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Infective endocarditis (IE) represents an important medical challenge, particularly in patients with congenital heart diseases (CHD). Its early and accurate diagnosis is crucial for effective management to improve patient outcomes. Multimodality imaging is emerging as a powerful tool in the diagnosis and management of IE in CHD patients, offering a comprehensive and integrated approach that enhances diagnostic accuracy and guides therapeutic strategies. This review illustrates the utilities of each single multimodality imaging, including transthoracic and transoesophageal echocardiography, cardiac computed tomography (CCT), cardiovascular magnetic resonance imaging (CMR), and nuclear imaging modalities, in the diagnosis of IE in CHD patients. These imaging techniques provide crucial information about valvular and intracardiac structures, vegetation size and location, abscess formation, and associated complications, helping clinicians make timely and informed decisions. However, each one does have limitations that influence its applicability.

Tetralogy of Fallot (TOF) is the most common complex congenital heart disease with long-term survivors, demanding serial monitoring of the possible complications that can be encountered from the diagnosis to long-term follow-up. Cardiovascular imaging is key in the diagnosis and serial assessment of TOF patients, guiding patients' management and providing prognostic information. Thorough knowledge of the pathophysiology and expected sequalae in TOF, as well as the advantages and limitations of different non-invasive imaging modalities that can be used for diagnosis and follow-up, is the key to ensuring optimal management of patients with TOF. The aim of this manuscript is to provide a comprehensive overview of the role of each modality and common protocols used in clinical practice in the assessment of TOF patients.

When patients perform musculoskeletal rehabilitation exercises, it is of great importance to observe the correctness of their performance. The aim of this study is to increase the accuracy of recognizing human movements during exercise. The process of monitoring and evaluating musculoskeletal rehabilitation exercises was modeled using various tracking systems, and the necessary algorithms for processing information for each of the tracking systems were formalized. An approach to classifying exercises using machine learning methods is presented. Experimental studies were conducted to identify the most accurate tracking systems (virtual reality trackers, motion capture, and computer vision). A comparison of machine learning models is carried out to solve the problem of classifying musculoskeletal rehabilitation exercises, and 96% accuracy is obtained when using multilayer dense neural networks. With the use of computer vision technologies and the processing of a full set of body points, the accuracy of classification achieved is 100%. The hypotheses on the ranking of tracking systems based on the accuracy of positioning of human target points, the presence of restrictions on application in the field of musculoskeletal rehabilitation, and the potential to classify exercises are fully confirmed.

Predicting cardiorespiratory fitness levels can be useful for measuring progress in an exercise program as well as for stratifying cardiovascular risk in asymptomatic adults. This study proposes a model to predict fitness level in terms of maximal oxygen uptake using anthropometric, heart rate, and step count data. The model was trained on a diverse cohort of 3115 healthy subjects (1035 women and 2080 men) aged 42 ± 10.6 years and tested on a cohort of 779 healthy subjects (260 women and 519 men) aged 42 ± 10.18 years. The developed model is capable of making accurate and reliable predictions with the average test set error of 3.946 ml/kg/min. The maximal oxygen uptake labels were obtained using wearable devices (Apple Watch and Garmin) during recorded workout sessions. Additionally, the model was validated on a sample of 10 subjects with maximal oxygen uptake determined directly using a treadmill protocol in a laboratory setting and showed an error of 4.982 ml/kg/min. Unlike most other models, which use accelerometer readings as additional input data, the proposed model relies solely on heart rate and step counts-data readily available on the majority of fitness trackers. The proposed model provides a point estimation and a probabilistic prediction of cardiorespiratory fitness level, thus it can estimate the prediction's uncertainty and construct confidence intervals., (© 2023. Springer Nature Limited.)

Aims: We aimed to confirm that three-dimensional echocardiography-derived right ventricular ejection fraction (RVEF) is better associated with adverse cardiopulmonary outcomes than the conventional echocardiographic parameters., Methods: We performed a meta-analysis of studies reporting the impact of unit change of RVEF, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strain (FWLS) on clinical outcomes (all-cause mortality and/or adverse cardiopulmonary outcomes). Hazard ratios (HRs) were rescaled by the within-study SDs to represent standardized changes. Within each study, we calculated the ratio of HRs related to a 1 SD reduction in RVEF versus TAPSE, or FAC, or FWLS, to quantify the association of RVEF with adverse outcomes relative to the other metrics. These ratios of HRs were pooled using random-effects models., Results: Ten independent studies were identified as suitable, including data on 1,928 patients with various cardiopulmonary conditions. Overall, a 1 SD reduction in RVEF was robustly associated with adverse outcomes (HR = 2.64 [95% CI, 2.18-3.20], P < .001; heterogeneity: I 2  = 65%, P = .002). In studies reporting HRs for RVEF and TAPSE, or RVEF and FAC, or RVEF and FWLS in the same cohort, head-to-head comparison revealed that RVEF showed significantly stronger association with adverse outcomes per SD reduction versus the other 3 parameters (vs TAPSE, HR = 1.54 [95% CI, 1.04-2.28], P = .031; vs FAC, HR = 1.45 [95% CI, 1.15-1.81], P = .001; vs FWLS, HR = 1.44 [95% CI, 1.07-1.95], P = .018)., Conclusion: Reduction in three-dimensional echocardiography-derived RVEF shows stronger association with adverse clinical outcomes than conventional right ventricular functional indices; therefore, it might further refine the risk stratification of patients with cardiopulmonary diseases., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: A systematic review showed that the accuracy of Mycobacterium tuberculosis antigen-based skin tests (TBSTs) for tuberculosis is similar to that of interferon γ release assay, but the safety of TBSTs has not been systematically reviewed., Methods: We searched for studies reporting injection site reactions (ISRs) and systemic adverse events associated with TBSTs. We searched Medline, Embase, e-library, the Chinese Biomedical Literature Database, and the China National Knowledge Infrastructure database for studies through 30 July 2021, and the database search was updated until 22 November 2022., Results: We identified 7 studies for Cy-Tb (Serum Institute of India), 7 (including 2 found through the updated search) for C-TST (Anhui Zhifei Longcom), and 11 for Diaskintest (Generium). The pooled risk of any injection site reactions (ISRs) due to Cy-Tb (n = 2931; 5 studies) did not differ significantly from that for tuberculin skin tests (TSTs; risk ratio, 1.05 [95% confidence interval, .70-1.58]). More than 95% of ISRs were reported as mild or moderate; common ISRs included pain, itching, and rash. In 1 randomized controlled study, 49 of 153 participants (37.6%) given Cy-Tb experience any systemic adverse event (eg, fever and headache), compared with 56 of 149 participants (37.6%) given TST (risk ratio, 0.85 [95% confidence interval, .6-1.2]). In a randomized controlled study in China (n = 14 579), the frequency of systemic adverse events in participants given C-TST was similar to that for TST, and the frequency of ISRs was similar to or lower than that for TST. Reporting of the safety data on Diaskintest was not standardized, precluding meta-analysis., Conclusion: The safety profile of TBSTs appears similar to that of TSTs and is associated with mostly mild ISRs., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aims: To investigate contraction patterns of the systemic right ventricle (SRV) in patients with transposition of great arteries (TGA) post-atrial switch operation and with congenitally corrected transposition of great arteries (ccTGA)., Methods and Results: Right ventricular (RV) volumes and ejection fraction (EF) were measured by three-dimensional echocardiography in 38 patients with the SRV (24 TGA and 14 ccTGA; mean age 45 ± 12 years, 63% male), and in 38 healthy volunteers. The RV contraction was decomposed along the longitudinal, radial, and anteroposterior directions providing longitudinal, radial, and anteroposterior EF (LEF, REF, and AEF, respectively) and their contributions to total right ventricular ejection fraction (LEFi, REFi, and AEFi, respectvely). SRV was significantly larger with lower systolic function compared with healthy controls. SRV EF and four-chamber longitudinal strain strongly correlated with B-type natriuretic peptide (BNP) level (Rho -0.73, P < 0.0001 and 0.70, P < 0.0001, respectively). In patients with TGA, anteroposterior component was significantly higher than longitudinal and radial components (AEF 17 ± 4.5% vs. REF 13 ± 4.9% vs. LEF 10 ± 3.3%, P < 0.0001; AEFi 0.48 ± 0.09 vs. REFi 0.38 ± 0.1 vs. LEFi 0.29 ± 0.08, P < 0.0001). In patients with ccTGA, there was no significant difference between three SRV components. AEFi was significantly higher in TGA subgroup compared with ccTGA (0.48 ± 0.09 vs. 0.36 ± 0.08, P = 0.0002)., Conclusion: Contraction patterns of the SRV are different in TGA and ccTGA. Anteroposterior component is dominant in TGA providing compensation for impaired longitudinal and radial components, while in ccTGA all components contribute equally to the total EF. SRV EF and longitudinal strain demonstrate strong correlation with BNP level and should be a part of routine echocardiographic assessment of the SRV., Competing Interests: Conflict of interest: A.K., B.K.L., M.T., and A.F. report personal consulting fees from Argus Cognitive, Inc. Other co-authors have nothing to disclose., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Assessment of right ventricular (RV) function is crucial for the evaluation of the dyspnoeic patient and/or with systemic venous congestion and provides powerful prognostic insights. It can be performed using different imaging modalities including standard and advanced echocardiographic techniques, cardiac magnetic resonance imaging, computed tomography, and radionuclide techniques, which should be used in a complementary fashion. Each modality has strengths and weaknesses based on which the choice of their use and in which combination may vary according to the different clinical scenarios as will be detailed in this review. The conclusions from multiple studies using different imaging techniques are concordant: RV function can be reliably assessed and is a critical predictor of clinical outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Type 2 diabetes (Т2DM) both directly and indirectly impacts the development of morphological and functional changes of the central nervous system., Aim: The study was to determine clinical and neurophysiological patterns of cognitive impairment (CI) in patients with chronic cerebrovascular diseases (CCD) and Т2DM., Materials and Methods: We examined 132 patients with CCD. First group included 58 patients without Т2DM aged 64.5 [58; 72], second group 74 patients with CCD and Т2DM 63 [57; 70]. Clinical, neurological, neuropsychological, neurophysiological (cognitive evoked potentials (EP) and neurovisualisation (brain MRI) examination was carried out to all patients., Results: Somatic and neurological characteristics of the patients were similar in both groups with the exception of more distinct metabolic changes in Т2DM patients. Neurovisualisation study of the brain MRI in Т2DM patients revealed more distinct changes in the form of white matter hyperintensity and subarachnoidal spaces enlargement. Neuropsychological examination in patients revealed the reduction of intellectual flexibility, constructive praxis disruption, optical spatial dysfunction and deteoration of delayed word recall. Significant disorders in the way of overall cognitive impairment, lobar dysfunction and impaired verbal associative productivity, proved by statistically lower amplitude and higher latency of P300 EP peak were noted in Т2DM patients. Correlation links were detected: for P300 amplitude and direct and inverse number listing test (r=0.366 and r=0.520; p=0.006 and p0.001 respectively); P300 latency and HbA1c (r=0.32; р0.05) in group 2 and glucose levels in both groups (r=0.30; p0.05); inverse relationship of latency with control functions evaluation (r=-0.34; p=0.008)., Conclusion: CCD especially with Т2DM manifests with neurocognitive imbalance, including control functions disruption and are accompanied by neurophysiological and neurovisualistion changes.

Background: The functional adaptation of the right ventricle (RV) to the different degrees of left ventricular (LV) dysfunction remains to be clarified. We sought to (1) assess the changes in RV contraction pattern associated with the reduction of LV ejection fraction (EF) and (2) analyze whether the assessment of RV longitudinal, radial, and anteroposterior motion components of total RVEF adds prognostic value., Methods: Consecutive patients with left-sided heart disease who underwent clinically indicated transthoracic echocardiography were enrolled in a single-center prospective observational study. Adverse outcome was defined as heart failure hospitalization or cardiac death. Cross-sectional analysis using the baseline 3-dimensional echocardiography studies was performed to quantify the relative contribution of the longitudinal, radial, and anteroposterior motion components to total RVEF., Results: We studied 292 patients and followed them for 6.7±2.2 years. In patients with mildly and moderately reduced LVEF, the longitudinal and the anteroposterior components of RVEF decreased significantly, while the radial component increased resulting in preserved total RVEF (RVEF: 50% [46%-54%] versus 47% [44%-52%] versus 46% [42%-49%] in patients with no, mild, or moderate LV dysfunction, respectively; data presented as median and interquartile range). In patients with severe LV systolic dysfunction (n=34), a reduction in all 3 RV motion components led to a significant drop in RVEF (30% [25%-39%], P <0.001). In patients with normal RVEF (>45%), the anteroposterior component of total RVEF was a significant and independent predictor of outcome (hazard ratio, 0.960 [CI, 0.925-0.997], P <0.001)., Conclusions: In patients with left-sided heart disease, there is a significant remodeling of the RV associated with preservation of the RVEF in patients with mild or moderate LV dysfunction. In patients with normal RVEF, the measurement of the anteroposterior component of RV motion provided independent prognostic value.

Background: Data about the right ventricular (RV) mechanics adaptation to volume overload in patients with repaired tetralogy of Fallot (rToF) are limited. Accordingly, we sought to assess the mechanics of the functional remodeling occurring in the RV of rToF with severe pulmonary regurgitation., Methods: We used three-dimensional transthoracic echocardiography (3DTE) to obtain RV data sets from 33 rToF patients and 30 age- and sex- matched controls. A 3D mesh model of the RV was generated, and RV global and regional longitudinal (LS) and circumferential (CS) strain components, and the relative contribution of longitudinal (LEF), radial (REF) and anteroposterior (AEF) wall motion to global RV ejection fraction (RVEF) were computed using the ReVISION method., Results: Corresponding to decreased global RVEF (45 ± 6% vs 55 ± 5%, p < 0.0001), rToF patients demonstrated lower absolute values of LEF (17 ± 4 vs 28 ± 4), REF (20 ± 5 vs 25 ± 4) and AEF (17 ± 5 vs 21 ± 4) than controls (p < 0.01). However, only the relative contribution of LEF to global RVEF (0.39 ± 0.09 vs 0.52 ± 0.05, p < 0.0001) was significantly decreased in rToF, whereas the contribution of REF (0.45 ± 0.08 vs 0.46 ± 0.04, p > 0.05) and AEF (0.38 ± 0.09 vs 0.39 ± 0.04, p > 0.05) to global RVEF was similar to controls. Accordingly, rToF patients showed lower 3D RV global LS (-16.94 ± 2.9 vs -23.22 ± 2.9, p < 0.0001) and CS (-19.79 ± 3.3 vs -22.81 ± 3.5, p < 0.01) than controls. However, looking at the regional RV deformation, the 3D CS was lower in rToF than in controls only in the basal RV free-wall segment (p < 0.01). 3D RV LS was reduced in all RV free-wall segments in rToF (p < 0.0001), but similar to controls in the septum (p > 0.05)., Conclusions: 3DTE allows a quantitative evaluation of the mechanics of global RVEF. In rToF with chronic volume overload, the relative contribution of the longitudinal shortening to global RVEF is affected more than either the radial or the anteroposterior components., (© 2021. The Author(s).)

The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10% to 15% of patients are cured by the procedure. Preclinical studies indicate that substitution of post-transplantation cyclophosphamide with bendamustine (PTB) in a prophylaxis regimen may be associated with an augmented graft-versus-leukemia (GVL) reaction. The aim of this study was to establish the optimal dose of PTB and evaluate the antileukemic effect of HSCT with this type of graft-versus-host disease (GVHD) prophylaxis. In the prospective trial (NCT02799147), PTB was administered in doses of 140, 100, and 70 mg/m 2 on days +3 and +4. Myeloablative conditioning with fludarabine and oral busulfan was provided to all patients. The first 12 patients received single-agent PTB, and subsequent patients received combination therapy with tacrolimus and mycophenolate mofetil (MMF). Inclusion criteria were acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to at least one induction course of chemotherapy or target therapy and ≥5% clonal blasts in the bone marrow. The study cohort comprised 22 patients with AML and 5 with ALL. Seven patients were enrolled in the 140 mg/m 2 group (due to a stopping rule), and 10 each were enrolled in the 100 mg/m 2 and 70 mg/m 2 groups. Primary refractory disease was documented in 41% of the patients, and secondary refractory was documented in 59%. The median blast count in the bone marrow at the start of the conditioning was 18% (range, 6% to 97%). Transplantation was performed with a matched sibling donor in 5 patients, a matched or mismatched unrelated donor in 15, and a haploidentical donor in 7. Engraftment was documented in 93% of the patients, including 89% with complete remission and 63% without measurable residual disease. After PTB prophylaxis, we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3 to 5 CRS in 44%. The most frequent clinical symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation in 37%, and central nervous system toxicity in 26%. The development of CRS was associated with use of an HLA-mismatched donor (75% versus 20%; P = .0043). Classic acute GVHD was documented in 44% of the patients. Grade II-IV acute GVHD was associated with grade 3 to 5 CRS (67% versus 25%; P = .031). Moderate and severe chronic GVHD in the 100-day survivors were more often observed after single-agent PTB than after the combination immunosuppression (100% versus 18%; P = .002). A relatively low relapse rate was observed for this patient population. Three-year overall survival was 28% (95% confidence interval [CI], 13% to 46%), and event-free survival was 29% (95% CI, 13% to 46%). Nonrelapse mortality was 46% (95% CI, 25% to 64%), and the cumulative incidence of relapse was 26% (95% CI, 11% to 44%). No relapses were documented after day +100. There were no statistically significant differences among the dose groups (P = .3481); however, survival was higher in the 100 mg/kg group. Survival was higher in patients with AML compared with those with ALL (35% versus 0%; P = .0157). PTB represents a promising option to augment the GVL effect in refractory AML; however, the high CRS-associated mortality necessitates additional studies to reduce the risk of this complication. Thus, routine clinical application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications, at least in the setting of HLA-matched allografts. Biological mechanisms of CRS and GVL after PTB require further elucidation., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Accurate echocardiographic evaluation of the systemic right ventricle is challenging because of its specific morphology and contraction patterns. We present a detailed multimodality assessment of the systemic right ventricle, analyze the relative contribution of the longitudinal, radial, and anteroposterior components of systolic function, and identify reasons for a potential discrepancy among imaging modalities. ( Level of Difficulty: Intermediate. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Our aim was to assess the regional right ventricular (RV) shape changes in pressure and volume overload conditions and their relations with RV function and mechanics. The end-diastolic and end-systolic RV endocardial surfaces were analyzed with three-dimensional echocardiography (3DE) in 33 patients with RV volume overload (rToF), 31 patients with RV pressure overload (PH), and 60 controls. The mean curvature of the RV inflow (RVIT) and outflow (RVOT) tracts, RV apex and body (both divided into free wall (FW) and septum) were measured. Zero curvature defined a flat surface, whereas positive or negative curvature indicated convexity or concavity, respectively. The longitudinal and radial RV wall motions were also obtained. rToF and PH patients had flatter FW (body and apex) and RVIT, more convex interventricular septum (body and apex) and RVOT than controls. rToF demonstrated a less bulging interventricular septum at end-systole than PH patients, resulting in a more convex shape of the RVFW (r = - 0.701, p < 0.0001), and worse RV longitudinal contraction (r = - 0.397, p = 0.02). PH patients showed flatter RVFW apex at end-systole compared to rToF (p < 0.01). In both groups, a flatter RVFW apex was associated with worse radial RV contraction (r = 0.362 in rToF, r = 0.482 in PH at end-diastole, and r = 0.555 in rToF, r = 0.379 in PH at end-systole, respectively). In PH group, the impairment of radial contraction was also related to flatter RVIT (r = 0.407) and more convex RVOT (r = - 0.525) at end-systole (p < 0.05). In conclusion, different loading conditions are associated to specific RV curvature changes, that are related to longitudinal and radial RV dysfunction.

Aims: Comprehensive echocardiography assessment of right ventricular (RV) impairment has not been reported in critically ill patients with COVID-19. We detail the specific phenotype and clinical associations of RV impairment in COVID-19 acute respiratory distress syndrome (ARDS)., Methods: Transthoracic echocardiography (TTE) measures of RV function were collected in critically unwell patients for associations with clinical, ventilatory and laboratory data., Results: Ninety patients (25.6% female), mean age 52.0 ± 10.8 years, veno-venous extracorporeal membrane oxygenation (VVECMO) (42.2%) were studied. A significantly higher proportion of patients were identified as having RV dysfunction by RV fractional area change (FAC) (72.0%,95% confidence interval (CI) 61.0-81.0) and RV velocity time integral (VTI) (86.4%, 95 CI 77.3-93.2) than by tricuspid annular plane systolic excursion (TAPSE) (23.8%, 95 CI 16.0-33.9), RVS' (11.9%, 95% CI 6.6-20.5) or RV free wall strain (FWS) (35.3%, 95% CI 23.6-49.0). RV VTI correlated strongly with RV FAC (p ≤ 0.01). Multivariate regression demonstrated independent associations of RV FAC with NTpro-BNP and PVR. RV-PA coupling correlated with PVR (univariate p < 0.01), as well as RVEDAi (p < 0.01), and RVESAi (p < 0.01), and was associated with P/F ratio (p 0.026), PEEP (p 0.025), and ALT (p 0.028)., Conclusions: Severe COVID-19 ARDS is associated with a specific phenotype of RV radial impairment with sparing of longitudinal function. Clinicians should avoid interpretation of RV health purely on long-axis parameters in these patients. RV-PA coupling potentially provides important additional information above standard measures of RV performance in this cohort., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The study aimed to assess the relation between echocardiographic parameters of subpulmonary left ventricular (LV) size and function, and the severity of heart failure in patients with a systemic right ventricle (SRV)., Methods and Results: A total of 157 patients (89 post Mustard/Senning operations, 68 with congenitally corrected transposition of great arteries [ccTGA]) were included. The size and function of the SRV and subpulmonary LV were assessed on the most recent echocardiographic exam. Clinical data were collected from the electronic records. The majority (133, 84.7%) were in NYHA functional class 1-2. Median BNP concentration was 79.5[38.3-173.3] ng/l, and 100 (63.7%) patients were receiving heart failure therapy. Both LV and SRV fractional area change (FAC) differed significantly between patients with NYHA class 1-2 vs 3-4 (48[41.5-52.8]% vs 34[28.6-38.6]%, p < 0.0001 and 29.5[23-35]% vs 22[20-27]%, p < 0.0001, respectively), but LV FAC had a higher discriminative power for functional class >2 than SRV FAC (AUC 0.90, p < 0.0001 vs 0.79; p < 0.0001, respectively). A LV FAC cut-off value <39.2% had the highest accuracy in identifying patients with NYHA class 3-4 (sensitivity 83% and specificity 88%). In multivariable logistic regression analysis, LV FAC and SRV FAC independently associated to NYHA class 3-4 (OR 0.80 [95%CI 0.72-0.88], p < 0.0001 and OR 0.85 [95%CI 0.76-0.96], p = 0.007, respectively)., Conclusions: Subpulmonary LV systolic dysfunction is associated with NYHA functional class 3-4 in patients with ccTGA or after Mustard or Senning operation. Careful evaluation of the subpulmonary LV should be a part of the routine assessment of patients with a SRV., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Accurate assessment of etiology of mitral regurgitation (MR) is one of the key steps in the decision-making process and further clinical management of patients with severe MR. Our clinical case illustrates the added value of three-dimensional echocardiography (3DE) in assessment of mitral valve morphology and identification of an unexpected mechanism of MR which was not previously diagnosed using conventional echocardiography. 3DE helped to choose appropriate management strategy in this patient., (© 2020 Wiley Periodicals LLC.)

Background and Aims: Statin associated muscle symptoms are common and affect adherence to statin treatment. The objective of this study was to assess whether patients with statin-associated myalgia can be successfully treated with Coenzyme Q10 (CoQ10) to improve symptoms and maintain them on statin therapy., Methods: This systematic review was performed in line with the 2015 PRISMA statement. Relevant studies were identified via a search of MEDLINE, EMBASE and the Cochrane Library. Studies were screened to include randomised controlled trials of oral CoQ10 supplementation versus a placebo in adults with statin-associated myalgia. Continuation of statin therapy was a secondary outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. Pooled and sensitivity analyses were performed., Results: 413 records were identified by the search strategy. Eight studies were selected for review, and 7 of them (with 321 patients) were included in the meta-analysis. Selected studies were published between 2007 and 2016 with the number of participants ranging from 37 to 76. Only two of these studies demonstrated a positive effect of CoQ10 therapy in relieving muscle pain. The meta-analysis did not demonstrate any benefit of CoQ10 supplementation in improving myalgia symptoms compared to placebo (weighted mean difference -0.42; 95% Confidence Interval [CI] -1.47 to 0.62). Similarly, CoQ10 did not improve the proportion of patients remaining on the statin treatment (RR 0.99; 95%CI, 0.81 to 1.20)., Conclusions: This systematic review and meta-analysis did not demonstrate that CoQ10 supplementation was beneficial for patients with statin-associated muscle pain or improved adherence to statin therapy., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Transthoracic 3D echocardiography (3DE) has been shown to be feasible and accurate to measure right ventricular (RV) ejection fraction (EF) when compared with cardiac magnetic resonance (CMR). However, RV EF, either measured with CMR or 3DE, has always been reported as normal (RV EF > 45%) or abnormal (RV EF ≤ 45%). We therefore sought to identify the partition values of RV EF to stratify RV dysfunction in mildly, moderately, or severely reduced as we are used to do with the left ventricle., Methods and Results: We used 3DE to measure RV EF in 412 consecutive patients (55 ± 18 years, 65% men) with various cardiac conditions who were followed for 3.7 ± 1.4 years to obtain the partition values which defined mild, moderate, and severe reduction of RV EF (derivation cohort). Then, the prognostic value of these partition values was tested in an independent population of 446 patients (67 ± 14 years, 58% men) (validation cohort). During follow-up, we recorded 59 cardiac deaths (14%) in the derivation cohort. Using K-Adaptive partitioning for survival data algorithm we identified four groups of patients with significantly different mortality according to RV EF: very low > 46%, 40.9% < low ≤ 46%, 32.1% < moderate ≤ 40.9%, and high ≤ 32.1%. To make the partition values easier to remember, we approximated them to 45%, 40%, and 30%. During 4.1 ± 1.2 year follow-up, 38 cardiac deaths and 88 major adverse cardiac events (MACE) (cardiac death, non-fatal myocardial infarction, ventricular fibrillation, or admission for heart failure) occurred in the validation cohort. The partition values of RV EF identified in the derivation cohort were able to stratify both the risk of cardiac death (log-rank = 100.1; P < 0.0001) and MACEs (log-rank = 117.6; P < 0.0001) in the validation cohort too., Conclusion: Our study confirms the independent prognostic value of RV EF in patients with heart diseases, and identifies the partition values of RV EF to stratify the risk of cardiac death and MACE., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

In recent years, the possibility of using intranasally administered insulin to treat Alzheimers disease and other cognitive disorders has been widely studied. At the same time, the possibility of its use in the treatment of diabetes mellitus is practically not investigated, which is due to the insufficient study of the molecular mechanisms of its action on the hormonal and metabolic status of the organism. The review discusses literature data and the results of our own research on the role of insulin in the central regulation of energy homeostasis, as well as on the experience of using intranasally administered insulin to correct eating disorders and metabolic and hormonal dysfunctions developing under conditions of experimental diabetes mellitus and metabolic syndrome. In studies involving healthy volunteers, various effects of intranasally administered insulin were shown, including effects on cognitive function, eating behavior and weight loss, and the gender specificity of its action was found. In the course of numerous studies of intranasally administered insulin in animal models of diabetes mellitus, not only stabilization of carbohydrate homeostasis was shown, but also a positive effect in the form of restoration of the functional activity of insulin signaling pathways in the hypothalamus and other parts of the brain. We have presented and analyzed data on the systemic effects of intranasally administered insulin in rodents with experimental models of diabetes mellitus, as well as in healthy individuals.

Background: The study aimed (1) to assess the prognostic value of three-dimensional echocardiography (3DE) derived right ventricular (RV) ejection fraction (EF) and (2) to evaluate relative prognostic importance of reduced and preserved left ventricular (LV) EF and RVEF to predict all-cause mortality and cardiac death in a large cohort of patients with cardiac diseases., Methods: LV and RV volumes and EF were assessed by 3DE in 394 patients with various cardiovascular diseases. Patients were divided into four groups: (1) normal LVEF (≥50%) and normal RVEF (≥45%), n = 183; (2) reduced LVEF (<50%) and normal RVEF (≥45%), n = 75; (3) normal LVEF (≥50%) and reduced RVEF (<45%), n = 61; (4) reduced LVEF (<50%) and reduced RVEF (<45%), n = 75. The patients were followed up for 3.7 ± 1.1 years., Results: Reduced 3DE-derived RVEF was associated with all-cause mortality (P < .0001). The four groups had significantly different survival (P < .0001). Both all-cause mortality and cardiac death in patients with reduced RVEF and normal LVEF were significantly higher than in those with reduced LVEF and normal RVEF (P = .0007 and P = .0091, respectively) and did not differ significantly from patients with reduced EF of both ventricles (P = .2198 and P = .0846, respectively)., Conclusions: Reduced 3DE-derived RVEF was associated with all-cause mortality and cardiac death in patients with various cardiovascular diseases. Impairment of RVEF carried a significantly higher risk of mortality independent of LVEF., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the potential clinical impact of using 3-dimensional echocardiography (3DE) to measure left ventricular ejection fraction (LVEF) in patients considered for implantable cardioverter-defibrillator (ICD) implantation and to assess the predictive value of 3DE LVEF for arrhythmic events., Background: ICD therapy is currently recommended to prevent sudden cardiac death in patients with symptomatic heart failure and LVEF ≤35%, and in asymptomatic patients with ischemic heart disease and LVEF ≤30%. Two-dimensional echocardiography (2DE) is currently used to calculate LVEF. However, 3DE has been reported to be more reproducible and accurate than 2DE to measure LVEF., Methods: The study prospectively enrolled 172 patients with LV dysfunction (71% ischemic). Both 2DE and 3DE LVEF were obtained during the same study. The outcome was the occurrence of major arrhythmic events (sudden cardiac death, aborted cardiac arrest, appropriate ICD therapy)., Results: After a median follow up of 56 (range 18 to 65) months, major arrhythmic events occurred in 30% of the patients. Compared with 2DE, 3DE changed the assignment above or below the LVEF thresholds for ICD implantation in 20% of patients, most of them having 2DE LVEFs within ± 10% from threshold. By cause-specific hazard model, 3DE LVEF was the only independent predictor of the occurrence of major arrhythmic events., Conclusions: LVEF by 3DE was an independent predictor of major arrhythmic events and improved arrhythmic risk prediction in patients with LV dysfunction. When compared with 2DE LVEF, 3DE measurement of LVEF may change the decision to implant an ICD in a sizable number of patients., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Rodents play an important role in rangelands through the engineering of extensive burrow systems, which provides key habitats for many animal and plant species. We have analyzed the long-term variation in the abundance and distribution of rodent burrows in grazing ecosystems of southern Russia (Kalmykia) under the landscape change from desert to steppe caused by the drastic reduction of livestock after the collapse of the USSR in the early 1990s. We conducted burrow surveys in the "desert" (1980) and "steppe" (2017) periods on 19 3-km transects. We found considerable changes in burrow abundance and distribution, as well as evidence of desert habitat fragmentation and isolation caused by the expansion of tall-grass communities. Burrows of the open-dwelling diurnal ground squirrel (Spermophilus pygmaeus), the dominant and the keystone species during the "desert" period, almost completely disappeared from the rodent burrow network by 2017, indicating significant habitat loss. In contrast, the burrows of the folivorous social vole (Microtus socialis) which was rare in the 1980s, became abundant and ubiquitously distributed. The burrow density of the desert-dwelling psammophilous midday gerbil (Meriones meridianus) decreased, while the distances between occupied patches increased, indicating desert habitat fragmentation and loss of population connectivity. Burrows of the folivorous tamarisk gerbils (M. tamariscinus) were recorded only sporadically in both 1980 and 2017. The observed changes in the rodent burrow network, the key component of grazing ecosystems, correlate with rodent species ecology and can have long-term and important consequences for ecosystem functioning., (© 2019 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Studying abrupt ecological shifts under gradual environmental change caused, in particular, by human activity is important for understanding the fundamental aspects and underlying mechanisms of ecological resilience. One of the rare well-documented examples of an abrupt ecological shift is the delayed step transition of the population of a desert rodent, the midday gerbil (Meriones meridianus), from high-abundance (1994-2002) to low-abundance (2003-2017) regimes. This was in response to landscape transformation from desert to steppe caused by the drastic reduction of livestock in the rangelands of southern Russia after the collapse of the USSR in the early 1990s. In this study, we tested whether demographic parameters were correlated with the observed abrupt downward population shift. We found that reproductive activity (the percentage of breeding females, the number of litters, fecundity and the number of young recruited per female) showed no trend over time and did not differ between periods of high and low abundance. In contrast, the adult sex ratio (SR = males: females) decreased significantly with time and was as much as twice more female-biased for the low-abundance population regime. However, SR was not related to any reproductive parameter, including the percentage of breeding females. We conclude that proximate reasons for an abrupt population decline in M. meridianus are not associated with the changes in breeding patterns or mate limitation caused by the Allee effect but relate to the increased mortality as a result of the desert landscape being fragmented by steppezation. The mortality is expected to be higher for males as the mobile and dispersing sex., (© 2018 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Despite the well-studied effect of insulin in peripheral tissues, its role in functioning of the central nervous system is much less understood. The effects of insulin in the brain are extremely diverse: insulin plays an important role in neuron growth and differentiation, affects higher cognitive functions (in particular, the formation of long-term memory), and also has a neuroprotective effect. Both peripheral and central insulin resistance as well as absolute insulin deficiency impairs the functional activity of neurons and neurogenesis. Several studies have investigated intranasal administration of insulin as a potential way for correction of these disorders. The review presents data on abnormalities of the insulin signaling system in the brain in diabetes mellitus, which is accompanied by cognitive dysfunction of varying severity and is associated with the development of neurodegenerative disorders, including Alzheimer's disease. We analyzed the results of studies on the use of intranasal insulin in animal models with diabetes mellitus, healthy volunteers, and patients with cognitive impairments.

Transthoracic echocardiography is the principal imaging modality for assessment of patients with atrioventricular septal defects. Three-dimensional echocardiography streamlines and simplifies data acquisition offering a unique realistic en-face display of heart valves and septal defects and enables accurate evaluation of the cardiac anatomy, dynamic, and function. We demonstrated an added value of three-dimensional echocardiography in assessment of an adult patient with atrioventricular septal defect and its advantages over conventional echocardiography., (© 2019 Wiley Periodicals, Inc.)

Recent studies showed that B cells play a major role in the pathogenesis of neurodegeneration in multiple sclerosis (MS). In this study, we aimed to determine the possible link between immunoglobulin free light chains (FLC) and brain atrophy in patients with MS. Ninety-two patients (32 males and 60 females) with MS were included. Kappa and lambda FLC concentrations in serum and cerebrospinal fluid (CSF) samples of MS patients were measured using ELISA assay. FLC quotients (Q-k and Q-λ, respectively) were calculated. In a cross-sectional group (n = 92), the MRI data were acquired within 6 months from the date of the lumbar puncture. Twenty patients from this cohort performed a follow-up MRI after 1 year of observation. Brain volumes were calculated with SIENAX and the brain atrophy (percentage brain volume change (PBVC)) was assessed with SIENA. Spearman's test was performed to assess correlations. We have shown statistically significant correlation of Expanded Disability Status Scale (EDSS) level with normalized brain volume (NBV, r = - 0.2721, p = 0.0062), white matter volume (WMV, r = - 0.2425, p = 0.015), and gray matter volume (GMV, r = - 0.216, p = 0.0309). Multiple Sclerosis Severity Score (MSSS) score correlated with NBV (r = - 0.2521, p = 0.0352) and WMV (r = - 0.315, p = 0.0079). Neither EDSS, nor MSSS scores correlated with the age of patients and relapse rate during the first year and 5 years. In our study, we found statistically significant correlations of k-FLC in the CSF with NBV (r = - 0.311, p = 0.003) and with GMV (r = - 0.213, p = 0.0423). Q-k correlated only with NBV (r = - 0.340, p = 0.006) and Q-λ were negatively correlated with WMV (r = - 0.366, p = 0.003). We did not find correlations of k-FLC in CSF, λ-FLC in CSF, Q-k, and Q-λ with duration of MS course, EDSS, MSSS, number of relapses during the first year, and during the first 5 years of disease. Additionally, we subdivided the study population in accordance with level of k-FLC CSF, Q-k, and Q-λ on the 25th and 75th percentile subgroups (25-k-FLC CSF /75-k-FLC CSF ; 25-λ-FLC CSF /75-λ-FLC CSF ; 25-Q-k/75-Q-k; 25-Q-λ/75-Q-λ). We found statistically significant difference of NBV and GMV between 25-k-FLC CSF and 75-k-FLC CSF subgroups (p = 0.0047, p = 0.0297 respectively), NBV between 25-Q-k and 75-Q-k subgroups (p = 0.038), and NBV and WMV between 25-Q-λ and 75-Q-λ subgroups (p = 0.0446, p = 0.0026 respectively). PBVC in the prospective group showed negative correlation with kappa FLC in the CSF (r = - 0.4853, p = 0.0301) and Q-k (r = - 0.6132, p = 0.0224), but not with other clinical, epidemiological data. In this study, we showed a strong negative correlation of k-FLC, Q-k, and Q-λ with brain atrophy in MS patients. Additionally, patients with high concentration of FLC had lower brain volumes. We did not find correlations of FLC with the relapse rate, age of patients, and MS time course. In the prospective group, the rate of atrophy was correlated with k-FLC and Q-k. We suggest that level of intrathecal production of FLC can be a good prognostic biomarker for MS.

Background: Right ventricular (RV) remodeling involves changes in size, wall thickness, function, and shape. Previous studies have suggested that regional curvature indices (rCI) may be useful for RV shape analysis. The aim of this study was to establish normal three-dimensional echocardiographic values of rCI in a large group of healthy subjects to facilitate future three-dimensional echocardiographic study of adverse RV remodeling., Methods: RV endocardial surfaces were reconstructed at end-diastole and end-systole in 245 healthy subjects (mean age, 42 ± 12 years) and analyzed using custom software to calculate mean curvature in six regions: RV inflow tract (RVIT) and RV outflow tract, apex, and body (both divided into free wall and septal regions). Associations with age and gender were studied., Results: The apical free wall was convex, while the septum (apex and body) was more concave than the body free wall. Septal curvature did not change significantly from end-diastole to end-systole. The RV outflow tract and RVIT became flatter from end-diastole to end-systole. In keeping with the "bellows-like" action of RV contraction, the body free wall became flatter, while the apex free wall changed to a more convex surface. There were no intergender differences in rCI. In older subjects (≥55 years of age), the RV free wall and RV outflow tract were flatter, and from end-diastole to end-systole, the RVIT became less flattened and the apex less pointed. These changes suggest that the right ventricle is stiffer in older subjects, with less dynamic contraction of the RVIT and less bellows-like movement., Conclusions: This study established normal three-dimensional echocardiographic values for RV rCI, which are needed to further study RV diastolic dysfunction and remodeling with disease., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest.

Background: The 2015 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations for chamber quantification suggest new abnormality threshold and severity partition values for left atrial (LA) volume that are equally valid for the biplane method of disk (MOD) summation and the area-length method (ALM). However, they have never been clinically validated. Thus, we compared the clinical and prognostic impact of LA volume assessed by MOD and ALM by using both the 2015 and 2005 abnormality thresholds., Methods: In a retrospective study of 467 patients with sinus rhythm and various cardiac conditions (median age 61 years, 68% men), maximal LA volumes were measured with MOD and ALM. Patients were followed for 3.7 ± 1.1 years to record both all-cause mortality and cardiac death., Results: Applying the 2015 cutoff values, 21% of patients with dilated LA according to the 2005 recommendations were reclassified as normal. Severity of LA dilatation was reclassified in 48% (222/467) patients. ALM provided significantly larger LA volumes than MOD (41 [32; 58] mL/m 2 vs 39 [30; 55] mL/m 2 ; P = .0150), reclassifying 18% (84/467) of patients. Patients who died had larger LA volumes measured with both MOD (57 [38; 77] mL/m 2 vs 37 [30; 51] mL/m 2 ; P < .0001) and ALM (58 [40; 82] mL/m 2 vs 40 [32; 54] mL/m 2 ; P < .0001). Regardless of the method used, LA volume was a significant factor associated with mortality, with both the 2015 and 2005 cutoff values providing similar prognostic power., Conclusions: The use of 2015 partition values and different methods of LA volume measurement leads to significant changes in patients' clinical profiles. LA enlargement is an important prognostic indicator independent of cutoff values and methods used. Care should be taken to ensure consistent measurements and interpretation of two-dimensional echocardiography LA volume during patient follow-up., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Left bundle branch block (LBBB) results in an altered pattern of left ventricular (LV) activation and subsequent contraction, causing remarkable changes in LV mechanics, perfusion and workload and ultimately leading to pathologic cardiac remodelling. Clinical and diagnostic notions about the LBBB phenomenon had evolved from just an electrocardiographic pattern to a critically important finding affecting diagnostic and clinical management of many patients and adversely influencing their outcomes. Recent advances in imaging techniques significantly improved the assessment of patients with LBBB and provided additional insights into pathophysiological mechanisms of LV remodelling. In the current review we summarized currently available data on the LBBB epidemiology, diagnosis, its impact on clinical management and prognosis, and the role and place of various imaging modalities in assessing cardiac mechanics and perfusion abnormalities, as well as their potential implications for diagnostic and treatment strategies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

The effect of the tetrapeptide bronchogen on the structural and functional state of the bronchial epithelium and inflammatory activity in the lungs was studied in the chronic obstructive pulmonary disease (COPD) model, created in rats by a 60-day intermittent exposure to nitrogen dioxide. The cell composition and cytokine-enzyme profile of bronchoalveolar lavage fluid (BALF), the content of secretory immunoglobulin A and surfactant protein B in BALF were determined. Following the course of peptide treatment the decreased activity of neutrophilic inflammation with the normalization of cellular composition and profile of pro-inflammatory cytokines and enzymes in the bronchoalveolar space was observed. The structure of bronchial epithelium, disturbed during formation of COPD model, was restored and accompanied by restoration of its functional activity as evidenced by an increase of secretory immunoglobulin A (local immunity marker) and surfactant protein B, responsible for reducing the alveolar surface tension.

Advances in ultrasound, computer, and electronics technology have permitted three-dimensional echocardiography (3DE) to become a clinically viable imaging modality, with significant impact on patient diagnosis, management, and outcome. Thanks to the inception of a fully sampled matrix transducer for transthoracic and transesophageal probes, 3DE now offers much faster and easier data acquisition, immediate display of anatomy, and the possibility of online quantitative analysis of cardiac chambers and heart valves. The clinical use of transthoracic 3DE has been primarily focused, albeit not exclusively, on the assessment of cardiac chamber volumes and function. Transesophageal 3DE has been applied mostly for assessing heart valve anatomy and function. The advantages of using 3DE to measure cardiac chamber volumes derive from the lack of geometric assumptions about their shape and the avoidance of the apical view foreshortening, which are the main shortcomings of volume calculations from two-dimensional echocardiographic views. Moreover, 3DE offers a unique realistic en face display of heart valves, congenital defects, and surrounding structures allowing a better appreciation of the dynamic functional anatomy of cardiac abnormalities in vivo. Offline quantitation of 3DE data sets has made significant contributions to our mechanistic understanding of normal and diseased heart valves, as well as of their alterations induced by surgical or interventional procedures. As reparative cardiac surgery and transcatheter procedures become more and more popular for treating structural heart disease, transesophageal 3DE has expanded its role as the premier technique for procedure planning, intra-procedural guidance, as well as for checking device function and potential complications after the procedure.

The human recombinant β-interferon is most frequently applied for treatment of remittent recurrent form of multiple sclerosis using pharmaceuticals. The clinical response to applied therapy is absent in some of patients that can be conditioned by development of antibodies too preparations. Depending on possibility of blocking binding of human recombinant β-interferon with its receptor, all antibodies are divided on binding and neutralizing ones. The purpose of study is to investigate analytical and clinical diagnostic parameters of tests using for detection of different types of antibodies synthesized against human recombinant β-interferon. The study sampling consisted of 33 patients with remittent recurrent form of multiple sclerosis receiving therapy with human recombinant β-interferon and also of 40 donors and 15 patients with multiple sclerosis without therapy with human recombinant β-interferon. The concentration of binding antibodies was measured by enzyme-linked immunosorbent assay. Also immune blotting assay was applied. The titer of neutralizing antibodies was determined using cell line HL-116 sensitive to human recombinant β-interferon. The binding and neutralizing antibodies were not detected in donors and patients without human recombinant β-interferon therapy. The prevalence of binding antibodies to human recombinant β-interferon amounted to 57.6% when analysis of samples using immune blotting assay was used and 60.6% when commercial testing system was applied. The statistical analysis of results demonstrated high convergence and correlation of values of concentrations of binding antibodies obtained using immune blotting assay and enzyme-linked immunosorbent assay (r=0.9159, p<0.0001). The clinically significant titers of neutralizing antibodies were detected in 21.21°% of patients. All patients with clinically significant titer of neutralizing antibodies were positive in relation to binding antibodies measured by immune blotting assay and enzyme-linked immunosorbent assay. The high correlation between values of titers of neutralizing antibodies and concentration of binding antibodies measured by immune blotting assay (r=0.7909, p=0.0055). The application in clinical practice of data concerning presence of binding and neutralizing antibodies to human recombinant β-interferon can input into optimization of therapy with expensive biologic preparations in patients with multiple sclerosis and other autoimmune diseases.

Right ventricular (RV) size and function have been found to be important predictors of cardiovascular morbidity and mortality in patients with various conditions. However, non-invasive assessment of the RV is a challenging task due to its complex anatomy and location in the chest. Although cardiac magnetic resonance (CMR) is considered a "gold standard" for RV assessment, the development of novel echocardiographic techniques, including three-dimensional (3DE) and two-dimensional speckle-tracking echocardiography (2DSTE) opened new exciting opportunities in RV imaging. 3DE has proven accurate in measuring RV volumes and ejection fraction when compared with CMR while 2DSTE plays a critical role in measuring RV myocardial deformation, which is a powerful predictor of patients' functional capacity and survival. Cardiac computed tomography provides an accurate and reproducible assessment of the RV volumes and can be considered a reliable alternative for patients who are not suitable for either echocardiography or CMR. The purpose of this review is to summarize currently available data on the role of the different noninvasive cardiac imaging modalities in assessment of RV size, function and mechanics, with an emphasis on the benefits of novel imaging techniques and on how the latter can be applied in the various clinical settings., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Current knowledge of functional tricuspid regurgitation (FTR) as a progressive entity, worsening the prognosis of patients irrespective of its aetiology, has led to renewed interest in the pathophysiology and assessment of FTR. For the proper management of FTR, not only its severity, but also the mechanisms, the mode of leaflet coaptation, the degree of tricuspid annulus enlargement and leaflet tenting, and the haemodynamic consequences for right atrial and right ventricular morphology and function have to be taken into account. A better assessment of the anatomy and function of tricuspid apparatus and tricuspid regurgitation severity should help with the appropriate selection of patients who will benefit from either surgical tricuspid valve repair/replacement or a percutaneous procedure, especially among patients who are to undergo or have undergone primary left-sided valvular surgery. In this article, we review the anatomy, pathophysiology and the use of imaging techniques to assess patients with FTR, as well as the various treatment options for FTR, including emerging transcatheter procedures. The limitations affecting the current approach to FTR patients and the unmet clinical needs for their management have also been discussed.

Effect of mast cell degranulation blockade on the inflammatory response and character of the lung tissue structure-functional changes were evaluated in the chronic obstructive pulmonary disease model produced in rats by 60-day intermittent exposure to nitrogen dioxide. The membrane stabilizer sodium cromoglicate was used to blockade of mast cell degranulation. Lung tissue sections were stained with toluidine blue to identify mast cells. Bronchoalveolar lavage fluid (BALF) cytogram was determined. The levels of mast cell tryptase and chymase, proinflammatory cytokine TNF-α, surfactant protein B were measured in BALF. Suppression of mast cell degranulation prevented the release of proteases in the bronchoalveolar space and reduced activity of the inflammatory process. The influx of inflammatory cells and TNF-α concentration decreased. There was no interstitial inflammatory infiltration. Bronchoalveolar epithelium structure was recovered that is the basis of its functional usefulness. The results confirm the active involvement of mast cells in the development of the inflammatory process in obstructive pulmonary diseases and allow us to consider them as a possible therapeutic target.

Background: Most international studies on epidemiology of transient loss of consciousness (TLC) were performed many years ago. There are no data about the lifetime prevalence of TLC in Russia., Objective: To identify the lifetime prevalence and presumed mechanisms of TLC in an urban Russian population., Methods: 1796 individuals (540 males [30.1%] and 1256 females [69.9%]) aged 20 to 69 years (mean age 45.8 ± 11.9 years) were randomly selected and interviewed within the framework of multicentre randomised observational trial., Results: The overall prevalence of TLC in the studied population was 23.3% (418/1796), with the highest proportion (28%) seen in 40-49 year age group. TLC was significantly more common in women than in men (27.5% vs 13.5%). The mean age of patients at the time of the first event was 16 (11; 23) years, with 333 (85%) individuals experiencing the first episode of TLC under 30 years. The average time after the first episode of TLC was 27 (12; 47) years. The following mechanisms of TLC were determined using the questionnaire: neurally-mediated syncope (56.5%), arrhythmogenic onset of syncope (6.0%), nonsyncopal origin of TLC (1.4%), single episode during lifetime (2.1%). Reasons for TLC remained unidentified in 34% cases. 27 persons (6.5%) reported a family history of sudden death, mainly patients with presumably arrhythmogenic origin (24%)., Conclusion: Our findings suggest that the overall prevalence of TLC in individuals aged 20-69 years is high. The most common cause of TLC is neurally-mediated syncope. These data about the epidemiology can help to develop cost-effective management approaches to TLC.

The content of free light chains of immunoglobulins kappa and lambda and also ratio of their concentrations in blood serum are important diagnostic and prognostic markers in case of monoclonal gammopathy. The technique FreelightTM based on nephelometric detection of free light chains using polyclonal antibodies is one of common modes of detection of free light chains. The actual study was carried out with purpose of validating of national test-system for detection of level of free light chains in blood serum using technique of enzyme-linked immunosorbent assay. The samples of blood serum were taken from 89 healthy donors and 165 patients with monoclonal gammopathy. To detect the level of free light chains enzyme-linked immunosorbent assay testsystem "Polygnost" was used based on application of monoclonal a ntibodies. The number of analytical characteristics of reagents set was determined including limit of detection and range of linearity. The limit of detection of free light chains using enzymelinked immunosorbent assay test-system was two times lower than claimed by manufacturer of nephelometric set "FreelightTM". Hence, analytical characteristics of enzyme-linked immunosorbent assay set make it possible to detect the level of free light chains within range of standard values. The reference limits were established concerning concentration of free light chains kappa (3.25-15.81 mkg/ml), free light chains lambda (3.23-28.05 mkg/ml) and their ratio (0.3-1.9) in blood serum that factually matched the recommended intervals for "FreelightTM" set. In patients with monoclonal gammopathy the level of free light chains was reliably higher (p<0.01) as compared with control group of healthy donors. In case of paraproteinemia reliable alteration (p<0.01) of ratio free light chains kappa/free light chains lambda was observed in comparison with control group. The results of actual study testify that national enzyme-linked immunosorbent assay set has good analytical and diagnostic characteristics and it can be used in laboratory practice., Competing Interests: The authors declare no conflict of interest.