Malignant desmoplastic infantile astrocytoma? a case report and review of the literature.

Desmoplastic infantile astrocytoma (DIA) and ganglioglioma (DIG) are uncommon and generally benign intracranial tumors that typically affect infants. Unusual cases bearing aggressive clinical and malignant histological features have been described in the literature. We report a patient who was diagnosed at the age of 6 weeks with a DIA that relapsed 3 months postoperatively despite gross total resection (GTR). Pathologic examination revealed several mitoses, not only in the primitive neuroectodermal tumor (PNET)-like areas, but also unexpectedly in the predominating spindle cell component. The Ki67 proliferative index within the spindled component was 25%. The tumor continued to grow after initial relapse despite 2 courses of intensive chemotherapy (including vincristine, carboplatin, and temozolomide), but the recurrence was eventually controlled with oral etoposide. Currently, the patient is stable at 9 months after her initial diagnosis. This case illustrates that rare cases of DIA may display malignant histologic features in the typically benign and predominating spindle cell component and behave in an aggressive clinical manner despite GTR. As such, we recommend early and extended clinical follow-up of all DIA and DIG cases.

Intracranial pressure monitors in traumatic brain injury: a systematic review.

We conducted a systematic review to examine the relationship between intracranial pressure monitors (ICP) monitors and mortality in traumatic brain injury (TBI). We systematically searched for articles that met the following criteria: (1) adults patients, (2) TBI, (3) use of an ICP monitor, (4) point estimate for mortality with ICP monitoring (5) adjustment for potential confounders. Six observational studies were identified with 11,371 patients. There was marked between-study heterogeneity that precluded a pooled analysis. Patients with ICP monitors had different clinical characteristics and received more ICP targeted therapy in the ICU. Four studies found no significant relationship between ICP monitoring and survival, while the other two studies demonstrated conflicting results. Significant confounding by indication in observational studies limits the examination of isolated TBI interventions. More research should focus on interventions that affect TBI careplan systems. Further research is needed to identify which subset of severe TBI patients may benefit from ICP monitoring.

Modulation of neutrophil apoptosis by murine pulmonary microvascular endothelial cell inducible nitric oxide synthase.

Neutrophils contribute significantly to ALI (acute lung injury) through adhesion to pulmonary microvascular endothelial cells (PMEC), trans-PMEC migration and alveolar infiltration. Trans-PMEC migration delays expression of neutrophil apoptosis, which promotes intra-alveolar neutrophil survival and neutrophil mediated ALI. We assessed the role of neutrophil vs PMEC inducible nitric oxide (NO) synthase (iNOS) in modulating neutrophil apoptosis. Apoptosis of wild-type vs iNOS-/- neutrophils was quantified by microscopy and FACS annexin-V binding. In a murine model of ALI, neutrophils isolated by BAL(broncho-alveolar lavage) from iNOS-/- mice had increased expression of apoptosis after 24h culture ex vivo than wild-type neutrophils (15.2±3.3 vs 3.0±0.4%, mean±sd, p<0.01). Apoptosis rates of isolated bone marrow iNOS+/+ vs iNOS-/- neutrophils were similar under basal and LPS/IFN-γ stimulation, and following LPS/IFN-γ-stimulated trans-PMEC migration. Apoptosis of both iNOS+/+ and iNOS-/- neutrophils was inhibited by trans-PMEC migration only across iNOS+/+ PMEC (1.6±0.3 and 1.5±0.3%, respectively; p<0.05 for each vs non-migrated neutrophils) but not across iNOS-/- PMEC (4.3±1 and 3.1±0.6%, respectively). PMEC iNOS-dependent inhibition of neutrophil apoptosis was independent of changes in neutrophil caspase-3 activity. We conclude that PMEC iNOS, but not neutrophil iNOS, has an important inhibitory effect on neutrophil apoptosis during trans-PMEC neutrophil migration, which is independent of caspase-3 activity. Further studies will define the mechanism of PMEC iNOS-dependent inhibition of neutrophil apoptosis and assess the potential relevance of this phenomenon in human neutrophils and ALI.