Protocol for long-term treatment of lowly aggressive cancer cell lines with low concentrations of anti-tumor drugs.

The understanding of anti-tumor drug effects requires specific experimental settings which model clinical scenarios. We describe a protocol for 10-day treatment of lowly aggressive tumor cell lines with antineoplastic agents at concentrations which do not affect cell growth. We describe steps for seeding cells and treating cells with anti-tumor drugs. We then detail steps for cell sensitivity, cell proliferation, and mRNA and protein expression assays. We also detail assays to determine modifications in compound efflux. For complete details on the use and execution of this protocol, please refer to Rios Medrano et al.1.

Natural Prevalence, Molecular Characteristics, and Biological Activity of Metarhizium rileyi (Farlow) Isolated from Spodoptera frugiperda (J. E. Smith) Larvae in Mexico.

Entomopathogenic fungi have been considered potential biological control agents against the fall armyworm Spodoptera frugiperda (J. E. Smith), the world's most important pest of maize. In this study, we evaluated the natural infection, molecular characteristics, and biological activity of Metarhizium rileyi (Farlow) isolated from S. frugiperda larvae of this insect, collected from maize crops in five Mexican locations. Natural infection ranged from 23% to 90% across all locations analyzed. Twenty-four isolates were evaluated on S. frugiperda second instars at a concentration of 1.0 × 108 conidia/mL, causing 70% to 98.7% mortality and 60.5% to 98.7% sporulation. Isolates T9-21, Z30-21, PP48-21, and L8-22 were selected to determine their phylogenetic relationships by ß-tubulin gene analysis and to compare median lethal concentration (CL50), median lethal time (LT50), and larval survival. These isolates were grouped into three clades. The T9-21, PP48-21, and J10-22 isolates were closely related (clade A), but phylogenetically distant from Z30-21 (clade B) and L8-22 (clade C) isolates. These genetic differences were not always reflected in their pathogenicity characteristics since no differences were observed among the LC50 values. Furthermore, isolates T9-21, J10-22, and L8-22 were the fastest to kill S. frugiperda larvae, causing lower survival rates. We conclude that native M. rileyi isolates represent an important alternative for the biocontrol of S. frugiperda.

Acyl-CoA synthetase 4 modulates mitochondrial function in breast cancer cells.

Mitochondria are dynamic organelles that respond to cellular stress through changes in global mass, interconnection, and subcellular location. As mitochondria play an important role in tumor development and progression, alterations in energy metabolism allow tumor cells to survive and spread even in challenging conditions. Alterations in mitochondrial bioenergetics have been recently proposed as a hallmark of cancer, and positive regulation of lipid metabolism constitutes one of the most common metabolic changes observed in tumor cells. Acyl-CoA synthetase 4 (ACSL4) is an enzyme catalyzing the activation of long chain polyunsaturated fatty acids with a strong substrate preference for arachidonic acid (AA). High ACSL4 expression has been related to aggressive cancer phenotypes, including breast cancer, and its overexpression has been shown to positively regulate the mammalian Target of Rapamycin (mTOR) pathway, involved in the regulation of mitochondrial metabolism genes. However, little is known about the role of ACSL4 in the regulation of mitochondrial function and metabolism in cancer cells. In this context, our objective was to study whether mitochondrial function and metabolism, processes usually altered in tumors, are modulated by ACSL4 in breast cancer cells. Using ACSL4 overexpression in MCF-7 cells, we demonstrate that this enzyme can increase the mRNA and protein levels of essential mitochondrial regulatory proteins such as nuclear respiratory factor 1 (NRF-1), voltage-dependent anion channel 1 (VDAC1) and respiratory chain Complex III. Furthermore, respiratory parameters analysis revealed an increase in oxygen consumption rate (OCR) and in spare respiratory capacity (SRC), among others. ACSL4 knockdown in MDA-MB-231 cells led to the decrease in OCR and in SCR, supporting the role of ACSL4 in the regulation of mitochondrial bioenergetics. Moreover, ACSL4 overexpression induced an increase in glycolytic function, in keeping with an increase in mitochondrial respiratory activity. Finally, there was a decrease in mitochondrial mass detected in cells that overexpressed ACSL4, while the knockdown of ACSL4 expression in MDA-MB-231 cells showed the opposite effect. Altogether, these results unveil the role of ACSL4 in mitochondrial function and metabolism and expand the knowledge of ACSL4 participation in pathological processes such as breast cancer.

Characterization of Retinoblastoma Patients in a Referral Center on the Colombian North Coast / Caracterización de pacientes con retinoblastoma en un centro de referencia de la costa norte de Colombia

ABSTRACT Purpose: The purpose of the following study was to describe the sociodemographic, clinical, and therapeutic characteristics of patients with retinoblastoma (RB), the most common intraocular tumor in children, receiving medical care in an eyecare institution in the Caribbean region of Colombia. Methods: A case series between 2016 and 2021 was carried out. Eyes of patients with RB, receiving medical care in a single health care institution, and in compliance with the established follow-up protocol, were included. Descriptive analyzes of relevant variables were performed. Results: In this study, a total of 21 eyes of 16 patients were examined. The average age at the time of diagnosis was 17.7 months, and 50% of children were male. Using the International Classification for Intraocular Retinoblastoma, 42.9% of the total cases were classified as group D. Out of the 21 cases, 71.4% went into total remission without the necessity for enucleation, and the most common treatment was chemotherapy, using Melphalan® via intraarterial or intravitreal administration. Conclusion: Specific findings of patients with RB in the Caribbean Coast of Colombia were identified. These findings imply that, despite the obstacles to healthcare access, an early diagnosis and a treatment plan using intraarterial chemotherapy may provide a satisfactory clinical outcome (remission).

RESUMEN. Objetivo: El propósito del siguiente estudio fue describir las características sociodemográ-ficas, clínicas y terapéuticas de los pacientes con retinoblastoma (RB), el tumor intraocular más frecuente en niños, que reciben atención médica en una institución oftalmológica de la región Caribe de Colombia. Métodos: Se realizó una serie de casos entre 2016 y 2021. Se incluyeron ojos de pacientes con RB, que recibían atención médica en una sola institución de salud y cumplían con el protocolo de seguimiento establecido. Se realizaron análisis descriptivos de variables relevantes. Resultados: En este estudio se examinaron un total de 21 ojos de 16 pacientes. La edad media en el momento del diagnóstico fue de 17,7 meses y el 50% de los niños eran varones. Utilizando la Clasificación Internacional para el retinoblastoma intraocular, el 42,9% del total de los casos se clasificaron en el grupo D. De los 21 casos, el 71,4% entraron en remisión total sin necesidad de enucleación, y el tratamiento más habitual fue la quimioterapia con Melfalán® vía intraarterial o intravítrea. Conclusiones: Se identificaron hallazgos específicos de pacientes con RB en la costa caribe de Colombia. Estos hallazgos implican que, a pesar de los obstáculos en el acceso a la salud, un diagnóstico temprano y un plan de tratamiento con quimioterapia intraarterial pueden proporcionar un resultado clínico satisfactorio (remisión).

Specific cellular microenvironments for spatiotemporal regulation of StAR and steroid synthesis.

For many years, research in the field of steroid synthesis has aimed to understand the regulation of the rate-limiting step of steroid synthesis, i.e. the transport of cholesterol from the outer to the inner mitochondrial membrane, and identify the protein involved in the conversion of cholesterol into pregnenolone. The extraordinary work by B Clark, J Wells, S R King, and D M Stocco eventually identified this protein and named it steroidogenic acute regulatory protein (StAR). The group's finding was also one of the milestones in understanding the mechanism of nonvesicular lipid transport between organelles. A notable feature of StAR is its high degree of phosphorylation. In fact, StAR phosphorylation in the acute phase is required for full steroid biosynthesis. As a contribution to this subject, our work has led to the characterization of StAR as a substrate of kinases and phosphatases and as an integral part of a mitochondrion-associated multiprotein complex, essential for StAR function and cholesterol binding and mitochondrial transport to yield maximum steroid production. Results allow us to postulate the existence of a specific cellular microenvironment where StAR protein synthesis and activation, along with steroid synthesis and secretion, are performed in a compartmentalized manner, at the site of hormone receptor stimulation, and involving the compartmentalized formation of the steroid molecule-synthesizing complex.

Manejo familiar da criança que espera por um transplante de órgãos / Family management of child waiting for a organ transplant / Manejo familiar del niño en espera de un trasplante de órganos

Objetivo: conhecer a experiência de manejo familiar da criança à espera de um transplante de órgãos sólidos de acordo com o Modelo de estilos de manejo familiar. Método: foi realizado um estudo qualitativo que utilizou o modelo supracitado como referencial teórico. Foram aplicadas entrevistas, de forma remota, a nove familiares de crianças que aguardavam por um transplante de órgãos. Os dados foram analisados através do modelo híbrido de análise temática. Resultados: as famílias definem que essa fase oscila entre o medo do transplante, da rejeição do órgão e possibilidade de morte em fila de espera, e a esperança na melhora do quadro clínico. Considerações finais: identificar as necessidades da família que aguarda por um transplante possibilita ao profissional de saúde implementar intervenções

Objective: to understand the family management experience of children waiting for a solid organ transplant in accordance with the Family Management Styles Model. Method: a qualitative study was carried out using the aforementioned model as a theoretical framework. Interviews were conducted remotely with nine family members of children waiting for an organ transplant. Data were analyzed using the hybrid thematic analysis model. Results: families define that this phase oscillates between fear of transplantation, organ rejection and the possibility of death on the waiting list, and hope for an improvement in the clinical condition. Final considerations: identifying the needs of the family waiting for a transplant allows the health professional to implement interventions

Objetivos:comprender la experiencia de gestión familiar de niños en espera de trasplante de órgano sólido de acuerdo con el Modelo de Estilos de Gestión Familiar. Método: se realizó un estudio cualitativo utilizando como marco teórico el modelo antes mencionado. Las entrevistas se realizaron de forma remota con nueve familiares de niños que esperaban un trasplante de órgano. Los datos se analizaron utilizando el modelo de análisis temático híbrido. Resultados: las familias definen que esta fase oscila entre el miedo al trasplante, el rechazo del órgano y la posibilidad de muerte en lista de espera, y la esperanza de mejora del cuadro clínico. Consideraciones finales: identificar las necesidades de la familia en espera de un trasplante permite al profesional de la salud implementar intervenciones

Manejo familiar da criança que espera por um transplante de órgãos / Family management of child waiting for a organ transplant / Manejo familiar del niño en espera de un trasplante de órganos

Objetivo: conhecer a experiência de manejo familiar da criança à espera de um transplante de órgãos sólidos de acordo com o Modelo de estilos de manejo familiar. Método: foi realizado um estudo qualitativo que utilizou o modelo supracitado como referencial teórico. Foram aplicadas entrevistas, de forma remota, a nove familiares de crianças que aguardavam por um transplante de órgãos. Os dados foram analisados através do modelo híbrido de análise temática. Resultados: as famílias definem que essa fase oscila entre o medo do transplante, da rejeição do órgão e possibilidade de morte em fila de espera, e a esperança na melhora do quadro clínico. Considerações finais: identificar as necessidades da família que aguarda por um transplante possibilita ao profissional de saúde implementar intervenções

Objective: to understand the family management experience of children waiting for a solid organ transplant in accordance with the Family Management Styles Model. Method: a qualitative study was carried out using the aforementioned model as a theoretical framework. Interviews were conducted remotely with nine family members of children waiting for an organ transplant. Data were analyzed using the hybrid thematic analysis model. Results: families define that this phase oscillates between fear of transplantation, organ rejection and the possibility of death on the waiting list, and hope for an improvement in the clinical condition. Final considerations: identifying the needs of the family waiting for a transplant allows the health professional to implement interventions

Objetivos:comprender la experiencia de gestión familiar de niños en espera de trasplante de órgano sólido de acuerdo con el Modelo de Estilos de Gestión Familiar. Método: se realizó un estudio cualitativo utilizando como marco teórico el modelo antes mencionado. Las entrevistas se realizaron de forma remota con nueve familiares de niños que esperaban un trasplante de órgano. Los datos se analizaron utilizando el modelo de análisis temático híbrido. Resultados: las familias definen que esta fase oscila entre el miedo al trasplante, el rechazo del órgano y la posibilidad de muerte en lista de espera, y la esperanza de mejora del cuadro clínico. Consideraciones finales: identificar las necesidades de la familia en espera de un trasplante permite al profesional de la salud implementar intervenciones

Prevalence and gender disparities of type 2 diabetes mellitus and obesity in Esmeraldas, Ecuador: a population-based survey in a hard-to-reach setting.

BACKGROUND: Type 2 Diabetes (T2DM) prevalence is increasing in low- and middle-income countries along with high levels of obesity which vary according to socioeconomic and contextual characteristics. We aim to estimate the prevalence of T2DM and obesity in men and women in a hard-to-reach rural area in northern Ecuador considering socio-demographic characteristics. METHODS: Cross-sectional descriptive study based on a population-based survey in the Eloy Alfaro health district of Esmeraldas between October 2020 and January 2022. We collected sociodemographic information and risk factors for non-communicable diseases with an adapted version of the STEPS survey, performed oral glucose tolerance tests, biochemistry and took physical measurements. We estimated the prevalence of T2DM, obesity, and calculated Odds Ratios (OR) with confidence intervals by logistic regression in Stata v.15. RESULTS: The overall prevalence of T2DM was 6.8% (CI95%: 4.9-8.7), markedly higher among women compared to men (10.4%, CI95% 7.3-13.4%, compared 2.0%, CI95% 0.4-3.7% respectively). The risk of having T2DM in women was 5 times higher than in men adjusting for age, ethnicity, employment, household earnings and obesity (OR: 5.03; 95%CI: 1.68-15.01). Regarding age, the risk of T2DM increased by 6% per year (adjusted OR: 1.06; 95%CI: 1.03-1.08). Obesity prevalence was 30.8% (CI95%: 27.3-34.3), in women was nearly three times higher than in men (43.2% CI95%: 38.2-48.2, compared to 14.7% prevalence, CI95%: 10.6-18.8). Indigenous women had a lower prevalence of obesity compared with the Afro-Ecuadorian women (OR: 0.05; 95%CI: 0.02-0.18) after adjusting for age, employment status, household earnings and setting. CONCLUSION: We found alarming differences between the prevalence of T2DM and obesity in women and men that may be explained by gender roles, exacerbated in the rural context. Health promotion measures with a gender perspective should be adapted according to the characteristics of isolated rural contexts.

Access to health services for chronic disease care during the COVID-19 pandemic in Ecuador: A qualitative analysis using a Social Determinants of Health approach.

This qualitative study aims to explore how the COVID-19 pandemic impacted healthcare access for patients with chronic conditions in Ecuador from the patient's perspective. We interviewed 19 patients diagnosed with arterial hypertension or type 2 diabetes in rural and urban areas of Ecuador during August and September 2020. We used the Framework Method to analyse the interview transcripts with ATLAS.Ti 8.4 and organised the ideas discussed using categories from the World Health Organization Commission on the Social Determinants of Health conceptual framework. Reorganization of health services during the pandemic meant that patients with arterial hypertension or diabetes could no longer attend face-to-face appointments for disease follow-up. System failures related to medication supply led to increased out-of-pocket payments, which, together with reduced or absent earnings, and in a context with limited social protection policies, meant that patients frequently went for prolonged periods without medication. Rural health initiatives, support from family and use of traditional medicine were reported as ways to manage their chronic condition during this time. Barriers to disease management disproportionately affected individuals with low socioeconomic positions. Stock shortages, lack of protective labour policies and limited reach of anticipatory policies for health emergencies likely worsened pre-existing health inequities in Ecuador.

An efficient transformation method for genome editing of elite bread wheat cultivars.

An efficient genetic transformation protocol is necessary to edit genes for trait improvement directly in elite bread wheat cultivars. We used a protein fusion between a wheat growth-regulating factor 4 (GRF4) and its interacting factor (GIF1) to develop a reproducible genetic transformation and regeneration protocol, which we then used to successfully transform elite bread wheat cultivars Baj, Kachu, Morocco, Reedling, RL6077, and Sujata in addition to the experimental cultivar Fielder. Immature embryos were transformed with the vector using particle bombardment method. Transformation frequency increased nearly 60-fold with the GRF4-GIF1-containing vectors as compared to the control vector and ranged from ~5% in the cultivar Kachu to 13% in the cultivar RL6077. We then edited two genes that confer resistance against leaf rust and powdery mildew directly in the aforementioned elite cultivars. A wheat promoter, TaU3 or TaU6, to drive the expression of guide RNA was effective in gene editing whereas the OsU3 promoter failed to generate any edits. Editing efficiency was nearly perfect with the wheat promoters. Our protocol has made it possible to edit genes directly in elite wheat cultivars and would be useful for gene editing in other wheat varieties, which have been recalcitrant to transformation thus far.

New insights into signal transduction pathways in adrenal steroidogenesis: role of mitochondrial fusion, lipid mediators, and MAPK phosphatases.

Hormone-receptor signal transduction has been extensively studied in adrenal gland. Zona glomerulosa and fasciculata cells are responsible for glucocorticoid and mineralocorticoid synthesis by adrenocorticotropin (ACTH) and angiotensin II (Ang II) stimulation, respectively. Since the rate-limiting step in steroidogenesis occurs in the mitochondria, these organelles are key players in the process. The maintenance of functional mitochondria depends on mitochondrial dynamics, which involves at least two opposite events, i.e., mitochondrial fusion and fission. This review presents state-of-the-art data on the role of mitochondrial fusion proteins, such as mitofusin 2 (Mfn2) and optic atrophy 1 (OPA1), in Ang II-stimulated steroidogenesis in adrenocortical cells. Both proteins are upregulated by Ang II, and Mfn2 is strictly necessary for adrenal steroid synthesis. The signaling cascades of steroidogenic hormones involve an increase in several lipidic metabolites such as arachidonic acid (AA). In turn, AA metabolization renders several eicosanoids released to the extracellular medium able to bind membrane receptors. This report discusses OXER1, an oxoeicosanoid receptor which has recently arisen as a novel participant in adrenocortical hormone-stimulated steroidogenesis through its activation by AA-derived 5-oxo-ETE. This work also intends to broaden knowledge of phospho/dephosphorylation relevance in adrenocortical cells, particularly MAP kinase phosphatases (MKPs) role in steroidogenesis. At least three MKPs participate in steroid production and processes such as the cellular cycle, either directly or by means of MAP kinase regulation. To sum up, this review discusses the emerging role of mitochondrial fusion proteins, OXER1 and MKPs in the regulation of steroid synthesis in adrenal cortex cells.

Self-limited epilepsy with autonomic seizures: A case report.

Self-limited epilepsy with autonomic seizures, formerly known as benign occipital epilepsy of childhood or Panayiotopoulos syndrome is a focal epilepsy that is part of the epileptic syndromes with onset during childhood. The objective of this report is to raise awareness about its importance and describe the clinical manifestations, timely diagnosis, and treatment. A pediatric patient admitted with gastrointestinal manifestations is presented. The autonomic manifestations must be considered as part of the clinical spectrum that includes this disease and the digestive and autonomic manifestations that mask the diagnosis, sometimes even in the absence of motor seizures themselves. Electroencephalographic confirmation was performed, avoiding cataloging it in other differential diagnoses.

Connecting to (Re)connect: Video Calling as a Resource to Unite Families and Children in a Pediatric Intensive Care Unit During the COVID-19 Era.

Video calling emerged as an important resource during coronavirus disease 2019 (COVID-19) to reconnect child and family, bringing the possibility of communication even during isolation. The objective of this study was to understand the experiences of families who communicated with their children through video calls during isolation by COVID-19 in the pediatric intensive care unit (PICU). This was a qualitative study employing the theory of symbolic interactionism and the research method of grounded theory, with 14 families of children in PICU who used video calling as a communication resource. The data were collected through semi-structured interviews. The analysis revealed the main category of "Connecting to (re)connect: Video calling as a resource to unite families and children in PICU in the COVID-19 era," from which a theoretical model explaining the experience was built. Video calling is an important resource to mitigate the effects of family-child separation during hospitalization, and its use is encouraged in other contexts.

Social Inequalities in Mental Health and Self-Perceived Health in the First Wave of COVID-19 Lockdown in Latin America and Spain: Results of an Online Observational Study.

COVID-19 lockdowns greatly affected the mental health of populations and collectives. This study compares the mental health and self-perceived health in five countries of Latin America and Spain, during the first wave of COVID 19 lockdown, according to social axes of inequality. This was a cross-sectional study using an online, self-managed survey in Brazil, Chile, Ecuador, Mexico, Peru, and Spain. Self-perceived health (SPH), anxiety (measured through GAD-7) and depression (measured through PHQ-9) were measured along with lockdown, COVID-19, and social variables. The prevalence of poor SPH, anxiety, and depression was calculated. The analyses were stratified by gender (men = M; women = W) and country. The data from 39,006 people were analyzed (W = 71.9%). There was a higher prevalence of poor SPH and bad mental health in women in all countries studied. Peru had the worst SPH results, while Chile and Ecuador had the worst mental health indicators. Spain had the lowest prevalence of poor SPH and mental health. The prevalence of anxiety and depression decreased as age increased. Unemployment, poor working conditions, inadequate housing, and the highest unpaid workload were associated with worse mental health and poor SPH, especially in women. In future policies, worldwide public measures should consider the great social inequalities in health present between and within countries in order to tackle health emergencies while reducing the health breach between populations.

Determinants of self-reported health status during COVID-19 lockdown among surveyed Ecuadorian population: A cross sectional study.

OBJECTIVE: To examine the associations of sociodemographic, socioeconomic, and behavioral factors with depression, anxiety, and self-reported health status during the COVID-19 lockdown in Ecuador. We also assessed the differences in these associations between women and men. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional survey between July to October 2020 to adults who were living in Ecuador between March to October 2020. All data were collected through an online survey. We ran descriptive and bivariate analyses and fitted sex-stratified multivariate logistic regression models to assess the association between explanatory variables and self-reported health status. RESULTS: 1801 women and 1123 men completed the survey. Their median (IQR) age was 34 (27-44) years, most participants had a university education (84%) and a full-time public or private job (63%); 16% of participants had poor health self-perception. Poor self-perceived health was associated with being female, having solely public healthcare system access, perceiving housing conditions as inadequate, living with cohabitants requiring care, perceiving difficulties in coping with work or managing household chores, COVID-19 infection, chronic disease, and depression symptoms were significantly and independently associated with poor self-reported health status. For women, self-employment, having solely public healthcare system access, perceiving housing conditions as inadequate, having cohabitants requiring care, having very high difficulties to cope with household chores, having COVID-19, and having a chronic disease increased the likelihood of having poor self-reported health status. For men, poor or inadequate housing, presence of any chronic disease, and depression increased the likelihood of having poor self-reported health status. CONCLUSION: Being female, having solely public healthcare system access, perceiving housing conditions as inadequate, living with cohabitants requiring care, perceiving difficulties in coping with work or managing household chores, COVID-19 infection, chronic disease, and depression symptoms were significantly and independently associated with poor self-reported health status in Ecuadorian population.

Clinical experience of thoracoplasty with absorbable rib substitutes.

PURPOSE: Malignant chest wall tumors are rare in pediatrics. They require multimodal oncological treatment and local surgical control. Resections are extensive; therefore, thoracoplasty should be planned to protect intrathoracic organs, prevent herniation, future deformities, preserve ventilatory dynamics, and enable radiotherapy. METHODS: We present a case series of children with malignant chest wall tumors and our surgical experience with thoracoplasty using absorbable rib substitutes (BioBridge®), after local surgical control. BioBridge® is a copolymer made of a polylactide acid blend (70% L-lactic acid y 30% DL-lactide). RESULTS: In 2 years, we had three patients with malignant chest wall tumors. Resection margins were negative, without recurrence at follow-up. We achieved good cosmetic and functional results, and no postoperative complications. CONCLUSION: Alternative reconstruction techniques such as absorbable rib substitutes provide protection, guarantee a flexible chest wall, and do not interfere with adjuvant radiotherapy. Currently, there are no management protocols in thoracoplasty. This option represents an excellent alternative for patients with chest wall tumors. Knowledge of different approaches and reconstructive principles is essential to offer children the best onco-surgical option.

Multisystem Inflammatory Syndrome in Children (MIS-C) temporally related to COVID-19: the experience at a pediatric reference hospital in Colombia / Síndrome inflamatória multissistêmica em criança associada à COVID-19: experiência em um hospital pediátrico de referência na Colômbia

Abstract Objective: This study aimed to describe the clinical characteristics and the different phenotypes of children with multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19 and to evaluate the risk conditions that favored a greater severity of the disease during a 12-month period at a pediatric reference hospital in Colombia. Methods: A 12-month retrospective observational study of children under the age of 18 years who met criteria for MIS-C. Results: A total of 28 children presented MIS-C criteria. The median age was 7 years. Other than fever (100%) (onset 4 days prior to admission), the most frequent clinical features were gastrointestinal (86%) and mucocutaneous (61%). Notably, 14 (50%) children had Kawasaki-like symptoms. The most frequent echocardiographic abnormalities were pericardial effusion (64%), valvular involvement (68%), ventricular dysfunction (39%), and coronary artery abnormalities (29%). In addition, 75% had lymphopenia. All had at least one abnormal coagulation test. Most received intravenous immunoglobulin (89%), glucocorticoids (82%), vasopressors (54%), and antibiotics (64%). Notably, 61% had a more severe form of the disease and were admitted to an intensive care unit (median 4 days, mean 6 days); the severity predictors were patients with the inflammatory/MIS-C phenotype (OR 26.5; 95%CI 1.40-503.7; p=0.029) and rash (OR 14.7; 95%CI 1.2-178.7; p=0.034). Two patients had macrophage activation syndrome. Conclusions: Coronary artery abnormalities, ventricular dysfunction, and intensive care unit admission were frequent, which needs to highlight the importance of early clinical suspicion.

Resumo Objetivo: Descrever as características clínicas e os diferentes fenótipos de crianças com síndrome inflamatória multissistêmica na criança temporalmente relacionada com a COVID-19 (do inglês multisystem inflammatory syndrome in children — MIS-C) e avaliar as condições de risco que favorecem a maior gravidade da doença durante um período de 12 meses em um hospital pediátrico de referência na Colômbia. Métodos: Estudo retrospectivo de 12 meses de observação de crianças menores de 18 anos que cumprem os critérios para o MIS-C. Resultados: Vinte e oito crianças foram apresentadas com os critérios do MIS-C. A idade média era de sete anos, e 54% eram do sexo masculino. Para além da febre (100%) (com início quatro dias antes da admissão), as características clínicas mais frequentes eram gastrointestinais (86%) e mucocutâneas (61%). Quatorze crianças (50%) apresentavam sintomas semelhantes aos de Kawasaki. As anomalias ecocardiográficas mais frequentes foram derrame pericárdico (64%), envolvimento valvar (68%), disfunção ventricular (39%) e anomalias coronárias (29%). Tinham linfopenia 75% das crianças. Todas tinham algum teste de coagulação anormal. A maioria recebeu imunoglobulina intravenosa (89%), glucocorticoides (82%), vasopressores (54%) e antibióticos (64%). Tiveram envolvimento mais grave 61% dos pacientes, que precisaram ser internados em unidade de terapia intensiva (mediana de quatro dias, média de seis dias); os preditores de gravidade foram pacientes com fenótipo inflamatório/ MIS-C (odds ratio — OR 26,5; intervalo de confiança — IC95% 1,4-503,7; p=0,029) e erupção cutânea (OR 14,7; IC95% 1,2-178,7; p=0,034). Dois pacientes (7%) apresentavam síndrome de ativação macrofágica. Conclusões: Alteração da artéria coronária, disfunção ventricular e internação na unidade de terapia intensiva foram frequentes, o que nos alerta sobre a importância da suspeita clínica precoce.

Escala Humpty Dumpty: adaptação transcultural e validação para cultura brasileira / Escala Humpty Dumpty: adaptación transcultural y validación para la cultura brasileña / The Humpty Dumpty Scale: cross-cultural adaptation and validation for Brazilian culture

Resumo Objetivo Adaptar e validar a The Humpty Dumpty Falls Scale para a cultura brasileira. Métodos Estudo metodológico, que seguiu, para a adaptação transcultural, os estágios de tradução, síntese, retrotradução, avaliação por especialistas, pré-teste e avaliação pela autora do instrumento original. Foram selecionadas 103 crianças/adolescentes internados em um hospital público do interior do estado de São Paulo. Foram utilizados ficha de caracterização, The Humpty Dumpty Falls Scale e o Instrumento de Classificação de Pacientes Pediátricos, o qual foi utilizado para avaliar a validade de construto, com o coeficiente de correlação de Spearman. A confiabilidade interobservador foi avaliada pelo Coeficiente de Correlação Intraclasse e pelo coeficiente Kappa. Resultados O comitê de 12 especialistas avaliou as equivalências, a clareza e a relevância dos itens e, após três rodadas, foi alcançado o percentual de 100% de concordância. As reformulações tornaram os itens mais compreensíveis e, após avaliação da autora, foi obtida a versão final do instrumento. Correlações positivas e significantes foram encontradas entre a Escala Humpty Dumpty e os domínios Paciente (r=0,5184; p<0,0001) e Procedimentos terapêuticos (r=0,2143; p<0,0332) do instrumento de classificação de pacientes. Com o domínio Família (r=0,0676; p=0,5060), não foram alcançadas relações significantes. Evidências satisfatórias de confiabilidade (Coeficiente de Correlação Intraclasse de 0,93 e coeficiente Kappa de 0,80) foram observadas. Conclusão The Humpty Dumpty Falls Scale foi adaptada transculturalmente, sendo denominada Ferramenta de Avaliação de Risco de Queda - Escala Humpty Dumpty. Demonstrou evidências satisfatórias de validade e confiabilidade para avaliar o risco de queda em crianças e adolescentes, no cenário brasileiro.

Resumen Objetivo Adaptar y validar The Humpty Dumpty Falls Scale para la cultura brasileña. Métodos Estudio metodológico, en el que se realizaron las siguientes etapas para la adaptación transcultural: traducción, síntesis, retrotraducción, evaluación por especialistas, prueba piloto y evaluación por la autora del instrumento original. Se seleccionaron 103 infantes/adolescentes internados en un hospital público del interior del estado de São Paulo. Se utilizó la ficha de caracterización, The Humpty Dumpty Falls Scale y el Instrumento de Clasificación de Pacientes Pediátricos, que se usó para evaluar la validad del constructo, con el coeficiente de correlación de Spearman. La fiabilidad interobservador fue evaluada por el coeficiente de correlación intraclase y por el coeficiente Kappa. Resultados El comité de 12 especialistas evaluó las equivalencias, la claridad y la relevancia de los ítems y, después de tres rondas, se llegó al 100 % de concordancia. Con las reformulaciones los ítems quedaron más comprensibles y, luego de la evaluación de la autora, se obtuvo la versión final de instrumento. Se observaron correlaciones positivas y significativas entre la Escala Humpty Dumpty y los dominios Paciente (r=0,5184; p<0,0001) y Procedimientos terapéuticos (r=0,2143; p<0,0332) del instrumento de clasificación de pacientes. En el dominio Familia (r=0,0676; p=0,5060) no se encontraron relaciones significativas. Se observaron evidencias satisfactorias de fiabilidad (coeficiente de correlación intraclase de 0,93 y coeficiente Kappa de 0,80). Conclusión The Humpty Dumpty Falls Scale fue adaptada transculturalmente y se la denominó Herramienta de Evaluación de Riesgo de Caída - Escala Humpty Dumpty. Demostró evidencias satisfactorias de validez y de fiabilidad para evaluar el riesgo de caída en infantes y adolescentes, en el contexto brasileño.

Abstract Objective To adapt and validate The Humpty Dumpty Scale for Brazilian culture. Methods Methodological study that followed the steps of translation, synthesis, back-translation, evaluation by specialists, pre-test and evaluation by the author of the original instrument for the cross-cultural adaptation. A total of 103 children/adolescents admitted to a public hospital in the countryside of the state of Sao Paulo were selected. We used a characterization form, The Humpty Dumpty Scale and the Pediatric Patient Classification Instrument, which was used to assess construct validity, with Spearman's correlation coefficient. Interobserver reliability was assessed using the Intraclass Correlation Coefficient and the Kappa coefficient. Results The committee of 12 experts evaluated the equivalence, clarity and relevance of the items and after three rounds, the percentage of 100% agreement was reached. The reformulations made the items more understandable and, after the author's evaluation, the final version of the instrument was obtained. Positive and significant correlations were found between The Humpty Dumpty Scale and the Patient (r=0.5184; p<0.0001) and Therapeutic Procedures (r=0.2143; p<0.0332) domains of the patient classification instrument. With the Family domain (r=0.0676; p=0.5060), no significant relationships were achieved. Satisfactory evidence of reliability (Intraclass Correlation Coefficient of 0.93 and Kappa coefficient of 0.80) was observed. Conclusion The Humpty Dumpty Scale was cross-culturally adapted and is now called (in Portuguese) the Ferramenta de Avaliação de Risco de Quedas - Escala Humpty Dumpty. It demonstrated satisfactory evidence of validity and reliability to assess the risk of falling in children and adolescents in the Brazilian context.

Multisystem Inflammatory Syndrome in Children (MIS-C) temporally related to COVID-19: the experience at a pediatric reference hospital in Colombia.

OBJECTIVE: This study aimed to describe the clinical characteristics and the different phenotypes of children with multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19 and to evaluate the risk conditions that favored a greater severity of the disease during a 12-month period at a pediatric reference hospital in Colombia. METHODS: A 12-month retrospective observational study of children under the age of 18 years who met criteria for MIS-C. RESULTS: A total of 28 children presented MIS-C criteria. The median age was 7 years. Other than fever (100%) (onset 4 days prior to admission), the most frequent clinical features were gastrointestinal (86%) and mucocutaneous (61%). Notably, 14 (50%) children had Kawasaki-like symptoms. The most frequent echocardiographic abnormalities were pericardial effusion (64%), valvular involvement (68%), ventricular dysfunction (39%), and coronary artery abnormalities (29%). In addition, 75% had lymphopenia. All had at least one abnormal coagulation test. Most received intravenous immunoglobulin (89%), glucocorticoids (82%), vasopressors (54%), and antibiotics (64%). Notably, 61% had a more severe form of the disease and were admitted to an intensive care unit (median 4 days, mean 6 days); the severity predictors were patients with the inflammatory/MIS-C phenotype (OR 26.5; 95%CI 1.40-503.7; p=0.029) and rash (OR 14.7; 95%CI 1.2-178.7; p=0.034). Two patients had macrophage activation syndrome. CONCLUSIONS: Coronary artery abnormalities, ventricular dysfunction, and intensive care unit admission were frequent, which needs to highlight the importance of early clinical suspicion.

Recommendations for the diagnosis and management of persons with suspected vaccine-induced immune thrombotic thrombocytopenia (VITT) / Recomendaciones para diagnostico y manejo de personas con trombocitopenia trombotica inmune inducida por vacunas (VITT)

Abstract In recent months, rare cases of thrombosis at unusual sites associated with thrombocytopenia, occurring within a typical risk window (i.e., 4-28 days) after receiving SARS CoV2 vaccines, have been reported. Healthcare professionals should be prepared to detect these cases on time. The Expert Panel of the Knowledge Management and Transfer Network conducted a free search of the related literature. With the available information and the clinical expertise of the working group, we formulated, reviewed, and endorsed recommendations for the timely suspicion, diagnosis (case definitions, the use of initial laboratory and imaging tests, specific tests), and management of these thrombotic conditions. This document is considered a living document that will be updated as new evidence emerges, and recommendations may change over time.

Resumen En meses recientes se han reportado casos raros de trombocitopenia y trombosis en sitios inusuales, que ocurren dentro de una ventana de riesgo típica ( por ejemplo de 4 a 28 días) luego de recibir vacunas de SARS CoV 2. Los profesionales de la salud deben estar preparados para detectar estos casos a tiempo. Un panel de expertos y una red de transferencia de conocimiento realizó una búsqueda libre de literatura seleccionada. Con la información disponible y la experticia clínica del grupo de trabajo revisamos y dimos recomendaciones para la sospecha temprana, el diagnostico (definición de caso, el uso de pruebas de laboratorio especificas y de imágenes diagnósticas) para le manejo de estas condiciones tromboticas. Este documento es considerado un documento vivo que debe ser actualizado a medida que surja nueva evidencia y las recomendaciones vayan cambiando con el tiempo