Spinal cord ischemia rates and prophylactic spinal drainage in patients treated with fenestrated/branched endovascular repair for thoracoabdominal aneurysms.

OBJECTIVE: Spinal cord ischemia (SCI) is a devastating complication after thoracoabdominal aortic aneurysm (TAAA) repair. The benefit of prophylactic cerebrospinal fluid drainage (pCSFD) to prevent SCI is still under investigation. The aim of this study was to evaluate the SCI rate and the impact of pCSFD following complex endovascular repair (fenestrated or branched endovascular repair [F/BEVAR]) for type I to IV TAAA. METHODS: The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was followed. A single-center retrospective study was conducted, including all consecutive patients, managed for TAAA type I to IV using F/BEVAR, between January 1, 2018, and November 1, 2022, for degenerative and post-dissection aneurysms. Patients with juxta- or pararenal aneurysms were excluded, as well as cases managed urgently for aortic rupture or acute dissection. After 2020, pCSFD in type I to III TAAAs was abandoned and replaced by therapeutic CSFD (tCSFD), performed only in patients presenting SCI. The primary outcome was the perioperative SCI rate for the entire cohort and the role of pCSFD for type I to III TAAAs. RESULTS: In total, 198 patients were included (mean age, 71.1±3.4 years; 81.8% males), including 50.5% with type I to III TAAA. The primary technical success was 94.9%. The perioperative mortality was 2.5%. and the major adverse cardiovascular event (MACE) rate was 10.6%; 4.5% presented SCI of any type (2.5% paraplegia). When comparing the SCI group with the remaining cohort, patients with SCI presented higher MACE (66.7% vs 7.9%; P < .001) rate and longer intensive care unit stay (3.5 vs 1 day; P = .002). Following type I to III repair, similar SCI, paraplegia, and paraplegia with no recovery rates were reported in the pCSFD and tCSFD groups (7.3% vs 5.1%; P = .66; 4.8% vs 3.3%; P = .72; and 2% vs 0%; P = .37). CONCLUSIONS: The incidence of SCI after TAAA I to IV endovascular repair was low. SCI was associated with significantly increased MACE and intensive care unit stay. The prophylactic use of CSFD in type I to III TAAAs was not associated with lower SCI rates and may not be justified routinely.

Spinal drain-related complications after complex endovascular aortic repair using a prophylactic automated volume-directed drainage protocol.

OBJECTIVE: A common measure to lower the risk for spinal cord ischemia (SCI) during complex endovascular aortic repair (cEVAR) is prophylactic cerebrospinal fluid drainage (CSFD). This method has caused controversy because of drain-related complications. Spinal drains are usually pressure directed. The objective of this study was to evaluate the risk of CSFD-related complications and SCI within the context of an automated volume-directed drain protocol. METHODS: This is a retrospective, single-center study of all cEVARs with CSFD at a tertiary vascular center between January 2014 and December 2020. Demographics, complications, and spinal drain data were recorded. All drainages were volume based using an automatic drainage system (LiquoGuard7; Möller Medical GmbH). Spinal drain complications were categorized as disabling and nondisabling according to the modified Rankin scale. The primary end point was any CSFD-related complication. RESULTS: A total of 448 cEVAR patients were identified, of whom 147 (32.8%) had prophylactic CSFD. The mean age was 69 years (63% male). The most common pathology (61%) was thoracoabdominal aortic aneurysm, and the most common procedure was branched EVAR (55.1%). Eighteen (12.2%) patients developed a CSFD-related complication, whereof three (2%) were disabling. Nineteen (13%) patients developed SCI: 12 (8.4%) paraparetic, 5 (3.4%) paraplegic, and 2 (1.4%) paresthesias. Of these, 13 (68%) had full reversal of symptoms, whereas 6 patients (4%) had residual symptoms and were deemed disabling. Drain-related complications were more common in patients with SCI (31.6%) compared with those without (9.4%, P = .014). In the latter group, only two patients (1.6%) developed a disabling drain-related complication. CONCLUSIONS: Selective use of prophylactic, automated volume-directed CSFD in patients at high risk for SCI was associated with a high incidence of complications and should be used with caution. Among those developing SCI, reversal was achieved frequently with increased CSFD volume, but at the price of more bleeding complications.

Intranasal administration of polysulfide prevents neurodegeneration in spinal cord and rescues mice from delayed paraplegia after spinal cord ischemia.

BACKGROUND: Delayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Hydrogen sulfide (H2S) was reported to be protective in a mouse model of spinal cord ischemia and the beneficial effect of H2S has been attributed to polysulfides. The objective of this study was to investigate the effects of polysulfides on delayed paraplegia after spinal cord ischemia. METHODS AND RESULTS: Spinal cord ischemia was induced in male and female C57BL/6J mice by clamping the aortic arch and the left subclavian artery. Glutathione trisulfide (GSSSG), glutathione (GSH), glutathione disulfide (GSSG), or vehicle alone was administered intranasally at 0, 8, 23, and 32 h after surgery. All mice treated with vehicle alone developed paraplegia within 48 h after surgery. GSSSG, but not GSH or GSSG, prevented paraplegia in 8 of 11 male mice (73%) and 6 of 8 female mice (75%). Intranasal administration of 34S-labeled GSSSG rapidly increased 34S-labeled sulfane sulfur species in the lumbar spinal cord. In mice treated with intranasal GSSSG, there were increased sulfane sulfur levels, and decreased neurodegeneration, microglia activation, and caspase-3 activation in the lumbar spinal cord. In vitro studies using murine primary cortical neurons showed that GSSSG increased intracellular levels of sulfane sulfur. GSSSG, but not GSH or GSSG, dose-dependently improved cell viability after oxygen and glucose deprivation/reoxygenation (OGD/R). Pantethine trisulfide (PTN-SSS) also increased intracellular sulfane sulfur and improved cell viability after OGD/R. Intranasal administration of PTN-SSS, but not pantethine, prevented paraplegia in 6 of 9 male mice (66%). CONCLUSIONS: Intranasal administration of polysulfides rescued mice from delayed paraplegia after transient spinal cord ischemia. The neuroprotective effects of GSSSG were associated with increased levels of polysulfides and sulfane sulfur in the lumbar spinal cord. Targeted delivery of sulfane sulfur by polysulfides may prove to be a novel approach to the treatment of neurodegenerative diseases.

Preparing the spinal cord - priming or preconditioning? A systematic review of experimental studies.

Objectives. Paraplegia is devastating complication associated with thoracic and thoracoabdominal aortic aneurysm repair. Vast evidence has been gathered on pre-, peri- and postoperative protective adjuncts aiming to minimize spinal cord ischemia. This review focuses on the pretreatment phase of open surgical or endovascular aortic procedures and gathers the experimental data on the interventional preconditioning and priming methods that increase the spinal cord ischemic tolerance. Design. By the start of March 2021, a systematic review was performed in PubMed, Scopus and Web of Science core collection to identify the articles that reported (i) either an ischemic preconditioning, remote ischemic preconditioning or priming method prior to (ii) experimental spinal cord ischemia performed in endovascular or open surgical fashion mimicking either thoracic, abdominal or thoracoabdominal aortic aneurysm procedures. (iii) The outcomes were reported via neurological, motor-evoked potential, somatosensory-evoked potential, histopathological, immunohistochemical, physiological analysis, or in different combinations of these measurements. Results. The search yielded 7802 articles, and 57 articles were included in the systematic review. The articles were assessed by the evaluated species, the utilized pretreatment, the measured protective effects, and the suggested underlying mechanisms. Conclusions. The reviewed articles showed several possible mechanisms in ischemic and remote ischemic preconditioning for prevention of spinal cord ischemia. The main suggested method for priming was arteriogenetic stimulus. Future studies should confirm these hints of arteriogenetic stimulus with more precise quantification of the protective recruitment process.

Impact of Reconstructing Intercostal Artery on Spinal Cord Circulation During Open Surgery for Thoracoabdominal Aortic Aneurysm.

INTRODUCTION: We evaluated the outcomes of the selective intercostal artery reconstruction for preventing spinal cord injury during thoracoabdominal aortic aneurysm repair. METHODS: We retrospectively assessed 84 consecutive patients who underwent thoracoabdominal aortic aneurysm repairs between 2004 and 2016. The mean age of the patients was 57.3 years. We performed preoperative multidetector computed tomography in 74 patients (88.0%) to identify the Adamkiewicz artery. Spinal cord injury preventive measures included motor evoked potential monitoring, hypothermia induction, Adamkiewicz artery or other intercostal artery reconstruction, and cerebrospinal fluid drainage. RESULTS: The hospital death rate was 5.9%, and paraplegia occurred in four patients (4.7%). The Adamkiewicz artery or other intercostal arteries were reconstructed selectively in 46 patients (54.7%). Of these patients, 41 underwent postoperative multidetector computed tomography, which revealed occlusion of the reconstructed grafts in 23 patients (56.0%). There was no paraplegia in the patients who underwent reconstruction of the Adamkiewicz artery, which was patent on postoperative multidetector computed tomography. Univariate analysis showed no significant effect of various risk factors on the development of spinal cord injury. CONCLUSION: Outcome of open surgery for thoracoabdominal aortic aneurysm in our institution regarding spinal cord injury was satisfactory. The benefits of Adamkiewicz artery reconstruction remain inconclusive, and further larger studies are required to identify its validation for spinal cord protection in thoracoabdominal aortic aneurysm repair.

Multicenter Study to Evaluate Endovascular Repair of Extent I-III Thoracoabdominal Aneurysms Without Prophylactic Cerebrospinal Fluid Drainage.

OBJECTIVE: To assess outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) of Extent I-III thoracoabdominal aortic aneurysms (TAAAs) without prophylactic cerebrospinal fluid drainage (CSFD). BACKGROUND: Prophylactic CSFD has been routinely used during endovascular TAAA repair, but concerns about major drain-related complications have led to revising this paradigm. METHODS: We reviewed a multicenter cohort of 541 patients treated for Extent I-III TAAAs by FB-EVAR without prophylactic CSFD. Spinal cord injury (SCI) was graded as ambulatory (paraparesis) or nonambulatory (paraplegia). Endpoints were any SCI, permanent paraplegia, response to rescue treatment, major drain-related complications, mortality, and patient survival. RESULTS: There were 22 Extent I, 240 Extent II and 279 Extent III TAAAs. Thirty-day mortality was 3%. SCI occurred in 45 patients (8%), paraparesis occurring in 23 (4%) and paraplegia in 22 patients (4%). SCI was more common in patients with Extent I-II compared with Extent III TAAAs (12% vs. 5%, P =0.01). Rescue treatment included permissive hypertension in all patients, with CSFD in 22 (4%). Symptom improvement was noted in 73%. Twelve patients (2%) had permanent paraplegia. Two patients (0.4%) had major drain-related complications. Independent predictors for SCI by multivariate logistic regression were sustained perioperative hypotension [odds ratio (OR): 4.4, 95% confidence interval (95% CI): 1.7-11.1], patent collateral network (OR: 0.3, 95% CI: 0.1-0.6), and total length of aortic coverage (OR: 1.05, 95% CI: 1.01-1.10). Patient survival at 3 years was 72%±3%. CONCLUSION: FB-EVAR of Extent I-III TAAAs without CSFD has low mortality and low rates of permanent paraplegia (2%). SCI occurred in 8% of patients, and rescue treatment improved symptoms in 73% of them.

Preoperative spinal angiography decreases risk of spinal ischemia in pediatric posterior thoracic tumor resection.

PURPOSE: Resection of pediatric posterior thoracic tumors (PTTs) can be complicated by Artery of Adamkiewicz (AKA) injury. Post-op spinal ischemia occurs in approx. 3.2% of patients, typically due to iatrogenic vascular injury. Pre-op angiography (PSA) may help to avoid this complication. Herein, we aim to evaluate outcomes after initiation of routine PSA prior to PTT resection. METHODS: A single-institution retrospective review identified 25 children (< 18 years) treated for PTTs from 2009 to 2021. PTTs included: posterior mediastinum, paraspinal thorax and posterior chest wall tumors. PSA patients were compared to those without pre-operative angiography (NA). Demographics, perioperative and long-term outcomes and event-free survival (EFS) were assessed. RESULTS: Prior to 2012, eleven patients were treated without PSA. However, the last developed post-operative paraplegia secondary to spinal ischemia. Since this event, PSA has become routine for all PTTs (n = 14) identifying six AKAs and nine accessory spinal arteries. Resection was performed in ten (90.1%) NA patients and eight (57.1%) PSA patients. Based on PSA findings, resection was not offered to six patients and planned partial resection was performed in three patients. Five PSA patients required radiation therapy for local control vs two NA patients. There were no differences in recurrence or overall EFS. CONCLUSION: PSA aids in identifying patients with high-risk thoracic vascular anatomy and may prevent risk of post-operative paraplegia associated with PTT resection.

Paraplegia after thoracotomy: a single center experience with pediatric patients and a review of the literature.

AIM: Paraplegia is an infrequent although fearsome complication of anesthesia and surgical procedures, such as epidural anesthesia and thoracotomy. It may occur in both adults and children and a medullary lesion may be confirmed by magnetic resonance imaging, rather than computed tomography. The aim of this study is to describe the experience of two pediatric tertiary centers, contextualizing it with the other cases reported in literature. MATERIAL AND METHODS: We reported three pediatric cases of post-operative paraplegia in oncological patients, focusing on the potential causes and underling the possible strategies to prevent this complication. RESULTS: From our study, two principal features emerged: 1) Epidural anesthesia may expose children to a greater risk of spinal cord permanent damage due to the execution of the procedure under general anesthesia, which deprives the anesthesiologist of an important feedback about the position of the device; 2) In thoracotomy, the risk of paraplegia tends to increase along with the proximity to the costo-vertebral angle, especially if electrocautery or hemostatic materials are used. CONCLUSIONS: A prompt post-surgical neurological status routine assessment in pediatric patients undergoing epidural anesthesia or thoracotomy should be mandatory and, associated with the correct imaging study, may lead to the most appropriate therapeutic pathway and to a better prognosis. KEY WORDS: Anesthesia, Children, Epidural, Thoracotomy, Paraplegia.

Prospective Assessment of a Protocol Using Neuromonitoring, Early Limb Reperfusion, and Selective Temporary Aneurysm Sac Perfusion to Prevent Spinal Cord Injury During Fenestrated-branched Endovascular Aortic Repair.

OBJECTIVE: The aim of this study was to analyze the outcomes of a standardized protocol using routine CSFD, neuromonitoring, LL reperfusion, and selective TASP to prevent SCI during F-BEVAR. BACKGROUND: SCI is to be the most devastating complication for the patient, family, and surgeon, with impact on patient's quality of life and long-term prognosis. An optimal standardized protocol may be used to improve outcomes. METHODS: Patients enrolled in a prospective, nonrandomized single-center study between 2013 and 2018. A SCI prevention protocol was used for TAAAS or complex abdominal aneurysms with ≥5-cm supraceliac coverage including CSFD, neuromonitoring, LL reperfusion, and selective TASP. Endpoints included mortality and rates of SCI. RESULTS: SCI prevention protocol was used in 170 of 232 patients (73%) treated by F-BEVAR. Ninety-one patients (55%) had changes in neuromonitoring, which improved with maneuvers in all except for 9 patients (10%) who had TASP. There was one 30-day or in-hospital mortality (0.4%). Ten patients (4%) developed SCIs including in 1% (1/79) of patients with normal neuromonitoring and 10% (9/91) of those who had decline in neuromonitoring ( P = 0.02). Permanent paraplegia occurred in 2 patients (1%). Factors associated with SCI included total operating time (odds ratio 1.5, 95% confidence interval 1.1-2.2, P = 0.02) and persistent changes in neuromonitoring requiring TASP (odds ratio 15.7, 95% confidence interval 2.9-86.2, P = 0.001). CONCLUSION: This prospective nonrandomized study using a standardized strategy to prevent SCI was associated with low incidence of the SCI during F-BEVAR. Permanent paraplegia occurred in 1%.

Priming protects the spinal cord in an experimental aortic occlusion model.

OBJECTIVES: Paraplegia is a devastating complication in aortic aneurysm surgery. Modifying the spinal cord vasculature is a promising method in spinal cord protection. The aim of this study was to assess whether the spinal cord can be primed by occluding thoracic segmental arteries before simulated aneurysm repair in a porcine model. METHODS: Twelve piglets were randomly assigned to the priming group (6) and the control group (6). Eight uppermost thoracic segmental arteries were occluded at 5-minute intervals in the priming group before a 25-minute aortic crossclamp. In the control group, the aorta was crossclamped for 25 minutes. During the first 5 minutes, 8 segmental arteries were occluded. After the aortic crossclamping, piglets were observed under anesthesia for 5 hours and followed up 5 days postoperatively. Near-infrared spectroscopy, motor-evoked potentials, blood samples, neurology with the modified Tarlov score, and histopathology of the spinal cord were assessed. RESULTS: The median Tarlov score during the first postoperative day was higher in the priming group than in the control group (P = .001). At the end, 50% of the control animals had paraplegia compared with 0% of paraplegia in the priming group. The mean regional histopathologic score differed between the priming group and the control group (P = .02). The priming group had higher motor-evoked potentials during the operation at separate time points. The lactate levels were lower in the priming group compared with the control group (Pg = .001, Pg×t = .18). CONCLUSIONS: Acute priming protects the spinal cord from ischemic injury in an experimental aortic crossclamp model.

The short-term safety and effectiveness of a new distal perforating stent graft in Type B aortic dissection: a retrospective study.

BACKGROUND: Spinal artery ischemia (SCI) events can result from over coverage of the descending thoracic aorta with a coated stent during Thoracic Endovascular Aortic Repair (TEVAR). The aim of this study was to determine whether a new distal perforating stent could reduce the incidence of spinal cord ischemia while remodeling the true lumen. METHODS: TBAD patients treated with Talos stent in the vascular surgery Department of Yan 'an Hospital affiliated to Kunming Medical University between December 2017 and October 2019 were retrospectively analyzed to investigate the short-term safety and effectiveness of Talos stent. RESULTS: A total of the 20 patients, including 14 males and 6 females, with an average age of 52.65 ± 8.98 years (range 37-68 years), were included in the analysis. Stent-grafts were successfully implanted in all patients under local anesthesia, with a technical success rate of 100%. The average operation time was 50.75 ± 13.01 min. A total of 2 cases (10%) presented chest pain associated with intercostal artery ischemia that was relieved on the 3rd and 5th postoperative day, respectively. Postoperative mean follow-up was 16.15 ± 3.99 months. No paraplegia or other complications occurred. And stenting did not induce new tears. No migration, deformation, or fracture of the stents occurred. There was a significant difference in the remolding of the true lumen preoperatively and at 12 months postoperatively (P < 0.05). CONCLUSIONS: Talos stent has achieved satisfactory clinical treatment results in short term.

Transplantation of viable mitochondria attenuates neurologic injury after spinal cord ischemia.

OBJECTIVES: Spinal cord ischemia (SCI) is one of the major concerns of postoperative paraplegia during major vascular or aortic surgery. Since mitochondrial dysfunction develops at the early stage of SCI, this study tested the neuronal protective effect of transplantation of viable mitochondria to the ischemic cord in rats. METHODS: SCI was induced by crossclamping of thoracic aorta at T6 level for 25 minutes, followed by release of vascular clip to restore aortic blood flow in the anesthetized rats. Mitochondria (100 µg) were isolated from freshly harvested soleus muscle and delivered via the internal jugular vein before releasing of vascular clip. The motor function was assessed independently up to 7 days after reperfusion. Spinal cords were harvested and analyzed for molecular and histological changes. RESULTS: Whole-body in vivo images acquired by an in vivo imaging system confirmed the enhancement of MitoTracker fluorescence at the regions below crossclamping and in the ischemic cord. Compared with control vehicles, transplantation of mitochondria significantly improved the lower-limb locomotor function of rats subjected to cord ischemia up to 7 days after surgery. Mitochondrial transplantation suppressed the regional endoplasmic reticulum stress in the ischemic cord by attenuating CCAAT-enhancer-binding protein homologous protein expression and restoring binding immunoglobulin protein levels. In accordance, tissue levels of interleukin-6, tumor necrosis factor-α, and caspase-3 were attenuated in the mitochondrial transplanted group. Histologic examination also showed significant increase in numbers of Nissls bodies in the neurons at the ventral horn of ischemic cord following mitochondrial transplantation. CONCLUSIONS: Our study showed that transplantation of freshly isolated mitochondria during the early stage of spinal cord ischemia-reperfusion injury suppressed the oxidative stress in endoplasmic reticulum of the injured cord, thereby reducing neuroapoptosis and improving locomotor function of rats with SCI.

Protocolized Based Management of Cerebrospinal Fluid Drains in Thoracic Endovascular Aortic Aneurysm Repair Procedures.

BACKGROUND: Spinal cord ischemia (SCI) resulting in paraplegia is a devastating complication associated with thoracic endovascular aortic aneurysm repair (TEVAR) whose incidence has significantly declined over time. In this review, we present our experience with a multidisciplinary clinical protocol for cerebrospinal fluid (CSF) drain management in patients undergoing TEVAR. Furthermore, we aimed to characterize complications of CSF drain placement in a large, single center experience of patients who underwent TEVAR. METHODS: This retrospective review is of patients undergoing TEVAR with and without CSF drain placement between January 2014 and December 2019 at a single institution. Patient demographics, hospital course, and drain-related complications were analyzed to assess the incidence of CSF drain-related complications. RESULTS: A total of 235 patients were included in this study, of which 85 received CSF drains. Eighty patients (94.1%) were placed by anesthesiologists, while 5 (5.9%) were placed under fluoroscopic guidance by interventional neurosurgery. The most common level of placement was L3-L4 in 38 (44.7%) cases followed by L4-L5 in 36 (42.4%) cases. The mean duration of CSF drain was 1.9 ± 1.4 days. Complications due to CSF drainage occurred in 5 (5.9%) patients and included partial retainment of catheter, subdural edema, epidural hematoma, headache, and bleeding near the drain site. The overall 30-day mortality rate was 5.5% and did not differ between those who received a CSF drain and those who did not (P = 0.856). The overall incidence of SCI resulting in paraplegia was 1.7% in the studied patients. CONCLUSIONS: A protocol-based CSF drainage program for spinal cord protection involves a multifaceted approach in identification and selection of patients meeting criteria for prophylactic drain placement, direct closed loop communication, and perioperative management by an experienced team. Despite the inherent advantages of CSF drain placement, it is not without complications, thus risk and benefit need to be weighed in context of the procedure and the patient with close communication and team approach.

Radiation Disrupts the Protective Function of the Spinal Meninges in a Mouse Model of Tumor-induced Spinal Cord Compression.

BACKGROUND: Recent advances in multidisciplinary treatments for various cancers have extended the survival period of patients with spinal metastases. Radiotherapy has been widely used to treat spinal metastases; nevertheless, long-term survivors sometimes undergo more surgical intervention after radiotherapy because of local tumor relapse. Generally, intradural invasion of a spinal tumor seldom occurs because the dura mater serves as a tissue barrier against tumor infiltration. However, after radiation exposure, some spinal tumors invade the dura mater, resulting in leptomeningeal dissemination, intraoperative dural injury, or postoperative local recurrence. The mechanisms of how radiation might affect the dura have not been well-studied. QUESTIONS/PURPOSES: To investigate how radiation affects the spinal meninges, we asked: (1) What is the effect of irradiation on the meningeal barrier's ability to protect against carcinoma infiltration? (2) What is the effect of irradiation on the meningeal barrier's ability to protect against sarcoma infiltration? (3) What is the effect of irradiation on dural microstructure observed by scanning electron microscopy (SEM)? (4) What is the effect of irradiation on dural microstructure observed by transmission electron microscopy (TEM)? METHODS: Eighty-four 10-week-old female ddY mice were randomly divided into eight groups: mouse mammary tumor (MMT) implantation 6 weeks after 0-Gy irradiation (nonirradiation) (n = 11), MMT implantation 6 weeks after 20-Gy irradiation (n = 10), MMT implantation 12 weeks after nonirradiation (n = 10), MMT implantation 12 weeks after 20-Gy irradiation (n = 11), mouse osteosarcoma (LM8) implantation 6 weeks after nonirradiation (n = 11), LM8 implantation 6 weeks after 20-Gy irradiation (n = 11), LM8 implantation 12 weeks after nonirradiation (n = 10), and LM8 implantation 12 weeks after 20-Gy irradiation (n = 10); female mice were used for a mammary tumor metastasis model and ddY mice, a closed-colony mice with genetic diversity, were selected to represent interhuman diversity. Mice in each group underwent surgery to generate a tumor-induced spinal cord compression model at either 6 weeks or 12 weeks after irradiation to assess changes in the meningeal barrier's ability to protect against tumor infiltration. During surgery, the mice were implanted with MMT (representative of a carcinoma) or LM8 tumor. When the mice became paraplegic because of spinal cord compression by the growing implanted tumor, they were euthanized and evaluated histologically. Four mice died from anesthesia and 10 mice per group were euthanized (MMT-implanted groups: MMT implantation occurred 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]; LM8-implanted groups: LM8 implantation performed 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]); 80 mice were evaluated. The spines of the euthanized mice were harvested; hematoxylin and eosin staining and Masson's trichrome staining slides were prepared for histologic assessment of each specimen. In the histologic assessment, intradural invasion of the implanted tumor was graded in each group by three observers blinded to the type of tumor, presence of irradiation, and the timing of the surgery. Grade 0 was defined as no intradural invasion with intact dura mater, Grade 1 was defined as intradural invasion with linear dural continuity, and Grade 2 was defined as intradural invasion with disruption of the dural continuity. Additionally, we euthanized 12 mice for a microstructural analysis of dura mater changes by two observers blinded to the presence of irradiation. Six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were quantitatively analyzed for defects on the dural surface with SEM. The other six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were analyzed for layer structure of collagen fibers constituting dura mater by TEM. In the SEM assessment, the number and size of defects on the dural surface on images (200 µm × 300 µm) at low magnification (× 2680) were evaluated. A total of 12 images (two per mouse) were evaluated for this assessment. The days from surgery to paraplegia were compared between each of the tumor groups using the Kruskal-Wallis test. The scores of intradural tumor invasion grades and the number of defects on dural surface per SEM image were compared between irradiation group and nonirradiation group using the Mann-Whitney U test. Interobserver reliabilities of assessing intradural tumor invasion grades and the number of dural defects on the dural surface were analyzed using Fleiss'κ coefficient. P values < 0.05 were considered statistically significant. RESULTS: There was no difference in the median (range) time to paraplegia among the MMT implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (16 days [14 to 17] versus 14 days [12 to 18] versus 16 days [14 to 17] versus 14 days [12 to 15]; χ2 = 4.7; p = 0.19). There was also no difference in the intradural invasion score between the MMT implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (8 of 10 Grade 0 and 2 of 10 Grade 1 versus 10 of 10 Grade 0; p = 0.17). On the other hand, there was a higher intradural invasion score in the MMT implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (5 of 10 Grade 0, 3 of 10 Grade 1 and 2 of 10 Grade 2 versus 10 of 10 Grade 0; p = 0.02). Interobserver reliability of assessing intradural tumor invasion grades in the MMT-implanted group was 0.94. There was no difference in the median (range) time to paraplegia among in the LM8 implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (12 days [9 to 13] versus 10 days [8 to 13] versus 11 days [8 to 13] versus 9 days [6 to 12]; χ2 = 2.4; p = 0.50). There was also no difference in the intradural invasion score between the LM8 implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (7 of 10 Grade 0, 1 of 10 Grade 1 and 2 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.51), whereas there was a higher intradural invasion score in the LM8 implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (3 of 10 Grade 0, 3 of 10 Grade 1 and 4 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.04). Interobserver reliability of assessing intradural tumor invasion grades in the LM8-implanted group was 0.93. In the microstructural analysis of the dura mater using SEM, irradiated mice had small defects on the dural surface at low magnification and degeneration of collagen fibers at high magnification. The median (range) number of defects on the dural surface per image in the irradiated mice was larger than that of nonirradiated mice (2 [1 to 3] versus 0; difference of medians, 2/image; p = 0.002) and the median size of defects was 60 µm (30 to 80). Interobserver reliability of assessing number of defects on the dural surface was 1.00. TEM revealed that nonirradiated mice demonstrated well-organized, multilayer structures, while irradiated mice demonstrated irregularly layered structures at low magnification. At high magnification, well-ordered cross-sections of collagen fibers were observed in the nonirradiated mice. However, disordered alignment of collagen fibers was observed in irradiated mice. CONCLUSION: Intradural tumor invasion and disruptions of the dural microstructure were observed in the meninges of mice after irradiation, indicating radiation-induced disruption of the meningeal barrier. CLINICAL RELEVANCE: We conclude that in this form of delivery, radiation is associated with disruption of the dural meningeal barrier, indicating a need to consider methods to avoid or limit Postradiation tumor relapse and spinal cord compression when treating spinal metastases so that patients do not experience intradural tumor invasion. Surgeons should be aware of the potential for intradural tumor invasion when they perform post-irradiation spinal surgery to minimize the risks for intraoperative dural injury and spinal cord injury. Further research in patients with irradiated spinal metastases is necessary to confirm that the same findings are observed in humans and to seek irradiation methods that prevent or minimize the disruption of meningeal barrier function.

＜Editors' Choice＞ Which is superior, the frozen elephant trunk technique alone or the classical elephant trunk technique followed by second-stage thoracic endovascular aortic repair for extensive aortic arch repair?

Paraplegia is one of the most devastating complications during extensive aortic arch repair. We retrospectively analyzed our results by comparing primary repair using the frozen elephant trunk technique (FET) and the classical elephant trunk technique (CET) followed by second-stage thoracic endovascular aortic repair (TEVAR), which has been performed since 2009. Between March 1997 and September 2015, 91 patients (the mean age: 70 ± 8.6 years old, 73 men and 18 women) underwent total aortic arch replacement with either the FET (54 cases) or CET (37 cases). The CET was followed by second-stage TEVAR with a median duration of 36 days. The number of in-hospital deaths was 2 (3.7%) in FET and none in CET. The overall survival was 73% in FET and 83% in CET at 5 years with no significant difference (p=0.73). Aortic events occurred in 12 cases (22%) in FET and 3 (8%) in CET. The rate of freedom from aortic events was 77% in FET and 91% in CET at 5 years with no significant difference (p=0.45). Five neurologic events (9%) occurred after the FET, and 3 events (8%) occurred after the CET (p=0.85). No patients in the CET group experienced paraplegia, while the FET group showed a relatively high paraplegia rate (17%, p=0.014).The FET with primary repair for extensive aortic arch repair had an acceptable hospital mortality rate and aortic events but was associated with a high incidence of paraplegia. The CET followed by second-stage TEVAR achieved better early results with a low risk of paraplegia and may produce a favorable mid-term surgical outcome for extensive aortic arch repair.

Remote Ischemic Preconditioning in Spinal Cord Protection: A Surviving Porcine Study.

Surgical repair of thoracic aorta can compromise blood flow of the spinal cord. To mitigate spinal cord ischemia (SCI) additional protection methods are needed. In experimental studies remote ischemic preconditioning (RIPC) has proven to be an effective method of protecting organs from ischemia. The aim of the study was to assess efficacy of RIPC in spinal cord protection in a chronic porcine model. Sixteen piglets were assigned into the RIPC group (8) and the control group (8). RIPC was performed using blood pressure cuff in a 5-minute ischemia followed by a 5-minute reperfusion repeating cycles 4 times. The left subclavian artery and all segmental arteries above diaphragm were ligated at 5-minute intervals to accomplish SCI. The follow-up comprised a 4-hour intensive monitoring and a 7-day recovery phase. Blood samples were obtained, motor-evoked potentials and near-infrared spectroscopy (NIRS) of longitudinal back muscles were measured. Paraplegia was assessed every day postoperatively. Histopathological analysis of the spinal cord was performed after 7 days. NIRS values 4 hours after SCI were higher in the RIPC group, 45.5 (44.5-47.0), than in the control group, 41.5 (40.5-44.0) (P = 0.042). Nadir value of NIRS was 43.4 (39.3-46.0) in the RIPC group and 38.9 (38.-40.0) in the control group (P = 0.014). On the first postoperative day the RIPC group reached modified Tarlov score of 3 (2-3) vs 2 (1-2) in the control group (P = 0.024). RIPC hastens the recovery from SCI during the first postoperative day.

Prediction of the Vaccine-derived Poliovirus Outbreak Incidence: A Hybrid Machine Learning Approach.

Recently, significant attention has been devoted to vaccine-derived poliovirus (VDPV) surveillance due to its severe consequences. Prediction of the outbreak incidence of VDPF requires an accurate analysis of the alarming data. The overarching aim to this study is to develop a novel hybrid machine learning approach to identify the key parameters that dominate the outbreak incidence of VDPV. The proposed method is based on the integration of random vector functional link (RVFL) networks with a robust optimization algorithm called whale optimization algorithm (WOA). WOA is applied to improve the accuracy of the RVFL network by finding the suitable parameter configurations for the algorithm. The classification performance of the WOA-RVFL method is successfully validated using a number of datasets from the UCI machine learning repository. Thereafter, the method is implemented to track the VDPV outbreak incidences recently occurred in several provinces in Lao People's Democratic Republic. The results demonstrate the accuracy and efficiency of the WOA-RVFL algorithm in detecting the VDPV outbreak incidences, as well as its superior performance to the traditional RVFL method.

Arteriogenesis of the Spinal Cord-The Network Challenge.

Spinal cord ischemia (SCI) is a clinical complication following aortic repair that significantly impairs the quality and expectancy of life. Despite some strategies, like cerebrospinal fluid drainage, the occurrence of neurological symptoms, such as paraplegia and paraparesis, remains unpredictable. Beside the major blood supply through conduit arteries, a huge collateral network protects the central nervous system from ischemia-the paraspinous and the intraspinal compartment. The intraspinal arcades maintain perfusion pressure following a sudden inflow interruption, whereas the paraspinal system first needs to undergo arteriogenesis to ensure sufficient blood supply after an acute ischemic insult. The so-called steal phenomenon can even worsen the postoperative situation by causing the hypoperfusion of the spine when, shortly after thoracoabdominal aortic aneurysm (TAAA) surgery, muscles connected with the network divert blood and cause additional stress. Vessels are a conglomeration of different cell types involved in adapting to stress, like endothelial cells, smooth muscle cells, and pericytes. This adaption to stress is subdivided in three phases-initiation, growth, and the maturation phase. In fields of endovascular aortic aneurysm repair, pre-operative selective segmental artery occlusion may enable the development of a sufficient collateral network by stimulating collateral vessel growth, which, again, may prevent spinal cord ischemia. Among others, the major signaling pathways include the phosphoinositide 3 kinase (PI3K) pathway/the antiapoptotic kinase (AKT) pathway/the endothelial nitric oxide synthase (eNOS) pathway, the Erk1, the delta-like ligand (DII), the jagged (Jag)/NOTCH pathway, and the midkine regulatory cytokine signaling pathways.