Detection of PatIent-Level distances from single cell genomics and pathomics data with Optimal Transport (PILOT).

Although clinical applications represent the next challenge in single-cell genomics and digital pathology, we still lack computational methods to analyze single-cell or pathomics data to find sample-level trajectories or clusters associated with diseases. This remains challenging as single-cell/pathomics data are multi-scale, i.e., a sample is represented by clusters of cells/structures, and samples cannot be easily compared with each other. Here we propose PatIent Level analysis with Optimal Transport (PILOT). PILOT uses optimal transport to compute the Wasserstein distance between two individual single-cell samples. This allows us to perform unsupervised analysis at the sample level and uncover trajectories or cellular clusters associated with disease progression. We evaluate PILOT and competing approaches in single-cell genomics or pathomics studies involving various human diseases with up to 600 samples/patients and millions of cells or tissue structures. Our results demonstrate that PILOT detects disease-associated samples from large and complex single-cell or pathomics data. Moreover, PILOT provides a statistical approach to find changes in cell populations, gene expression, and tissue structures related to the trajectories or clusters supporting interpretation of predictions.

Student survey after ten years of continuous blended teaching of echocardiography.

OBJECTIVE: To analyse the impact of 10 years of blended echocardiography teaching. METHODS AND RESULTS: A questionnaire was emailed to all medical doctors who graduated from the blended learning diploma in echocardiography developed by the University of Chile and taught by a team from Chile and Spain. One hundred and forty of the 210 students who graduated from the program between 2011 and 2020 completed the questionnaire: 53.57% were anaesthesiologists, and 26.42% were intensivists. More than 85% of respondents indicated that the online teaching met their expectations, and 70.2% indicated that the hands-on practice fulfilled the stated objectives. In a retrospective analysis using self-reported data, graduates reported that their use of transthoracic and transoesophageal echocardiography has increased from 24.29% to 40.71% and from 13.57% to 27.86%, repectively, after the programme compared to before the programme. They used echocardiography mainly in the perioperative period (56.7%) and during intensive care (32.3%), while only 11% of respondents used it in emergency care units. Nearly all (92.4%) respondents reported that the skills learned was very useful in their professional practice. CONCLUSIONS: Ten years after its launch, the blended learning diploma in echocardiography was well rated by graduate specialists, and is associated with a significant increase in the use of echocardiography in the perioperative period and during intensive care. The main challenges are to establish a longer period of practice and achieve greater implantation in emergency medicine.

Assessment of tricuspid annulus: anatomic and echocardiographic correlation.

Tricuspid regurgitation is associated with a poor outcome and its quantification remains a challenge. Tricuspid annulus dilatation is one of the parameters that influences clinical decision-making. The aim of this study was to compare the use of 2D transoesophageal echocardiography with surgical assessment for the measurement of the tricuspid annulus. Sixty-one cardiac patients (median age 64 years) were included in the study. Echocardiographic tricuspid annulus measurements were obtained from four chamber and transgastric short axis views and compared with the surgical measurements of this valve. The study was approved by the Ethics Committee of our institution. The tricuspid annulus measurements were obtained from the four chamber and the short axis views in 57 and 49 patients, respectively, while surgical measurement was performed in all 61 patients. Bland-Altman analysis of 49 tricuspid annulus-matched dimensions of the short axis view and surgical values showed a mean bias of 0.223 mm/m2, with limits of agreement of -5.86 to 6.31 mm/m2. Echocardiographic measurements of the tricuspid annulus dimension were accurate (90% sensitivity and 90% specificity for a four chamber view cut-off value ≥ 24.5 mm/m2, and 89% sensitivity and 97% specificity for a short axis view cut-off value ≥ 37.6 mm/m2, P < 0.0001; both cases) for detecting directly assessed annular dilatation by the surgeon in the operative field. Echocardiographic values of tricuspid annulus dimension have a good predictive value to detect surgically assessed annular dilatation and may help identify patients who require surgical tricuspid intervention.

In Situ LSPR Sensing of Secreted Insulin in Organ-on-Chip.

Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing.

A Radiometric Technique for Monitoring the Desulfurization Process of Blister Copper.

In this paper, a novel optical technique for following the progress of the blister copper desulfurization process is presented. The technique is based on the changes observed in the continuous spectrum of the visible-near-infrared (VIS-NIR) radiation that the blister melt emits while the chemical reactions of the sulfur elimination process are taking place. Specifically, the proposed technique uses an optical probe composed of an optical fiber, a collimating lens, and a quartz tube, which is immersed in the melt. This optical probe provides a field of view of the blowing zone where the desulfurization reaction occurs. The experimental results show that the melt VIS-NIR total irradiance evolves inversely to the SO2 concentration reported by a gas analyzer based on differential optical absorption spectroscopy. Furthermore, the blister copper spectral emissivity as well as the total emissivity observed throughout the process show strong correlation with the sulfur content during desulfurization reaction.

Erratum: Toro, C. et al. On the Detection of Spectral Emissions of Iron Oxides in Combustion Experiments of Pyrite Concentrates. Sensors 2020, 20, 1284.

The authors wish to make the following corrections to this paper [...].

[Recurrent hypoxemia secondary to a patent foramen ovale. Report of one case]. / Hipoxemia recurrente y formen oval permeable. Unidad diagnóstica fácilmente inadvertida. Caso clínico.

Patent foramen ovale (PFO) is a prevalent congenital septal atrial defect usually without pathological significance. In certain pathogenic situations, PFO can trigger episodes of recurrent hypoxemia, a specific condition known as platipnea-orthodeoxia syndrome (POS). We report a 73 years old female presenting with dyspnea and low arterial oxygen saturation. On admission the patient had a hemoglobin saturation of 81% and an arterial oxygen partial pressure of 50 mmHg. After breathing 100% a 17% arterial-venous shunt was found (normal: less than 12%). A transesophageal echocardiogram and a cardiac catheterization showed the presence of a PFO. A percutaneous closure was performed.

On the Detection of Spectral Emissions of Iron Oxides in Combustion Experiments of Pyrite Concentrates.

In this paper, we report on the spectral detection of wustite, Fe(II) oxide (FeO), and magnetite, Fe(II, III) oxide (Fe3O4), molecular emissions during the combustion of pyrite (FeS2), in a laboratory-scale furnace operating at high temperatures. These species are typically generated by reactions occurring during the combustion (oxidation) of this iron sulfide mineral. Two detection schemes are addressed: the first consisting of measurements with a built-in developed spectrometer with a high sensitivity and a high spectral resolution. The second one consisting of spectra measured with a low spectral resolution and a low sensitivity commercial spectrometer, but enhanced and analyzed with post signal processing and multivariate data analysis such as principal component analysis (PCA) and a multivariate curve resolution - the alternating least squares method (MCR-ALS). A non-linear model is also proposed to reconstruct spectral signals measured during pyrite combustion. Different combustion conditions were studied to evaluate the capacity of the detection schemes to follow the spectral emissions of iron oxides. The results show a direct correlation between FeO and Fe3O4 spectral features intensity, and non-linear relations with key combustion variables such as flame temperature, and the combusted sulfide mineral particle size.

Hipoxemia recurrente y formen oval permeable. Unidad diagnóstica fácilmente inadvertida. Caso clínico / Recurrent hypoxemia secondary to a patent foramen ovale. Report of one case

Patent foramen ovale (PFO) is a prevalent congenital septal atrial defect usually without pathological significance. In certain pathogenic situations, PFO can trigger episodes of recurrent hypoxemia, a specific condition known as platipnea-orthodeoxia syndrome (POS). We report a 73 years old female presenting with dyspnea and low arterial oxygen saturation. On admission the patient had a hemoglobin saturation of 81% and an arterial oxygen partial pressure of 50 mmHg. After breathing 100% a 17% arterial-venous shunt was found (normal: less than 12%). A transesophageal echocardiogram and a cardiac catheterization showed the presence of a PFO. A percutaneous closure was performed.

[Ventricular contractility: Physiology and clinical projection]. / Contractilidad ventricular: Fisiología y proyección clínica.

The contractile state of the heart is the result of myocardial contractility, the intrinsic mechanism that regulates the force and the shortening of the ventricle and determines the ventricular ejection volume. However, the ejection volume is also modulated by ventricular preload (diastolic ventricular volume) and afterload (resistance to ejection). Accordingly, a decrease in contractility may be masked by changes in preload or afterload, maintaining a normal ejection volume and delaying the diagnosis of myocardial damage. Thus, it is necessary to develop a non-invasive method to measure contractility in the clinical practice. We review in this article the basic principles of cardiac contraction, the concept of contractility and its measurement with the ventricular pressure-volume loop, an experimental method that also measures most of the hemodynamic variables of the cardiac cycle including preload, afterload, ventricular work, ventricular lusitropy and arterial elastance. This method has been recently validated in cardiac patients and allows to evaluate the evolution of contractility in heart failure in a non invasive way. Although some modifications are still necessary, it will probably have an extensive use in practical cardiology in the near future.

Contractilidad ventricular: fisiología y proyección clínica / Ventricular contractility: physiology and clinical projection

The contractile state of the heart is the result of myocardial contractility, the intrinsic mechanism that regulates the force and the shortening of the ventricle and determines the ventricular ejection volume. However, the ejection volume is also modulated by ventricular preload (diastolic ventricular volume) and afterload (resistance to ejection). Accordingly, a decrease in contractility may be masked by changes in preload or afterload, maintaining a normal ejection volume and delaying the diagnosis of myocardial damage. Thus, it is necessary to develop a non-invasive method to measure contractility in the clinical practice. We review in this article the basic principles of cardiac contraction, the concept of contractility and its measurement with the ventricular pressure-volume loop, an experimental method that also measures most of the hemodynamic variables of the cardiac cycle including preload, afterload, ventricular work, ventricular lusitropy and arterial elastance. This method has been recently validated in cardiac patients and allows to evaluate the evolution of contractility in heart failure in a non invasive way. Although some modifications are still necessary, it will probably have an extensive use in practical cardiology in the near future.

Studies on the role of apoptosis after transient myocardial ischemia: genetic deletion of the executioner caspases-3 and -7 does not limit infarct size and ventricular remodeling.

Although it is widely accepted that apoptosis may contribute to cell death in myocardial infarction, experimental evidence suggests that adult cardiomyocytes repress the expression of the caspase-dependent apoptotic pathway. The aim of this study was to analyze the contribution of caspase-mediated apoptosis to myocardial ischemia-reperfusion injury. Cardiac-specific caspase-3 deficient/full caspase-7-deficient mice (Casp3/7DKO) and wild type control mice (WT) were subjected to in situ ischemia by left anterior coronary artery ligation for 45 min followed by 24 h or 28 days of reperfusion. Heart function was assessed using M-mode echocardiography. Deletion of caspases did not modify neither infarct size determined by triphenyltetrazolium staining after 24 h of reperfusion (40.0 ± 5.1 % in WT vs. 36.2 ± 3.6 % in Casp3/7DKO), nor the scar area measured by pricosirius red staining after 28 days of reperfusion (41.1 ± 5.4 % in WT vs. 44.6 ± 8.7 % in Casp3/7DKO). Morphometric and echocardiographic studies performed 28 days after the ischemic insult revealed left ventricular dilation and severe cardiac dysfunction without statistically significant differences between WT and Casp3/7DKO groups. These data demonstrate that the executioner caspases-3 and -7 do not significantly contribute to cardiomyocyte death induced by transient coronary occlusion and provide the first evidence obtained in an in vivo model that argues against a relevant role of apoptosis through the canonical caspase pathway in this context.

Experiencia inicial del implante percutáneo de válvula aórtica en el Instituto Nacional del Tórax: Experience in 26 patients / Transcatheter aortic valve implantation

Background: Aortic valve stenosis (AS) is the most common valvular disease. Its surgical indication is undisputed in symptomatic severe AS, however, 30% of patients are at high surgical risk or inoperable. Transcatheter Valve Implantation (TAVI) is an alternative for this group of patients. Aim: To describe the clinical outcomes of TAVI in a group of patients treated at the Instituto Nacional del Tórax, Santiago, Chile. Patients and Methods: Prospective study including all patients referred for TAVI due to their high surgical risk or being inoperable. All-cause mortality, secondary stroke, permanent pacemaker implantation, vascular complications, prosthetic and periprosthetic regurgitation, Karnosfky test and Functional Capacity (FC) were assessed as endpoints. Results: We evaluated 26 patients with a mean age of 82 years (74% women) in whom 27 procedures were done. The mean Society of Thoracic Surgeons score was 8.8%. Overall mortality at 30 days, one and two years was 11.1, 18.5 and 29.6% respectively. Karnofsky score increased significantly from 62.3% at baseline to 83.9; 88.6 and 88.8% at six months, one and two years, respectively. Prior to the procedure, FC was 3.1 ± 0.6, decreasing significantly to 1.2; 1.3 and 1 at six months, one and two years of follow up. Conclusions: TAVI is an effective alternative treatment for patients with severe symptomatic AS and high surgical risk.

Exercise preconditioning of myocardial infarct size in dogs is triggered by calcium.

We showed that exercise induces early and late myocardial preconditioning in dogs and that these effects are mediated through nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase activation. As the intracoronary administration of calcium induces preconditioning and exercise enhances the calcium inflow to the cell, we studied if this effect of exercise triggers exercise preconditioning independently of its hemodynamic effects. We analyzed in 81 dogs the effect of blocking sarcolemmal L-type Ca channels with a low dose of verapamil on early and late preconditioning by exercise, and in other 50 dogs, we studied the effect of verapamil on NADPH oxidase activation in early exercise preconditioning. Exercise reduced myocardial infarct size by 76% and 52% (early and late windows respectively; P < 0.001 both), and these effects were abolished by a single low dose of verapamil given before exercise. This dose of verapamil did not modify the effect of exercise on metabolic and hemodynamic parameters. In addition, verapamil blocked the activation of NADPH oxidase during early preconditioning. The protective effect of exercise preconditioning on myocardial infarct size is triggered, at least in part, by calcium inflow increase to the cell during exercise and, during the early window, is mediated by NADPH oxidase activation.

[Transcatheter aortic valve implantation.Experience in 26 patients]. / Experiencia inicial del implante percutáneo de válvula aórtica en el Instituto Nacional del Tórax.

BACKGROUND: Aortic valve stenosis (AS) is the most common valvular disease. Its surgical indication is undisputed in symptomatic severe AS, however, 30% of patients are at high surgical risk or inoperable. Transcatheter Valve Implantation (TAVI) is an alternative for this group of patients. AIM: To describe the clinical outcomes of TAVI in a group of patients treated at the Instituto Nacional del Tórax, Santiago, Chile. PATIENTS AND METHODS: Prospective study including all patients referred for TAVI due to their high surgical risk or being inoperable. All-cause mortality, secondary stroke, permanent pacemaker implantation, vascular complications, prosthetic and periprosthetic regurgitation, Karnosfky test and Functional Capacity (FC) were assessed as endpoints. RESULTS: We evaluated 26 patients with a mean age of 82 years (74% women) in whom 27 procedures were done. The mean Society of Thoracic Surgeons score was 8.8%. Overall mortality at 30 days, one and two years was 11.1, 18.5 and 29.6% respectively. Karnofsky score increased significantly from 62.3% at baseline to 83.9; 88.6 and 88.8% at six months, one and two years, respectively. Prior to the procedure, FC was 3.1 ± 0.6, decreasing significantly to 1.2; 1.3 and 1 at six months, one and two years of follow up. CONCLUSIONS: TAVI is an effective alternative treatment for patients with severe symptomatic AS and high surgical risk.

Utilidad del suplemento de probioticos (Lactobacillus acidophilus y bulgaricus) en el tratamiento del Síndrome de Intestino Irritable / Probiotic supplement (Lactobacillus acidophilus and bulgaricus) utility in the treatment of irritable bowel syndrome

El Sindrome de Intestino Irritable (SII), es un transtorno funcional muy común y causa frecuente de consulta en gastroenterología, su fisiopatología es multifactorial y se caracteriza por dolor abdominal, distensión y alteración de los hábitos defecatorios, su terapia es básicamente sintomática (loperamida, antiespasmódicos, antidepresivos,etc).Recientemente se ha incorporado al tratamiento, el uso de probióticos que podrían mejorar su sintomatología. POBLACIÓN Y MÉTODO: Ensayo Clínico doble ciego aleatorizado simple, multicentrico que incluyó pacientes con diagnóstico de SII basado en criterios de Roma III. A estos se les administró Bromuro de Pinaverio mas placebo o Bromuro de Pinaverio mas Probiótico. La intensidad de los síntomas y el efecto del tratamiento fue valorado de acuerdo a Score de Francis antes y al final del tratamiento. Los cálculos fueron hechos con el programa SPSS 12.0.IC 95% RESULTADO. Se evaluaron 51 pacientes con promedio de edad de 43 años, mayoritariamente mestizos, 75%(38) casados y 55%(28) del sexo femenino, se encontró diferencias significativas en 4 variables de comparación: Dolor abdominal, Severidad del dolor, Días de dolor, y el Score total al final del tratamiento. CONCLUSIONES Los Probióticos utilizados como suplemento son efectivos en mejorar la sintomatología del SII.

Background: Irritable bowel syndrome (IBS) is a very common functional condition and a frequent cause of consultation in gastroenterology. With a multifactorial pathophysiology IBS is characterized by abdominal pain, distension and altered bowel habits. Loperamide, antispasmodics and antidepressants are symptomatic relievers of this disorder. Recently probiotics were incorporated to therapy, and could improve the symptomatology. Methods: multicenter randomized placebo-controlled trial that included IBS patients, diagnosed with Rome III criteria. The patients were given pinaverium bromure and placebo or pinaverium bromure and probiotics for 3 weeks. The intensity of symptoms and the effect of therapy were evaluated with the Francis Score, before and after the treatment. Statistics were done with SPSS 12.0 (C.I 95%). Results: 51 patients were evaluated, with an average age of 43 years old, mostly mestizo, 75% (38) married and 55% (28) female. There were statistical differences in four variables: abdominal pain, intensity of pain, days of pain and total score at the end of therapy. Conclusions: Probiotics used as supplement are effective in improving symptomatology of IBS.

[Probiotic supplement (Lactobacillus acidophilus and bulgaricus) utility in the treatment of irritable bowel syndrome]. / Utilidad del suplemento de probioticos (Lactobacillus acidophilus y bulgaricus) en el tratamiento del sindrome de intestino irritable.

BACKGROUND: Irritable bowel syndrome (IBS) is a very common functional condition and a frequent cause of consultation in gastroenterology. With a multifactorial pathophysiology IBS is characterized by abdominal pain, distension and altered bowel habits. Loperamide, antispasmodics and antidepressants are symptomatic relievers of this disorder. Recently probiotics were incorporated to therapy, and could improve the symptomatology. METHODS: multicenter randomized placebo-controlled trial that included IBS patients, diagnosed with Rome III criteria. The patients were given pinaverium bromure and placebo or pinaverium bromure and probiotics for 3 weeks. The intensity of symptoms and the effect of therapy were evaluated with the Francis Score, before and after the treatment. Statistics were done with SPSS 12.0 (C.I 95%). RESULTS: 51 patients were evaluated, with an average age of 43 years old, mostly mestizo, 75% (38) married and 55% (28) female. There were statistical differences in four variables: abdominal pain, intensity of pain, days of pain and total score at the end of therapy. CONCLUSIONS: Probiotics used as supplement are effective in improving symptomatology of IBS.

Disfunción cognitiva después de cirugía cardiaca: Saturación cerebral e índice biespectral: estudio longitudinal / Neuropsychological dysfunction after cardiac surgery: Cerebral saturation and bispectral index: A longitudinal study

Background: Neuropsychological dysfunction is a major cause of morbidity and mortality after cardiac surgery. Aim: To evaluate if intraoperative cerebral desatu-ration and depth of anesthesia measured by bispectral index are related to postoperative cognitive dysfunction in cardiac surgery. Material and Methods: Prospective study in patients undergoing elective cardiac surgery with cardiopulmonary bypass. A comprehensive neuropsychological assessment was applied preoperatively and 3 months after surgery. Postoperative dysfunction was defined as a decrease of at least one standard deviation in two or more neuropsychological tests. Cerebral oxygenation and bispectral index were continuously recorded and corrected throughout surgery. Cerebral oxygenation data were analyzed by the mean value and at three thresholds: 50%, 40% and < 25% of the basal value. Bispectral index was analyzed at threshold of 45. Results: Fifty-six patients were initially enrolled and 48 completed the study. Nine of these (18.8 %) presented postoperative cognitive dysfunction. Mean cerebral saturation and bispectral index data were not different among the patients with or without cognitive dysfunction. There was no association between cerebral desaturation and bispectral index with changes in neurocognitive tests or with length of stay in the intensive care unit. A significant but weak correlation was found between baseline Ray-neurocognitive score and intensive care unit stay (rho = -0.46; P = 0.001). Conclusions: We did not find a significant association between cerebral desaturation and depth of anesthesia with postoperative cognitive decline in this population of patients.

[Neuropsychological dysfunction after cardiac surgery: Cerebral saturation and bispectral index: A longitudinal study]. / Disfunción cognitiva después de cirugía cardiaca: Saturación cerebral e índice biespectral: estudio longitudinal.

BACKGROUND: Neuropsychological dysfunction is a major cause of morbidity and mortality after cardiac surgery. AIM: To evaluate if intraoperative cerebral desaturation and depth of anesthesia measured by bispectral index are related to postoperative cognitive dysfunction in cardiac surgery. MATERIAL AND METHODS: Prospective study in patients undergoing elective cardiac surgery with cardiopulmonary bypass. A comprehensive neuropsychological assessment was applied preoperatively and 3 months after surgery. Postoperative dysfunction was defined as a decrease of at least one standard deviation in two or more neuropsychological tests. Cerebral oxygenation and bispectral index were continuously recorded and corrected throughout surgery. Cerebral oxygenation data were analyzed by the mean value and at three thresholds: 50%, 40% and < 25% of the basal value. Bispectral index was analyzed at threshold of 45. RESULTS: Fifty-six patients were initially enrolled and 48 completed the study. Nine of these (18.8 %) presented postoperative cognitive dysfunction. Mean cerebral saturation and bispectral index data were not different among the patients with or without cognitive dysfunction. There was no association between cerebral desaturation and bispectral index with changes in neurocognitive tests or with length of stay in the intensive care unit. A significant but weak correlation was found between baseline Ray-neurocognitive score and intensive care unit stay (rho = -0.46; P = 0.001). CONCLUSIONS: We did not find a significant association between cerebral desaturation and depth of anesthesia with postoperative cognitive decline in this population of patients.