Objectives
Extrapulmonary manifestations of bronchiolitis have been previously studied, with some identifying right ventricle (RV) diastolic/systolic dysfunction. We hypothesized that severe cases of ...bronchiolitis would have cardiac dysfunction resulting an increase in N‐terminal pro‐hormone B‐type natriuretic peptide (NT‐proBNP) values and worse outcomes. Therefore, the objective was to evaluate the existence of cardiac dysfunction and to determine its association with severe bronchiolitis.
Methods
This prospective cohort study included children hospitalized for bronchiolitis under 1‐year old between January 2019 and March 2020. At admission, an echocardiography was performed and plasma levels of NT‐proBNP were measured. To analyze outcomes, the cohort was divided into two groups based on the need for positive pressure respiratory support (PPRS), and both were compared to healthy infants. Statistics: bivariant analysis, significant differences p < 0.05.
Results
One hundred eighty‐one patients were included; median age was 2 months. Seventy‐three patients required PPRS. Compared to controls, patients requiring PPRS showed worse RV systolic function, with lower tricuspid annular‐plane systolic excursion (p = 0.002) and parameters of worse right and left diastolic function (trans‐tricuspid E and A wave p = 0.004 and p = 0.04, respectively and tricuspid tissue doppler imaging TDI e′ p = 0.003, trans‐mitral E and mitral TDI a′ p = 0.02 and p = 0.005, respectively). An NT‐ProBNP greater than 3582 pg/dl predicts the need for longer necessity of PPRS in patients younger than 2 months.
Conclusions
In addition to the expected RV systolic dysfunction, patients with severe bronchiolitis have parameters of global diastolic worse function possibly secondary to intrinsic myocardial involvement. NT‐ProBNP values at admission had strong discriminatory power to predict worse outcomes.
Background During the SARS-CoV2 pandemic, there has been increase in hyperinflammatory presentation in previously healthy children with a variety of cardiac manifestations. Our objective is to ...describe the cardiac manifestations found in an international cohort of 55 pediatric cases with multi-system inflammatory syndrome (MIS-C) during the SARS-CoV2 pandemic. Methods and Results We reviewed data on previously healthy pediatric patients (≤18 years) with structurally normal hearts who presented at hospitals in the United States, United Kingdom, Spain and Pakistan with MIS-C and had consultation with a pediatric cardiologist. Data collected included demographics, clinical presentation, laboratory values, electrocardiographic abnormalities, echocardiographic findings and initial therapies. A total of 55 patients presented with MIS-C. Thirty-five patients (64%) had evidence of decreased left ventricular function, 17 (31%) had valvulitis, 12 (22%) with pericardial effusion and 11 (20%) with coronary abnormalities. Twenty-seven (49%) required ICU admission and 24 (44%) had evidence of shock. Eleven patients (20%) fulfilled complete Kawasaki disease criteria and had lower NT pro-BNP, D-dimer and ferritin levels compared with those who did not fulfill criteria. Electrophysiologic abnormalities occurred in 6 patients and included complete atrioventricular (AV) block, transient AV block and ventricular tachycardia. Conclusions We describe the first international cohort of pediatric patients with MIS-C during the SARS-CoV2 pandemic with a range of cardiac manifestations. This paper brings awareness and alertness to the global medical community to recognize these children during the pandemic and understand the need for early cardiology evaluation and follow-up.
In fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD), poor hemodynamic status is associated with worse neonatal outcome. It is not known whether EA/TVD fetuses with more favorable ...physiology earlier in gestation progress to more severe disease in the third trimester. We evaluated if echocardiographic indexes in EA/TVD fetuses presenting <24 weeks of gestation are reliable indicators of physiologic status later in pregnancy. This multicenter, retrospective study included 51 fetuses presenting at <24 weeks of gestation with EA/TVD and serial fetal echocardiograms ≥4 weeks apart. We designated the following as markers of poor outcome: absence of anterograde flow across the pulmonary valve, pulmonary valve regurgitation, cardiothoracic area ratio >0.48, left ventricular (LV) dysfunction, or tricuspid valve (TV) annulus Z-score >5.6. Median gestational age at diagnosis was 21 weeks (range, 18 to 24). Eighteen fetuses (35%) had no markers for poor hemodynamic status initially, whereas only 7 of these continued to have no markers of poor outcome in the third trimester. Nine of 27 fetuses (33%) with anterograde pulmonary blood flow on the first echocardiogram developed pulmonary atresia; 7 of 39 (18%) developed new pulmonary valve regurgitation. LV dysfunction was present in 2 (4%) patients at <24 weeks but in 14 (37%) later (p <0.001). The TV annulus Z-score and cardiothoracic area both increased from diagnosis to follow-up. In conclusion, progressive hemodynamic compromise was common in this cohort. Our study highlights that care must be taken in counseling before 24 weeks, as the absence of factors associated with poor outcome early in pregnancy may be falsely reassuring.
Ebstein anomaly and tricuspid valve dysplasia are rare congenital tricuspid valve malformations associated with high perinatal mortality. The literature consists of small, single-center case series ...spanning several decades. We performed a multicenter study to assess the outcomes and factors associated with mortality after fetal diagnosis in the current era.
Fetuses diagnosed with Ebstein anomaly and tricuspid valve dysplasia from 2005 to 2011 were included from 23 centers. The primary outcome was perinatal mortality, defined as fetal demise or death before neonatal discharge. Of 243 fetuses diagnosed at a mean gestational age of 27±6 weeks, there were 11 lost to follow-up (5%), 15 terminations (6%), and 41 demises (17%). In the live-born cohort of 176 live-born patients, 56 (32%) died before discharge, yielding an overall perinatal mortality of 45%. Independent predictors of mortality at the time of diagnosis were gestational age <32 weeks (odds ratio, 8.6; 95% confidence interval, 3.5-21.0; P<0.001), tricuspid valve annulus diameter z-score (odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P<0.001), pulmonary regurgitation (odds ratio, 2.9; 95% confidence interval, 1.4-6.2; P<0.001), and a pericardial effusion (odds ratio, 2.5; 95% confidence interval, 1.1-6.0; P=0.04). Nonsurvivors were more likely to have pulmonary regurgitation at any gestational age (61% versus 34%; P<0.001), and lower gestational age and weight at birth (35 versus 37 weeks; 2.5 versus 3.0 kg; both P<0.001).
In this large, contemporary series of fetuses with Ebstein anomaly and tricuspid valve dysplasia, perinatal mortality remained high. Fetuses with pulmonary regurgitation, indicating circular shunt physiology, are a high-risk cohort and may benefit from more innovative therapeutic approaches to improve survival.
Patients with heterotaxy syndrome (HS) have a range of anomalies and outcomes. There are limited data on perinatal outcomes after prenatal diagnosis. To determine the factors influencing perinatal ...and infant outcomes, we analyzed prenatal and postnatal variables in fetuses with HS from 1995 to 2011. Of 154 fetuses with HS, 61 (40%) had asplenia syndrome (ASP) and 93 (60%) had polysplenia syndrome (PSP). In the ASP group, 22 (36%) patients were elected for termination of pregnancy, 4 (10%) had fetal death, and 35 of 39 (90%) continued pregnancies were live born. In the PSP group, 12 (13%) patients were elected for termination of pregnancy, 5 (6%) had fetal death (4 with bradyarrhythmia), and 76 of 81 (94%) continued pregnancies were live born. Bradyarrhythmia was the only predictor of fetal death. In the live-born ASP group, 43% (15 of 35) died, 7 because of pulmonary vein stenosis, 4 postoperatively, and 4 because of noncardiac causes. In the live-born PSP group, 13% (10 of 76) died, 5 postoperatively, 2 from bradyarrhythmia, 1 from a cardiac event, and 2 from noncardiac causes. Pulmonary vein stenosis and noncardiac anomalies were independent risk factors for postnatal death. Only 8% of ASP patients achieved biventricular circulation, compared with 65% of PSP patients. In the live-born cohort, the 5-year survival rate was 53% for ASP and 86% for PSP. In conclusion, most PSP patients are currently alive with biventricular circulation in contrast with few ASP patients. Bradyarrhythmia was the only predictor of fetal death. Pulmonary vein stenosis and noncardiac anomalies were predictors of postnatal death.
Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia, we found that one third of live-born patients died before hospital ...discharge. We sought to further describe postnatal management strategies and to define risk factors for neonatal mortality and circulatory outcome at discharge. Methods and Results This 23-center, retrospective study from 2005 to 2011 included 243 fetuses with Ebstein anomaly or tricuspid valve dysplasia. Among live-born patients, clinical and echocardiographic factors were evaluated for association with neonatal mortality and palliated versus biventricular circulation at discharge. Of 176 live-born patients, 7 received comfort care, 11 died <24 hours after birth, and 4 had insufficient data. Among 154 remaining patients, 38 (25%) did not survive to discharge. Nearly half (46%) underwent intervention. Mortality differed by procedure; no deaths occurred in patients who underwent right ventricular exclusion. At discharge, 56% of the cohort had a biventricular circulation (13% following intervention) and 19% were palliated. Lower tricuspid regurgitation jet velocity (odds ratio OR, 2.3 1.1-5.0, 95% CI, per m/s;
=0.025) and lack of antegrade flow across the pulmonary valve (OR, 4.5 1.3-14.2;
=0.015) were associated with neonatal mortality by multivariable logistic regression. These variables, along with smaller pulmonary valve dimension, were also associated with a palliated outcome. Conclusions Among neonates with Ebstein anomaly or tricuspid valve dysplasia diagnosed in utero, a variety of management strategies were used across centers, with poor outcomes overall. High-risk patients with low tricuspid regurgitation jet velocity and no antegrade pulmonary blood flow should be considered for right ventricular exclusion to optimize their chance of survival.
Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic ...evaluation of left heart defects. A multicenter prospective cohort (2013−2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor β, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4−3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor β (normal heart median 15.5 ng/mL (6.8−21.4) vs. favorable outcome 51.7 ng/mL (13.8−73.9) vs. poor outcome 25.1 ng/mL (6.9−39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8−23.9) vs. favorable outcome 12.8 pg/mL (11.7−13.6) vs. poor outcome 11.0 pg/mL (8.8−15.4), p < 0.001). Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide (normal heart 508.0 pg/mL (287.5−776.3) vs. favorable outcome 617.0 pg/mL (389.8−1087.8) vs. poor outcome 1450.0 pg/mL (919.0−1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3−2715.8) vs. favorable outcome (1848.3 pg/mL (646.9−2313.6) vs. poor outcome 259.0 pg/mL (182.0−606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome.
There is no data regarding COVID-19 in Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients in Latin America.
The objective of this study was to describe the clinical ...characteristics and outcomes of patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with COVID-19.
RELACOEM is a longitudinal, strictly observational registry of MS and NMOSD patients who suffer COVID-19 and Dengue in LATAM. Inclusion criteria to the registry were either: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a COVID-19 polymerase chain reaction (PCR) test on a nasopharyngeal swab; or (2) COVID-19-typical symptoms (triad of cough, fever, and asthenia) in an epidemic zone of COVID-19. Descriptive statistics were performed on demographic and clinical variables. The cohort was later stratified for MS and NMOSD and univariate and multivariate logistic regression analysis was performed to identify variables associated with hospitalizations/intensive critical units (ICU) admission.
145 patients were included in the registry from 15 countries and 51 treating physicians. A total of 129 (89%) were MS patients and 16 (11%) NMOSD. 81.4% patients had confirmed COVID-19 and 18.6% were suspected cases. 23 (15.8%) patients were hospitalized, 9 (6.2%) required ICU and 5 (3.4 %) died due to COVID-19. In MS patients, greater age (OR 1.17, 95% CI 1.05 - 1.25) and disease duration (OR 1.39, 95%CI 1.14-1.69) were associated with hospitalization/ICU. In NMOSD patients, a greater age (54.3 vs. 36 years, p=<0.001), increased EDSS (5.5 vs 2.9, p=0.0012) and disease duration (18.5 vs. 10.3 years, p=0.001) were significantly associated with hospitalization/ICU.
we found that in MS patients, age and disease duration was associated with hospitalization and ICU admission requirement, while age, disease duration and EDSS was associated in NMOSD.
High-intensity interval training (HIIT) is considered one of the most effective methods for improving cardiorespiratory and metabolic functions. However, it is necessary to clarify their effects on ...neurophysiological responses and coginitive functioning. Thus, this study aimed to determine the effects of an acute bout of HIIT on neurocognitive and stress-related biomarkers and their association with working memory (WM) capacity in healthy young adults. Twenty-five male college students performed a single bout of HIIT consisting of 10 × 1 min of cycling at their VO
peak power output. Plasma Brain-Derived Neurotrophic Factor (BDNF) and cortisol (CORT) levels, and WM (Digit Span Test (DST)), were assessed pre-, post- and 30 min post-intervention. Significant post-exercise increases in circulating BDNF and CORT levels were observed coinciding with the highest DST performance; however, no statistical associations were found between cognitive and neurophysiological variables. Moreover, DST scores obtained 30 min after exercise remained higher than those assessed at pre-exercise. In conclusion, the stress induced by a single bout of HIIT induces a remarkable response of BDNF and CORT boosting WM capacity in healthy young males. Future research should clarify the association between cognitive and neurobiological markers during intense exercise stimulation.
Antibody therapeutics show great potential to treat a variety of diseases. Often, the dose that can be safely administered is limited by side effects that arise from the interaction with the target ...outside the diseased tissue. Conditionally-active antibodies provide an additional layer of selectivity to improve safety. Distinct external stimuli or internal cues enable different control strategies and applications. However, current antibody masking strategies have low transferability across stimuli. Here we propose a versatile approach to conditionally mask antibody derivatives and its application to a single chain variable fragment (scFv) against a receptor expressed on cancer stem cells in several tumours. Our strategy relies on the site-specific conjugation of a polymer to an engineered cysteine residue through a chemically-synthesised linker that can be cleaved in response to the target stimulus. We show that the masking efficiency depends on the conjugation site and the size of the mask. An optimised mask decreases antigen binding by up to 20-fold and affinity can be fully recovered upon activation by exposure to light at 365 nm or by incubation with matrix metalloproteinases overexpressed in solid tumours. This approach opens up the possibility to rapidly engineer antibodies activatable with any internal or external stimulus.
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