, and evaluation data were obtained with samples from 33 patients with multiple sclerosis.

The Diagnostic Value of Alpha-1-Antitrypsin Phenotype in Patients with Granulomatosis with Polyangiitis.

The deficiency of alpha-1 protease inhibitor, or alpha-1-antitrypsin (A1AT), predisposes to chronic lung diseases and extrapulmonary pathology. Besides classical manifestations, such as pulmonary emphysema and liver disease, alpha-1-antitrypsin deficiency (A1ATD) is also known to be associated with granulomatosis with polyangiitis (GPA or Wegener's granulomatosis). The aim of our study was to evaluate the frequency of allelic isoforms of A1AT and their clinical significance among GPA patients. Detailed clinical information, including Birmingham Vasculitis Activity Score (BVAS), incidence of lung involvement, anti-proteinase 3 (PR3) antibodies concentrations, and other laboratory data were collected in 38 GPA patients. We also studied serum samples obtained from 46 healthy donors. In all collected samples A1AT phenotyping by isoelectrofocusing (IEF) and turbidimetric A1AT measurement were performed. Abnormal A1AT variants were found in 18.4% (7/38) of cases: 1 ZZ, 4 MZ, 2 MF, and only 1 MZ in control group (2%). The mean A1AT concentration in samples with atypical A1AT phenotypes was significantly lower (P = 0.0038) than in normal A1AT phenotype. We found that patients with abnormal A1AT phenotypes had significantly higher vasculitis activity (BVAS) as well as anti-PR3 antibodies concentration. We conclude that A1AT deficiency should be considered in all patients with GPA.

[Diagnosis of isolated angiitis of the central nervous system].

We have analyzed clinical presentations, neuroimaging data, blood and cerebrospinal fluid diagnostic tests in isolated angiitis of the central nervous system on the basis of data of recent publications and 22 our own cases. Due to the insufficient diagnostic value of invasive methods including biopsy of leptomeningeal and intracerebral vessels, we considered practical approaches to the diagnosis of cerebral vasculitis and ways of its optimization. We suggested the stratification of clinical, neuroimaging and laboratory criteria for the evaluation of their sensitivity and specificity and for the development of diagnostic algorithms.

[Single preoperative radiation exposure for stage II breast cancer]. / Odnokratnoe predoperatsionnoe obluchenie pri rake molochnoi zhelezy II stadii.

The efficacy of different combinations of radiotherapy and mastectomy after Madden was compared in 411 patients with stage II breast tumors. The least likelihood of local reccurence (4.5 +/- 1.3%) was recorded after single exposure before mastectomy and with/without adjuvant irradiation of the regional lymphatics (group I); it appeared 1.5 times as high (7.0 +/- 2.1%) after mastectomy + postoperative irradiation (group II) while the highest frequency (14.8 +/- 5.4%) was registered after surgery alone (group III). Relapse-free 10-year survival was observed in 63.5 +/- 4.7 (group I), 77.4 +/- 4.6 (group II) and 46.2 +/- % (group III), respectively, the difference between group I and II being significant. Therefore, postoperative radiotherapy in conjunction with mastectomy (Madden) should be recommended for stage II breast carcinoma when the breast cannot be salvaged.