DAB2IP associates with hereditary angioedema: Insights into the role of VEGF signaling in HAE pathophysiology.

BACKGROUND: In the recent years, there was an important improvement in the understanding of the pathogenesis of hereditary angioedema (HAE). Notwithstanding, in a large portion of patients with unknown mutation (HAE-UNK) the genetic cause remains to be identified. OBJECTIVES: To identify new genetic targets associated with HAE, a large Argentine family with HAE-UNK spanning 3 generations was studied. METHODS: Whole exome sequencing was performed on affected family members to identify potential genetic variants associated with HAE-UNK. In silico analyses and experimental studies were applied to assess the role of the identified gene variant. RESULTS: A missense variant (p.D239N) in DAB2IP was identified. The variant occurred in the C2-domain, the region interacting with vascular endothelial growth factor receptor 2 (VEGFR2). It was found to be rare, and predicted to have a detrimental effect on the functionality of DAB2IP. Protein structure modeling predicted changes in the mutant p.D239N protein structure, impacting protein stability. The p.D239N variant affected the subcellular localization of VEGFR2. Cells transfected with the DAB2IP-239N transcript exhibited an intracellular distribution, and VEGFR2 remained associated with the cell membrane. The altered localization pattern indicated reduced colocalization of the mutant protein with VEGFR2, suggesting a diminished ability of VEGFR2 binding. CONCLUSIONS: The study identified a novel missense variant (p.D239N) in DAB2IP in a family with HAE-UNK and highlighted the role of dysregulated VEGF-mediated signaling in altered endothelial permeability. DAB2IP loss-of-function pathogenic variants lead to the impairment of the endothelial VEGF/VEGFR2 ligand system and represent a new pathophysiologic cause of HAE-UNK.

Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL) / Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis

Introducción y objetivos: La amiloidosis cardiaca (AC) es una patología asociada a un elevado número de ingresos hospitalarios. Dada la escasa información disponible al respecto, planteamos un análisis de la incidencia y las causas de hospitalización en esta enfermedad.Material y métodosSe evaluaron 143 pacientes (128 por transtiretina [AC-ATTR] y 15 por cadenas ligeras [AC-AL]) incluidos en el Registro de Amiloidosis Cardiaca de Galicia (AMIGAL), recogiendo todas sus hospitalizaciones.ResultadosDurante un seguimiento mediano de 959 días se produjeron 179 hospitalizaciones no programadas (tasa de incidencia [TI] 512,6 ingresos hospitalarios por 1.000 pacientes-año), siendo las más habituales las de causa cardiovascular (n=109, TI 312,2). El motivo individual de ingreso hospitalario más frecuente fue la insuficiencia cardiaca (IC) (n=87, TI 249,2).La AC-AL se asoció con una TI de hospitalizaciones no programadas más elevada que la AC-ATTR (TI 781 vs. 483,2; HR 1,62; p=0,029) a expensas de las de causa no cardiovascular (TI 376 vs. 181,2; HR 2,07; p=0,027). La supervivencia libre de hospitalización no programada al año y a los tres años en la AC-AL fue menor que en la AC-ATTR (46,7 y 20,0% vs. 73,4 y 35,2%, respectivamente; p=0,021). (AU)

Introduction and objetives: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease.Material and methodsOne hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations.ResultsDuring a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2).AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). (AU)

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Introduction and objectives: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Methods: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Results: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Conclusion: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

Impact of medication intensification on 30-day hospital readmissions in a geriatric trauma population: A multicenter cohort study.

BACKGROUND: Fall-related injuries are a significant health issue that occur in 25% of older adults and account for a significant number of trauma-related hospitalizations. Although medication intensification may increase the risk of hospital readmissions in non-trauma patients, data on a geriatric trauma population are lacking. OBJECTIVE: The primary objective was to evaluate the effect of medication intensification on 30-day hospital readmissions in geriatric patients hospitalized for fall-related injuries. METHODS: This multicenter, retrospective cohort study included patients with geriatric who presented to one of three trauma centers within a large, health-system between January 1, 2018 and December 31, 2020. Patients at least 65 years old admitted with a fall-related injury were eligible for inclusion. Patients were grouped according to medication changes at discharge, which included intensified and non-intensified groups. Medication intensification included increased dose(s) or initiation of new agents. The primary outcome was the 30-day hospital readmission rate. RESULTS: Of the 870 patients included (median [interquartile range, IQR] age, 82 [74-89] years, 522 (60%) female, and 220 (25%) with a previous fall), there were 471 (54%) and 399 (46%) patients in the intensified and non-intensified groups, respectively. The intensified group had a higher 30-day hospital readmission rate (21% intensified vs. 16% non-intensified, p = 0.043; number needed to harm 20) based on an unweighted analysis. According to a weighted propensity score logistic regression, medication intensification was associated with higher 30-day hospital readmissions (24% [95% confidence interval [CI] 19-31%] intensified vs. 15% [95% CI 11-20%] non-intensified, p = 0.018). These results were consistent within competing risk models accounting for death (cause-specific model: hazard ratio [HR] 1.63 [95% CI 1.07-2.49], p = 0.023; Fine-Gray model: HR 1.64 [95% CI 1.07-2.50], p = 0.022). CONCLUSIONS: In a geriatric trauma population hospitalized after a fall, intensification of medications may pose an increased risk of 30-day hospital readmission.

Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus.

OBJECTIVE: To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. METHODS: We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann-Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. RESULTS: Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6-14) in comparison to that at follow-up (6 (4-8), P = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. CONCLUSION: Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.

Third National Registry of Cardiac Rehabilitation Programs in Mexico (RENAPREC III-2022) / Tercer Registro Nacional de Programas de Rehabilitación Cardiaca en México (RENAPREC III-2022)

Abstract Introduction: In Mexico, cardiac rehabilitation (CR) as an interdisciplinary intervention with therapeutic impact in patients with heart disease is growing. There is the need to know actual conditions of CR in our country. Objectives: The objective of this National Registry is to follow-up those existing and new CR units in Mexico through the comparison between the two previous registries, RENAPREC-2009 and RENAPREC II-2015 studies. This is a descriptive study focused on diverse CR activities such as assistance training, and certification of health professionals, barriers, reference, population attended, interdisciplinarity, permanence over time, growth prospects, regulations, post-pandemic condition, integrative characteristics, and scientific research. Results: Data were collected from 45 CR centers in the 32 states, 75.5% are private practice units, 67% are new, 33% were part of RENAPREC II-2015, and 17 have continued since 2009. With a better distribution of CR units along the territory, the median reference of candidates for CR programs is 9% with a significant reduction into tiempo of enrollment to Phase II admission (19 ± 11 days). Regarding to previous registries, the coverance of Phases I, II, and III is 71%, 100%, and 93%, respectively; and a coverance increases in evaluation, risk stratification, and prescription, more comprehensive attendance and prevention strategies. Conclusions: CR in Mexico has grown in the past 7 years. Even there is still low reference and heterogeneity in specific processes, there are strengths such as interdisciplinarity, scientific professionalization of specialists, national diversification, and an official society that are consolidated over time.

resumen está disponible en el texto completo

Measurement of Cutting Temperature in Interrupted Machining Using Optical Spectrometry.

This research presents an experimental study focused on measuring temperature at the tool flank during the up-milling process at high cutting speed. The proposed system deals with emissivity compensation through a two-photodetector system and during calibration. A ratio pyrometer composed of two photodetectors and a multimode fiber-optic coupler is employed to capture the radiation emitted by the cutting insert. The pyrometer is calibrated using an innovative calibration system that addresses theoretical discrepancies arising from various factors affecting the measurement of cutting temperature. This calibration system replicates the milling process to generate a calibration curve. Experimentally, AISI 4140 steel is machined with coated tungsten carbide inserts, using cutting speeds of 300 and 400 m/min, and feed rates of 0.08 and 0.16 mm/tooth. The results reveal a maximum recorded cutting temperature of 518 °C and a minimum of 304 °C. The cutting temperature tends to increase with higher cutting speeds and feed rates, with cutting speed being the more influential factor in this increase. Both the pyrometer calibration and experimental outcomes yield satisfactory results. Finally, the results showed that the process and the device prove to be a convenient, effective, and precise method of measuring cutting temperature in machine processes.

[Health related to quality life of patients with hereditary angioedema in Argentina. A multicenter study]. / Calidad de vida relacionada con la salud en pacientes con angioedema hereditario de Argentina. Estudio multicéntrico.

OBJECTIVE: To describe health relaed quality of life in a cohort of stable adult outpatients with hereditary an-gioedema (HAE) with validated tools. METHODS: An observational, cross-sectional, and descriptive study was performed, carried out in patients with hereditary angioedema, coming from the City of Buenos Aires and its provinces: Corrientes, Chubut, Entre Ríos and Santa Fe. The HAE-QoL and SF-12v2 health questionnaires were applied to assess the related quality of life. with health. RESULTS: 100 patients were included; median age: 41.5 years (range: 18-77); 65% were female, and 79% had type 1 HAE. Asymptomatic, mild, moderate and severe cases accounted for 6, 29, 38, and 27% of participants, respectively. Seventeen percent of patients were receiving long-term prophylaxis. Icatibant was the most fre-quent treatment for acute episodes. All health domains SF-12v2 scores were lower than expected in general population, excepting "vitality" and "physical functioning". Total and all specific domains HAE-QoL scores were reduced. Differences between women and men and in every age-defined group were demonstrated for sev-eral specific domains. CONCLUSIONS: Health relaed to quality life was notably reduced in Argentinean patients with HAE, when imple-menting the HAE.QoL, and SF-12v2 questionnaries. The need for multidisciplinary strategies approaching this complex disease is highlighted.

OBJECTIVO: Describir la calidad de vida relacionada con la saluden pacientes adultos, ambulatorios y estables con angioedema hereditario, mediante cuestionarios validados. MÉTODOS: Estudio descriptivo, transversal y observacional, llevado a cabo en pacientes con angioedema here-ditario, procedentes de la Ciudad de Buenos Aires y sus provincias: Corrientes, Chubut, Entre Ríos y Santa Fe. Se aplicaron los cuestionarios HAE-QoL y SF-12v2 para evaluar la calidad de vida relacionada con la salud. RESULTADOS: Se incluyeron 100 pacientes, con mediana de edad de 41.5 años (rango: 18-77), principalmente de género femenino (65%). La forma más frecuente de angioedema hereditario fue el tipo 1 (79%). Los casos asintomáticos, leves, moderados y severos representaron el 6, 29, 38 y 27%, respectivamente. El 17% recibía profilaxis a largo plazo. Icatibant fue el tratamiento más prescrito para los episodios agudos de angioedema. Todos los puntajes de los dominios de salud del SF-12v2 fueron menores de lo esperado, excepto "vitalidad" y "funcionamiento físico". Se observó disminución en los puntajes totales y en todos los dominios del HAE-QoL. Se reconocieron diferencias entre las mujeres y los hombres, y para grupo etario en los puntajes de los dominios específicos. CONCLUSIONES: La calidad de vida relacionada con la salud disminuyó considerablemente en pacientes argentinos con angioedema hereditario al aplicar los cuestionarios HAE-QoL y SF-12v2. Es importante desarrollar estra-tegias multidisciplinarias para abordar esta enfermedad compleja.

Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value.

Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. This study reports mechanistic insights into the electromechanical remodeling process associated with AF progression and further demonstrates its prognostic value in the clinic. In pigs, sequential electromechanical assessment during AF progression shows a progressive decrease in mechanical activity and early dissociation from its electrical counterpart. Atrial tissue samples from animals with AF reveal an abnormal increase in cardiomyocytes death and alterations in calcium handling proteins. High-throughput quantitative proteomics and immunoblotting analyses at different stages of AF progression identify downregulation of contractile proteins and progressive increase in atrial fibrosis. Moreover, advanced optical mapping techniques, applied to whole heart preparations during AF, demonstrate that AF-related remodeling decreases the frequency threshold for dissociation between transmembrane voltage signals and intracellular calcium transients compared to healthy controls. Single cell simulations of human atrial cardiomyocytes also confirm the experimental results. In patients, non-invasive assessment of the atrial electromechanical relationship further demonstrate that atrial electromechanical dissociation is an early prognostic indicator for acute and long-term rhythm control.

[Third National Registry of Cardiac Rehabilitation Programs in Mexico (RENAPREC III-2022)]. / Tercer Registro Nacional de Programas de Rehabilitación Cardiaca en México (RENAPREC III-2022).

Introduction: In Mexico, cardiac rehabilitation (CR) as an interdisciplinary intervention with therapeutic impact in patients with heart disease is growing. There is the need to know actual conditions of CR in our country. Objectives: The objective of this National Registry is to follow-up those existing and new CR units in Mexico through the comparison between the two previous registries, RENAPREC-2009 and RENAPREC II-2015 studies. This is a descriptive study focused on diverse CR activities such as assistance training, and certification of health professionals, barriers, reference, population attended, interdisciplinarity, permanence over time, growth prospects, regulations, post-pandemic condition, integrative characteristics, and scientific research. Results: Data were collected from 45 CR centers in the 32 states, 75.5% are private practice units, 67% are new, 33% were part of RENAPREC II-2015, and 17 have continued since 2009. With a better distribution of CR units along the territory, the median reference of candidates for CR programs is 9% with a significant reduction into tiempo of enrollment to Phase II admission (19 ± 11 days). Regarding to previous registries, the coverance of Phases I, II, and III is 71%, 100%, and 93%, respectively; and a coverance increases in evaluation, risk stratification, and prescription, more comprehensive attendance and prevention strategies. Conclusions: CR in Mexico has grown in the past 7 years. Even there is still low reference and heterogeneity in specific processes, there are strengths such as interdisciplinarity, scientific professionalization of specialists, national diversification, and an official society that are consolidated over time.

Introducción: En México, la Rehabilitación Cardíaca (RC) como intervención interdisciplinaria con impacto terapéutico en paciente con cardiopatía está en crecimiento. Existe la necesidad de conocer las condiciones actuales de la RC en nuestro país. Objetivo: El objetivo de este Registro es dar seguimiento comparativo de las unidades nuevas y existentes entre los registros anteriores, RENAPREC-2009 y RENAPREC II-2015. Se trata de un estudio descriptivo centrado en diversas actividades de la RC: formación asistencial y certificación de sus profesionales, barreras, referencia, población atendida, interdisciplinariedad, permanencia en el tiempo, perspectivas de crecimiento, normativa, condición pospandemia, características integradoras e investigación. Resultados: Se recolectaron datos de 45 centros en los 32 estados, 67% son nuevos 75.5% son de práctica privada, 33% fueron parte de RENAPREC II-2015 y 17 desde 2009. Con una mejor distribución de las unidades de RC a lo largo del territorio, la mediana de referencia de pacientes candidatos a RC es ahora del 9% con reducción significativa del tiempo de admisión a Fase II (19 ± 11 días). Respecto a registros anteriores las coberturas de las Fases I, II y III son del 71%, 100% y 93%, respectivamente; con un aumento de la cobertura en evaluación, estratificación de riesgo y prescripción, atención más integral y estrategias de prevención. Conclusiones: La RC en México ha crecido en los últimos 7 años. Si bien aún existe baja referencia y heterogeneidad en procesos específicos, existen fortalezas como la interdisciplinariedad, la profesionalización científica de los especialistas, la diversificación nacional y una sociedad oficial que se consolida en el tiempo.

Impact of a pulmonary embolism response team initiative on hospital mortality of patients with bilateral pulmonary embolism / Impacto de una iniciativa de equipo de respuesta a la embolia pulmonar en la mortalidad hospitalaria de pacientes con embolia pulmonar bilateral

Introduction Pulmonary embolism (PE) response teams (PERT) for the management of high-risk PE (HR-PE) and intermediate-high risk PE (IHR-PE) are encouraged in PE guidelines. We aimed to assess the impact of a PERT initiative on mortality in these groups of patients, compared with standard care. Methods We conducted a prospective, single-center registry, including consecutive patients with HR-PE and IHR-PE with PERT activation from February-2018 to December-2020 (PERT group, n=78 patients) and compared it with an historic cohort of patients admitted to our hospital in a previous 2-year period (2014–2016), managed with standard of care (SC-group, n=108 patients). Results Patients in the PERT group were younger and less comorbid. The risk profile at admission and the percentage of HR-PE was similar in both cohorts (13% in SC-group and 14% in PERT-group, p=0.82). Reperfusion therapy was more frequently indicated in PERT-group (24.4% vs 10.2%, p=0.01), with no differences in fibrinolysis treatment, while catheter-directed therapy (CDT) was more frequent in PERT group (16.7% vs 1.9%, p<0.001). Reperfusion and CDT were associated with lower in-hospital mortality (2.9% vs 15.1%, p=0.001 for reperfusion and 1.5% vs 16.5%, p=0.001 for CDT). The primary outcome, 12-month mortality, was lower in the PERT-group (9% vs 22.2%, p=0.02), There were no differences in 30-day readmissions. In multivariate analysis PERT activation was associated with lower mortality at 12 months (HR 0.25, 95% confidence interval 0.09–0.7, p=0.008). Conclusion A PERT initiative in patients with HR-PE and IHR-PE was associated with a significant reduction in 12-month mortality compared with standard of care, and also with an increase in the use of reperfusion, especially catheter-directed therapies (AU)

Introducción Las guías de manejo de embolia pulmonar (EP) recomiendan organizar equipos de respuesta a la embolia pulmonar (PERT) para el manejo de la EP de riesgo intermedio-alto (EP-IAR) y de alto riesgo (EP-AR). Nuestro objetivo fue evaluar el impacto de una iniciativa PERT sobre la mortalidad en estos pacientes, en comparación con la atención estándar. Métodos Realizamos un registro prospectivo unicéntrico, incluyendo pacientes consecutivos con EP-IAR y EP-AR con activación del PERT desde febrero de 2018 hasta diciembre de 2020 (grupo PERT, n=78 pacientes) y lo comparamos con una cohorte histórica de pacientes ingresados en nuestro hospital en un período previo de 2 años (2014-2016), manejados con atención estándar (grupo SC, n=108 pacientes). Resultados Los pacientes del grupo PERT eran más jóvenes y con menos comorbilidades. El perfil de riesgo al ingreso y el porcentaje de EP-AR fue similar en ambas cohortes (13% en el grupo SC y 14% en el grupo PERT, p=0,82). La terapia de reperfusión fue más frecuentemente indicada en el grupo PERT (24,4% vs. 10,2%, p=0,01), sin diferencias en el uso de fibrinólisis, mientras que la terapia dirigida por catéter (CDT) fue más frecuente en el grupo PERT (16,7% vs. 1,9%, p<0,001). La reperfusión y la CDT se asociaron con una menor mortalidad hospitalaria (2,9% vs. 15,1%, p=0,001 para reperfusión y 1,5% vs. 16,5%, p=0,001 para CDT). El objetivo primario, la mortalidad a los 12 meses, fue menor en el grupo PERT (9% frente al 22,2%, p=0,02). No hubo diferencias en los reingresos a los 30 días. En el análisis multivariado la activación de PERT se asoció con una menor mortalidad a los 12 meses (hazard ratio 0,25, intervalo de confianza del 95%: 0,09-0,7, p=0,008)(AU)

Systemic inflammation and cortical neurochemistry in never-medicated first episode-psychosis individuals.

Studies of cellular and cytokine profiles have contributed to the inflammation hypothesis of schizophrenia; however, precise markers of inflammatory dysfunction remain elusive. A number of proton magnetic resonance spectroscopy (1H-MRS) studies in patients with first-episode psychosis (FEP) have shown higher brain levels of metabolites such as glutamate, myo-inositol (mI) and choline-containing compounds (tCho), suggesting neuroinflammation. Here, we present peripheral inflammatory profiles in antipsychotic-naive FEP patients and age-and-sex matched healthy controls, as well as cortical glutamate, mI and tCho levels using 1H-MRS. Inflammatory profiles were analyzed using cytokine production by peripheral blood mononuclear cells, that were either spontaneous or stimulated, in 48 FEP patients and 23 controls. 1H-MRS of the medial prefrontal cortex was obtained in 29 FEP patients and 18 controls. Finally, 16 FEP patients were rescanned after 4 weeks of treatment (open-label) with Risperidone. FEP patients showed a higher proportion of proinflammatory Th1/Th17 subset, and an increased spontaneous production of Interleukin (IL)-6, IL-2 and IL-4 compared with the control group. Results obtained from 1H-MRS showed no significant difference in either glutamate, mI or tCho between FEP and control groups. At baseline, CD8% showed a negative correlation with glutamate in FEP patients; after 4 weeks of risperidone treatment, the FEP group exhibited a decrease in glutamate levels which positively correlated with CD4 + T cells. Nevertheless, these correlations did not survive correction for multiple comparisons. FEP patients show evidence of immune dysregulation, affecting both the innate and adaptive immune response, with a predominantly Th2 signature. These findings, along with the changes produced by antipsychotic treatment, could be associated with both systemic and central inflammatory processes in schizophrenia.

Salivary IgA subtypes as novel disease biomarkers in systemic lupus erythematosus.

Introduction: Immunoglobulin A (IgA) is the main antibody isotype in body fluids such as tears, intestinal mucous, colostrum, and saliva. There are two subtypes of IgA in humans: IgA1, mainly present in blood and mucosal sites, and IgA2, preferentially expressed in mucosal sites like the colon. In clinical practice, immunoglobulins are typically measured in venous or capillary blood; however, alternative samples, including saliva, are now being considered, given their non-invasive and easy collection nature. Several autoimmune diseases have been related to diverse abnormalities in oral mucosal immunity, such as rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus (SLE). Methods: We decided to evaluate the levels of both IgA subtypes in the saliva of SLE patients. A light chain capture-based ELISA measured specific IgA1 and IgA2 levels in a cohort of SLE patients compared with age and gender-matched healthy volunteers. Results: Surprisingly, our results indicated that in the saliva of SLE patients, total IgA and IgA1 subtype were significantly elevated; we also found that salivary IgA levels, particularly IgA2, positively correlate with anti-dsDNA IgG antibody titers. Strikingly, we also detected the presence of salivary anti-nucleosome IgA antibodies in SLE patients, a feature not previously reported elsewhere. Conclusions: According to our results and upon necessary validation, IgA characterization in saliva could represent a potentially helpful tool in the clinical care of SLE patients with the advantage of being a more straightforward, faster, and safer method than manipulating blood samples.