Minimally-Invasive and Efficient Method to Accurately Fit the Bergman Minimal Model to Diabetes Type 2.

Introduction: Diabetes mellitus is a global burden that is expected to grow 25 % by 2030. This will increase the need for prevention, diagnosis and treatment of diabetes. Animal and individualized in silico models will allow understanding and compensation for inter and intra-individual differences in treatment and management strategies for diabetic patients. The method presented here can advance the concept of personalized medicine. Methods: Twenty experiments were performed with Sprague-Dawley rats with streptozotocin induced experimental diabetes in which the insulin-glucose response curve was recorded over 60-100 min using only an insulin pump and a percutaneous glucose sensor. The information was used to fit the five-parameter Bergman Minimal Model to the experimental results using a genetic algorithm with a root-mean-squared optimization rule. Results: The Bergman Minimal Model parameters were estimated with high accuracy, low prediction bias, and low average root-mean-squared error of 15.27 mg/dl glucose. Conclusions: This study demonstrates a simple method to accurately parameterize the Bergman Minimal Model. We used Sprague-Dawley rats since their physiology is close to that of humans. The parameters can be used to objectively characterize the physiological severity of diabetes. In this way, planned treatments can compensate for natural variations of conditions both inter and intra patients. Changes in parameters indicate the patient's diabetic condition using values of glucose effectiveness ( S G = p 1 ) and insulin sensitivity ( S I = p 3 / p 2 ). Quantifying the diabetic patient's condition is consistent with the trend toward personalized medicine. Parameter values can also be used to explain atypical research results of other studies and increase understanding of diabetes.

Tromboelastografía para cirugía general / Thromboelastography for general surgery

Resumen: Las pruebas convencionales de coagulación evalúan el tiempo en que los factores de coagulación se activan en el plasma sanguíneo, el cual carece de componentes celulares, como enzimas y plaquetas que intervienen en el desarrollo de la hemostasia. La tromboelastografía (TEG) realiza un análisis in vitro de la relación entre plaquetas, enzimas, fibrinógeno y otros elementos de la coagulación de manera integral; por lo que se utiliza con mayor frecuencia en cirugías cardíacas, trasplantes y cirugías de malformaciones arteriovenosas, donde la pérdida sanguínea esperada es mayor a 40% del volumen sanguíneo circulante. La inclusión de la TEG en la valoración preanestésica permite evaluar la actividad plaquetaria en los pacientes que utilizan antiagregantes, como clopidogrel o ácido acetilsalicílico, a través del mapeo plaquetario (Platelet Mapping®). Cuando se presenta hemorragia en el período transanestésico, la TEG permite identificar de manera específica el tipo de tratamiento necesario para mejorar la coagulación o la transfusión de elementos formes de la sangre. La TEG permite realizar protocolos más sofisticados de terapia transfusional, lo que implica una disminución de las complicaciones asociadas con la politransfusión y, por ende, la disminución de costos, por lo que estos beneficios justifican el uso rutinario de la TEG para cualquier cirugía general.

Abstract: Conventional coagulation tests evaluate the time in which the coagulation factors are activated in the blood plasma, which lacks cellular components such as enzymes and platelets that are involved in the development of hemostasis. Thromboelastography (TEG) performs an in vitro analysis of the relationship between platelets, enzymes, fibrinogen, and other coagulation elements in an integral way; reason why it is used more frequently in cardiac surgeries, transplants, and surgeries of arteriovenous malformations, where the expected blood loss is greater than 40% of the circulating blood volume. The inclusion of TEG in the pre-anesthetic evaluation allows evaluating platelet activity in patients who use antiplatelets therapy, such as clopidogrel or acetylsalicylic acid, through platelet mapping (Platelet Mapping®). When bleeding occurs in the trans-anesthetic period, TEG specifically identifies the type of treatment necessary to improve coagulation or transfusion of formed blood elements. The TEG allows more sophisticated transfusion therapy protocols to be carried out, which implies a decrease in complications associated with polytransfusion and a reduction in costs, so these benefits justify the routine use of TEG for any general surgery.

Accurate diagnosis of sepsis using a neural network: Pilot study using routine clinical variables.

BACKGROUND AND OBJECTIVES: Sepsis is a severe infection that increases mortality risk and is one if the main causes of death in intensive care units. Accurate detection is key to successful interventions, but diagnosis of sepsis is complicated because the initial signs and symptoms are not specific. Biomarkers that have been proposed have low specificity and sensitivity, are expensive, and not available in every hospital. In this study, we propose the use of artificial intelligence in the form of a neural network to diagnose sepsis using only common laboratory tests and vital signs that are routine and widely available. METHODS: A retrospective, cross sectional cohort of 113 patients from an intensive care unit, each with 48 routinely evaluated vital signs and biochemical parameters was used to train, validate and test a neural network with 48 inputs, 10 neurons in a single hidden layer and one output. The sensitivity and specificity of the neural network as a point sampled diagnostic test was calculated. RESULTS: All but one case were correctly diagnosed by the neural network, with 91% sensitivity and 100% specificity in the validation data set, and 100% sensitivity and specificity in the test data set. CONCLUSIONS: The designed neural network system can identify patients with sepsis, with minimal resources using standard laboratory tests widely available in most health care facilities. This should reduce the burden on the medical staff of a difficult diagnosis and should improve outcomes for patients with sepsis.

Significant and safe reduction of propofol sedation dose for geriatric population undergoing pacemaker implantation: randomized clinical trial.

OBJECTIVE: A previous multidisciplinary pilot study based on computer simulations for the geriatric population showed that a dose of 0.5 mg/kg/h of propofol could sedate patients older than 65 for pacemaker implantation. The present study validates that the pacemaker implantation can be done in the elderly using 0.5-1 mg/kg/h of propofol with hemodynamic stability. METHODS: 66 patients from 65 to 88 years old scheduled for pacemaker implantation were randomly assigned one of three doses of propofol. The first group received 2 mg/kg/h of propofol (P2) that is within normal range of the sedation dose. The second group received 1 mg/kg/h (P1) dose and the third group received the dose of 0.5 mg/kg/h (P0.5) according to the simulation-predicted dose for geriatric populations. RESULTS: All patients kept MAP between 76 and 85 mmHg, with no hypotension episodes in any of the groups; therefore, they were all hemodynamically stable during the procedure. BIS was between 80 and 65 during the pacemaker implantation for the three groups, BIS of group P2 was significantly lower than the other groups. BIS in groups P1 and P0.5 was within the appropriated range for moderate sedation. Brice was positive for auditory recalls only when there was arousing noise in the operating room. CONCLUSIONS: Moderate sedation, adequate for pacemaker implantation, can be achieved infusing 0.5-1 mg/kg/h of propofol in elderly patients when the patient has proper analgesia management at the device implantation site. The second important condition is to avoid unnecessary and alerting auditory and mechanical stimuli in the operating room, so that the patient will remain calm.

Clinical testing of propofol geriatic dose for sedation designed via in silico trial.

The geriatric population shows significant physiological changes due to aging and the multiple co-morbidities that they often present. Conventionally the propofol sedation dose for patients older than 65 years is 80% of the adult dose. We performed an in silico trial for elderly population and the results showed that the necessary simulated dose of propofol was lower than the conventional dose; therefore, a clinical trial was implemented to test three different propofol doses, two of them lower than the conventional dose, during a pacemaker implantation. The clinical trial showed that there was no clinical difference between the effects of the doses. A BIS monitor was used to measure the level of sedation, which proved to be adequate and well maintained by all patients. All the patients maintained an acceptable level of sedation, measured by a BIS monitor. Since propofol has some dose-dependent secondary effects, the use of lower doses, especially the ones designed for this age group, helps to avoid them.

High-order sliding-mode control for anesthesia.

Depth of anesthesia can be indirectly measured by Bispectral Index (BIS), therefore it is possible to administer propofol in a closed loop to maintain the optimal level of anesthesia while minimizing the dose to improve the postanesthesia recovery. High-Order Sliding-Mode control can be used to individualize drug dosing. In this study, the controller is tested with four in silico patients.