Therapeutic ketosis decreases methacholine hyperresponsiveness in mouse models of inherent obese asthma.

Obese asthmatics tend to have severe, poorly controlled disease and exhibit methacholine hyperresponsiveness manifesting in proximal airway narrowing and distal lung tissue collapsibility. Substantial weight loss in obese asthmatics or in mouse models of the condition decreases methacholine hyperresponsiveness. Ketone bodies are rapidly elevated during weight loss, coinciding with or preceding relief from asthma-related comorbidities. As ketone bodies may exert numerous potentially therapeutic effects, augmenting their systemic concentrations is being targeted for the treatment of several conditions. Circulating ketone body levels can be increased by feeding a ketogenic diet or by providing a ketone ester dietary supplement, which we hypothesized would exert protective effects in mouse models of inherent obese asthma. Weight loss induced by feeding a low-fat diet to mice previously fed a high-fat diet was preceded by increased urine and blood levels of the ketone body ß-hydroxybutyrate (BHB). Feeding a ketogenic diet for 3 wk to high-fat diet-fed obese mice or genetically obese db/db mice increased BHB concentrations and decreased methacholine hyperresponsiveness without substantially decreasing body weight. Acute ketone ester administration decreased methacholine responsiveness of normal mice, and dietary ketone ester supplementation of high-fat diet-fed mice decreased methacholine hyperresponsiveness. Ketone ester supplementation also transiently induced an "antiobesogenic" gut microbiome with a decreased Fermicutes/Bacteroidetes ratio. Dietary interventions to increase systemic BHB concentrations could provide symptom relief for obese asthmatics without the need for the substantial weight loss required of patients to elicit benefits to their asthma through bariatric surgery or other diet or lifestyle alterations.

Diagnosis and treatment of anomalous aortic origin of coronary artery: A twenty-year retrospective study of experience and decision-making in children and young adults.

BACKGROUND: Anomalous aortic origin of a coronary artery, particularly in the presence of inter-arterial course between the great arteries, has been found to be associated with sudden death in young people. METHODS: This study reports a single-center experience in the management of anomalous aortic origin of a coronary artery, with or without inter-arterial course, by focusing specifically on presentation, diagnosis, and patient outcome. RESULTS: From March 1993 to February 2018, 100 patients (70 males) were diagnosed with anomalous aortic origin of a coronary artery, including 27 left coronary artery from the right sinus, 60 right coronary artery from the left sinus, and 13 other anomalies. Patients with inter-arterial course between the great arteries presented more frequently with syncope and/or sudden death compared to patients without (23.4% vs. 0%, p = 0.026). Diagnosis was reached using first-line transthoracic echocardiography in 65% of cases. Surgical repair was performed in 61 patients (61%). All operated patients (60 direct implantations, 1 unroofing) had been diagnosed with inter-arterial course between the great arteries, and were asymptomatic at a mean (±SD) postoperative follow-up of 4.9 ± 5.3 years. CONCLUSIONS: An inter-arterial course of the anomalous right or left coronary arteries arising from the opposite sinus is associated with life-threatening events. Direct reimplantation of coronary artery is reliable, and should be discussed even in asymptomatic patients.

Outcomes of Newborns with Prenatal Ventricular Asymmetry not Requiring Neonatal Surgical Intervention: a 22-Year Retrospective Single-Center Study.

To assess the outcomes of neonates prenatally diagnosed with ventricular asymmetry and not operated on within the neonatal period and to determine the risk factors for left heart obstruction occurrence at follow-up. All neonates with prenatal asymmetry of the ventricles, diagnosed from August 1993 to July 2015, not operated on within the neonatal period, were retrospectively included in the study. Left heart echocardiographic measurements at birth and at last follow-up were collected and compared. Left heart anomaly included isthmus and/or aortic valve and/or mitral valve obstruction. There were a total of 34 newborns included in the study. The median follow-up was 2 years. There was no death. Eleven patients were operated on at a median age of three months; seven of them had an obstruction of the left heart (five coarctations of the aorta, one sub-aortic and aortic valve stenosis, and one mitral stenosis). Estimated freedom of left heart surgery was 80% at 6 months and 75% at 10 years. The main risk factor for progression to a left heart anomaly was a hypoplasia of the aortic isthmus (p = 0.0003), while the presence of a left superior vena cava was more frequent in these patients although the difference was not significant. Patients with an aortic isthmus z-score below - 2 at the closure of arterial duct are at risk of later coarctation and therefore follow-up should be extended to at least 3 months. Furthermore, the prenatal ventricular asymmetry does not only identify patients at risk of coarctation but also of other left heart anomalies. This last point should be a better approach with future parents to improve prenatal counseling on a more complex postnatal diagnostic than a simple isolated coarctation.