Oftalmopatía tiroidea: determinación de parámetros de actividad clínica de la oftalmopatía tiroidea como factor pronóstico de respuesta al tratamiento inmunosupresor

Objective: To determine the usefulness of the clinical, biochemical and thyroid imaging parameters in patients with thyroid-associated ophthalmopathy, in predicting their response to immunosuppressive treatment. Methods: This retrospective study of 16 patients with thyroid ophthalmopathy considered a number of variables including sex, age, thyroid hormone levels, treatment of the thyroid dysfunction, clinical activity score (CAS), severity (NOSPECS) of the ophthalmopathy, signs in standardized A-mode ultrasonography, in CAT and/or NMR, and previously used treatments and their effectiveness. Results: The average age of the patients was 50.81 (S.D: 11.89) years; there were 5 males (31.3%) and 11 females (68.8%). The ophthalmopathy was classified as active in 10/16 patients (62.5%) and inactive in 6/16 (37.5%); and as moderate in 9/16 (56.25%) and severe in 7/16 (43.75%) according to the severity defined in NOSPECS. Ultrasonography was diagnostic in 100% of the cases. The severity decreased significantly (p ≤ 0.05), however the clinical activity decrease did not reach significance (p=0.38) during immunosuppressive therapy. Better results were obtained during treatment of patients with a higher CAS (p=0.04) and in those with more severe ophthalmopathy (p=0.02). There was a tendency for the patients with higher levels of TSI to respond better to the treatment (p=0.06). Conclusions: The CAS is the best parameter to quantify the activity of the disease and predicting the response to treatment. The higher the CAS and the more severe the ophthalmopathy, the better the response to treatment. No association existed between thyroid function and the activity or severity of the ophthalmopathy; or the effectiveness of treatmen

Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock : The ANDROMEDA-SHOCK Randomized Clinical Trial

IMPORTANCE: Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. OBJECTIVE: To determine if a peripheral perfusion–targeted resuscitation during early septic shock in adults is more effective than a lactate level–targeted resuscitation for reducing mortality. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. INTERVENTIONS: Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation–, renal replacement therapy–, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. RESULTS: Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, −8.5% [95% CI, −18.2% to 1.2%]). Peripheral perfusion–targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, −1.00 [95% CI, −1.97 to −0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. CONCLUSIONS AND RELEVANCE: Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality.Facultad de Ciencias Médica

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

ANFIS, SVM and ANN soft-computing techniques to estimate daily global solar radiation in a warm sub-humid environment

Daily solar radiation is an important variable in many models. In this paper, the accuracy and performance of three soft computing techniques (i.e., adaptive neuro-fuzzy inference system (ANFIS), artificial neural network (ANN) and support vector machine (SVM) were assessed for predicting daily horizontal global solar radiation from measured meteorological variables in the Yucatán Peninsula, México. Model performance was assessed with statistical indicators such as root mean squared error (RMSE), mean absolute error (MAE) and coefficient of determination (R2). The performance assessment indicates that the SVM technique with requirements of daily maximum and minimum air temperature, extraterrestrial solar radiation and rainfall has better performance than the other techniques and may be a promising alternative to the usual approaches for predicting solar radiation

Role of Pv-aCO2 gradient and Pv-aCO2/Ca-vO2 ratio during cardiac surgery: a retrospective observational study

Introduction: Arterial lactate, mixed venous O2 saturation, venous minus arterial CO2 partial pressure (Pv-aCO2) and the ratio between this gradient and the arterial minus venous oxygen content (Pv-aCO2/Ca-vO2) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of Pv-aCO2 and Pv-aCO2/Ca-vO2, and the interchangeability of the variables calculated from mixed and central venous samples. Methods: 35 cardiac surgery patients were included. Variables were measured or calculated: after anesthesia induction (T1), end of surgery (T2), and at 6...8.ßhours intervals after ICU admission (T3 and T4). Results: Macrohemodynamics was characterized by increased cardiac index and low systemic vascular resistances after surgery (p.ß<.ß0.05). Hemoglobin, arterial-pH, lactate, and systemic O2 metabolism showed significant changes during the study (p.ß<.ß0.05). Pv-aCO2 remained high and without changes, Pv-aCO2/Ca-vO2 was also high and decreased at T4 (p.ß<.ß0.05). A significant correlation was observed globally and at each time interval, between Pv-aCO2 or Pv-aCO2/Ca-vO2 with factors that may affect the CO2 hemoglobin dissociation. A multilevel linear regression model with Pv-aCO2 and Pv-aCO2/Ca-vO2 as outcome variables showed a significant association for Pv-aCO2 with SvO2, and BE (p.ß<.ß0.05), while Pv-aCO2/Ca-vO2 was significantly associated with Hb, SvO2, and BE (p.ß<.ß0.05) but not with cardiac output. Measurements and calculations from mixed and central venous blood were not interchangeable. Conclusions: Pv-aCO2 and Pv-aCO2/Ca-vO2 could be influenced by different factors that affect the CO2 dissociation curve, these variables should be considered with caution in cardiac surgery patients. Finally, central venous and mixed values were not interchangeable

How many RPAS can be safely integrated in non–segregated airspace?

The forthcoming integration of Remotely Piloted Aircraft System (RPAS) is one of the cmost omplex challenges for aviation. Europe draws to allow operating RPAS and conventional aircraft in non-segregated airspace by 2025, but this demanding perspective entails a thorough analysis of the different aspects involved. The RPAS integration in non-segregated airspace cannot imply an increase in the safety levels. This paper assesses how the RPAS integration affects safety levels. The goal is to regulate the number of RPAS that can jointly operate with conventional aircraft regarding conflict risk. This approach benchmarks a Calculated Level of Safety (CLS) with a Target Level of Safety (TLS). Monte Carlo (MC) simulations quantify the TLS based on schedules of conventional aircraft. Then, different combinations of conventional aircraft and RPAS provide different CLS. MC simulations are performed based on probabilistic distributions of aircraft performances, entry times and geographical distribution of aircraft. The safety levels are based on a conflict-risk model because the primary metrics are average number of conflicts and average conflict duration. The methodology is applied to one flight level of en-route airspace. The results provide restrictions to the number of RPAS that can jointly operate with conventional aircraft. Particularly, the TLS is quantified for four conventional aircraft and MC simulations provide the combinations of conventional aircraft and RPAS that fulfil the CLS. The same number of RPAS than conventional aircraft shows an increase over 90% average number of conflicts and 300% average conflict time

Efecto de la Suplementación con una Mezcla Probiótica sobre el Comportamiento Productivo de Cuyes (Cavia porcellus) durante la Fase de Crecimiento y Acabado

The study evaluated the effect of addition of a probiotic mix in the diet on body weight gain, feed intake and feed conversion of growing and finishing guinea pigs. A total of 64 male guinea pigs, 1 day-old from an experimental farm in Huncayo, Peru were selected. The animals were randomly allocated to four feed treatments consisting of a rye grass-clover forage basal diet supplemented with wheat bran plus 0, 100, 150 or 200 ml of a Lactobacillus-Bifidobacterium-Saccharomyces probiotic mix suspension. The probiotic was mixed with 1 kg of the supplement and supplied during 10 weeks. Significant linear response patterns to the probiotic levels were observed for body weight gain (y = 631.04571 + 0.60537x; r2=0.2971, p=0.029) and feed conversion (y = 6.21121 - 0.0339x; r2=0.625, p=0.0003). There was no significant effect on feed intake. It is concluded that the probiotic mix has the potential for improving the productivity and feed efficiency of guinea pigs, but higher levels should be explored in order to obtain biological and practical optimal results.Se evaluó el efecto de la adición de una mezcla probiótica en la dieta sobre la ganancia de peso, consumo de alimento y conversión alimenticia de cuyes en crecimiento y engorde. Se trabajó con 64 cuyes machos de un día de edad de una granja experimental en Huancayo, Perú. Los animales fueron distribuidos al azar en cuatro tratamientos consistentes en una dieta base de forraje (ryegrass-trébol rojo) suplementada con afrechillo de trigo, más 0, 100, 150 o 200 ml de una mezcla probiótica en suspensión de Lactobacillus-Bifidobacterium-Saccharomyces. La suspensión probiótica fue mezclada con 1 kg del suplemento y administrada por 10 semanas. Se observaron patrones significativos de respuesta lineal a los niveles del probiótico en ganancia de peso (y = 631.04571 + 0.60537x; r2=0.2971, p=0.029) y conversión alimenticia (y = 6.21121 - 0.0339x; r2=0.625, p=0.0003), sin que hubiera una respuesta significativa en consumo total de alimento. Se concluye que la mezcla probiótica tiene el potencial de incrementar la productividad y la eficiencia alimenticia en cuyes en crecimiento y acabado; sin embargo, mayores niveles del probiótico deberían ser explorados para obtener resultados biológicos y prácticos óptimos