Memory and language risk assessment with Wada test in patients candidates for epilepsy surgery. / Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.

AIM: To determine post-surgical cognitive risk and associated factors according to lesion location in a sample of patients evaluated for epilepsy surgery with Wada test at the Fundacion Instituto Neurologico de Colombia. MATERIALS AND METHODS: An observational, retrospective, analytical study was completed in patients with drug-resistant temporal lobe epilepsy candidates for epilepsy surgery treated from 2001 to 2021, who completed the Wada test as part of the pre-surgical evaluation. A descriptive analysis of sociodemographic, clinical, imaging and neuropsychological variables was completed; a multivariate logistic regression was performed analyzing factors associated with resection risk in patients with left lesions. RESULTS A total of 369 patients were included, 54.74% of the cases were women, with a median age of seizure onset of 11 years. 92.66% of the cases had lesional epilepsy and 68.56% were secondary to hippocampal sclerosis. Left hemisphere was the most frequently affected (65.68%) being dominant for memory and language in most of the patients with a proportion of 42.82% and 81.3%, respectively. The median functional adequacy was 43.75 (IQR 0-75) and the functional reserve was 75 (IQR 25 -93.75). In 104 patients, the Wada test determined a resection risk. In patients with a left lesion, it was found that functional reserve (PRadjusted 0.99, CI 95% 0.9997-0.9998) and having a right hemispheric dominance for memory (PRadjusted 0.92, CI 95% 0.547-0.999) were protective factors for post-surgical resection risk. CONCLUSION: Wada test is a useful tool for surgical decision-making in patients with drug-resistant temporal lobe epilepsy. When considering cognitive risk, components such as memory dominance and functional reserve should be considered as protective factors for postsurgical cognitive function preservation in patients with left lesions.

TITLE: Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.Objetivo. Determinar el riesgo cognitivo posquirúrgico y factores asociados según la localización de la lesión en una muestra de pacientes evaluados para cirugía de epilepsia con el test de Wada en la Fundación Instituto Neurológico de Colombia. Materiales y métodos. Se realizó un estudio observacional, retrospectivo y analítico en pacientes con epilepsia farmacorresistente del lóbulo temporal candidatos a cirugía de epilepsia tratados entre 2001 y 2021, que completaron el test de Wada como parte de la evaluación prequirúrgica. Se realizó un análisis descriptivo de variables sociodemográficas, clínicas, imagenológicas y neuropsicológicas. Se realizó una regresión logística multivariada analizando factores asociados al riesgo de resección en pacientes con lesiones izquierdas. Resultados. Se incluyó a 369 pacientes, el 54,74% de los casos fueron mujeres, con una mediana de edad de inicio de las convulsiones de 11 años. El 92,66% de los casos presentó epilepsia lesional; de éstos, el 68,56% fue secundario a esclerosis hipocampal. El hemisferio izquierdo fue el más frecuentemente afectado (65,68%), y éste fue dominante para la memoria y el lenguaje en la mayoría de los pacientes, con una proporción del 42,82 y el 81,3%, respectivamente. La mediana de adecuación funcional fue de 43,75 (rango intercuartílico: 0-75) y la reserva funcional de 75 (rango intercuartílico: 25-93,75). En 104 pacientes, el test de Wada determinó un riesgo de resección. En pacientes con lesiones izquierdas se encontró que la reserva funcional (razón de prevalencia ajustada: 0,99; intervalo de confianza al 95%: 0,9997-0,9998) y tener dominancia del hemisferio derecho para la memoria (razón de prevalencia ajustada: 0,92; intervalo de confianza al 95%: 0,547-0,999) fueron factores asociados para determinar el riesgo de resección posquirúrgico en el test de Wada. Conclusión. El test de Wada es una herramienta útil para la toma de decisiones quirúrgicas en pacientes con epilepsia del lóbulo temporal farmacorresistente. Componentes como la dominancia de la memoria y la reserva funcional en el test de Wada deben considerarse como factores que se deben tener en cuenta en la predicción de la preservación de la función cognitiva posquirúrgica en pacientes con lesiones izquierdas.

Differential accumulation of human ß-amyloid and tau from enriched extracts in neuronal and endothelial cells.

While Aß and Tau cellular distribution has been largely studied, the comparative internalization and subcellular accumulation of Tau and Aß isolated from human brain extracts in endothelial and neuronal cells has not yet been unveiled. We have previously demonstrated that controlled enrichment of Aß from human brain extracts constitutes a valuable tool to monitor cellular internalization in vitro and in vivo. Herein, we establish an alternative method to strongly enrich Aß and Tau aggregates from human AD brains, which has allowed us to study and compare the cellular internalization, distribution and toxicity of both proteins within brain barrier endothelial (bEnd.3) and neuronal (Neuro2A) cells. Our findings demonstrate the suitability of human enriched brain extracts to monitor the intracellular distribution of human Aß and Tau, which, once internalized, show dissimilar sorting to different organelles within the cell and differential toxicity, exhibiting higher toxic effects on neuronal cells than on endothelial cells. While tau is strongly concentrated preferentially in mitochondria, Aß is distributed predominantly within the endolysosomal system in endothelial cells, whereas the endoplasmic reticulum was its preferential location in neurons. Altogether, our findings display a picture of the interactions that human Aß and Tau might establish in these cells.

Navigating the Mental Lexicon: Network Structures, Lexical Search and Lexical Retrieval.

This paper examines the implications of the association patterns in our understanding of the mental lexicon. By applying the principles of graph theory to word association data, we intend to explore which measures tap better into lexical knowledge. To that end, we had different groups of English as Foreign language learners complete a lexical fluency task. Based on these empirical data, a study was undertaken on the corresponding lexical availability graph (LAG). It is observed that the aggregation (mentioned through human coding) of all lexical tokens on a given topic allows the emergence of some lexical-semantic patterns. The most important one is the existence of some key terms, featuring both high centrality in the sense of network theory and high availability in the LAG, which define a hub of related terms. These communities of words, each one organized around an anchor term, or most central word, are nicely apprehended by a well-known network metric called modularity. Interestingly enough, each module seems to describe a conceptual class, showing that the collective lexicon, at least as approximated by LA Graphs, is organised and traversed by semantic mechanisms or associations via hyponymy or hiperonymy, for instance. Another empirical observation is that these conceptual hubs can be appended, resulting in high diameters compared to same-sized random graphs; even so it seems that the small-world hypothesis holds in LA Graphs, as in other social and natural networks.

Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain.

BACKGROUND: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). OBJECTIVES: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. METHODS: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). RESULTS: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. CONCLUSIONS: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.

Fluctuation Relations to Calculate Protein Redox Potentials from Molecular Dynamics Simulations.

The tunable design of protein redox potentials promises to open a range of applications in biotechnology and catalysis. Here, we introduce a method to calculate redox potential changes by combining fluctuation relations with molecular dynamics simulations. It involves the simulation of reduced and oxidized states, followed by the instantaneous conversion between them. Energy differences introduced by the perturbations are obtained using the Kubo-Onsager approach. Using a detailed fluctuation relation coupled with Bayesian inference, these are postprocessed into estimates for the redox potentials in an efficient manner. This new method, denoted MD + CB, is tested on a de novo four-helix bundle heme protein (the m4D2 "maquette") and five designed mutants, including some mutants characterized experimentally in this work. The MD + CB approach is found to perform reliably, giving redox potential shifts with reasonably good correlation (0.85) to the experimental values for the mutants. The MD + CB approach also compares well with redox potential shift predictions using a continuum electrostatic method. The estimation method employed within the MD + CB approach is straightforwardly transferable to standard equilibrium MD simulations and holds promise for redox protein engineering and design applications.

PERFORMANCE OF SIX SCREENING SCORES FOR OBSTRUCTIVE SLEEP APNOEA IN AN AFRICAN POPULATION.

Introduction: A screening tool for obstructive sleep apnoea (OSA) is useful in low-income countries where it may be difficult to access sleep recordings. The objective of this study was to assess the performance of six screening scores compared with objective sleep recording in an African population sample. Methods: This analysis is based on the "Benin Sleep and Society" (BeSAS) populational study in which respiratory polygraphy (PG) was performed using a type III device and OSA screening questionnaires (STOP, STOP-Bang, Berlin, NOSAS [≥ 8 and ≥ 5), No-Apnea, GOAL) were administered to participants. PG-defined OSA severity categories were defined according to the apnoea-hypopnoea index (AHI): mild (AHI 5 to <15/h), moderate (AHI 15 to <30/h) or severe (AHI≥30/h), and these were compared to score findings. Results: A total of 1810 subjects (mean age 45.4±14.6 years; 57.3% women) were included. For moderate to severe OSA, the area under the receiving operating characteristic (ROC) curve was greatest for GOAL and No-Apnea (0.70), followed by NoSAS5 (0.69). The highest sensitivity values were for NoSAS5 (0.73), No-Apnea (0.72), and GOAL (0.69), while NoSAS8 had the highest specificity (0.91), followed by Berlin (0.88) and GOAL (0.71). All scores performed poorly with respect to the positive predictive value (PPV), which was highest with NoSAS8 (0.38). Conclusion: This study provides the first comparison of the performance of screening scores for OSA in an African population. Although still low, PPV was highest with NoSAS8. Hence, NoSAS8 would be the screening method of choice for OSA in resource-constrained settings where formal sleep recordings are not accessible.

EVALUATION OF A MODIFIED EPWORTH SLEEPINESS SCALE TO RELIABLY ASSESS EXCESSIVE DAYTIME SLEEPINESS IN LOW-INCOME COUNTRIES: RESULTS FROM THE BENIN SOCIETY AND SLEEP (BESAS) STUDY.

Background: The Epworth Sleepiness Scale (ESS) is a tool widely used to assess excessive daytime sleepiness. Unfortunately, it is not reliable in low-income countries where situations such as reading a book, watching TV or driving a car are not common. The aim of this study was thus to assess the performance of a modified version of the Epworth scale in a low-income country. Methods: We used data from the Benin Society and Sleep (BeSAS) study where the ESS and a modified ESS (mESS) were administered to participants. In the mESS, questions four questions over eight were redesigned to reflect common living situations in Benin. The internal coherence of the mESS was assessed using the Cronbach alpha coefficient (CAC). The discriminatory ability of the scale was assessed by comparing the mean scores according to reported sleep quality, insomnia complaints and apnea-hypopnea index (AHI). Results: A total of 2909 participants were recruited, 1129 were male (38.9%) with a mean age (SD) of 44.7 (14.5) y. Overall, 52.4% (1526) completed all the mESS questions while 453 (15.6%) completed the standard ESS. The CAC of the mES was 0.86 showing good internal coherence. Concerning the discriminatory ability, mean scores for mESS were 7.8 for participants with ISI < 8 vs 9.2 for participants with ISI≥8 (p<0.001), 7.8 for participants withPSQI<5 vs 8.3 for participants with PSQI≥5 (p=0.03). No difference was found when comparing the participants participants using different cut-offs of AHI (15 and 30). Conclusion: The mES is more reliable than ES in the Beninese population. mESS shows good internal coherence and differentiates between insomniacs vs non-insomniacs and between good and poor sleepers. Although the mES is not a perfect score, it appears more relevant in the Benin population than the original Epworth scale but needs further validation/improvement in other low-income countries.

External validation of the InShape II study algorithm for exclusion of chronic thromboembolic pulmonary hypertension in patients with pulmonary thromboembolism.

BACKGROUND AND AIM: The most severe long-term complication of pulmonary embolism (PE) is chronic thromboembolic pulmonary hypertension (CTEPH), and its early diagnosis often requires numerous diagnostic tests. The InShape II study proposes an early screening algorithm that aims to reduce the number of echocardiographic studies. The objective of our study is to validate this algorithm in our patient cohort. MATERIALS AND METHODS: We retrospectively analyzed patients admitted to Hospital Rey Juan Carlos between November 2017 and February 2020, who were diagnosed with PE based on computed tomography angiography (CTA). Patients were followed for at least one year, and clinical, laboratory, and complementary test data were collected at three months and one year. The InShape II algorithm was applied to these patients to validate its results. RESULTS: During the study period, 236 patients were diagnosed with PE, of which 137 were excluded. The algorithm was validated in 99 patients. Applying the InShape II score, 19 echocardiograms would have been performed (three of them with intermediate-high probability of CTEPH), while 80 echocardiograms would have been avoided (two of them with intermediate-high probability). This yielded a sensitivity of 60% and a specificity of 83% for the score, with an area under the curve (AUC) of 0.715 (95% CI: 0.472-0.958). CONCLUSIONS: Our results support the notion that the InShape II algorithm could be a useful tool for initial screening of CTEPH in low-incidence settings, as it would avoid unnecessary echocardiograms that do not provide additional value.

Controlled Ovarian Stimulation Initiated at Different Phases of the Menstrual Cycle for Fertility Preservation in Oncological Patients: a Retrospective Study.

The purpose of this study is to compare conventional start in early follicular phase (EFP) with late follicular phase (LFP) and luteal phase (LP) in controlled ovarian stimulation (COS) for fertility preservation (FP) to assess differences in clinical outcomes. Retrospective study of the first cycles of COS for FP in oncological patients between 2012 and 2020 in a tertiary hospital. Two-hundred forty-eight cycles were classified into 3 groups: 176 cycles in EFP, 8 cycles in LFP, and 52 cycles in LP. Comparing LFP to EFP, there were no differences in number of oocytes (10.0 [6.3-16.0] vs 12.0 [8.0-18.0]; p = 0.253) or number of metaphase II (MII) obtained (7.0 [2.3-13.3] vs 9.0 [6.0-13.0]; p = 0.229). Total number of days needed was higher in LFP (14.5 [12.5-16.0] vs 3.0 vs 10.0 [8.3-11.0 p = 0.000) but without significant differences in number of days of usage of gonadotropins (11.5 [8.3-12.8] vs 10.0 [8.3-11.0] p = 0.308). No differences were found between LP and EFP in number of oocytes (14.5 [9.0-20.0] p = 0.151) or MII (11.5 [7.0-16.0] p = 0.084). Number of days of gonadotropins (11.0 [10.0-12.0] p = 0.00) and total dosing (3000.0 [2475.0-3600.0] p = 0.013) were significantly higher in LP. FORT and FOI were similar in all groups. COS with a random start in fertility preservation has similar outcomes to EFP start. Therefore, we can initiate COS at any phase of the menstrual cycle with optimal results. However, LP may need more days of stimulation.

Conducting Action Research to Improve Operational Efficiency in Manufacturing: The Case of a First-Tier Automotive Supplier.

Optimising available resources and minimising production costs and throughput time is vital for first-tier suppliers in the worldwide automotive sector. To develop this type of optimisation and efficiency, MAHLE applied Action Research (AR) in one of its factories located in Spain. A multidisciplinary collaborative work team was created with the aim of deploying the AR initiative in combination with Lean Manufacturing and Six Sigma tools. Four improvement and learning cycles were deployed and key performance metrics were defined to collect and measure data in order to analyse the improvements achieved. The application of the AR initiative in the production line of a power filter device enabled improvements in both production times and quality indicators in the manufacturing process. The most outstanding results were the improvements made in the decrease in initial throughput time (34.78%) and in average daily rejections (73.53%). In addition, the AR initiative generated practical and theoretical contributions for business and academia, allowing the AR initiative to be applied in other areas of the company, and contributing to the current state of the art in the industrial application of this methodology.

SAS CARE 1: Sleep architecture changes in a cohort of patients with Ischemic Stroke/TIA.

OBJECTIVE: Changes in sleep architecture following ischemic stroke have been poorly investigated. Our objective was to explore changes of sleep structure in patients with ischemic stroke or transient ischemic attack in order to verify a possible predictive value of sleep with respect to clinical outcome. METHODS: Patients recruited in the prospective SAS-CARE study received two polysomnographies (PSG) in the acute and chronic phases after stroke/TIA. Sleep parameters were compared between the two time-points and matched with a non-stroke population randomly selected from the HypnoLaus cohort. RESULTS: Of the 169 patients investigated with PSG in the acute phase, 104 were again studied 3 months after stroke symptom onset and compared with 162 controls. The acute phase of stroke/TIA was associated with sleep disruption, which significantly improved in the chronic phase, but remained worse than controls (total sleep time improve from 318.8 ± 90.8 to 348.4 ± 81.5 min, compared to 388.2 ± 71.3 in controls, sleep latency from 49.9 ± 58.4 to 27.9 min, compared to 20.2 ± 22 in controls, sleep efficiency from 58.2 ± 18.1% to 27.9 ± 36.4 min, compared to 83.4 ± 10.3% in controls, wakefulness after sleep onset percentage from 36.5 ± 17.3 to 29.3 ± 15.6, compared to 13.2 ± 9.2 in controls). The percentage of REM sleep was negatively associated with stroke severity, whereas stroke topography did not correlate with sleep parameters. CONCLUSIONS: This study confirmed a severe sleep disruption in the acute phase of stroke. Although a significant improvement of sleep quality was observed during the three months after stroke, sleep architecture did not normalize. In particular, sleep efficiency and REM sleep seem to be particularly affected by stroke in the acute phase, with a relative preservation of NREM sleep. We suggest that these sleep architecture changes represent a persistent marker of brain damage due to stroke. Further studies are needed to assess the relationship with stroke topographic and outcome.

Eudragit® L100/chitosan composite thin bilayer films for intravaginal pH-responsive release of Tenofovir.

The high rate of HIV new infections and AIDS-related deaths each year make prevention tools still necessary today. Different dosage forms - including films - for vaginal administration of antiretroviral drugs have been developed for this purpose. Six batches of Tenofovir-loaded films were formulated based on Eudragit® L100 (EL100) and chitosan, containing triethyl citrate and glycerol. In all the cases films structured in two layers - the upper layer mainly attributed to EL100 and the lower layer to chitosan - were revealed by SEM. A higher content in EL100 and plasticizers improves the mechanical properties and control over drug release in the vaginal medium without affecting mucoadhesion. The EL100-based layer acts as a structuring agent that controls Tenofovir release for days in the vaginal medium while it occurs in a few hours in the presence of seminal fluid. Bilayer films with the highest tested content of EL100 and plasticizers would be the most suitable as vaginal microbicides as they are easier to administer due to their excellent mechanical properties and they offer more comfortable posology and enhanced protection against HIV during intercourse due to their pH-responsive release of Tenofovir.

Intrinsic and selective activity of functionalized carbon nanotube/nanocellulose platforms against colon cancer cells.

Given their large surface area and versatile chemical reactivity, single-walled carbon nanotubes (SWCNTs) are regarded as the basis of new pharmacological complexes. In this study, SWCNTs are chemically functionalized with fluorescein, folic acid, and capecitabine, a drug that is commonly used against colorectal cancer. These functionalized SWCNTs are dispersed in water by taking advantage of their synergistic interaction with type-II nanocrystalline cellulose (II-NCC), and the resulting colloidal system is tested in vitro on both normal (differentiated) and cancerous (proliferative) human colon cells (Caco-2). The functionalized SWCNT/II-NCC hybrids show a higher activity than the reference (capecitabine) against the Caco-2 cancer cell line. However, this effect appears to be intrinsically associated with the SWCNT/II-NCC complex, particularly boosted by fluorescein, as the presence of capecitabine is not required. In addition, confocal microscopy fluorescence imaging using cell cultures highlights the enormous potential of this nanohybrid platform for colon cancer theranostics.

Comprehensive management of risk factors in peripheral vascular disease. Expert consensus.

INTRODUCTION: There is currently a degree of divergence among the main clinical practice guidelines on the management of risk factors for peripheral arterial disease (PAD). This project aims to gain understanding of the management of PAD risk factors in clinical practice and to reach a multidisciplinary consensus on the strategies to be followed in order to optimize its identification, treatment, and follow-up. METHODOLOGY: A multidisciplinary consensus following the Delphi methodology. RESULTS: Professionals (n = 130) with extensive experience in PAD participated in this consultation. The results suggest that in order to optimize the control of risk factors, efforts should be aimed at: (1) promoting the involvement and awareness of all specialists in the identification of and screening for the disease; (2) guaranteeing the possibility of evaluating the ankle-brachial index (ABI) in all the medical specialties involved; (3) promoting strategies for patients to quit smoking through the use of drugs, programs, or referrals to specialized units; (4) promoting an appropriate Mediterranean-based diet and the prescription of daily exercise; (5) raising awareness of the importance of ensuring LDL cholesterol values below 70 mg/dL, especially in symptomatic but also in asymptomatic patients (<55 mg/dL following the publication of the ESC/EAS guide); (6) recommending the use of antiplatelet therapy in asymptomatic patients with diabetes mellitus (DM) and/or a pathological ABI; and (7) protocolizing the annual evaluation of ABI in high-risk patients. CONCLUSION: This document presents the 22 agreed-upon strategies which are intended to help professionals optimize multidisciplinary management of PAD risk factors.

Caution with the use of dexamethasone in patients with COVID-19 in its initial phases.

INTRODUCTION: The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. METHOD: A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution. RESULTS: All patients received a 6 mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died. CONCLUSION: Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.

[Evaluation of the diagnostic test for rapid detection of covid-19 antigen (Panbio Covid rapid test) in primary care]. / Evaluación de la prueba diagnóstica de detección rápida de antígeno de covid-19 (Panbio Covid rapid test) en atención primaria.

OBJECTIVE: COVID-19 infection requires early diagnosis, with PCR being the gold standard test. The protocols advocate the use of rapid antigenic tests that require evaluation in actual clinical practice. The objective was to evaluate the diagnostic test for rapid antigen detection, Panbio Covid rapid test, compared with PCR, in patients with symptoms of 5 or less days of evolution and with a high-suspicion of infection by COVID-19 in a health center. MATERIALS AND METHODS: 103 patients over 14 years of age who attended an urban health center located in the Usera District of Madrid, with high-suspicion of COVID-19 infection, in the first 5 days of evolution from the onset of symptoms during the month of November 2020. INTERVENTIONS: diagnostic tests for COVID-19 are performed: antigen and PCR. RESULTS: The prevalence of the disease was 24.3% according to the PCR test and 17.5% according to the rapid antigenic test. The sensitivity was 72% (95% CI: 54.3-89.6%). The specificity was 100%. The positive and negative predictive values were 100% and 91.8% respectively. In the bivariate analysis, there was no relationship between symptoms and the presence of disease, except for myalgias (p=0.030). The multivariate analysis found a relationship between cough, dyspnea, fever, myalgia, anosmia/ageusia, and ocular symptoms and the presence of disease. CONCLUSIONS: The sensitivity and specificity for the Panbio rapid antigen test are similar to other studies performed in primary care. In high-prevalence of disease and with highly suspected symptoms, positive test results can be considered definitive, but negative results will require confirmation. Myalgia, fever, dyspnea, anosmia/ageusia, and ocular symptoms may be more related to the presence of COVID-19.

[Caution with the use of dexamethasone in patients with COVID-19 in its initial phases]. / Precaución con el uso de dexametasona en pacientes con COVID-19 en sus fases iniciales.

INTRODUCTION: The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. METHOD: A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution. RESULTS: All patients received a 6 mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died. CONCLUSION: Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.

Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment.

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

Association of NFκß, TNFα, IL-6, IL-1ß, and LPL Polymorphisms with Type 2 Diabetes Mellitus and Biochemical Parameters in a Mexican Population.

Chronic low-grade inflammation is strongly related to the etiology of diabetes mellitus type 2 (T2DM), and the expression of inflammatory cytokines may be modulated by polymorphisms located in the regulatory regions of the NFκß, IL-1ß, IL-6, TNFα, and LPL genes. We considered it particularly important to investigate the relationship of gene polymorphisms involved in chronic inflammation with the risk of T2DM or uncontrolled biochemical parameters. METHODS: We included 199 individuals with a T2DM diagnosis and 213 individuals without a T2DM diagnosis. Restriction fragment length polymorphism (RFLP) analyses were used to assess polymorphisms. RESULTS: We found a risk association between T2DM and uncontrolled biochemical parameters in a Mexican population for the genotypes del/del of NFκß, -174 and -572 of IL-6, C/C of IL-1ß, -308 and -238 of TNFα, and T/T of LPL. In subjects without diabetes (controls), we found an association between the G/C genotype of the -572 polymorphism and the G/C and C/C genotypes of the -597 polymorphism of IL-6 with the risk of glucose levels > 131 mg/dL. Genotype C/C of polymorphism -174 of the IL-6 gene was associated with high triglyceride levels, and levels > 5.8% of HbA1c were associated with the G/A genotype of TNFα -308. CONCLUSION: Here, we describe for the first time the relationship of T2DM risk and uncontrolled biochemical parameters with polymorphisms in the NFκß, IL-6, TNFα, IL-1ß, and LPL genes in a Mexican population. We also showed that for the population included in this study, there is an additive effect of the polymorphisms of the studied genes that considerably increases the risk of developing T2DM.We also showed that there are interactions between genes related to chronic inflammation that affect the risk of T2DM.