Background The minimally invasive lateral transpsoas retroperitoneal approach to address lumbar stenosis offers advantages to traditional approaches, including sparing of the AP annulus and longitudinal ligament and less risk to the peritoneal contents and retroperitoneal vascular structures. Few studies have presented longitudinal measures of radiographic indirect decompression and relief of pain and restoration of function using the lateral approach to spine fusion. Question/purposes We determined (1) whether radiographic measures suggestive of decompression were achieved after surgery and maintained 1 year after surgery, (2) whether the intervention resulted in sustained improvements in patient-reported outcomes scores 1 year after surgery, and (3) the frequency of pseudarthrosis on CT scans at 1 year after surgery in patients with moderate or severe lumbar stenosis treated with the approach. Methods Between 2008 and 2012, 158 patients were surgically treated to alleviate symptoms associated with degenerative lumbar stenosis, of whom 60 (38%) were treated with lateral lumbar interbody fusion. Of these 60 patients, 36 (60%) received CT scans preoperatively and at 1-year postoperatively and were available for radiographic analysis. Of the 60 treated patients, 16 (27%) were lost to followup before 12 months, leaving the records of 44 patients available for review of patient-reported improvements in pain and return to function. Radiographic increases in disc height, foraminal area, and canal area were measured by one observer on CT scans postoperatively and at 1 year and compared to preoperative values. Patient-reported scores, including VAS pain score and Oswestry Disability Index (ODI), were collected preoperatively and at 3 and 12 months postoperatively.
These preliminary data suggest that DT imaging in patients with spinal cord tumors is capable of predicting the resectability of the lesion. A further prospective study is needed to confirm these results and any effect on patient outcome.
A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of vorinostat with bevacizumab and CPT-11 in recurrent glioblastoma. Vorinostat was combined with bevacizumab and CPT-11 and was escalated using a standard 3 + 3 design. Vorinostat was escalated up to 2 actively investigated doses of this compound or until the MTD was identified on the basis of DLTs. Correlative science involving proteomic profiling of serial patient plasma samples was performed. Nineteen patients were treated. The MTD of vorinostat was established at 400 mg on days 1-7 and 15-21 every 28 days when combined with bevacizumab and CPT-11. Common toxicities were fatigue and diarrhea. DLTs included fatigue, hypertension/hypotension, and central nervous system ischemia. Although the MTD was established, CPT-11 dose reductions were common early in therapy. High-dose vorinostat had an improved progression-free survival and overall survival when compared with low-dose vorinostat. Serum proteomic profiling identified IGFBP-5 and PDGF-AA as markers for improved PFS and recurrence, respectively. A MTD for the combination of vorinostat with bevacizumab and CPT-11 has been established, although it has poor long-term tolerability. With the increased toxicities associated with CPT-11 coupled with its unclear clinical significance, investigating the efficacy of vorinostat combined with bevacizumab alone may represent a more promising strategy to evaluate in the context of a phase II clinical trial.
Background and Purpose: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. Methods: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS. Results: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P =0.78), death (4.9% versus 8.5%, P =0.68), fatal strokes (2.4% versus 8.5%, P =0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P =0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. Conclusions: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. REGISTRATION: URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT02283294.
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