Citations

Current delivery of chemotherapy drugs to osteosarcoma is limited by the difficulties in overcoming the solid tumor microenvironment and the cardiotoxicity of doxorubicin (DOX). In previous work we found that phase separation could generate microspheres with high porosity. In this study, we applied these phase-separated porous microspheres as carriers for long-term anticancer drug delivery. Novel poly(propylene fumarate)- co -poly( l -lactic acid) microspheres incorporating DOX were fabricated by thermally induced phase separation. Following embedding into oligo(poly[ethylene glycol] fumarate) hydrogel, the composite system showed prolonged and pH-responsive release of DOX. In vitro cytotoxicity study using osteosarcoma 143B cells showed substantial long-term cytotoxic effects for up to 30 days. As a result, the DOX drug delivery hydrogel developed in this work may have significant potential as a long-term and localized chemotherapy device that would be sensitive to the acidic microenvironment of osteosarcoma and other cancers. Impact Statement A composite hydrogel embedded with porous microspheres fabricated by phase separation methods was developed and showed excellent long-term anticancer drug delivery capability to cancer cells.

Objective To determine the efficacy of high‐volume anesthetic suboccipital nerve blocks (HVSON) for chronic cluster headache (CCH) and to define consistency of response over long‐term use. Background There are studies showing efficacy of greater occipital and suboccipital nerve block injections for CCH and also their possible use as a preventive treatment modality. There are scant data about the long‐term efficacy of repetitive greater occipital and suboccipital nerve injections in CCH. HVSON has not been studied for CH. Methods This was an open label, observational, case series study. Patients with CCH seen at a dedicated headache clinic over a 7‐year time period and injected on at least 2 separate occasions were used for analysis. All were deemed medicinal treatment refractory. HVSON consisted of 9 mL 1% lidocaine and 1 mL triamcinolone 40 mg/mL injected on the side of CH. Results Ten CCH patients were retrospectively studied. Range of mean average response to HVSON (all patients had complete pain freedom) was 1.5–31 weeks (longest: 44 weeks in 2 patients). Only one patient did not respond; 2 patients had 1.5–2 weeks of response; the remainder had at least 4 weeks of response. The mean average duration of effect was 10.3 weeks in the responders. Five patients were injected serially for 2–4 years (30x, 17x, 15x, 10x and 3x, respectively) with a consistent response of 6 weeks, 4 weeks, 12 weeks, 4 weeks, and 31 weeks, respectively, after each injection. Response duration was very reliable per individual patient. All 5 patients felt HVSON was effective as a preventive treatment. Smoking history did not appear to alter treatment response (8/10 were chronic current smokers and 7/8 responded to HVSON). The one patient who received the most injections developed avascular necrosis of the hip; the remainder of the subjects had no adverse events. Conclusion HVSON from this open label study appears to be effective in the preventive treatment of medicinal refractory CCH and shows consistent response over long‐term use with high rates of pain freedom.

OBJECTIVEFollowing traumatic brain injury (TBI), midline shift of the brain at the level of the septum pellucidum is often caused by unilateral space-occupying lesions and is associated with increased intracranial pressure and worsened morbidity and mortality. While outcome has been studied in this population, the recovery trajectory has not been reported in a large cohort of patients with TBI. The authors sought to utilize the Citicoline Brain Injury Treatment (COBRIT) trial to analyze patient recovery over time depending on degree of midline shift at presentation.METHODSPatient data from the COBRIT trial were stratified into 4 groups of midline shift, and outcome measures were analyzed at 30, 90, and 180 days postinjury. A recovery trajectory analysis was performed identifying patients with outcome measures at all 3 time points to analyze the degree of recovery based on midline shift at presentation.RESULTSThere were 892, 1169, and 895 patients with adequate outcome data at 30, 90, and 180 days, respectively. Rates of favorable outcome (Glasgow Outcome Scale–Extended [GOS-E] scores 4–8) at 6 months postinjury were 87% for patients with no midline shift, 79% for patients with 1–5 mm of shift, 64% for patients with 6–10 mm of shift, and 47% for patients with > 10 mm of shift. The mean improvement from unfavorable outcome (GOS-E scores 2 and 3) to favorable outcome (GOS-E scores 4–8) from 1 month to 6 months in all groups was 20% (range 4%–29%). The mean GOS-E score for patients in the 6- to 10-mm group crossed from unfavorable outcome (GOS-E scores 2 and 3) into favorable outcome (GOS-E scores 4–8) at 90 days, and the mean GOS-E of patients in the > 10-mm group nearly reached the threshold of favorable outcome by 180 days postinjury.CONCLUSIONSIn this secondary analysis of the Phase 3 COBRIT trial, TBI patients with less than 10 mm of midline shift on admission head CT had significantly improved functional outcomes through 180 days after injury compared with those with greater than 10 mm of midline shift. Of note, nearly 50% of patients with > 10 mm of midline shift achieved a favorable outcome (GOS-E score 4–8) by 6 months postinjury.

Background Navigable, large diameter aspiration catheters demonstrate markedly improved recanalization rates over smaller lumen devices in suction embolectomy. We evaluated the performance of a novel aspiration catheter system designed to maximize lumen size, and compare it to other commercially available aspiration catheters. Methods The 6F R4Q aspiration catheter system comprises a proximal pusher wire of 117 cm length connected to a distal catheter of 25 cm length. When placed through standard guide catheters and into the cerebral circulation, the proximal catheter makes a tight seal between its outer surface and the guide catheter’s inner surface. During aspiration, in vitro flow rates and tip suction force under gentle retraction were compared among 10 commercially available aspiration catheters and the R4Q system. Results The R4Q 6F, 5F, 4F, and 3F catheters achieved flow rates at least 21.9%, 24.7%, 61.9%, and 244.7% greater than the other catheters tested respectively and the R4Q 6F produced a 140.2% higher tip force than a catheter of similar size. Fluid flow rate in the R4Q 6F increased on retraction into the guide catheter, delivering a 58.2% increase from fully extended to fully retracted. Conclusion The R4Q design demonstrates a substantial increase in aspirated flow rate and suction force due to an increased effective diameter than standard tubular catheter designs tested. The prominent increase in the aspiration parameters measured in vitro supports the potential for improved clinical results during stroke thrombectomy procedures.