Characterization and Investigation of Risk Factors for Late-Relapsing Hepatitis After Yellow Fever.

BACKGROUND: Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46-60 days after YF symptom onset. METHODS: Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post-symptom onset. RESULTS: From 46 to 60 days post-symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF. CONCLUSIONS: These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

Comparative study of two histopathological classifications for oral squamous cell carcinoma / Estudo comparativo de duas classificações histopatológicas para carcinoma de células escamosas bucal

ABSTRACT Introduction: Squamous cell carcinoma (SCC) is the most common tumor among all cancers in the oral cavity. Despite advances, the prognosis of this neoplasm remains a challenge for professionals. Faced with this situation, several studies try to associate the histopathological analysis with prognosis, so that therapeutic planning becomes more accurate. Objectives: This research aimed to conduct an epidemiological study of oral SCC and classify them histopathological assessment according to the World Health Organization (WHO) and the Budding and Depth of Invasion (BD) model. A retrospective research was conducted. Methodology: Data from medical records filed at UOPECCAN Hospital between 2009 and 2015 were analyzed. The sample consisted of 57 patients. Epidemiological data were collected and the blocks were rescued and cut for histopathological analysis. Associations were performed using the chi-square test with a significance level of 5% (p = 0.05) by the GraphPad Prism program. The two histopathological analyzes were correlated using Spearman's statistical test. Results: After analyzing the samples, we found a higher prevalence of oral SCC in male smokers aged above 40 years. There was no correlation between the BD and WHO methods. The WHO classification was significantly associated with age (p = 0.03), and follow-up care (p = 0.05). However, the BD model associated lymph node involvement (p = 0.005) and clinical staging (p = 0.005). Conclusion: The BD classification was more objective for histopathological analysis and may be an important tool for analyzing patient prognosis, assisting in the treatment decision.

RESUMEN Introducción: El carcinoma de células escamosas (CCE), denominado además carcinoma epidermoide, es el tumor más común entre todos los cánceres de la cavidad oral. A pesar de los avances, el pronóstico de esta neoplasia sigue siendo un desafío para los cirujanos/profesionales/clínicos. Ante esta situación, varios estudios intentan asociar el análisis histopatológico con el pronóstico, para que la planificación terapéutica sea más precisa. Objectivos: Esta investigación tuvo como objetivo realizar un estudio epidemiológico del CCE oral y clasificarlo histopatológicamente de acuerdo con la Organización Mundial de la Salud (OMS) y el modelo Budding and Depth of Invasion (BD). Se realizó una investigación retrospectiva. Metodología: Se analizaron los datos de las historias clínicas archivadas en el Hospital UOPECCAN entre 2009 y 2015. La muestra estuvo formada por 57 pacientes. Se recolectaron datos epidemiológicos y los bloques fueron rescatados y cortados para análisis histopatológico. Las asociaciones se realizaron mediante la prueba de chi-cuadrado con un nivel de significancia del 5% (p = 0.05) por el programa GraphPad Prism. Los dos análisis histopatológicos se correlacionaron mediante la prueba estadística de Spearman. Resultados: Tras analizar las muestras, encontramos una mayor prevalencia de CCE oral en varones fumadores mayores de 40 años. No hubo correlación entre los métodos BD y OMS. La clasificación de la OMS se asoció significativamente con la edad (p = 0,03) y seguimiento del del tratamiento (p = 0,05). Sin embargo, el modelo de BD asoció la afectación de los ganglios linfáticos (p = 0,005) y la estadificación clínica (p = 0,005). Conclusión: La clasificación BD fue más objetiva para el análisis histopatológico y puede ser una herramienta importante para analizar el pronóstico del paciente, asistiendo en la decisión del tratamiento.

RESUMO Introdução: O carcinoma de células escamosas (CCE) é o tumor mais frequente entre todos os cânceres localizados na cavidade bucal. Apesar dos avanços, o prognóstico dessa neoplasia ainda é um desafio para os cirurgiões. Diante dessa situação, vários estudos tentam associar a análise histopatológica ao prognóstico, a fim de que os planejamentos terapêuticos se tornem mais precisos. Objetivos: Esta pesquisa teve como objetivo realizar o estudo epidemiológico dos CCEs e classificá-los histopatologicamente conforme a Organização Mundial da Saúde (OMS) e o modelo "Budding and Depth of Invasion" (BD). Um estudo retrospectivo foi realizado. Metodologia: Foram analisados dados dos prontuários arquivados no Hospital UOPECCAN entre 2009 e 2015. A amostra foi composta por 57 pacientes. Os dados epidemiológicos foram coletados e os blocos resgatados e cortados para análise histopatológica. As associações foram realizadas por meio do teste qui-quadrado, com nível de significância de 5% (p = 0,05) pelo programa GraphPad Prism. As duas análises histopatológicas foram correlacionadas por meio do teste estatístico de Spearman. Resultados: Após análise das amostras, verificamos mais prevalência de CCE nos pacientes fumantes do sexo masculino com idade superior a 40 anos. Não houve correlação entre os métodos BD e OMS. A classificação da OMS apresentou associação significante com a idade (p = 0,03) e a sequência de tratamento (p = 0,05). Já o modelo BD associou comprometimento linfonodal (p = 0,005) e estadiamento clínico (p = 0,005). Conclusão: A classificação BD foi mais objetiva para a análise histopatológica e pode ser uma importante ferramenta para análise do prognóstico do paciente, auxiliando na decisão do tratamento.

Characterization of Retinopathy Among Patients With Yellow Fever During 2 Outbreaks in Southeastern Brazil.

IMPORTANCE: Yellow fever still threatens people in endemic areas, and besides conjunctival icterus, little is known about the ocular changes that occur in these patients. OBJECTIVE: To characterize retinal changes in patients with confirmed yellow fever during 2 recent outbreaks of the disease in Minas Gerais, Southeastern Brazil. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, observational study conducted at a single referral center for infectious diseases in Southeastern Brazil collected data between January 2017 and February 2018 from 94 consecutive patients with suspicion of yellow fever who were eligible for the study. MAIN OUTCOMES AND MEASURES: Patients underwent ophthalmic examination. Clinical findings, laboratory results, and occurrence of retinopathy and death during hospitalization were reported, including age, sex, comorbidities, disease severity, serum aspartate aminotransferase level, total bilirubin level, serum creatinine level, arterial lactate level, international normalized ratio, and platelet count at hospital admission. RESULTS: In total, 64 patients were included who had received a confirmed diagnosis of yellow fever, with a median (interquartile range) age of 47 (38-56) years, and 12 patients (19%) were women. Twenty eyes (16%) of 13 patients (20%) had retinopathy at the same time as yellow fever. The most common fundus changes among the 20 eyes were retinal nerve fiber layer infarcts (11 [55%]), superficial hemorrhages (7 [35%]) and grayish deep lesions (6 [30%]), possibly at the level of the outer retina or choroid. Aspartate aminotransferase levels higher than 3000 U/L (odds ratio [OR], 14.2; 95% CI, 3.5-77.8; P < .001), total bilirubin levels higher than 2.3 mg/dL (OR, 20.0; 95% CI, 4.4-159.7; P < .001), serum creatinine levels higher than 2.0 mg/dL (OR, 8.2; 95% CI, 2.1-36.0; P = .003), arterial lactate levels higher than 17.1/mg/dL (OR, 4.6; 95% CI, 1.1-19.0; P = .03), platelet count lower than 94 × 103/µL (OR, 7.8; 95% CI, 1.8-59.9; P = .004), and classification of disease as severe (OR, 11.7; 95% CI, 2.0-301.0; P = .003) were associated with retinopathy. Arterial hypertension, diabetes, international normalized ratio, and death were not associated with retinopathy. CONCLUSIONS AND RELEVANCE: Retinopathy was present in 20% of patients with yellow fever and appeared to be associated with more severe systemic disease. Retinal nerve fiber layer infarcts and superficial hemorrhages, but not the grayish deep lesions, resembled those associated with other flavivirus (eg, dengue virus) infections. The clinical relevance of these findings may warrant further investigation.

Cardiac Involvement by Yellow Fever(from the PROVAR+ Study).

Incidence of Yellow Fever (YF) has increased in Brazil, and cardiac findings such as bradyarrhythmias and conduction abnormalities have been described. We aimed to perform a comprehensive cardiac evaluation of patients with YF, and to assess the association between cardiac involvement and disease severity. Patients hospitalized with YF from February to March 2018 underwent clinical and laboratory evaluation, focused bedside echocardiography (GE Vivid IQ), electrocardiogram and, in case of alterations, 24-hours Holter. Patients were divided into 2 groups according to YF severity. Five patients underwent magnetic resonance imaging and 3 had necropsy. Seventy patients had confirmed YF, 69% with severe form. Mean age was 48 ± 14 years, 63 (90%) were males and 5 (7%) died. Significant electrocardiogram abnormalities were present in 52% of patients with mild/moderate form of YF (G1) and 77% of those with severe form (G2), p = 0.046. Sinus bradycardia was observed in 24% (N = 17): G1 23% versus G2 25%, p = 0.67. Among 32 patients who underwent Holter, 14 (44%) had mean HR <60 beats per minute, being 8 from G2. Echocardiogram revealed left ventricular dysfunction in 4 (6%) patients, from G2. Left ventricular wall thickening with a hyper-refringent myocardial texture suggesting infiltration was observed in 17 patients (G1 18% vs G2 27%, p = 0.55). One magnetic resonance (G2) was suggestive of myocarditis, and one necropsy revealed areas of myocardial necrosis and acute myocarditis. In conclusion, cardiac involvement was observed in patients with YF, most commonly bradycardia and myocardial hyper-refringent texture suggestive of infiltration.