Increased monocytes are associated with overweight in children and adolescents with autism spectrum disorder.

Introduction: Objective: to investigate the monocyte count and its association with nutritional status in children and adolescents with autism spectrum disorder (ASD). Methods: a cross-sectional study carried out at a Neurodevelopmental Center in the south of Brazil, with 68 ASD patients aged 3 to 18 years. The number of monocytes (per mm3) was determined in blood samples. Nutritional status was defined as BMI-for-age according to WHO standards. The Children's Eating Behaviour Questionnaire and a standard questionnaire to collect sociodemographic and clinical characteristics were administered to caregivers. Comparisons between sociodemographic, clinical, and eating behavior variables were performed with parametric tests. Linear regression was used to test the association between nutritional status and monocyte count. Results: mean age was 8.6 ± 3.3 years, 79 % were males and 66 % were overweight. In the unadjusted regression overweight was associated with higher monocyte counts compared to those non-overweight (B: 64.0; 95 % CI, 13.9 to 114.1; ß: 0.30, p = 0.01). This association remained significant after adjustment for the subscale of "emotional overeating" (B: 37.0; 95 % CI, 17.1 to 91.3; ß: 0.29; p = 0.02). The variability in monocyte count attributed to overweight was 14 %. Conclusions: overweight is associated with a higher monocyte count in children and adolescents with ASD. Nutritional intervention to control overweight is essential to mitigate the negative impact on inflammatory activity and immune dysfunction in these patients.

Introducción: Objetivo: investigar el recuento de monocitos y su asociación con el estado nutricional en niños y adolescentes con trastorno del espectro autista (TEA). Método: estudio transversal realizado en el Centro de Neurodesarrollo, en el sur de Brasil, con 68 pacientes con TEA de 3 a 18 años de edad. Se determinó el número de monocitos (por mm3) en muestras de sangre. El estado nutricional se definió como IMC para la edad según los estándares de la OMS. Se aplicó a los cuidadores el Cuestionario de Conducta Alimentaria Infantil y un cuestionario estándar para recoger características sociodemográficas y clínicas. Las comparaciones entre las variables sociodemográficas, clínicas y de conducta alimentaria se realizaron con pruebas paramétricas. Se utilizó la regresión lineal para probar la asociación entre el estado nutricional y el recuento de monocitos. Resultados: la edad media fue de 8,6 ± 3,3 años, el 79 % eran varones y el 66 % tenían sobrepeso. En la regresión no ajustada, el sobrepeso se asoció a un mayor número de monocitos en comparación con los que no tenían sobrepeso (B: 64,0; IC 95 %: 13,9 a 114,1; ß: 0,30; p = 0,01). Esta asociación siguió siendo significativa tras ajustar la subescala de "sobrealimentación emocional" (B: 37,0; IC 95 %: 17,1 a 91,3; ß: 0,29; p = 0,02). La variabilidad en el recuento de monocitos atribuida al sobrepeso fue del 14 %. Conclusiones: el sobrepeso se asocia a un mayor recuento de monocitos en niños y adolescentes con TEA. La intervención nutricional para controlar el sobrepeso es esencial para mitigar el impacto negativo sobre la actividad inflamatoria y la disfunción inmune en estos pacientes.

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation.

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88-8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29-9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74-93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80-0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.

Impact of high neutrophil-to-lymphocyte ratio on survival in hospitalized cancer patients with COVID-19.

Neutrophil-to-lymphocyte ratio (NLR) has been studied as a prognostic factor for mortality in COVID-19 patients. Our study aimed to evaluate the association between NLR at COVID-19 diagnosis and survival during the following 90 days in hospitalized patients with solid cancer. Between May 2020 and June 2021, 120 patients were included in a retrospective cohort study. Univariable analysis showed patients with an NLR > 8.3 were associated with an increased risk of death (HR: 4.34; 95% CI: 1.74-10.84) compared to patients with NLR < 3.82 and with NLR ≥3.82 and ≤8.30 (HR: 2.89; 95% CI: 1.32-6.36). Furthermore, on multivariable analysis, NLR > 8.30 independently correlated with increased mortality. In patients with solid malignancies with COVID-19, an NLR > 8.3 is associated with an increased risk of death.

Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma.

OBJECTIVE: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models. DESIGN: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, K-Ras +/LSL-G12D;Trp53 LSL-R172H;Pdx1-Cre mice (KPC) and the K-Ras +/LSL-G12D;Pdx1-Cre mice (KC) were crossed with Loxl2 allele floxed mice (Loxl2Exon2 fl/fl) or conditional Loxl2 overexpressing mice (R26Loxl2 KI/KI) to generate KPCL2KO or KCL2KO and KPCL2KI or KCL2KI mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation. RESULTS: Using these PDAC mouse models, we show that while Loxl2 ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling. Loxl2 overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affects Osm and Loxl2 expression and collagen fibre alignment. CONCLUSION: Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic disease.

Weight gain speed and z-score behavior in large prematures for gestational age.

Introduction: Objective: to investigate the speed of weight gain (WG) and the z-score (E-z) of weight in premature neonates large for gestational age (LGA) during four weeks of hospitalization. Methods: a retrospective longitudinal study with premature neonates in a neonatal intensive care unit at a university hospital. Data were obtained from January 2017 to December 2018; 115 babies with gestational age (GA) ≥ 27 and < 37 weeks, non-twin, AGA or LGA were included. The WG (g/kg/day) was obtained from the nadir weight and the E-z was calculated online based on the Intergrowth-21st curves. Repeated-measures ANOVA and multiple linear regression were used to assess the association between WP and E-z and explanatory variables; p < 5 %. Results: mean GA was 32.5 weeks, birth weight was 1910 g and weight loss was 5 % at 7 days. WG was lower in LGA babies, with GI between 32 and 37 weeks (LGA, 9.2 ± 5.6 g/kg/day vs AGA, 13.9 ± 6.0 g/kg/day). The change in WG was explained by protein supply in AGA (B = 2.5 g/kg/day; 95 % CI, 0.7 to 4.3; and ß = 0.543) and by GA in LGA (B = -0.05 g/kg/day; 95 % CI, -0.09 to -0.02; and ß = -0.574). In the 4th week of hospitalization, weight E-z decreased similarly for LGAs and AGAs, and this variation was explained by growth. Conclusions: premature LGAs had lower WG compared to AGAs during the neonatal period. The linear and brain growth explained the variation in weight E-z among these preterms.

Introducción: Objetivo: Investigar la velocidad de la ganancia de peso (GP) y la puntuación z (E-z) de peso en neonatos prematuros grandes para la edad gestacional (GEG) durante cuatro semanas de hospitalización. Métodos: estudio longitudinal retrospectivo con neonatos prematuros de una unidad de cuidados intensivos neonatales de un hospital universitario. Los datos se obtuvieron desde enero de 2017 hasta diciembre de 2018. Se incluyeron 115 bebés con edad gestacional (EG) ≥ 27 y < 37 semanas, no gemelos, AEG o GEG. El GP (g/kg/día) se obtuvo a partir del peso nadir y el E-z se calculó en línea basado en las curvas Intergrowth-21st. Se utilizaron el ANOVA de medidas repetidas y la regresión lineal múltiple para evaluar la asociación entre GP y E-z y las variables explicativas; p < 5 %. Resultados: la EG media fue de 32,5 semanas, el peso al nacer de 1910 g y la pérdida de peso del 5 % a los 7 días. El GP fue menor en los bebés GEG, con EG entre 32 y 37 semanas (GEG: 9,2 ± 5,6 g/kg/día vs. AEG: 13,9 ± 6,0 g/kg/día). El cambio en el GP se explicó por el suministro de proteínas en los AEG (B = 2,5 g/kg/día; IC 95 %: 0,7 a 4,3; y ß = 0,543) y por EG en los GEG (B = -0,05 g/kg/día; IC 95 %: -0,09 a -0,02; y ß = -0,574). En la 4ª semana de hospitalización, el peso E-z se redujo de manera similar en los GEG y los AEG, y esta variación se explicó por el crecimiento. Conclusiones: los prematuros GEG tuvieron un menor GP en comparación con los AEG durante el periodo neonatal. El crecimiento lineal y cerebral explicó la variación del peso E-z de estos prematuros.

Behavior of weight z-score in preterm infants who are small for gestational age.

Introduction: Introduction: the follow-up of small for gestational age (SGA) preterm infants is critical due to their differentiated postnatal growth pattern. Objective: to investigate the weight z-score behavior in SGA preterm infants during a four-week stay in a Neonatal Intensive Care Unit. Methods: a retrospective longitudinal study with data from nutritional anamneses of 190 preterm infants admitted to a Neonatal Intensive Care Unit between January/2017 and December/2019, classified according to nutritional status at birth as either SGA or appropriate for gestational age (AGA). Linear regression was used to verify association between weight z-score with gestational age, birth weight, initiation of enteral nutrition and relative amount of energy and protein administered. Results: SGA preterm infants accounted for 23 % of the study participants. In SGA, the difference in weight score was observed at week 1 when compared to admission (p < 0.05), while in AGA there was a difference sustained during the whole period (p < 0.05). In SGA, the linear regression analysis showed that the change in z-score was explained by time to start of enteral nutrition (p = 0.033), gestational age (p = 0.003) and birth weight (p = 0.001). In AGA the change was explained by gestational age (p = 0.000) and birth weight (p = 0.000). Conclusion: the weight z-score behavior in preterm infants was downward compared to admission, stable at the end of 4 weeks, and different according to nutritional status at birth. In the AGA group the decline in nutritional status was not recovered throughout hospitalization and in the SGA group the unfavorable nutritional status was maintained.

Introducción: Introducción: el seguimiento de los prematuros pequeños para la edad gestacional (PEG) es crítico debido al patrón de crecimiento posnatal diferenciado. Objetivo: investigar el comportamiento de la puntuación z del peso en recién nacidos prematuros PEG durante cuatro semanas de estancia en una unidad de cuidados intensivos neonatales. Métodos: estudio longitudinal retrospectivo con datos de anamnesis nutricionales de 190 prematuros ingresados en una unidad de cuidados intensivos neonatales entre enero/2017 y diciembre/2019, clasificados según el estado nutricional al nacer como PEG o como adecuado para la edad gestacional (AEG). Se utilizó la regresión lineal para verificar la asociación entre la puntuación z del peso con la edad gestacional, el peso al nacer, el inicio de la nutrición enteral y la cantidad relativa de energía y proteínas administradas. Resultados: los bebés prematuros PEG representaron el 23 % de los participantes en el estudio. En el grupo PEG, la diferencia de la puntuación z del peso se observó en la semana 1 en comparación con el ingreso (p < 0,05), mientras que en el grupo AEG hubo diferencia durante todo el período evaluado (p < 0,05). En los PEG, el análisis de regresión lineal mostró que el cambio de la puntuación z se explicaba por el tiempo transcurrido hasta el inicio de la nutrición enteral (p = 0,033), la edad gestacional (p = 0,003) y el peso al nacer (p = 0,001). En el caso de la AEG, el cambio se explicaba por la edad gestacional (p = 0,000) y el peso al nacer (p = 0,000). Conclusión: el comportamiento de la puntuación z del peso en los prematuros fue descendente en comparación con la admisión, estable al final de 4 semanas y diferente según el estado nutricional al nacer. En el caso de los AEG, el estado nutricional no se recuperó a lo largo de la investigación y, en el caso de los PEG, el estado nutricional desfavorable se mantuvo.

Uncovering Causes of Childhood Death Using the Minimally Invasive Autopsy at the Community Level in an Urban Vulnerable Setting of Argentina: A Population-Based Study.

BACKGROUND: Precise determination of the causal chain that leads to community deaths in children in low- and middle-income countries is critical to estimating all causes of mortality accurately and to planning preemptive strategies for targeted allocation of resources to reduce this scourge. METHODS: An active surveillance population-based study that combined minimally invasive tissue sampling (MITS) and verbal autopsies (VA) among children under 5 was conducted in Buenos Aires, Argentina, from September 2018 to December 2020 to define the burden of all causes of community deaths. RESULTS: Among 90 cases enrolled (86% of parental acceptance), 81 had complete MITS, 15.6% were neonates, 65.6% were post-neonatal infants, and 18.9% were children aged 1-5 years. Lung infections were the most common cause of death (CoD) in all age groups (57.8%). Among all cases of lung infections, acute bronchiolitis was the most common CoD in infants aged <12 months (23 of 36, 63.9%), and bacterial pneumonia was the most common cause in children aged >12 months (8 of 11, 72.7%). The most common comorbid condition in all age groups was undernutrition in 18 of 90 (20%). It was possible to find an immediate CoD in 78 of 81 subjects where MITS could be done. With this combined approach, we were able to determine that sudden infant death syndrome was overestimated in state reports. CONCLUSIONS: CoD determination by a combination of MITS and VA provides an accurate estimation of the chain of events that leads to death, emphasizing possible interventions to prevent mortality in children.

Chronic hemodialysis patients: A comparison of clinical, laboratory and nutritional parameters among elderly and non-elderly patients

ABSTRACT Aim: To compare nutritional, clinical and laboratory parameters data among elderly and non-elderly patients on hemodialysis. Methods: It is a cross-sectional study, with a sample of 34 patients (17 non-elderly participants between 18 to 59 years of age, and 17 elderly participants aged 60 years or older), from the Nephrology Unit, Hospital Santa Casa de Misericórdia, Pelotas/RS/BR. Demographic, socioeconomic, clinical, laboratory, anthropometric data and information on food consumption were collected. Results: Most elderly and non-elderly patients had low income and education. Among elderly participants, weight values, pre and post-dialysis, interdialytic weight gain, median diastolic blood pressure pre and post-dialysis and urea, were higher than among the non-elderly. About 65% of the non-elderly and 70.6% of the elderly subjects had inadequate caloric intake. The same occurred with protein intake, for which 58.8% of the non-elderly and 82.3% of the elderly patients presented inadequate protein intake. Conclusion: There was a tendency of weight gain in the elderly, which may increase the risks of treatment. Evidence indicates an association between the intake of energy and protein in the diet of patients on hemodialysis, requiring an adequate diet and dialysis, in order to avoid complications related to kidney disease.

RESUMEN Objetivos: Comparar parámetros nutricionales, clínicos y de laboratorio de pacientes ancianos y no ancianos sometidos a hemodiálisis. Métodos: Estudio transversal, realizado con una muestra de 34 pacientes, de los cuales 17 eran no ancianos de 18 años y más y menos de 60 años y 17 ancianos de 60 años y más, de la Unidad de Nefrología del Hospital Santa Casa. de Misericórdia de Pelotas / RS / BR. Se recopilaron datos demográficos, socioeconómicos, clínicos, de laboratorio, antropométricos y de consumo de alimentos. Resultados: La mayoría de los pacientes ancianos y no ancianos eran de bajos ingresos y educación. En los ancianos, se encontraron valores de peso, pre y posdiálisis, aumento de peso interdialítico, mediana de la presión arterial diastólica pre y posdiálisis y urea más alta en comparación con los no ancianos. Aproximadamente el 65% de las personas no ancianas y el 70,6% de las personas mayores presentaban una ingesta calórica inadecuada, lo mismo ocurrió con la ingesta proteica, donde el 58,8% de las personas no ancianas y el 82,3% de las personas mayores presentaban una ingesta proteica inadecuada. Conclusión: Hubo una tendencia al aumento de peso en los ancianos, lo que puede traer riesgos al tratamiento. La evidencia indica una asociación entre la ingesta energética y proteica en la dieta de pacientes en hemodiálisis, requiriendo adaptación de la dieta y diálisis para evitar complicaciones relacionadas con la enfermedad renal.

Estudio multicéntrico argentino sobre la utilidad del panel BCID2 del Sistema FilmArrayTM en la detección de bacteriemias / Argentine multicenter study on the usefulness of the BCID2 panel of the FilmArray™ System in the detection of bacteremia

Resumen El panel BCID2 de BioFire® (BioFire, Salt Lake City, EE.UU.) utiliza un análisis de PCR múltiple a partir de hemocultivos positivos con resultados en una hora. El objetivo de este estudio fue determinar el desempeño del método a partir de hemocultivos positivos de pacientes sépticos en 5 hospitales de la Argentina. Se incluyeron 121 pacientes y 124 episodios. Con respecto a la identificación microbiana, la sensibilidad global y la correspondiente a los microorganismos incluidos en la base de datos fue del 94% y 97% respectivamente. La sensibilidad del BCID2 para detectar CTX-M, KPC, NDM, VIM, IMP, mecA/C, vanA/B fue del 100% y la especificidad fue del 99% para NDM y VIM y del 100% para el resto. Esto llevó a cambios en el tratamiento antimicrobiano en 57/98 episodios (58%). El panel BCID2 es una herramienta importante para la adecuación del tratamiento antimicrobiano de pacientes con sepsis.

Abstract The BioFire® BCID2 panel (BioFire, Salt Lake City, UT) uses multiplex PCR analysis from positive blood cultures with results within one hour. The objective of this study was to determine the performance of the method from positive blood cultures of septic patients in 5 hospitals in Argentina. A total of 121 patients and 124 episodes were included. With regard to microbial identification, the global sensitivity and that corresponding to the microorganisms included in the database was 94% and 97%, respectively. The sensitivity of BCID2 to detect CTX-M, KPC, NDM, VIM, IMP, mecA/C, vanA/B was 100% and the specificity was 99% for NDM and VIM and 100% for the rest. This led to changes in antimicrobial treatment in 57/98 episodes (58%). The BCID2 panel is an important tool for the adequacy of antimicrobial treatment of patients with sepsis.

Resumo Estudo multicêntrico argentino sobre a utilidade do painel BCID2 do Sistema FilmArray™ na detecção de bacteremia O painel BCID2 de BioFire® B (BioFire, Salt Lake City, EUA) utiliza uma análise de PCR múltipla de hemoculturas positivas com resultados em uma hora. O objetivo deste estudo foi determinar o desempenho do método a partir de hemoculturas positivas de pacientes sépticos em 5 hospitais da Argentina. Cento e vinte e um pacientes e 124 episódios foram incluídos. No que se refere à identificação microbiana, a sensibilidade global e correspondente aos microrganismos incluídos na base de dados foi de 94% e 97%, respectivamente. A sensibilidade do BCID2 para detectar CTX-M, KPC, NDM, VIM, IMP, mecA/C, vanA/B foi de 100% e a especificidade foi de 99% para NDM e VIM e 100% para o resto. Isso levou a mudanças no tratamento antimicrobiano em 57/98 episódios (58%). O painel BCID2 é uma ferramenta importante para a adequação do tratamento antimicrobiano de pacientes com sepse.

The effect of paraoxonase 1 (PON1) gene polymorphisms T(-107)C and L55M and diet composition on serum PON1 activity in women

ABSTRACT Objective: The aim of this study was to evaluate the serum activity of PON1 in women according to SNPs L55M and T-107C and diet composition. Materials and methods: Blood and serum samples from 26 women were used. DNA extraction, PCR and digestion with restriction enzymes of the PCR fragment were performed for genotyping the PON1 SNPs T-107C and L55M. Serum PON1 activity was measured in a single time point. Patients completed the semi-quantitative food frequency questionnaire and diet composition was estimated. Results: Genotypic distribution for L55M SNP was 56% for the LL genotype, 32% for LM and 12% for MM; for the PON1 C(-107)T SNP it was 28% for the TT genotype, 41% for CT and 31% for CC. Individuals with C and L alleles had higher serum PON1 activity. Combining the two SNPs, we observed that individuals carrying the LL and CC genotypes had twice the activity of carriers of the TT and MM genotypes. Considering food intake, no significant difference was observed between genotypes and intake levels. Conclusion: PON1 T(-107)C and L55M SNPs exert a strong effect on serum PON1 activity in an additive manner and are more important than diet to predict serum PON1 activity.

The effect of paraoxonase 1 (PON1) gene polymorphisms T(-107)C and L55M and diet composition on serum PON1 activity in women.

OBJECTIVE: The aim of this study was to evaluate the serum activity of PON1 in women according to SNPs L55M and T-107C and diet composition. METHODS: Blood and serum samples from 26 women were used. DNA extraction, PCR and digestion with restriction enzymes of the PCR fragment were performed for genotyping the PON1 SNPs T-107C and L55M. Serum PON1 activity was measured in a single time point. Patients completed the semi-quantitative food frequency questionnaire and diet composition was estimated. RESULTS: Genotypic distribution for L55M SNP was 56% for the LL genotype, 32% for LM and 12% for MM; for the PON1 C(-107)T SNP it was 28% for the TT genotype, 41% for CT and 31% for CC. Individuals with C and L alleles had higher serum PON1 activity. Combining the two SNPs, we observed that individuals carrying the LL and CC genotypes had twice the activity of carriers of the TT and MM genotypes. Considering food intake, no significant difference was observed between genotypes and intake levels. CONCLUSION: PON1 T(-107)C and L55M SNPs exert a strong effect on serum PON1 activity in an additive manner and are more important than diet to predict serum PON1 activity.

[Clinical outcomes in cancer patients hospitalized with COVID-19]. / Evolución clínica de pacientes internados con cáncer e infección por COVID-19.

Cancer patients are exposed to more complications from COVID-19 than non-cancer patients. We report a cohort of 74 cancer patients (87.8% with solid neoplasia and 12.2% with hematological diseases) with COVID-19 infection admitted to a tertiary medical cancer center in Argentina. Pulmonary infiltrates were diagnosed at admission in 78.3% (N = 58) of the cases. COVID-19 infection was hospital-acquired in 20 (27.0%) patients. Thirty-nine patients (52.7%) received anticancer therapy within the 30 days prior to COVID-19 diagnosis; one was on radiation therapy. Twenty-four (32.4%) patients were admitted in the intensive care unit (ICU) and 18 (75.0%) required mechanical ventilation. All cause in-hospital mortality was 32.4% (N = 24) and ICU mortality was 62.5% (N = 15). Mortality under mechanical ventilation was 72.2% (N = 13). In the univariate analysis age, neutrophil count, neutrophil/lymphocyte index, D-dimer, ferritin, smoking, and nosocomial acquired infection were associated with in-hospital mortality. There were no statistically significant differences in mortality related to disease stage for solid tumors, neither cancer treatment within 30 days of COVID-19 diagnosis. Age and smoking were associated with mortality in the multivariate analysis. The adjusted odds ratios (95 CI) for age = 65 years and smoking were 8.87 (1.35-58.02) and 8.64 (1.32 - 56.64), respectively. Our experience can be useful for other institutions that assist cancer patients during the pandemic.

Los pacientes con cáncer y COVID-19 tienen más complicaciones que la población general. Comunicamos una cohorte de 74 pacientes con cáncer y COVID-19 internados en una institución oncológica. El 87.8% tenía diagnóstico de tumores sólidos y 12.2% oncohematológicos. Entre los tumores sólidos, el 61.5% presentó enfermedad metastásica. El 78.3% (N = 58) tenía infiltrados pulmonares al diagnóstico de COVID-19. La infección fue intrahospitalaria en 20 pacientes. Habían recibido tratamiento antineoplásico dentro de los 30 días anteriores al diagnóstico 39 pacientes (52.7%); uno se encontraba recibiendo radioterapia. Veinticuatro pacientes (32.4%) se derivaron a terapia intensiva (UTI) y 18 (75%) de ellos requirieron asistencia respiratoria mecánica (ARM). La mortalidad general durante la internación fue 32.4% (N = 24). La mortalidad en UTI fue 62.5% (N = 15). La mortalidad en ARM fue 72.2% (N = 13). La edad, recuento de neutrófilos, índice neutrófilo/linfocito, dímero D, ferritina, tabaquismo y haber adquirido la infección durante la internación resultaron estadísticamente significativos en el análisis univariado para mortalidad. No hallamos diferencias en mortalidad por estadio de enfermedad, en los pacientes con tumores sólidos, ni por haber recibido tratamiento antineoplásico dentro de los 30 días del diagnóstico de COVID-19. En el análisis multivariado con el modelo de regresión logística, solo la edad y el tabaquismo fueron predictores de mortalidad. Los odds ratios (IC 95) ajustados para la edad =65 años y el tabaquismo fueron 8.87 (1.35-58.02) y 8.64 (1.32-56.64), respectivamente. Este trabajo puede resultar de utilidad para instituciones polivalentes que asistan pacientes oncológicos durante la pandemia.

Evolución clínica de pacientes internados con cáncer e infección por COVID-19 / Clinical outcomes in cancer patients hospitalized with COVID-19

Resumen Los pacientes con cáncer y COVID-19 tienen más complicaciones que la población general. Comunicamos una cohorte de 74 pacientes con cáncer y COVID-19 internados en una institución on cológica. El 87.8% tenía diagnóstico de tumores sólidos y 12.2% oncohematológicos. Entre los tumores sólidos, el 61.5% presentó enfermedad metastásica. El 78.3% (N = 58) tenía infiltrados pulmonares al diagnóstico de COVID-19. La infección fue intrahospitalaria en 20 pacientes. Habían recibido tratamiento antineoplásico den tro de los 30 días anteriores al diagnóstico 39 pacientes (52.7%); uno se encontraba recibiendo radioterapia. Veinticuatro pacientes (32.4%) se derivaron a terapia intensiva (UTI) y 18 (75%) de ellos requirieron asistencia respiratoria mecánica (ARM). La mortalidad general durante la internación fue 32.4% (N = 24). La mortalidad en UTI fue 62.5% (N = 15). La mortalidad en ARM fue 72.2% (N = 13). La edad, recuento de neutrófilos, índice neutrófilo/linfocito, dímero D, ferritina, tabaquismo y haber adquirido la infección durante la internación resultaron estadísticamente significativos en el análisis univariado para mortalidad. No hallamos diferencias en mortalidad por estadio de enfermedad, en los pacientes con tumores sólidos, ni por haber recibido tratamiento antineoplá sico dentro de los 30 días del diagnóstico de COVID-19. En el análisis multivariado con el modelo de regresión logística, solo la edad y el tabaquismo fueron predictores de mortalidad. Los odds ratios (IC 95) ajustados para la edad ≥65 años y el tabaquismo fueron 8.87 (1.35-58.02) y 8.64 (1.32-56.64), respectivamente. Este trabajo puede resultar de utilidad para instituciones polivalentes que asistan pacientes oncológicos durante la pandemia.

Abstract Cancer patients are exposed to more complications from COVID-19 than non-cancer patients. We report a cohort of 74 cancer patients (87.8% with solid neoplasia and 12.2% with hematological diseases) with COVID-19 infection admitted to a tertiary medical cancer center in Argentina. Pulmonary infiltrates were diagnosed at admission in 78.3% (N = 58) of the cases. COVID-19 infection was hospital-acquired in 20 (27.0%) patients. Thirty-nine patients (52.7%) received anticancer therapy within the 30 days prior to COVID-19 diagnosis; one was on radiation therapy. Twenty-four (32.4%) patients were admitted in the intensive care unit (ICU) and 18 (75.0%) required mechanical ventilation. All cause in-hospital mortality was 32.4% (N = 24) and ICU mortality was 62.5% (N = 15). Mortality under me chanical ventilation was 72.2% (N = 13). In the univariate analysis age, neutrophil count, neutrophil/lymphocyte index, D-dimer, ferritin, smoking, and nosocomial acquired infection were associated with in-hospital mortality. There were no statistically significant differences in mortality related to disease stage for solid tumors, neither cancer treatment within 30 days of COVID-19 diagnosis. Age and smoking were associated with mortality in the multivariate analysis. The adjusted odds ratios (95 CI) for age ≥ 65 years and smoking were 8.87 (1.35-58.02) and 8.64 (1.32 - 56.64), respectively. Our experience can be useful for other institutions that assist cancer patients during the pandemic.

Community Mortality Due to Respiratory Syncytial Virus in Argentina: Population-based Surveillance Study.

BACKGROUND: Many deaths in infants from low-middle income countries (LMICs) occur at home or upon arrival to health facilities. Although acute lower respiratory tract illness plays an important role in community mortality, the accuracy of mortality rates due to respiratory syncytial virus (RSV) remains unknown. METHODS: An active surveillance study among children aged under 5 years old (U5) was performed in Buenos Aires, Argentina, between January and December 2019, to define the burden and role of RSV in childhood community mortality. RESULTS: A total of 63 families of children U5 participated in the study. Based on a combined approach of tissue sampling, verbal autopsies, and expert's analysis, RSV infection was found in the causal chain of 11 from 12 cases with positive molecular biology results in respiratory samples. The estimated mortality rate due to RSV among infants was 0.27 deaths/1000 live births. The mean age of RSV-related household deaths was 2.8 months of age (standard deviation [SD] 1.7), and 8/12 were male infants (66.7%). Dying at home from RSV was associated with Streptococcus pneumoniae and/or Moraxella catarrhalis lung coinfection (75%), living in slums and settlement (odds ratio [OR], 17.09; 95% confidence interval [CI], 1.3-219.2), and other underlying comorbidities (OR, 14.87; 95% CI, 1.3-164.6). CONCLUSIONS: Infant community mortality rates due to RSV are higher than those reported in industrialized countries and similar to those reported in hospital-based studies in the same catchment population.

Interest in food and triglyceride concentrations in children and adolescents with autistic spectrum disorder

Abstract Objective: To investigate eating behavior and serum concentration of triglycerides in children and adolescents with autistic spectrum disorder. Methods: Cross-sectional study conducted in the neurodevelopment nucleus, from October 2018 to April 2019 in a neurodevelopment center in the city of Pelotas/RS. Blood samples were collected, and serum was essayed for triglycerides by colorimetric enzymatic reaction. The Children's Eating Behavior Questionnaire was applied to the parents. The comparison between two or three categories of variables was performed with nonparametric tests. Linear regression was used to access the association between the log triglyceride serum concentration and the score above or below the median score of the food response and emotional overeating subscales. Results: Sixty patients were evaluated. The average age was 8.6 ± 3.2 years and most were white (75 %), male (80 %), and overweight (66%). Half of the sample had elevated triglycerides. Triglyceride concentrations were higher among overweight children and adolescents with higher median scores on the "food response" and "emotional overeating" subscales. In the adjusted analysis, the association between triglycerides and higher scores on subscales reflecting interest in food remained significant. Conclusion: Children and adolescents with autistic spectrum disorder present high triglyceride concentrations associated with a greater interest in food. Knowledge of this eating behavior may provide more effective nutritional intervention in this population.

Interest in food and triglyceride concentrations in children and adolescents with autistic spectrum disorder.

OBJECTIVE: To investigate eating behavior and serum concentration of triglycerides in children and adolescents with autistic spectrum disorder. METHODS: Cross-sectional study conducted in the neurodevelopment nucleus, from October 2018 to April 2019 in a neurodevelopment center in the city of Pelotas/RS. Blood samples were collected, and serum was essayed for triglycerides by colorimetric enzymatic reaction. The Children's Eating Behavior Questionnaire was applied to the parents. The comparison between two or three categories of variables was performed with nonparametric tests. Linear regression was used to access the association between the log triglyceride serum concentration and the score above or below the median score of the food response and emotional overeating subscales. RESULTS: Sixty patients were evaluated. The average age was 8.6±3.2 years and most were white (75 %), male (80 %), and overweight (66%). Half of the sample had elevated triglycerides. Triglyceride concentrations were higher among overweight children and adolescents with higher median scores on the "food response" and "emotional overeating" subscales. In the adjusted analysis, the association between triglycerides and higher scores on subscales reflecting interest in food remained significant. CONCLUSION: Children and adolescents with autistic spectrum disorder present high triglyceride concentrations associated with a greater interest in food. Knowledge of this eating behavior may provide more effective nutritional intervention in this population.

Combination of ACTN3 R577X and ACE I/D polymorphisms as a tool for prediction of obesity risk in children.

The genetic influence in obesity prevalence is well described, but the role of genetic markers related to athletic strength/ endurance performance remains controversial. We investigated associations between obesity and the genetic polymorphisms alpha-actinin-3 (ACTN3) R577X and angiotensin-converting enzyme (ACE) I/D in schoolchildren aged 4-13 years from Southern Brazil. We collected sociodemographic data from parents through a questionnaire and conducted an anthropometric assessment. DNA was extracted from buccal cells and genotyping was performed by PCR. We found that 1.9% of the individuals were classified as low weight-for-age, 57.6% as normal weight and 40.5% as overweight/ obesity. Regarding allelic distribution, we found that 52.5% of individuals were DD, 30.8% ID, and 16.7% II for ACE; and 38.8% of individuals were RR, 40.2% RX and 21.0% XX for ACTN3. When both polymorphisms were combined, we observed a clear association between the composed genetic profile of these alleles and severe obesity in schoolchildren. Our data suggest that the combined analysis of ACTN3 R577X and ACE I/D polymorphisms may serve as a predictor for the risk of severe obesity in children. These data can contribute to a better understanding of the relationship between these polymorphisms and the body weight development of school-age children.

Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells.

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7-9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies.

Influence of nutritional factors and the PON1 C(-107)T polymorphism on paraoxonase-1 activity in childhood / Influência de fatores nutricionais e do polimorfismo PON1 C(-107)T sobre a atividade da Paraoxonase 1 na infância

Abstract Objective: The cardioprotective enzyme paraoxonase-1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(-107)T polymorphism on PON1 arylesterase activity in children. Methods: This was a cross-sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(-107)T polymorphism were performed. The Hardy-Weinberg equilibrium was tested with the chi-squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. Results: In the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15-30 U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy-Weinberg equilibrium (p = 0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(-107)T polymorphism. Conclusions: During childhood, a good-quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(-107)T polymorphism of the PON1 gene.

Resumo Objetivo: A enzima cardioprotetora Paraoxonase 1 (PON1) sofre importante influência de polimorfismos genéticos e fatores nutricionais. O objetivo deste estudo foi investigar a influência da alimentação, do estado nutricional e do polimorfismo C(-107)T sobre a atividade arilesterase da PON1 em crianças. Métodos: Estudo transversal com 97 crianças entre 5 e 8 anos, de ambos os sexos, de um ambulatório de pediatria no sul do Brasil. Realizou-se questionário sociodemográfico, de comportamento e de consumo alimentar, medidas antropométricas e coleta de sangue em laboratório. A atividade arilesterase da PON1 foi mensurada pela extinção de fenol (U/mL), realizada extração do DNA e análise do polimorfismo PON1 C(-107)T. O equilíbrio de Hardy-Weinberg foi testado com qui-quadrado e usada regressão linear para estimar a atividade da PON1 segundo quatro modelos de ajuste, erro aceitável de 5%. Resultados: Na amostra o sexo masculino representou 50,5%, 39,2% tinham 6 anos, 54,5% eram eutróficos e 51,5% tinha atividade da PON1 inferior à mediana (90,0;15-30 U/ml). A frequência dos genótipos foi 54,6% (53/97), 31,0% (30/97) e 14,4% (14/97), respectivamente, para CT, CC e TT, estiveram em equilíbrio de Hardy-Weinberg (p = 0,22). Na análise de regressão o modelo que incluiu variáveis sociodemográficas, de frequência do consumo de frutas, verduras, legumes, laticínios e feijões estimou uma variabilidade de 14,8% na atividade da PON1 combinada ao polimorfismo PON1 C(-107)T. Conclusões: Na infância uma alimentação de boa qualidade, com maior participação de alimentos saudáveis foi importante para predizer a atividade da enzima cardioprotetora PON1 combinada ao polimorfismo C(-107)T do gene da PON1.