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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 0.05) 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 0.05). 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.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often complicated by cytokine storm syndrome. Although many interleukins (IL) have predictive value, the sensitivity and specificity of a single marker is limited. AIM: The purpose of the study is to develop an objective and informative cytokine storm scale for assessing the risk of developing a critical course in patients with COVID-19 associated pneumonia. MATERIALS AND METHODS: A total of 226 cases of COVID-19 were investigated, 36 (16 %) of which were with poor outcomes. The cytokines IL-1b, IL-2, IL-6, IL-8, IL-10, IL-18, TNF-, IFN, IFN- were studied by enzyme immunoassay, commercial kits manufactured by Vector-Best, RF. RESULTS: Since IL-6, IL-10, IL-18, and procalcitonin were associated with disease severity and death, these indicators were integrated into a 12-point scale called the cytokine storm scale. The patients who scored more than 6 points had a high risk of a poor outcome of the disease. According to ROC analysis, the area under the curve for the cytokine storm scale was larger than for each of the four markers separately [AUC 0.90 (95% CI 0.84550.9592), p 0.001]. CONCLUSIONS: Thus, the cytokine storm scale system presents superior performance in determining patients with favorable and fatal outcomes to each individual cytokine.

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

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

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.

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% 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.

Background. Secondary hemophagocytic syndrome (SHPS) and sepsis, although very similar in their clinical manifestations and laboratory parameters, essentially differ in terms of methods of their treatment. SHPS therapy is aimed at immunosuppression, whereas in sepsis anti-infectious treatment is required. To choose the correct therapy a rapid differential diagnosis is necessary. Aim. Search and analysis of criteria of differential diagnosis between SHPS and sepsis. Materials & Methods. The data of 102 patients were analyzed: 55 SHPS patients (median age 60 and range 18-81 years) and 47 sepsis patients (median age 60 and range 18-89 years). SHPS was diagnosed on the basis of HLH-2004 and H-Score criteria. Sepsis was confirmed by documented inflammatory lesions and systemic inflammatory reactions. Microbiologically confirmed sepsis was reported in 10 (21 %) patients. In all sepsis patients multiple organ failure was identified. Results. The study of SHPS and sepsis groups revealed significant differences (p < 0.05) in the levels of C-reactive protein, procalcitonin, creatinine, albumin, and sodium. It was also found out that splenomegaly rate and the levels of triglycerides, ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in SHPS were significantly higher than in sepsis, but the levels of glycosylated ferritin (%GF), fibrinogen, leukocytes, neutrophils, and thrombocytes were lower. The following medians (quartiles 1-3) were reported in SHPS and sepsis, respectively: triglycerides (mmol/L) were 3.1 (2.3-3.8) and 1.5 (0.8-2.7), total ferritin (ng/mL) was 7,170 (3,159.2-12,551.0) and 1,274 (559.0-3,041.5), %GF was 26.5 (16.7-37.3) and 54.5 (37.7-71.8), fibrinogen (g/L) was 2.8 (1.4-4.4) and 5.3 (2.8-6.8), ALT (IU/L) was 50 (20-102) and 30 (15.3-55.5), AST (IU/L) was 66 (40.0-105.6) and 36 (24.678.0), leukocytes (x109/L) were 3.7 (2.1-5.5) and 8.9 (6.5-14.5), thrombocytes (X109/L) were 56 (25.2-93.5) and 157 (97-308). According to ROC analysis the areas under the curve were as follows: 0.88 for neutrophil level, 0.85 for total ferritin, %GF, leukocytes, and thrombocytes, 0.74 for triglycerides, 0.71 for fibrinogen, 0.65 for sodium, and 0.61 for ALT and AST. Conclusion. In differential diagnosis between SHPS and sepsis most important are the levels of total ferritin, its glycosylated fraction, and triglycerides; less important are fibrinogen, neutrophils, thrombocytes and spleen size. As diagnosis and differential diagnosis between SHPS and sepsis are based on the sum total of clinical and laboratory markers, none of the specified characteristics can serve as a reliable parameter if taken separately.

Kewwords Systemic right ventricle Subpulmonary left ventricle Systolic function Heart failure

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/m2 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/m2 group (due to a stopping rule), and 10 each were enrolled in the 100 mg/m2 and 70 mg/m2 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.

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 2 than SRV FAC (AUC 0.90, p

Take-Home Message.This study provides a new diagnostic index based on the antibodies to mutated citrullinated vimentin concentration and the level of different B subsets. Determination of index over 5 Units proved to be characteristic of sarcoidosis, what might help to differentiate SD from TB.Abstract. In some cases there is a problem of differential diagnosis of sarcoidosis(SD) and tuberculosis(TB)because of the similarities in clinical, X-ray and laboratory features. The aim of this study was to search for new differential diagnostic criteria for sarcoidosis and tuberculosis by calculating the index, based on the level of autoantibodies to modified citrullinated vimentin (anti-MCV) and the level of B-cell subpopulations. These parameters were measured in patients with sarcoidosis (n = 93), tuberculosis (n = 40) and healthy donors (n = 40) using the ELISA and cytometry. The absence of a statistically significant difference when comparing the level of anti-MCV, the number of B-cells in SD and TB suggests that these changes may be characteristic of granulomatous diseases. The use of the formula Ds=([B-naïve%]\[B-memory%])*([B-CD38%]+[B-CD5%])/[anti-MCV] might allow to differentiate SD with an increase in the calculated index of more than 5 units with a sensitivity of 80.00% and specificity of 93.10% (AUC = 0.926).

Various congenital or acquired valvular heart diseases (VHD) may be present in pregnant women, and may significantly increase the maternal and fetal risk associated with pregnancy. Pregnancy is associated with significant haemodynamic changes that may aggravate VHD, precipitate or exacerbate symptoms, and increase the risk of thrombo-embolic events. Cardiac imaging modalities, particularly echocardiography and cardiac magnetic resonance, are pivotal for the diagnosis and management of pregnant women with VHD. Valve lesions with a fixed cardiac output, such as severe mitral or aortic stenosis, are at greatest risk of decompensation, while regurgitant lesions are likely to be well tolerated, as the fall in vascular resistance compensates for the volume loading induced by pregnancy. Despite the increased risk, with appropriate cardiologic evaluation and treatment most pregnant women with VHD can successfully deliver healthy children. Women with moderate and high risk of complications during pregnancy should be evaluated in an expert center in VHD by a pregnancy multidisciplinary heart team.

Background Although tricuspid regurgitation in patients with cardiac diseases is an established predictor of adverse outcomes, prevalence, mechanisms and clinical/prognostic value of non-systemic mitral regurgitation (MR) in patients with congenitally corrected transposition of great arteries (ccTGA) or simple transposition after Mustard or Senning procedures (TGA) are still poorly understood. Purpose To assess prevalence, mechanisms of MR and its association with severity of heart failure in patients with a systemic right ventricle (SRV). Methods From our digital echocardiographic database, we have identified all patients with a SRV who underwent echocardiography between 2014 and 2018. Severity of MR, size and function of SRV and subpulmonary LV were assessed from the latest echocardiographic studies. Results 157 patients fulfilled inclusion criteria (89 post-Mustard/Senning, 68 ccTGA), median age 40.6 (33.1; 46.8) years, 57% male, median BNP 79.5 [38.3; 173.3] ng/l. More than trivial MR was present in 44 (28.0%), further classified as mild, moderate and severe in 26 (16.6%), 15 (9.6%) and 3 (1.9%), respectively. Principal mechanisms of MR included (i) device lead interference with the leaflet(s) in 26, (ii) organic pathology of mitral valve in 5 (2 prolapse, 2 cleft and 1 parachute mitral valve) and (iii) systolic leaflet(s) tethering ± annular dilatation in 4; no obvious cause of MR was identified in 10 patients. Presence of more than trivial MR was significantly associated with NYHA class 3-4 (Chi-square 25.74, p MR was less common in patients post-Mustard/Senning procedures compared to ccTGA (p Conclusions Non-systemic MR in patients with a SRV is relatively uncommon, but when present is associated with LV dilatation and systolic dysfunction, raised BNP levels, and heart failure symptoms. Predominant underlying mechanisms were device leads, organic pathology, and valve tethering. MR should be routinely assessed in SRV patients, particularly those with previous Mustard/Senning procedures, and be taken into account in decision making and timing interventions. Characteristics of 157 patients with SRV Parameter No/trivial MR (N = 113) Mild-severe MR (N = 44) P value Age, years Mustard/Senning ccTGA Pulmonary stenosis NYHA class 3-4 ICD/Pacemaker lead 39.5 (33.1; 45.7) 75 (66%) 38 (34%) 13 (12%) 7 (6%) 31 (27%) 44.4 (32.7; 52) 14 (32%) 30 (68%) 12 (27%) 17 (39%) 32 (73%) 0.105 Abstract P1292 Figure. SRV patients with more than trivial MR

Background Dysfunction of systemic right ventricle (SRV) in patients with congenitally corrected transposition of great arteries (ccTGA) or simple transposition (TGA) is commonly associated with exercise intolerance, heart failure and death. However, the relevance of subpulmonary left ventricular (LV) function in these settings is unknown. Purpose To examine the relation between severity of heart failure and echocardiographic parameters of subpulmonary LV size and function in patients with SRV. Methods We identified all patients with SRV from our digital echocardiographic database between 2014 and 2018. The size and function of SRV and subpulmonary LV were assessed in the most recent examination. Clinical data were collected from electronic patient records. Results We included 157 patients with SRV, median age 40.6 [33.1; 46.8] years, 57% male. 133 (85%) patients had NYHA functional class 1-2 and 24 (15%) NYHA class 3-4. Patients with NYHA class 3-4 were older, had larger SRV and subpulmonary LV with poorer function and higher BNP level (Table, Figure A). LV fractional area change (FAC) had higher sensitivity and specificity in differentiation of patients with severe heart failure than SRV FAC (Figurel B) with LV FAC cut-off value 100 ng/l. LV end-diastolic diameter and area, MAPSE and FAC significantly correlated with BNP level (p In Multivariate Cox regression analysis LV FAC and RV FAC were the only independent associates of NYHA class 3-4 (HR 0.69 [95%CI 0.55-0.86], p = 0.001 and HR 0.71 [95%CI 0.55-0.93], p = 0.012, respectively), while age, degree of tricuspid regurgitation and BNP were not. Conclusions Subpulmonary LV dysfunction is strongly associated with NYHA class 3-4 heart failure in patients with SRV. LV FAC is more accurate than SRV FAC in predicting heart failure symptoms. Subpulmonary LV should be accurately assessed in all SRV patients and be taken into account in clinical decision making and timing for interventions. Characteristics of 157 patients with SRV Parameter NYHA Class 1-2 (N = 133) NYHA Class 3-4 (N = 24) P value Age, years 39.1 (31.9; 45.7) 46.5 (43.9; 58.1) Abstract P679 Figure.

Introduction: This prospective study evaluated a calcineurin inhibitor-free graft-versus-host disease (GVHD) prophylaxis regimen of ruxolitinib in combination with post-transplant cyclophosphamide (PTCy). Patents and Methods: Twenty patients with primary or secondary myelofibrosis were prospectively enrolled. Reduced intensity conditioning was performed, followed by allogeneic stem cell transplantation from related (n = 7) or unrelated (n = 13) donors. GVHD prophylaxis included only PTCy and ruxolitinib (45 mg) from day–7 to day–2, and 15 mg from day+5 to day+100. This trial was registered at www.clinicaltrials.gov as #NCT02806375. Results: Primary engraftment was documented in 17 patients. One patient experienced primary graft failure and 2 died before engraftment. Eleven patients demonstrated severe poor graft function (SPGF), which required ruxolitinib dose reduction. The regimen was well tolerated, with grade 3–4 non-haematological toxicity in 30%, viral reactivation in 45%, and severe sepsis in 15% of patients. The incidence of acute GVHD grade II–IV was 25%, grade III-IV GVHD was 15%, and moderate chronic GVHD was 20%, with no severe cases. Only 2 patients required systemic steroids. Haematological relapse was documented in 1 patient. Two-year non-relapse mortality was 15%, 2-year overall survival was 85%, and 2-year event-free survival was 72%. Conclusion: GVHD prophylaxis with PTCy and ruxolitinib is associated with low toxicity, good acute and chronic GVHD control, and low relapse incidence. However, the relatively high rate of SPGF should be taken into account. SPGF could possibly be mitigated by ruxolitinib dose reduction.

Objective. To assess the diagnostic value of assaying immunoglobulin (IgG) light chains at the onset of multiple sclerosis (MS). Materials and methods. A total of 226 patients took part in the study; group 1 (n = 111) were patients with clinically isolated syndrome (CIS) with development to MS within the first two years; group 2 (n = 49) were patients with CIS who did not progress to MS in the first two years; group 3 (n = 20) consisted of patients with inflammatory diseases of the central nervous system. The reference group (group 4, n = 46) consisted of patients with noninflammatory CNS diseases. The following immunological indicators were assessed in the patients: the clonal nature of cerebrospinal fluid (CSF) IgG and the concentrations of free ϰ and λ light chains in the CSF and their ratio. Results. Synthesis of free light chains was significantly greater in group 1 than groups 2 and 4. Free light chain synthesis in group 3 was significantly greater than that in groups 2 and 4 but was not significantly different from that in group 1. Free light chain production was significantly greater in patients with oligoclonal IgG synthesis than in patients without oligoclonal synthesis. The level of production of free light chains in patients of group 1 was significantly greater than that in group 2, regardless of whether or not oligoclonal IgG was produced. The most valuable diagnostic markers were the concentration and the coefficient of CSF:serum concentrations of κ light chains. Use of these parameters along with assessment of the clonality of IgG synthesis produced a 50% reduction in number of false negative results. Independently of other factors, increases in κ chain levels led to a 9.718-fold increase in the probability of a diagnosis of MS. Conclusions. Assay of free light chains as a lab marker increases the accuracy of diagnoses of MS and provides an indirect evaluation of the risk that CIS will progress to complete MS in the next two years.

Multimodality imaging in cardiology, and particularly congenital heart disease, has evolved into a critical tool, essential for clinical decision-making and management. Understanding the strengths and weaknesses of each imaging modality allows for timely and accurate diagnosis, enables their complementary use in answering specific clinical questions, facilitates management and prevents overuse of cardiovascular imaging ensuring the most appropriate and cost-effective diagnostic strategy for each patient. We provide herewith an expert consensus on the role of different cardiovascular imaging modalities in the assessment of the atrial septal defect and its haemodynamic consequences in adults, highlighting each modality's strengths and weaknesses, and clarifying how they are best applied in various clinical settings.

Background: Tuberculosis is a granulomatous disease of infectious origin, etiology factor of it is M.Tuberculosis. M.Tuberculosis is known to induce autoimmune processes because of mimicry of bacterial proteins with autoantigens. Recently the attention of scientist was attracted to protein vimentin, that could be an autoantigen after micobaterial infection. The aim of the study is to measure the concentration of different autoantibodies to vimentin in patients with tuberculosis (TB) and different granulomatous lung diseases (GLD). Material and Methods: There were studied the serum samples of patients with TB (n=28), a group of GLD (n=30), that included 15 patients with granulomatous polyangiitis and 15 with various alveolites, and a control group (n=40) (healthy subjects). The level of antibodies to modified citrullinated vimentin (anti-MCV) and to cyclic citrullinated peptide (anti-CCP) were measured with ELISA. Statistical analysis was performed with the Microsoft Office software and GraphPad Prism 6. Supported by Grant (contract №14.W03.31.0009 of 13.02.2017). Results: High level of anti-MCV was found in all groups, but more frequently in patients with TB in 60.7% cases (17/28) with the significant difference with group of GLD and healthy subjects (p=0,0003 vs. p=0.0002). High level of anti-CCP wasn’t identified in the studied groups. Conclusions: High concentration of anti-MCV is more common for patients with TB, while anti-CCP has no significance for all studied lung diseases. Absence of anti-CCP can be evidence, that citrullination of vimentin is not necessary for development of autoimmune reaction in tuberculosis patients.

Chronic obstructive pulmonary disease (COPD) is multifactorial disease, which is characterized by airflow limitation and can be provoked by genetic factors, including carriage of the PiZ allele of the protease inhibitor (Pi) gene, encoding alpha-1 antitrypsin (A1AT). Both homozygous and heterozygous PiZ allele carriers can develop COPD. It was found recently that normal A1AT regulates cytokine levels, including IL-17, which is involved in COPD progression. The aim of this study was to determine whether homozygous or heterozygous PiZ allele carriage leads to elevated level of IL-17 and other proinflammatory cytokines in COPD patients. Materials and Methods. Serum samples and clinical data were obtained from 44 COPD patients, who included 6 PiZZ, 8 PiMZ, and 30 PiMM A1AT phenotype carriers. Serum concentrations of IL-17, IL-6, IL-8, IFN-γ, and TNF-α were measured by the enzyme-linked immunosorbent assay (ELISA). All A1AT phenotypes were verified by narrow pH range isoelectrofocusing with selective A1AT staining. A turbidimetric method was used for quantitative A1AT measurements. Results. COPD patients with both PiZZ and PiMZ phenotypes demonstrated elevated IL-17 and decreased IFN-γ levels in comparison to patients with the PiMM phenotype of A1AT. Thereafter, the ratio IL-17/IFN-γ in PiZZ and PiMZ groups greatly exceeded the values of the PiMM group. Homozygous PiZ allele carriers also had significantly higher levels of IL-6 and lower levels of IL-8, and IL-6 values correlated negatively with A1AT concentrations. Conclusions. The presence of the PiZ allele in both homozygous and heterozygous states is associated with altered serum cytokine levels, including elevated IL-17, IL-17/IFN-γ ratio, and IL-6 (only PiZZ), but lower IFN-γ and IL-8.

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-FLCCSF/75-k-FLCCSF; 25-λ-FLCCSF/75-λ-FLCCSF; 25-Q-k/75-Q-k; 25-Q-λ/75-Q-λ). We found statistically significant difference of NBV and GMV between 25-k-FLCCSF and 75-k-FLCCSF 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.

Alpha-1-antitrypsin (A1AT) exerts a wide spectrum of protective effects, being focused on reduction of secondary injury in inflammation. Moreover, A1AT inhibits some serine proteases, and down-regulates production of proinflammatory cytokines. A number of known A1AT phenotypes is accompanied by affection of cytokine profile in inflammatory processes, thus increasing the risk of disorders associated with A1AT deficiency. The aim of our study was to evaluate cytokine profiles in the patients with different A1AT phenotypes. Were collected eighty-six blood sera from the persons with suspected A1AT deficiency. The A1AT phenotypes and concentrations were determined in these samples. The patients were divided into four groups, depending on their A1AT variants, i.e., PiMM, PiZZ, PiMZ and rare A1AT phenotypes. The serum levels of IFN γ , TNF α , IL-6, IL-8, and IL-17 were measured in these groups by means of ELISA technique. The mean levels of IL-6 comprised 73.52±4.363 pg/ml in the patients with PiZZ phenotype, being higher than in cases of PiMM phenotype (45.61±8.01 pg/ml, p < 0.05). The IL-17 levels were also found to be increased in the groups with PiZZ and PiMZ phenotypes, as compared with PiMM phenotype (p < 0.001). The mean IL-17 values in the samples with PiZZ, PiMZ, and PiMM phenotypes were 80.13±13.56 pg/ml, 106.7±26.28 pg/ml and 42.73±18.52 pg/ml, respectively. Meanwhile, there were no significant differences in IL-8, IFN γ and TNF α levels among different A1AT phenotypes. The results of this study let us conclude that the cytokine imbalance may be crucial to onset of diseases associated with A1AT deficiency.

There is an opinion, that the local inhibition of hypoxia-inducible factor-1α (HIF-1α) in lung may represent a therapeutic strategy for the treatment of inflammatory pulmonary diseases. Aim: to evaluate the modifying effect of cyclooxygenase-2 (COX-2) inhibition on lung inflammation and change of HIF-1α in COPD model. Methods: Model of COPD was induced in rats by nitrogen dioxide (15-19 ppm) exposure: three 30-min exposures/day with 30-min intervals for 60 days. Celecoxib (C) was used as a COX-2 inhibitor. From 30th to 60th day rats of 1st group received C via esophageal probe, rats of 2nd group (control) received 0,9% NaCl. 3rd group was intact. Bronchoalveolar lavage fluid (BALF) cytogram was determined. The levels of COX-2, HIF-1α, IL-17, surfactant protein D (SP-D) were measured in BALF by ELISA. Results: Treatment with C decreased COX-2 level in BALF: 18,8±2,2 vs. 26,5±2,3 pg/ml in control group, p Conclusion: The inhibition of COX-2 had a supressive effect on lung inflammation. It can be assumed that COX-2-dependent mechanism is involved in the inhibition of HIF-1α signalling, that can contribute to restoring the structure of bronchial epithelium.

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.

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.

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 contribution of mast cells (MCs) to inflammatory response and lung remodeling in COPD is not well documented. Aim: to assess the effect of MC degranulation blockade on inflammatory response outcome and lung tissue structure in COPD model. Methods: Model of COPD was induced in rats by NO 2 (15-19 ppm) exposure: 1,5-2 h/day for 60 days. Sodium cromoglicate (SC, Aventis) was used as MC membrane stabilizer. From 30th to 60th day one group was inhaled with SC before NO 2 exposure, control group received 0.9% NaCl. Lung sections were stained with H&E and toluidine blue for MCs. Bronchoalveolar lavage fluid (BALF) cytogram was determined. The levels of mast cell tryptase (MCT) and chymase (MCC), TNFa, surfactant protein B (SP-B) were measured in BALF by ELISA. Results: A lot of MCs, inflammatory infiltration, foci of emphysema were revealed in control lung tissue. The BALF levels of TNFa, SP-B, MCT and MCC increased respectively 10-, 2-, 6- and 3-fold (p Conclusion: The results confirm the involvement of MCs in the development of airway inflammation. Prevention of MC degranulation reduces the activity of the airway inflammation and severity of lung tissue remodeling in rats with COPD model.

A characteristic feature of COPD is systemic inflammation. The migration of neutrophils from the bloodstream in the center of inflammation is regulated by a number of adhesion molecules. The aim of the study was to determine the amount of protein markers of endothelial dysfunction in the blood of patients with moderate and severe COPD, with different types of disturbances of the microcirculation: predominantly upper lungs, lower lungs, diffuse type. Materials and methods: 114 males from 53 to 70 years old; 54 with moderate COPD, 60 patients with a severe course were examined by means of single photon emission computed tomography (SPECT). The level of adhesion molecules was detected by ELISA method. Results: In all patients, regardless of the severity of the process and the type disturbances of microcirculation, increase of endothelin index (p Conclusion: With the progression of the inflammatory process the number of endothelial dysfunction marker proteins is increasing in patients with lower lobe and diffuse type, characterized with increased production and release of several adhesion molecules and increase of endothelial dysfunction.

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.

Right heart failure is a complex clinical syndrome, which includes structure and/or function alterations of the right heart circulatory system leading to suboptimal delivery of blood flow to the pulmonary circulation and/or elevated venous pressures at rest and/or with exercise. Variety of underlying conditions may contribute to the development of right heart failure with the left ventricular pathology and pulmonary hypertension remaining the primary reasons. Recent recognition of the right ventricular (RV) dysfunction as an important predictor of cardiovascular morbidity and mortality in various conditions highlighted a need in a more comprehensive understanding of RV anatomy, physiology, pathophysiology and development of management strategies. These include early diagnosis of RV dysfunction, judicious fluid management, decrease of afterload, improvement of myocardial contractility, as well as identification and treatment of the underlying cause of right heart failure. Development of RV-specific diagnostic and treatment methodologies should be considered one of the primary aims of future research.

In patients with heart failure, right ventricular (RV) function is an independent predictor of cardiovascular morbidity and mortality. However, non-invasive assessment of the RV is a challenging task due to its complex anatomy and location in the chest.Moreover, the high load dependency of RV function can also lead to inaccurate or misleading interpretation of intrinsic RV function parameters if they are taken in isolation form RV pre- and afterload conditions. No single imaging modality is able to provide a comprehensive assessment of RV global and regional functions, mechanics, shape and tissue structure. Accordingly, a multimodality and multiparameteric approach is recommended. The following chapter summarizes currently available data on the role of non-invasive imaging techniques in the assessment of RV performance, their advantages, limitations and pitfalls in heart failure patients, with an emphasis on the relative merits of newer imaging parameters and practical approach to data acquisition and analysis.

Aim: to reveal the role of biomarkers in the progression of OILD. Methods: 13 pneumoconiosis (PC), 26 exogenous allergic alveolitis (EAA) and 20 exogenous toxic alveolitis (ETA) patients (mean age 54,8±0,7 yrs, 59,4±2,5 yrs. and 57,1±2,1 yrs. correspondingly) were investigated. Exposition factors in PC were silica (0,7), welding aerosols (0,3) 59,4±2,5, ETA were metals (0,15), irritants (0,15), drugs (0,4), dyes (0,3); in EAA – animals and birds (0,25), dyes (0,4), antibiotics (0,35). The blood levels of CC16, Alveomucin (Alv) and KL6 were detected by ELISA methods. Results: Clinical, CT signs, lung function parameters proved the activity of the disease in EAA-, ETA-patients. The progression/remission of alveolites was observed in 15/12 cases of ETA, in 14/6 cases of EAA correspondingly. The level of Alv, KL6 and CC16 were significant higher in active EAA (p Conclusion: Alv, KL6 and CC16 may be useful in evaluation of the activity of alveolitis and in differential diagnosis with PC. In alveolitis remission, Alv is more preferable as the marker of fibrosis in PC and ETA. CC16 as injury marker is in value only for the disease activity, but not in PC diagnostics.

To evaluate the diagnostic value of determination of free immunoglobulin light chains (IgG) in the debut of multiple sclerosis (MS).Data from 226 patients, including 111 patients with clinically isolated syndrome with conversion to multiple sclerosis within the first 2 years of the disease (group 1), 49 patients with clinically isolated syndrome who did not develop multiple sclerosis within the first 2 years of the disease (group 2), 20 patients with other inflammatory diseases of the central nervous system (group 3) were analyzed. The control group consisted of 46 patients with non-inflammatory diseases of the central nervous system. The clonality of immunoglobulins in the CSF, concentration of kappa and lambda free light chains and their ratio were studied.Concentrations of free light chains were significantly higher in the first group in comparison with group 2 and the control group, but didn't differ from group 3. In group 3, concentrations of free light chains were significantly higher compared to group 2 and controls. In oligoclonal-positive patients with clinically isolated syndrome (groups 1 and 2), concentrations of kappa and lambda free light chains were significantly higher than in oligoclonal-negative patients. The production of free light chains in patients from the first group was considerably higher than in group 2 regardless of the oligoclonal status. The concentration of kappa chains and quotient of kappa free light chains in the CSF had the best diagnostic characteristics. Their use, along with the evaluation of IgG clonality, reduced the risk of false-negative results by 50%. Regardless of other factors, elevated concentrations of kappa chains increase the likelihood of MS diagnosis by 9.718 times.The use of free light chains as a laboratory marker can increase the accuracy of MS diagnosis. These markers can help indirectly assess the risk of transformation of a clinically isolated syndrome into definite multiple sclerosis within the first 2 years of disease.Цель исследования. Оценка диагностической значимости определения свободных легких цепей иммуноглобулинов (IgG) в дебюте рассеянного склероза (РС). Материал и методы. В исследовании участвовали 226 пациентов; 1-я группа (n=111) - пациенты с клинически изолированным синдромом (КИС) с переходом в РС в течении первых 2-х лет, 2-я (n=49) - пациенты с КИС, который не трансформировался в РС в течении первых 2-х лет, 3-я (n=20) - пациенты с воспалительными заболеваниями центральной нервной системы. Группу сравнения (4-я; n=46) составили пациенты с невоспалительными заболеваниями ЦНС. У пациентов были изучены следующие иммунологические показатели: клональность IgG в цереброспинальной жидкости (ЦСЖ), концентрация свободных легких цепей каппа и лямбда в ЦСЖ и их соотношение. Результаты. Обнаружено, что синтез свободных легких цепей значительно выше в 1-й группе, чем во 2-й и 4-й. В 3-й группе синтез свободных легких цепей был значительно выше, чем во 2-й и 4-й группах, хотя значимо не отличался от значений в 1-й группе. У пациентов с олигоклональным синтезом IgG продукция свободных легких цепей была значительно выше, чем у пациентов без олигоклонального синтеза. Уровень продукции свободных легких цепей у пациентов из 1-й группы был значимо выше, чем во 2-й, вне зависимости от продукции олигоклональных IgG. Также было показано, что наиболее ценными диагностическими маркерами являются концентрация и коэффициент концентрации каппа легких цепей в ЦСЖ. Их использование вместе с оценкой клональности синтеза IgG на 50% уменьшало количество ложноотрицательных результатов. Вне зависимости от других факторов повышенные значения каппа цепей в 9,718 раза увеличивали вероятность диагноза РС. Вывод. Показано, что использование определения свободных легких цепей в качестве лабораторного маркера может повышать точность диагностики РС, а также дает возможность косвенно оценить риск перехода КИС в достоверный РС в течении последующих 2-х лет.

Syncope may develop in 9-35% of patients with pulmonary embolism (PE). Despite its severity and importance, the prognostic value of syncope in PE is unclear. We aimed to assess the value of syncope in patients with high-to-intermediate risk PE.A total of 117 patients (62 males and 55 females, median age 51,86 ± 13,4 years) were enrolled into the study. According to the presence of syncope at the onset of PE, all patients were divided into two groups: the syncope group (SG) comprised 35 patients (48.8 ± 15.5 years, male 54.3%) who experienced at least one syncopal episode. The remaining 82 patients (53.4 ± 12.6 years, male 42.7%) without syncope comprised the control group (CG).The main predisposing risk factors of PE were the same except fewer recurrent episodes of PE (8.5 vs. 24.5% in patients from SG (p=0.048). Clinical probability of PE according to the Revised Geneva and Wells scores was high almost in every second patient in both groups (p=NS). There were twice as many patients with a high risk of fatal outcome among patients with syncope in comparison with CG patients (45.7 vs. 25.6%, respectively, p=0.032). Massive PE on computed tomography scans was found again significantly more frequently in patients with syncope (60 vs. 39%, p=0.036). The vast majority (60%) of patients with a history of syncope were treated by thrombolytic therapy (21/35) vs. only 29% of patients without syncopal events (24/82; p=0.001). In-hospital mortality was higher in patients with syncope than the control group (14.2 vs. 8.5%, p=NS).The history of syncope in patients with suspected PE should be considered as a possible criterion of high risk of fatal complications of in-hospital period due to frequent embolism of the pulmonary trunk and its main branches. The use of thrombolytic therapy showed a tendency in improving outcomes.

Episodes of transient loss of consciousness (TLOC) are commonly due to syncope or epileptic seizures. The distinction between both entities on clinical grounds and eyewitness accounts can be challenging and is often hampered by similar clinical features. We briefly summarize syncope-related symptoms and present the case of a female patient who suffered from TLOC episodes due to both reflex syncope and epileptic seizures. Seizure-induced syncope is a rare complication particularly of non-generalized temporal lobe seizures and may be suspected in people with epilepsy who report new semiological features with sudden onset of atonia, TLOC and seizure-related falls. We review epidemiological, clinical and electroencephalographic aspects of seizure-related asystole and syncope and discuss their clinical relevance. The implantation of a cardiac pacemaker appears to efficiently prevent seizure-related falls and consecutive injuries and is an important treatment option if full seizure-control cannot be achieved in these patients. We describe a second case of a patient with refractory temporal lobe epilepsy and seizure-related syncope which ceased after the implantation of a cardiac pacemaker.

Background and objectiveIn this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS).MethodsWe compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients.ResultsThe levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056).ConclusionThe concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression.