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Objective: It remains unclear whether viral infections interfere with multiple sclerosis (MS) disease progression. We evaluated the prognostic role of antibody responses toward viruses determined at disease onset on long-term disease outcomes.Methods: Humoral immune responses against Epstein-Barr virus (EBV)-encoded nuclear antigen EBNA1, viral capsid antigen (VCA) and early antigen, and toward cytomegalovirus (HCMV), human herpesvirus 6 and measles were investigated in a cohort of 143 patients with MS for their association with long-term disability and inflammation disease outcomes.Results: Median (IQR) follow-up was 20 (17.2-22.8) years. In univariable analysis, increased HCMV levels were associated with a lower risk to Expanded Disability Status Scale 4.0 (HR 0.95; 95% CI 0.91 to 0.99; p=0.03), to develop a secondary progressive MS (HR 0.94; 95% CI 0.90 to 0.99; p=0.02) and to first-line treatment (HR 0.98; 95% CI 0.96 to 0.99; p=0.04). High HCMV IgG levels were associated with a longer time to first-line treatment (p=0.01). Increased immune responses against EBV-VCA were associated with higher risk for first-line (HR 1.45; 95% CI 1.12 to 1.88; p=0.005) and second-line treatments (HR 2.03; 95% CI 1.18 to 3.49; p=0.01), and high VCA IgG levels were associated with shorter time to first-line (p=0.004) and second-line (p=0.02) therapies. EBNA1-specific IgG levels correlated with disease severity (0.17; p=0.04) and with an increased relapse rate during follow-up (relapse rate 1.26; 95% CI 1.03 to 1.56; p=0.02) that remained stable in multivariable analysis.Conclusions: These results indicate that elevated immune responses against HCMV at disease onset have protective effects on long-term disability and inflammation disease outcomes. Our data also indicate that increased immune responses against EBV in early phases may influence long-term disease prognosis. [ABSTRACT FROM AUTHOR]

Infection by cytomegalovirus (HCMV) and Epstein–Barr virus (EBV) play a prognostic role in multiple sclerosis (MS).To explore whether humoral immune responses to HCMV and EBV at disease onset were associated with changes in serum and cerebrospinal fluid (CSF) levels of inflammatory and neurodegeneration biomarkers.Ninety-eight MS patients with a median follow-up of 20 years were included in the study. The levels of a panel of nine biomarkers were measured in serum (N = 60) and CSF (N = 61) samples of patients at the time of the first demyelinating event.Immune responses to HCMV inversely correlated with serum neurofilament light chain (sNfL) levels (rho = −0.367; p = 0.039). sNfL levels were reduced in patients with high immune responses to HCMV (p = 0.006). Elevated sNfL levels were associated with higher risk of Expanded Disability Status Scale (EDSS) 3.0 (p = 0.016), 4.0 (p = 0.009) and 6.0 (p = 0.003), and with higher risk of developing secondary progressive MS (p = 0.003) and to receive treatment (p = 0.032). Serum soluble CD21 levels were increased in patients with high immune responses to EBV nuclear antigen 1 (p = 0.020).High immune responses to HCMV are associated with limited disease progression and central nervous system (CNS) injury in MS patients. These findings reinforce the protective role of HCMV infection in MS. [ABSTRACT FROM AUTHOR]

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Aims Aortic dilation in bicuspid aortic valve (BAV) might extend to the proximal arch. Arch flow dynamics and their relationship with this segment dilation are still unexplored. Using 4D-flow cardiovascular magnetic resonance, we analysed flow dynamics in the arch for each BAV morphotype and their association with this segment dilation. Methods and results One hundred and eleven BAV patients (aortic diameters ≤55 mm, non-severe valvular disease), 21 age-matched tricuspid aortic valve (TAV) patients with dilated arch and 24 healthy volunteers (HV) underwent 4D-flow. BAV were classified per fusion morphotype: 75% right-left (RL-BAV), and per arch dilation: 57% dilated, mainly affecting the right-noncoronary (RN) BAV (86% dilated vs. 47% in RL-BAV). Peak velocity, jet angle, normalized displacement, in-plane rotational flow (IRF), wall shear stress, and systolic flow reversal ratio (SFRR) were calculated along the thoracic aorta. ANCOVA and multivariate linear regression analyses were used to identify correlates of arch dilation. BAV had higher rotational flow and eccentricity than TAV in the proximal arch. Dilated compared with non-dilated BAV had higher IRF being more pronounced in the RN-morphotype. RN-BAV, IRF, and SFRR were independently associated with arch dilation. Aortic stenosis and male sex were independently associated with arch dilation in RL-BAV. Flow parameters associated with dilation converged to the values found in HV in the distal arch. Conclusion Increased rotational flow could explain dilation of the proximal arch in RN-BAV and in RL-BAV patients of male sex and with valvular stenosis. These patients may benefit from a closer follow-up with cardiac magnetic resonance or computed tomography. [ABSTRACT FROM AUTHOR]

This study sought to ascertain whether patients with a bicuspid aortic valve (BAV) have an intrinsic alteration in regional aortic stiffness compared with patients with tricuspid aortic valve (TAV) and Marfan syndrome (MFS) patients with similar aortic sizes, as well as to assess the influence of ascending aorta (AAo) dilation on regional stiffness parameters in BAV patients. Imaging biomarkers as predictors of BAV, MFS, and degenerative AAo aneurysms in TAV patients (DA-TAV) are lacking. Biomechanical characterization has been proposed as a possible tool for further aneurysm stratification. A total 234 subjects (136 BAV, 44 MFS, and 18 DA-TAV patients and 36 healthy control subjects) were included. The cardiac magnetic resonance protocol comprised 4-dimensional flow to assess AAo and descending aorta (DAo) pulse wave velocities (PWVs) and double-oblique, 2-dimensional, steady-state free-precession cine cardiac magnetic resonance to compute aortic distensibility (AD). On adjusted analysis, nondilated BAV patients had similar PWV and AD as healthy control subjects in both AAo and DAo, whereas dilated BAV did not differ from DA-TAV. In contrast, AAo and DAo stiffness in MFS patients was markedly greater than in BAV patients, increasing slightly with dilation severity. AAo PWV showed a biphasic pattern in BAV patients: it first decreased and then increased throughout AAo dilation, with a clear turning point at 50 mm, whereas distensibility did not discern mildly dilated aorta. In multivariate analysis adjusted for clinical and demographic characteristics, only PWV was related to AAo dilation in BAV patients. The mechanical properties of AAo aneurysms are similar in BAV and TAV patients, whereas MFS patients have a stiffer aorta. Aortic stiffness strongly depends on dilation severity. AAo PWV resulted in a potentially clinically useful biphasic trend with respect to aneurysm diameter, whereas distensibility did not discern mildly dilated aorta. Beyond clinical risk factors, PWV but not AD was independently related to AAo dilation in BAV patients. [ABSTRACT FROM AUTHOR]

Background: Chagas disease (CD) is a major cause of cardiomyopathy in Latin America, and migration movements have now spread the disease worldwide. However, data regarding Chagas cardiomyopathy (CC) and the usefulness of echocardiography in non endemic countries are still scarce. Methods and results: We selected 485 patients in the chronic phase of CD from two Spanish settings. Data from physical examination, electrocardiogram (EKG), x-ray, and two dimensional transthoracic echocardiogram were recorded. Trypanosoma cruzi DNA was assessed by PCR in peripheral blood. Patients were stratified according to the Kuschnir classification and a combination of echocardiogram and electrocardiogram findings. Patients mainly came from Bolivia (459; 94.6%). One hundred and forty three patients (31.5%) had at least one electrocardiogram abnormality. Twenty seven patients (5.3%) had an abnormal echocardiography. Patients with abnormal echocardiography were older (47 (IQR 38–57) years vs 41 (IQR 38–57) years); p = 0.019) and there was a greater proportion of males (66.7% vs 29.7%); p<0.001). Among echocardiographic variables, diastolic dysfunction was associated with poor cardiac status. In the multivariate analysis, abnormal EKG and gender were associated with abnormal echocardiography. Echocardiography may be spared for males under 30 and females under 45 years old with normal EKG as the likelihood of having an abnormal echocardiography is minimal. Association between T. cruzi DNA in the peripheral blood and cardiac involvement was not observed. Conclusion: CC rates in the studied population are low. Age and sex are important determinants for the development of CC, and with the EKG should guide echocardiogram performance. [ABSTRACT FROM AUTHOR]

Objective: Bicuspid aortic valve (BAV) is associated with early valvular dysfunction and proximal aorta dilation with high heterogeneity. This study aimed to assess the determinants of these complications.Methods: Eight hundred and fifty-two consecutive adults diagnosed of BAV referred from cardiac outpatient clinics to eight echocardiographic laboratories of tertiary hospitals were prospectively recruited. Exclusion criteria were aortic coarctation, other congenital disorders or intervention. BAV morphotype, significant valve dysfunction and aorta dilation (≥2 Z-score) at sinuses and ascending aorta were established.Results: Three BAV morphotypes were identified: right-left coronary cusp fusion (RL) in 72.9%, right-non-coronary (RN) in 24.1% and left-non-coronary (LN) in 3.0%. BAV without raphe was observed in 18.3%. Multivariate analysis showed aortic regurgitation (23%) to be related to male sex (OR: 2.80, p<0.0001) and valve prolapse (OR: 5.16, p<0.0001), and aortic stenosis (22%) to BAV-RN (OR: 2.09, p<0.001), the presence of raphe (OR: 2.75, p<0.001), age (OR: 1.03; p<0.001), dyslipidaemia (OR: 1.77, p<0.01) and smoking (OR: 1.63, p<0.05). Ascending aorta was dilated in 76% without differences among morphotypes and associated with significant valvular dysfunction. By contrast, aortic root was dilated in 34% and related to male sex and aortic regurgitation but was less frequent in aortic stenosis and BAV-RN.Conclusions: Normofunctional valves are more prevalent in BAV without raphe. Aortic stenosis is more frequent in BAV-RN and associated with some cardiovascular risk factors, whereas aortic regurgitation (AR) is associated with male sex and sigmoid prolapse. Although ascending aorta is the most commonly dilated segment, aortic root dilation is present in one-third of patients and associated with AR. Remarkably, BAV-RL increases the risk for dilation of the proximal aorta, whereas BAV-RN spares this area. [ABSTRACT FROM AUTHOR]

Purpose: To identify entry tear variables that are related to adverse clinical events by using CT angiography (CTA) performed during the subacute phase of aortic dissection., Materials and Methods: In this prospective study conducted from January 2000 to December 2013, participants with an aortic dissection with a patent false lumen and no comorbidities underwent CTA during the subacute phase. Participants were followed up for a survival analysis to assess the time to an adverse aortic event (AAE). The maximum aortic diameter (MAD), proximal and distal tear areas and difference between these areas, and partial false-lumen thrombosis were assessed by using Cox regression for adverse events., Results: Seventy-two participants (mean age, 55 years ± 12 [standard deviation]; 55 men) were evaluated: 47 were surgically treated (type A aortic dissection) and 25 were medically treated (type B aortic dissection). Twenty-two participants had an AAE manifest during follow-up (9.22 years ± 5.78): There were 18 elective surgeries for aneurysmal degeneration, two emergent surgeries for acute aortic syndrome, and two aortic condition-related deaths. A categorical model composed of genetic aortic disease (GAD) (hazard ratio [HR], 3.4 [95% CI: 1.2, 9.9]; P = .02), MAD greater than 45 mm (HR, 6.1 [95% CI: 2.4, 15.8]; P < .001), and tear dominance (HR, 5.2 [95% CI: 2.1, 13]; P < .001), defined as an absolute tear area difference of greater than 1.2 cm 2 , was used to stratify participants into three risk groups: low, without any risk factors (57% [41 of 72] and 7% [three of 41] had events); intermediate, with one risk factor (31% [22 of 72] and 50% [11 of 22] had events); and high, with two or more risk factors (13% [nine of 72] and 89% [eight of nine] had events; log rank P < .001)., Conclusion: Tear dominance demonstrated at CTA performed in the subacute phase of aortic dissection was related to long-term adverse events. Participants without GAD, dominant tears, or MAD greater than 45 mm had conditions that were safely managed with optimal medical treatment and imaging follow-up. Keywords: CT Angiography, Vascular, Aorta, Dissection Supplemental material is available for this article. © RSNA, 2021See also commentary by Fleischmann and Burris in this issue., Competing Interests: Disclosures of Conflicts of Interest: H.C.C. disclosed no relevant relationships. G.B. disclosed no relevant relationships. A.R. disclosed no relevant relationships. J.R.P. disclosed no relevant relationships. G.T. disclosed no relevant relationships. R.R. disclosed no relevant relationships. S.B. disclosed no relevant relationships. N.Z. disclosed no relevant relationships. J.R.J. disclosed no relevant relationships. A.S.A. disclosed no relevant relationships. M.E. disclosed no relevant relationships. A.E. disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Objectives: The optimal myocardial protective solution in the neonatal arterial switch operation remains controversial. The aim of this study was to demonstrate that Bretschneider's histidine-tryptophan-ketoglutarate crystalloid solution (Custodiol) offers protection at least similar to that of cold blood cardioplegia., Methods: Patients who underwent the neonatal arterial switch operation with Custodiol between January 2016 and December 2018 (n = 23) were compared with an historical cohort from August 2010 to December 2015 in which cold blood cardioplegia was used (n = 41). A linear mixed-effect model for repeated measures was performed to test the recovery of myocardial function based on inotropic and vasoactive inotropic scores, cardiac enzyme release and left ventricular ejection fraction., Results: Patients in the cold blood cardioplegia group had higher inotropic scores in the first 24 h (0 h, P = 0.001 and 24 h, P = 0.006) and higher vasoactive inotropic scores in the first 72 h (0 h, 24 h and 48 h, P < 0.001; 72 h, P = 0.012). Cardiac troponin-I concentrations were higher in the cold blood cardioplegia group at postoperative hours 1-72 (1 h, 6 h, 12 h and 24 h, P < 0.001; 48 h, P = 0.001 and 72 h, P = 0.003). Creatinine-kinase-MB concentrations were higher in the cold blood cardioplegia group at postoperative hours 1-24 (1 h, 6 h and 12 h, P < 0.001; 24 h, P = 0.042). The left ventricular ejection fraction was higher in the Custodiol group just after the operation (P = 0.005), at 24 h (P = 0.001) and on the first day without inotropic support (P = 0.011)., Conclusions: Neonatal myocardium protected with Custodiol during the arterial switch operation presented optimal ventricular function recovery with less inotropic support and less myocardial damage compared with cold blood cardioplegia., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Aortic dilation in bicuspid aortic valve (BAV) might extend to the proximal arch. Arch flow dynamics and their relationship with this segment dilation are still unexplored. Using 4D-flow cardiovascular magnetic resonance, we analysed flow dynamics in the arch for each BAV morphotype and their association with this segment dilation., Methods and Results: One hundred and eleven BAV patients (aortic diameters ≤55 mm, non-severe valvular disease), 21 age-matched tricuspid aortic valve (TAV) patients with dilated arch and 24 healthy volunteers (HV) underwent 4D-flow. BAV were classified per fusion morphotype: 75% right-left (RL-BAV), and per arch dilation: 57% dilated, mainly affecting the right-noncoronary (RN) BAV (86% dilated vs. 47% in RL-BAV). Peak velocity, jet angle, normalized displacement, in-plane rotational flow (IRF), wall shear stress, and systolic flow reversal ratio (SFRR) were calculated along the thoracic aorta. ANCOVA and multivariate linear regression analyses were used to identify correlates of arch dilation. BAV had higher rotational flow and eccentricity than TAV in the proximal arch. Dilated compared with non-dilated BAV had higher IRF being more pronounced in the RN-morphotype. RN-BAV, IRF, and SFRR were independently associated with arch dilation. Aortic stenosis and male sex were independently associated with arch dilation in RL-BAV. Flow parameters associated with dilation converged to the values found in HV in the distal arch., Conclusion: Increased rotational flow could explain dilation of the proximal arch in RN-BAV and in RL-BAV patients of male sex and with valvular stenosis. These patients may benefit from a closer follow-up with cardiac magnetic resonance or computed tomography., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Benznidazole is the drug of choice for Chagas disease. The major drawback of this drug is the high adverse events rate, being cutaneous reactions the most frequent one, leading to definitive withdrawal of treatment in 15%-30% of patients., Methods: Prospective observational study where adult Chagas disease patients accepting to receive benznidazole (100 mg/8 hours for 60 days) were included. The objective was to characterize the skin toxicity of benznidazole in patients with Chagas disease, determine the serum cytokine profile, and evaluate the potential association with specific HLA alleles and benznidazole concentration. Serum cytokine levels were measured at day 0, 15, and 60 of treatment. Class I and II HLA alleles were determined. When cutaneous reaction was detected, a skin biopsy was performed. Serum benznidazole concentration was determined at the time of cutaneous reaction, or at day 15 of treatment., Results: Fifty-two patients were included, 20(38.5%) had cutaneous reaction, and median time of appearance was 9 days. Skin biopsies showed histopathological findings consistent with drug eruption. Patients with cutaneous drug-reaction had higher proportion of eosinophilia during treatment, and higher interleukin (IL)-5 and IL-10 serum concentrations at day 15 of treatment than those without cutaneous reaction. Treatment interruption (that included moderate-severe cutaneous reactions) was more frequent in patients carrying HLA-B*3505 allele (45.5% vs 15.4%, P = .033). No differences in benznidazole serum concentration were found., Conclusions: Benznidazole related cutaneous reaction rate is high, and it was produced by a delayed hypersensitivity reaction with a Th2 response. Carrying HLA-B*3505 allele could be associated with moderate-severe cutaneous reaction., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)