Identification of novel biomarkers with potential for diagnosis and prognosis of gastric cancer: a bioinformatics approach

INTRODUCTION: Gastric cancer (GC) is the fifth most diagnosed neoplasia and the third leading cause of cancer-related deaths. A substantial number of patients exhibit an advanced GC stage once diagnosed. Therefore, the search for biomarkers contributes to the improvement and development of therapies. OBJECTIVE: This study aimed to identify potential GC biomarkers making use of in silico tools. METHODS: Gastric tissue microarray data available in Gene Expression Omnibus and The Cancer Genome Atlas Program was extracted. We applied statistical tests in the search for differentially expressed genes between tumoral and non-tumoral adjacent tissue samples. The selected genes were submitted to an in-house tool for analyses of functional enrichment, survival rate, histological and molecular classifications, and clinical follow-up data. A decision tree analysis was performed to evaluate the predictive power of the potential biomarkers. RESULTS: In total, 39 differentially expressed genes were found, mostly involved in extracellular structure organization, extracellular matrix organization, and angiogenesis. The genes SLC7A8, LY6E, and SIDT2 showed potential as diagnostic biomarkers considering the differential expression results coupled with the high predictive power of the decision tree models. Moreover, GC samples showed lower SLC7A8 and SIDT2 expression, whereas LY6E was higher. SIDT2 demonstrated a potential prognostic role for the diffuse type of GC, given the higher patient survival rate for lower gene expression. CONCLUSION: Our study outlines novel biomarkers for GC that may have a key role in tumor progression. Nevertheless, complementary in vitro analyses are still needed to further support their potential.

Rhinovirus as the main co-circulating virus during the COVID-19 pandemic in children

Abstract Objective: Changes in the epidemiology of respiratory infections during the restrictions imposed as a response to the coronavirus disease 2019 (COVID-19) pandemic have been reported elsewhere. The present study's aim was to describe the prevalence of a large array of respiratory pathogens in symptomatic children and adolescents during the pandemic in Southern Brazil. Methods: Hospitalized and outpatients aged 2 months to 18 years with signs and symptoms of acute COVID-19 were prospectively enrolled in the study from May to November 2020 in two hospitals in a large metropolitan area in a Brazilian city. All participants performed a real-time PCR panel assessing 20 respiratory pathogens (three bacteria and 17 viruses). Results: 436 participants were included, with 45 of these hospitalized. Rhinovirus was the most prevalent pathogen (216/436) followed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 97/436), with a coinfection of these two viruses occurring in 31/436 participants. The remaining pathogens were found in 24 symptomatic participants (adenovirus, n = 6; Chlamydophila pneumoniae, n = 1; coronavirus NL63, n = 2; human enterovirus, n = 7; human metapneu-movirus, n = 2; Mycoplasma pneumoniae, n = 6). Hospitalization was more common among infants (p = 0.004) and those with pathogens other than SARS-CoV-2 (p = 0.001). Conclusion: During the period of social distancing in response to COVID-19, the prevalence of most respiratory pathogens was unusually low. Rhinovirus remained as the main virus co-circulating with SARS-CoV-2. COVID-19 in symptomatic children was less associated with hospitalization than with other respiratory infections in children and adolescents.

Association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil: a prospective cohort study

ABSTRACT Objective: To evaluate the association between obesity and hospitalization in mild COVID-19 adult outpatients in Brazil. Subjects and methods: Adults with signs and symptoms suggestive of acute SARS-CoV-2 infection who sought treatment in two hospital (public and private) emergency departments were prospectively enrolled. Patients with confirmed COVID-19 at inclusion were followed by phone calls at days D7, D14 and D28. Multivariable logistic regression models were employed to explore the association between obesity and other potential predictors for hospitalization. Results: A total of 1,050 participants were screened, and 297 completed the 28-day follow-up and were diagnosed with COVID-19 by RT-PCR. The median age was 37.2 (IQR 29.7-44.6) years, and 179 (60.0%) were female. The duration of symptoms was 3.0 (IQR 2.0-5.0) days, and 10.0 (IQR 8.0-12.0) was the median number of symptoms at inclusion. Ninety-five (32.0%) individuals had obesity, and 233 (78.5%) had no previous medical conditions. Twenty-three participants (7.7%) required hospitalization during the follow-up period. After adjusting, obesity (BMI ≥ 30.0 kg/m2) (OR = 2.69, 95% CI 1.63-4.83, P < 0.001) and older age (OR = 1.05, 95% CI 1.01-1.09, P < 0.001) were significantly associated with higher risks of hospitalization. Conclusion: Obesity, followed by aging, was the main factor associated with hospital admission for COVID-19 in a young population in a low-middle income country. Our findings highlighted the need to promote additional protection for individuals with obesity, such as vaccination, and to encourage lifestyle changes.

Low performance of a SARS-CoV-2 point-of-care lateral flow immunoassay in symptomatic children during the pandemic

Abstract Objective: to evaluate the accuracy of an antibody point-of-care lateral flow immunoassay (LFI -Wondfo Biotech Co., Guangzhou, China) in a pediatric population. Methods: children and adolescents (2 months to 18 years) with signs and symptoms suggestive of acute SARS-CoV-2 infection were prospectively investigated with nasopharyngeal RT-PCR and LFI at the emergency room. RT-PCR was performed at baseline, and LFI at the same time or scheduled for those with less than 7 days of the clinical picture. Overall accuracy, sensitivity and specificity were assessed, as well as according to the onset of symptoms (7-13 or ≥14 days) at the time of the LFI test. Results: In 175 children included, RT-PCR and LFI were positive in 51 (29.14%) and 36 (20.57%), respectively. The overall sensitivity, specificity, positive and negative predictive value was 70.6% (95%CI 56.2-82.5), 96.8% (95%CI 91.9-99.1), 90.0% (95%CI 77.2-96.0), and 88.9% (95%CI 83.9-92.5), respectively. At 7-13 and ≥14 days after the onset of symptoms, sensitivity was 60.0% (95%CI 26.2-87.8) and 73.2% (95%CI 57.1-85.8) and specificity was 97.9% (95%CI 88.7-99.9) and 96.1% (95%CI 89.0-99.2), respectively. Conclusion: Despite its high specificity, in the present study the sensitivity of LFI in children was lower (around 70%) than most reports in adults. Although a positive result is informative, a negative LFI test cannot rule out COVID-19 in children.

Diagnostic accuracy of a SARS-CoV-2 rapid test and optimal time for seropositivity according to the onset of symptoms / Acurácia diagnóstica de um teste rápido para SARS-CoV-2 e tempo ótimo para a soropositividade a partir do início dos sintomas / Precisión diagnóstica del test rápido SARS-CoV-2 y período óptimo para la seropositividad según la aparición de síntomas

Point-of-care serological tests for SARS-CoV-2 have been used for COVID-19 diagnosis. However, their accuracy over time regarding the onset of symptoms is not fully understood. We aimed to assess the accuracy of a point-of-care lateral flow immunoassay (LFI). Subjects, aged over 18 years, presenting clinical symptoms suggestive of acute SARS-CoV-2 infection were tested once by both nasopharyngeal and oropharyngeal RT-PCR and LFI. The accuracy of LFI was assessed in periodic intervals of three days in relation to the onset of symptoms. The optimal cut-off point was defined as the number of days required to achieve the best sensitivity and specificity. This cut-off point was also used to compare LFI accuracy according to participants' status: outpatient or hospitalized. In total, 959 patients were included, 379 (39.52%) tested positive for SARS-CoV-2 with RT-PCR, and 272 (28.36%) tested positive with LFI. LFI best performance was achieved after 10 days of the onset of symptoms, with sensitivity and specificity of 84.9% (95%CI: 79.8-89.1) and 94.4% (95%CI: 91.0-96.8), respectively. Although the specificity was similar (94.6% vs. 88.9%, p = 0.051), the sensitivity was higher in hospitalized patients than in outpatients (91.7% vs. 82.1%, p = 0.032) after 10 days of the onset of symptoms. Best sensitivity of point-of-care LFI was found 10 days after the onset of symptoms which may limit its use in acute care. Specificity remained high regardless of the number of days since the onset of symptoms.

Os testes sorológicos no local de atendimento (point-of-care) para a infecção pelo SARS-CoV-2 têm sidos utilizados para o diagnóstico da COVID-19. Entretanto, não está plenamente elucidada a acurácia dos testes ao longo do tempo em relação ao início dos sintomas. Nosso objetivo foi de avaliar a acurácia, no local de atendimento, do imunoensaio de fluxo lateral (LFI). Pacientes com ≥ 18 anos de idade que apresentavam sintomas clínicos sugestivos de infecção aguda pelo SARS-CoV-2 foram testados uma vez com RT-PCR da nasofaringe e orofaringe, além do LFI. A acurácia do LFI foi avaliada com intervalos periódicos de 3 dias a partir do início dos sintomas. O ponto de corte ótimo foi definido como o número necessário de dias para atingir a melhor sensibilidade e especificidade. Esse ponto foi utilizado também para comparar a acurácia do LFI de acordo com a situação do paciente (ambulatorial ou hospitalizado). Foram incluídos 959 pacientes, dos quais 379 (39,52%) testaram positivos para SARS-CoV-2 pelo RT-PCR e 272 (28,36%) pelo LFI. Foi atingido o melhor desempenho para o LFI com 10 dias a partir do início dos sintomas, com sensibilidade e especificidade de 84,9% (IC95%: 79,8-89,1) e 94,4% (IC95%: 91,0-96,8), respectivamente. Embora a especificidade não tenha sido diferente entre os grupos de pacientes (94,6% vs. 88,9%, p = 0,051), a sensibilidade foi mais alta nos pacientes hospitalizados que nos ambulatoriais (91,7% vs. 82,1%, p = 0,032) no dia 10 depois do início dos sintomas. A melhor sensibilidade do LFI no local de atendimento ocorre 10 dias depois do início dos sintomas, o que pode limitar seu uso no atendimento agudo. A especificidade permanece alta, independentemente do número de dias desde o início dos sintomas.

Los puestos de atención para pruebas serológicas del SARS-CoV-2 han sido usado para la diagnosis de la COVID-19. No obstante, su precisión a lo largo del tiempo, en lo que respecta a la aparición de los síntomas, no se ha comprendido completamente. Nuestro objetivo fue evaluar la precisión de un puesto de atención de inmunoanálisis de flujo lateral (LFI). Se hizo pruebas a individuos ≥ 18 años, presentando síntomas clínicos compatibles con una infección aguda de SARS-CoV-2, tanto vía nasofaríngea y orofaríngea RT-PCR, como LFI. La precisión de LFI fue evaluada en intervalos periódicos de 3 días con respecto a la aparición de los síntomas. El punto óptimo de corte se definió como el número de días requerido para alcanzar la mejor sensibilidad y especificidad. Este punto también se usó para comparar la precisión del LFI, según el estatus de los participantes: ambulatorios u hospitalizados. Se incluyeron a 959 pacientes, 379 (39,52%) dieron positivo en las pruebas de SARS-CoV-2 RT-PCR, y 272 (28,36%) fueron positivos en los LFI. Se alcanzó el mejor rendimiento de los LFI tras 10 días de la aparición de los síntomas, con una sensibilidad y especificidad de un 84,9% (IC95%: 79,8-89,1) y 94,4% (IC95%: 91,0-96,8), respectivamente. A pesar de que la especificidad no fue diferente (94,6% vs. 88,9%, p = 0,051), la sensibilidad fue mayor en pacientes hospitalizados que en los ambulatorios (91,7% vs. 82,1%, p = 0,032) tras 10 días desde la aparición de los síntomas. La mejor sensibilidad LFI del puesto de cuidado se produce tras 10 días de la aparición de los síntomas, lo que quizás limite su uso en el cuidado de urgencias. La especificidad permanece alta independientemente del número de días desde la aparición de los síntomas.

The use of micro-costing in an economic analysis of allogeneic HSCT in Brazil / O uso do microcusteio na análise econômica do TCTH alogênico no Brasil

Objetivo: O objetivo deste estudo foi estimar os custos do tratamento do transplante de células--tronco hematopoéticas (TCTH) em um centro de referência no Brasil. Métodos: A população do estudo foi composta por pacientes provenientes da lista de TCTH do Sistema Único de Saúde submetidos ao TCTH em um hospital do sul do Brasil, entre 2016 e 2019. A avaliação de custos foi realizada por meio de um estudo de microcusteio, baseado no Time-Driven Activity-based Costing (TDABC) adaptado para estudos econômicos em saúde e incluiu as seguintes etapas: definição da questão de pesquisa, coleta de dados estruturada e análise estatística dos resultados. Resultados: O custo total do TCTH foi de $ 155.110 ($ 92.794 ­ $ 249.146 USD). O TCTH de doador não aparentado compatível foi mais caro do que o TCTH de doador aparentado compatível. Os principais fatores de custo envolvem complicações pós-transplante, principalmente a ocorrência de infecções. Em relação à composição dos custos, exames e procedimentos representam o maior custo em TCTH (45%). Conclusão: Essas estimativas podem ser aplicáveis a novas avaliações de custo-efetividade do TCTH e ajudar os gestores na tomada de decisão em saúde, especialmente em países de média renda

Objective: The objective of this study was to estimate treatment costs of Hematopoietic stem cell transplantation (HSCT) at a reference center in Brazil. Methods: The study population consisted of patients from the Unified Health System HSCT who underwent HSCT in southern Brazil between 2016 and 2019. Costs were measured using a micro-costing approach, based on Time-Driven Activity-based Costing (TDABC) adapted for economic studies in health and included the following steps: definition of the research question, structured data collection, and statistical analysis of results. Results: The total cost of HSCT was $155,110 ($92,794 ­ $249,146 USD). Matched unrelated donor HSCT was more expensive than matched related donor HSCT. The major cost factors involve post- -transplant complications, mainly the occurrence of infections. Concerning cost composition, exams and procedures represent the largest expense in HSCT (45%). Conclusion: These estimates could be applicable to further evaluations for HSCT cost-effectiveness and help healthcare decision-makers in middle-income countries