Bases Clínicas e Laboratoriais para o Diagnóstico e Compreensão das Doenças Metabólicas Neonatais

The authors divide neonatal metabolic diseases into two major groups: intoxication and energy deficiency. The main signs which allow for the suspicion of the diagnosis are indicated for each group. The complementary examinations to be carried out by the Clinical Pathology Service of the Central Hospital and those which must be carried out by the metabolic diseases Reference Centre are reviewed. Based on the clinical framework and on the examination results, the authors establish five syndromatic groups to orientate diagnosis. The authors conclude by presenting differential diagnosis tables based on the original systematic classification by Jean-Marie Saudubray, with up-dated modifications from their own experience.

Anesthesia for Ex Utero Intrapartum Treatment: Renewed Insight on a Rare Procedure

The ex utero intrapartum treatment is a rare surgical procedure performed in cases of expected postpartum fetal airway obstruction. The technique lies on a safe establishment of a patent airway during labor in anticipation of a critical respiratory event, without interrupting maternal-fetal circulation. Anesthetic management is substantially different from that regarding standard cesarean delivery and its main goals include uterine relaxation, fetal anesthesia and preservation of placental blood flow. We present the case of an ex utero intrapartum treatment procedure performed on a fetus with a large cervical lymphangioma and prenatal evidence of airway compromise. Modifications to the classic ex utero intrapartum treatment management strategies were successfully adopted and will be discussed in the following report.

Adult B-Cell Acute Lymphoblastic Leukemia Cells Display Decreased PTEN Activity and Constitutive Hyperactivation of PI3K/Akt Pathway Despite High PTEN Protein Levels

Adult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge, requiring a better characterization of the molecular determinants underlying disease progression and resistance to treatment. Here, using a phospho-flow cytometry approach we show that adult diagnostic B-cell acute lymphoblastic leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of their BCR-ABL status and despite paradoxically high basal expression of PTEN, the major negative regulator of the pathway. Protein kinase CK2 is known to phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant PTEN functional inactivation. In agreement, we found that adult B-cell acute lymphoblastic leukemia samples show significantly higher CK2 kinase activity and lower PTEN lipid phosphatase activity than healthy controls. Moreover, the clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in leukemia cells to those observed in healthy controls, and promoted leukemia cell death without significantly affecting normal bone marrow cells. Our studies indicate that CK2-mediated PTEN posttranslational inactivation, associated with PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid, novel therapeutic tool in this malignancy.