Background: Elevated intracranial pressure (ICP) is frequent after traumatic brain injury (TBI) and may cause abnormal pupillary reactivity, which in turn is associated with a worse prognosis. Using automated infrared pupillometry, we examined the relationship between the Neurological Pupil index (NPi) and invasive ICP in patients with severe TBI. Methods: This was an observational cohort of consecutive subjects with severe TBI (Glasgow Coma Scale [GCS] < 9 with abnormal lesions on head CT) who underwent parenchymal ICP monitoring and repeated NPi assessment with the NPi-200® pupillometer. We examined NPi trends over time (four consecutive measurements over intervals of 6 h) prior to sustained elevated ICP > 20 mmHg. We further analyzed the relationship of cumulative abnormal NPi burden (%NPi values < 3 during total ICP monitoring time) with intracranial hypertension (ICHT)-categorized as refractory (ICHT-r; requiring surgical decompression) vs. non-refractory (ICHT-nr; responsive to medical therapy)-and with the 6-month Glasgow Outcome Score (GOS). Results: A total of 54 patients were studied (mean age 54 ± 21 years, 74% with focal injuries on CT), of whom 32 (59%) had ICHT. Among subjects with ICHT, episodes of sustained elevated ICP (n = 43, 172 matched ICP-NPi samples; baseline ICP [T − 6 h ] 14 ± 5 mmHg vs. ICPmax [T 0 h ] 30 ± 9 mmHg) were associated with a concomitant decrease of the NPi (baseline 4.2 ± 0.5 vs. 2.8 ± 1.6, p < 0.0001 ANOVA for repeated measures). Abnormal NPi values were more frequent in patients with ICHT-r (n = 17; 38 [3-96]% of monitored time vs. 1 [0-9]% in patients with ICHT-nr [n = 15] and 0.5 [0-10]% in those without ICHT [n = 22]; p = 0.007) and were associated with an unfavorable 6-month outcome (15 [1-80]% in GOS 1-3 vs. 0 [0-7]% in GOS 4-5 patients; p = 0.002). Conclusions: In a selected cohort of severe TBI patients with abnormal head CT lesions and predominantly focal cerebral injury, elevated ICP episodes correlated with a concomitant decrease of NPi. Sustained abnormal NPi was in turn associated with a more complicated ICP course and worse outcome.

Meropenem, a carbapenem broad-spectrum antibiotic, is regularly used in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). Its disposition was studied over one dosage interval in 15 patients under CVVHDF on a steady regimen of 500 or 1000 mg every 8 to 12 hours. Meropenem levels were measured in plasma and filtrate-dialysate by high-performance liquid chromatography (HPLC) with UV detection. The mean CVVHDF flow rates were 7.1 +/- 0.9 L/h for blood (mean +/- SD), 0.5 +/- 0.3 L/h for predilution solution, 1.2 +/- 0.3 L/h for countercurrent dialysate, and 1.8 +/- 0.5 L/h for the total filtrate-dialysate. The pharmacokinetic analysis was based both on a noncompartmental approach and on a four-compartment modeling. The mean (coefficient of variation [CV]) total body clearance, volume of distribution at steady state, and mean residence time were, respectively, 5.0 L/h (46%), 14.3 L (29%), and 4.8 h (36%). The hemodiafiltration clearances calculated from plasma data alone and plasma with filtrate-dialysate data were 1.2 L/h (26%) and 1.6 L/h (39%), respectively. The compartmental model was used to optimize the therapeutic schedule of meropenem, considering reference minimal inhibitory concentration (MIC) of sensitive strains (4 mg/L). The results indicate that two different therapeutic schedules of meropenem are equally applicable to patients receiving CVVHD: either 750 mg tid or 1500 bid.

Reduced quantitative PLR correlates with postanoxic brain injury and, when compared to standard multimodal assessment, is highly accurate in predicting long-term prognosis after CA. This is the first prognostication study to show the value of automated pupillometry using a blinded approach to minimize self-fulfilling prophecy. Ann Neurol 2017;81:804-810.

Bisphosphonates seem to be effective as antiresorptive agents in the prevention and treatment of osteoporosis. However, the optimal dose and route of administration as well as the specific effects on cortical or trabecular bone have not been clarified. To compare pamidronate (APD) with fluoride (F) in the therapy of postmenopausal osteoporosis, 32 osteoporotic women were treated for 2 years either with APD (30 mg as a single intravenous infusion over 1 h every 3 months, n = 16, mean age 65 years) or with fluoride orally (20-30 mg F/day, n = 16, mean age 67 years) in an open study. Both groups received 1 g calcium and 1000 U vitamin D per day, but no estrogens or other drugs acting on bone. Both groups showed the same initial mean number of fractures per patient (2.8 and 2.7). Bone densitometry was performed every 6 months at three sites: lumbar spine and hip with dual-energy X-ray absorptiometry (BMD), distal forearm with single photon absorptiometry and lumbar spine with quantitative computed tomography. Biochemical assessment was performed in blood and urine every 3 months. Lumbar BMD (g/cm2, mean +/- SEM) increased from 0.632 (+/- 0.030) at time 0 to 0.696 (+/- 0.028) at 24 months in the APD group (p < 0.001), and from 0.684 (+/- 0.025) to 0.769 (+/- 0.028) in the fluoride group (p < 0.001). Femoral neck BMD increased significantly from 0.558 (+/- 0.025) to 0.585 (+/- 0.025) (p < 0.01) in the APD group, whereas it did not change in the fluoride group.(ABSTRACT TRUNCATED AT 250 WORDS)