Fatal COVID-19 Infection in Two Children with STAT1 Gain-of-Function.

While SARS-CoV-2 infection causes a mild disease in most children, SARS-CoV-2 infection may be lethal in a few of them. In the defense against SARS-CoV-2, type I interferons are key players, and several studies have identified a defective or neutralized interferon response as the cause of overwhelming viral infection. However, inappropriate, untimely, or excessive interferon production may also be detrimental to the host. Here, we describe two patients with STAT1 gain-of-function (GOF), a known type I interferonopathy, who died of COVID-19. Whole-exome sequencing and interferon-gamma-activated sequence (GAS) and interferon-sensitive responsive element (ISRE) reporter assay were performed to identify and characterize STAT1 variants. Patient 1 developed hemophagocytic lymphohistiocytosis (HLH) in the context of COVID-19 infection and died in less than a week at the age of 4 years. Patient 2 developed a high fever, cough, and hypoxemia and succumbed to COVID-19 pneumonia at the age of 5 years. Two heterozygous missense variants, p.E563Q and p.K344E, in STAT1 were identified. Functional validation by reporter assay and immunoblot confirmed that both variants are gain-of-function (GOF). GOF variants transiently expressing cells exhibited enhanced upregulation of downstream genes, including ISG15, MX1, and OAS1, in response to IFN-α stimulation. A catastrophic course with HLH or acute respiratory failure is thought to be associated with inappropriate immunoregulatory mechanisms to handle SARS-CoV-2 in STAT1 GOF. While most patients with inborn errors of immunity who developed COVID-19 seem to handle it well, these cases suggest that patients with STAT1-GOF might be at risk of developing fatal complications due to SARS-CoV-2.

Mast Cell and Astrocyte Hemichannels and Their Role in Alzheimer's Disease, ALS, and Harmful Stress Conditions.

Considered relevant during allergy responses, numerous observations have also identified mast cells (MCs) as critical effectors during the progression and modulation of several neuroinflammatory conditions, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). MC granules contain a plethora of constituents, including growth factors, cytokines, chemokines, and mitogen factors. The release of these bioactive substances from MCs occurs through distinct pathways that are initiated by the activation of specific plasma membrane receptors/channels. Here, we focus on hemichannels (HCs) formed by connexins (Cxs) and pannexins (Panxs) proteins, and we described their contribution to MC degranulation in AD, ALS, and harmful stress conditions. Cx/Panx HCs are also expressed by astrocytes and are likely involved in the release of critical toxic amounts of soluble factors-such as glutamate, adenosine triphosphate (ATP), complement component 3 derivate C3a, tumor necrosis factor (TNFα), apoliprotein E (ApoE), and certain miRNAs-known to play a role in the pathogenesis of AD, ALS, and other neurodegenerative disorders. We propose that blocking HCs on MCs and glial cells offers a promising novel strategy for ameliorating the progression of neurodegenerative diseases by reducing the release of cytokines and other pro-inflammatory compounds.

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice.

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice (p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1ß and TNF-α were diminished after 10 days' treatment compared with control group (p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

Serum leptin is associated with metabolic syndrome in obese Mexican subjects.

BACKGROUND: The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including insulin resistance, dyslipidemia, high blood pressure, and abdominal adiposity. Obese patients develop leptin resistance, and an increased waist circumference (WC) due to deposition of abdominal fat. The aim of this study was to evaluate the association between circulating leptin levels and MetS among sample adult Mexican workers. METHOD: A total of 204 workers aged 20-56 were evaluated. Anthropometric index, blood pressure, fasting plasma glucose, and lipid profile were measured by spectrophotometric methods. Fasting insulin and leptin were measured by inmunoenzimatic methods. Furthermore, homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. RESULTS: The prevalence of MetS according to the ATP-III criteria was 33.8% and leptin concentrations were 2.5 times higher in women than men. Subjects with MetS had higher levels of leptin (26.7 ± 13.7) compared with those without MetS (20.1 ± 13.9; P <0.001). Leptin increased significantly while BMI increased as well (normal 14.0 ± 8.9, overweight 22.7 ± 11.7 and obese 31.4 ± 14.6) in addition to other variables such as WC, HDL-C, insulin levels, and HOMA index. Each component of MetS was stratified by sex and submitted by linear regression with a 95% of accuracy. The 50% and 53% of the BMI is explained by the concentration of leptin in men and women, respectively (P < 0.001). CONCLUSION: This study found that leptin was associated with the MetS, especially in obesity and insulin resistance, indicating a high risk for university workers to develop hypertension, DM2, and cardiovascular disease.

Exploring Indicators for Training Load Control in Young Swimmers: The Role of Inspiratory Spirometry Outcomes.

One of the most important implications of technology in swimming is to control training loads. Lactate control, video-analysis of the technique or the assessment of specific actions, i.e., the vertical jump, have helped to provide load adaptation indicators in swimmers in recent decades. However, these indicators have led to a longer application time, due to their indirect procedure and the need to analyze each variable. The aim of this study was to analyze whether inspiratory spirometry values can serve as a training load control tool in swimmers. Countermovement jump (CMJ), Inspiratory Force Index (S-INDEX) and Peak Inspiratory Flow (PIF) were evaluated with a load of 3 cm H2O before, during and after performing a swimming performance test (critical speed test: specific warming up, 400 m and 100 m freestyle). Positive correlations were found between S-INDEX and jump height after warm-up, after 400 m and at the end of 100 m (Spearman = 0.470, R2 = 0.280; Spearman = 0.508, R2 = 0.392; Spearman = 0.458, R2 = 0.359, p < 0.05, respectively). Moreover, positive correlations were also found between PIF and jump height at the same evaluated moments (Spearman = 0.461, R2 = 0.305; Spearman = 0.493, R2 = 0.386; Spearman = 0.454, R2 = 0.374, p < 0.05). Both the S-INDEX and the PIF could serve as useful tools for swimmer load control, allowing coaches to make more immediate decisions.

The Effect of a Novel Video Game on Young Soccer Players' Sports Performance and Attention: Randomized Controlled Trial.

Background: Currently, the fusion of technology and sports is inevitable. The integration of various systems and devices has brought about significant transformations in established sports practices, impacting not only the rules but also physiological, biomechanical, and even psychological aspects. Objective: The purpose of this study was to analyze the effect of an attention intervention through a video game on young soccer players. Methods: Twelve young male soccer players (age: mean 8.5, SD 1 years) were divided into 2 groups: a control group (CG; n=10) and an experimental group (EG; n=10). During the 6-week training program, the EG received attention training through a video game twice a week for 15 minutes per session. Pre- and postintervention measurements included a specific decision-making soccer test and interviews with coaching staff. Additionally, success in the video game, muscular activity, and sweat levels were monitored. Results: The EG demonstrated a significant improvement in video game success following the intervention program, as indicated by the achieved level (P<.001). However, no significant differences were found between groups regarding electromyographic (EMG) activity (P=.21) and sweating (P=.20). Prior to implementing the attention training program, both groups exhibited similar data for variables related to decision-making and execution mechanisms (≤10%). Only 2 decision-making variables exceeded 10% but remained below 15% (Shot_D=13.35%; Marking_with_Ball_D=-12.64%). Furthermore, changes in attacking action variables were more pronounced in execution-related variables, except for dribbling and fixing. Conversely, in defensive action variables, changes were greater in decision-related variables, except for marking with the ball and marking without the ball. Conclusions: Our findings reveal that incorporating a specific attentional video game into a soccer training program enhances decision-making compared to a program without the video game. Therefore, it is advisable for practitioners to consider using this tool due to its high efficiency in terms of economic and temporal costs, particularly in improving a key psychological variable.

Albumin Redox Modifications Promote Cell Calcification Reflecting the Impact of Oxidative Status on Aortic Valve Disease and Atherosclerosis.

Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels. In addition, valvular interstitial cells were treated with reduced, oxidized, and native albumin to study how this protein and its modifications affect cell calcification. The differences we found suggest that oxidative status is distinct in CAVD and CAD, with differences in redox markers and thiol levels. Importantly, the in vitro interstitial cell model revealed that modified albumin affects cell calcification, accelerating this process. Hence, we show here the importance of the redox system in the development of CAVD, emphasizing the relevance of multimarker scores, while also offering evidence of how the redox state of albumin influences vascular calcification. These data highlight the relevance of understanding the overall redox processes involved in these diseases, opening the door to new studies on antioxidants as potential therapies for these patients.

Reduction in the Use of Some Herbicides Favors Nitrogen Fixation Efficiency in Phaseolus vulgaris and Medicago sativa.

In recent decades, the quality of agricultural soils has been seriously affected by the excessive application of pesticides, with herbicides being one of the most abundant. Continuous use of herbicides alters the soil microbial community and beneficial interactions between plants and bacteria such as legume-rhizobia spp. symbiosis, causing a decrease in the biological nitrogen fixation, which is essential for soil fertility. Therefore, the aim of this work was to study the effect of two commonly used herbicides (pendimethalin and clethodim) on the legume-rhizobia spp. symbiosis to improve the effectiveness of this process. Phaseolus vulgaris plants grown in pots with a mixture of soil:perlite (3:1 v/v), showed a 44% inhibition of nitrogen fixation rate with pendimethalin. However, clethodim, specifically used against monocots, did not induce significant differences. Additionally, we analyzed the effect of herbicides on root exudate composition, detecting alterations that might be interfering with the symbiosis establishment. In order to assess the effect of the herbicides at the early nodulation steps, nodulation kinetics in Medicago sativa plants inoculated with Sinorhizobium meliloti were performed. Clethodim caused a 30% reduction in nodulation while pendimethalin totally inhibited nodulation, producing a reduction in bacterial growth and motility as well. In conclusion, pendimethalin and clethodim application reduced the capacity of Phaseolus vulgaris and Medicago sativa to fix nitrogen by inhibiting root growth and modifying root exudate composition as well as bacterial fitness. Thus, a reduction in the use of these herbicides in these crops should be addressed to favor a state of natural fertilization of the soil through greater efficiency of leguminous crops.

A cryptic splice-altering KCNQ1 variant in trans with R259L leading to Jervell and Lange-Nielsen syndrome.

Here we report an infant with clinical findings suggestive of Jervell and Lange-Nielsen syndrome (JLNS), including a prolonged QT interval (LQTS) and chronic bilateral sensorineural deafness. NGS analysis revealed one known heterozygous pathogenic missense variant, KCNQ1 p.R259L, previously associated with LQTS but insufficient to explain the cardioauditory disorder. In a screening of proximal intronic regions, we found a heterozygous variant, KCNQ1 c.1686-9 T > C, absent from controls and previously undescribed. Several splicing prediction tools returned low scores for this intronic variant. Driven by the proband's phenotype rather than the neutral predictions, we have characterized this rare intronic variant. Family analysis has shown that the proband inherited the missense and the intronic variants from his mother and father, respectively. A minigene splicing assay revealed that the intronic variant induced an additional transcript, arising from skipping of exon 14, which was translated into a truncated protein in transfected cells. The splice-out of exon 14 creates a frameshift in exon 15 and a stop codon in exon 16, which is the last exon of KCNQ1. This mis-spliced transcript is expected to escape nonsense-mediated decay and predicted to encode a truncated loss-of-function protein, KCNQ1 p.L563Kfs*73. The analysis of endogenous KCNQ1 expression in the blood of the proband's parents detected the aberrant transcript only in the patient's father. Taken together, these analyses confirmed the proband's diagnosis of JLNS1 and indicated that c.1686-9 T > C is a cryptic splice-altering variant, expanding the known genetic spectrum of biallelic KCNQ1 variant combinations leading to JLNS1.

Nitazoxanide Exerts Immunomodulatory Effects on Peripheral Blood Mononuclear Cells from Type 2 Diabetes Patients.

BACKGROUND: Type 2 diabetes (T2D) is a low-grade inflammatory condition with abnormalities in the immune response mediated by T lymphocytes and macrophages. Drug repositioning for immunomodulatory molecules is an attractive proposal for treating T2D. Nitazoxanide (NTZ) is a broad-spectrum drug with promising immunomodulatory effects. Thus, we investigated the immunomodulatory effect of NTZ on peripheral blood mononuclear cells (PBMCs) from patients with T2D. METHODS: Fifty patients with T2D were selected, and the proliferative response of T lymphocytes and the M1/M2 ratio of macrophages post cell culture were evaluated by flow cytometry, as well as measuring the concentration of cytokines by ELISA and the relative expression of microRNAs (miRNAs) related to the immune response by real-time PCR. RESULTS: NTZ exerts an inhibitory effect on the cell proliferation of T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies without modifying cell viability, and significant decreases in the supernatant concentrations of interleukin (IL)-1ß, IL-2, IL-6, IL-10, and IL-12. Furthermore, NTZ negatively regulates the relative expression of miR-155-5p without changes in miR-146a-5p. The M1/M2 ratio of monocytes/macrophages decreased the M1 and increased the M2 subpopulation by NTZ. CONCLUSIONS: Our results suggest that NTZ exerts immunomodulatory effects on PBMCs from T2D patients, and shows potential alternative therapeutic benefits.

The p.(Cys150Tyr) variant in CSRP3 is associated with late-onset hypertrophic cardiomyopathy in heterozygous individuals.

INTRODUCTION AND OBJECTIVES: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. Mutations in CSRP3 have been associated with HCM, but evidence supporting pathogenicity is inconclusive. In this study, we describe an HCM cohort with a missense variant in CSRP3 (p.Cys150Tyr) with supporting evidence for pathogenicity and a description of the associated phenotype. METHODS: CSRP3 was sequenced in 6456 index cases with a diagnosis of HCM and in 5012 probands with other cardiomyopathies. In addition, 3372 index cases with hereditary cardiovascular disorders other than cardiomyopathies (mainly channelopathies and aortopathies) were used as controls. RESULTS: The p.(Cys150Tyr) variant was identified in 11 unrelated individuals of the 6456 HCM probands, and it was not identified in patients with other cardiomyopathies (p < 0.0001) or in our control population (p < 0.0001). Ten of the index cases were heterozygous and one was homozygous. Homozygous had a more severe phenotype. Family screening identified 17 other carriers. Wild-type individuals showed no signs of disease. The mean age at diagnosis of affected individuals was 55 ±â€¯13 years, and the mean left ventricular wall thickness was 18 ±â€¯3 mm. The variant showed highly age-dependent penetrance. After a mean follow-up of 11 (±8) years, no adverse events were reported in any of the HCM patients. CONCLUSIONS: The p.(Cys150Tyr) variant in CSRP3 causes late-onset and low risk form of hypertrophic cardiomyopathy in heterozygous carriers.

Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis.

Despite promising advances in the medical management of spinal cord injury (SCI), there is still no available effective therapy to repair the neurological damage in patients who experience this life-transforming condition. Recently, we performed a phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone (GH) treatment in incomplete chronic traumatic spinal cord injury. The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo slightly improves the SCI individual motor score. Moreover, we found that an intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals. To understand the possible mechanisms of the improvement due to GH treatment (motor score) and due to rehabilitation (functional outcome), we used a proteomic approach. Here, we used a multiple proteomic strategy to search for recovery biomarkers in blood plasma with the potential to predict response to somatropin treatment and to delayed intensive rehabilitation. Forty-six patients were recruited and followed for a minimum period of 1 year. Patients were classified into two groups based on their treatment: recombinant somatropin (0.4 mg) or placebo. Both groups received rehabilitation treatment. Our strategy allowed us to perform one of the deepest plasma proteomic analyses thus far, which revealed two proteomic signatures with predictive value: (i) response to recombinant somatropin treatment and (ii) response to rehabilitation. The proteins implicated in these signatures are related to homeostasis, inflammation, and coagulation functions. These findings open novel possibilities to assess and therapeutically manage patients with SCI, which could have a positive impact on their clinical response.

Why Does COVID-19 Affect Patients with Spinal Cord Injury Milder? A Case-Control Study: Results from Two Observational Cohorts.

The COVID-19 pandemic represents an unprecedented global challenge in this century. COVID-19 is a viral respiratory infection, yet the clinical characteristics of this infection differ in spinal cord injury patients from those observed in the general population. Cough and asthenia are the most frequent symptoms in this population. Moreover, infected spinal cord injury patients rarely present complications that require admission to an Intensive Care Unit, in contrast to the general population. Thus, there is a clear need to understand how COVID-19 affects spinal cord injury patients from a molecular perspective. Here, we employed an -omics strategy in order to identify variations in protein abundance in spinal cord injury patients with and without COVID-19. After a quantitative differential analysis using isobaric tags and mass spectrometry and a verification phase, we have found differences mainly related to coagulation and platelet activation. Our results suggest a key role of heparin in the response of spinal cord injury patients to COVID-19 infection, showing a significant correlation between these proteins and heparin dose. Although the number of patients is limited, these data may shed light on new therapeutic options to improve the management these patients and, possibly, those of the general population as well.

Effects of Orientations, Aspect Ratios, Pavement Materials and Vegetation Elements on Thermal Stress inside Typical Urban Canyons.

The analysis of local climate conditions to test artificial urban boundaries and related climate hazards through modelling tools should become a common practice to inform public authorities about the benefits of planning alternatives. Different finishing materials and sheltering objects within urban canyons (UCs) can be tested, predicted and compared through quantitative and qualitative understanding of the relationships between the microclimatic environment and subjective thermal assessment. This process can work as support planning instrument in the early design phases as has been done in this study that aims to analyze the thermal stress within typical UCs of Bilbao (Spain) in summertime through the evaluation of Physiologically Equivalent Temperature using ENVI-met. The UCs are characterized by different orientations, height-to-width aspect ratios, pavement materials, trees' dimensions and planting pattern. Firstly, the current situation was analyzed; secondly, the effects of asphalt and red brick stones as streets' pavement materials were compared; thirdly, the benefits of vegetation elements were tested. The analysis demonstrated that orientation and aspect ratio strongly affect the magnitude and duration of the thermal peaks at pedestrian level; while the vegetation elements improve the thermal comfort up to two thermophysiological assessment classes. The outcomes of this study, were transferred and visualized into green planning recommendations for new and consolidated urban areas in Bilbao.

Changes in cardiovascular risk and clinical outcomes in a HIV/AIDS cohort study over a 1-year period at a specialized clinic in Mexico.

INTRODUCTION: The third report of the National Cholesterol Education Program guidelines recommends calculating the 10-year morbidity of atherosclerotic cardiovascular disease (ASCVD) using risk calculators when treating high blood cholesterol in adults. We analyzed the changes in cardiovascular risk (CVR) among Mexican patients with HIV. PATIENTS AND METHODS: This observational, prospective cohort study compared the CVR after 1 year of antiretroviral treatment among 460 HIV patients from a Mexican clinic. Changes using the ASCVD risk estimator and changes in clinical outcomes were analyzed. The results were categorized as low or high CVR using a cutoff of 7.5%. RESULTS: The CVR initially had a median of 2.3% (interquartile range [IQR]: 1%-4.8%), which changed to 2.4% (IQR: 1.5%-5.5%) after 1 year (P=0.001). After CVR stratification, we found that 84.3% of the patients had a low CVR, and 18% in this subgroup had metabolic syndrome (MS). Moreover, 15.7% had high CVR, and 47% in this subgroup had MS. The 4.3% of patients had an increase in CVR from the low to high subgroup, and 2.6% had a decrease in CVR from the high to low subgroup. Out of all patients, 22.3% had MS. CONCLUSION: More than 50% of the population had an increase in CVR after 1 year. Of these patients, 4.3% changed from the low to high CVR group. Although the guidelines proposed different time periods for performing CVR estimations, this study showed that such assessments offered valuable clinical data over a relatively short-term period.

[Prevalence of atrial fibrillation and predictors of its occurrence in patients with dual-chamber pacemakers]. / Prevalencia de fibrilación auricular y factores predictores de su aparición en pacientes portadores de marcapasos bicamerales.

OBJECTIVES: To assess the prevalence of atrial fibrillation (AF) in patients with dual-chamber pacemakers (DP), determine the variables associated with development of AF and evaluate the changes in AF's management by physicians. METHODS: Five hundred patients with DP were prospectively included and interrogated. When AF was detected physicians in charge of the patient were warned. Changes in AF's management were evaluated. RESULTS: Mean age of the study population was 77 years, with 51% of men. AF was detected in 13.2% of patients. These findings led treatment changes in 64.7%. The variables analyzed by logistic regression model which were associated with the occurrence of AF were: arterial hypertension (OR=2.62; CI 95% 1.01-6.8; P<.048), history of AF (OR=4.30; CI 95% 2.26-8.32; P<.001), sick sinus syndrome as cause of device implantation (OR=2.09; CI 95% 1.09-3.97; P<.025) and burden of supraventricular extrasystoles series(OR= 1.000033 per serie; CI 95% 0.000011-0.000055; P<.003.). CONCLUSION: We have detected a high prevalence of AF in patients with DP. The diagnose of AF led to change in treatment. Four clinical variables increase the likelihood of developing this arrhythmia.

[Estimation of the "vascular age" based on body mass index in a population in primary prevention. Association with subclinical carotid atherosclerosis]. / Estimación de la «edad vascular¼ basada en el índice de masa corporal en una población en prevención primaria. Asociación con la aterosclerosis carotídea subclínica.

BACKGROUND AND OBJECTIVES: To know the relationship between "vascular age" (VA) and the diagnosis of subclinical atherosclerosis could improve cardiovascular risk stratification. OBJECTIVES: 1) to know the VA in a primary prevention population, and 2) to determine the relationship between VA and the presence of carotid atherosclerotic plaque (CAP). PATIENTS AND METHODS: We calculated VA based on body mass index (BMI). We obtained the difference between VA and chronological age (Delta). The screening of CAP was done by ultrasound. We analyzed the association between quintiles of VA and Delta with the presence of CAP. ROC analysis was performed. RESULTS: In total, 411 patients were included (age 47 [10] years, 54% men). The VA and Delta were 55 (15) and 7 (9) years respectively. In 75% of the patients VA was higher than the chronological age (50%≥ 6 years). Subjects with CAP had significantly higher VA (66 [11] versus 50 [14] years, P<.0001) and Delta (13 [9] versus 5 [7] years, P<.0001) than subjects without CAP. We observed a positive association of quintiles of VA and Delta with the prevalence of CAP. The area under de curve and the optimal cutoff point of VA for the detection of CAP were 0.813 and 60 years, respectively, and for Delta, 0,771 and 11 years, respectively. CONCLUSIONS: The VA based on BMI could be a simple tool to estimate the presence of CAP and improve cardiovascular risk stratification in patients in primary prevention.

Prevalencia de fibrilación auricular y factores predictores de su aparición en pacientes portadores de marcapasos bicamerales / Prevalence of atrial fibrillation and predictors of its occurrence in patients with dual-chamber pacemakers

Resumen Objetivos Evaluar la prevalencia de fibrilación auricular (FA) en pacientes portadores de marcapasos bicamerales (MB), las variables asociadas a su aparición y los cambios de conducta clínica que este hallazgo ha generado. Métodos Se incluyó prospectivamente a 500 pacientes ambulatorios portadores de MB. Se realizó interrogatorio sobre el MB. Se contactó a los médicos de cabecera ante la aparición de FA y luego se determinó si esta información resultaba en cambios de conducta terapéutica. Resultados La media de edad de la población fue de 77 años, con un 51% de hombres. Se detectó FA en un 13.2% de los pacientes. Esto generó modificaciones en el tratamiento en un 64.7% de ellos. En el modelo de regresión logística, a través de un análisis multivariado, se asociaron a la aparición de FA las siguientes variables: hipertensión arterial (OR = 2.62; IC 95% 1.01-6.8; p < 0.048), antecedente de FA (OR = 4.30; IC 95% 2.26-8.32; p < 0.001), enfermedad del nodo sinusal como causa de implante (OR = 2.09; IC 95% 1.09-3.97; p < 0.025) y la cantidad de series de extrasístoles supraventriculares detectadas (OR = 1.000033 por cada serie; IC 95% 0.000011-0.000055; p < 0.003). Una cantidad de series de extrasístoles supraventriculares igual o mayor de 77 en un control de marcapasos presenta un área bajo la curva de 0.81 para la detección de FA. Conclusión Se ha detectado una alta prevalencia de FA en pacientes portadores de MB. Este hallazgo condujo a importantes cambios en el tratamiento. Se han detectado 4 variables asociadas independientemente a la detección de FA.

Abstract Objectives To assess the prevalence of atrial fibrillation (AF) in patients with dual-chamber pacemakers (DP), determine the variables associated with development of AF and evaluate the changes in AF's management by physicians. Methods Five hundred patients with DP were prospectively included and interrogated. When AF was detected physicians in charge of the patient were warned. Changes in AF's management were evaluated. Results Mean age of the study population was 77 years, with 51% of men. AF was detected in 13.2% of patients. These findings led treatment changes in 64.7%. The variables analyzed by logistic regression model which were associated with the occurrence of AF were: arterial hypertension (OR = 2.62; CI 95% 1.01-6.8; P < .048), history of AF (OR = 4.30; CI 95% 2.26-8.32; P < .001), sick sinus syndrome as cause of device implantation (OR = 2.09; CI 95% 1.09-3.97; P < .025) and burden of supraventricular extrasystoles series(OR = 1.000033 per serie; CI 95% 0.000011-0.000055; P < .003.). Conclusion We have detected a high prevalence of AF in patients with DP. The diagnose of AF led to change in treatment. Four clinical variables increase the likelihood of developing this arrhythmia.

Decreased expression of T-cell costimulatory molecule CD28 on CD4 and CD8 T cells of mexican patients with pulmonary tuberculosis.

Patients with tuberculosis frequently develop anergy, a state of T-cell hyporesponsiveness in which defective T-cell costimulation could be a factor. To know if the expression of T-cell costimulatory molecules was altered in tuberculosis, we analyzed the peripheral blood T-cell phenotype of 23 Mexican patients with pulmonary tuberculosis. There was severe CD4 (P < .001) and CD8 (P < .01) lymphopenia and upregulation of costimulatory molecule CD30 on CD4 and CD8 T cells (P < .05); this increase was higher in relapsing tuberculosis. The main finding was severe downregulation of the major costimulatory molecule CD28 on both CD8 and CD4 T cells (P < .001). Depletion of the CD4/CD28 subset, a hitherto undescribed finding, is relevant because CD4 T cells constitute the main arm of the cell-mediated antimycobacterial immune response.

Impact of opportunistic Mycobacterium tuberculosis infection on the phenotype of peripheral blood T cells of AIDS patients.

While the detrimental consequences of opportunistic tuberculosis (TB) in the course and outcome of HIV-1 infection are well studied, little information about the impact of the mycobacterial infection on the phenotype of T lymphocytes is available. In this study we analyzed by cytofluorimetry the peripheral blood T cell phenotype of 13 patients with AIDS, 23 HIV-1 negative patients with active pulmonary TB, nine HIV-1/Mycobacterium tuberculosis coinfected individuals, and 21 age- and sex-matched healthy controls. CD4+ T cells were equally depleted in AIDS and coinfection (P<0.001). The findings suggest a rescuing effect of the added mycobacterial infection. CD3 T cell loss was not observed in coinfection, whereas it was severe in AIDS (P<0.001). Similar (albeit less striking) effects were observed with other markers (CD45RA, CD45RO, and CD27) that were diminished in CD4+ T cells of AIDS patients. Apparent detrimental effects of the added mycobacterial infection were the increased expression of the proapoptotic molecule CD95 on CD4+ T cells, and decreased expression of the major costimulatory molecule CD28 on CD8+ T cells. In this work we show that M. tuberculosis infection modifies the T cell phenotype of the HIV-1 infected individual.