Ventricular Assist Device Driveline Infection and Development of Intracranial Hemorrhage: A Case Series.

Durable left ventricular assist devices (LVAD) are frequently complicated by driveline infection. The objective of this case series was to examine whether an association exists between driveline infection and intracranial hemorrhage. This retrospective case series included patients at a single tertiary care hospital on durable LVAD support who developed intracranial hemorrhage. Physical examination data, vital signs, and laboratory markers of sepsis including blood cultures and imaging of driveline sites were reviewed. A total of nine patients were included in the case series. At the time of hemorrhagic event, five patients had active driveline infection, and five patients were found to be bacteremic. All bacteremic patients were found to have supratherapeutic INR at the time of presentation. Although five patients experienced subarachnoid hemorrhage, only one patient was found to have a cerebral aneurysm. This case series highlights a possible association between LVAD driveline infection and intracranial hemorrhage, and the need for further research to better understand the pathophysiology driving this association.

Streptococcus Oralis meningitis from right sphenoid Meningoencephalocele and cerebrospinal fluid leak.

BACKGROUND: Streptococcus oralis belongs to the Streptococcus mitis group and is part of the normal flora of the nasal and oropharynx (Koneman et al., The Gram-positive cocci part II: streptococci, enterococci and the 'Streptococcus-like' bacteria. Color atlas and textbook of diagnostic microbiology, 1997). Streptococcus oralis is implicated in meningitis in patients with decreased immune function or from surgical manipulation of the central nervous system. We report a unique case of meningitis by Streptococcus oralis in a 58-year-old patient with cerebral spinal fluid leak due to right sphenoid meningoencephalocele. CASE PRESENTATION: A 58-year-old female presented in the emergency department due to altered mental status, fevers, and nuchal rigidity. Blood cultures were positive for Streptococcus oralis. Magnetic resonance stereotactic imaging of head with intravenous gadolinium showed debris in lateral ventricle occipital horn and dural thickening/enhancement consistent with meningitis. There was also a right sphenoidal roof defect, and meningoencephalocele with cerebrospinal fluid leak as a result. The patient was treated with ceftriaxone and had endoscopic endonasal repair of defect. She had complete neurologic recovery 3 months later. CONCLUSIONS: Cerebrospinal fluid leak puts patients at increased risk for meningitis. Our case is unique in highlighting Streptococcus oralis as the organism implicated in meningitis due to cerebrospinal fluid leak.

MPI depletion enhances O-GlcNAcylation of p53 and suppresses the Warburg effect.

Rapid cellular proliferation in early development and cancer depends on glucose metabolism to fuel macromolecule biosynthesis. Metabolic enzymes are presumed regulators of this glycolysis-driven metabolic program, known as the Warburg effect; however, few have been identified. We uncover a previously unappreciated role for Mannose phosphate isomerase (MPI) as a metabolic enzyme required to maintain Warburg metabolism in zebrafish embryos and in both primary and malignant mammalian cells. The functional consequences of MPI loss are striking: glycolysis is blocked and cells die. These phenotypes are caused by induction of p53 and accumulation of the glycolytic intermediate fructose 6-phosphate, leading to engagement of the hexosamine biosynthetic pathway (HBP), increased O-GlcNAcylation, and p53 stabilization. Inhibiting the HBP through genetic and chemical methods reverses p53 stabilization and rescues the Mpi-deficient phenotype. This work provides mechanistic evidence by which MPI loss induces p53, and identifies MPI as a novel regulator of p53 and Warburg metabolism.