Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.

Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder.

Severity of ineffective esophageal motility is associated with utilization of skeletal muscle relaxant medications.

BACKGROUND: Ineffective esophageal motility (IEM) is the most common finding on high-resolution esophageal manometry (HREM). The underlying mechanisms for IEM remain to be fully elucidated. The aim of this study was to determine if utilization of skeletal muscle relaxants is associated with IEM, and with more severe subtypes of the disorder. METHODS: Patients with diagnosis of IEM were gender and age matched to patients with normal HREM. Demographic information, symptoms, endoscopic findings, medication usage and medical comorbidities were recorded. Patients with a diagnosis of IEM were divided into subgroups based on mean distal contractile integral (DCI) and percentage of ineffective swallows, and assessed for clinically significant differences among patients with varying severity of underlying IEM. KEY RESULTS: A total of 118 patients were included in each group. There were no significant clinical differences between the group of patients with IEM and the group of patients with normal manometry. Within the group of IEM patients, those with mean DCI < 250 mm Hg/s/cm were more likely to be prescribed skeletal muscle relaxants (27.8% vs 11.0%, P = .044), and those using skeletal muscle relaxants had a larger mean percentage of ineffective swallows (81.1% vs 71.5%, P = .029). There were no significant differences across mean DCI subgroups in usage of any other medication, or in any of the demographic variables or disease comorbidities examined in this study. CONCLUSIONS & INFERENCES: Use of skeletal muscle relaxants is associated with more severe IEM, which may suggest a causal association between this class of medications and weaker esophageal peristalsis.