PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modulation.

Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.

Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population.

The SARS CoV-2 antibody and CD4+ T cell responses induced by natural infection and/or vaccination decline over time and cross-recognize other viral variants at different levels. However, there are few studies evaluating the levels and durability of the SARS CoV-2-specific antibody and CD4+ T cell response against the Mu, Gamma, and Delta variants. Here, we examined, in two ambispective cohorts of naturally-infected and/or vaccinated individuals, the titers of anti-RBD antibodies and the frequency of SARS-CoV-2-specific CD4+ T cells up to 6 months after the last antigen exposure. In naturally-infected individuals, the SARS-CoV-2 antibody response declined 6 months post-symptoms onset. However, the kinetic observed depended on the severity of the disease, since individuals who developed severe COVID-19 maintained the binding antibody titers. Also, there was detectable binding antibody cross-recognition for the Gamma, Mu, and Delta variants, but antibodies poorly neutralized Mu. COVID-19 vaccines induced an increase in antibody titers 15-30 days after receiving the second dose, but these levels decreased at 6 months. However, as expected, a third dose of the vaccine caused a rise in antibody titers. The dynamics of the antibody response upon vaccination depended on the previous SARS-CoV-2 exposure. Lower levels of vaccine-induced antibodies were associated with the development of breakthrough infections. Vaccination resulted in central memory spike-specific CD4+ T cell responses that cross-recognized peptides from the Gamma and Mu variants, and their duration also depended on previous SARS-CoV-2 exposure. In addition, we found cross-reactive CD4+ T cell responses in unexposed and unvaccinated individuals. These results have important implications for vaccine design for new SARS-CoV-2 variants of interest and concern.

Corrigendum: Cross-reactive humoral and CD4+ T cell responses to Mu and Gamma SARS-CoV-2 variants in a Colombian population.

[This corrects the article DOI: 10.3389/fimmu.2023.1241038.].

Post-COVID syndrome. A case series and comprehensive review.

The existence of a variety of symptoms with a duration beyond the acute phase of COVID-19, is referred to as post-COVID syndrome (PCS). We aimed to report a series of patients with PCS attending a Post-COVID Unit and offer a comprehensive review on the topic. Adult patients with previously confirmed SARS-CoV-2 infection and PCS were systematically assessed through a semi-structured and validated survey. Total IgG, IgA and IgM serum antibodies to SARS-CoV-2 were evaluated by an electrochemiluminescence immunoassay. A systematic review of the literature and meta-analysis were conducted, following PRISMA guidelines. Univariate and multivariate methods were used to analyze data. Out of a total of 100 consecutive patients, 53 were women, the median of age was 49 years (IQR: 37.8-55.3), the median of post-COVID time after the first symptoms was 219 days (IQR: 143-258), and 65 patients were hospitalized during acute COVID-19. Musculoskeletal, digestive (i.e., diarrhea) and neurological symptoms including depression (by Zung scale) were the most frequent observed in PCS patients. A previous hospitalization was not associated with PCS manifestation. Arthralgia and diarrhea persisted in more than 40% of PCS patients. The median of anti-SARS-CoV-2 antibodies was 866.2 U/mL (IQR: 238.2-1681). Despite this variability, 98 patients were seropositive. Based on autonomic symptoms (by COMPASS 31) two clusters were obtained with different clinical characteristics. Levels of anti-SARS-CoV-2 antibodies were not different between clusters. A total of 40 articles (11,196 patients) were included in the meta-analysis. Fatigue/muscle weakness, dyspnea, pain and discomfort, anxiety/depression and impaired concentration were presented in more than 20% of patients reported. In conclusion, PCS is mainly characterized by musculoskeletal, pulmonary, digestive and neurological involvement including depression. PCS is independent of severity of acute illness and humoral response. Long-term antibody responses to SARS-CoV-2 infection and a high inter-individual variability were confirmed. Future studies should evaluate the mechanisms by which SARS-CoV-2 may cause PCS and the best therapeutic options.

Cocaine, ethanol, cannabis and benzodiazepines co-consumption among patients assisted at the emergency room.

INTRODUCTION: Cocaine and ethanol (EtOH) co-consumption is a risk factor for physiologically and clinically negative outcomes. We describe the occurrence of cocaine consumption alone or co-consumption with EtOH and others psychotropics. PATIENTS AND METHODS: The descriptive research used data on medical records of patients positive to cocaine test who attended an emergency room between 2016 and 2017. We determined the frequency of cocaine consumption alone and co-consumption with EtOH, cannabis or benzodiazepines (BZDs). RESULTS: Over one year period, 88 patients (13.3%) were positive to cocaine test, mainly attended on weekends, in holiday months, young adults or men. Among those positive for cocaine, 72% were also positive for EtOH, cannabis or BZD. Cocaine co-consumption with one or two out of three substance was 55.2% (CI95%; 44.7-65.8%) and 16.4% (CI95%;8.58-24.3%), respectively. Co-consumption was more frecuently wih EtOH, followed by cannabis or BZD. CONCLUSION: Co-consumption of cocaine with EtOH is very common and could be associated with acute or chronic consumption of cannabis or acute exposure to BZDs. It is important that emergency physicians use a systematic approach to diagnose and treat more than one psychotropic substance in cocaine positive patients.

Impacto del COVID-19 en la salud reproductiva: mortalidad materna / Impact of COVID-19 on reproductive health: maternal mortality / Impacto da COVID-19 na saúde reprodutiva: mortalidade materna

El presente artículo tiene como propósito analizar los efectos e impacto de la pandemia COVID-19 en la mortalidad materna de Perú, lo cual afectó la disponibilidad de recursos, equipos, demanda y acceso a los servicios de salud; se agrega el desvío de los recursos humanos, financieros para combatir el brote de la enfermedad infecciosa, el retraso de normas, políticas e insuficiente presupuesto público, fragmentación, desarticulación de los prestadores de salud y vulnerabilidad de los profesionales de salud. Es una investigación de enfoque cualitativo descriptivo y crítico, analizado en el aspecto social y económico de la mortalidad materna, datos epidemiológicos, normas técnicas, y la afectación del COVID-19 en la población gestante. Se analizó el incremento de la mortalidad materna de 45.4% y 56% el año 2020 y 2021 con respecto al año 2019, asimismo el logro alcanzado al 2015 a 68 muertes maternas y una disminución notable de 50% entre el año 2000 y 2019, para sucumbir por la pandemia en un retroceso de 12 años y convertirse la enfermedad COVID-19 en la tercera y primera causa de muerte materna indirecta el año 2020 y 2021. Destacando la aplicación de estrategias que tuvo la Región Lima, como una de las regiones con menor incidencia de 2 y 6 muertes maternas respectivamente. Ante esta problemática se concluyó la priorización de la capacidad resolutiva del primer nivel de atención, capacitación continua del profesional obstetra y la aplicación de estrategias promovidas por la Región Lima.

The purpose of this article is to analyze the effects and impact of the COVID-19 pandemic on maternal mortality in Peru, which affected the availability of resources, equipment, demand and access to health services; in addition to the diversion of human and financial resources to combat the outbreak of the infectious disease, the delay of standards, policies and insufficient public budget, fragmentation, disarticulation of health providers and vulnerability of health professionals. It is a qualitative descriptive and critical research approach, analyzed in the social and economic aspect of maternal mortality, epidemiological data, technical norms, and the affectation of COVID-19 in the pregnant population. The increase in maternal mortality of 45.4% and 56% in 2020 and 2021 with respect to 2019 was analyzed, also the achievement reached in 2015 to 68 maternal deaths and a remarkable decrease of 50% between 2000 and 2019, to succumb to the pandemic in a setback of 12 years and become the disease COVID-19 in the third and first cause of indirect maternal death in 2020 and 2021. It is worth highlighting the implementation of strategies that had the Lima Region as one of the regions with the lowest incidence of 2 and 6 maternal deaths respectively. In view of this problem, it was concluded that priority should be given to the capacity of the first level of care, continuous training of obstetricians and the application of strategies promoted by the Lima Region.

O objetivo deste artigo é analisar os efeitos e o impacto da pandemia COVID-19 na mortalidade materna no Peru, que afetou a disponibilidade de recursos, equipamentos, demanda e acesso a serviços de saúde; além do desvio de recursos humanos e financeiros para combater o surto da doença infecciosa, o atraso das normas, políticas e orçamento público insuficiente, a fragmentação, a desarticulação dos provedores de saúde e a vulnerabilidade dos profissionais de saúde. É uma abordagem de pesquisa qualitativa, descritiva e crítica, analisando os aspectos sociais e econômicos da mortalidade materna, dados epidemiológicos, padrões técnicos e o impacto da COVID-19 sobre a população grávida. Foi analisado o aumento da mortalidade materna de 45,4% e 56% em 2020 e 2021 em relação a 2019, bem como a conquista alcançada em 2015 para 68 mortes maternas e uma diminuição notável de 50% entre 2000 e 2019, para sucumbir à pandemia em um retrocesso de 12 anos e se tornar a doença COVID-19 na terceira e primeira causa de morte materna indireta em 2020 e 2021. A implementação de estratégias na Região de Lima foi destacada como uma das regiões com menor incidência de 2 e 6 mortes maternas, respectivamente. Diante deste problema, concluiu-se que deveria ser dada prioridade à capacidade do primeiro nível de atendimento, ao treinamento contínuo dos obstetras e à aplicação das estratégias promovidas pela Região de Lima.

Osteoprotegerin Polymorphisms in a Mexican Population with Rheumatoid Arthritis and Generalized Osteoporosis: A Preliminary Report.

Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. The system formed by receptor activator for nuclear factor-κB (RANK), receptor activator for nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG): RANK/RANKL/OPG is a crucial molecular pathway for coupling between osteoblasts and osteoclasts, since OPG is able to inhibit osteoclast differentiation and activation. We aim to evaluate the association between SNPs C950T (rs2073617), C209T (rs3134069), T245G (rs3134070) in the TNFRSF11B (OPG) gene, and osteoporosis in RA. We included 81 women with RA and 52 healthy subjects in a cross-sectional study, genotyped them, and measured bone mineral density (BMD) at the lumbar spine and the femoral neck. Mean age in RA was 50 ± 12 with disease duration of 12 ± 8 years. According to BMD results, 23 (33.3%) were normal and 46 (66.7%) had osteopenia/osteoporosis. We found a higher prevalence of C allele for C950T SNP in RA. Polymorphisms C209T and T245G did not reach statistical significance in allele distribution. Further studies including patients from other regions of Latin America with a multicenter design to increase the sample size are required to confirm our findings and elucidate if C950T SNP could be associated with osteoporosis in RA.

Sesgo en la estratificación del síndrome coronario agudo al calcular el grace- score con 1ª, 2ª o troponina Δ / Grace score bias in acute coronary syndrome due to use 1th, 2th or troponin Δ

Introducción: el síndrome coronario agudo (SCA) es la primera causa de mortalidad en Colombia. Una estratificación de riesgo errónea, en la sala de emergencias (ER), afecta las intervenciones realizadas y la tasa de eventos adversos cardiovasculares puede ser mayor. El objetivo de esta investigación fue medir la diferencia en el puntaje GRACE y la estratificación del riesgo coronario, utilizando los resultados de las troponinas medidas secuencialmente durante la atención inicial. Metodología: con un diseño descriptivo retrospectivo, se evaluaron los registros clínicos de pacientes tratados por dolor precordial de probabilidad intermedia para SCA, sin indicación de manejo invasivo inmediato, atendidos en la sala de emergencias de una clínica del tercer nivel de Bogotá, durante el año 2017. Se determinó la diferencia entre la puntuación GRACE calculada con la primera troponina (GRACE-1), la segunda troponina (GRACE-2) o la troponina delta (GRACE-delta) [prueba T pareada], y la proporción de pacientes poco estratificados se midió al usar la primera troponina [X2, puntaje Z]. Resultados: se identificaron 44 pacientes en un período de 6 meses. La mayoría hombres con edad mediana de 73 años. El promedio (DE) de los puntajes GRACE-1, GRACE-2 y GRACE-delta, fue de 114.14 (30.73), 115.55 (30.14) y 111.11 (28.79), respectivamente; al comparar GRACE-delta con GRACE-1 y GRACE-2 se identificaron diferencias significativas (p:<0.05). Se identificó un error en la estratificación del riesgo coronario en 10/44 pacientes (22.7%) y 9/44 (20.4%) presentaron sobreestratificación. Conclusión: la estratificación del riesgo coronario con la primera troponina, a diferencia de la troponina delta (ítem no aclarado en las guías), evidenció una sobreestratificación en al menos 20% de los pacientes, estableciendo la necesidad de procedimientos más invasivos y posiblemente hospitalización más prolongada permanecer.

Background: Acute coronary syndrome (ACS) is the first cause of mortality in Colombia. An erroneous risk stratification, in the emergency room (ER), affects the interventions performed and the rate of major cardiovascular adverse events. We measured the difference in GRACE score and stratification of coronary risk, by using the results of troponins measured sequentially during initial care. Methods: With a retrospective descriptive design, clinical records of patients treated for precordial pain of ≥ intermediate probability for ACS were evaluated, without indication of immediate invasive management, attended in the ER of a clinic of the third level of Bogotá, during 2017. De-termined the difference between the GRACE score calculated with the first (GRACE-1), second (GRACE-2) or troponin delta (GRACE-delta [paired T-test], and the proportion of poorly stratified patients was measured when using the first troponin [X2, Z-score]. Results: 44 patients in a period of 6 months were identified. The majority men, older adults, middle age 73 years. The average (SD) of scores GRACE-1, GRACE-2 and GRACE-delta, was 114.14 (30.73), 115.55 (30.14) and 111.11 (28.79), respectively; when comparing GRACE-delta with GRACE-1 and GRACE-2 significant differences were identified (p:<0.05). Error in the stratification of coronary risk was identified in 10/44 patients (22.7%), and 9/44 (20.4%) presented over-stratification. Conclusion: The stratification of coronary risk using the first troponin, unlike the troponin delta (item not clarified in the guidelines), evidenced an over-stratification in at least 20% of the patients, establishing the need for more invasive procedures and possibly longer hospital stay.

Performance of risk indices for identifying low bone mineral density and osteoporosis in Mexican Mestizo women with rheumatoid arthritis.

OBJECTIVE: We evaluated the utility of 6 generic and 2 specific risk indices for identifying low bone mineral density (BMD) or osteoporosis in women with rheumatoid arthritis (RA); and their correlation with 10-year probability of fractures as assessed with the World Health Organization fracture risk assessment (FRAX) tool. METHODS: Mexican Mestizo women with RA were evaluated in this cross-sectional study using 6 generic indices [Simple Calculated Osteoporosis Risk Estimation (SCORE); Osteoporosis Risk Assessment Instrument (ORAI); Osteoporosis Self-Assessment Tool; Age, Body Size, No Estrogen; Osteoporosis Index of Risk (OSIRIS); and Guidelines of the US National Osteoporosis Foundation], 2 specific indices (Amsterdam and modified Amsterdam), and FRAX. BMD results on dual-energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck were considered the "gold standard." Sensitivity, specificity, and predictive values (PV) of the indices and their correlations with FRAX results were estimated. RESULTS: Among 191 patients, 46 had osteoporosis (24.1%) and 119 had low BMD (62.3%). For predicting osteoporosis, SCORE showed the highest sensitivity (96%), whereas OSIRIS (87%) and ORAI (82%) showed the highest specificities. OSIRIS also had the greatest positive PV (92%). The specific indices had low sensitivity and low specificity (Amsterdam, 50% and 79%, respectively; modified Amsterdam, 56% and 70%). All the indices had a low but significant correlation with FRAX. CONCLUSION: These findings support the use of some generic indices to identify patients with RA who should undergo DEXA testing. Currently available specific indices did not perform satisfactorily. New specific risk indices for osteoporosis in RA should be developed to increase sensitivity and specificity for predicting osteoporosis.