Standards for psychosocial care in pediatric cancer: adapted proposal for Latin American and Caribbean countries.

Objective: To highlight the objectives, achievements, challenges, and next steps for the World Health Organization's Global Initiative for Childhood Cancer (GICC) framework, a project designed to improve psychosocial care (PSC) in pediatric cancer centers across Latin America and the Caribbean (LAC). Methods: The project was launched in Peru, the first GICC focal country, in November 2020. The diagnosis phase included a survey and a semistructured interview with health professionals to assess PSC practices in institutions, and a needs assessment survey for caregivers. In the second phase, a strategic plan was developed to address the identified needs, including the adaptation of PSC standards, the establishment of multicenter working groups, the expansion of the proposal, and the development of materials. Results: The study found that PSC was not being adequately provided in accordance with international standards. Six adapted standards were proposed and validated, and more than 50 regional health professionals participated in online activities to support the project. The implementation process is currently ongoing, with the establishment of five multidisciplinary working groups, one regional committee, and the production of 16 technical outputs. Conclusion: This project represents a substantial step forward to improve PSC for pediatric patients with cancer and their families in LAC countries. The establishment of working groups and evidence-based interventions strengthen the proposal and its implementation. Development of health policies that include PSC according to standards is needed to achieve sustainable results in the quality of life of children with cancer and their families.

TGFß Governs the Pleiotropic Activity of NDRG1 in Triple-Negative Breast Cancer Progression.

In triple-negative breast cancer (TNBC), the pleiotropic NDRG1 (N-Myc downstream regulated gene 1) promotes progression and worse survival, yet contradictory results were documented, and the mechanisms remain unknown. Phosphorylation and localization could drive NDRG1 pleiotropy, nonetheless, their role in TNBC progression and clinical outcome was not investigated. We found enhanced p-NDRG1 (Thr346) by TGFß1 and explored whether it drives NDRG1 pleiotropy and TNBC progression. In tissue microarrays of 81 TNBC patients, we identified that staining and localization of NDRG1 and p-NDRG1 (Thr346) are biomarkers and risk factors associated with shorter overall survival. We found that TGFß1 leads NDRG1, downstream of GSK3ß, and upstream of NF-κB, to differentially regulate migration, invasion, epithelial-mesenchymal transition, tumor initiation, and maintenance of different populations of cancer stem cells (CSCs), depending on the progression stage of tumor cells, and the combination of TGFß and GSK3ß inhibitors impaired CSCs. The present study revealed the striking importance to assess both total NDRG1 and p-NDRG1 (Thr346) positiveness and subcellular localization to evaluate patient prognosis and their stratification. NDRG1 pleiotropy is driven by TGFß to differentially promote metastasis and/or maintenance of CSCs at different stages of tumor progression, which could be abrogated by the inhibition of TGFß and GSK3ß.

Standards for psychosocial care in pediatric cancer: adapted proposal for Latin American and Caribbean countries / Normas para la atención psicosocial en el cáncer pediátrico: una propuesta adaptada para los países de América Latina y el Caribe / Padrões de atendimento psicossocial em câncer pediátrico: proposta adaptada para países da América Latina e do Caribe

ABSTRACT Objective. To highlight the objectives, achievements, challenges, and next steps for the World Health Organization's Global Initiative for Childhood Cancer (GICC) framework, a project designed to improve psychosocial care (PSC) in pediatric cancer centers across Latin America and the Caribbean (LAC). Methods. The project was launched in Peru, the first GICC focal country, in November 2020. The diagnosis phase included a survey and a semistructured interview with health professionals to assess PSC practices in institutions, and a needs assessment survey for caregivers. In the second phase, a strategic plan was developed to address the identified needs, including the adaptation of PSC standards, the establishment of multicenter working groups, the expansion of the proposal, and the development of materials. Results. The study found that PSC was not being adequately provided in accordance with international standards. Six adapted standards were proposed and validated, and more than 50 regional health professionals participated in online activities to support the project. The implementation process is currently ongoing, with the establishment of five multidisciplinary working groups, one regional committee, and the production of 16 technical outputs. Conclusion. This project represents a substantial step forward to improve PSC for pediatric patients with cancer and their families in LAC countries. The establishment of working groups and evidence-based interventions strengthen the proposal and its implementation. Development of health policies that include PSC according to standards is needed to achieve sustainable results in the quality of life of children with cancer and their families.

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RESUMO Objetivo. Destacar os objetivos, as conquistas, os desafios e as próximas etapas da Iniciativa Global para o Câncer Infantil (GICC), um projeto criado pela Organização Mundial da Saúde para melhorar a atenção psicossocial em centros de câncer pediátrico na América Latina e no Caribe. Métodos. O projeto foi lançado no Peru, o primeiro país focal da GICC, em novembro de 2020. A fase de diagnóstico incluiu uma pesquisa e uma entrevista semiestruturada com profissionais de saúde para avaliar as práticas de atenção psicossocial nas instituições, bem como uma pesquisa para avaliar as necessidades dos cuidadores. Na segunda fase, foi desenvolvido um plano estratégico para atender às necessidades identificadas, incluindo uma adaptação de padrões de atenção psicossocial, o estabelecimento de grupos de trabalho multicêntricos, a expansão da proposta e o desenvolvimento de materiais. Resultados. O estudo constatou que, de acordo com padrões internacionais, a atenção psicossocial não estava sendo adequadamente oferecida. Seis padrões adaptados foram propostos e validados, e mais de 50 profissionais de saúde da região participaram de atividades on-line para apoiar o projeto. O processo de implementação está em andamento, com a formação de cinco grupos de trabalho multidisciplinares e um comitê regional e a produção de 16 relatórios técnicos. Conclusão. Este projeto representa um avanço substancial para melhorar a atenção psicossocial para pacientes pediátricos com câncer e suas famílias nos países da América Latina e do Caribe. A criação de grupos de trabalho e intervenções baseadas em evidências fortalecem a proposta e sua implementação. É preciso desenvolver políticas de saúde que incluam atenção psicossocial segundo padrões estabelecidos para alcançar resultados sustentáveis na qualidade de vida das crianças com câncer e de suas famílias.

Capsaicin Decreases Kidney Iron Deposits and Increases Hepcidin Levels in Diabetic Rats with Iron Overload: A Preliminary Study.

Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg-1·day-1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.

Características clínicas y microbiológicas de infecciones de piel y partes blandas en pacientes pediátricos de dos hospitales de Buenos Aires / Skin and soft tissue infections in pediatrics

Las infecciones de piel y partes blandas (IPPB) en niños son una de las principales causas de prescripción de antimicrobianos. El objetivo del estudio fue describir las características clínicas y microbiológicas de las IPPB ambulatorias de niños asistidos en dos hospitales zonales. Se realizó un estudio prospectivo entre el 1/11/2017 y el 1/11/2018. Se incluyeron pacientes entre 1 mes y 15 años internados en dos hospitales. Se evaluó: edad, sexo, localidad, factores predisponentes, tipo de IPPB, muestras biológicas realizadas, aislamiento microbiológico, tratamiento empírico indicado y evolución del cuadro. Se realizó antibiograma y determinación genética. Se calculó chi2, IC95, OR; α=5%. N= 94. 58,7% masculinos. 12 pacientes <1 año, 85 >1 año (promedio de edad 4 años, 1-15). El 36% de Tandil y 63,8% de Florencio Varela. El 59,6% corresponden a IPPB purulentas. Se aislaron microorganismos en un 59,6%. Los aislamientos principales: SAMR (40,4%), SAMS (7,4%), S. agalactiae (2,1%) y S. pyogenes (2,1%). El 100% de SAMR son portadores de gen mecA y SCCmec tipo IV, sin multirresistencia. No hubo diferencia estadística entre los factores de riesgo evaluados para el desarrollo de IPPB por SAMR. El 52,1% de los niños recibió tratamiento antibiótico combinado, siendo la más indicada TMS-SMX + CLI en 36 eventos. (38,3%). La evolución fue favorable: no hubo diferencia significativa entre el subgrupo que se aisló SAMR y el que no se aisló SAMR; 91,9% (34/37) y 92,6% (50/54) correspondientemente (chi2: 0,01; p= 0,97 IC95: 0,26-3,88). El principal agente etiológico fue SAMRco, debiendo adecuar los tratamientos a este microorganismo.

Skin and soft tissue infections (SSIs) in children are one of the main causes of antimicrobial prescription. The aim of the study was to describe the clinical and microbiological characteristics of outpatient SSIs in children attended in two hospitals. A prospective study was conducted between 11/1/2017 and 11/1/2018. Patients between 1 month and 15 years old, hospitalized were included. We evaluated: age, sex, locality, predisposing factors, type of IPPB, biological samples taken, microbiological isolation, empirical treatment indicated and evolution of the condition. An antibiogram and genetic determination were performed. Chi2, CI95, OR; α=5% were calculated. N= 94. 58.7% male. 12 patients <1 year, 85 >1 year (mean age 4 years, 1-15). 36% were from Tandil and 63.8% from Florencio Varela. 59.6% corresponded to purulent SSIs. The diagnostic yield was 59.6%. Main isolates: MRSA (40.4%), MSSA (7.4%), S. agalactiae (2.1%) and S. pyogenes (2.1%). 100% of MRSA carried the mecA gene and SCCmec type IV, with no multidrug resistance. There was no statistical difference between the risk factors evaluated. 52.1% of children received combined antibiotic treatment, the most indicated being TMS-SMX + CLI in 36 events. (38,3%). Evolution was favorable: there was no significant difference between the subgroup that isolated MRSA and the subgroup that did not isolate MRSA; 91.9% (34/37) and 92.6% (50/54) respectively (chi2: 0.01; p= 0.97 CI95: 0.26-3.88). The main etiological agent was MRSA, and treatments should be adapted to this microorganism

CD19 CAR T cell product and disease attributes predict leukemia remission durability.

BACKGROUND: Chimeric antigen receptor (CAR) T cells can induce remission in highly refractory leukemia and lymphoma subjects, yet the parameters for achieving sustained relapse-free survival are not fully delineated. METHODS: We analyzed 43 pediatric and young adult subjects participating in a Phase I trial of defined composition CD19CAR T cells (NCT02028455). CAR T cell phenotype, function and expansion, as well as starting material T cell repertoire, were analyzed in relation to therapeutic outcome (defined as achieving complete remission within 63 days) and duration of leukemia free survival and B cell aplasia. RESULTS: These analyses reveal that initial therapeutic failures (n = 5) were associated with attenuated CAR T cell expansion and/or rapid attrition of functional CAR effector cells following adoptive transfer. The CAR T products were similar in phenotype and function when compared to products resulting in sustained remissions. However, the initial apheresed peripheral blood T cells could be distinguished by an increased frequency of LAG-3+/TNF-αlow CD8 T cells and, following adoptive transfer, the rapid expression of exhaustion markers. For the 38 subjects who achieved an initial sustained MRD-neg remission, remission durability correlated with therapeutic products having increased frequencies of TNF-α-secreting CAR CD8+ T cells, and was dependent on a sufficiently high CD19+ antigen load at time of infusion to trigger CAR T cell proliferation. CONCLUSION: These parameters have the potential to prospectively identify patients at risk for therapeutic failure and support the development of approaches to boost CAR T cell activation and proliferation in patients with low levels of CD19 antigen. TRIAL REGISTRATION: ClinicalTrials.gov NCT02028455. FUNDING: Partial funding for this study was provided by Stand Up to Cancer & St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113), RO1 CA136551-05, Alex Lemonade Stand Phase I/II Infrastructure Grant, Conquer Cancer Foundation Career Development Award, Washington State Life Sciences Discovery Fund, Ben Towne Foundation, William Lawrence & Blanche Hughes Foundation, and Juno Therapeutics, Inc., a Celgene Company.

Toxocara canis en humanos, perros y suelos en ribera del Río de la Plata, provincia de Buenos Aires / Toxocara canis in humans, dogs and soil on the river side of Rio de la Plata, province of Buenos Aires / Toxocara canis em humanos, cães e solos nas margens do Rio da Prata, província de Buenos Aires

El objetivo de este trabajo fue describir la situación epidemiológica de toxocariosis en un hábitat ribereño. Se determinaron anticuerpos anti-toxocara por ELISA en sueros de 34 niños y 64 adultos, y se hallaron seroprevalencias de 32,3% y 45,3%, respectivamente. Esta fue alta en adultos y en niños de 2 a 3 años. Se realizaron 217 análisis coproparasitológicos de caninos y 23,04% fueron positivos para huevos de Toxocara canis. La distribución de caninos positivos por rango etario fue de 66% entre 1 y 6 meses; de 20,7% entre 6 y 12 meses; y de 10,3% en mayores de 12 meses. El porcentaje de animales parasitados por T. canis fue significativamente menor en relación a otros parásitos y disminuyó marcadamente con el aumento de la edad. Se analizaron 104 muestras de suelo y 1,92% de las mismas fueron positivas para huevos de T. canis. La escasa cantidad de huevos en suelos podría deberse a que los cachorros no se encontraban libres en los espacios públicos. En este barrio podría inferirse que el suelo no actuó como diseminador de esta parasitosis, sino que fueron de mayor relevancia factores como la tenencia de caninos menores de 1 año, el contacto estrecho con los mismos en ámbitos domiciliarios y las condiciones higiénico-sanitarias poco saludables.

The aim of this study was to describe the epidemiological situation of toxocariasis in a coastal habitat. Blood samples of 34 children and 64 adults were analyzed in order to determinate antibodies anti-toxocara by ELISA method. Prevalences of 32.3% and 45.3% were obtained respectively. A total of 217 coproparasitological canine analyses were performed, and 104 soil samples were analyzed. In humans, the seroprevalence of 32.4% in children and 45.3% in adults was found. In dogs, 50 samples were positive for T. canis eggs (23.04%). The distribution of canine positive for each age range yielded the following results: from 1 to 6 months, 66%; from 6 to 12 months, 20.7% and over 12 months, 10.3%. In soils, only 2 samples (1.92%) were positive for T. canis eggs. Seroloprevalence in humans was high, especially in adults and children aged 2 to 3 years. The percentage of parasitized animals by Toxocara was significantly lower in relation to other canine parasites and the percentage of dogs parasitized diminished significantly by increasing the age range. The low number of eggs found in soils could be due to the absence of puppies in public spaces. In this neighborhood, it can be inferred that the ground of public spaces did not act as a disseminator of this parasitosis, but that there were more relevant factors such as the possession of canines under 1 year of age, the close contact with them in residential areas, and unhealthy sanitary conditions.

O objetivo deste trabalho foi descrever a situação epidemiológica da toxocaríase em um habitat ripícola. Os anticorpos anti-toxocara foram determinados por ELISA em soros de 34 crianças e 64 adultos, com soroprevalência de 32,3% e 45,3%, respectivamente. Ela foi alta em adultos e em crianças de 2 a 3 anos de idade. Foram realizadas 217 análises coproparasitológicas caninas e 23,04% foram positivas para os ovos de Toxocara canis. A distribuição de caninos positivos por faixa etária foi de 66%, entre 1 e 6 meses, de 20,7%, entre 6 e 12 meses, e de 10,3% em maiores de 12 meses. A porcentagem de animais parasitados por T. canis foi significativamente menor em relação a outras parasitas e diminuiu marcadamente com o aumento da idade. Foram analisadas 104 amostras de solo e 1,92% delas foram positivas para ovos de T. canis. A escassa quantidade de ovos nos solos pode ser o resultado do fato de que os filhotes não estivessem livres nos espaços públicos. Poderia ser inferido que, nesse bairro, o solo não atuou como disseminador dessa parasitose, mas fatores como a posse de caninos menores de 1 ano de idade, um contato próximo com eles em ambientes domésticos e condições higiênico-sanitárias insalubres foram fatores de maior relevância.

In vitro evaluation of MgSr and MgCaSr alloys via direct culture with bone marrow derived mesenchymal stem cells.

Magnesium (Mg) and its alloys have been widely investigated as the most promising biodegradable metals to replace conventional non-degradable metals for temporary medical implant applications. New Mg alloys have been developed for medical applications in recent years; and the concept of alloying Mg with less-toxic elements have aroused tremendous interests due to the promise to address the problems associated with rapid degradation of Mg without compromising its cytocompatibility and biocompatibility. Of particular interests for orthopedic/spinal implant applications are the additions of calcium (Ca) and strontium (Sr) into Mg matrix because of their beneficial properties for bone regeneration. In this study, degradation and cytocompatibility of four binary MgSr alloys (Mg-xSr, x = 0.2, 0.5, 1 and 2 wt%) and four ternary MgCaSr alloys (Mg-1Ca-xSr, x = 0.2, 0.5, 1 and 2 wt%) were investigated and compared via direct culture with bone marrow-derived mesenchymal stem cells (BMSCs). The influence of the alloy composition on the degradation rates were studied and compared. Moreover, the cellular responses to the binary MgSr alloys and the ternary MgCaSr alloys were comparatively evaluated; and the critical factors influencing BMSC behaviors were discussed. This study screened the degradability and in vitro cytocompatibility of the binary MgSr alloys and the ternary MgCaSr alloys. Mg-1Sr, Mg-1Ca-0.5Sr and Mg-1Ca-1Sr alloys are recommended for further in vivo studies toward clinical translation due to their best overall performances in terms of degradation and cytocompatibility among all the alloys studied in the present work. STATEMENT OF SIGNIFICANCE: Traditional Mg alloys with slower degradation often contain aluminum or rare earth elements as alloying components, which raised safety and regulatory concerns. To circumvent unsafe elements, nutrient elements such as calcium (Ca) and strontium (Sr) were selected to create Mg-Sr binary alloys and Mg-Ca-Sr ternary alloys to improve the safety and biocompatibility of bioresorbable Mg alloys for medical implant applications. In this study, in vitro degradation and cellular responses to four binary Mg-xSr alloys and four ternary Mg-1Ca-xSr alloys with increasing Sr content (up to 2 wt%) were evaluated in direct culture with bone marrow derived mesenchymal stem cells (BMSCs). The roles of Sr and Ca in tuning the alloy microstructure, degradation behaviors, and BMSC responses were collectively compared in the BMSC direct culture system for the first time. The most promising alloys were identified and recommended for further in vivo studies toward clinical translation.

Ablación por radiofrecuencia de una taquicardia ventricular tras la cirugía reparadora de la tetralogía de Fallot / Radiofrequency Catheter Ablation of Ventricular Tachycardia after Repair of Tetralogy of Fallot / Radiofrequency Catheter Ablation of Ventricular Tachycardia after Repair of Tetralogy of Fallot

La taquicardia ventricular monomórfica sostenida (TVMS) es una complicación tardía de la cirugía reparadora de la tetralogía de Fallot y si bien puede ser tratada por técnicas convencionales de ablación por radiofrecuencia, las características de los pacientes hacen que la tasa de éxito de su utilización no supere el 50%. El advenimiento de métodos de cartografía electroanatómica tridimensional favorece una ablación exitosa. En esta presentación se describe el caso de un paciente de 53 años con cirugía previa reparadora de tetralogía de Fallot, a quien le fue colocado un cardiodesfibrilador automático implantable por una TVMS sintomática por síncope. Se decidió indicar una ablación por radiofrecuencia por la presentación de recurrencias a pesar del tratamiento con amiodarona. Asimismo, se describen las técnicas de cartografía electroanatómica tridimensional que, complementando a la electrofisiología convencional, permiten la caracterización correcta de los circuitos arritmogénicos, posibilitando así la abolición de la arritmia mediante radiofrecuencia. A nuestro entender, este es el primer caso publicado en la Argentina de ablación de TVMS en pacientes con cirugía reparadora de tetralogía de Fallot.

Sustained monomorphic ventricular tachycardia (SMVT) is a late complication of corrective surgery for tetralogy of Fallot. The success rate of conventional radiofrequency ablation is <50% due to patients' characteristics. Threedimensional electroanatomic mapping system is associated with favorable outcomes. We describe the case of a 53 year-old male patient with a history of previous corrective surgery for tetralogy of Fallot and an implantable cardioverter defibrillator due to syncope secondary to SMTV. Despite being treated with amiodarone, radiofrequency catheter ablation was indicated due to recurrences. In addition, we describe three-dimensional electroanatomic mapping system as a complement to conventional electrophysiology for an adequate characterization of the arrhythmogenic circuits undergoing radiofrequency catheter ablation. To our understanding, this is the first case published in Argentina of radiofrequency catheter ablation of a SMVT in patients with corrective surgery for tetralogy of Fallot.

Aplicación de normas de radioprotección en los servicios de radiología

Este trabajo tuvo por objeto verificar si los hospitales de la Ciudad Autónoma de Buenos Aires y del Gran Buenos Aires (GBA) cumplen con las normas básicas de seguridad radiológica en los servicios de radiología particularmente referidas al registro diario del dosímetro; al uso correcto del dosímetro, al uso correcto de los elementos de protección; al registro de placas radiológicas realizadas; al control de ingreso a las áreas restringidas de personas ajenas a los servicios; al uso de elementos de protección personal y finalmente si las instalaciones cuentan con los materiales aislantes adecuados y si se realiza el mantenimiento y supervisión de los equipos. Los resultados señalan que solo el Hospital Pirovano de la ciudad de Buenos Aires cumple con el 100 por ciento de las normas, seguido por los hospitales Roffo, Roca y San Isidro (GBA) con el 85 por ciento de cumplimiento. La investigación ha demostrado que existen graves irregularidades en la aplicación de las normas en la mayoría de los hospitale encuestados, especialmente en lo referente a la proteccion de las personas que ingresan en las areas restringidas ajenas a los servicios. Asimismo la investigacion remarca la importante diferencia entre los hospitales municipales de la Ciudad de Buenos Aires y provinciales del GBA respecto al uso de los elementos de proteccion por parte del personal (medicos y tecnicos radiologos) a favor de los primeros, infiriendose como factores a destacar en la falta de cumplimiento de las normas, la falta de concientizacion de los riesgos por el personal y la irresponsabilidad institucional, al no ejercer un adecuado control