Hospital de Santa Maria
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Melanoma brain metastases presenting as delirium: a case report
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Controversies in the management of hyperglycaemic emergencies in adults with diabetes
No full textHyperglycaemic emergencies are associated with significant morbi-mortality and healthcare costs. Management consists on fluid replacement, insulin therapy, and electrolyte correction. However, some areas of patient management remain debatable. In patients without respiratory failure or haemodynamic instability, arterial and venous pH and bicarbonate measurements are comparable. Fluid choice varies upon replenishment phase and patient's condition. If patient is severely hypovolaemic, normal saline solution should be the first option. However, if patient has mild/moderate dehydration, fluid choice must take in consideration sodium concentration. Insulin therapy should be guided by β-hydroxybutyrate normalization and not by blood glucose. Variations of conventional insulin infusion protocols emerged recently. Priming dose of insulin may not be required, and fixed rate insulin infusion represents the best option to suppress hepatic glucose production, ketogenesis, and lipolysis. Concomitant administration of basal insulin analogues with regular insulin infusion accelerates ketoacidosis resolution and prevents rebound hyperglycaemia. Simpler protocols using subcutaneous rapid-acting insulin analogues for mild/moderate diabetic ketoacidosis treatment have proven to be safe and effective, but further studies are required to confirm these results. Treatment with bicarbonate, phosphate, and low-molecular-weight heparin is still disputable, and randomized controlled trials are urgently needed to optimize patient management and decrease the morbi-mortality of hyperglycaemic emergencies.info:eu-repo/semantics/publishedVersio
Impacto económico dos neuromoduladores recarregáveis – Muda o paradigma?
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Combined study of ADAMTS13 and complement genes in the diagnosis of thrombotic microangiopathies using next-generation sequencing
Get PDFBACKGROUND:
The 2 main forms of thrombotic microangiopathy (TMA) are thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS). Deficiency of ADAMTS13 and dysregulation of the complement pathway result in TTP and aHUS, respectively; however, overlap of their clinical characteristics makes differential diagnosis challenging.
OBJECTIVES AND METHODS:
We aimed to develop a TMA diagnosis workflow based on ADAMTS13 activity and screening of ADAMTS13 and complement genes using a custom next-generation sequencing (NGS) gene panel.
PATIENTS:
For this, from a cohort of 154 Portuguese patients with acute TMA, the genotype-phenotype correlations were analyzed in 7 hereditary TTP (ADAMTS13 activity <10%, no inhibitor), 36 acquired TTP (ADAMTS13 activity <10%, presence of an inhibitor), and in 34 presumable aHUS.
RESULTS:
In total, 37 different rare variants, 8 of which novel (in ADAMTS13,CFH, and CD46), were identified across 7 genes. Thirteen TTP patients were homozygous (n=6), compound heterozygous (n=2), and heterozygous (n=5) for 11 ADAMTS13 variants (6 pathogenic mutations). Among the 34 aHUS patients, 17 were heterozygous for 23 variants in the different complement genes with distinct consequences, ranging from single pathogenic mutations associated with complete disease penetrance to benign variants that cause aHUS only when combined with other variants and/or CFH and CD46 risk haplotypes or CFHR1-3 deletion.
CONCLUSIONS:
Our study provides evidence of the usefulness of the NGS panel as an excellent technology that enables more rapid diagnosis of TMA, and is a valuable asset in clinical practice to discriminate between TTP and aHUS.info:eu-repo/semantics/publishedVersio
Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency
No full textLeigh syndrome (LS) is a rare, progressive neurodegenerative mitochondrial disorder of infancy. It is a genetically heterogeneous disease. The mutations in SURF1 gene are the most frequently known cause. Here two cases of LS likely caused by SURF1 gene variants are reported: a 39-year-old male patient with a novel homozygous deletion (c.-11_13del), and a case of a 6-year-old boy with the same deletion and a nonsense mutation (c.868dupT), both in heterozygosity. Blue native PAGE showed absence of assembled complex IV. This is the first report of a variant that may abolish the SURF1 gene initiation codon in two LS patients.info:eu-repo/semantics/publishedVersio
MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease
Get PDFINTRODUCTION:
Mononuclear phagocytes play a critical role during Alzheimer's disease (AD) pathogenesis due to their contribution to innate immune responses and amyloid beta (Aβ) clearance mechanisms.
METHODS:
Blood-derived monocytes (BDMs) and monocyte-derived macrophages (MDMs) were isolated from blood of AD, mild cognitive impairment (MCI) patients, and age-matched healthy controls for molecular and phenotypic comparisons.
RESULTS:
The chemokine/chemokine receptor CCL2/CCR2 axis was impaired in BDMs from AD and MCI patients, causing a deficit in cell migration. Changes were also observed in MDM-mediated phagocytosis of Aβ fibrils, correlating with alterations in the expression and processing of the triggering receptor expressed on myeloid cells 2 (TREM2). Finally, immune-related microRNAs (miRNAs), including miR-155, -154, -200b, -27b, and -128, were found to be differentially expressed in these cells.
DISCUSSION:
This work provides evidence that chemotaxis and phagocytosis, two crucial innate immune functions, are impaired in AD and MCI patients. Correlations with miRNA levels suggest an epigenetic contribution to systemic immune dysfunction in AD.info:eu-repo/semantics/publishedVersio
Newborn Urinary Metabolic Signatures of Prematurity and Other Disorders: A Case Control Study
Get PDFThis work assesses the urinary metabolite signature of prematurity in newborns by nuclear magnetic resonance (NMR) spectroscopy, while establishing the role of possible confounders and signature specificity, through comparison to other disorders. Gender and delivery mode are shown to impact importantly on newborn urine composition, their analysis pointing out at specific metabolite variations requiring consideration in unmatched subject groups. Premature newborns are, however, characterized by a stronger signature of varying metabolites, suggestive of disturbances in nucleotide metabolism, lung surfactants biosynthesis and renal function, along with enhancement of tricarboxylic acid (TCA) cycle activity, fatty acids oxidation, and oxidative stress. Comparison with other abnormal conditions (respiratory depression episode, large for gestational age, malformations, jaundice and premature rupture of membranes) reveals that such signature seems to be largely specific of preterm newborns, showing that NMR metabolomics can retrieve particular disorder effects, as well as general stress effects. These results provide valuable novel information on the metabolic impact of prematurity, contributing to the better understanding of its effects on the newborn's state of health.info:eu-repo/semantics/publishedVersio
