Intra-Arterial Therapy for Acute Stroke and the Effect of Technological Advances on Recanalization: Findings in a Community Hospital.

BACKGROUND: Recent randomized controlled studies have shown improvement in recanalization outcomes when physicians use the latest intra-arterial therapy devices in patients with acute, large-vessel, intracranial occlusions. The goal of this study was to explore how new procedures affected degree of and time to recanalization at a single center over the past 12 years as technology has improved. METHODS: Patients were included in the study if they had a large or medium intracranial vessel occlusion and had undergone intra-arterial therapy for acute stroke during the period 2002-2013. Therapies were categorized as intra-arterial thrombolysis with tissue plasminogen activator (IA tPA), mechanical thrombectomy using 1st-generation devices (Merci and Penumbra), or mechanical thrombectomy using 2nd-generation devices (stent-trievers). Recanalization was defined using a modified Thrombolysis in Cerebral Infarction (TICI) scale. RESULTS: Primary treatment was IA tPA in 24 (12.4%) patients, 1st-generation devices in 128 (66.0%) patients, and 2nd-generation devices in 42 (21.6%) patients. TICI 2b was achieved in 7 (29.2%) patients treated with IA tPA, in 79 (61.7%) patients treated with 1st-generation devices, and in 38 (90.5%) patients treated with 2nd-generation devices. Compared to patients treated with IA tPA, patients treated with 2nd-generation devices were more likely to reach TICI 2b recanalization (odds ratio, 11.66; 95% CI, 1.56-87.01), and they did so in shorter times. CONCLUSION: Technological advances over 12 years in endovascular stroke treatments significantly improved the chance of and reduced time to achieving TICI 2b recanalization in our community hospital. This shows the importance of adopting new technologies in a rapidly evolving field in order to provide the best-practice standard of care for the people of our region.

Breast cancer-induced bone remodeling, skeletal pain, and sprouting of sensory nerve fibers.

UNLABELLED: Breast cancer metastasis to bone is frequently accompanied by pain. What remains unclear is why this pain tends to become more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression, sensory nerve fibers that innervate the breast cancer bearing bone undergo a pathological sprouting and reorganization, which in other nonmalignant pathologies has been shown to generate and maintain chronic pain. Injection of human breast cancer cells (MDA-MB-231-BO) into the femoral intramedullary space of female athymic nude mice induces sprouting of calcitonin gene-related peptide (CGRP(+)) sensory nerve fibers. Nearly all CGRP(+) nerve fibers that undergo sprouting also coexpress tropomyosin receptor kinase A (TrkA(+)) and growth-associated protein-43 (GAP43(+)). This ectopic sprouting occurs in periosteal sensory nerve fibers that are in close proximity to breast cancer cells, tumor-associated stromal cells, and remodeled cortical bone. Therapeutic treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. The present data suggest that the breast cancer cells and tumor-associated stromal cells express and release NGF, which drives bone pain and the pathological reorganization of nearby CGRP(+)/TrkA(+)/GAP43(+) sensory nerve fibers. PERSPECTIVE: Therapies that block breast cancer pain by reducing the tumor-induced pathological sprouting and reorganization of sensory nerve fibers may provide insight into the evolving mechanisms that drive breast cancer pain and lead to more effective therapies for attenuating this chronic pain state.

Pathological sprouting of adult nociceptors in chronic prostate cancer-induced bone pain.

Pain frequently accompanies cancer. What remains unclear is why this pain frequently becomes more severe and difficult to control with disease progression. Here we test the hypothesis that with disease progression, sensory nerve fibers that innervate the tumor-bearing tissue undergo a pathological sprouting and reorganization, which in other nonmalignant pathologies has been shown to generate and maintain chronic pain. Injection of canine prostate cancer cells into mouse bone induces a remarkable sprouting of calcitonin gene-related peptide (CGRP(+)) and neurofilament 200 kDa (NF200(+)) sensory nerve fibers. Nearly all sensory nerve fibers that undergo sprouting also coexpress tropomyosin receptor kinase A (TrkA(+)). This ectopic sprouting occurs in sensory nerve fibers that are in close proximity to colonies of prostate cancer cells, tumor-associated stromal cells and newly formed woven bone, which together form sclerotic lesions that closely mirror the osteoblastic bone lesions induced by metastatic prostate tumors in humans. Preventive treatment with an antibody that sequesters nerve growth factor (NGF), administered when the pain and bone remodeling were first observed, blocks this ectopic sprouting and attenuates cancer pain. Interestingly, reverse transcription PCR analysis indicated that the prostate cancer cells themselves do not express detectable levels of mRNA coding for NGF. This suggests that the tumor-associated stromal cells express and release NGF, which drives the pathological reorganization of nearby TrkA(+) sensory nerve fibers. Therapies that prevent this reorganization of sensory nerve fibers may provide insight into the evolving mechanisms that drive cancer pain and lead to more effective control of this chronic pain state.

Mission Hospital's code stroke team: implications for an aging population.

OBJECTIVE: To evaluate the success of an acute stroke program designed to streamline the evaluation and treatment of acute ischemic stroke patients, with particular regard to the risk of symptomatic intracerebral hemorrhage and discharge disposition based on age in those patients treated with acute stroke intervention. METHODS: Retrospective review of patients at Mission Hospitals in Asheville, North Carolina from January 2006 to October 2007 with sudden neurological deficit identified within six hours of onset. Data were obtained from Mission Hospital's in-house spreadsheet database and the American Stroke Association's "Get With the Guidelines" (GWTG) database. Patients were evaluated by a code stroke protocol that included early involvement of stroke-treating neurologists. A chart review of all code stroke patients established the number of patients treated with acute intervention, disposition, and follow-up information. RESULTS: Over the 22-month study period, there were 568 code stroke evaluations. Of all code stroke patients, 27.1% (n=154) were treated with an acute intervention for stroke, usually intravenous thrombolysis. We analyzed treated patients on the basis of age, with the younger age group (YAG) being 79 years or younger and the older age group (OAG) being 80 years or older. Of the patients treated with acute intervention, 58 (37.7%) were OAG. Discharge disposition varied with age: 42.7% of YAG patients went home alone or with home health assistance, whereas only 20.7% of OAG patients went home alone or with home health assistance. The inhospital mortality rate was 10.4% for YAG patients and 22.4% for OAG patients. Symptomatic intracerebral hemorrhage was noted in one patient under age 80 and one patient over age 80. This is a symptomatic hemorrhage rate of 1.3%. LIMITATIONS: This was a retrospective, observational, post hoc analysis without a standardized follow-up program. CONCLUSIONS: Our Code Stroke Team, with an inpatient neurology service, increased the proportion of stroke patients treated with acute intervention benchmarking with other GWTG participating hospitals in this time period. Aggressive stroke treatment with thrombolytic therapy in patients over age 80 did not show an increased rate of symptomatic intracerebral hemorrhage.