Neurodevelopmental outcomes in infants treated with intravitreal bevacizumab versus laser.

OBJECTIVE: To compare neurodevelopmental and visual outcomes in preterm infants treated with intravitreal bevacizumab (IVB) to laser ablation at 18-24 months corrected age. STUDY DESIGN: A retrospective study was performed. The primary outcome was neurodevelopmental impairment (NDI). Secondary neurodevelopmental outcomes were significant NDI (sNDI), cerebral palsy, hearing loss, and composite scores of the Bayley Scales of Infant Development, Third edition. Visual outcomes included structural and refractive outcomes. Adjusted odds ratios (AOR) were calculated controlling for GA, sex, and ROP severity and confounding baseline characteristics using a cutoff of p < 0.20. RESULTS: Thirty-four (60 eyes) infants receiving IVB and 30 (51 eyes) laser were included. No significant differences were identified in NDI (AOR 1.77, 95% CI 0.46, 6.73) or sNDI (AOR 2.31, 95% CI 0.75, 7.14). There were no other differences in outcomes. CONCLUSIONS: Larger randomized trials are required to establish long-term efficacy and safety of IVB in preterm neonates.

Adenovirus-Associated Central Nervous System Disease in Children.

OBJECTIVE: To characterize the spectrum and salient clinical features of adenovirus-associated neurologic disease in immunocompetent children. STUDY DESIGN: Previously healthy children (aged 1 month-18 years) with central nervous system (CNS) disease associated with adenovirus infection were identified via the Encephalitis Registry (1996-2016) and Microbiology Database (2000-2016) at The Hospital for Sick Children, Toronto, and by systematic review of the literature. The data were pooled and analyzed to identify the spectrum of illness, clinical outcome, and risk factors for death or neurologic impairment. RESULTS: Neurologic complications associated with adenovirus infection in our institution included febrile seizures, encephalitis, acute disseminated encephalomyelitis, and aseptic meningitis. A total of 48 immunocompetent children with adenovirus-associated CNS disease were included in the pooled analysis-38 from the literature and 10 from our institution. In 85% of cases, the virus was detected in the respiratory or gastrointestinal tract, but not the cerebrospinal fluid. Eighteen of the 48 (38%) patients either died or suffered permanent neurologic sequelae. Predictors of adverse outcome included younger age, coagulopathy, the absence of meningismus, serotype 2 virus, and the presence of seizures. After multivariable adjustment, only seizures remained a significant risk factor. CONCLUSION: Adenovirus is a rare cause of CNS disease in immunocompetent children. Disease spectrum is variable, ranging from mild aspetic meningitis and fully reversible encephalopathy to severe, potentially fatal, acute necrotizing encephalopathy.

Inhaled corticosteroids in ventilated preterm neonates: a non-randomized dose-ranging study.

BACKGROUND: Inhaled corticosteroids (ICS) offer targeted treatment for bronchopulmonary dysplasia (BPD) with minimal systemic effects compared to systemic steroids. However, dosing of ICS in the management of infants at high-risk of developing BPD is not well established. The objective of this study was to determine an effective dose of ICS for the treatment of ventilator-dependent infants to facilitate extubation or reduce fractional inspired oxygen concentration. METHODS: Forty-one infants born at < 32 weeks gestational age (GA) or < 1250 g who were ventilator-dependent at 10-28 days postnatal age were included. A non-randomized dose-ranging trial was performed using aerosolized inhaled beclomethasone with hydrofluoralkane propellant (HFA-BDP). Four dosing groups (200, 400, 600 and 800 µg twice daily for 1 week) with 11, 11, 10 and 9 infants in each group, respectively, were studied. The primary outcome was therapeutic efficacy (successful extubation or reduction in FiO2 of > 75% from baseline) in ≥60% of infants in the group. Oxygen requirements, complications and long-term neurodevelopmental outcomes were also assessed. RESULTS: The median age at enrollment was 22 (10-28) postnatal days. The primary outcome, therapeutic efficacy as defined above, was not achieved in any group. However, there was a significant reduction in post-treatment FiO2 at a dose of 800 µg bid. No obvious trends were seen in long-term neurodevelopmental outcomes. CONCLUSIONS: Therapeutic efficacy was not achieved with all studied doses of ICS. A significant reduction in oxygen requirements was noted in ventilator-dependent preterm infants at 10-28 days of age when given 800 µg of HFA-BDP bid. Larger randomized trials of ICS are required to determine efficacy for the management of infants at high-risk for development of BPD. TRIAL REGISTRATION: This clinical trial was registered retrospectively on clinicaltrials.gov. The registration number is NCT03503994 .

Impact of flap reconstruction on perineal wound complications following ablative surgery for advanced and recurrent rectal cancers.

BACKGROUND: To determine the effect of flap reconstruction on perineal complications in locally advanced rectal cancers (LARC) and locally recurrent rectal cancers (LRRC). Prior studies have suggested that flap reconstruction may decrease wound complications after ablative surgery for rectal cancer but are limited by small sample sizes, heterogeneity of pathologies, and lack of comparison groups. METHODS: A retrospective cohort study (1999-2010) was performed on consecutive patients undergoing abdominoperineal resection (APR) or pelvic exenteration for locally advanced/locally recurrent rectal cancers. Differences in perineal complications between patients treated with and without perineal flap reconstruction were analyzed by using univariable, multivariable, and propensity score regression analyses. RESULTS: Flap reconstruction was performed in 52 of 177 patients (29 %). Patients receiving flap reconstruction had multiple risk factors for perineal morbidity, including longer operative times and more complex procedures. In our final multivariable analyses that were stratified by type of ablative procedure, we found a trend toward lower odds of perineal complications in patients receiving flaps (p = 0.065) compared with primary closure after pelvic exenteration. Although operative time and sacrectomy were significant determinants of perineal morbidity for pelvic exenteration patients, no significant predictors of perineal outcomes were identified for patients undergoing APR. CONCLUSIONS: This study suggests that flap reconstruction may provide some protective effect against perineal complications in patients undergoing pelvic exenteration, although this was not observed for APR. The most important determinants of perineal complications after pelvic exenteration were operative time and sacral resection, but no predictive factors for post-APR perineal outcomes were identified.

Genotypic and functional diversity of phenotypically defined primitive hematopoietic cells in patients with chronic myeloid leukemia.

Much progress has been made in the management of chronic-phase chronic myeloid leukemia (CP-CML), but there is a continuing imperative to develop curative treatments, predict patient responses to specific modalities, and anticipate disease relapse or progression. These needs underlie continuing interest in methods to detect and quantify the relevant leukemic cells in clinical samples with improved reliability and specificity. We report the results of comparing three methods to enumerate primitive CP-CML cells in the same samples: genotyping CD34(+)38(-) cells directly by fluorescence in situ hybridization, and measuring BCR-ABL1 transcript-genotyped colony-forming cell outputs in either 5-week long-term cultures (LTCs) containing non-engineered mouse fibroblasts or in 6-week LTCs containing mouse fibroblasts engineered to produce human Steel factor, granulocyte colony-stimulating factor, and IL-3. The results demonstrate that the first two methods significantly overestimate the prevalence of primitive CP-CML cells by comparison to the third. In additional studies, we found that CML-CD34(+) cells can repopulate the marrow and spleen of serially transplanted adult NOD/SCID-IL-2Rγ chain-null mice for more than 1 year with an almost exclusive myeloid differentiation in primary and secondary recipients and without evidence of disease progression. These findings underscore the importance of long-term functional in vitro and in vivo endpoints to identify and characterize CP-CML stem cells.