Antiangiogenic therapy inhibits venous thrombus resolution.

OBJECTIVE: Venous thromboembolism is a common complication in patients with cancer, resulting in significant morbidity and mortality. Clinical studies suggest that the incidence of venous thromboembolic events increased after treatment of these patients with antiangiogenic agents. Thrombi resolve through a process of remodeling, involving the formation of microvascular channels within the thrombus. Our aim was to determine whether inhibiting angiogenesis affects venous thrombus resolution. APPROACH AND RESULTS: Thrombus was induced in the inferior vena cava of mice. These mice were treated with axitinib (50 mg/kg per day), 2-methoxyestradiol (2ME, 150 mg/kg per day), or vehicle control. Thrombus size, recanalization, neovascularization, inflammatory cell content, and collagen content were assessed after axitinib (days 3, 10, 17) and 2ME (day 10 only) treatment (n=6/group). Axitinib treatment resulted in reduced thrombus resolution (P<0.002) and vein recanalization (P<0.001) compared with vehicle-treated controls. This was associated with inhibition of organization as seen through reduced thrombus neovascularization (P<0.0001) and collagen (P<0.0001) content, as well as reduced macrophage accumulation in the thrombus (P<0.001). Treatment with a second antiangiogenic agent, 2ME, mirrored these findings, with a similar order of magnitude of effect of treatment over vehicle control in all of the parameters measured, with the exception of neutrophil content, which was significantly reduced after 2ME treatment but not affected by axitinib. CONCLUSIONS: Antiangiogenic therapy (using axitinib and 2ME) inhibits the resolution of venous thrombi, which could lead to persistent venous obstruction and the possibility of thrombus extension. This potential prolongation of venous occlusion by antiangiogenic agents should therefore be taken into consideration in trials of these agents and when managing the complications of venous thromboembolic events in patients with cancer.

Accuracy of clinical scoring tools for the diagnosis of pediatric obstructive sleep apnea.

OBJECTIVES: To assess the diagnostic test accuracy of questionnaire and clinical examination-based scoring tools in the diagnosis of pediatric obstructive sleep apnea (OSA). METHODS: A comprehensive literature search was performed to identify studies published from 1960 to 2018 that evaluated the accuracy of clinical scoring tools in the diagnosis of pediatric OSA. Studies that did not include attended polysomnography as a reference standard were excluded. The study populations were children under 18 years old without craniofacial abnormalities, congenital syndromes, or other complex medical conditions. Outcomes measures were diagnostic test accuracy (DTA) statistics including sensitivity, specificity, and area under the curve (AUC) from receiver operating characteristic curve analysis. RESULTS: Fifteen different scoring tools were identified. Authors chose different polysomnographic criteria to diagnose OSA. Four of the tools had undergone multiple DTA studies by different authors (OSA Score, Sleep-Related Breathing Disorder [SRBD] scale, Severity Score, and OSA-18). The Pediatric Sleep Questionnaire SRBD scale, which is widely used, has a sensitivity of 71% to 84% in included studies, but specificity as low as 13% and a low AUC of 0.57-0.69, indicating poor diagnostic accuracy. None of the 15 scoring tools performed well enough to be considered accurate diagnostic tests for pediatric OSA. CONCLUSIONS: A well-designed questionnaire can provide crucial information on the impact of sleep-disordered breathing on a child's physical and psychological health, which may not be adequately reflected in objective polysomnography outcomes measures. However, DTA results indicate that published clinical scoring tools do not accurately predict a diagnosis of pediatric OSA as defined by polysomnography outcome measures. Laryngoscope, 130:1034-1043, 2020.

Management and outcomes in children with sinogenic intracranial abscesses.

OBJECTIVE: To report our experience of sinogenic intracranial abscesses in the paediatric population and to guide medical and surgical management. METHODS: All children with sinogenic intracranial abscesses presenting to a large university teaching hospital over a five-year period were included in the study. Data on clinical presentation, radiological findings, microbiology, medical and surgical management and follow-up were recorded and analysed. RESULTS: We identified 27 children aged 12.9 ± 3.4 years of which 56% were male. Fourteen (52%) children had extradural abscesses, nine (33%) subdural abscesses and four (15%) parenchymal abscesses. Early sinus drainage procedures were performed on 24 (89%) patients, and the same number required neurosurgical drainage. Streptococcus milleri was isolated in 18 (67%) cases. An initial conservative neurosurgical approach failed in 50% of cases where trialled, and was associated with longer length of stay (p = 0.025). In comparison to extradural abscesses, subdural abscesses were more likely to present with neurological deficits (p < 0.001) and reduced consciousness (p = 0.018), and required multiple neurosurgical procedures (p < 0.001), longer stays (p = 0.017), and had greater morbidity at six months (p = 0.017). A third of children had significant morbidity at six months, which included cognitive and behavioural problems (25%), residual hemiparesis (19%) and expressive dysphasia (7%). There were no mortalities. CONCLUSION: Sinusitis complicated by intracranial abscess remains a contemporary problem. We demonstrate good outcomes with an early combined rhinological and neurosurgical approach. S. milleri is identified as the causative organism in the majority of cases, and empirical antimicrobial treatments should reflect this.