Tongue surgeries for pediatric obstructive sleep apnea: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the international literature for studies reporting outcomes for obstructive sleep apnea (OSA) in children undergoing isolated tongue surgeries. METHODS: Two authors searched from inception through November 14, 2016 in four databases including PubMed/MEDLINE. RESULTS: 351 studies were screened. Eleven studies (116 children) met criteria. Most children were syndromic and had craniofacial disorders, co-morbidities, or other serious medical issues. Surgeries included base-of-tongue (BOT) reduction (n = 114), tongue suspension (n = 1), and hypoglossal nerve stimulation (n = 1). The pre- and post-BOT reduction surgeries decreased apnea-hypopnea index (AHI) from a mean (M) and standard deviation (SD) of 16.9 ± 12.2/h to 8.7 ± 10.6/h (48.5% reduction) in 114 patients. Random effects modeling (109 patients) demonstrated a standardized mean difference for AHI of -0.78 (large magnitude of effect) [95% CI -1.06, -0.51], p value <0.00001. For BOT surgery in 53 non-syndromic children, the AHI decreased 59.2% from 14.0 ± 11.4 to 5.7 ± 6.7/h, while in 55 syndromic children, the AHI decreased 40.0% from 20.5 ± 19.1 to 12.3 ± 18.2/h. BOT reduction improved lowest oxygen saturation from M ± SD of 84.7 ± 7.4-87.9 ± 6.5% in 113 patients. Hypoglossal nerve stimulation and tongue-base suspension are limited to case reports. CONCLUSIONS: Most children undergoing tongue surgeries in the literature were syndromic and had craniofacial disorders, co-morbidities, or other serious medical issues. Children with a body mass index <25 kg/m2 and non-syndromic children have had the most improvement in AHI. The specific type of surgery must be tailored to the patient. Patients with co-morbidities should undergo treatment in centers that are equipped to provide appropriate perioperative care.

Loss of CCR2 expressing non-classical monocytes are associated with cognitive impairment in antiretroviral therapy-naïve HIV-infected Thais.

HIV DNA in monocytes has been linked to HIV-associated neurocognitive disorders (HAND), however, characterization of monocyte subsets associated with HAND remains unclear. We completed a prospective study of antiretroviral therapy-naïve, HIV-infected Thais, with varying degrees of cognitive impairment, compared to HIV-uninfected controls. Monocyte subsets' CCR2, CCR5 and CD163 expression were profiled and inflammatory markers in plasma and cerebrospinal fluid (CSF), measured. Lower numbers of CCR2(+)non-classical monocytes were associated with worse neuropsychological test performance (r=0.43, p=0.024). CCR2(+)non-classical monocyte count inversely correlated with CSF neopterin (r=-0.43, p=0.035) and plasma TNF-α levels (r=-0.40, p=0.041). These data benchmark CCR2(+)non-classical monocytes as an independent index of cognitive impairment.

Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND).

HIV-associated neurocognitive disorders (HAND) continues to be prevalent (30-50%) despite plasma HIV-RNA suppression with combination antiretroviral therapy (cART). There is no proven therapy for individuals on suppressive cART with HAND. We have shown that the degree of HIV reservoir burden (HIV DNA) in monocytes appear to be linked to cognitive outcomes. HIV infection of monocytes may therefore be critical in the pathogenesis of HAND. A single arm, open-labeled trial was conducted to examine the effect of maraviroc (MVC) intensification on monocyte inflammation and neuropsychological (NP) performance in 15 HIV subjects on stable 6-month cART with undetectable plasma HIV RNA (<48 copies/ml) and detectable monocyte HIV DNA (>10 copies/10(6) cells). MVC was added to their existing cART regimen for 24 weeks. Post-intensification change in monocytes was assessed using multiparametric flow cytometry, monocyte HIV DNA content by PCR, soluble CD163 (sCD163) by an ELISA, and NP performance over 24 weeks. In 12 evaluable subjects, MVC intensification resulted in a decreased proportion of circulating intermediate (median; 3.06% (1.93, 6.45) to 1.05% (0.77, 2.26)) and nonclassical (5.2% (3.8, 7.9) to 3.2% (1.8, 4.8)) CD16-expressing monocytes, a reduction in monocyte HIV DNA content to zero log10 copies/10(6) cells and in levels of sCD163 of 43% by 24 weeks. This was associated with significant improvement in NP performance among six subjects who entered the study with evidence of mild to moderate cognitive impairment. The results of this study suggest that antiretroviral therapy with potency against monocytes may have efficacy against HAND.