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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.

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.

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. ispartof: EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING vol:23 issue:7 pages:885-897 ispartof: location:England status: published

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.

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.

AimsWe aimed to confirm that three-dimensional echocardiography (3DE)-derived right ventricular (RV) ejection fraction (EF) is a more robust predictor of adverse cardiopulmonary outcomes than the conventional echocardiographic parameters.Methods and ResultsWe 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 (HR) were rescaled by the within-study standard deviations (SD) to represent standardized changes. Within each study, we calculated the ratio of HRs related to 1 SD reduction in RVEF versus TAPSE, or FAC, or FWLS, to quantify the predictive value of RVEF relative to the other metrics. These ratios of HRs were pooled using random-effects models.Ten independent studies were identified as suitable, including data on 1,928 patients with various cardiopulmonary conditions. Overall, 1 SD reduction in RVEF was robustly associated with adverse outcomes (HR: 2.64 [95% CI: 2.18 to 3.20], p2=65%, p=0.002). In studies reporting HRs for RVEF and TAPSE, FAC, or FWLS in the same cohort, RVEF had superior predictive value per SD reduction versus the other three parameters (vs. TAPSE, HR: 1.54 [95% CI: 1.04 to 2.28], p=0.031; vs. FAC, HR: 1.45 [95% CI: 1.15 to 1.81], p=0.001; vs. FWLS, HR: 1.44 [95% CI: 1.07 to 1.95], p=0.018).Conclusion3DE-derived RVEF has superior prognostic value compared with conventional RV indices, therefore, it might further refine the risk stratification of patients with cardiopulmonary diseases.Graphical AbstractAdded predictive value of three-dimensional (3D) echocardiography-derived right ventricular ejection fraction (RVEF) versus conventional metrics of RV systolic function on clinical outcomes: a meta-analysis of 10 studies. FAC: fractional area change, FWLS: free-wall longitudinal strain, HR: hazard ratio, SD: standard deviation, TAPSE: tricuspid annular plane systolic excursion

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

Background. Secondary hemophagocytic syndrome (SHPS) is a reaction of systemic hyperinflammation triggered by infectious, tumor, or autoimmune processes. With no immunosuppressive (modulating) therapy most patients die from multiple organ failure. Aim. To describe organ lesions characteristic of SHPS patients. Materials & Methods. The retrospective study included patients treated from June 2009 to June 2019. SHPS was diagnosed using HLH-2004 criteria and H-Score. The analysis focused on the incidence and character of lesions in lungs, central nervous system, liver, skin, and cardiovascular system. All patients with persistent fever received anti-infective treatment with broad-spectrum antibiotics in line with local hospital practice. Patients with collagenosis and tumors, which caused SHPS, received standard immunosuppressive and antitumor therapy, respectively. Results. The analysis covered the data of 91 patients (41 man and 50 women), median age was 58 years (range 2-90 years). SHPS was caused by hematological malignancies (n = 52; 57 %), infections (n = 11; 12 %), autoimmune diseases (n = 5; 6 %), and allogeneic hematopoietic stem cell transplantation (n = 13; 14 %). In 10 (11 %) patients no cause was identified. Immunosuppressive therapy was administered to 71 (78 %) patients. Overall survival was 27 % (median 15 days) with median follow-up for alive of 540 days (range from 7 days to 10 years). Clinically significant organ lesions were identified in 76 (83 %) patients. Most commonly SHPS was reported together with polyserositis, respiratory and hepatic disorders, and neurological symptoms from focal deficit to seizure status. Less often skin lesions (from macular rash to epidermolysis bullosa) and such cardiovascular disorders as arrhythmia and/or arterial hypotension were observed. The effective SHPS therapy resulted in restoration of organ functions. Conclusion. SHPS can cause respiratory disorders, polyserositis, different neurological disorders, cytopenia in patients with unexplained fever and cytolytic and/or cholestatic syndrome. Primary organ lesions as well as clinical and laboratory manifestations of SHPS may vary in different patients.

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

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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.

“We must accept finite disappointment but never lose infinite hope.”—Martin Luther King Jr. ([1][1]) The foregoing quotation holds true in the hearts of many immigrants who often navigate troubled waters in hopes of a better future. Traditionally, international medical graduates (IMGs) have

Supplemental Digital Content is available in the text., 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%], P45%), the anteroposterior component of total RVEF was a significant and independent predictor of outcome (hazard ratio, 0.960 [CI, 0.925–0.997], P

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.

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.

The predictive value of graft composition and plasma biomarkers on the outcome of allogeneic HSCT is well known for conventional GVHD prophylaxis based on calcineurin inhibitors with or without antithymocyte globulin. Currently, there is limited data whether these results could be translated to post transplantation cyclophosphamide (PTCy). The prospective extension cohort of NCT02294552 trial enrolled 79 adult patients with acute leukemia in CR. Twenty-six received matched-related bone marrow (BM) grafts with single-agent PTCy and 53 received unrelated peripheral blood stem cell graft (PBSC) with PTCy, tacrolimus, and MMF. The grafts were studied by the flow cytometry, and plasma samples were analyzed by ELISA. In the cluster and major component analysis, we determined that transplantation from donors with high content of CD3, NKT, and CD16-CD56 + subpopulations in the PBSC grafts was associated with poor immunological recovery and compromised event-free survival (50% vs. 80%, HR 2.93, p = 0.015) both due to increased relapse incidence and non-relapse mortality. The significant independent predictor of moderate and severe chronic GVHD was the high prevalence of and iNKT, Vβ11, and double-positive cells in the PBSC grafts from young donors (HR 2.75, p = 0.0483). No patterns could be identified for BM grafts and for plasma biomarkers.

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.

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.

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.), Central Illustration

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.