Genomic insights in ascending aortic size and distensibility.

BACKGROUND: Alterations in the anatomic and biomechanical properties of the ascending aorta (AAo) can give rise to various vascular pathologies. The aim of the current study is to gain additional insights in the biology of the AAo size and function. METHODS: We developed an AI based analysis pipeline for the segmentation of the AAo, and the extraction of AAO parameters. We then performed genome-wide association studies of AAo maximum area, AAo minimum area and AAo distensibility in up to 37,910 individuals from the UK Biobank. Variants that were significantly associated with AAo phenotypes were used as instrumental variables in Mendelian randomization analyses to investigate potential causal relationships with coronary artery disease, myocardial infarction, stroke and aneurysms. FINDINGS: Genome-wide association studies revealed a total of 107 SNPs in 78 loci. We annotated 101 candidate genes involved in various biological processes, including connective tissue development (THSD4 and COL6A3). Mendelian randomization analyses showed a causal association with aneurysm development, but not with other vascular diseases. INTERPRETATION: We identified 78 loci that provide insights into mechanisms underlying AAo size and function in the general population and provide genetic evidence for their role in aortic aneurysm development.

Uncertainty estimation for deep learning-based automated analysis of 12-lead electrocardiograms.

Aims: Automated interpretation of electrocardiograms (ECGs) using deep neural networks (DNNs) has gained much attention recently. While the initial results have been encouraging, limited attention has been paid to whether such results can be trusted, which is paramount for their clinical implementation. This study aims to systematically investigate uncertainty estimation techniques for automated classification of ECGs using DNNs and to gain insight into its utility through a clinical simulation. Methods and results: On a total of 526 656 ECGs from three different datasets, six different methods for estimation of aleatoric and epistemic uncertainty were systematically investigated. The methods were evaluated based on ranking, calibration, and robustness against out-of-distribution data. Furthermore, a clinical simulation was performed where increasing uncertainty thresholds were applied to achieve a clinically acceptable performance. Finally, the correspondence between the uncertainty of ECGs and the lack of interpretational agreement between cardiologists was estimated. Results demonstrated the largest benefit when modelling both epistemic and aleatoric uncertainty. Notably, the combination of variational inference with Bayesian decomposition and ensemble with auxiliary output outperformed the other methods. The clinical simulation showed that the accuracy of the algorithm increased as uncertain predictions were referred to the physician. Moreover, high uncertainty in DNN-based ECG classification strongly corresponded with a lower diagnostic agreement in cardiologist's interpretation (P < 0.001). Conclusion: Uncertainty estimation is warranted in automated DNN-based ECG classification and its accurate estimation enables intermediate quality control in the clinical implementation of deep learning. This is an important step towards the clinical applicability of automated ECG diagnosis using DNNs.

On stethoscopes, patient records, artificial intelligence, and zettabytes: A glimpse into the future of digital medicine in Mexico.

Science and technology are modifying medicine at a dizzying pace. Although access in our country to the benefits of innovations in the area of devices, data storage and artificial intelligence are still very restricted, the advance of digital medicine offers the opportunity to solve some of the biggest problems faced by medical practice and public health in Mexico. The potential areas where digital medicine can be disruptive are accessibility to quality medical care, centralization of specialties in large cities, dehumanization of medical treatment, lack of resources to access evidence-supported treatments, and among others. This review presents some of the advances that are guiding the new revolution in medicine, discusses the potential barriers to implementation, and suggest crucial elements for the path of incorporation of digital medicine in Mexico.

La ciencia y la tecnología han modificado la medicina a un ritmo vertiginoso. Si bien el acceso en México a los beneficios de las innovaciones en el área de dispositivos, almacenamiento de datos e inteligencia artificial aún es muy restringido, el avance de la medicina digital ofrece la oportunidad de solventar algunos de los problemas más grandes que enfrenta la práctica médica y la salud pública en este país. Las potenciales áreas en las que la medicina digital puede resultar innovadora son la accesibilidad a cuidados médicos de calidad, la centralización de las especialidades en grandes urbes, la deshumanización del trato médico, la falta de recursos para acceder a tratamientos avalados por evidencia, entre otros. Esta revisión presenta algunos de los avances que guían la nueva revolución en la medicina, revisa el potencial y las posibles barreras para su aplicación, además de sugerir elementos cruciales para el trayecto de incorporación de la medicina digital en México.

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery.

BACKGROUND AND AIMS: Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients. METHODS AND RESULTS: We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002). CONCLUSION: Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity. CLINICAL TRIAL REGISTRATION NUMBER: NCT01373892.

On stethoscopes, patient records, artificial intelligence, and zettabytes: A glimpse into the future of digital medicine in Mexico / Sobre estetoscopios, expedientes clínicos, inteligencia artificial y zettabytes: una mirada al futuro de la medicina digital en México

Abstract Science and technology are modifying medicine at a dizzying pace. Although access in our country to the benefits of innovations in the area of devices, data storage and artificial intelligence are still very restricted, the advance of digital medicine offers the opportunity to solve some of the biggest problems faced by medical practice and public health in Mexico. The potential areas where digital medicine can be disruptive are accessibility to quality medical care, centralization of specialties in large cities, dehumanization of medical treatment, lack of resources to access evidence-supported treatments, and among others. This review presents some of the advances that are guiding the new revolution in medicine, discusses the potential barriers to implementation, and suggest crucial elements for the path of incorporation of digital medicine in Mexico.

Resumen La ciencia y la tecnología han modificado la medicina a un ritmo vertiginoso. Si bien el acceso en México a los beneficios de las innovaciones en el área de dispositivos, almacenamiento de datos e inteligencia artificial aún es muy restringido, el avance de la medicina digital ofrece la oportunidad de solventar algunos de los problemas más grandes que enfrenta la práctica médica y la salud pública en este país. Las potenciales áreas en las que la medicina digital puede resultar innovadora son la accesibilidad a cuidados médicos de calidad, la centralización de las especialidades en grandes urbes, la deshumanización del trato médico, la falta de recursos para acceder a tratamientos avalados por evidencia, entre otros. Esta revisión presenta algunos de los avances que guían la nueva revolución en la medicina, revisa el potencial y las posibles barreras para su aplicación, además de sugerir elementos cruciales para el trayecto de incorporación de la medicina digital en México.

On stethoscopes, patient records, artificial intelligence and zettabytes: a glimpse into the future of digital medicine in Mexico.

Science and technology are modifying medicine at a dizzying pace. Although access in our country to the benefits of innovations in the area of devices, data storage and artificial intelligence is still very restricted, the advance of digital medicine offers the opportunity to solve some of the biggest problems faced by medical practice and public health in Mexico. The potential areas where digital medicine can be disruptive are: accessibility to quality medical care, centralization of specialties in large cities, dehumanization of medical treatment, lack of resources to access evidence-supported treatments, among others. This review presents some of the advances that are guiding the new revolution in medicine, discusses the potential and potential barriers to implementation, and suggests crucial elements for the path of incorporation of digital medicine in Mexico.

La ciencia y la tecnología han modificado la medicina a un ritmo vertiginoso. Si bien el acceso en México a los beneficios de las innovaciones en el área de dispositivos, almacenamiento de datos e inteligencia artificial aún es muy restringido, el avance de la medicina digital ofrece la oportunidad de solventar algunos de los problemas más grandes que enfrenta la práctica médica y la salud pública en este país. Las potenciales áreas en las que la medicina digital puede resultar innovadora son la accesibilidad a cuidados médicos de calidad, la centralización de las especialidades en grandes urbes, la deshumanización del trato médico, la falta de recursos para acceder a tratamientos avalados por evidencia, entre otros. Esta revisión presenta algunos de los avances que guían la nueva revolución en la medicina, revisa el potencial y las posibles barreras para su aplicación, además de sugerir elementos cruciales para el trayecto de incorporación de la medicina digital en México.

Repeated social defeat induces transient glial activation and brain hypometabolism: A positron emission tomography imaging study.

Psychosocial stress is a risk factor for the development of depression. Recent evidence suggests that glial activation could contribute to the development of depressive-like behaviour. This study aimed to evaluate in vivo whether repeated social defeat (RSD) induces short- and long-term inflammatory and metabolic alterations in the brain through positron emission tomography (PET). Male Wistar rats ( n = 40) were exposed to RSD by dominant Long-Evans rats on five consecutive days. Behavioural and biochemical alterations were assessed at baseline, day 5/6 and day 24/25 after the RSD protocol. Glial activation (11C-PK11195 PET) and changes in brain metabolism (18F-FDG PET) were evaluated on day 6, 11 and 25 (short-term), and at 3 and 6 months (long-term). Defeated rats showed transient depressive- and anxiety-like behaviour, increased corticosterone and brain IL-1ß levels, as well as glial activation and brain hypometabolism in the first month after RSD. During the third- and six-month follow-up, no between-group differences in any investigated parameter were found. Therefore, non-invasive PET imaging demonstrated that RSD induces transient glial activation and reduces brain glucose metabolism in rats. These imaging findings were associated with stress-induced behavioural changes and support the hypothesis that neuroinflammation could be a contributing factor in the development of depression.

Myocardial bridging of the left anterior descending coronary artery is associated with reduced myocardial perfusion reserve: a 13N-ammonia PET study.

Myocardial Bridging (MB) refers to the band of myocardium that abnormally overlies a segment of a coronary artery. This paper quantitatively evaluates the influence of MB of the left anterior descending artery (LAD) on myocardial perfusion of the entire left ventricle. We studied 131 consecutive patients who underwent hybrid rest/stress 13N-ammonia positron emission tomography (PET) and coronary computed tomography angiography (CCTA) due to suspected myocardial ischemia. Patients with previous myocardial infarction and/or significant coronary artery disease (≥ 50% stenosis) were excluded. Myocardial perfusion measurements were compared between patients with and without LAD-MB. Additionally, we evaluated the relationship between anatomical characteristics (length and depth) of LAD-MB and myocardial perfusion measurements. 17 (13%) patients presented a single LAD-MB. Global myocardial perfusion reserve (MPR) was lower in patients with LAD-MB than in patients without LAD-MB (1.9 ± 0.5 vs. 2.3 ± 0.6, p < 0.01). Global stress myocardial blood flow (MBF) was similar in patients with and without LAD-MB (2.2 ± 0.4 vs. 2.3 ± 0.7 ml/g/min, p = 0.40). Global rest MBF was higher in patients with LAD-MB than in patients without LAD-MB (1.2 ± 0.3 vs. 1.0 ± 0.2 ml/g/min, p < 0.01). Global rest MBF, stress MBF, and MPR quantifications were similar in patients with superficial and deep LAD-MB (all p = NS). We did not find any correlation between length and global rest MBF, stress MBF nor MPR (r = - 0.14, p = 0.59; r = 0.44, p = 0.07; and r = 0.45, p = 0.07 respectively). Quantitative myocardial perfusion suggests that LAD-MB may be related to impaired perfusion reserve, an indicator of microvascular dysfunction. Anatomical characteristics of LAD-MB were not related to changes in myocardial perfusion.

Effect of linagliptin on pulse wave velocity in early type 2 diabetes: A randomized, double-blind, controlled 26-week trial (RELEASE).

AIMS: To evaluate the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on aortic pulse wave velocity (PWV) as a surrogate marker of arterial stiffness and early atherosclerosis in people with early type 2 diabetes. METHODS: A total of 45 people with type 2 diabetes (median [interquartile range] age 63 [54-66] years, 61% men, mean ± standard deviation glycated haemoglobin [HbA1c] 6.3% ± 0.4% [45 ± 4.6 mmol/mol]), without cardiovascular disease and naïve to antidiabetic treatment, were randomized (1:1) to treatment with linagliptin 5 mg once daily or placebo for 26 weeks in a double-blind fashion. PWV was assessed at baseline, 4 and 26 weeks of treatment, and again at 30, 4 weeks after treatment. The primary endpoint was between-group difference in PWV (corrected for systolic blood pressure [SBP]) at week 26. Secondary endpoints included differences in central SBP and augmentation index (AIx). RESULTS: Compared with placebo, 26 weeks of linagliptin decreased PWV by an average of 0.91 m/s (95% confidence interval -1.76 to -0.06; P = .035). PWV returned to baseline after 4 weeks washout. Differences in central SBP and AIx were not different between linagliptin and placebo. Linagliptin decreased HbA1c (-0.4%; P < .001), fasting plasma glucose (-0.7 mmol/L; P = .002) and triglycerides (-0.49 mmol/L; P = .019) as compared with placebo. The changes in body weight, cholesterol and high-sensitivity C-reactive protein did not differ between groups. CONCLUSIONS: Linagliptin decreased aortic PWV in people with early-stage type 2 diabetes as compared with placebo after 26 weeks of treatment. These results suggest that linagliptin has a favourable effect on arterial stiffness.

Imaging of cardiac and renal perfusion in a rat model with 13N-NH 3 micro-PET.

Cardiac dysfunction leads to decreased organ perfusion. We aimed to measure cardiac and renal perfusion simultaneously with the use of (13)N-NH3-microPET in different rat models. Ten male Wistar rats underwent sham surgery (n = 5) or permanent coronary artery ligation to induce myocardial infarction (MI, n = 5). Eleven weeks later (13)N-NH3-microPET scan was performed to study the cardiac and renal perfusion. Cardiac perfusion was significantly reduced in MI group, directly correlated with ejection fraction and inversely correlated with MI size (r = 0.89; p < 0.001 and r = -0.86; p < 0.001 respectively). Renal perfusion showed a notional 17 % non-significant reduction in MI group when compared to sham (3.44 ± 0.40 vs. 4.12 ± 0.48 ml/g/min). There was a trend towards greater reduction of perfusion in cortical than medullar region. Cortex perfusion was negatively correlated with histological changes. (13)N-NH3-microPET may be a potential tool for evaluation of cardiac and renal functional and perfusion changes in presence of cardiac dysfunction in rat models.