Interferon-gamma gene diplotype (AA-rs2069716 / AG-rs2069727) may play an important role during secondary outcomes of severe dengue in Brazilian patients.

Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.

Human Genome Polymorphisms and Computational Intelligence Approach Revealed a Complex Genomic Signature for COVID-19 Severity in Brazilian Patients.

We present a genome polymorphisms/machine learning approach for severe COVID-19 prognosis. Ninety-six Brazilian severe COVID-19 patients and controls were genotyped for 296 innate immunity loci. Our model used a feature selection algorithm, namely recursive feature elimination coupled with a support vector machine, to find the optimal loci classification subset, followed by a support vector machine with the linear kernel (SVM-LK) to classify patients into the severe COVID-19 group. The best features that were selected by the SVM-RFE method included 12 SNPs in 12 genes: PD-L1, PD-L2, IL10RA, JAK2, STAT1, IFIT1, IFIH1, DC-SIGNR, IFNB1, IRAK4, IRF1, and IL10. During the COVID-19 prognosis step by SVM-LK, the metrics were: 85% accuracy, 80% sensitivity, and 90% specificity. In comparison, univariate analysis under the 12 selected SNPs showed some highlights for individual variant alleles that represented risk (PD-L1 and IFIT1) or protection (JAK2 and IFIH1). Variant genotypes carrying risk effects were represented by PD-L2 and IFIT1 genes. The proposed complex classification method can be used to identify individuals who are at a high risk of developing severe COVID-19 outcomes even in uninfected conditions, which is a disruptive concept in COVID-19 prognosis. Our results suggest that the genetic context is an important factor in the development of severe COVID-19.

Interferon-gamma gene diplotype (AA-rs2069716 / AG-rs2069727) may play an important role during secondary outcomes of severe dengue in Brazilian patients

ABSTRACT Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.

Neck Circumference Predicts Mortality in Hospitalized COVID-19 Patients.

We aimed to determine whether neck circumference predicts mortality among hospitalized COVID-19 patients with respiratory failure. We performed a prospective multicenter (Italy and Brasil) study carried out from March to December 2020 on 440 hospitalized COVID-19 patients with respiratory failure. Baseline neck circumference was measured. The study outcome was 30- and 60-days mortality. Female and male participants were classified as "large neck" when exceeding fourth-quartile. Patients had a median age of 65 years (IQR 54-76), 68% were male. One-quarter of patients presented with grade-1 or higher obesity. The median neck circumference was 40 cm (IQR 38-43): 38 cm (IQR 36-40) for female and 41 cm (IQR 39-44) for male subjects. "Large neck" patients had a significantly higher prevalence of hypertension (63 vs. 48%), diabetes (33 vs. 19%), obesity (26 vs. 14%), and elevated C-reactive protein (CRP) (98 vs. 88%). The cumulative mortality rate was 13.1% (n = 52) and 15.9% (n = 63) at 30 and 60 days, respectively. After adjusting for age, BMI, relevant comorbidities, and high C-reactive protein to albumin ratio, "large neck" patients showed a significantly increased risk of death at 30- (adjusted HR 2.50; 95% CI 1.18-5.29; p = 0.017) and 60-days (adjusted HR 2.26; 95% CI 1.14-4.46; p = 0.019). Neck circumference is easy to collect and provides additional prognostic information to BMI. Among hospitalized COVID-19 patients with respiratory failure, those with large neck phenotype had a more than double risk of death at 30 and 60 days.

Use of the Coding Causes of Death in HIV in the classification of deaths in Northeastern Brazil.

OBJECTIVE: Describe the coding process of death causes for people living with HIV/AIDS, and classify deaths as related or unrelated to immunodeficiency by applying the Coding Causes of Death in HIV (CoDe) system. METHODS: A cross-sectional study that codifies and classifies the causes of deaths occurring in a cohort of 2,372 people living with HIV/AIDS, monitored between 2007 and 2012, in two specialized HIV care services in Pernambuco. The causes of death already codified according to the International Classification of Diseases were recoded and classified as deaths related and unrelated to immunodeficiency by the CoDe system. We calculated the frequencies of the CoDe codes for the causes of death in each classification category. RESULTS: There were 315 (13%) deaths during the study period; 93 (30%) were caused by an AIDS-defining illness on the Centers for Disease Control and Prevention list. A total of 232 deaths (74%) were related to immunodeficiency after application of the CoDe. Infections were the most common cause, both related (76%) and unrelated (47%) to immunodeficiency, followed by malignancies (5%) in the first group and external causes (16%), malignancies (12 %) and cardiovascular diseases (11%) in the second group. Tuberculosis comprised 70% of the immunodeficiency-defining infections. CONCLUSIONS: Opportunistic infections and aging diseases were the most frequent causes of death, adding multiple disease burdens on health services. The CoDe system increases the probability of classifying deaths more accurately in people living with HIV/AIDS. OBJETIVO: Descrever o processo de codificação das causas de morte em pessoas vivendo com HIV/Aids, e classificar os óbitos como relacionados ou não relacionados à imunodeficiência aplicando o sistema Coding Causes of Death in HIV (CoDe). MÉTODOS: Estudo transversal, que codifica e classifica as causas dos óbitos ocorridos em uma coorte de 2.372 pessoas vivendo com HIV/Aids acompanhadas entre 2007 e 2012 em dois serviços de atendimento especializado em HIV em Pernambuco. As causas de óbito já codificadas a partir da Classificação Internacional de Doenças foram recodificadas e classificadas como óbitos relacionados e não relacionados à imunodeficiência pelo sistema CoDe. Foram calculadas as frequências dos códigos CoDe das causas do óbito em cada categoria de classificação. RESULTADOS: Ocorreram 315 (13%) óbitos no período do estudo; 93 (30%) tinham como causa uma doença definidora de Aids da lista do Centers for Disease Control and Prevention. No total 232 óbitos (74%) foram relacionados à imunodeficiência após aplicar o CoDe. As infecções foram as causas mais comuns, tanto nos óbitos relacionados (76%) como não relacionados (47%) à imunodeficiência, seguindo-se de malignidades (5%) no primeiro grupo e de causas externas (16%), malignidades (12%) e doenças cardiovasculares (11%) no segundo. A tuberculose compreendeu 70% das infecções definidoras de imunodeficiência. CONCLUSÕES: Infecções oportunistas e doenças do envelhecimento foram as causas mais frequentes de óbito, imprimindo carga múltipla de doenças aos serviços de saúde. O sistema CoDe aumenta a probabilidade de classificar os óbitos com maior precisão em pessoas vivendo com HIV/Aids.

[Anthropometric assessment of nutritional status in pregnancy: comparison of five diagnostic methods used in Latin AmericaClasificación antropométrica de las embarazadas: comparación de cinco métodos de diagnóstico utilizados en América Latina]. / Classificação antropométrica de gestantes: comparação entre cinco métodos diagnósticos utilizados na América Latina.

OBJECTIVE: To determine the agreement between five anthropometric methods used for nutritional assessment in pregnancy and to compare the distribution of nutritional status obtained with each method to that of the population of non-pregnant young women in Brazil. METHOD: This is a cross-sectional study with data from 1 108 pregnant women aged 19 to 35 years who received prenatal care from September 2011 to April 2012 in health services in the state of Pernambuco, Brazil. Nutritional status (underweight, appropriate weight, overweight/obesity) was determined using the criteria of Mardones and Rosso, Mardones et al., Atalah et al., Centro Latino Americano de Perinatologia (CLAP), and the Institute of Medicine (IOM-2009). Kappa agreement was estimated for the pairs of methods, and the chi-square goodness of fit test was performed to compare the frequency distribution of each nutritional category in each of the methods in comparison to the distribution in non-pregnant women classified according to body mass index (BMI, WHO cut-off points). RESULTS: Agreement between the methods was observed for overweight/obesity (kappa > 0.60), but not for underweight (kappa ≤ 0.60), particularly in the comparison of IOM-2009 (which relies on prepregnancy BMI) with other methods. The frequency distributions obtained with the five methods showed lower percentages of overweight/obesity and higher percentages of underweight as compared to the reference population of non-pregnant women (P < 0.001). CONCLUSION: The disparities observed in the present study may have resulted from the heterogeneity among the methods. This suggests that additional surveys are needed to establish population-specific anthropometric standards.

OBJETIVO: Verificar si hay concordancia entre cinco métodos antropométricos de clasificación nutricional de las embarazadas y comparar las clasificaciones obtenidas con la clasificación nutricional de la población brasileña de mujeres jóvenes no embarazadas. MÉTODO: Estudio transversal con datos de 1 108 embarazadas de 19 a 35 años atendidas desde septiembre del 2011 hasta abril del 2012 en servicios de atención prenatal en el estado de Pernambuco (Brasil). La clasificación nutricional (peso bajo, peso adecuado y sobrepeso u obesidad) se realizó de acuerdo con los criterios de Mardones y Rosso, de Mardones et al., de Atalah et al., del Centro Latinoamericano de Perinatología (CLAP) y del Instituto de Medicina del 2009 (IOM-2009). Se estimaron los coeficientes kappa de concordancia para los pares de métodos y la prueba del ji-cuadrado de la bondad del ajuste para comparar la distribución de frecuencias de cada categoría nutricional obtenida con cada método con la distribución en las mujeres que no están embarazadas clasificadas según el índice de masa corporal (IMC, puntos de corte de la OMS). RESULTADOS: Los métodos concordaron en lo que respecta al diagnóstico de sobrepeso y obesidad (kappa 0,60) y no concordaron en relación con el peso bajo (kappa ≤ 0,60), particularmente cuando se compararon las clasificaciones basadas en los criterios de la IOM-2009 (que utiliza el IMC pregestacional) con los demás. Las distribuciones de frecuencias muestrales obtenidas con los cinco métodos difirieron de la población de referencia de mujeres no embarazadas (P < 0,001), observándose porcentajes de sobrepeso y obesidad inferiores a la prevalencia nacional y porcentajes de peso bajo superiores a la prevalencia nacional. CONCLUSIÓN: Las disparidades observadas pueden atribuirse a la heterogeneidad de los métodos. Se justifica la realización de investigaciones para definir patrones antropométricos específicos para determinadas poblaciones.

Use of the coding causes of death in HIV in the classification of deaths in Northeastern Brazil / Uso do coding causes of death in HIV na classificação de óbitos no Nordeste do Brasil

ABSTRACT OBJECTIVE Describe the coding process of death causes for people living with HIV/AIDS, and classify deaths as related or unrelated to immunodeficiency by applying the Coding Causes of Death in HIV (CoDe) system. METHODS A cross-sectional study that codifies and classifies the causes of deaths occurring in a cohort of 2,372 people living with HIV/AIDS, monitored between 2007 and 2012, in two specialized HIV care services in Pernambuco. The causes of death already codified according to the International Classification of Diseases were recoded and classified as deaths related and unrelated to immunodeficiency by the CoDe system. We calculated the frequencies of the CoDe codes for the causes of death in each classification category. RESULTS There were 315 (13%) deaths during the study period; 93 (30%) were caused by an AIDS-defining illness on the Centers for Disease Control and Prevention list. A total of 232 deaths (74%) were related to immunodeficiency after application of the CoDe. Infections were the most common cause, both related (76%) and unrelated (47%) to immunodeficiency, followed by malignancies (5%) in the first group and external causes (16%), malignancies (12 %) and cardiovascular diseases (11%) in the second group. Tuberculosis comprised 70% of the immunodeficiency-defining infections. CONCLUSIONS Opportunistic infections and aging diseases were the most frequent causes of death, adding multiple disease burdens on health services. The CoDe system increases the probability of classifying deaths more accurately in people living with HIV/AIDS.

RESUMO OBJETIVO Descrever o processo de codificação das causas de morte em pessoas vivendo com HIV/Aids, e classificar os óbitos como relacionados ou não relacionados à imunodeficiência aplicando o sistema Coding Causes of Death in HIV (CoDe). MÉTODOS Estudo transversal, que codifica e classifica as causas dos óbitos ocorridos em uma coorte de 2.372 pessoas vivendo com HIV/Aids acompanhadas entre 2007 e 2012 em dois serviços de atendimento especializado em HIV em Pernambuco. As causas de óbito já codificadas a partir da Classificação Internacional de Doenças foram recodificadas e classificadas como óbitos relacionados e não relacionados à imunodeficiência pelo sistema CoDe. Foram calculadas as frequências dos códigos CoDe das causas do óbito em cada categoria de classificação. RESULTADOS Ocorreram 315 (13%) óbitos no período do estudo; 93 (30%) tinham como causa uma doença definidora de Aids da lista do Centers for Disease Control and Prevention. No total 232 óbitos (74%) foram relacionados à imunodeficiência após aplicar o CoDe. As infecções foram as causas mais comuns, tanto nos óbitos relacionados (76%) como não relacionados (47%) à imunodeficiência, seguindo-se de malignidades (5%) no primeiro grupo e de causas externas (16%), malignidades (12%) e doenças cardiovasculares (11%) no segundo. A tuberculose compreendeu 70% das infecções definidoras de imunodeficiência. CONCLUSÕES Infecções oportunistas e doenças do envelhecimento foram as causas mais frequentes de óbito, imprimindo carga múltipla de doenças aos serviços de saúde. O sistema CoDe aumenta a probabilidade de classificar os óbitos com maior precisão em pessoas vivendo com HIV/Aids.

Classificação antropométrica de gestantes: comparação entre cinco métodos diagnósticos utilizados na América Latina / Anthropometric assessment of nutritional status in pregnancy: comparison of five diagnostic methods used in Latin America / Clasificación antropométrica de las embarazadas: comparación de cinco métodos de diagnóstico utilizados en América Latina

RESUMO Objetivo Verificar a concordância entre cinco métodos antropométricos na classificação nutricional de gestantes e comparar as classificações obtidas com a classificação nutricional da população brasileira de mulheres jovens não gestantes. Método Estudo transversal com dados de 1 108 gestantes com idade de 19 a 35 anos atendidas de setembro de 2011 a abril de 2012 em serviços de pré-natal no estado de Pernambuco, Brasil. A classificação nutricional (baixo peso, peso adequado e sobrepeso/obesidade) foi realizada conforme os critérios de Mardones e Rosso, de Mardones et al., de Atalah et al., do Centro Latino Americano de Perinatologia (CLAP) e do Institute of Medicine de 2009 (IOM-2009). Estimaram-se os coeficientes kappa de concordância para os pares de métodos. O teste do qui-quadrado de bondade de ajuste foi utilizado para comparar a distribuição de frequências de cada categoria nutricional em cada método com a distribuição em não gestantes classificadas de acordo com índice de massa corporal (IMC, pontos de corte da OMS). Resultados Os métodos concordaram entre si para o diagnóstico de sobrepeso/obesidade (kappa > 0,60) e discordaram em relação ao baixo peso (kappa ≤ 0,60), particularmente nas comparações do IOM-2009 (que utiliza o IMC pré-gestacional) com os demais. As distribuições de frequências amostrais obtidas com os cinco métodos diferiram da população de referência de não gestantes (P < 0,001), observando-se percentuais de sobrepeso/obesidade inferiores à prevalência nacional e percentuais de baixo peso superiores à prevalência nacional. Conclusão As disparidades observadas podem ser atribuídas à heterogeneidade entre os métodos, justificando a realização de inquéritos para definir padrões antropométricos específicos para determinadas populações.

Objective To determine the agreement between five anthropometric methods used for nutritional assessment in pregnancy and to compare the distribution of nutritional status obtained with each method to that of the population of non-pregnant young women in Brazil. Method This is a cross-sectional study with data from 1 108 pregnant women aged 19 to 35 years who received prenatal care from September 2011 to April 2012 in health services in the state of Pernambuco, Brazil. Nutritional status (underweight, appropriate weight, overweight/obesity) was determined using the criteria of Mardones and Rosso, Mardones et al., Atalah et al., Centro Latino Americano de Perinatologia (CLAP), and the Institute of Medicine (IOM-2009). Kappa agreement was estimated for the pairs of methods, and the chi-square goodness of fit test was performed to compare the frequency distribution of each nutritional category in each of the methods in comparison to the distribution in non-pregnant women classified according to body mass index (BMI, WHO cut-off points). Results Agreement between the methods was observed for overweight/obesity (kappa > 0.60), but not for underweight (kappa ≤ 0.60), particularly in the comparison of IOM-2009 (which relies on prepregnancy BMI) with other methods. The frequency distributions obtained with the five methods showed lower percentages of overweight/obesity and higher percentages of underweight as compared to the reference population of non-pregnant women (P < 0.001), Conclusion The disparities observed in the present study may have resulted from the heterogeneity among the methods. This suggests that additional surveys are needed to establish population-specific anthropometric standards.

RESUMEN Objetivo Verificar si hay concordancia entre cinco métodos antropométricos de clasificación nutricional de las embarazadas y comparar las clasificaciones obtenidas con la clasificación nutricional de la población brasileña de mujeres jóvenes no embarazadas. Método Estudio transversal con datos de 1 108 embarazadas de 19 a 35 años atendidas desde septiembre del 2011 hasta abril del 2012 en servicios de atención prenatal en el estado de Pernambuco (Brasil). La clasificación nutricional (peso bajo, peso adecuado y sobrepeso u obesidad) se realizó de acuerdo con los criterios de Mardones y Rosso, de Mardones et al., de Atalah et al., del Centro Latinoamericano de Perinatología (CLAP) y del Instituto de Medicina del 2009 (IOM-2009). Se estimaron los coeficientes kappa de concordancia para los pares de métodos y la prueba del ji-cuadrado de la bondad del ajuste para comparar la distribución de frecuencias de cada categoría nutricional obtenida con cada método con la distribución en las mujeres que no están embarazadas clasificadas según el índice de masa corporal (IMC, puntos de corte de la OMS). Resultados Los métodos concordaron en lo que respecta al diagnóstico de sobrepeso y obesidad (kappa 0,60) y no concordaron en relación con el peso bajo (kappa ≤ 0,60), particularmente cuando se compararon las clasificaciones basadas en los criterios de la IOM-2009 (que utiliza el IMC pregestacional) con los demás. Las distribuciones de frecuencias muestrales obtenidas con los cinco métodos difirieron de la población de referencia de mujeres no embarazadas (P < 0,001), observándose porcentajes de sobrepeso y obesidad inferiores a la prevalencia nacional y porcentajes de peso bajo superiores a la prevalencia nacional. Conclusión Las disparidades observadas pueden atribuirse a la heterogeneidad de los métodos. Se justifica la realización de investigaciones para definir patrones antropométricos específicos para determinadas poblaciones.

Could the erythrocyte indices or serum ferritin predict the therapeutic response to a trial with oral iron during pregnancy? Results from the Accuracy study for Maternal Anaemia diagnosis (AMA).

BACKGROUND: Treatment of maternal iron-deficiency anaemia can reduce risks of prematurity and low birth weight; hence a reliable diagnosis of maternal iron needs is critical. However, erythrocyte indices and serum ferritin have shown a weak correlation with iron status during pregnancy. This study verified the accuracy of those tests to predict the responsiveness to a therapeutic test with oral iron as reference standard for iron deficiency in pregnant women. METHODS: A prospective diagnostic study phase 3 was conducted in a single prenatal care center in Northeast Brazil. Between August 2011 and October 2012 a consecutive sampling included 187 women in their 2(nd)-3(rd) trimesters of low-risk pregnancy and having anaemia (haemoglobin <11.0 g/dL). Until December 2012, 139 women completed a trial with daily pills of ferrous sulfate (40 mg of iron), during 23 to 125 days. Haemoglobin (Hb), other erythrocyte indices and ferritin (index-tests) were assessed pre-treatment by automated analyzers. Hb was performed also post-treatment to assess the therapeutic response by its post-pretreatment differences. We estimated sensitivity (Se), specificity (Sp), predictive values (PV), likelihood ratios (LR), diagnostic Odds Ratio (OR), area under Receiver Operating Characteristic curve (AUC), accuracy ratio and agreement coefficient of the index-tests against an increase of at least 0.55 Hb Z-score (reference standard test). We calculated the Z-scores according to the reference population from Centers for Disease Control and Prevention. RESULTS: Hb had a mean increase of 0.24 Z-score after 30 iron pills (p 0.013). All index-tests demonstrated PV- above 70 %, PV+ around 40 %, LR around 1.0, and AUC of 0.5 to 0.6. Hb and haematocrit had Se of 50 % (95 % CI 40 to 70); and Sp of 59 % (95 % CI 43 to 74) and 47 % (95 % CI 38 to 57), respectively. Ferritin, Mean Corpuscular Volume, Mean Corpuscular Haemoglobin, Mean Corpuscular Haemoglobin Concentration and Red blood cell Distribution Width had Se below 40 % with Sp above 70 %. CONCLUSIONS: Erythrocyte indices and ferritin could not predict the iron needs of anemic pregnant women. Increases of Hb Z-scores after a short treatment with oral iron may be a reliable therapeutic test. TRIAL REGISTRATION: World Health Organization International Clinical Trials Registry Platform U1111-1123-2605; Brazilian Registry of Clinical Trials RBR-237wbg , registered 28 July 2011.