The state-of-the-art in ultrasound-guided spine interventions.

During the last two decades, intra-operative ultrasound (iUS) imaging has been employed for various surgical procedures of the spine, including spinal fusion and needle injections. Accurate and efficient registration of pre-operative computed tomography or magnetic resonance images with iUS images are key elements in the success of iUS-based spine navigation. While widely investigated in research, iUS-based spine navigation has not yet been established in the clinic. This is due to several factors including the lack of a standard methodology for the assessment of accuracy, robustness, reliability, and usability of the registration method. To address these issues, we present a systematic review of the state-of-the-art techniques for iUS-guided registration in spinal image-guided surgery (IGS). The review follows a new taxonomy based on the four steps involved in the surgical workflow that include pre-processing, registration initialization, estimation of the required patient to image transformation, and a visualization process. We provide a detailed analysis of the measurements in terms of accuracy, robustness, reliability, and usability that need to be met during the evaluation of a spinal IGS framework. Although this review is focused on spinal navigation, we expect similar evaluation criteria to be relevant for other IGS applications

Evaluation of an Ultrasound-Based Navigation System for Spine Neurosurgery: A Porcine Cadaver Study

During the last two decades, intra-operative ultrasound (iUS) imaging has been employed for various surgical procedures of the spine, including spinal fusion and needle injections. Accurate and efficient registration of pre-operative computed tomography or magnetic resonance images with iUS images are key elements in the success of iUS-based spine navigation. While widely investigated in research, iUS-based spine navigation has not yet been established in the clinic. This is due to several factors including the lack of a standard methodology for the assessment of accuracy, robustness, reliability, and usability of the registration method. To address these issues, we present a systematic review of the state-of-the-art techniques for iUS-guided registration in spinal image-guided surgery (IGS). The review follows a new taxonomy based on the four steps involved in the surgical workflow that include pre-processing, registration initialization, estimation of the required patient to image transformation, and a visualization process. We provide a detailed analysis of the measurements in terms of accuracy, robustness, reliability, and usability that need to be met during the evaluation of a spinal IGS framework. Although this review is focused on spinal navigation, we expect similar evaluation criteria to be relevant for other IGS applications

Ultrasound-based navigated pedicle screw insertion without intraoperative radiation: feasibility study on porcine cadavers

BACKGROUND Navigation systems for spinal fusion surgery rely on intraoperative computed tomography (CT) or fluoroscopy imaging. Both expose patient, surgeons and operating room staff to significant amounts of radiation. Alternative methods involving intraoperative ultrasound (iUS) imaging have recently shown promise for image-to-patient registration. Yet, the feasibility and safety of iUS navigation in spinal fusion have not been demonstrated. PURPOSE To evaluate the accuracy of pedicle screw insertion in lumbar and thoracolumbar spinal fusion using a fully automated iUS navigation system. STUDY DESIGN Prospective porcine cadaver study. METHODS Five porcine cadavers were used to instrument the lumbar and thoracolumbar spine using posterior open surgery. During the procedure, iUS images were acquired and used to establish automatic registration between the anatomy and preoperative CT images. Navigation was performed with the preoperative CT using tracked instruments. The accuracy of the system was measured as the distance of manually collected points to the preoperative CT vertebral surface and compared against fiducial-based registration. A postoperative CT was acquired, and screw placements were manually verified. We report breach rates, as well as axial and sagittal screw deviations. RESULTS A total of 56 screws were inserted (5.50 mm diameter n=50, and 6.50 mm diameter n=6). Fifty-two screws were inserted safely without breach. Four screws (7.14%) presented a medial breach with an average deviation of 1.35±0.37 mm (all <2 mm). Two breaches were caused by 6.50 mm diameter screws, and two by 5.50 mm screws. For vertebrae instrumented with 5.50 mm screws, the average axial diameter of the pedicle was 9.29 mm leaving a 1.89 mm margin in the left and right pedicle. For vertebrae instrumented with 6.50 mm screws, the average axial diameter of the pedicle was 8.99 mm leaving a 1.24 mm error margin in the left and right pedicle. The average distance to the vertebral surface was 0.96 mm using iUS registration and 0.97 mm using fiducial-based registration. CONCLUSIONS We successfully implanted all pedicle screws in the thoracolumbar spine using the ultrasound-based navigation system. All breaches recorded were minor (<2 mm) and the breach rate (7.14%) was comparable to existing literature. More investigation is needed to evaluate consistency, reproducibility, and performance in surgical context. CLINICAL SIGNIFICANCE Intraoperative US-based navigation is feasible and practical for pedicle screw insertion in a porcine model. It might be used as a low-cost and radiation-free alternative to intraoperative CT and fluoroscopy in the future

A Systematic Review and Meta-Analysis of Efficacy, Cost-Effectiveness, and Safety of Selected Complementary and Alternative Medicine for Neck and Low-Back Pain

Background. Back pain is a common problem and a major cause of disability and health care utilization. Purpose. To evaluate the efficacy, harms, and costs of the most common CAM treatments (acupuncture, massage, spinal manipulation, and mobilization) for neck/low-back pain. Data Sources. Records without language restriction from various databases up to February 2010. Data Extraction. The efficacy outcomes of interest were pain intensity and disability. Data Synthesis. Reports of 147 randomized trials and 5 nonrandomized studies were included. CAM treatments were more effective in reducing pain and disability compared to no treatment, physical therapy (exercise and/or electrotherapy) or usual care immediately or at short-term follow-up. Trials that applied sham-acupuncture tended towards statistically nonsignificant results. In several studies, acupuncture caused bleeding on the site of application, and manipulation and massage caused pain episodes of mild and transient nature. Conclusions. CAM treatments were significantly more efficacious than no treatment, placebo, physical therapy, or usual care in reducing pain immediately or at short-term after treatment. CAM therapies did not significantly reduce disability compared to sham. None of the CAM treatments was shown systematically as superior to one another. More efforts are needed to improve the conduct and reporting of studies of CAM treatments

Neural Stem/Progenitor Cells from the Adult Human Spinal Cord Are Multipotent and Self-Renewing and Differentiate after Transplantation

Neural stem/progenitor cell (NSPC) transplantation is a promising therapy for spinal cord injury (SCI). However, little is known about NSPC from the adult human spinal cord as a donor source. We demonstrate for the first time that multipotent and self-renewing NSPC can be cultured, passaged and transplanted from the adult human spinal cord of organ transplant donors. Adult human spinal cord NSPC require an adherent substrate for selection and expansion in EGF (epidermal growth factor) and FGF2 (fibroblast growth factor) enriched medium. NSPC as an adherent monolayer can be passaged for at least 9 months and form neurospheres when plated in suspension culture. In EGF/FGF2 culture, NSPC proliferate and primarily express nestin and Sox2, and low levels of markers for differentiating cells. Leukemia inhibitory factor (LIF) promotes NSPC proliferation and significantly enhances GFAP expression in hypoxia. In differentiating conditions in the presence of serum, these NSPC show multipotentiality, expressing markers of neurons, astrocytes, and oligodendrocytes. Dibutyryl cyclic AMP (dbcAMP) significantly enhances neuronal differentiation. We transplanted the multipotent NSPC into SCI rats and show that the xenografts survive, are post-mitotic, and retain the capacity to differentiate into neurons and glia

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Economic evaluation of advanced practice physiotherapy models of care: a systematic review with meta-analyses

International audienceBackground: The objective of this systematic review is to appraise evidence on the economic evaluations of advanced practice physiotherapy (APP) care compared to usual medical care. Methods: Systematic searches were conducted up to September 2021 in selected electronic bibliographical databases. Economic evaluation studies on an APP model of care were included. Economic data such as health care costs, patient costs, productivity losses were extracted. Methodological quality of included studies was assessed with the Effective Public Health Practice Project tool and the Critical Appraisal Skills Programme checklist. Meta-analyses were performed and mean differences (MD) in costs per patient were calculated using random-effect inverse variance models. Certainty of the evidence was assessed with the GRADE Approach. Results: Twelve studies (n = 14,649 participants) including four randomized controlled trials, seven analytical cohort studies and one economic modeling study were included. The clinical settings of APP models of care included primary, emergency and specialized secondary care such as orthopaedics, paediatrics and gynaecology. The majority of the included participants were adults with musculoskeletal disorders (n = 12,915). Based on low quality evidence, health system costs including salaries, diagnostic tests, medications, and follow-up visits were significantly lower with APP care than with usual medical care, at 2 to 12-month follow-up (MD: − 145.02 €/patient; 95%CI: − 251.89 to − 38.14; n = 7648). Based on low quality evidence, patient costs including travel and paid medication prescriptions, or treatments were significantly higher with APP care compared to usual medical care, at 2 to 6-month follow-up (MD: 22.18 €/patient; 95%CI: 0.40 to 43.96; n = 1485). Based on very low quality evidence, no significant differences in productivity losses per patient were reported between both types of care (MD: 450 €/patient; 95%CI: − 80 to 970; n = 819). Conclusions: This is the first systematic review and meta-analysis on the economic evaluation of APP models of care. Low quality evidence suggests that APP care might result in lower health care costs, but higher patient costs compared to usual medical care. Costs differences may vary depending on various factors such as the cost methodology used and on the clinical setting. More evidence is needed to evaluate cost benefits of APP models of care

The role of ultrasound and ultrasound-guided fine needle aspiration biopsy of lymph nodes in patients with skin tumours

BACKGROUND: The primary aim of this study was to evaluate the diagnostic accuracy of ultrasound (US) in the study of superficial lymph nodes during the follow-up of patients surgically treated for skin tumours. The secondary objective was to compare positive cytological results with histological reports. PATIENTS AND METHODS: From 2004 to 2011, 480 patients (male/female: 285/195; median age 57 years; prevalent skin tumour: melanoma) underwent US-guided fine-needle aspiration biopsy (FNAB) of suspicious recurrent lymph nodes. An expert radiologist first performed US testing of the lymph nodes, expressing either a negative or positive outcome of the test. Subsequently, US-guided FNAB was performed. FNAB positive patients were subjected to lymphadenectomy; the patients who tested negative underwent the follow-up. RESULTS: The size of lymph nodes was ≤ 2 cm in 90% of cases. Out of the 336 (70%) US “positive” patients, 231 (68.8%) were FNAB positives. Out of the 144 (30%) US “negatives”, 132 (91.7%) were FNAB negatives. The sensitivity and specificity of the US were 95% and 55.7%, respectively; the negative predictive value was 91.7% and the positive predictive value was 68.8%. Definitive histological results confirmed FNAB positivity in 97.5% of lymphadenectomies. CONCLUSIONS: US is a sensitive method in the evaluation of superficial lymph nodes during the follow-up of patients with skin tumours. High positive predictive value of cytology was confirmed

Advanced practice physiotherapy surgical triage and management of adults with spinal disorders referred to specialized spine medical care: a retrospective observational study

In this novel advanced practice physiotherapy (APP) model of care, advanced practice physiotherapists (APPTs) assess, triage, and manage adults with spinal disorders to alleviate the growing demands in specialized spine medical care. To describe this APP model of care, to assess change in disability 3 months after rehabilitation care and to assess surgical triage and diagnostic concordance between APPTs and spine surgeons. In this retrospective observational study, consecutive patients who completed the 3-month follow-up data were analyzed. Sociodemographic, clinical characteristics, and self-reported disabilities including the Oswestry Disability Index (ODI) and Neck Disability Index (NDI) at baseline and 3 months were extracted. Paired t-tests were used to assess changes in disability. Surgical triage and diagnostic concordance between APPTs and surgeons were measured with raw agreement, Cohen’s Kappa, and PABAK. In this model, trained APPTs triaged surgical candidates and provided rehabilitation care including education and exercises to patients with spinal disorders. The APPTs referred only 18/46 participants to spine surgeons. Surgical triage and diagnostic concordance were high with raw agreement of 94% and 89%. At the 3-month follow-up, significant improvements in disability were observed among nonsurgical candidates with back (mean difference (MD): −13.0/100 [95%CI: −19.8 to −6.3], n = 23) or neck disorders (MD: −16.0/100 [95%CI: −29.6 to −2.4], n = 5), but not among surgical candidates referred by APPTs to spine surgeons. In this limited sample, adults with spinal disorders that were initially referred to a spine surgeon by family physicians were effectively assessed, triaged, and managed by an APPT.</p