A Neurotrophin Signaling Cascade Coordinates Sympathetic Neuron Development through Differential Control of TrkA Trafficking and Retrograde Signaling

AbstractA fundamental question in developmental biology is how a limited number of growth factors and their cognate receptors coordinate the formation of tissues and organs endowed with enormous morphological complexity. We report that the related neurotrophins NGF and NT-3, acting through a common receptor, TrkA, are required for sequential stages of sympathetic axon growth and, thus, innervation of target fields. Yet, while NGF supports TrkA internalization and retrograde signaling from distal axons to cell bodies to promote neuronal survival, NT-3 cannot. Interestingly, final target-derived NGF promotes expression of the p75 neurotrophin receptor, in turn causing a reduction in the sensitivity of axons to intermediate target-derived NT-3. We propose that a hierarchical neurotrophin signaling cascade coordinates sequential stages of sympathetic axon growth, innervation of targets, and survival in a manner dependent on the differential control of TrkA internalization, trafficking, and retrograde axonal signaling

Diagnosis and Treatment of Thoracic Outlet Syndrome

Thoracic outlet syndrome (TOS) is a spectrum of disorders resulting from the compression of the neurovascular structures within the thoracic outlet. The three main subtypes of TOS are defined by the anatomic structure affected by the extrinsic compression. In the most common subtype—neurogenic TOS—the brachial plexus is compressed and symptoms include pain, arm paresthesias, and sometimes weakness. Venous TOS is characterized by the compression of the subclavian vein and its resultant thrombosis. Arterial TOS is the least common and is distinguished by the compression of the subclavian artery and the development of aneurysms or stenoses with distal embolization. Treatment options include physical therapy and surgical first rib resection via the transaxillary or supraclavicular approach. The diagnosis of TOS and appropriate patient selection for intervention are challenging due to the frequent presence of vague symptoms in neurogenic TOS. Due to the relative rarity of this condition, different approaches to diagnosis and management exist, and optimum management strategies continue to evolve. The primary goals of this Special Issue on the “Diagnosis and Treatment of Thoracic Outlet Syndrome” are to describe new and established diagnostic and treatment modalities for TOS; to discuss approaches to complex clinical situations, such as reoperative treatment; and to review new research developments in the field of TOS

Choosing Surgery for Neurogenic TOS: The Roles of Physical Exam, Physical Therapy, and Imaging

Neurogenic thoracic outlet syndrome (nTOS) is characterized by arm and hand pain, paresthesias, and sometimes weakness resulting from compression of the brachial plexus within the thoracic outlet. While it is the most common subtype of TOS, nTOS can be difficult to diagnose. Furthermore, patient selection for surgical treatment can be challenging as symptoms may be vague and ambiguous, and diagnostic studies may be equivocal. Herein, we describe some approaches to aid in identifying patients who would be expected to benefit from surgical intervention for nTOS. We describe the role of physical examination, physical therapy, and imaging in the evaluation and diagnosis of nTOS

Effect of Patching on Reducing Restenosis in the Carotid Revascularization Endarterectomy Versus Stenting Trial

Background and purposeThe purpose is to determine whether patching during carotid endarterectomy (CEA) affects the perioperative and long-term risks of restenosis, stroke, death, and myocardial infarction as compared with primary closure.MethodsWe identified all patients who were randomized and underwent CEA in Carotid Revascularization Endarterectomy versus Stenting Trial. CEA patients who received a patch were compared with patients who underwent CEA with primary closure without a patch. We compared periprocedural and 4-year event rates, 2-year restenosis rates, and rates of reoperation between the 2 groups. We further analyzed results by surgeon specialty.ResultsThere were 1151 patients who underwent CEA (753 [65%] with patch and 329 [29%] with primary closure). We excluded 44 patients who underwent eversion CEA and 25 patients missing CEA data (5%). Patch use differed by surgeon specialty: 89% of vascular surgeons, 6% of neurosurgeons, and 76% of thoracic surgeons patched. Comparing patients who received a patch versus those who did not, there was a significant reduction in the 2-year risk of restenosis, and this persisted after adjustment by surgeon specialty (hazard ratio, 0.35; 95% confidence interval, 0.16-0.74; P=0.006). There were no significant differences in the rates of periprocedural stroke and death (hazard ratio, 1.58; 95% confidence interval, 0.33-7.58; P=0.57), in immediate reoperation (hazard ratio, 0.6; 95% confidence interval, 0.16-2.27; P=0.45), or in the 4-year risk of ipsilateral stroke (hazard ratio, 1.23; 95% confidence interval, 0.42-3.63; P=0.71).ConclusionsPatch closure in CEA is associated with reduction in restenosis although it is not associated with improved clinical outcomes. Thus, more widespread use of patching should be considered to improve long-term durability.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00004732

Effect of Patching on Reducing Restenosis in the Carotid Revascularization Endarterectomy Versus Stenting Trial

BACKGROUND AND PURPOSE: The purpose is to determine whether patching during carotid endarterectomy (CEA) affects the perioperative and long-term risks of restenosis, stroke, death, and MI as compared to primary closure. METHODS: We identified all patients who were randomized and underwent CEA in CREST. CEA patients who received a patch were compared to patients who underwent CEA with primary closure without a patch. We compared peri-procedural and 4-year event rates, 2-year restenosis rates, and rates of reoperation between the two groups. We further analyzed results by surgeon specialty. RESULTS: There were 1,151 patients who underwent CEA (753 (65%) with patch; 329 (29%) with primary closure). We excluded 44 patients who underwent eversion CEA and 25 patients missing CEA data (5%). Patch use differed by surgeon specialty: 89% of vascular surgeons, 6% of neurosurgeons, and 76% of thoracic surgeons patched. Comparing patients who received a patch versus those who did not, there was a significant reduction in the two-year risk of restenosis, and this persisted after adjustment by surgeon specialty (HR 0.35, 95% CI 0.16–0.74, P=.006). There were no significant differences in the rates of periprocedural stroke and death (HR 1.58, 95% CI 0.33–7.58, P=.57), in immediate re-operation (HR 0.6, 95% CI 0.16–2.27, P=.45), or in the four-year risk of ipsilateral stroke (HR 1.23, 95% CI 0.42–3.63, P=.71). CONCLUSIONS: Patch closure in CEA is associated with reduction in restenosis though it is not associated with improved clinical outcomes. Thus, more widespread use of patching should be considered to improve long-term durability. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/show/NCT0000473