Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection.

This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.

[Gastrointestinal stromal tumor: a report of eight cases]. / Tumor estromal gastrointestinal: estudo de oito casos.

INTRODUCTION: Diagnosis and treatment of Gastrointestinal Stromal Tumor have changed because of recent genetic and molecular biological studies which have a direct impact on longer survival. METHODS: A retrospective research was carried out from November 1998 to July 2004 at the university and in the private clinics of the authors who identified GIST cases based upon positive tests to c-kit (CD117). RESULTS: The eight patients that were evaluated had an average age of 53.2 and 75% were females. The most common clinical feature was abdominal mass (62.5%). The more frequent tumor site was the stomach (62.5%) followed by the small bowel (37.5%). Mean tumor size was 10.6 cm. Resection with negative microscopic margins was possible in all patients. Tumor recurrence occurred in four cases which were treated with imatinib mesilate (STI-571) with partial response in three cases and complete response in the other. Seven patients (87.5%) are alive with a mean follow-up of 33.4 months (9 to 60 months). Due to the limited number of patients it was not possible to correlate biological behavior of the tumor with its size and mitotic count. CONCLUSIONS: There was prevalence in the female gender. Most common tumor site was the stomach. Histological examinations did not disclose any correlation between tumor size and number of mitosis. At an average follow-up of 33.4 months, the mean survival was 87.5%.

Tumor estromal gastrointestinal: estudo de oito casos / Gastrointestinal stromal tumor: a report of eight cases

OBJETIVO: O diagnóstico e tratamento dos tumores estromais gastrointestinais (TEGI) têm evoluído a partir de estudos recentes de genética e biologia molecular. Tais avanços têm refletido em melhor sobrevivência dos doentes. MÉTODOS: Foi realizado estudo retrospectivo no período de novembro/1998 a julho/2004, em instituição universitária e em clínica privada dos autores, que identificou portadores de TEGI a partir de positividade para c-kit (CD 117), ao exame imunoistoquímico. RESULTADOS: Dos oito pacientes estudados, seis eram do sexo feminino (75 por cento), a idade média foi de 53,2 anos. A presença de massa abdominal palpável foi a apresentação mais comum (62,5 por cento). O estômago foi o órgão mais acometido (62,5 por cento) seguido pelo intestino delgado (37,5 por cento). O tamanho médio do tumor foi de 10,6 cm. Em todos, foi possível a ressecção com margens livres. Em quatro doentes houve recidiva local ou à distância, todos esses foram tratados com mesilato de imatinib, com resposta parcial em três e completa em um deles. Sete pacientes (87,5 por cento) estão vivos em um período de seguimento médio de 33,4 meses. Não foi possível avaliar o comportamento biológico do tumor a partir das variáveis estudadas em virtude da pequena casuística. CONCLUSÕES: Com base nos dados obtidos de oito pacientes com TEGI do presente estudo, observamos: prevalência dos TEGI em doentes do sexo feminino o estômago como órgão preferencialmente acometido, ausência de correlação entre tamanho do tumor e número de mitoses à análise histológica e taxa de sobrevivência de 87,5 por cento com um seguimento médio de 33,4 meses.