Cerebral arteriovenous malformations (AVMs) are leading causes of lesional hemorrhagic stroke in both the pediatric and young adult population, with sporadic AVMs accounting for the majority of ...cases. Recent evidence has identified somatic mosaicism in key proximal components of the RAS-MAPK signaling cascade within endothelial cells collected from human sporadic cerebral AVMs, with early preclinical models supporting a potential causal role for these mutations in the pathogenesis of these malformations. Germline mutations that predispose to deregulation of the RAS-MAPK signaling axis have also been identified in hereditary vascular malformation syndromes, highlighting the key role of this signaling axis in global AVM development. Herein, we review the most recent genomic and preclinical evidence implicating somatic mosaicism in the RAS-MAPK signaling pathway in the pathogenesis of sporadic cerebral AVMs. Also, we review evidence for RAS-MAPK dysregulation in hereditary vascular malformation syndromes and present a hypothesis suggesting that this pathway is central for the development of both sporadic and syndrome-associated AVMs. Finally, we examine the clinical implications of these recent discoveries and highlight potential therapeutic targets within this signaling pathway.
•The authors present a decade-long analysis of the short-term outcomes in surgically managed metastatic breast cancer to the spine stratified by procedure performed.•Notable surgical trends include ...an increase in the use of spinal stabilization procedures with a concomitant decrease in the use of vertebral augmentation procedures.•A weighted logistic regression model is employed for prediction of short-term outcomes based on patient demographics, comorbidities and procedure type.•Higher risk of complications was associated with more invasive procedures; this increased risk abated with increased pre-operative comorbidities.
Management of metastatic breast cancer to the spine (MBCS) incorporates a multimodal approach. Improvement in screening and nonsurgical therapies may alter the trends in surgical management of MBCS. The objective of this study is to assess trends in surgical management of MBCS and short-term outcomes based on the National Inpatient Sample (NIS) database. The NIS database was queried for patients with MBCS who underwent surgery from 2005 to 2014. The weighted frequencies of spinal decompression alone, spinal stabilization +/- decompression, and vertebral augmentation were calculated. Multivariate analysis was performed to analyze the effect of patient characteristics on outcomes stratified by procedure. The most common procedure performed was vertebral augmentation (11,114, 53.4%), followed by stabilization +/− decompression (6,906, 33.2%) and then decompression alone (3,312, 13.4%). The total population-adjusted rate of surgical management for MBCS remained stable, while the rate of spinal stabilization increased (P < 0.001) and vertebral augmentation decreased (p < 0.003). The risk of complication increased with spinal stabilization and decompression compared to vertebral augmentation procedures in those with fewer comorbidities. This relative increase in risk abated in patients with higher numbers of pre-operative comorbidities. Any single complication was associated with increases in length of stay, cost, and mortality. The rate of in-hospital interventions remained stable over the study period. Stratified by procedure, the rate of stabilizations increased with a concomitant decrease in vertebral augmentations, which suggests that patients who require hospitalization for MBCS are becoming more likely to represent advanced cases that are not amenable to palliative vertebral augmentation procedures.
•A database analysis of surgical outcomes for metastatic lung cancer to the spine.•Trends include increased stabilization surgeries with stable overall procedure rate.•Similar complication rates ...among procedures in patients with little comorbidity.•Increased complication rates among procedures in patients with higher comorbidities.•A single complication was associated with increases in mortality and costs.
Optimal management of metastatic lung cancer to the spine (MLCS) incorporates a multidisciplinary approach. With improvements in lung cancer screening andnonsurgical treatment, the role for surgerymay be affected. The objective of this study is to assess trends in the surgical management of MLCS using the National Inpatient Sample (NIS) database. The NIS was queried for patients with MLCS who underwent surgery from 2005 to 2014. The frequencies of spinal decompression alone, spinal stabilization with or without (+/-) decompression, and vertebral augmentation were calculated. Statistical analysis was performed to analyze the effect of patient characteristics on outcomes. The most common procedure performed was vertebral augmentation (10719, 44.3%), followed by spinal stabilization +/− decompression (8634, 35.7%) and then decompression alone (4824, 20.0%). The total number of surgeries remained stable, while the rate of spinal stabilizations increased throughout the study period (p < 0.001). Invasive procedures such as stabilization and decompression were associated with greater costs, length of stay,complications and mortality. Increasingcomorbidity was associated with increased odds of complication, especially in patients undergoing more invasive procedures. In patients with lowpre-operative comorbidity, the type of procedure did not influence the odds of complication. Graded increases in length of stay, cost and mortality were seen with increasing complication rate.The rate of spinal stabilizations increased, which may be due to either increased early detection of disease facilitating use of outpatient vertebral augmentation procedures and/or the recognition that surgical decompression and stabilization are necessary for optimal outcome in the setting of MLCS with neurological deficit.
The authors report the case of a 30-year-old female patient with suspected Cushing's disease with an anatomical variation of hypoplastic inferior petrosal sinuses and nearly exclusive anterior ...drainage from the cavernous sinus, who underwent external jugular venous blood sampling with successful disease confirmation and microadenoma localization. The patient presented with signs and symptoms consistent with Cushing's syndrome, but with discordant preliminary diagnostic testing. She underwent attempted bilateral inferior petrosal sinus sampling; however, she had hypoplastic inferior petrosal sinuses bilaterally and predominantly anterior drainage from the cavernous sinus into the external jugular circulation. Given this finding, the decision was made to proceed with external jugular venous access and sampling in addition to internal jugular venous sampling. A positive adrenocorticotropic hormone (ACTH) response to corticotropin-releasing factor was obtained in the right external jugular vein alone, suggesting a right-sided pituitary microadenoma as the cause of her Cushing's disease. The patient subsequently underwent a transsphenoidal hypophysectomy that confirmed the presence of a right-sided ACTH-secreting microadenoma, which was successfully resected. She was hypocortisolemic on discharge and has had no signs of recurrence or relapse at 6 months postoperation.
Background:
The postoperative length of stay (LOS) is an important prognostic indicator for patients undergoing instrumented spinal fusion surgery. Increased LOS can be associated with higher ...infection rates, higher incidence of venous thromboembolisms, and a greater frequency of hospital-acquired delirium. The day of surgery and early postoperative mobilization following single-level posterior thoracolumbar stabilizations may impact the LOS. In this study, we evaluated the effects of weekday (Monday–Thursday) versus weekend (Friday–Sunday) surgery and postoperative rehabilitation services on LOS following primarily transforaminal lumbar interbody fusion (TLIF) for degenerative spondylolisthesis (DS).
Methods:
In this single-institution retrospective chart review, we identified 198 adults who received a one-level thoracolumbar instrumented fusion through a posterior only approach (2017–2019). The majority of these patients underwent TLIF for DS. A zero truncated negative binomial model was used for predictors of the primary outcome of LOS (weekday of surgery, duration of operation, first or repeat surgery, and physical therapy/ occupational therapy PT/OT evaluation). Covariates were sex, age, and body mass index.
Results:
We found that operative duration, repeat surgery, and in-hospital PT/OT all significantly increased the LOS (
P
< 0.05). Furthermore, those undergoing weekday surgery (Monday–Thursday) had 1.29 times longer LOS than those on the weekend (Friday–Sunday), but this did not reach statistical significance (
P
= 0.09).
Conclusion:
In our patient sample, duration, repeat surgery, and in-hospital PT/OT increased the LOS following primarily TLIF for DS. The increased LOS in these cases is likely due to higher overall disease burden and case complexity. In addition, those patients with a greater likelihood of extended recovery and ongoing neurologic deficits are more likely to have PT/OT evaluations. Notably, LOS was not significantly impacted by the day of surgery at our institution.
•Collaboration agreements can improve epilepsy surgery referral volumes.•Standardized referral pathways may help address epilepsy surgery gap.•Internal and external process changes can improve ...referral process.•Sociodemographic variables continue to influence referral completion.
To assess whether a formal collaboration between a non-surgical, community epilepsy center and a surgical, tertiary-care epilepsy center can improve patient progress throughout the pre-surgical referral process, and to elucidate predictors of referral completion among inter-center referrals.
The inter-center referral process was tracked, and the number of patients completing surgical conference (primary outcome) and epilepsy surgery at the tertiary center were collected and compared in the 45-month immediate pre/post-collaboration periods. Demographic and clinical variables were collected on post-collaboration inter-center patient referrals to explore factors associated with completion of the referral process.
Compared to the pre-collaboration period, the proportion of tertiary center epilepsy surgery conference patients referred from the community epilepsy center increased from 3/88 to 14/113 (263% increase, p = .01) during the post-collaboration period. The proportion of patients completing surgery via the community to tertiary referral process increased from 2/63 pre-collaboration to 8/71 post-collaboration (254% increase, p = .04). Referral completion was associated with higher seizure frequency, shorter travel distance, private insurance status and positive employment status (p < 0.05).
Collaboration agreements between community and tertiary-care epilepsy centers may improve patient completion of the epilepsy surgery referral process. Implementation of similar programs at other centers may be beneficial in reducing the epilepsy surgery gap.
BackgroundThe oblique lumbar interbody fusion or anterior-to-psoas (OLIF/ATP) technique relies on a corridor anterior to the psoas and posterior to the vasculature for lumbar interbody fusion. This ...is evaluated preoperatively with CT and/or MRI. To date, there have been no studies examining how intraoperative, lateral decubitus positioning may change the dimensions of this corridor when compared to preoperative imaging.ObjectiveOur objective was to evaluate changes in the intraoperative corridor in the supine and lateral positions utilizing preoperative and intraoperative imaging.MethodsWe performed a retrospective analysis among patients who have undergone an OLIF/ATP approach at two tertiary care centers from 2016 to 2018 by measuring the distance between the left lateral border of the aorta or iliac vessels and anteromedial border of the psoas muscle from L1-L2 through L4-5 disc spaces. We compared this corridor between supine, preoperative MRI axial and intraoperative CT acquired in the right lateral decubitus position.ResultsThirty-three patients, 15 of whom were female, were included in our study. The average age of the patients was 65.4 years and the average BMI was 31 kg/m2. The results revealed a statistically significant increase (p<.05) in the intraoperative corridor from supine to lateral decubitus positioning at all levels. However, age, BMI, and gender had no statistically significant impact on the preoperative versus intraoperative corridor.ConclusionThis is the first study to provide objective evidence that lateral decubitus positioning increases the intraoperative corridor for OLIF/ATP. Our study demonstrates that lateral decubitus positioning provides a more favorable corridor for the OLIF/ATP technique from L1-L5 disc levels.
Latex perfusion is an effective tool to study cerebrovascular pathology in the animal brain. It provides, low-cost, high fidelity anatomical information on ex-vivo analysis, and can be utilized to ...study multiple, states. However, current methods of latex casting and tissue-clearance do not allow for immunohistochemical analysis following sample processing. This results in experiments that require increased numbers of animals to attain adequate data.
In this paper, we present a modified latex perfusion and tissue processing protocol for ex-vivo analysis, of the cerebral vasculature. The method consists of injection of the arterial tree with liquid latex, followed by tissue clearance with a scale solution.
Our results demonstrate effective and reliable perfusion of the murine cerebrovascular tree, rendering the arterial morphology of the brain in high detail, while allowing for post-perfusion, immunohistochemistry of the sample.
Our technique bypasses the limitations of previous latex angiography protocols by allowing for postperfusion, pathologic analysis of casted cerebrovascular tissue.
This protocol provides a reliable, low-cost, method of cerebrovascular perfusion that reduces the number of animals required to generate robust data from latex-casted brain tissue.
•The authors present a protocol for latex perfusion of the cerebrovascular tree.•The method preserves fluorescent signals in clarified structures.•This is a low-cost method for generating pre-clinical data with minimized resources.
A primary etiology of adolescent idiopathic scoliosis (AIS) is currently unknown, but poor postural control of the spinal extensor musculature has been identified as an AIS risk factor. Identifiable ...postural differences would aid in advancing the precise postural behaviors that should be modified during Physiotherapy Scoliosis Specific Exercise (PSSE) to help limit the progression of AIS.
Are there any determinable differences in lumbopelvic posture or range of motion between subjects with AIS and controls?
This prospective cohort pilot study consisted of 53 subjects (27 AIS and 26 control) aged 11–17 years. Subjects had their lumbopelvic posture assessed and monitored using the ViMove DorsaVi sensor package. All subjects underwent a live assessment to obtain initial lumbopelvic (LP) range of motion (ROM) measurements. Subjects were then monitored while continuing with normal activities of daily living (ADLs) for 12 h. With an alpha level of 0.05, nonparametric analyses were performed for each variable via a Mann-Whitney U-test.
During the live assessment, controls exhibited a significantly greater anterior pelvic tilt ROM in the sitting position than the AIS group (p = 0.0433). When compared to female controls, females with AIS had a sitting pelvic tilt ROM that was significantly more retroverted (p = 0.0232) and less anteverted (p = 0.0010). During ADLs, female controls exhibited a higher total number of extension events than their female with AIS (p = 0.0263). These associations did not strengthen with greater spinal deformity.
This work demonstrates postural differences between patients with AIS and controls. Further study is necessary to determine why patients with AIS adopt these postures, and if PSSEs can be utilized to limit the progression of AIS.
•Patients with adolescent idiopathic scoliosis have a more retroverted pelvis at baseline.•Female controls exhibit more frequent spinal extension events during ADLs.•Postural differences in patients with AIS have been identified.
Cerebral arteriovenous malformations (AVMs) are a leading cause of intracerebral hemorrhage in both children and young adults. With the continued advancement of science and technology, the ...understanding of the pathophysiology behind the development of these lesions has evolved. From early theory published by Harvey Cushing and Percival Bailey in 1928, Tumors Arising from the Blood-vessels of the Brain: Angiomatous Malformations and Hemangioblastoma, which regarded AVMs as tumors arising from blood vessels, to the meticulous artistry of Dorcas Padget's embryological cataloguing of the cerebral vasculature in 1948, to the proliferative capillaropathy theory of Yaşargil in 1987, to Ramey's 2014 hierarchical model of vascular development, there have been multiple hypotheses of congenital, developmental, and genetic two-hit theories in the pathogenesis of AVMs. Most recent evidence implicates somatic KRAS mutations in the cerebral endothelium, producing an important understanding of the pathogenesis of this disease, which is critical to the development of targeted therapeutics. The authors present the historical progression of their understanding of AVM pathogenesis. They focus on the foundation laid by early pioneers, discussing embryological anatomy and vasculogenesis, the prominent theories of AVM development that have emerged over time, and culminate in an overview of the most current understanding of the pathogenesis of these complex vascular lesions and the clinical implications of our scientific progress.
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