Developmentally Arrested Basket/Stellate Cells in Postnatal Human Brain as Potential Tumor Cells of Origin for Cerebellar Hemangioblastoma in von Hippel-Lindau Patients.

von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary cancer disorder caused by a germline mutation in the VHL tumor suppressor gene. Loss of the wild-type allele results in VHL deficiency and the potential formation of cerebellar hemangioblastomas, which resemble embryonic hemangioblast proliferation and differentiation processes. Multiple, microscopic, VHL-deficient precursors, termed developmentally arrested structural elements (DASEs), consistently involve the cerebellar molecular layer in VHL patients, indicating the tumor site of origin. Unlike hemangioblastomas, however, cerebellar DASEs do not express brachyury, a mesodermal marker for hemangioblasts. In this study, neuronal progenitors occupying the molecular layer were investigated as tumor cells of origin. By immunohistochemistry, cerebellar DASEs and hemangioblastomas lacked immunoreactivity with antibody ZIC1 (Zic family member 1), a granule cell progenitor marker with concordance from oligonucleotide RNA expression array analyses. Rather, cerebellar DASEs and hemangioblastomas were immunoreactive with antibody PAX2 (paired box 2), a marker of basket/stellate cell progenitors. VHL cerebellar cortices also revealed PAX2-positive cells in Purkinje and molecular layers, resembling the histological and molecular development of basket/stellate cells in postnatal non-VHL mouse and human cerebella. These data suggest that VHL deficiency can result in the developmental arrest of basket/stellate cells in the human cerebellum and that these PAX2-positive, initiated cells await another insult or signal to form DASEs and eventually, tumors.

Update on Perioperative Pediatric Pulmonary Hypertension Management.

Pediatric pulmonary hypertension is a disease that has many etiologies and can present anytime during childhood. Its newly revised hemodynamic definition follows that of adult pulmonary hypertension: a mean pulmonary artery pressure >20 mmHg. However, the pediatric definition stipulates that the elevated pressure must be present after the age of three months. The definition encompasses many different etiologies, and diagnosis often involves a combination of noninvasive and invasive testing. Treatment often is extrapolated from adult studies or based on expert opinion. Moreover, although general anesthesia may be required for pediatric patients with pulmonary hypertension, it poses certain risks. A thoughtful, multidisciplinary approach is needed to deliver excellent perioperative care.

Factors Associated With Pediatric Emergency Airway Management by the Difficult Airway Response Team.

Background The goal of this study was to determine if difficult airway risk factors were similar in children cared for by the difficult airway response team (DART) and those cared for by the rapid response team (RRT). Methods In this retrospective database analysis of prospectively collected data, we analyzed patient demographics, comorbidities, history of difficult intubation, and intubation event details, including time and place of the emergency and devices used to successfully secure the airway. Results Within the 110-patient cohort, median age (IQR) was higher among DART patients than among RRT patients [8.5 years (0.9-14.6) versus 0.3 years (0.04-3.6); P < 0.001]. The odds of DART management were higher for children ages 1-2 years (aOR, 43.3; 95% CI: 2.73-684.3) and >5 years (aOR, 13.1; 95% CI: 1.85-93.4) than for those less than one-year-old. DART patients were more likely to have craniofacial abnormalities (aOR, 51.6; 95% CI: 2.50-1065.1), airway swelling (aOR, 240.1; 95% CI: 13.6-4237.2), or trauma (all DART managed). Among patients intubated by the DART, children with a history of difficult airway were more likely to have musculoskeletal (P = 0.04) and craniofacial abnormalities (P < 0.001), whereas children without a known history of difficult airway were more likely to have airway swelling (P = 0.04). Conclusion Specific clinical risk factors predict the need for emergency airway management by the DART in the pediatric hospital setting. The coordinated use of a DART to respond to difficult airway emergencies may limit attempts at endotracheal tube placement and mitigate morbidity.