Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth, which leads to hydrocephalus, cerebral palsy, and mental retardation. There are no available therapies to cure IVH, and standard treatment is supportive care. Unrestricted somatic stem cells (USSCs) from human cord blood have reparative effects in animal models of brain and spinal cord injuries. USSCs were administered to premature rabbit pups with IVH and their effects on white matter integrity and neurobehavioral performance were evaluated. USSCs were injected either via intracerebroventricular (ICV) or via intravenous (IV) routes in 3 days premature (term 32d) rabbit pups, 24 hours after glycerol-induced IVH. The pups were sacrificed at postnatal days 3, 7, and 14 and effects were compared to glycerol-treated but unaffected or nontreated control. Using in vivo live bioluminescence imaging and immunohistochemical analysis, injected cells were found in the injured parenchyma on day 3 when using the IV route compared to ICV where cells were found adjacent to the ventricle wall forming aggregates; we did not observe any adverse events from either route of administration. The injected USSCs were functionally associated with attenuated microglial infiltration, less apoptotic cell death, fewer reactive astrocytes, and diminished levels of key inflammatory cytokines (TNFα and IL1ß). In addition, we observed better preservation of myelin fibers, increased myelin gene expression, and altered reactive astrocyte distribution in treated animals, and this was associated with improved locomotor function. Overall, our findings support the possibility that USSCs exert anti-inflammatory effects in the injured brain mitigating many detrimental consequences associated with IVH. Stem Cells Translational Medicine 2019;8:1157-1169.

Middle ear cholesteatoma treated with a mastoidectomy: a systematic review of the measures used.

OBJECTIVES: The inconsistent measures used to report outcomes after mastoidectomy to treat cholesteatoma make it impossible for clinicians to compare results and apply them appropriately to patient care. We sought to identify and assess the type and relative frequency of the reported measures. DATA SOURCES: PubMed, EMBASE, the Web of Science. REVIEW METHODS: We searched 3 independent databases for articles that reported outcomes of middle ear cholesteatoma treated with mastoidectomy. Articles were assessed for eligibility using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and data were extracted by 2 independent investigators. Observational studies and randomized controlled trials from the past 30 years were included. Articles with less than 50 subjects and nonsurgical studies were excluded. The measures used by each study were recorded, and the relative frequency of each measure was calculated. RESULTS: Forty-three of 380 articles met criteria. Time to follow up was inconsistent. Most articles reported on preoperative qualitative parameters (77%); however, few reported on the severity of disease (19%) or formally staged the disease (12%). Not all studies reported on the presence of recurrent or residual disease (88%) or the postoperative audiogram results (70%). Only 12% presented results as a Kaplan-Meier disease-free curve. Most studies reported on complications (70%). CONCLUSION: Reported measures were inconsistent among the studies, which makes comparisons between studies unreliable. Standardization will optimize future reporting and will allow for the establishment of best practices.