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Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response.

Resumen: Introducción: La parotiditis crónica recurrente juvenil es una enfermedad infrecuente de causa desconocida. Existe un creciente interés por su etiología autoinmune y su relación con disfunciones de la inmunidad celular y humoral aunque no existe un protocolo consensuado de investigaciones complementarias para su estudio. Se presenta una serie consecutiva de casos donde se investigan las alteraciones inmunes y trastornos autoinmunes asociados, proponiendo un algoritmo de estudio. Pacientes y métodos: Se realizó un estudio retrospectivo de pacientes que presentaron parotiditis crónica recurrente juvenil durante el periodo de 2013 a 2016 y seguimiento de al menos 2 años. Tras su diagnóstico clínico y ecográfico se realizaron de forma sistemática exámenes complementarios para investigación de patologías infecciosas, inmunes y autoinmunes asociadas. Resultados: De un total de 36 pacientes con criterios de inclusión, se encontraron 16 (44%) con alguna alteración analítica de carácter inmunológico inespecífico (ANA positivo, IgG elevada, factor 4 del complemento bajo) o asociada a un diagnóstico específico como ocurrió en 11 pacientes: déficit selectivo de IgA (2), síndrome de Sjögren asociado o no a lupus eritematoso sistémico (3), celiaquía asociada o no a diabetes mellitus (4), tiroiditis de Hashimoto (1) y síndrome de inmunodeficiencia adquirida (1). Conclusión: La parotiditis crónica recurrente juvenil puede considerarse un signo centinela de otras enfermedades de etiología inmunológica/autoinmune cuyo diagnóstico, seguimiento y tratamiento precoz puede mejorar su pronóstico. La etiología infecciosa vírica, exceptuando el VIH, no es prioritaria en el estudio de recurrencias. Abstract: Introduction: Juvenile recurrent chronic parotitis is a rare disease of unknown cause. There is a growing interest in its autoimmune aetiology and its relationship with dysfunctions of cellular and humoral immunity, although there is no agreed protocol for complementary investigations for its study. A consecutive series of cases is presented where the immune alterations and associated autoimmune disorders are investigated, proposing a study algorithm. Patients and methods: A retrospective study was carried out on patients who had juvenile recurrent chronic parotitis during the period from 2013 to 2016 and a follow-up of at least 2 years. After its clinical and ultrasound diagnosis, complementary examinations were systematically carried out to investigate infectious, immune, and autoimmune diseases. Results: Of a total of 36 patients with inclusion criteria, 16 (44%) were found with some analytical alteration of a non-specific immunological nature (positive ANA, high IgG, low complement factor 4), or associated with a specific diagnosis, as occurred in 11 patients: Selective IgA deficiency (2), Sjögren's syndrome associated or not with systemic lupus erythematosus (3), coeliac disease associated or not with diabetes mellitus (4), Hashimoto's thyroiditis (1), and acquired immunodeficiency syndrome (1). Conclusion: Juvenile recurrent chronic parotitis can be considered a sentinel sign of other diseases of immunological/autoimmune aetiology for which the diagnosis, monitoring and early treatment can improve its prognosis. Viral infectious aetiology, with the exception of HIV, is not a priority in the study of recurrences.

Introduction: Juvenile recurrent chronic parotitis (JRCP) is a rare disease of unknown cause. There is a growing interest in its autoimmune aetiology and its relationship with dysfunctions of cellular and humoral immunity, although there is no agreed protocol for complementary investigations for its study. A consecutive series of cases is presented where the immune alterations and associated autoimmune disorders are investigated, proposing a study algorithm. Patients and methods: A retrospective study was carried out on patients who had JRCP during the period from 2013 to 2016 and a follow-up of at least 2 years. After its clinical and ultrasound diagnosis, complementary examinations were systematically carried out to investigate infectious, immune, and autoimmune diseases. Results: Of a total of 36 patients with inclusion criteria, 16 (44%) were found with some analytical alteration of a non-specific immunological nature (positive ANA, high IgG, low complement factor 4), or associated with a specific diagnosis, as occurred in 11 patients: Selective IgA deficiency (2), Sjögren’s syndrome associated or not with systemic lupus erythematosus (3), coeliac disease associated or not with diabetes mellitus (4), Hashimoto’s thyroiditis (1), and acquired immunodeficiency syndrome (1). Conclusion: Juvenile recurrent chronic parotitis can be considered a sentinel sign of other diseases of immunological/autoimmune aetiology for which the diagnosis, monitoring and early treatment can improve its prognosis. Viral infectious aetiology, with the exception of HIV, is not a priority in the study of recurrences. Resumen: Introducción: La parotiditis crónica recurrente juvenil (PCRJ) es una enfermedad infrecuente de causa desconocida. Existe un creciente interés por su etiología autoinmune y su relación con disfunciones de la inmunidad celular y humoral aunque no existe un protocolo consensuado de investigaciones complementarias para su estudio. Se presenta una serie consecutiva de casos donde se investigan las alteraciones inmunes y trastornos autoinmunes asociados, proponiendo un algoritmo de estudio. Pacientes y métodos: Se realizó un estudio retrospectivo de pacientes que presentaron PCRJ durante el periodo de 2013 a 2016 y seguimiento de al menos 2 años. Tras su diagnóstico clínico y ecográfico se realizaron de forma sistemática exámenes complementarios para investigación de patologías infecciosas, inmunes y autoinmunes asociadas. Resultados: De un total de 36 pacientes con criterios de inclusión, se encontraron 16 (44%) con alguna alteración analítica de carácter inmunológico inespecífico (ANA positivo, IgG elevada, factor 4 del complemento bajo) o asociada a un diagnóstico específico como ocurrió en 11 pacientes: déficit selectivo de IgA (2), síndrome de Sjögren asociado o no a lupus eritematoso sistémico (3), celiaquía asociada o no a Diabetes mellitus (4), tiroiditis de Hashimoto (1) y síndrome de inmunodeficiencia adquirida (1). Conclusión: La parotiditis crónica recurrente juvenile puede considerarse un signo centinela de otras enfermedades de etiología inmunológica/autoinmune cuyo diagnóstico, seguimiento y tratamiento precoz puede mejorar su pronóstico. La etiología infecciosa vírica, exceptuando el VIH, no es prioritaria en el estudio de recurrencias.

Resumen: Introducción: La nefritis focal bacteriana aguda es una infección intersticial bacteriana, localizada en el parénquima renal, que entraña mayor gravedad que la pielonefritis aguda. El objetivo del estudio es el análisis de factores predictivos que permitan su diagnóstico precoz, fundamental para un adecuado abordaje terapéutico. Pacientes y métodos: Estudio multicéntrico de casos y control retrospectivo. Centros participantes: hospitales de Castellón y Valencia. Periodo de estudio: 2010-2018. Casos: nefritis focal bacteriana. Controles: pielonefritis aguda. Resultados: Se incluyó a un total de 158 pacientes (1:1). La mediana de edad de los casos fue 2 años. El 75% de sexo femenino. No existieron diferencias en la presentación clínica. En el análisis univariante la nefritis focal se relacionó con malformaciones del tracto urinario, bacteriemia, recuento de neutrófilos y la procalcitonina, así como las convulsiones febriles en el límite de la significación. Valores de procalcitonina ≥ 2 ng/ml tiene una OR de 4,9 (IC del 95: 1,77-13,85) de presentar nefritis focal. En el análisis multivariante las malformaciones urológicas mantuvieron la significación estadística y la procalcitonina en el límite de la significación. Conclusiones: Las malformaciones del tracto urinario predisponen al desarrollo de nefritis focal bacteriana. Ante pacientes con infección del tracto urinario y factores predictivos de nefritis focal bacteriana aguda, sería recomendable la realización de una ecografía Doppler renal en fase aguda para un diagnóstico y un tratamiento adecuado. Abstract: Introduction: Acute focal bacterial nephritis is an interstitial bacterial infection, localised in the renal parenchyma, which can be more serious than acute pyelonephritis. The aim of this study is the analysis of predictive factors that may lead to its early diagnosis, which is essential for an adequate therapeutic approach. Patients and methods: A retrospective, multicentre case and control study. The participant centres were hospitals in Castellon and Valencia. The study period was 2010-2018, with the cases being patients with focal bacterial nephritis and the patients with pyelonephritis as controls. Results: A total of 158 (1:1) patients were included. The median age of the cases was 2 years and there were 75% females. There were no differences in the clinical presentation. In the univariate analysis, focal nephritis was associated with malformations of the urinary tract, bacteraemia, the neutrophil count, and procalcitonin, as well as febrile convulsions of borderline significance. Procalcitonin values ≥2 ng/ml had an OR of 4.9 (95%CI; 1.77-13.85) of presenting with focal nephritis. In the multivariate analysis, the urological malformations still maintained statistical significance and borderline significance for procalcitonin. Conclusions: The urinary tract malformations predispose the development of focal bacterial nephritis. In patients with a urinary tract infection and predictive factors of acute focal bacterial nephritis it would be worthwhile performing a renal Doppler ultrasound in the acute phase for its appropriate diagnosis and treatment.

Introduction: Acute focal bacterial nephritis is an interstitial bacterial infection, localised in the renal parenchyma, which can be more serious than acute pyelonephritis. The aim of this study is the analysis of predictive factors that may lead to its early diagnosis, which is essential for an adequate therapeutic approach. Patients and methods: A retrospective, multicentre case and control study. The participant centres were hospitals in Castellon and Valencia. The study period was 2010–2018, with the cases being patients with focal bacterial nephritis and the patients with pyelonephritis as controls. Results: A total of 158 (1:1) patients were included. The median age of the cases was 2 years and there were 75% females. There were no differences in the clinical presentation. In the univariate analysis, focal nephritis was associated with malformations of the urinary tract, bacteraemia, the neutrophil count, and procalcitonin, as well as febrile convulsions of borderline significance. Procalcitonin values ≥2 ng/mL had an OR of 4.9 (95% CI; 1.77–13.85) of presenting with focal nephritis. In the multivariate analysis, the urological malformations still maintained statistical significance and borderline significance for procalcitonin. Conclusions: The urinary tract malformations predispose the development of focal bacterial nephritis. In patients with a urinary tract infection and predictive factors of acute focal bacterial nephritis it would be worthwhile performing a renal Doppler ultrasound in the acute phase for its appropriate diagnosis and treatment. Resumen: Introducción: La nefritis focal bacteriana aguda es una infección intersticial bacteriana, localizada en el parénquima renal, que entraña mayor gravedad que la pielonefritis aguda. El objetivo del estudio es el análisis de factores predictivos que permitan su diagnóstico precoz, fundamental para un adecuado abordaje terapéutico. Pacientes y métodos: Estudio multicéntrico de casos y control retrospectivo. Centros participantes: hospitales de Castellón y Valencia. Periodo de estudio: 2010-2018. Casos: nefritis focal bacteriana. Controles: pielonefritis aguda. Resultados: Se incluyó a un total de 158 pacientes (1:1). La mediana de edad de los casos fue 2 años. El 75% de sexo femenino. No existieron diferencias en la presentación clínica. En el análisis univariante la nefritis focal se relacionó con malformaciones del tracto urinario, bacteriemia, recuento de neutrófilos y la procalcitonina, así como las convulsiones febriles en el límite de la significación. Valores de procalcitonina ≥ 2 ng/mL tiene una OR de 4,9 (IC del 95: 1,77-13,85) de presentar nefritis focal. En el análisis multivariante las malformaciones urológicas mantuvieron la significación estadística y la procalcitonina en el límite de la significación. Conclusiones: Las malformaciones del tracto urinario predisponen al desarrollo de nefritis focal bacteriana. Ante pacientes con infección del tracto urinario y factores predictivos de nefritis focal bacteriana aguda, sería recomendable la realización de una ecografía Doppler renal en fase aguda para un diagnóstico y un tratamiento adecuado.

Introduction: COVID-19 has a less severe course in children. In April 2020, some children presented with signs of multisystem inflammation with clinical signs overlapping with Kawasaki disease (KD), most of them requiring admission to the pediatric intensive care unit (PICU). This study aimed to describe the prevalence and clinical characteristics of KD SARS-CoV-2 confirmed and negative patients during the pandemic in Spain.Material and Methods: Medical data of KD patients from January 1, 2018 until May 30, 2020 was collected from the KAWA-RACE study group. We compared the KD cases diagnosed during the COVID-19 period (March 1–May 30, 2020) that were either SARS-CoV-2 confirmed (CoV+) or negative (CoV–) to those from the same period during 2018 and 2019 (PreCoV).Results: One hundred and twenty-four cases were collected. There was a significant increase in cases and PICU admissions in 2020 (P-trend = 0.001 and 0.0004, respectively). CoV+ patients were significantly older (7.5 vs. 2.5 yr) and mainly non-Caucasian (64 vs. 29%), had incomplete KD presentation (73 vs. 32%), lower leucocyte (9.5 vs. 15.5 × 109) and platelet count (174 vs. 423 × 109/L), higher inflammatory markers (C-Reactive Protein 18.5vs. 10.9 mg/dl) and terminal segment of the natriuretic atrial peptide (4,766 vs. 505 pg/ml), less aneurysm development (3.8 vs. 11.1%), and more myocardial dysfunction (30.8 vs. 1.6%) than PreCoV patients. Respiratory symptoms were not increased during the COVID-19 period.Conclusion: The KD CoV+ patients mostly meet pediatric inflammatory multisystem syndrome temporally associated with COVID-19/multisystem inflammatory syndrome in children criteria. Whether this is a novel entity or the same disease on different ends of the spectrum is yet to be clarified.