Validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay / Validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay

Introducción: El dengue es la enfermedad arboviral más común en los seres humanos. Un diagnóstico temprano y preciso del dengue puede respaldar el manejo clínico, la vigilancia y el control de la enfermedad y es fundamental, por ello en el diagnóstico del dengue es importante contar con pautas clínicas y epidemiológicas que permitan la identificación oportuna y una conducta terapéutica adecuada. Objetivos: Evaluar la validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay durante los años de 2012 a 2020. Materiales y métodos: Estudio analítico de tipo observacional, retrospectivo correspondientes a pacientes pediátricos (0 a 18 años) internados en el Hospital de Referencia de Paraguay el periodo enero 2012 a julio 2020 con diagnostico presuntivo de dengue al ingreso. Se realizó́ un análisis bivariado relacionando las frecuencias de 20 grupos de criterios diagnósticos combinados y 3 criterios diagnósticos aislados (OMS 2009, nexo epidemiológico y antigenemia NS1 para dengue) con el gold standard de diagnóstico que fue la conversión serológica. Resultados: Participaron del estudio 342 sujetos. EL 44% tenía edad escolar y 70% tenía 5 años o más. El 52,76% (191) fueron masculinos. Se encontraron desnutrición y sobrepeso en el 13% y 2%, respectivamente. La combinación de proteína C reactiva con plaquetopenia se encontró́ en 0.45% de los pacientes sin dengue y en el 6% de los pacientes con diagnóstico final de dengue (p=0.004). Conclusión: Este resultado aporta la alternativa de uso de una combinación sencilla de exámenes de laboratorio que puede replicarse en salas de urgencias como en salas de internación en un primer contacto con pacientes febriles con sospecha de fiebre dengue.

Introduction: Dengue is the most common arboviral disease in humans. An early and accurate diagnosis of dengue can support the clinical management, surveillance and control of the disease and is essential, therefore in the diagnosis of dengue it is important to have clinical and epidemiological guidelines that allow timely identification and appropriate therapeutic conduct. Objectives: To evaluate the validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay during the years 2012 to 2020. Materials and methods: Analytical study of case and control type, observational, longitudinal, retrospective corresponding to pediatric patients (0 to 18 years) admitted to the Reference Hospital of Paraguay from January 2012 to July 2020 with a presumptive diagnosis of dengue at income. A bivariate analysis was performed relating the frequencies of 20 groups of combined diagnostic criteria and 3 isolated diagnostic criteria (WHO 2009, epidemiological link and NS1 antigenemia for dengue) with the gold standard of diagnosis, which was serological conversion. Results: 342 subjects participated in the study. 44% were school age and 70% were 5 years old or older. 52.76% (191) were male. Malnutrition and overweight were found in 13% and 2%, respectively. The combination of C-reactive protein with thrombocytopenia was found in 0.45% of patients without dengue and in 6% of patients with a final diagnosis of dengue (p=0.004). Conclusion: This result provides the alternative of using a simple combination of laboratory tests that can be replicated in emergency rooms and inpatient wards in a first contact with febrile patients with suspected dengue fever.

Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination.

Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination in male and female mice. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.

Vacunación contra el SARS-CoV-2 en pacientes paraguayos con artritis reumatoide

Introducción: La vacunación en poblaciones expuestas a mayor riesgo de enfermedad grave y muerte consecuentes a la infección por SARS-CoV-2, ha generado un gran impacto en la salud pública mundial. Indudablemente, el beneficio ha sido evidenciado mayormente en personas con comorbilidades crónicas, donde la artritis reumatoide (AR) juega un rol importante. Objetivo: Analizar la vacunación contra Sars-CoV-2 en pacientes paraguayos con AR, durante la pandemia COVID-19. Métodos: Se realizó un estudio multicéntrico, en el que se analizó transversalmente a una cohorte de pacientes con AR, durante el periodo de octubre a diciembre del año 2022. Para el estudio se registraron variables clínico-epidemiológicas y relacionadas con la vacunación (i.e. acceso a la vacunación, tipo, número de dosis). Se realizó un análisis descriptivo de las variables con el software R-4.3.2. Resultados: Se incluyeron 568 pacientes, 84,1% eran mujeres, con un promedio de edad de 55,5±13,9 años. El 88,7% (504) pacientes, recibieron al menos una dosis de vacuna contra SARS-CoV-2. 85% (483) recibieron dos dosis, mientras que el 60,9% (344) pacientes recibieron el primer refuerzo, y 21,2% el segundo refuerzo. Conclusiones: En esta serie de pacientes paraguayos con AR el porcentaje de vacunación contra SARS-CoV-2 fue más elevado que el registrado en la población general del país. Esto podría estar relacionado con la prioridad de esta población para acceder a las vacunas y a la insistencia de sus médicos en completar el esquema de vacunación.

Introduction: Vaccination in populations exposed to increased risk of severe disease and death consequent to SARS-CoV-2 infection has generated a major impact on global Public Health. Certainly, the benefit has been evidenced mostly in people with chronic comorbidities, where rheumatoid arthritis (RA) plays an important role. Objective: To analyze vaccination against Sars-CoV-2 in paraguayan patients with rheumatoid arthritis (RA) during the COVID19 pandemic. Methods: A multicenter study was carried out, in which a cohort of patients with RA was analyzed cross-sectionally, during the period from October to December 2022. For the study, clinical-epidemiological and vaccination-related variables were recorded (i.e. access to vaccination, type, number of doses). A descriptive analysis of the variables was carried out with the R-4.3.2 software. Results: 568 patients were included, 84.1% were female, with an average age of 55.5±13.9 years. 88.7% (504) patients received at least one dose of SARS-CoV-2 vaccine, 85% (483) received two doses, while 60.9% (344) patients received the first booster, and 21.2% the second booster. Conclusions: In this series of Paraguayan patients with RA the percentage of vaccination against SARS-CoV-2 was higher than that registered in the general population of the country. This could be related to the priority of this population to access vaccines and the insistence of their physicians to complete the vaccination schedule.

METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer.

Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N7-methylguanosine (m7G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m7G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m7G tRNA methylation in cancer cell translation control and tumour biology.

Tubulointerstitial nephritis and uveitis syndrome and SARS-CoV-2 infection in an adolescent: just a coincidence in time?

BACKGROUND: Despite recent well-established kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), usually presenting as acute kidney injury (AKI), there are few published cases with SARS-CoV-2-related tubulointerstitial nephritis (TIN). We report an adolescent with TIN and delayed association with uveitis (TINU syndrome), where SARS-CoV-2 spike protein was identified in kidney biopsy. CASE-DIAGNOSIS/TREATMENT: A 12-year-old girl was assessed for a mild elevation of serum creatinine detected during the evaluation of systemic manifestations including asthenia, anorexia, abdominal pain, vomiting, and weight loss. Data of incomplete proximal tubular dysfunction (hypophosphatemia and hypouricemia with inappropriate urinary losses, low molecular weight proteinuria, and glucosuria) were also associated. Symptoms had initiated after a febrile respiratory infection with no known infectious cause. After 8 weeks, the patient tested positive in PCR for SARS-CoV-2 (Omicron variant). A subsequent percutaneous kidney biopsy revealed TIN and immunofluorescence staining with confocal microscopy detected the presence of SARS-CoV-2 protein S within the kidney interstitium. Steroid therapy was started with gradual tapering. Ten months after onset of clinical manifestations, as serum creatinine remained slightly elevated and kidney ultrasound showed mild bilateral parenchymal cortical thinning, a second percutaneous kidney biopsy was performed, without demonstrating acute inflammation or chronic changes, but SARS-CoV-2 protein S within the kidney tissue was again detected. At that moment, simultaneous routine ophthalmological examination revealed an asymptomatic bilateral anterior uveitis. CONCLUSIONS: We present a patient who was found to have SARS-CoV-2 in kidney tissue several weeks following onset of TINU syndrome. Although simultaneous infection by SARS-CoV-2 could not be demonstrated at onset of symptoms, since no other etiological cause was identified, we hypothesize that SARS-CoV-2 might have been involved in triggering the patient's illness.

Adipose tissue plasticity in pheochromocytoma patients suggests a role of the splicing machinery in human adipose browning.

Adipose tissue from pheochromocytoma patients acquires brown fat features, making it a valuable model for studying the mechanisms that control thermogenic adipose plasticity in humans. Transcriptomic analyses revealed a massive downregulation of splicing machinery components and splicing regulatory factors in browned adipose tissue from patients, with upregulation of a few genes encoding RNA-binding proteins potentially involved in splicing regulation. These changes were also observed in cell culture models of human brown adipocyte differentiation, confirming a potential involvement of splicing in the cell-autonomous control of adipose browning. The coordinated changes in splicing are associated with a profound modification in the expression levels of splicing-driven transcript isoforms for genes involved in the specialized metabolism of brown adipocytes and those encoding master transcriptional regulators of adipose browning. Splicing control appears to be a relevant component of the coordinated gene expression changes that allow human adipose tissue to acquire a brown phenotype.

Type I interferon subtypes differentially activate the anti-leukaemic function of natural killer cells.

Natural killer (NK) cells have an intrinsic ability to detect and eliminate leukaemic cells. Cellular therapies using cytokine-activated NK cells have emerged as promising treatments for patients with advanced leukaemia. However, not all patients respond to current NK cell therapies, and thus improvements in efficacy are required. Type I interferons (IFN-I) are a family of potent immunomodulatory cytokines with a known ability to modulate NK cell responses against cancer. Although the human IFN-I family comprises 16 distinct subtypes, only IFNα2 has been widely explored as an anti-cancer agent. Here, we investigated the individual immunomodulatory effects each IFNα subtype and IFNß had on NK cell functionality to determine whether a particular subtype confers enhanced effector activity against leukaemia. Importantly, IFNα14 and IFNß were identified as superior activators of NK cell effector function in vitro. To test the ability of these subtypes to enhance NK cell activity in vivo, IFN-I stimulation was overlaid onto a standard ex vivo expansion protocol to generate NK cells for adoptive cell therapy. Interestingly, infusion of NK cells pre-activated with IFNα14, but not IFNß, significantly prolonged survival in a preclinical model of leukaemia compared to NK cells expanded without IFN-I. Collectively, these results highlight the diverse immunomodulatory potencies of individual IFN-I subtypes and support further investigation into the use of IFNα14 to favourably modulate NK cells against leukaemia.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). CONCLUSIONS: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

La formación del operario en vigilancia y lucha antivectorial. Matanzas, 2019

RESUMEN Introducción: para la formación de operarios integrales en vigilancia y lucha antivectorial, está diseñado un curso de habilitación. El claustro de profesores de la provincia de Matanzas ha encontrado algunas dificultades en la adquisición de conocimientos por parte de los estudiantes. Objetivo: caracterizar la fuerza laboral de vigilancia y lucha antivectorial de la provincia de Matanzas, para diseñar un conjunto de indicaciones que complementen los contenidos del curso de habilitación de operarios, de forma que los estudiantes se sientan motivados y entiendan mejor los contenidos ya incluidos. Materiales y métodos: se realizó una investigación descriptiva, retrospectiva y longitudinal, de enero a diciembre de 2019. Resultados: el grupo de trabajadores de los operarios es el más numeroso. El nivel educacional que predominó fue el de secundaria básica. En 2019 se realizaron 17 cursos de formación, en cuyas evaluaciones el claustro de profesores encontró dificultades en las respuestas a las preguntas de tres de los temas del curso, al igual que en el uso de la lengua materna. Conclusiones: se propuso introducir contenidos en cada tema del curso de formación, que se impartirán de acuerdo a las formas de enseñanza y aprendizaje ya definidas en el programa. El profesor responsable del tema lo dará en el momento en que la situación docente lo requiera, para que el futuro trabajador logre una mejor comprensión de los contenidos.

ABSTRACT Introduction: there is an enabling course designed for the training of comprehensive operators in surveillance and vector control. The teacher staff of Matanzas province has found some difficulties in the acquisition of knowledge by students. Objective: to characterize the surveillance and anti-vector labor force of the province of Matanzas, in order to design a set of indications that complement the contents of the course of enabling operators, so that students feel motivated and better understand the contents already included. Materials and methods: a descriptive, retrospective and longitudinal investigation was carried out from January to December 2019. Results: the group of operators is the most numerous. The educational level that prevailed was that of secondary school. In 2019, 17 training courses were conducted, in whose evaluations the teacher staff found difficulties in answering the questions of three of the course subjects, as well as in the use of the mother tongue. Conclusions: it was proposed to introduce new contents in each topic of the training course, which will be taught according to the forms of teaching and learning already defined in the programme. The teacher responsible for the subject will teach it at the moment when the teaching situation requires it, in order for the future worker to achieve a better understanding of the contents.

Textbook outcome and survival after gastric cancer resection with curative intent: A population-based analysis.

BACKGROUND: The concept of textbook outcome (TO) has been proposed for analyzing quality of surgical care. This study assessed the incidence of TO among patients undergoing curative gastric cancer resection, predictors for TO achievement, and the association of TO with survival. METHOD: All patients with gastric and gastroesophageal junction cancers undergoing curative gastrectomy between January 2014-December 2017 were identified from a population-based database (Spanish EURECCA Registry). TO included: macroscopically complete resection at the time of operation, R0 resection, ≥15 lymph nodes removed and examined, no serious postoperative complications (Clavien-Dindo ≥II), no re-intervention, hospital stay ≤14 days, no 30-day readmissions and no 90-day mortality. Logistic regression was used to assess the adjusted achievement of TO. Cox survival regression was used to compare conditional adjusted survival across groups. RESULTS: In total, 1293 patients were included, and TO was achieved in 541 patients (41.1%). Among the criteria, "macroscopically complete resection" had the highest compliance (96.5%) while "no serious complications" had the lowest compliance (63.7%). Age (OR 0.53 for the 65-74 years and OR 0.34 for the ≥75 years age group), Charlson comorbidity index ≥3 (OR 0.53, 95%CI 0.34-0.82), neoadjuvant chemoradiotherapy (OR 0.24, 95%CI 0.08-0.70), multivisceral resection (OR 0.55, 95%CI 0.33-0.91), and surgery performed in a community hospital (OR 0.65, CI95% 0.46-0.91) were independently associated with not achieving TO. TO was independently associated with conditional survival (HR 0.67, 95%CI 0.55-0.83). CONCLUSION: TO was achieved in 41.1% of patients who underwent gastric cancer resection with curative intent and was associated with longer survival.

Characterising the Phenotypic Diversity of Antigen-Specific Memory B Cells Before and After Vaccination.

The diversity of B cell subsets and their contribution to vaccine-induced immunity in humans are not well elucidated but hold important implications for rational vaccine design. Prior studies demonstrate that B cell subsets distinguished by immunoglobulin (Ig) isotype expression exhibit divergent activation-induced fates. Here, the antigen-specific B cell response to tetanus toxoid (TTd) booster vaccination was examined in healthy adults, using a dual-TTd tetramer staining flow cytometry protocol. Unsupervised analyses of the data revealed that prior to vaccination, IgM-expressing CD27+ B cells accounted for the majority of TTd-binding B cells. 7 days following vaccination, there was an acute expansion of TTd-binding plasmablasts (PB) predominantly expressing IgG, and a minority expressing IgA or IgM. Frequencies of all PB subsets returned to baseline at days 14 and 21. TTd-binding IgG+ and IgA+ memory B cells (MBC) exhibited a steady and delayed maximal expansion compared to PB, peaking in frequencies at day 14. In contrast, the number of TTd-binding IgM+IgD+CD27+ B cells and IgM-only CD27+ B cells remain unchanged following vaccination. To examine TTd-binding capacity of IgG+ MBC and IgM+IgD+CD27+ B cells, surface TTd-tetramer was normalised to expression of the B cell receptor-associated CD79b subunit. CD79b-normalised TTd binding increased in IgG+ MBC, but remained unchanged in IgM+IgD+CD27+ B cells, and correlated with the functional affinity index of plasma TTd-specific IgG antibodies, following vaccination. Finally, frequencies of activated (PD-1+ICOS+) circulating follicular helper T cells (cTFH), particularly of the CXCR3-CCR6- cTFH2 cell phenotype, at their peak expansion, strongly predicted antigen-binding capacity of IgG+ MBC. These data highlight the phenotypic and functional diversity of the B cell memory compartment, in their temporal kinetics, antigen-binding capacities and association with cTFH cells, and are important parameters for consideration in assessing vaccine-induced immune responses.

Prácticas de alimentación del lactante y del niño pequeño en tres instituciones de salud en el Caribe colombiano, bajo la estrategia "Instituciones amigas de la mujer y la infancia integral" / Feeding practices of the infant and child, in three health institutions in the Colombian Caribbean / Práticas de alimentação do lactante y del niño pequeño en tres instituciones de salud en el Caribe colombiano, bajo la estrategia "Instituciones amigas de la mujer y la infancia integral "

Resumen Objetivo: Describir las prácticas de alimentación de niños lactantes y de niños pequeños atendidos en instituciones de tres municipios del Caribe colombiano, incluidos en el proceso de implementación de la estrategia "Instituciones amigas de la mujer y la infancia integral" de la Unicef. Metodología: Estudio cualitativo enmarcado en la etnografía, llevado a cabo mediante entrevistas semiestructuradas, cartografía social y grupos focales, dirigido a madres beneficiarias de instituciones de salud priorizadas. Resultados: Las madres reconocieron los beneficios nutricionales de la lactancia materna, y en dos de los territorios, los beneficios emocionales. Además, presentan apropiación en lo relacionado con la alimentación perceptiva. No obstante, no cumplen con el periodo de exclusividad de la lactancia, refieren algunas creencias populares acerca de la misma y se observa un inicio temprano de la alimentación complementaria. También reconocieron la importancia de las redes de apoyo familiar y social, como, por ejemplo, del Instituto Colombiano de Bienestar Familiar. Conclusión: Esta investigación permitió reconocer factores que favorecen y limitan las adecuadas prácticas de alimentación del lactante y del niño pequeño, en madres gestantes y lactantes y su red de apoyo, las cuales viven en condiciones de vulnerabilidad social y económica, y son atendidas en tres instituciones de salud del Caribe colombiano que se encuentran en proceso de implementación de la estrategia enunciada. Lo anterior brinda elementos para la formulación de procesos educativos en salud para la población materno infantil, tanto en la población objetivo como en instituciones que se encuentren en proceso de implementación de dicha estrategia, y de requerimientos políticos acerca de la salud materno infantil.

Abstract Objective: Describe the infant and young child feeding practices of children cared for in institutions of the Colombian Caribbean, includes in implementing the baby friendly hospital strategy. Methodology: Qualitative study framed in ethnography through semi-structured interviews, aimed at beneficiary mothers of prioritized health institutions. Results: The mothers recognized the nutrtitionals benefits of breastfeeding, in two territories also the emotional benefits. They also show appropriation in relation to perceptual feeding. However, they do not comply with the exclusive period of breastfeeding, they refer to some beliefs around it, an early start of complementary feeding is observed. In turn, the mothers recognized the importance of family and social support networks, such as the Instituto Colombiano de Bienestar Familiar. Conclusion: This research made it possible to recognize factors that favor and limit the adequate feeding practices of infants and young children, in pregnant and lactating mothers and their support network, who live in conditions of social and economic vulnerability and are cared for in three health institutions of the Colombian Caribbean that are in the process of implementing the baby-friendly hospitals initiative. The foregoing provides elements for the formulation of educational processes in health in the maternal and child population, both in the target population and in institutions that are in the process of implementing the baby-friendly hospitals initiative and policies to maternal and child health.

Resumo Objetivo: Descrever as práticas alimentares de lactentes e crianças atendidas em instituições de três municípios do Caribe colombiano, incluídas no processo de implementação da estratégia do Unicef "Instituições Amigas da Mulher e Infância Integral". Metodologia: Estudo qualitativo enquadrado na etnografia, realizado por meio de entrevistas semiestruturadas, cartografia social e grupos focais, dirigido a mães beneficiárias de instituições de saúde priorizadas. Resultados: As mães reconheceram os benefícios nutricionais da amamentação e, em dois dos territórios, os benefícios emocionais. Além disso, apresentam apropriação em relação à alimentação perceptiva. Porém, não cumprem o período exclusivo de aleitamento materno, referem-se a algumas crenças populares a respeito, e observa-se o início precoce da alimentação complementar. Também reconheceram a importância das redes de apoio familiar e social, como o Instituto Colombiano de Bem-Estar Familiar. Conclusão: Esta pesquisa permitiu reconhecer fatores que favorecem e limitam as práticas alimentares adequadas de lactentes e crianças pequenas, em gestantes e lactantes e sua rede de apoio, que vivem em condições de vulnerabilidade social e econômica, sendo atendidas em três. Instituições de saúde do Caribe colombiano que estão em processo de implementação da estratégia declarada. O exposto fornece elementos para a formulação de processos educativos em saúde para a população materno-infantil, tanto na população-alvo como nas instituições que estão em processo de implementação dessa estratégia, e de requisitos políticos relativos à saúde materno-infantil.

Safety and effectiveness of vedolizumab in paediatric patients with inflammatory bowel disease: an observational multicentre Spanish study.

Vedolizumab is a humanised monoclonal antibody that binds to integrin α4ß7 expressed in T-cells, inhibiting its binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is specifically expressed in the small intestine and colon, playing a fundamental role in T-cell migration to the gastrointestinal tract. Vedolizumab has been shown to be effective in treating adults with inflammatory bowel disease; however, efficacy data for paediatric use are scarce. The objective of the present study was to assess the effectiveness and safety of vedolizumab for inducing and maintaining clinical remission in children with inflammatory bowel disease. We conducted a retrospective multicentre study of patients younger than 18 years with inflammatory bowel disease refractory to anti-tumour necrosis factor alpha (anti-TNF-α) drugs, who underwent treatment with vedolizumab. Clinical remission was defined as a score < 10 points in the activity indices. We included 42 patients, 22 of whom were male (52.3%), with a median age of 13.1 years (IQR 10.2-14.2) at the start of treatment. Of the 42 patients, 14 (33.3%) had Crohn's disease (CD) and 28 (66.7%) had ulcerative colitis (UC). At the start of treatment with vedolizumab, the Paediatric Crohn's Disease Activity Index was 36 (IQR 24-40) and the Paediatric Ulcerative Colitis Activity Index was 47 (IQR 25-65). All of them had received prior treatment with anti-TNF and 3 patients ustekinumab. At week 14, 69% of the patients responded to the treatment (57.1% of those with CD and 75% of those with UC; p=0.238), and 52.4% achieved remission (35.7% with CD and 60.7% with UC; p=0.126). At 30 weeks, the response rate was 66.7% (46.2% and 78.3% for CD and UC, respectively; p=0.049), and 52.8% achieved remission (30.8% and 65.2% for CD and UC, respectively; p=0.047). Among the patients with remission at week 14, 80% of the patients with CD and 84.5% of those with UC maintained the remission at 52 weeks. Adverse effects were uncommon and mild. Three patients (7.1%) presented headaches, 1 presented alopecia, 1 presented anaemia and 1 presented dermatitis.Conclusion: The results show that treatment with vedolizumab is a safe and effective option for achieving clinical remission in paediatric patients with inflammatory bowel disease with primary failure or loss of response to other treatments, especially in UC. What is Known: • Vedolizumab is effective in inducing and maintaining remission in adult patients with inflammatory bowel disease. • Most studies and clinical trials have been performed on adult populations, and there is currently no indication for paediatric populations. What is New: • Children with inflammatory bowel disease refractory to anti-TNF presented higher clinical remission rates than those published for adults. • There are few publications of this magnitude on paediatric populations treated with vedolizumab and with long-term follow-up (52 weeks).

El indudable beneficio de las Vacunas en la Pandemia COVID19 / The undoubted benefit of Vaccines in the COVID19 Pandemic

A finales de diciembre 2019, la Provincia de Hubei, China nos actualizaba sobre una enfermedad respiratoria que generaba insuficiencia en muy breve tiempo. Los primeros días de enero 2020, identifican al nuevo Coronavirus, y su transmisión se expande, sin respetar espacio, condición ni tradición. Una nueva pandemia se instaló desde el 11 de marzo 2020 y la búsqueda de una vacuna segura y eficaz que la detenga, congregó en una maratónica carrera a varios proyectos, de tres plataformas diferentes y esquemas de vacunación contra el COVID19

At the end of December 2019, the Hubei Province, China updated us on a respiratory disease that generated insufficiency in a very short time. The first days of January 2020, they identify the new Coronavirus, and its transmission expands, without respecting space, condition or tradition. A new pandemic was installed since March 11, 2020 and the search for a safe and effective vaccine to stop it brought together several projects from three different platforms and vaccination schemes against COVID19 in a marathon race

Behavioral Activation and Acceptance and Commitment Therapy in the Treatment of Anxiety and Depression in Cancer Survivors: A Randomized Clinical Trial.

Behavioural Activation (BA) and Acceptance and Commitment Therapy (ACT) aim to reduce the inflexible avoidance of painful thoughts, feelings and memories and to encourage involvement in relevant activities, objectives which are clearly relevant to the situation of cancer survivors with emotional problems. With a view to evaluating and comparing the efficacy of both therapies, applied on a group basis, a randomized controlled trial was developed. Cancer survivors (age 18-65 years) with anxiety and/or depression were assigned at random to two experimental groups (BA; ACT) and a waiting list control group (WL). Of the 66 cancer survivors randomized to trial (intention-to-treat sample), 46 participants (M = 51.49; SD = 6.88) completed the intervention (BA, n = 17; ACT, n = 12; WL, n = 17) (per-protocol sample). The emotional state, experiential avoidance and behavioural activation of the participants was evaluated in the pre- and post-treatment and in a 3-month follow-up using standardized instruments. Both treatment groups showed statistically significant changes, indicating an improvement in all the result variables in the post-treatment and follow-up as compared to the pre-treatment. BA showed better results than ACT regarding impact on anxiety and activation. This greater efficacy may have been due to factors such as the emphasis placed in BA on behavioural activation and the central role played in it by functional analysis. The key role played by experiential avoidance and behavioral activation in the maintenance and treatment of emotional problems in cancer survivors is discussed. Raw data are available online (http://dx.doi.org/10.17632/m7w688khs8.1).

STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy.

BACKGROUND & AIMS: Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. METHODS: We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (<15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of <15 and ≤5. RESULTS: Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P = .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P = .012. CONCLUSIONS: Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.

Identifying the optimal donor for natural killer cell adoptive therapy to treat paediatric B- and T-cell acute lymphoblastic leukaemia.

OBJECTIVES: Natural killer (NK) cells are an attractive source of cells for an 'off the shelf' cellular therapy because of their innate capacity to target malignant cells, and ability to be transferred between donors and patients. However, since not all NK cells are equally effective at targeting cancer, selecting the right donor for cellular therapy is critical for the success of the treatment. Recently, cellular therapies utilising NK cells from cytomegalovirus (CMV)-seropositive donors have been explored. However, whether these NK cells are the best source to treat paediatric acute lymphoblastic leukaemia (ALL) remains unclear. METHODS: Using a panel of patient-derived paediatric B- and T-ALL, we assessed the ability of NK cells from 49 healthy donors to mount an effective functional response against these two major subtypes of ALL. RESULTS: From this cohort, we have identified a pool of donors with superior activity against multiple ALL cells. While these donors were more likely to be CMV+, we identified multiple CMVneg donors within this group. Furthermore, NK cells from these donors recognised B- and T-ALL through different activating receptors. Dividing functional NK cells into 29 unique subsets, we observed that within each individual the same NK cell subsets dominated across all ALL cells. Intriguingly, this occurred despite the ALL cells in our panel expressing different combinations of NK cell ligands. Finally, we can demonstrate that cellular therapy products derived from these superior donors significantly delayed leukaemia progression in preclinical models of ALL. CONCLUSIONS: We have identified a pool of superior donors that are effective against a range of ALL cells, representing a potential pool of donors that can be used as an adoptive NK cell therapy to treat paediatric ALL.

[Recommendations for the diagnosis and practical management of paediatric eosinophilic oesophagitis]. / Recomendaciones para el diagnóstico y manejo práctico de la esofagitis eosinofílica pediátrica.

Eosinophilic oesophagitis is an emerging and chronic disorder mediated by the immune system, and is characterised by symptoms of oesophageal dysfunction and inflammation with isolated eosinophil infiltration in the oesophagus. It is more common in males and in atopic subjects, and the symptoms vary with age. In younger children, there is vomiting, abdominal pain and dietary problems, with dysphagia and food impaction in older children and adolescents. The diagnosis is based on the presence of symptoms and oesophageal inflammation with ≥ 15 eosinophils / high power field, and after ruling out other causes of oesophageal eosinophilia. Without treatment, the disease usually persists and can progress to fibrostenotic forms more common in adults. The treatment options included proton pump inhibitors, empirical elimination diets, and swallowed topical corticosteroids. Maintenance therapy is advisable after the induction treatment. Diet is the only treatment that is directed at the cause of the disease, on identifying the triggering food or foods. The response to the treatments requires a histological assessment due to the poor agreement between the symptoms and the oesophageal inflammation. The practical management of Eosinophilic oesophagitis presents with challenges, due to, among other causes, the current lack of availability of specific drugs, and to its approach with, occasionally complex, diet treatments. The present document, prepared by the Working Group on Eosinophilic Gastrointestinal Disorders of the Spanish Society of Paediatric Gastroenterology, Hepatology and Nutrition, has as its objective to help in the diagnostic and therapeutic approach to paediatric eosinophilic oesophagitis, based on the recent evidence-based consensus guidelines.

Activación Conductual en formato grupal para ansiedad y depresión: una revisión sistemática / Behavioral Activation in group format for anxiety and depression: a systematic review

Resumen Dada la alta prevalencia de los Trastornos Mentales Comunes (TMC), la aplicación grupal de la Activación Conductual (AC) puede ser un abordaje eficaz, efectivo y más eficiente. El objetivo del presente trabajo es revisar los estudios publicados sobre la utilidad de la AC grupal para el tratamiento de la ansiedad y/o depresión. Método: Revisión sistemática. Resultados: Se incluyeron 17 estudios. Los pacientes que recibieron AC experimentaron mejoras en ansiedad y/o depresión y se informa de una mayor eficacia de AC frente a grupos control sin intervención. Conclusiones: La AC es útil para la prevención y el tratamiento de trastornos emocionales. No obstante, la heterogeneidad y limitaciones de los estudios impiden determinar los ingredientes terapéuticos exactos, y si éstos son específicos del enfoque y procedimiento de esta terapia. Sería necesario más investigación, de mayor calidad metodológica, y que evalúe los cambios en los patrones de activación/evitación objeto de intervención.

Abstract Given the high prevalence of Common Mental Disorders (CMD), group-based Behavioral Activation (BA) could be an efficacious, effective and more efficient approach. The objective of this work is to review the published studies about the usefulness of group-based BA for the treatment of anxiety and/or depression. Method: Systematic review. Results: 17 studies were included in the review. Patients who received BA experienced improvements in anxiety and/or depression and studies reported a greater efficacy of BA compared with no-intervention control groups. Conclusions: BA is useful for the prevention and treatment of emotional disorders. However, heterogeneity and limitations of the studies make it impossible to determine the exact therapeutic elements, and if they are specific to the approach and procedure of this therapy. More research would be necessary of a higher methodological quality to evaluate changes in the activation/avoidance patterns, which are the object of the intervention.

Targeting PML in triple negative breast cancer elicits growth suppression and senescence.

Oncogene addiction postulates that the survival and growth of certain tumor cells is dependent upon the activity of one oncogene, despite their multiple genetic and epigenetic abnormalities. This phenomenon provides a foundation for molecular targeted therapy and a rationale for oncogene-based stratification. We have previously reported that the Promyelocytic Leukemia protein (PML) is upregulated in triple negative breast cancer (TNBC) and it regulates cancer-initiating cell function, thus suggesting that this protein can be therapeutically targeted in combination with PML-based stratification. However, the effects of PML perturbation on the bulk of tumor cells remained poorly understood. Here we demonstrate that TNBC cells are addicted to the expression of this nuclear protein. PML inhibition led to a remarkable growth arrest combined with features of senescence in vitro and in vivo. Mechanistically, the growth arrest and senescence were associated to a decrease in MYC and PIM1 kinase levels, with the subsequent accumulation of CDKN1B (p27), a trigger of senescence. In line with this notion, we found that PML is associated to the promoter regions of MYC and PIM1, consistent with their direct correlation in breast cancer specimens. Altogether, our results provide a feasible explanation for the functional similarities of MYC, PIM1, and PML in TNBC and encourage further study of PML targeting strategies for the treatment of this breast cancer subtype.