Assessment of tumor hypoxia and perfusion in recurrent glioblastoma following bevacizumab failure using MRI and 18F-FMISO PET.

Tumoral hypoxia correlates with worse outcomes in glioblastoma (GBM). While bevacizumab is routinely used to treat recurrent GBM, it may exacerbate hypoxia. Evofosfamide is a hypoxia-targeting prodrug being tested for recurrent GBM. To characterize resistance to bevacizumab and identify those with recurrent GBM who may benefit from evofosfamide, we ascertained MRI features and hypoxia in patients with GBM progression receiving both agents. Thirty-three patients with recurrent GBM refractory to bevacizumab were enrolled. Patients underwent MR and 18F-FMISO PET imaging at baseline and 28 days. Tumor volumes were determined, MRI and 18F-FMISO PET-derived parameters calculated, and Spearman correlations between parameters assessed. Progression-free survival decreased significantly with hypoxic volume [hazard ratio (HR) = 1.67, 95% confidence interval (CI) 1.14 to 2.46, P = 0.009] and increased significantly with time to the maximum value of the residue (Tmax) (HR = 0.54, 95% CI 0.34 to 0.88, P = 0.01). Overall survival decreased significantly with hypoxic volume (HR = 1.71, 95% CI 1.12 to 12.61, p = 0.01), standardized relative cerebral blood volume (srCBV) (HR = 1.61, 95% CI 1.09 to 2.38, p = 0.02), and increased significantly with Tmax (HR = 0.31, 95% CI 0.15 to 0.62, p < 0.001). Decreases in hypoxic volume correlated with longer overall and progression-free survival, and increases correlated with shorter overall and progression-free survival. Hypoxic volume and volume ratio were positively correlated (rs = 0.77, P < 0.0001), as were hypoxia volume and T1 enhancing tumor volume (rs = 0.75, P < 0.0001). Hypoxia is a key biomarker in patients with bevacizumab-refractory GBM. Hypoxia and srCBV were inversely correlated with patient outcomes. These radiographic features may be useful in evaluating treatment and guiding treatment considerations.

The Effect of Morbid Obesity on Subarachnoid Hemorrhage Prognosis in the United States.

OBJECTIVE: The association between obesity and nontraumatic subarachnoid hemorrhage (SAH) patient outcome is unclear. The aim of this study was to determine the impact of morbid obesity (body mass index ≥40 kg/m2) on nontraumatic SAH outcomes. METHODS: Using the Nationwide Inpatient Sample, we identified hospitalized, nontraumatic SAH patients who received their diagnoses from 2008 to 2013 and tested the effect of obesity on their mortality and clinical outcomes. Odds ratios were estimated with a mixed effects linear logistic model with adjustment for hospital clustering. All statistical testing was 2-sided, with a significance level of 5%. RESULTS: Out of 224,561 discharged patients with a diagnosis of nontraumatic SAH, 4714 (2.10%) were defined as morbidly obese. Patients with morbid obesity were younger (54.3 ± 0.44 vs. 59.5 ± 0.08 years; P < 0.001) and had longer length of stay (LOS) (13 ± 0.46 vs. 11.5 ± 0.06 days; P = 0.002). Morbid obesity was associated with significantly higher hospital costs (P < 0.001) and charges (P < 0.001). The risk of acute respiratory failure was higher in morbidly obese patients (odds ratio [OR] 1.49, 95% confidence interval [CI]: 1.3-1.71, P < 0.001). In a multivariate analysis of hospital mortality, obesity had a negative impact on mortality (OR 0.83, 95% CI: 0.74-0.92, P < 0.001). Overall, in-hospital mortality was associated with age, morbid obesity, LOS, clipping and coiling, and acute respiratory failure but not the symptomatic vasospasm. CONCLUSIONS: Morbid obesity is associated with increased LOS, hospital costs and charges and with acute respiratory failure. However, it is also associated with a decrease in hospital mortality.

Changes in total body bone mineral density following a common bone health plan with two versions of a unique bone health supplement: a comparative effectiveness research study.

BACKGROUND: The US Surgeon General's Report on Bone Health suggests America's bone-health is in jeopardy and issued a "call to action" to develop bone-health plans that: (1) improve nutrition, (2) increase health literacy and, (3) increase physical activity. This study is a response to this call to action. METHODS: After signing an informed consent, 158 adults agreed to follow an open-label bone-health plan for six months after taking a DXA test of bone density, a 43-chemistry blood test panel and a quality of life inventory (AlgaeCal 1). Two weeks after the last subject completed, a second group of 58 was enrolled and followed the identical plan, but with a different bone-health supplement (AlgaeCal 2). RESULTS: There were no significant differences between the two groups in baseline bone mineral density (BMD) or in variables related to BMD (age, sex, weight, percent body fat, fat mass, or fat-free mass). In both groups, no significant differences in BMD or related variables were found between volunteers and non-volunteers or between those who completed per protocol and those who were lost to attrition.Both groups experienced a significant positive mean annualized percent change (MAPC) in BMD compared to expectation [AlgaeCal 1: 1.15%, p = 0.001; AlgaeCal 2: 2.79%, p = 0.001]. Both groups experienced a positive MAPC compared to baseline, but only AlgaeCal 2 experienced a significant change [AlgaeCal 1: 0.48%, p = 0.14; AlgaeCal 2: 2.18%, p < 0.001]. The MAPC in AlgaeCal 2 was significantly greater than that in AlgaeCal 1 (p = 0.005). The MAPC contrast between compliant and partially compliant subjects was significant for both plans (p = 0.001 and p = 0.003 respectively). No clinically significant changes in a 43-panel blood chemistry test were found nor were there any changes in self-reported quality of life in either group. CONCLUSIONS: Following The Plan for six months with either version of the bone health supplement was associated with significant increases in BMD as compared to expected and, in AlgaeCal 2, the increase from baseline was significantly greater than the increase from baseline in AlgaeCal 1. Increased compliance was associated with greater increases in BMD in both groups. No adverse effects were reported in either group. TRIAL REGISTRATION: ClinicalTrials.gov NCT01114685.