Realidad virtual y biomarcadores digitales: una herramienta clínica para el diagnóstico del autismo / Virtual reality and digital biomarkers: a clinical tool for early autism diagnosis

Resumen Introducción : El Trastorno del Espectro Autista (TEA) es un trastorno del neurodesarrollo, y sus procedimien tos tradicionales de evaluación encuentran ciertas li mitaciones. El actual campo de investigación sobre TEA está explorando y respaldando métodos innovadores para evaluar el trastorno tempranamente, basándose en la detección automática de biomarcadores. Sin embargo, muchos de estos procedimientos carecen de validez ecológica en sus mediciones. En este contexto, la reali dad virtual (RV) presenta un prometedor potencial para registrar objetivamente bioseñales mientras los usuarios experimentan situaciones ecológicas. Métodos : Este estudio describe un novedoso y lúdi co procedimiento de RV para la evaluación temprana del TEA, basado en la grabación multimodal de bio señales. Durante una experiencia de RV con 12 esce nas virtuales, se midieron la mirada, las habilidades motoras, la actividad electrodermal y el rendimiento conductual en 39 niños con TEA y 42 compañeros de control. Se desarrollaron modelos de aprendizaje automático para identificar biomarcadores digitales y clasificar el autismo. Resultados : Las bioseñales reportaron un rendimien to variado en la detección del TEA, mientras que el modelo resultante de la combinación de los modelos de las bioseñales demostró la capacidad de identificar el TEA con una precisión del 83% (DE = 3%) y un AUC de 0.91 (DE = 0.04). Discusión : Esta herramienta de detección pue de respaldar el diagnóstico del TEA al reforzar los resultados de los procedimientos tradicionales de evaluación.

Abstract Introduction : Autism Spectrum Disorder (ASD) is a neurodevelopmental condition which traditional as sessment procedures encounter certain limitations. The current ASD research field is exploring and endorsing innovative methods to assess the disorder early on, based on the automatic detection of biomarkers. How ever, many of these procedures lack ecological validity in their measurements. In this context, virtual reality (VR) shows promise for objectively recording biosignals while users experience ecological situations. Methods : This study outlines a novel and playful VR procedure for the early assessment of ASD, relying on multimodal biosignal recording. During a VR experience featuring 12 virtual scenes, eye gaze, motor skills, elec trodermal activity and behavioural performance were measured in 39 children with ASD and 42 control peers. Machine learning models were developed to identify digital biomarkers and classify autism. Results : Biosignals reported varied performance in detecting ASD, while the combined model resulting from the combination of specific-biosignal models demon strated the ability to identify ASD with an accuracy of 83% (SD = 3%) and an AUC of 0.91 (SD = 0.04). Discussion : This screening tool may support ASD diagnosis by reinforcing the outcomes of traditional assessment procedures.

Os Biomarcadores podem ser Utilizados para Prever Recorrência de Arritmia após a Ablação de Fibrilação Atrial Guiada pelo Ablation-Index? / Can Pre-Ablation Biomarkers Be Used to Predict Arrhythmia Recurrence after Ablation Index-Guided Atrial Fibrillation Ablation?

Resumo Fundamento: O software ablation index (AI) permitiu melhorar os resultados da ablação de fibrilação atrial (FA), mas as taxas de recorrência permanecem significativas. Biomarcadores séricos específicos têm sido associados a essa recorrência. Objetivos: Avaliar se certos biomarcadores podem ser utilizados (individualmente ou combinados) para predizer a recorrência de FA pós ablação guiada pelo AI. Métodos: Estudo multicêntrico, observacional, prospectivo de pacientes consecutivos, encaminhados para ablação de FA de janeiro de 2018 a março de 2021. Hemoglobina, peptídeo natriurético cerebral (BNP), proteína C reativa, troponina I ultrassensível, clearance de creatinina, Hormônio Tireoestimulante (TSH), e Tiroxina livre (T4) foram avaliados quanto à capacidade de prever a recorrência de arritmias durante o acompanhamento. Valores de p <0,05 foram aceitos como estatisticamente significativos. Resultados: Um total de 593 pacientes foram incluídos - 412 com FA paroxística e 181 com FA persistente. Durante o seguimento médio de 24±6 meses, 76,4% não apresentaram recidiva após ablação. Individualmente, os biomarcadores demonstraram um valor preditivo baixo ou nulo para recorrência. No entanto, TSH >1,8 μUI/mL [HR=1,82 (IC95%, 1,89-2,80), p=0,006] foi um preditor independente de recorrência. Avaliando-se a combinação de TSH, FT4 e BNP, a adição de cada valor "anormal" foi associada a uma menor sobrevida livre de recorrência (87,1% se nenhum vs. 83,5% se um vs. 75,1% se dois vs. 43,3% se três biomarcadores, p<0,001). Doentes com três biomarcadores "anormais" apresentaram três vezes maior probabilidade de recorrência de FA, comparativamente aos que não apresentaram nenhum biomarcador "anormal" (HR=2,88 [IC95%, 1,39-5,17], p=0,003). Conclusões: Quando combinados, valores anormais de TSH, FT4 e BNP podem ser uma ferramenta útil para prever a recorrência de FA pós ablação guiada pelo AI.

Abstract Background: Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. Objectives: To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. Methods: Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of<0.05. Results: A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value >1.8 μUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional "abnormal" biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p<0.001). Patients with three "abnormal" biomarkers had a threefold higher risk of AF recurrence compared with no "abnormal" biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). Conclusions: When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease

Abstract Objective: This study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). Methods: Pediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. Results: In all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. Conclusion: Serological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.

Elevated serum IL-6 levels predict treatment interruption in patients with moderate to severe psoriasis: a 6-year real-world cohort study

Abstract Background: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. Objective: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. Methods: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and inter-leukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. Results: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01-1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29-3.08; p = 0.002) were associated with treatment interruption. Study limitations: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. Conclusions: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

Clinical profile of vitiligo patients and relationship with immuno-inflammatory markers

Abstract Background Vitiligo is the most common pigmentary disorder and is considered a chronic, cumulative, multifactorial disease. The crucial role of cytotoxic CD8+ T lymphocytes and the IFNγ/CXCL10 axis has been demonstrated in its pathogenesis. Objective To evaluate the clinical profile and immuno-inflammatory markers in patients with vitiligo in a reference medical center. Methods Cross-sectional study in which all patients with vitiligo seen at the medical center the from 2019 to 2022 were evaluated, to outline the clinical profile. Moreover, cardiovascular risk biomarkers (neutrophil/lymphocyte ratio and C-reactive protein levels) were measured, as well as cytokines and chemokines (TNFα, IFNγ, IL10, IL15 and CXCL10) in the serum of a subgroup of 30 patients. Results There was a predominance of females, with a mean age of 43 years. Most were phototypes IV or V (71.3%), without comorbidities (77.55%), and without a family history of vitiligo (70.41%). Higher levels of neutrophil/lymphocyte ratio, C-reactive protein, and inflammatory cytokines/chemokines were documented in vitiligo patients when compared to the control group (non-significant). As relevant data, the highest values of CXCL10 were detected in patients with vitiligo versus controls, as well as in patients with disease of shorter duration (p < 0.05). Study limitations The number of assessed patients was small due to recruitment difficulties caused by the COVID-19 pandemic. Conclusion The present data contribute to confirming the relevant role of the IFNγ/CXCL10 axis in the pathogenesis of vitiligo, highlighting CXCL10 as a possible activity marker.

Identificação de Potenciais Biomarcadores Cruciais em IAMCSST por Meio de Análise Bioinformática Integrada / Identification of Potential Crucial Biomarkers in STEMI Through Integrated Bioinformatic Analysis

Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de -log2fold change- > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.

Abstract Background ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. Objectives In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. Methods We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of -log2fold change- > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. Results 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. Conclusions This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI.

Marcadores de Perfusão Tecidual como Preditores de Desfechos Adversos em Pacientes com Disfunção Ventricular Esquerda Submetidos à Revascularização Miocárdica (Bypass Coronário) / Markers of Tissue Perfusion as Predictors of Adverse Outcomes in Patients with Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Surgery

Resumo Fundamento: Pacientes submetidos à cirurgia cardíaca podem estar expostos à hipoperfusão tecidual e metabolismo anaeróbico. Objetivo: Verificar se os biomarcadores de hipoperfusão tecidual têm valor preditivo para permanência prolongada na Unidade de Terapia Intensiva (UTI) em pacientes com disfunção ventricular esquerda submetidos à cirurgia de bypass da artéria coronária. Métodos: Após aprovação pelo comitê de ética institucional e assinatura do termo de consentimento, 87 pacientes com disfunção ventricular esquerda (fração de ejeção <50%) submetidos à cirurgia de bypass coronário foram incluídos. Biomarcadores hemodinâmicos e metabólicos foram coletados em cinco momentos: após anestesia, ao final da cirurgia, na admissão na UTI, e a seis e 12 horas depois. Uma análise de variância para medidas repetidas seguida de um teste post-hoc de Bonferroni foi usado para variáveis contínuas repetidas (variáveis metabólicas e hemodinâmicas) para determinar diferenças entre os dois grupos ao longo do estudo. O nível de significância adotado foi de 5%. Resultados: Trinta e oito pacientes (43,7%) que apresentaram desfechos adversos eram mais velhos, apresentaram um Euroscore mais alto (p<0,001), e gradiente venoarterial de CO2 (ΔPCO2) elevado, analisados 12 horas após a admissão na UTI (p<0,01), enquanto uma concentração de lactato arterial aumentada seis horas após a cirurgia foi um fator preditivo negativo (p<0,01). Conclusões: EuroSCORE, lactato arterial seis horas após a cirurgia, ΔPCO212 horas após a cirurgia e QRe são preditores independentes de desfechos adversos em pacientes com disfunção ventricular esquerda após cirurgia cardíaca.

Abstract Background: Cardiac surgery patients may be exposed to tissue hypoperfusion and anaerobic metabolism. Objective: To verify whether the biomarkers of tissue hypoperfusion have predictive value for prolonged intensive care unit (ICU) stay in patients with left ventricular dysfunction who underwent coronary artery bypass surgery. Methods: After approval by the institution's Ethics Committee and the signing of informed consent, 87 patients with left ventricular dysfunction (ejection fraction < 50%) undergoing coronary artery bypass surgery were enrolled. Hemodynamic and metabolic biomarkers were collected at five time points: after anesthesia, at the end of the surgery, at ICU admission, and at six and twelve hours after. An analysis of variance for repeated measures followed by a Bonferroni post hoc test was used for repeated, continuous variables (hemodynamic and metabolic variables) to determine differences between the two groups over the course of the study period. The level of statistical significance adopted was 5%. Results: Thirty-eight patients (43.7%) who presented adverse outcomes were older, higher Euro score (p<0.001), and elevated ΔpCO2 as analyzed 12 hours after ICU admission (p<0.01), while increased arterial lactate concentration at 6 hours postoperatively was found to be a negative predictive factor (p<0.01). Conclusions: Euro SCORE, six-hour postoperative arterial lactate, 12-hour postoperative ΔPCO2, and eRQ are independent predictors of adverse outcomes in patients with left ventricular dysfunction after cardiac surgery.

Extracellular vesicles in Alzheimer's disease / Vesículas extracelulares na doença de Alzheimer

Abstract Extracellular vesicles (EVs) are small vesicles released by cells that facilitate cell signaling. They are categorized based on their biogenesis and size. In the context of the central nervous system (CNS), EVs have been extensively studied for their role in both normal physiological functions and diseases like Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by cognitive decline and neuronal death. EVs have emerged as potential biomarkers for AD due to their involvement in disease progression. Specifically, EVs derived from neurons, astrocytes, and neuron precursor cells exhibit changes in quantity and composition in AD. Neuron-derived EVs have been found to contain key proteins associated with AD pathology, such as amyloid beta (Aß) and tau. Increased levels of Aß in neuron-derived EVs isolated from the plasma have been observed in individuals with AD and mild cognitive impairment, suggesting their potential as early biomarkers. However, the analysis of tau in neuron-derived EVs is still inconclusive. In addition to Aß and tau, neuron-derived EVs also carry other proteins linked to AD, including synaptic proteins. These findings indicate that EVs could serve as biomarkers for AD, particularly for early diagnosis and disease monitoring. However, further research is required to validate their use and explore potential therapeutic applications. To summarize, EVs are small vesicles involved in cell signaling within the CNS. They hold promise as biomarkers for AD, potentially enabling early diagnosis and monitoring of disease progression. Ongoing research aims to refine their use as biomarkers and uncover additional therapeutic applications.

Resumo As vesículas extracelulares (VEs) são pequenas estruturas liberadas pelas células que agem na sinalização celular. No sistema nervoso central (SNC), as VEs são estudadas em relação à doença de Alzheimer (DA), um distúrbio neurodegenerativo que cursa com declínio cognitivo e morte neuronal. As VEs podem ser biomarcadores potenciais para a DA devido ao seu papel na progressão da doença. As VEs derivadas de neurônios, astrócitos e células precursoras apresentam alterações na DA, contendo proteínas associadas à patologia da DA, como beta-amiloide (Aß) e tau. Níveis elevados de Aß foram observados nas VEs de neurônios de indivíduos com DA, sugerindo seu potencial como biomarcadores precoces. A análise de tau nas VEs de neurônios ainda é inconclusiva. Além disso, as VEs neurais carregam outras proteínas relacionadas à DA, incluindo proteínas sinápticas. As VEs podem ser promissoras como biomarcadores para o diagnóstico precoce e monitoramento da DA, porém mais pesquisas são necessárias para validar seu uso e explorar aplicações terapêuticas. Em resumo, as VEs são vesículas envolvidas na sinalização celular no SNC, com potencial como biomarcadores para a DA.

Association of biomarkers with successful ventilatory weaning in COVID-19 patients: an observational study / Associação entre biomarcadores e sucesso do desmame ventilatório em pacientes com COVID-19: um estudo observacional

ABSTRACT Objective: To evaluate the association of biomarkers with successful ventilatory weaning in COVID-19 patients. Methods: An observational, retrospective, and single-center study was conducted between March 2020 and April 2021. C-reactive protein, total lymphocytes, and the neutrophil/lymphocyte ratio were evaluated during attrition and extubation, and the variation in these biomarker values was measured. The primary outcome was successful extubation. ROC curves were drawn to find the best cutoff points for the biomarkers based on sensitivity and specificity. Statistical analysis was performed using logistic regression. Results: Of the 2,377 patients admitted to the intensive care unit, 458 were included in the analysis, 356 in the Successful Weaning Group and 102 in the Failure Group. The cutoff points found from the ROC curves were −62.4% for C-reactive protein, +45.7% for total lymphocytes, and −32.9% for neutrophil/lymphocyte ratio. These points were significantly associated with greater extubation success. In the multivariate analysis, only C-reactive protein variation remained statistically significant (OR 2.6; 95%CI 1.51 - 4.5; p < 0.001). Conclusion: In this study, a decrease in C-reactive protein levels was associated with successful extubation in COVID-19 patients. Total lymphocytes and the neutrophil/lymphocyte ratio did not maintain the association after multivariate analysis. However, a decrease in C-reactive protein levels should not be used as a sole variable to identify COVID-19 patients suitable for weaning; as in our study, the area under the ROC curve demonstrated poor accuracy in discriminating extubation outcomes, with low sensitivity and specificity.

RESUMO Objetivo: Avaliar a associação de biomarcadores com o sucesso do desmame ventilatório em pacientes com COVID-19. Métodos: Trata-se de estudo observacional, retrospectivo e de centro único realizado entre março de 2020 e abril de 2021. Foram avaliados a proteína C-reativa, os linfócitos totais e a relação neutrófilos/linfócitos durante o atrito e a extubação; mediu-se a variação desses valores de biomarcadores. O desfecho primário foi o sucesso da extubação. As curvas ROC foram desenhadas para encontrar os melhores pontos de corte dos biomarcadores segundo a sensibilidade e a especificidade. A análise estatística foi realizada por meio de regressão logística. Resultados: Dos 2.377 pacientes admitidos na unidade de terapia intensiva, 458 foram incluídos na análise, 356 no Grupo Sucesso do desmame e 102 no Grupo Fracasso do desmame. Os pontos de corte encontrados nas curvas ROC foram −62,4% para proteína C-reativa, +45,7% para linfócitos totais e −32,9% para relação neutrófilo/linfócito. Esses pontos foram significativamente associados ao maior sucesso da extubação. Na análise multivariada, apenas a variação da proteína C-reativa permaneceu estatisticamente significativa (RC 2,6; IC95% 1,51 - 4,5; p < 0,001). Conclusão: Neste estudo, uma diminuição nos níveis de proteína C-reativa foi associada ao sucesso da extubação em pacientes com COVID-19. Os linfócitos totais e a relação neutrófilos/linfócitos não mantiveram a associação após a análise multivariada. No entanto, uma diminuição nos níveis de proteína C-reativa não deve ser usada como única variável para identificar pacientes com COVID-19 adequados para o desmame; como em nosso estudo, a área sob a curva ROC demonstrou baixa precisão na discriminação dos resultados de extubação, com baixas sensibilidade e especificidade.

Evaluation of some immunological markers in co-infection of COVID-19 with thrush candidiasis

SUMMARY OBJECTIVE: COVID-19 infection poses significant risks, including life-threatening consequences and fungus synchronization, making it a significant concern. This study seeks to assess the effect of concurrent infection of COVID-19 with Thrush Candida albicans on the patient's health state by measuring the proportion of immune cells and certain interleukins such as IL-8, -10, -17, and -33. METHODS: The study involved 70 patients (30 patients with COVID-19, 17 patients with thrush candidiasis, and 23 patients with Thrush Candida albicans) and 50 healthy individuals as a control group. COVID-19 was identified using RT-PCR, while C. albicans were identified through culture media, biochemical testing, and oral swabs. Ruby equipment and ELISA kits were used for blood counts and interleukin detection. RESULTS: COVID-19, thrush candidiasis, and Thrush Candida albicans infections occur in a wide range of age groups (4-80 years), with no significant differences between sexes (p>0.05). Immunologically, our study found that Thrush Candida albicans patients had the highest rate of neutrophils (89.6%) and basophils (2.01%), while corona patients had the highest percentage of lymphocytes (70.12%) and eosinophils (7.11%), and patients with thrush candidiasis had the highest percentage of monocytes. Thrush Candida albicans patients showed increased IL-8 (56.7 pg/mL) and IL-17 (101.1 pg/mL) concentrations, with the greatest concentration of IL-33 (200.5 pg/mL) in COVID-19, and a decrease in the level of IL-10 in patient groups compared with controls. CONCLUSION: Patient groups showed increased neutrophils, lymphocytes, monocytes, and IL-8 levels, with a significant linear association between proinflammatory interleukins and these cells.

Genetic variants in miR-146a and miR-196a2 in endometriosis: a Brazilian study

SUMMARY OBJECTIVE: The aim of this study was to determine the allelic and genotypic frequencies of the polymorphisms, rs2910164 miR-146a and rs11614913 miR-196a2, by investigating their association with endometriosis. METHODS: This is a case-control study performed with approximately 120 women. The polymorphisms were determined by real-time polymerase chain reaction. For the statistical analysis, the chi-square and logistic regression tests were used. RESULTS: There were no significant differences in the genotype and allele frequencies of rs2910164 and rs11614913 between cases and controls. The frequencies in both polymorphisms are in accordance with Hardy-Weinberg equilibrium regarding miR-146a (patients: χ2=1.64, p=0.20; controls: χ2=0.25, p=0.62) and miR-196a2 (patients: χ2=0.58, p=0.44; controls: χ2=2.78, p=0.10). No relationship was observed between rs2910164 and rs11614913 and endometriosis in the inheritance models analyzed. CONCLUSION: In this study, our results show that the studied polymorphisms are not implicated in the development of endometriosis.

Biomarkers and prediction of anthracyclic cardiotoxicity in breast cancer

SUMMARY BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.

Cáncer de mama en el norte del Perú: subtipos moleculares y HER2 low / Breast cancer in northern Peru: molecular subtypes and HER2 low

RESUMEN El objetivo del estudio fue conocer el perfil inmunohistoquímico del cáncer de mama e identificar el subgrupo HER2 low en la macrorregión norte del Perú. Se realizó un estudio transversal con una muestra de 1176 pacientes atendidos en el Instituto Regional de Enfermedades Neoplásicas Norte del Perú desde enero de 2016 a diciembre de 2023. Los datos recolectados (edad, tipo histológico, grado y resultados complementarios), se analizaron con frecuencias y porcentajes. El perfil correspondió a: luminal B (45,6%); luminal A (24,7%); triple negativo (18,2%); y HER2 positivo no luminal (11,5%). Además, HER2 low fueron 215 pacientes (25,1% de los considerados previamente negativos). Este estudio proporciona evidencia que la subtipificación de cáncer de mama ha cambiado, siendo luminal B más frecuente, y es esencial involucrar a políticas de salud para adquirir terapias dirigidas considerando a pacientes HER2 low.

ABSTRACT This study aimed to understand the immunohistochemical profile of breast cancer and to identify the HER2 low subgroup in the northern macro-region of Peru. A cross-sectional study was conducted in 1176 patients from the Regional Institute of Neoplastic Diseases Northern Peru, from January 2016 to December 2023. We analyzed the data (age, histological type, grade and complementary results), with frequencies and percentages. The profile corresponded to: luminal B (45.6%); luminal A (24.7%); triple negative (18.2%); and HER2 positive non luminal (11.5%). In addition, 215 patients presented HER2 low (25.1% of those previously considered negative). This study provides evidence that the subtyping of breast cancer has changed, being luminal B the most frequent. It is essential to involve health policies to acquire targeted therapies considering HER2 low patients.

Factores de estrés y su asociación con los biomarcadores del síndrome metabólico

Introducción: el síndrome metabólico es considerado como un conjunto de factores de riesgo para desarrollar enfermedades cardiovasculares y diabéticas, en adición a esto, los biomarcadores determinan un diagnóstico del síndrome metabólico. Existen diversos factores que pueden causar el síndrome metabólico, uno de ellos, el estrés, que se concibe como la reacción de un individuo ante eventos o situaciones que exceden los mecanismos de adaptación. Objetivos: explorar la literatura científica existente para identificar y sintetizar los diferentes factores de estrés fisiológico que se han investigado en relación con el síndrome metabólico, y evaluar críticamente la evidencia disponible sobre la asociación entre los factores de estrés identificados y los biomarcadores específicos del síndrome metabólico. Además, realizar un análisis de la calidad metodológica de los estudios incluidos en la revisión para evaluar la validez y la fiabilidad de los resultados obtenidos. Materiales y Métodos: se realizó una revisión sistemática usando bases de datos como PubMed, Redalyc, SciELO y Google Scholar, en donde se incluyeron investigaciones que busquen establecer una relación entre el estrés y los biomarcadores del síndrome metabólico en publicaciones desde enero del 2017 a noviembre del 2022. Se tomaron en cuenta criterios de la Declaración PRISMA. Resultados: se incluyeron un total de 32 artículos, en donde se pudo observar que los biomarcadores del estrés oxidativo que influyen en el padecimiento del síndrome metabólico son diversos y pueden afectar de múltiples formas al ser humano, generando enfermedades como la diabetes, enfermedades cardiovasculares, pulmonares y hasta neuropsicológicas. Conclusiones: los biomarcadores del estrés oxidativo influyen de manera directa en el padecimiento de síndrome metabólico y son identificados como un factor determinante para diagnosticar enfermedades desencadenantes de este síndrome.

Introduction: Metabolic syndrome is considered as a set of risks factors for developing cardiovascular and diabetic diseases. Additionally, biomarkers determine a diagnosis of metabolic syndrome. Several of them can cause metabolic syndrome, and one of them, stress, is conceived as an individual's reaction to events or situations that exceed adaptation mechanisms. Materials and methods: A systematic review was carried out using database such as PubMed, Redalyc, Scielo and Google Scholar, which included research that relates oxidative stress to biomarkers of metabolic syndrome in publications from January 2017 to November 2022. The criteria considered were those of the PRISMA Declaration. Results: A total of 32 articles were included, and it was possible to observe that the biomarkers of oxidative stress that influence the condition of metabolic syndrome are diverse and can affect humans in multiple ways, generating diseases such as diabetes, cardiovascular, pulmonary, and even neuropsychological. Conclusions: Oxidative stress biomarkers have a direct influence on suffering from metabolic syndrome and are identified as a determining factor in diagnosing diseases that trigger this syndrome.

Avaliação da lactoferrina e da calprotectina como marcadores de inflamação intestinal na pancreatite crônica / Evaluating lactoferrin and calprotectin as markers of intestinal inflammation inchronic pancreatitis

ABSTRACT Background: The treatment of chronic pancreatitis does not consistently solve intestinal abnormalities, and despite the implementation of various therapeutic measures, patients often continue to experience persistent diarrhea. Therefore, it is imperative to recognize that diarrhea may stem from factors beyond pancreatic insufficiency, and intestinal inflammation emerges as a potential contributing factor. Objective: The aim of this study was to assess fecal lactoferrin and calprotectin levels as indicators of intestinal inflammation in patients with chronic pancreatitis experiencing persistent diarrhea. Methods: In this study, 23 male patients with chronic pancreatitis primarily attributed to alcohol consumption and presenting with diarrhea (classified as Bristol stool scale type 6 or 7), underwent a comprehensive evaluation of their clinical and nutritional status. Fecal lactoferrin and calprotectin levels were mea­sured utilizing immunoassay techniques. Results: The average age of the participants was 54.8 years, 43.5% had diabetes, and 73.9% were smokers. Despite receiving enzyme replacement therapy and refraining from alcohol for over 4 years, all participants exhibited persistent diarrhea, accompanied by elevated calprotectin and lactoferrin levels indicative of ongoing intestinal inflammation. Conclusion: The findings of this study underscore that intestinal inflammation, as evidenced by elevated fecal biomarkers calprotectin and lactoferrin, may contribute to explaining the persistence of diarrhea in patients with chronic pancreatitis.

RESUMO Contexto: O tratamento da pancreatite crônica não resolve de forma consistente as anomalias intestinais e, apesar da implementação de várias medidas terapêuticas, os pacientes muitas vezes continuam a apresentar diarreia persistente. Portanto, é imperativo reconhecer que a diarreia pode resultar de fatores além da insuficiência pancreática, e a inflamação intestinal surge como um potencial fator contribuinte. Objetivo: O objetivo deste estudo foi avaliar os níveis fecais de lactoferrina e calprotectina como indicadores de inflamação intestinal em pacientes com pancreatite crônica com diarreia persistente. Métodos: Neste estudo, 23 pacientes do sexo masculino com pancreatite crônica atribuída principalmente ao consumo de álcool e apresentando diarreia (classificada na escala de fezes de Bristol tipo 6 ou 7), foram submetidos a uma avaliação abrangente de seu estado clínico e nutricional. Os níveis fecais de lactoferrina e calprotectina foram medidos utilizando técnicas de imunoensaio. Resultados: A idade média dos participantes foi de 54,8 anos, 43,5% tinham diabetes e 73,9% eram fumantes. Apesar de receber terapia de reposição enzimática e abster-se de álcool por mais de 4 anos, todos os participantes apresentaram diarreia persistente, acompanhada por níveis elevados de calprotectina e lactoferrina, indicativos de inflamação intestinal contínua. Conclusão: Os achados deste estudo ressaltam que a inflamação intestinal, evidenciada pelos biomarcadores fecais elevados calprotectina e lactoferrina, pode contribuir para explicar a persistência da diarreia em pacientes com pancreatite crônica.

Could signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 be a therapeutic target in the pathogenesis of preeclampsia?

SUMMARY OBJECTIVE: Determination of biomolecules that play a role in the etiopathogenesis of preeclampsia and their application as therapeutic targets may increase surveillance in this patient group. The aim of this study was to investigate the relationship between signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1, a marker of endothelial dysfunction and platelet activation, and the development of preeclampsia. METHODS: In this observational cross-sectional study conducted between April 2021 and December 2022, 73 consecutive pregnant women with preeclampsia and 73 healthy pregnant women were included. Blood samples were taken from all patients with preeclampsia to measure signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels at the time of hospitalization. Excluded from the study were pregnant women with certain medical conditions or treatments, and the signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels of the groups were compared according to the development of preeclampsia. RESULTS: Signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 levels were significantly higher in the preeclampsia group than in the controls (p<0.001). In multivariate analysis, signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 was determined as an independent predictor for preeclampsia (OR: 1.678, 95%CI 1.424-1.979, p<0.001). Receiver operating characteristic curve analysis showed that the best cutoff value of signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 at 3.25 ng/mL predicted the development of preeclampsia with 71% sensitivity and 68% specificity (area under the curve, 0.739; 95% confidence ınterval (95%CI), 0.681-0.798, p<0.001). CONCLUSION: Signal peptide complement C1r/C1s, Uegf, and Bmp1, and epidermal growth factor-containing protein 1 is significantly elevated in pregnant women with preeclampsia compared with healthy controls.

Del Nido vs. Cold Blood Cardioplegia for High-Risk Isolated Coronary Artery Bypass Grafting in Patients with Reduced Ventricular Function

ABSTRACT Introduction: The evidence for using del Nido cardioplegia protocol in high-risk patients with reduced ejection fraction undergoing isolated coronary surgery is insufficient. Methods: The institutional database was searched for isolated coronary bypass procedures. Patients with ejection fraction < 40% were selected. Propensity matching (age, sex, infarction, number of grafts) was used to pair del Nido (Group 1) and cold blood (Group 2) cardioplegia patients. Investigation of biomarker release, changes in ejection fraction, mortality, stroke, perioperative myocardial infarction, composite endpoint (major adverse cardiac and cerebrovascular events), and other perioperative parameters was performed. Results: Matching allowed the selection of 45 patient pairs. No differences were noted at baseline. After cross-clamp release, spontaneous sinus rhythm return was observed more frequently in Group 1 (80% vs. 48.9%; P=0.003). Troponin values were similar in both groups 12 and 36 hours after surgery, as well as creatine kinase at 12 hours. A trend favored Group 1 in creatine kinase release at 36 hours (median 4.9; interquartile range 3.8-9.6 ng/mL vs. 7.3; 4.5-17.5 ng/mL; P=0.085). Perioperative mortality, rates of myocardial infarction, stroke, or major adverse cardiac and cerebrovascular events were similar. No difference in postoperative ejection fraction was noted (median 35.0%; interquartile range 32.0-38.0% vs. 35.0%; 32.0-40.0%; P=0.381). There was a trend for lower atrial fibrillation rate in Group 1 (6.7% vs. 17.8%; P=0.051). Conclusion: The findings indicate that del Nido cardioplegia provides satisfactory protection in patients with reduced ejection fraction undergoing coronary bypass surgery. Further prospective trials are required.

Razões derivadas do hemograma durante a pandemia da Sars-Cov-2: um estudo observacional retrospectivo em pacientes em hemodiálise / Complete blood count derived ratios during the Sars-Cov-2 pandemic: a retrospective observational study in hemodialysis patients / Ratios derivados del hemograma durante la pandemia de Sars-Cov-2: un estudio observacional retrospectivo en pacientes en hemodiálisis

Biomarcadores de inflamação derivados do hemograma como a razão neutrófilos/linfócitos (NLR), a razão plaquetas/linfócitos (PLR), a razão neutrófilos/plaquetas (NPR) e o índice de inflamação imune sistêmico (SII) já foram investigados como preditores de prognóstico de doenças inflamatórias sistêmicas, cardiovasculares, malignas, etc., e com a ocorrência da pandemia de SARS-CoV-2, também passaram a ser estudadas como biomarcadores de interesse nessa doença. Objetivo: Comparar retrospectivamente o valor dessas 4 razões hematimétricas durante os dois anos da pandemia (2020-2021), com o período anterior (os anos de 2018-2019), em uma população de pacientes doentes renais em hemodiálise. Métodos: Esta pesquisa foi submetida ao Comitê de Ética e Pesquisa da Universidade Estadual de Ponta Grossa (CEP-UEPG) e foi aprovada sob o número do parecer 5.024.864. Foram incluídos pacientes tratados no setor de Terapia Renal Substitutiva do Hospital Santa Casa de Ponta Grossa durante os anos 2018 ­ 2021, com n amostral de 155 pacientes. A coleta dos dados se baseou na consulta de prontuários eletrônicos. O valor das razões NLR, NPR, PLR e SII foram calculados a partir da contagem dos neutrófilos, linfócitos e plaquetas dos hemogramas, considerou-se um hemograma a cada trimestre nesse intervalo de 4 anos. Como a normalidade dos dados não foi atestada, seguiu-se a metodologia não-paramétrica, o valor de α foi fixado em 0,05. Resultados: O teste de Skillings-Mack apresentou um valor de p-simulado significativo (< 2.2e-16) na comparação de cada uma das quatro razões. Na análise post-hoc, as comparações trimestrais das medianas do SII, não apresentaram diferença significativa, as razões PLR, NPR e NLR apresentaram respectivamente, duas, três e seis, comparações com diferenças significativas. Conclusão: Houve comparações com diferenças significativas pontuais, não houve um aumento geral no valor das razões SII, PLR, NPR e NLR durante o período de pandemia (2020 - 2021) entre os pacientes em hemodiálise.

Complete blood count derived inflammation biomarkers such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), neutrophil/platelet ratio (NPR) and systemic immune inflammation index (SII) have already been investigated as predictors of prognosis of systemic inflammatory, cardiovascular, malignant diseases, etc., and with the imminent SARS-CoV-2 pandemic, they also began to be studied as biomarkers of interest in this disease. Objective: To retrospectively compare the value of these 4 hematimetric ratios during the two years of the pandemic (2020-2021), with the previous period (2018-2019), in a population of kidney disease patients undergoing hemodialysis. Methods: This research was submitted to the Ethics and Research Committee of the State University of Ponta Grossa (CEP-UEPG) and was approved under protocol number 5.024.864. Patients treated in the Renal Replacement Therapy sector of Hospital Santa Casa de Ponta Grossa during the years 2018 ­ 2021 were included, with a sample size of 155 patients. Data collection was based on consultation of electronic medical records. The value of the NLR, NPR, PLR and SII ratios were calculated from the count of neutrophils, lymphocytes and platelets in the blood counts, considering one blood count every quarter in this 4-year interval. As the normality of the data was not attested, the non-parametric methodology was followed, the value of α was set at 0.05. Results: The Skillings-Mack test showed a significant simulated p-value (< 2.2e-16) when comparing each of the four ratios. In the post-hoc analysis, the quarterly comparisons of the SII medians did not show a significant difference, the PLR, NPR and NLR ratios showed two, three and six comparisons with significant differences, respectively. Conclusion: There were comparisons with significant specific differences, there was no general increase in the value of the SII, PLR, NPR and NLR ratios during the pandemic period (2020 - 2021) among hemodialysis patients.

Los biomarcadores de inflamación derivados del hemograma, como el índice de neutrófilos/linfocitos (NLR), el índice de plaquetas/linfocitos (PLR), el índice de neutrófilos/plaquetas (NPR) y el índice de inflamación inmune sistémica (SII), ya se han investigado como predictores del pronóstico de enfermedades sistémicas. enfermedades inflamatorias, cardiovasculares, malignas, etc., y con la inminente pandemia del SARS-CoV-2 también comenzaron a estudiarse como biomarcadores de interés en esta enfermedad. Objetivo: Comparar retrospectivamente el valor de estos 4 ratios hematimétricos durante los dos años de la pandemia (2020-2021), con el período anterior (2018-2019), en una población de pacientes con enfermedad renal en hemodiálisis. Métodos: Esta investigación fue presentada al Comité de Ética e Investigación de la Universidad Estadual de Ponta Grossa (CEP-UEPG) y fue aprobada con el dictamen número 5.024.864. Se incluyeron pacientes atendidos en el sector de Terapia de Reemplazo Renal del Hospital Santa Casa de Ponta Grossa durante los años 2018 ­ 2021, con un tamaño de muestra de 155 pacientes. La recolección de datos se basó en la consulta de historias clínicas electrónicas. El valor de los índices NLR, NPR, PLR y SII se calcularon a partir del recuento de neutrófilos, linfocitos y plaquetas en los hemogramas, considerando un hemograma cada trimestre en este intervalo de 4 años. Como no se comprobó la normalidad de los datos, se siguió la metodología no paramétrica, fijándose el valor de α en 0,05. Resultados: La prueba de Skillings-Mack mostró un valor p-simulado significativo (< 2,2e-16) al comparar cada una de las cuatro proporciones. En el análisis post-hoc, las comparaciones trimestrales de las medianas del SII no mostraron diferencia significativa, los ratios PLR, NPR y NLR presentaron, respectivamente, dos, tres y seis comparaciones con diferencias significativas. Conclusión: Hubo comparaciones con diferencias específicas significativas, no hubo un aumento general en el valor de los índices SII, PLR, NPR y NLR durante el período pandémico (2020 - 2021) entre los pacientes en hemodiálisis.