Cardiac magnetic resonance predictors for successful primary biventricular repair of unbalanced complete common atrioventricular canal.

BACKGROUND: Patients with unbalanced common atrioventricular canal can be difficult to manage. Surgical planning often depends on pre-operative echocardiographic measurements. We aimed to determine the added utility of cardiac MRI in predicting successful biventricular repair in common atrioventricular canal. METHODS: We conducted a retrospective cohort study of children with common atrioventricular canal who underwent MRI prior to repair. Associations between MRI and echocardiographic measures and surgical outcome were tested using logistic regression, and models were compared using area under the receiver operator characteristic curve. RESULTS: We included 28 patients (median age at MRI: 5.2 months). The optimal MRI model included the novel end-diastolic volume index (using the ratio of left ventricular end-diastolic volume to total end-diastolic volume) and the left ventricle-right ventricle angle in diastole (area under the curve 0.83, p = 0.041). End-diastolic volume index ≤ 0.18 and left ventricle-right ventricle angle in diastole ≤ 72° yield a sensitivity of 83% and specificity of 81% for successful biventricular repair. The optimal multimodality model included the end-diastolic volume index and the echocardiographic atrioventricular valve index with an area under the curve of 0.87 (p = 0.026). CONCLUSIONS: Cardiac MRI can successfully predict successful biventricular repair in patients with unbalanced common atrioventricular canal utilising the end-diastolic volume index alone or in combination with the MRI left ventricle-right ventricle angle in diastole or the echocardiographic atrioventricular valve index. A prospective cardiac MRI study is warranted to better define the multimodality characteristic predictive of successful biventricular surgery.

Mid-gestational fetal placental blood flow is diminished in the fetus with congenital heart disease.

OBJECTIVE: Data suggest fetuses with congenital heart disease (CHD) have placental abnormalities. Their abnormal placental vasculature may affect fetal placental blood flow, which has not previously been explored. METHOD: We performed a retrospective cross-sectional study comparing umbilical venous volume flow (UVVF) of single ventricle, D-transposition of the great arteries, and tetralogy of Fallot fetuses with fetuses without CHD. UVVF and combined cardiac output (CCO) were calculated from fetal echocardiography and compared using t tests, χ2 and Fisher's exact tests. RESULTS: Mean gestational age and fetal weight were greater in CHD fetuses (26.5 weeks, 1119.4 g; n = 81, P < .001) compared to controls (23.1 weeks, 675 g; n = 170, P < .001). UVVF/fetal weight was nevertheless decreased among cases (99.8 vs 115.3 mL/min/kg, P < .001). Subgroup analysis of 20- to 25-week fetuses demonstrated no significant differences in case and control baseline characteristics. In CHD fetuses (n = 31) compared to controls (n = 144), absolute UVVF (50.8 vs 62.1 mL/min, P = .006), and UVVF/fetal weight (98.8 vs 118.5 mL/min/kg, P < .001) were decreased. Findings were similar in single ventricle (n = 24) and hypoplastic left heart syndrome (n = 14). CONCLUSION: Mid-gestational placental blood flow in CHD fetuses is decreased compared to controls. Further study is needed to explore the relationship between UVVF and placental pathology, and impact on outcomes.

Improved Detection of Antibodies against SARS-CoV-2 by Microsphere-Based Antibody Assay.

Currently available COVID-19 antibody tests using enzyme immunoassay (EIA) or immunochromatographic assay have variable sensitivity and specificity. Here, we developed and evaluated a novel microsphere-based antibody assay (MBA) for detecting immunoglobulin G (IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (NP) and spike protein receptor binding domain (RBD). The seropositive cutoff value was set using a cohort of 294 anonymous serum specimens collected in 2018. The specificity was assessed using serum specimens collected from organ donors or influenza patients before 2020. Seropositive rate was determined among COVID-19 patients. Time-to-seropositivity and signal-to-cutoff (S/CO) ratio were compared between MBA and EIA. MBA had a specificity of 100% (93/93; 95% confidence interval (CI), 96-100%) for anti-NP IgG, 98.9% (92/93; 95% CI 94.2-100%) for anti-RBD IgG. The MBA seropositive rate for convalescent COVID-19 patients was 89.8% (35/39) for anti-NP IgG and 79.5% (31/39) for anti-RBD IgG. The time-to-seropositivity was shorter with MBA than EIA. MBA could better differentiate between COVID-19 patients and negative controls with higher S/CO ratio for COVID-19 patients, lower S/CO ratio with negative controls and fewer specimens in the equivocal range. MBA is robust, simple and is suitable for clinical microbiology laboratory for the accurate determination of anti-SARS-CoV-2 antibodies for diagnosis, serosurveillance, and vaccine trials.

A standardized imaging protocol improves quality and reduces practice variability in echocardiographic assessment of ventricular function by first-year pediatric cardiology fellows.

BACKGROUND: Echocardiography education for pediatric cardiology fellows has been a recent focus leading to the implementation of "boot camps." Less is described about continuing education through fellowship and improving image quality. We noticed practice variation in echocardiograms assessing ventricular function performed on nights and weekends. Thus, we implemented a standardized protocol and assessed its impact on imaging and reporting completeness. METHODS: We created an imaging protocol for the assessment of ventricular function in the acute setting. The protocol included demographic information, a list of images to be obtained, and the methods to quantify ventricular function. The protocol was explained to first-year fellows and distributed on an electronic quick reference card. Echocardiograms independently performed by first-year fellows during their first 4 months of on-call time were assessed pre- and postintervention using a standard rubric. RESULTS: Compliance with demographic reporting was high pre- and postintervention, but significantly improved after the standardized protocol (P < 0.001). Use of the protocol increased the median number of unique images obtained per echocardiogram from 13 to 17 (out of 23 required views, P < 0.001). Particularly improved was the performance of quantitative evaluations of function, including Simpson's method for left ventricular ejection fraction (four chamber: 40% vs 67%, P < 0.001; two chamber: 33% vs 67%, P < 0.001) and tricuspid annular plane systolic excursion (45% vs 80%, P < 0.001). CONCLUSIONS: The introduction of a standardized imaging protocol and its distribution to first-year fellows resulted in improvements in echocardiographic reporting completeness and increased the quality of information obtained by providing more quantitative assessments of ventricular function.

Postoperative Obstruction of the Pulmonary Veins in Mixed Total Anomalous Pulmonary Venous Connection.

Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease in which the pulmonary veins drain by various pathways to the right atrium instead of the left atrium. Postoperative obstruction of the pulmonary veins is a known complication. Identifying risk factors for morbidity and mortality is important for counseling and monitoring. We describe a pattern of postoperative obstruction in a specific arrangement of mixed TAPVC. Five patients with a type of mixed TAPVC, namely, three pulmonary veins connecting to the coronary sinus and the left upper pulmonary vein (LUPV) connecting to the innominate vein, were identified over an 11-year period at our institution. Two additional patients with this TAPVC arrangement were cared for at our institution after having surgery at other institutions. Of these, one patient received only comfort care at birth due to other clinical issues. The six other patients underwent surgical unroofing of the coronary sinus. The anomalous LUPV was not addressed during the initial surgery in any of these cases. Following repair, one patient died from non-cardiac reasons. The remaining five patients all developed obstruction of the repaired pulmonary veins with decompression through the unrepaired LUPV, requiring surgical revision. Three patients underwent a second reoperation as well. Three of the six repaired patients also developed refractory atrial arrhythmias. This cohort suggests that this mixed TAPVC pattern predisposes patients to obstruction after surgical repair. Further investigation may aid pediatric cardiologists in risk-stratifying and counseling these patients. Alternative surgical approaches may need to be considered.

Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis.

To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.

Metabolomic Profiling of Plasma from Patients with Tuberculosis by Use of Untargeted Mass Spectrometry Reveals Novel Biomarkers for Diagnosis.

Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n = 46) with those of community-acquired pneumonia (CAP) patients (n = 30) and controls without active infection (n = 30) using ultrahigh-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(R)-HETE], ceramide (d18:1/16:0), cholesterol sulfate, and 4α-formyl-4ß-methyl-5α-cholesta-8-en-3ß-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve (AUC) values of 0.914, 0.912, 0.905, and 0.856, sensitivities of 84.8%, 84.8%, 87.0%, and 89.1%, specificities of 90.0%, 86.7%, 86.7%, and 80.0%, and fold changes of 4.19, 26.15, 6.09, and 1.83, respectively. In a comparison of TB and CAP patients, the four metabolites demonstrated AUC values of 0.793, 0.717, 0.802, and 0.894, sensitivities of 89.1%, 71.7%, 80.4%, and 84.8%, specificities of 63.3%, 66.7%, 70.0%, and 83.3%, and fold changes of 4.69, 3.82, 3.75, and 2.16, respectively. 4α-Formyl-4ß-methyl-5α-cholesta-8-en-3ß-ol combined with 12(R)-HETE or cholesterol sulfate offered ≥70% sensitivity and ≥90% specificity for differentiating TB patients from controls or CAP patients. These novel plasma biomarkers, especially 12(R)-HETE and 4α-formyl-4ß-methyl-5α-cholesta-8-en-3ß-ol, alone or in combination, are potentially useful for rapid and noninvasive diagnosis of TB. The present findings may offer insights into the pathogenesis and host response in TB.

Effect of Race on the Prevalence of Congenital Malformations among Newborns in the United States.

BACKGROUND: Racial variability in certain prenatal risk factors, such as prenatal vitamin supplementation and termination of pregnancy for fetal anomaly, has altered the racial prevalence of congenital malformation (CM). Analysis of a single large representative population is required to analyze current racial differences in prevalence of CM in the United States. METHOD: This is a population-based cross-sectional study to analyze racial differences in prevalence of CM diagnoses. We reviewed all live births in the 2008 Nationwide Inpatient Sample (NIS) database and determined birth prevalence of 55 selected CM diagnoses in Caucasians. We then calculated the relative risk of these CM diagnoses in African American, Hispanics and Asians relative to Caucasians. RESULT: Overall CM prevalence was 29.2 per 1,000 in a cohort of 1,048,252 live births of which 51% were Caucasians. Compared to Caucasian, risk of overall CM was lower in African Americans (RR = .9, CI .8-9) and Hispanics (RR = .9, CI .8-.9). Risk of overall CM was similar in Caucasians and Asians. Relative to the Caucasians, African Americans had lower risk of cardiac, genitourinary, and craniofacial malformations but higher risk of musculoskeletal malformations. Hispanics had lower risk of genitourinary and gastrointestinal malformation. Asians had higher risk of craniofacial and musculoskeletal malformation. CONCLUSIONS: This is a comprehensive description of racial difference in risk of CM in the United States. Observed racial differences in risk of CM may be related to genetic susceptibilities, to cultural or social differences that could modify exposures, or to the many potential combinations between susceptibilities and exposures.

Racial/ethnic differences in the birth prevalence of congenital anomalies in the United States.

OBJECTIVES: This work aimed to analyze a single large representative population to determine racial/ethnic differences in the prevalence of congenital anomalies (CA). DESIGN: This is a population-based comprehensive analysis of racial/ethnic differences in the prevalence of CA diagnoses. We reviewed all live births in the 2008 Nationwide Inpatient Sample (NIS) database and determined the birth prevalence of 55 selected CA diagnoses in Caucasians. We then calculated the relative risk of these CA diagnoses in African American, Hispanics, and Asians relative to Caucasians. RESULT: Overall CA prevalence was 29.2 per 1000 in a cohort of 1,048,252 live births, of which 51% were Caucasians. Compared with Caucasians, risk of overall CA was lower in African Americans (RR=0.9, CI: 0.8-0.9) and Hispanics (RR=0.9, CI: 0.8-0.9). Risk of overall CA was similar in Caucasians and Asians. Relative to the Caucasians, African Americans had lower risk of cardiac, genitourinary, and craniofacial CA but higher risk of musculoskeletal anomalies. Hispanics had lower risk of genitourinary and gastrointestinal CA. Asians had higher risk of craniofacial and musculoskeletal CA. CONCLUSIONS: Observed racial/ethnic differences in risk of CA may be related to genetic susceptibilities, cultural or social differences that could modify exposures, or many potential combinations between susceptibilities and exposures.

Incidences and sociodemographics of specific congenital heart diseases in the United States of America: an evaluation of hospital discharge diagnoses.

Current estimates of the incidence of congenital heart disease (CHD) are derived from small clinical studies and metaanalyses. For the true incidence of CHD in the United States of America to be estimated, a single large representative population must be analyzed. All the data in this study were derived from the Nationwide Inpatient Sample database. The study determined the overall and lesion-specific incidences of CHD diagnoses among all birth hospitalizations in 2008, stratified by race, gender, socioeconomic status, and hospital geographic location. The study identified 13,093 CHD diagnoses among 1,204,887 birth hospitalizations, yielding an incidence of 10.8 per 1,000, with a predominance of mild lesions and septal defects. Atrial septal defect (ASD) and pulmonic stenosis were more common among females, whereas aortic stenosis, coarctation of the aorta, hypoplastic left heart syndrome, and d-transposition of great arteries were more common among males. No racial difference was observed in the overall CHD incidence. However, isolated patent ductus arteriosus (PDA) and ventricular septal defects (VSDs) were more common among Caucasians, whereas ASDs were more common among Hispanics. The incidences of CHD diagnoses were similar for all socioeconomic classes except the lowest socioeconomic class, which had a significantly lower CHD incidence. There was no geographic or seasonal variation in CHD incidence. This study demonstrated the incidence of echocardiographically confirmed CHD diagnosis to be 10.8 per 1,000 live births, marked by a high proportion of mild cardiac lesions and isolated PDAs. The high incidence of isolated PDAs in this study may be explained by the inclusion of only CHD diagnoses during birth hospitalization.

Changing prevalence of severe congenital heart disease: a population-based study.

Although the epidemiology of congenital heart disease (CHD) has been described, the authors believe changes in prenatal factors such as termination of pregnancy for fetal anomaly and prenatal vitamin supplementation have altered the birth prevalence of severe CHD. This population-based study reviewed the Nationwide Inpatient Sample (NIS) database and identified all cases with a severe CHD diagnosis among all live birth entries from 1999 to 2008. A time trend analysis then was performed for specific severe CHD diagnoses stratified by race, socioeconomic status, and geographic location. Overall, severe CHD prevalence was 147.4 per 100,000 live births, with a temporal decrease in prevalence from 168.9 per 100,000 in 1999 to 129.3 per 100,000 in 2008 (p = 0.03). Among the 12 severe CHD diagnoses included in our cohort, the prevalence of truncus arteriosus (p = 0.02), tetralogy of Fallot (p = 0.001), hypoplastic left heart syndrome (p = 0.001), and pulmonary atresia (p = 0.01) decreased significantly during the study period. The observed prevalence trends varied significantly by race (Caucasians), socioeconomic class (upper income quartiles), and geographic location (Northeast and West regions). The study findings showed a temporal decrease in severe CHD prevalence, which varied by race, socioeconomic status, and geographic location. The authors speculated that the observed trend might be due to increased termination of fetuses with prenatally diagnosed CHD. The impact of sociodemographic variables on the observed prevalence trend might be due to differences in access to specialized perinatal care and fetal heart programs or because of variability in termination of pregnancy.

Prevalence of associated extracardiac malformations in the congenital heart disease population.

The authors hypothesized that changes in prenatal factors such as termination of pregnancy for fetal anomalies and prenatal vitamin supplementation have altered the epidemiology of patients with multiple congenital anomalies and may have had an impact on their prevalence in the current era. This study reviewed the Nationwide Inpatient Sample database from 1998 to 2008 and compared the prevalence of ECM among live births with a CHD diagnosis (case) and that among live births without a CHD diagnosis (control). For this study, 42 ECM and 10 CHD diagnoses were selected for subanalysis. Longitudinal analysis also was performed to determine temporal variation of ECM prevalence in the CHD population during the 11-year study period. The cohort in this study consisted of 97,154 patients in the case group and 12,078,482 subjects in the control group. The prevalences in the CHD population were 11.4 % for nonsyndromic congenital malformation (NSCM), 2.2 % for genetic syndrome (GS), and 13.6 % for overall extracardiac congenital malformation (ECM). The prevalences in the control group were 6.7 % for NSCM, 0.3 % for GS, and 7.0 % for ECM. The findings showed a strong association of NSCM [odds ratio (OR) 1.88; 95 % confidence interval (CI) 1.73-1.94], GS (OR 2.52; 95 % CI 2.44-2.61), and overall ECM (OR 2.01; 95 % CI 1.97-2.14) with CHD. The prevalences of GS and multiple organ system CM decreased significantly during the study period. This study was the largest and most comprehensive population-based study to evaluate the association between CHD and ECM in newborns.

Results of the Double Switch Operation in Patients Who Previously Underwent Left Ventricular Retraining.

BACKGROUND: Congenitally corrected transposition of the great arteries (CC-TGA) is a complex form of congenital heart disease that has numerous subtypes. While most patients with CC-TGA have a large ventricular septal defect (VSD) and pulmonary stenosis, there are some patients who have either no VSD or a highly restrictive VSD. These patients will require left ventricular (LV) retraining prior to double switch. The purpose of this study was to review our experience with the double switch procedure in patients who had previously undergone LV retraining. METHODS: This was a retrospective review of a single institution experience with the double switch procedure in patients who had undergone LV retraining (2002-present). RESULTS: Forty-five patients underwent double switch following LV retraining. Of these, 39 had an arterial switch with hemi-Mustard/bidirectional Glenn and six had a Senning. The median cross-clamp time was 135 min (range 71-272) and median bypass time was 202 min (range 140-430 min). Median hospital length of stay was eight days (range 4-108). There were no in-hospital deaths. Median duration of follow-up was 30 months (range 0-175). One patient subsequently underwent heart transplantation and died 65 months following double switch. At follow-up, 41 of the 44 survivors (93%) have normal or low normal LV function and 40 of the 44 survivors (91%) have no or trace mitral regurgitation. CONCLUSIONS: The data demonstrate early and mid-term survival of 100% and 97%. Ninety-three percent had preserved LV function. These results suggest that patients with CC-TGA who undergo LV retraining and double switch can have excellent clinical outcomes.

Surgical Outcomes in Patients Undergoing a Double Switch Operation for Corrected Transposition.

BACKGROUND: Congenitally corrected transposition of the great arteries (CC-TGA) is a rare and complex form of congenital heart disease. Results of physiologic repair proved disappointing due to late right ventricular dysfunction and/or tricuspid regurgitation. The current study was performed to evaluate surgical outcomes in patients undergoing a double switch for CC-TGA. METHODS: This was a retrospective review of 121 patients who underwent a double switch over a 2-decade time frame (2002-2023). Patients were a median age of 32 months. Before the double switch, 49 of 121 patients (40%) had undergone left ventricular retraining. RESULTS: Sixty-seven patients underwent an arterial switch, and 54 underwent a Rastelli procedure. There were 4 in-hospital deaths (3.3%), including 3 who had a Rastelli procedure (5.6%) and 1 who had an arterial switch (1.5%). At a median follow-up of 30 months, there were 4 late deaths (2 Rastelli and 2 arterial switch). Combined early and late mortality was 9.3% for the Rastelli and 4.5% for arterial switch. Combined mortality was 2.0% for patients who required left ventricular retraining vs 9.7% for those who did not. For the 117 patients discharged from the hospital, 93% have normal or low-normal left ventricular function, and 96% have mild or less neoaortic insufficiency. CONCLUSIONS: Surgical outcomes in patients undergoing a double switch procedure have been excellent both in the short- and midterm. However, the Rastelli procedure was associated with a more than 2-fold increase in mortality risk compared with the arterial switch.

Biased brain and behavioral responses towards kin in males of a communally breeding species.

In complex social environments, individuals may interact with not only novel and familiar conspecifics but also kin and non-kin. The ability to distinguish between conspecific identities is crucial for most animals, yet how the brain processes conspecific type and how animals may alter behavior accordingly is not well known. We examined whether the communally breeding spiny mouse (Acomys cahirinus) responds differently to conspecifics that vary in novelty and kinship. In a group interaction test, we found that males can distinguish novel kin from novel non-kin, and preferentially spend time with novel kin over familiar kin and novel non-kin. To determine whether kinship and novelty status are differentially represented in the brain, we conducted immediate early gene tests, which revealed the dorsal, but not ventral, lateral septum differentially processes kinship. Neither region differentially processes social novelty. Further, males did not exhibit differences in prosocial behavior toward novel and familiar conspecifics but exhibited more prosocial behavior with novel kin than novel non-kin. These results suggest that communally breeding species may have evolved specialized neural circuitry to facilitate a bias to be more affiliative with kin, regardless of whether they are novel or familiar, potentially to promote prosocial behaviors, thereby facilitating group cohesion.

A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID.

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs-fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127-175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs-fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.

Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response.

The overall success of worldwide mass vaccination in limiting the negative effect of the COVID-19 pandemics is inevitable, however, recent SARS-CoV-2 variants of concern, especially Omicron and its sub-lineages, efficiently evade humoral immunity mounted upon vaccination or previous infection. Thus, it is an important question whether these variants, or vaccines against them, induce anti-viral cellular immunity. Here we show that the mRNA vaccine BNT162b2 induces robust protective immunity in K18-hACE2 transgenic B-cell deficient (µMT) mice. We further demonstrate that the protection is attributed to cellular immunity depending on robust IFN-γ production. Viral challenge with SARS-CoV-2 Omicron BA.1 and BA.5.2 sub-variants induce boosted cellular responses in vaccinated µMT mice, which highlights the significance of cellular immunity against the ever-emerging SARS-CoV-2 variants evading antibody-mediated immunity. Our work, by providing evidence that BNT162b2 can induce significant protective immunity in mice that are unable to produce antibodies, thus highlights the importance of cellular immunity in the protection against SARS-CoV-2.

Congenitally Corrected Transposition of the Great Arteries: Fetal Diagnosis, Associations, and Postnatal Outcome: A Fetal Heart Society Research Collaborative Study.

Background Fetal diagnosis of congenitally corrected transposition of the great arteries (ccTGA) has been increasingly reported; however, predictors of clinical outcomes remain underexplored. We undertook a multicenter, retrospective study to investigate natural history, associated anomalies, and outcomes of fetal ccTGA. Methods and Results Fetuses with ccTGA diagnosed from January 2004 to July 2020 within 20 North American programs were included. Fetuses with severe ventricular hypoplasia thought to definitively preclude biventricular repair were excluded. We included 205 fetuses diagnosed with ccTGA at a median gestational age of 23 (interquartile range, 21-27) weeks. Genetic abnormalities were found in 5.9% tested, with extracardiac anomalies in 6.3%. Associated cardiac defects were diagnosed in 161 (78.5%), with atrioventricular block in 23 (11.3%). On serial fetal echocardiogram, 39% demonstrated a functional or anatomic change, most commonly increased tricuspid regurgitation (6.7%) or pulmonary outflow obstruction (11.1%). Of 194 fetuses with follow-up, 26 were terminated, 3 experienced fetal death (2 with atrioventricular block), and 165 were live-born. Of 158 with postnatal data (median follow-up 3.7 years), 10 (6.6%) had death/transplant before 1 year. On univariable analysis, fetal factors associated with fetal death or death/transplant by 1 year included ≥ mild tricuspid regurgitation, pulmonary atresia, aortic obstruction, fetal arrhythmia, and worsening hemodynamics on serial fetal echocardiogram (defined as worse right ventricular function, tricuspid regurgitation, or effusion). Conclusions Associated cardiac lesions and arrhythmias are common in fetal ccTGA, and functional changes commonly occur through gestation. Worse outcomes are associated with fetal tricuspid regurgitation (≥mild), any arrhythmia, pulmonary atresia, aortic obstruction, and worsening hemodynamics on serial echocardiograms. These findings can inform prenatal counseling and perinatal management planning.

High-molecular-weight and total adiponectin levels and incident symptomatic peripheral artery disease in women: a prospective investigation.

BACKGROUND: Adiponectin is linked to reduced diabetes risk and may be antiatherogenic, yet clinical data show no consistent relationship with incident cardiovascular events, especially among women. To our knowledge, no prior prospective studies have evaluated adiponectin, including high-molecular-weight (HMW) adiponectin, and incident peripheral artery disease (PAD). METHODS AND RESULTS: We evaluated the relationship of total adiponectin, HMW adiponectin, and the HMW-to-total adiponectin ratio with incident symptomatic PAD in a prospective, nested case-control study conducted within the Women's Health Study (n=110 cases, n=230 controls, frequency matched in strata defined by 5-year age categories, smoking, fasting status, and follow-up time; median cohort follow-up=13.2 years). Baseline median levels of HMW and total adiponectin were significantly lower in women developing PAD than in those remaining event free (HMW: 3.3 versus 3.8 µg/mL, P=0.0005; total: 5.6 versus 7.4 µg/mL, P<0.0001). The ratio did not differ significantly between groups. Age-adjusted PAD odds ratios (95% confidence intervals) across tertiles were 1.0, 0.66 (0.39-1.13), and 0.40 (0.22-0.74) for HMW and 1.0, 0.74 (0.43-1.25), and 0.35 (0.18-0.65) for total adiponectin (P(trend)=0.004 and 0.001, respectively). Results were similar after adjustment for traditional cardiovascular risk factors, use of postmenopausal hormone therapy, high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, leptin, hemoglobin A(1c), and fasting insulin (adjusted odds ratio and 95% confidence interval for HMW: 1.0, 0.62 [0.29-1.34], 0.30 [0.12-0.74]; total: 1.0, 0.46 [0.22-1.00], 0.30 [0.12-0.76]; P(trend)=0.01 for both). CONCLUSIONS: Total and HMW adiponectin are inversely associated with incident PAD among initially healthy women. These prospective data support a protective role for this adipokine in peripheral atherosclerosis development.

Cardiovascular sequalae in uncomplicated COVID-19 survivors.

BACKGROUND: A high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance. METHODS: We performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1-4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results. RESULTS: The mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillation (1.0%), and newly detected left ventricular systolic dysfunction with elevated NT-proBNP level (1.0%). Significant sinus bradycardia with heart rate below 50 bpm was detected in 7.2% COVID-19 survivors, which appeared to be self-limiting and recovered over time. For COVID-19 survivors with persistent elevation of troponin level after discharge or newly detected T wave abnormality, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction. CONCLUSION: Cardiac abnormality is common amongst COVID-survivors with mild disease, which is mostly self-limiting. Nonetheless, cardiac surveillance in form of ECG and/or serum biomarkers may be advisable to detect more severe cardiac involvement including atrial fibrillation and left ventricular dysfunction.