Validation of Diffuse Correlation Spectroscopic Measurement of Cerebral Blood Flow Using Phase-Encoded Velocity Mapping Magnetic Resonance Imaging

Diffuse correlation spectroscopy (DCS) is a novel optical technique that appears to be an excellent tool for assessing cerebral blood flow in a continuous and non-invasive manner at the bedside. We present new clinical validation of the DCS methodology by demonstrating strong agreement between DCS indices of relative cerebral blood flow and indices based on phase-encoded velocity mapping magnetic resonance imaging (VENC MRI) of relative blood flow in the jugular veins and superior vena cava. Data were acquired from 46 children with single ventricle cardiac lesions during a hypercapnia intervention. Significant increases in cerebral blood flow, measured both by DCS and by VENC MRI, as well as significant increases in oxyhemoglobin concentration, and total hemoglobin concentration, were observed during hypercapnia. Comparison of blood flow changes measured by VENC MRI in the jugular veins and by DCS revealed a strong linear relationship, R = 0.88, p \u3c 0.001, slope = 0.91 ± 0.07. Similar correlations were observed between DCS and VENC MRI in the superior vena cava, R = 0.77, slope = 0.99 ± 0.12, p \u3c 0.001. The relationship between VENC MRI in the aorta and DCS, a negative control, was weakly correlated, R = 0.46, slope = 1.77 ± 0.45, p \u3c 0.001

Association of right ventricular dysfunction and pulmonary hypertension with adverse 30-day outcomes in COVID-19 patients

Background: Cardiac manifestations in COVID-19 are multifactorial and are associated with increased mortality. The clinical utility and prognostic value of echocardiography in COVID-19 inpatients is not clearly defined. We aim to identify echocardiographic parameters that are associated with 30-day clinical outcomes secondary to COVID-19 hospitalization. Methods: This retrospective cohort study was conducted in a large tertiary hospital in New York City during the COVID-19 pandemic. It included 214 adult inpatients with a laboratory-confirmed diagnosis of COVID-19 by reverse transcriptase polymerase chain reaction assay (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab and had a transthoracic echocardiogram performed during the index hospitalization. Primary outcome was 30-day all-cause inpatient mortality. Secondary outcomes were 30-day utilization of mechanical ventilator support, vasopressors, or renal replacement therapy. Results: Mild right ventricular systolic dysfunction (odds ratio (OR): 3.51, 95% confidence interval (CI): 1.63–7.57, p¼0.001), moderate to severe right ventricular systolic dysfunction (OR: 7.30, 95% CI: 2.20–24.25, p¼0.001), pulmonary hypertension (OR: 5.39, 95% CI: 1.96–14.86, p¼0.001), and moderate to severe tricuspid regurgitation (OR: 3.92, 95% CI: 1.71–9.03, p¼0.001) were each associated with increased odds of 30-day all-cause inpatient mortality. Pulmonary hypertension and moderate to severe right ventricular dysfunction were each associated with increased odds of 30-day utilization of mechanical ventilator support and vasopressors. Conclusions: Right ventricular dysfunction, pulmonary hypertension, and moderate to severe tricuspid regurgitation were associated with increased odds for 30-day inpatient mortality. This study highlights the importance of echocardiography and its clinical utility and prognostic value for evaluating hospitalized COVID-19 patients

Extraterrestrial nucleobases in the Murchison meteorite

Carbon-rich meteorites, carbonaceous chondrites, contain many biologically relevant organic molecules and delivered prebiotic material to the young Earth. We present compound-specific carbon isotope data indicating that measured purine and pyrimidine compounds are indigenous components of the Murchison meteorite. Carbon isotope ratios for uracil and xanthine of delta13C=+44.5per mil and +37.7per mil, respectively, indicate a non-terrestrial origin for these compounds. These new results demonstrate that organic compounds, which are components of the genetic code in modern biochemistry, were already present in the early solar system and may have played a key role in life's origin.Comment: 31 pages, 4 figures, 3 table

Primary brain calcification: an international study reporting novel variants and associated phenotypes.

Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (n = 34, 19.2%) or VUS (n = 11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic

Cardiovascular adaptation to the Fontan circulation

Although medium-term survival following Fontan operations in the modern era has improved dramatically, late cardiovascular and extracardiac morbidity are common and are associated with impaired quality of life and premature late mortality. This serves as a reminder of the extraordinary adaptations required of the cardiovascular system when the systemic arterial, systemic venous and pulmonary circulations are placed in series coupled to a single ventricular pump. This article reviews the key features and principles that govern interactions between the ventricle, systemic arterial circulation, the systemic venous and pulmonary circulatory compartments, the microcirculation, and lymphatic circulations. The overarching aim is to provide insight into the integrative pathophysiology that governs the Fontan circulation and stimulate thoughtful approaches to advance research.status: publishe