Citations

Abstract Aim To evaluate whether short‐term treatment with a selective 11β‐Hydroxysteroid dehydrogenase‐1 (11β‐HSD1) inhibitor, AZD4017, would block hepatic cortisol production and thereby decrease hepatic fat in patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), with or without type 2 diabetes (T2D). Materials and Methods This was a randomized, double‐blind, placebo‐controlled, phase 2 study conducted at two sites. Key inclusion criteria were the presence of NAFLD or NASH on magnetic resonance imaging (MRI) or recent biopsy positive for NASH. Enrolled patients were randomly assigned (1:1) to AZD4017 or placebo for 12 weeks. Primary outcomes were between‐group differences in mean change from baseline to week 12 in liver fat fraction (LFF) and conversion of 13 C cortisone to 13 C cortisol in the liver. Results A total of 93 patients were randomized; 85 patients completed treatment. The mean (standard deviation [SD]) change in LFF was −0.667 (5.246) and 0.139 (4.323) in the AZD4017 and placebo groups ( P = 0.441). For patients with NASH and T2D, the mean (SD) change in LFF was significantly improved in the AZD4017 versus the placebo group (−1.087 [5.374] vs. 1.675 [3.318]; P = 0.033). Conversion of 13 C cortisone to 13 C cortisol was blocked in all patients in the AZD4017 group. There were no significant between‐group differences (AZD4017 vs. placebo) in changes in fibrosis, weight, levels of liver enzymes or lipids, or insulin sensitivity. Conclusion Although the study did not meet one of the primary outcomes, AZD4017 blocked the conversion of 13 C cortisone to 13 C cortisol in the liver in all patients who received the drug. In patients with NASH and T2D, AZD4017 improved liver steatosis versus placebo.

Abstract We characterized coronavirus disease 2019 (COVID-19) breakthrough cases admitted to a single center in Florida. With the emergence of delta variant, an increased number of hospitalizations was seen due to breakthrough infections. These patients were older and more likely to have comorbidities. Preventive measures should be maintained even after vaccination.

Objectives: The objectives of the study were to estimate the impact of high matrix image reconstruction on chest computed tomography (CT) compared to standard image reconstruction. Material and Methods: This retrospective study included patients with interstitial or parenchymal lung disease, airway disease, and pulmonary nodules who underwent chest CT. Chest CT images were reconstructed using high matrix (1024 × 1024) or standard matrix (512 × 512), with all other parameters matched. Two radiologists, blinded to reconstruction technique, independently examined each lung, viewing image sets side by side and rating the conspicuity of imaging findings using a 5-point relative conspicuity scale. The presence of pulmonary nodules and confidence in classification of internal attenuation was also graded. Overall image quality and subjective noise/artifacts were assessed. Results: Thirty-four patients with 68 lungs were evaluated. Relative conspicuity scores were significantly higher using high matrix image reconstruction for all imaging findings indicative of idiopathic lung fibrosis (peripheral airway visualization, interlobular septal thickening, intralobular reticular opacity, and end-stage fibrotic change; P ≤ 0.001) along with emphysema, mosaic attenuation, and fourth order bronchi for both readers (P ≤ 0.001). High matrix reconstruction did not improve confidence in the presence or classification of internal nodule attenuation for either reader. Overall image quality was increased but not subjective noise/artifacts with high matrix image reconstruction for both readers (P < 0.001). Conclusion: High matrix image reconstruction significantly improves the conspicuity of imaging findings reflecting interstitial lung disease and may be useful for diagnosis or treatment response assessment.

Abstract Variable differences of nerve conduction amplitudes vs velocities and distal latencies (DLs) of healthy subjects assessed in ethnic cohorts. Introduction/Aims The variables affecting reference compound muscle (CMAP) and sensory nerve action potential (SNAP) amplitudes as compared to ones affecting conduction velocities and DLs have not been adequately evaluated in previous studies. In this report, this subject is studied in healthy subject cohorts mainly of Northern European extraction, Northern Plains Indians, and Latinos. Methods Nineteen variables and 18 attributes of nerve conductions (NCs) were assessed using highly standard testing conditions and techniques. Classification and Regression Tree analyses were used to assess variable differences among amplitudes, conduction velocities, and DLs. Results The most important variable affecting CMAP and SNAP amplitudes was age. For conduction velocities (CVs) and DLs, the variables were height, ethnic cohort, and age. Discussion The variables affecting attributes of NCs were similar for the three ethnic cohorts evaluated. The differences of variables affecting amplitudes compared to CVs and DLs need to be taken into account in interpretation of NC results and in setting reference limits for use in medical practice, epidemiology surveys, and therapeutic trials. Scores of CMAP and SNAP amplitudes are suitable measures of sensorimotor polyneuropathy severity, whereas conduction velocities and DLs reflect physiologic/pathologic abnormality of nerve fibers.

Abstract Aims Cardiovascular disease is a major threat to maternal health, with cardiomyopathy being among the most common acquired cardiovascular diseases during pregnancy and the postpartum period. The aim of our study was to evaluate the effectiveness of an electrocardiogram (ECG)-based deep learning model in identifying cardiomyopathy during pregnancy and the postpartum period. Methods and results We used an ECG-based deep learning model to detect cardiomyopathy in a cohort of women who were pregnant or in the postpartum period seen at Mayo Clinic. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. We compared the diagnostic probabilities of the deep learning model with natriuretic peptides and a multivariable model consisting of demographic and clinical parameters. The study cohort included 1807 women; 7%, 10%, and 13% had left ventricular ejection fraction (LVEF) of 35% or less, &lt;45%, and &lt;50%, respectively. The ECG-based deep learning model identified cardiomyopathy with AUCs of 0.92 (LVEF ≤ 35%), 0.89 (LVEF &lt; 45%), and 0.87 (LVEF &lt; 50%). For LVEF of 35% or less, AUC was higher in Black (0.95) and Hispanic (0.98) women compared to White (0.91). Natriuretic peptides and the multivariable model had AUCs of 0.85 to 0.86 and 0.72, respectively. Conclusions An ECG-based deep learning model effectively identifies cardiomyopathy during pregnancy and the postpartum period and outperforms natriuretic peptides and traditional clinical parameters with the potential to become a powerful initial screening tool for cardiomyopathy in the obstetric care setting.

Longitudinal studies assessing durability of the anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) humoral immune response have generated conflicting results. This has been proposed to be due to differences in patient populations, the lack of standardized methodologies, and the use of assays that measure distinct aspects of the humoral response.

Objective Observational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming. Methods A prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn–Tolosa–Marín tremor rating score compared to the preoperative baseline. Results Among the six patients, tremor rating scores differed significantly among the three experimental conditions ( P=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; P=0.031) and standard-of-care programming (50.7% ± 19.2%; P=0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R 2 =0.24; P=0.04). No significant adverse events were encountered. Conclusions Using a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.

Introduction: Identifying and mitigating factors that promote obesity will have a large public health impact. Sleep may be an important regulator of metabolism and energy expenditure. Voluntary sleep restriction is common, with 27% of US adults regularly getting ≤6 h of sleep per day. Epidemiologic evidence suggests a link between short sleep duration and obesity. Human experiments suggest that acute sleep deprivation reduces the anorexigenic hormone leptin, increases the orexigenic factor ghrelin, and promotes caloric intake. Meanwhile, increased energy expenditure during prolonged wakefulness may counterbalance any increased caloric intake associated with a lack of sleep. Hypothesis: We hypothesized that 8 days of modest sleep restriction would reduce leptin, increase ghrelin, promote caloric intake, and increase activity energy expenditure. Methods: We studied 17 healthy individuals age 18–40 y. Subjects completed a protocol consisting of one week of home actigraphy, a 3 night acclimation phase, followed by an 8 night experimental phase in which they were randomized to sleep ad lib or two-thirds of their normal sleep time. Blood was collected at the end of the two periods, food was freely available and caloric intake was calculated daily, and activity energy expenditure was assessed by a comprehensively validated system comprised of inclinometers and accelerometers. Sleep was confirmed using continuous electroencephalography. Mean change from the acclimation period ± standard deviation are presented, with statistical testing by two sample t tests on the changes between acclimation and experimental periods. Results: Subjects included 11 men and 6 women, of whom 8 were randomized to sleep deprivation and 9 served as controls. Sleep duration during the acclimation period averaged 6.5±0.9 h/day but fell to 5.2±0.1 h/d among those randomized to sleep deprivation. The sleep deprivation group consumed +549±583 kcal/d, whereas those randomized to ad lib sleep consumed −143±420 kcal/d (P<0.01). Activity energy expenditure by did not change in either group (+1.2±33.0% vs +8.4±34.0%, P=0.68). Sleep deprivation was associated with a trend towards increased leptin (+8.4±4.7% versus −9.8±13.5%, P=0.12) and decreased ghrelin (−4.9±5.3% vs +4.6±7.0%, P=0.38). Conclusions: Eight days of modest sleep restriction, similar to that encountered in everyday life, was associated with a striking increase in caloric intake with no change in activity energy expenditure. Contrary to expectations, we observed a trend towards increased circulating concentrations of leptin and reduced concentrations of ghrelin, more consistent with a consequence of a positive energy balance than a cause. Our data suggest that chronic sleep restriction may be an important and modifiable behavior promoting obesity.

Abstract The aim of the European Heart Journal (EHJ) is to attract innovative, methodologically sound, and clinically relevant research manuscripts able to change clinical practice and/or substantially advance knowledge on cardiovascular diseases. As the reference journal in cardiovascular medicine, the EHJ is committed to publishing only the best cardiovascular science adhering to the highest ethical principles. EHJ uses highly rigorous peer-review, critical statistical review and the highest quality editorial process, to ensure the novelty, accuracy, quality, and relevance of all accepted manuscripts with the aim of inspiring the clinical practice of EHJ readers and reducing the global burden of cardiovascular diseases. This review article summarizes the quality standards pursued by the EHJ to fulfill its mission.