El papel de los parámetros metabólicos de la 18F-FDG PET/TC en el linfoma linfoblástico pediátrico / The role of 18F-FDG PET/CT metabolic parameters in pediatric lymphoblastic lymphoma

Objetivo: Este estudio retrospectivo tuvo como objetivo evaluar el papel de los parámetros metabólicos de la 18F-FDG PET/TC en el linfoma linfoblástico pediátrico (LBL).Métodos: Treinta pacientes con LBL se sometieron a 42 exploraciones. Los parámetros metabólicos, que incluyeron el valor máximo de captación estandarizado (SUVmax), el volumen tumoral metabólico total (TMTV) y la glucólisis de lesión total (TLG), se midieron en la PET/TC basal. Se realizaron análisis univariantes y multivariantes de la supervivencia para evaluar su valor pronóstico. Doce pacientes se sometieron a PET/TC después del régimen de reinducción, y se calcularon la sensibilidad, la especificidad, el valor predictivo positivo (VPP), el valor predictivo negativo (VPN) y la precisión de la PET/TC para predecir la recaída.Resultados: Los pacientes con estadio IV tuvieron una TMTV más alta que los que tenían un estadio III (p=0,031). Además, los pacientes con T-LBL o afectación mediastínica tenían una TMTV y TLG altos (p<0,05). No hubo diferencias significativas en los parámetros metabólicos de la PET/TC entre los pacientes con diferente evolución (p>0,05). Los niños con una TMTV baja (<242,91cm3) tuvieron una mejor EFS a los 3 años comparados con aquellos con una TMTV elevada (88.9% vs. 56,3%; p=0,036). El SUVmax y el TLG no fueron predictivos de la EFS (p=0,874; p=0,152). Sin embargo, ninguno de los parámetros metabólicos de la PET/TC basales fueron factores pronósticos independientes para los resultados del LBL pediátrico. La PET/TC realizada después del régimen de reinducción presentó una mayor sensibilidad (50% vs. 0%) y VPN (90% vs. 83,3%) para predecir la recaída que la TC sola.Conclusiones: Los parámetros metabólicos de la PET/TC de referencia no fueron predictivos de los resultados en los niños con LBL. La PET/TC realizada después del régimen de reinducción tuvo una mejor sensibilidad y VPN que la TC sola, y una exploración

Objective: This retrospective study aimed to evaluate the role of metabolic parameters of 18F-FDG PET/CT in pediatric lymphoblastic lymphoma (LBL).Methods: Thirty patients with LBL underwent 42 scans. Metabolic parameters including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG) were measured at baseline PET/CT. Univariate and multivariate analysis for survival were performed to assess their prognostic value. Twelve patients underwent PET/CT after reinduction regime, and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for predicting relapse were calculated.Results: Patients with stage IV had a higher TMTV than those with stage III (P=0.031). Besides, patients with T-LBL or mediastinal involvement had a high TMTV and TLG (P<0.05). There was no significant difference in PET/CT metabolic parameters between patients with different outcomes (P>0.05). Children with a low TMTV (<242.91cm3) had a better 3-year EFS compared with those with a high TMTV (88.9% vs. 56.3%; P=0.036). SUVmax and TLG were not predictive of EFS (P=0.874; P=0.152). However, none of the metabolic parameters of baseline PET/CT were independent prognostic factors for outcomes of pediatric LBL. PET/CT underwent after reinduction regime present with higher sensitivity (50% vs. 0%) and NPV (90% vs. 83.3%) for predicting relapse than CT alone.Conclusions: Metabolic parameters of baseline PET/CT were not predictive of outcomes in children with LBL. PET/CT done after the reinduction regime had better sensitivity and NPV than CT alone, and a negative scan could be a reliable indicator for sustained remission (AU)

Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19

Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including a prominent neutrophil hyperactivation signature and monocytes with anti-inflammatory features. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention. One Sentence SummarySingle-cell profiling demonstrates multifarious dysregulation of innate immune phenotype associated with COVID-19 severity.

Additional analyses exploring the hypothesized transdifferentiation of plasmablasts to developing neutrophils in severe COVID-19

We thank Alquicira-Hernandez et al. for their reanalysis of our single-cell transcriptomic dataset profiling peripheral immune responses to severe COVID-19. We agree that careful analysis of single-cell sequencing data is important for generating cogent hypotheses but find several aspects of their criticism of our analysis to be problematic. Here we respond briefly to misunderstandings and inaccuracies in their commentary that may have led to misinformed interpretation of our results.

A single-cell atlas of the peripheral immune response to severe COVID-19

There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.