A Prospective, Observational, Open-Label, Non-Randomized, Multicenter Study Measuring Functional Outcomes in a Novel Interspinous Fusion Device in Subjects with Low Back Pain: REFINE Study.

INTRODUCTION: Lumbar degenerative disease and the accompanying pain and dysfunction affect a significant number of patients in the USA and around the world. As surgery and innovation are moving towards minimally invasive treatments, this study looks to explore interspinous fixation as a standalone posterior approach to treat lumbar degenerative disc disease in the presence of neurogenic claudication and spinal stenosis. METHODS: This study was approved by an institutional review board (IRB) and is actively enrolling in a single-arm, multicenter, prospective, open-label fashion. Patients are followed with reporting at 3 months, and 12 months for primary endpoint analysis of efficacy and safety based on improved composite endpoints relative to baseline, with success defined as greater than 20 mm back pain reduction in Visual Analog Scale 100 mm (VAS) while standing or walking, greater than 20 mm leg pain reduction in VAS while standing or walking, Zurich Claudication Questionnaire (ZCQ) improvement of 0.5 or greater in two or three domains, Oswestry Disability Index (ODI) improvement of a least 10 points and no reoperations or revisions at the index level(s). Secondary endpoints included a multidimensional assessment in the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v2.1 and Patient Global Impression of Change (PGIC). RESULTS: In this interim 3-month analysis, 82% of patients reported they were improved from the procedure, while 65% of patients demonstrated clinical meaningful improvement in their pain and function, as defined by the VAS, ODI, and ZCQ. There was only one adverse event and no complications were identified at last clinic research follow-up visit. CONCLUSIONS: This interim analysis of the first 20% of the enrolled patients out to 3 months was to determine safety of the procedure and report on adverse events, acknowledging the heterogeneity of surgical specialty. Further follow-up and greater numbers are needed as the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05504499.

Early Functional Outcomes in Low Back Pain Subjects with a Novel Interspinous Fusion Device: REFINE Study 6-Month Results.

Purpose: Lumbar interlaminar decompression with interspinous fixation is an established safe and effective treatment for spinal stenosis. Early maintenance of improvements in pain intensity and function are critical for durability of symptom relief. The purpose of this study was to investigate the efficacy of minimally invasive treatments for low back pain during the early period after treatment and their utility in setting the course for longer term success. Patients and Methods: This study utilized patient evaluations at 3- and 6-months following treatment and is part of an actively enrolling, institutional review board (IRB) approved, single-arm, multicenter, prospective, open-label 12-month study. Clinical efficacy was assessed primarily using the change from baseline in Oswestry Disability Index (ODI), Visual Analog Scale (VAS) of the back and leg pain during walking and standing, and Zurich Claudication Questionnaire (ZCQ), and secondarily using the Patient Global Impression of Change (PGIC) and Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v2.1. The safety endpoints were the adverse events and reoperations or revisions at the index level(s). Results: At 6-month post-op, 76%, 62%-64%, and 64% of patients demonstrated clinical meaningful, and statistically significant improvement in their pain as defined by ZCQ, VAS (back and leg), and ODI, respectively. In addition, 78% of patients noted improvement in PGIC. Two procedure-related adverse events were noted which fully resolved without surgical intervention. Conclusion: This 6-month interim analysis at 42% enrollment of patients was conducted to determine prolonged safety and efficacy of the interspinous fusion device. Our analysis showed a sustained improvement in clinical efficacy, and safety endpoints, when compared to the 3-months evaluations, across both interventional pain and neurosurgery specialties.

Preoperative validation of edema-corrected tractography in neurosurgical practice: translating surgeon insights into novel software implementation.

Background: Peritumoral edema alters diffusion anisotropy, resulting in false negatives in tractography reconstructions negatively impacting surgical decision-making. With supratotal resections tied to survival benefit in glioma patients, advanced diffusion modeling is critical to visualize fibers within the peritumoral zone to prevent eloquent fiber transection thereafter. A preoperative assessment paradigm is therefore warranted to systematically evaluate multi-subject tractograms along clinically meaningful parameters. We propose a novel noninvasive surgically-focused survey to evaluate the benefits of a tractography algorithm for preoperative planning, subsequently applied to Synaptive Medical's free-water correction algorithm developed for clinically feasible single-shell DTI data. Methods: Ten neurosurgeons participated in the study and were presented with patient datasets containing histological lesions of varying degrees of edema. They were asked to compare standard (uncorrected) tractography reconstructions overlaid onto anatomical images with enhanced (corrected) reconstructions. The raters assessed the datasets in terms of overall data quality, tract alteration patterns, and the impact of the correction on lesion definition, brain-tumor interface, and optimal surgical pathway. Inter-rater reliability coefficients were calculated, and statistical comparisons were made. Results: Standard tractography was perceived as problematic in areas proximal to the lesion, presenting with significant tract reduction that challenged assessment of the brain-tumor interface and of tract infiltration. With correction applied, significant reduction in false negatives were reported along with additional insight into tract infiltration. Significant positive correlations were shown between favorable responses to the correction algorithm and the lesion-to-edema ratio, such that the correction offered further clarification in increasingly edematous and malignant lesions. Lastly, the correction was perceived to introduce false tracts in CSF spaces and - to a lesser degree - the grey-white matter interface, highlighting the need for noise mitigation. As a result, the algorithm was modified by free-water-parameterizing the tractography dataset and introducing a novel adaptive thresholding tool for customizable correction guided by the surgeon's discretion. Conclusion: Here we translate surgeon insights into a clinically deployable software implementation capable of recovering peritumoral tracts in edematous zones while mitigating artifacts through the introduction of a novel and adaptive case-specific correction tool. Together, these advances maximize tractography's clinical potential to personalize surgical decisions when faced with complex pathologies.

Effect of foster care on young children's language learning.

This report examines 174 young children's language outcomes in the Bucharest Early Intervention Project, the first randomized trial of foster placement after institutional care. Age of foster placement was highly correlated with language outcomes. Placement by 15 months led to similar expressive and receptive language test scores as typical age peers at 30 and 42 months. Placement from 15 to 24 months also led to dramatic language improvement. In contrast, children placed after 24 months had the same severe language delays as children in institutional care. Language samples at 42 months confirmed that placement after 24 months led to lower expressive skill.

Improving the Management of Patients with Osteoporosis Undergoing Spinal Fusion: The Need for a Bone Mineral Density-Matched Interbody Cage.

With an increasingly aging population globally, a confluence has emerged between the rising prevalence of degenerative spinal disease and osteoporosis. Fusion of the anterior spinal column remains the mainstay surgical intervention for many spinal degenerative disorders. However, decreased vertebral bone mineral density (BMD), quantitatively measured by dual x-ray absorptiometry (DXA), complicates treatment with surgical interbody fusion as weak underlying bone stock increases the risk of post-operative implant-related adverse events, including cage subsidence. There is a necessity for developing cages with advanced structural designs that incorporate bioengineering and architectural principles to tailor the interbody fusion device directly to the patient's BMD status. Specifically, lattice-designed cages that mimic the web-like structure of native cancellous bone have demonstrated excellent resistance to post-operative subsidence. This article provides an introductory profile of a spinal interbody implant designed intentionally to simulate the lattice structure of human cancellous bone, with a similar modulus of elasticity, and specialized to match a patient's bone status across the BMD continuum. The implant incorporates an open pore design where the degree of pore compactness directly corresponds to the patient's DXA-defined BMD status, including patients with osteoporosis.

Rarebit perimetry for bedside testing: comparison with standard automated perimetry.

BACKGROUND: Rarebit perimetry (RBP), a technique developed for the detection of early damage to the afferent visual system, has not been extensively tested at the bedside. This study was designed to test the feasibility of bedside testing with RBP in comparison with standard automated perimetry (SAP) performed in the clinic. METHODS: We tested 29 eyes of 15 subjects admitted with neurologic or neurosurgical diseases affecting the afferent visual system. RBP was performed on a laptop computer at the bedside. SAP (Humphrey field analyzer) testing was performed later in the clinic. Results were evaluated by a masked neuro-ophthalmologist. RESULTS: Visual fields corresponded between RBP and SAP in 21(72%) of the 29 tested eyes. RBP detected defects in 5 subjects who had normal visual field results on SAP. All subjects preferred RBP for convenience. CONCLUSION: RBP is a convenient method of bedside visual field testing and is no less sensitive to visual field defects in this role than SAP.

Novel Technique of Coregistered Intraoperative Computed Tomography and Preoperative Magnetic Resonance Imaging and Diffusion Tensor Imaging Navigation in Spinal Cord Tumor Resection.

Background: Intradural spinal tumors are surgically challenging lesions, and intraoperative spinal navigation offers clear potential assistance. While intraoperative computed tomography (iCT) of bony anatomy is routinely performed, coregistration with magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to facilitate intradural spinal tumor resection is not widely described. We present 2 cases in which iCT was coregistered with MRI and DTI for navigational guidance in the resection of intradural spinal tumors to assess technical feasibility and surgical efficacy. Case Series: Navigation using coregistered iCT/MRI was used in the resection of one extramedullary and one intramedullary cervicomedullary tumor. The iCT was obtained following open midline exposure of bony anatomy. The images were then coregistered with preoperative MRI sequences to allow for optical tracking navigation via an optical tracking station (Brainlab). For the intramedullary tumor, preoperative DTI sequences were also coregistered for enhanced identification of relevant anatomy. Navigational accuracy for all cases was confirmed to be acceptable at the level of the posterior bony elements, the dura, and the tumor-parenchyma interface. Conclusion: The coregistration of preoperative MRI sequences and iCT images allowed for meaningfully enhanced navigation during resection. In the case involving the intramedullary cervicomedullary tumor with marked distortion of longitudinal tracts, iCT/DTI navigation allowed for accurate visualization of critical structures and facilitated delineation of tumor margins that otherwise would have been difficult. The use of combined iCT and preoperative MRI/DTI neuronavigational guidance is an effective approach in the resection of intradural extramedullary and intramedullary spinal cord tumors.

Language acquisition with limited input: Romanian institution and foster care.

PURPOSE: To provide the first detailed information about native language abilities of children who are or had been institutionalized. METHOD: The language of ten 30-month-old children raised in Romanian orphanages was compared with that of 30 chronological-age-matched peers: 10 children who had moved recently from orphanages to foster care, 10 children in foster families for at least 1 year, and 10 children raised in their biological families. Ten language measures were obtained from communication during play and from parent/caregiver report. RESULTS: Children who were institutionalized and children in foster care for a brief time showed substantial language delays, with some of these children not yet producing intelligible words. Children in foster care for at least 1 year approximated the expressive output and receptive language of children who had never been institutionalized; however, they showed lower expressive grammatical abilities. Within the group of children who were institutionalized, the presence of a preferred caregiver and a measure of development, greater height, were associated with greater language output. Although children in orphanages produced fewer complex forms than children in biological families, there were no systematic qualitative differences in language structure across groups. CONCLUSION: Foster care facilitated language growth after substantial language delays associated with institutionalization.

Ethical considerations in international research collaboration: The Bucharest early intervention project.

The Bucharest Early Intervention Project (BEIP) is the first ever randomized controlled trial of foster care as an alternative to institutional care for young children. It involved a collaboration between American investigators and Romanian health and child protection professionals. We present a brief description of the Romanian context and the project itself before discussing a number of ethical issues raised by the project. Organized around a discussion of exploitation, risk/benefit ratio, and cultural sensitivity, we evaluate a number of ethical issues involved in the BEIP using the Ethical Clinical Research Framework and the Fair Benefits Framework. Based on this review, we conclude that notwithstanding challenging ethical dilemmas, the benefits of the project outweighed its risks. Throughout the planning and implementation of the project, ethical issues were a central focus of discussion among the investigators and in the collaboration between Americans and Romanians. Thoughtful discussions from multiple perspectives are necessary to conduct research that is ethically sound and scientifically meaningful.

"Live cadavers" for training in the management of intraoperative aneurysmal rupture.

OBJECT: Intraoperative rupture occurs in approximately 9.2% of all cranial aneurysm surgeries. This event is not merely a surgical complication, it is also a real surgical crisis that requires swift and decisive action. Neurosurgical residents may have little exposure to this event, but they may face it in their practice. Laboratory training would be invaluable for developing competency in addressing this crisis. In this study, the authors present the "live cadaver" model, which allows repetitive training under lifelike conditions for residents and other trainees to practice managing this crisis. METHODS: The authors have used the live cadaver model in 13 training courses from 2009 to 2014 to train residents and neurosurgeons in the management of intraoperative aneurysmal rupture. Twenty-three cadaveric head specimens harboring 57 artificial and 2 real aneurysms were used in these courses. Specimens were specially prepared for this technique and connected to a pump that sent artificial blood into the vessels. This setting created a lifelike situation in the cadaver that simulates live surgery in terms of bleeding, pulsation, and softness of tissue. RESULTS: A total of 203 neurosurgical residents and 89 neurosurgeons and faculty members have practiced and experienced the live cadaver model. Clipping of the aneurysm and management of an intraoperative rupture was first demonstrated by an instructor. Then, trainees worked for 20- to 30-minute sessions each, during which they practiced clipping and reconstruction techniques and managed intraoperative ruptures. Ninety-one of the participants (27 faculty members and 64 participants) completed a questionnaire to rate their personal experience with the model. Most either agreed or strongly agreed that the model was a valid simulation of the conditions of live surgery on cerebral aneurysms and represents a realistic simulation of aneurysmal clipping and intraoperative rupture. Actual performance improvement with this model will require detailed measurement for validating its effectiveness. The model lends itself to evaluation using precise performance measurements. CONCLUSIONS: The live cadaver model presents a useful simulation of the conditions of live surgery for clipping cerebral aneurysms and managing intraoperative rupture. This model provides a means of practice and promotes team management of intraoperative cerebrovascular critical events. Precise metric measurement for evaluation of training performance improvement can be applied.

Growth and associations between auxology, caregiving environment, and cognition in socially deprived Romanian children randomized to foster vs ongoing institutional care.

OBJECTIVES: To determine effects of improved nurturing compared with institutional care on physical growth and to investigate the association between growth and cognitive development. DESIGN: A randomized controlled trial beginning in infants (mean age, 21.0 months; range, 5-32 months), with follow-up at 30, 42, and 54 months of age. SETTING: Institutionalized and community children in Bucharest, Romania. PARTICIPANTS: One hundred thirty-six healthy institutionalized children from 6 orphanages and 72 typically developing, never-institutionalized children. INTERVENTION: Institutionalized children were randomly assigned to receive foster care or institutional care as usual. OUTCOME MEASURES: Auxology and measures of intelligence over time. RESULTS: Growth in institutionalized children was compromised, particularly in infants weighing less than 2500 g at birth. Mean height and weight, though not head size, increased to near normal within 12 months in foster care. Significant independent predictors for greater catch-up in height and weight included age younger than 12 months at randomization, lower baseline z scores, and higher caregiving quality, particularly caregiver sensitivity and positive regard. Baseline developmental quotient, birth weight, and height catch-up were significant independent predictors of cognitive abilities at follow-up. Each incremental increase of 1 in standardized height scores between baseline and 42 months was associated with a mean increase of 12.6 points (SD, 4.7 points) in verbal IQ (P < .05). CONCLUSIONS: Foster care had a significant effect on growth, particularly with early placement and high-quality care. Growth and IQ in low-birth-weight children are particularly vulnerable to social deprivation. Catch-up growth in height under more nurturing conditions is a useful indicator of caregiving quality and cognitive improvement.

The caregiving context in institution-reared and family-reared infants and toddlers in Romania.

BACKGROUND: We assess individual differences in the caregiving environments of young children being raised in institutions in Romania in relation to developmental characteristics such as physical growth, cognitive development, emotional expression, and problem and competence behaviors. METHOD: Videotaped observations of the child and favorite caregiver in their 'home' environment were coded for caregiving quality, and this was related to child characteristics. Child emotional reactivity was assessed during responses to interactional tasks. Cognitive development was assessed from child responses to the Bayley Scales of Infant Development. Data regarding problem behaviors and competence were obtained from caregiver report. Children reared in institutions were compared on all of these measures to never institutionalized children to assist gauging degree of impairment. RESULTS: Children raised in institutions demonstrated marked delays in cognitive development, poorer physical growth, and marked deficits in competence. Individual differences in caregiving environment were associated with cognitive development, competence, and negative behavior among these young children being reared in institutions. CONCLUSIONS: These data confirm previous findings regarding deficits associated with institutional care and extend our understanding of the impact of individual differences in caregiving quality on the development of young children in institutions.

Attachment in institutionalized and community children in Romania.

This study examined attachment in institutionalized and community children 12-31 months of age in Bucharest, Romania. Attachment was assessed using ratings of attachment behaviors and ratings of caregiver descriptions in a structured interview. As predicted, children raised in institutions exhibited serious disturbances of attachment as assessed by all methods. Observed quality of caregiving was related to formation and organization of attachment in children living in institutions. These results held even when other variables, such as cognitive level, perceived competence, and quantitative interaction ratings, were controlled for. Ratings of attachment behavior in the Strange Situation and caregiver reports of signs of Reactive Attachment Disorder converged moderately. The implications of these findings for different perspectives on attachment are discussed.

Designing research to study the effects of institutionalization on brain and behavioral development: the Bucharest Early Intervention Project.

This paper provides an overview of the largest longitudinal investigation of institutionalized children less than 2 years old ever conducted. The Bucharest Early Intervention Project is an ongoing randomized controlled trial of foster placement as an alternative to institutionalization in abandoned infants and toddlers being conducted in Bucharest, Romania. In addition to describing the contexts in which this study is imbedded, we also provide an overview of the sample, the measures, and the intervention. We hope that the natural experiment of institutionalization will allow us to examine directly the effects of intervention on early deprivation. We hope it will provide answers to many of the critical questions that developmentalists have asked about the effects of early experience, the timing of deprivation, and the ameliorating effects of early intervention and provide clues to which underlying neurobiological processes are compromised by, and resilient to, dramatic changes in early experience.