Adjunctive Use of Bone Growth Stimulation Increases Cervical Spine Fusion Rates in Patients at Risk for Pseudarthrosis.

STUDY DESIGN: A prospective multicenter clinical trial (NCT03177473) was conducted with a retrospective cohort used as a control arm. OBJECTIVE: The purpose of this study was to evaluate cervical spine fusion rates in subjects with risk factors for pseudarthrosis who received pulsed electromagnetic field (PEMF) treatment. SUMMARY OF BACKGROUND DATA: Certain risk factors predispose patients to pseudarthrosis, which is associated with prolonged pain, reduced function, and decreased quality of life. METHODS: Subjects in the PEMF group were treated with PEMF for 6 months postoperatively. The primary outcome measure was fusion status at the 12-month follow-up period. Fusion status was determined using anterior/posterior, lateral, and flexion/extension radiographs and computed tomography (without contrast). RESULTS: A total of 213 patients were evaluated (PEMF, n=160; Control, n=53). At baseline, the PEMF group had a higher percentage of subjects who used nicotine ( P =0.01), had osteoporosis ( P <0.05), multi-level disease ( P <0.0001), and were >65 years of age ( P =0.01). The PEMF group showed over two-fold higher percentage of subjects that had ≥3 risk factors (n=92/160, 57.5%) compared with the control group (n=14/53, 26.4%). At the 12-month follow-up, the PEMF group demonstrated significantly higher fusion rates compared with the control (90.0% vs. 60.4%, P <0.05). A statistically significant improvement in fusion rate was observed in PEMF subjects with multi-level surgery ( P <0.0001) and high BMI (>30 kg/m 2 ; P =0.0021) when compared with the control group. No significant safety concerns were observed. CONCLUSIONS: Adjunctive use of PEMF stimulation provides significant improvements in cervical spine fusion rates in subjects having risk factors for pseudarthrosis. When compared with control subjects that did not use PEMF stimulation, treated subjects showed improved fusion outcomes despite being older, having more risk factors for pseudarthrosis, and undergoing more complex surgeries.

Increased global cropland greening as a response to the unusual reduction in atmospheric PM2.5 concentrations during the COVID-19 lockdown period.

The devastating effects of COVID-19 pandemic have widely affected human lives and economy across the globe. There were significant changes in the global environmental conditions in response to the lockdown (LD) restrictions made due to COVID-19. The direct impact of LD on environment is analysed widely across the latitudes, but its secondary effect remains largely unexplored. Therefore, we examine the changes in particulate matter (PM2.5) during LD, and its impact on the global croplands. Our analysis finds that there is a substantial decline in the global PM2.5 concentrations during LD (2020) compared to pre-lockdown (PreLD: 2017-2019) in India (10-20%), East China (EC, 10%), Western Europe (WE, 10%) and Nigeria (10%), which are also the cropland dominated regions. Partial correlation analysis reveals that the decline in PM2.5 positively affects the cropland greening when the influence of temperature, precipitation and soil moisture are limited. Croplands in India, EC, Nigeria and WE became more greener as a result of the improvement in air quality by the reduction in particulates such as PM2.5 during LD, with an increase in the Enhanced Vegetation Index (EVI) of about 0.05-0.1, 0.05, 0.05 and 0.05-0.1, respectively. As a result of cropland greening, increase in the total above ground biomass production (TAGP) and crop yield (TWSO) is also found in EC, India and Europe. In addition, the improvement in PM2.5 pollution and associated changes in meteorology also influenced the cropland phenology, where the crop development stage has prolonged in India for wet-rice (1-20%) and maize (1-10%). Therefore, this study sheds light on the response of global croplands to LD-induced improvements in PM2.5 pollution. These finding have implications for addressing issues of air pollution, global warming, climate change, environmental conservation and food security to achieve the Sustainable Development Goals (SDGs).

Reference Data for Diagnosis of Spondylolisthesis and Disc Space Narrowing Based on NHANES-II X-rays.

Robust reference data, representing a large and diverse population, are needed to objectively classify measurements of spondylolisthesis and disc space narrowing as normal or abnormal. The reference data should be open access to drive standardization across technology developers. The large collection of radiographs from the 2nd National Health and Nutrition Examination Survey was used to establish reference data. A pipeline of neural networks and coded logic was used to place landmarks on the corners of all vertebrae, and these landmarks were used to calculate multiple disc space metrics. Descriptive statistics for nine SPO and disc metrics were tabulated and used to identify normal discs, and data for only the normal discs were used to arrive at reference data. A spondylolisthesis index was developed that accounts for important variables. These reference data facilitate simplified and standardized reporting of multiple intervertebral disc metrics.

Five-Year Longitudinal Follow-up of Restorative Neurostimulation Shows Durability of Effectiveness in Patients With Refractory Chronic Low Back Pain Associated With Multifidus Muscle Dysfunction.

BACKGROUND: Adults with refractory, mechanical chronic low back pain associated with impaired neuromuscular control of the lumbar multifidus muscle have few treatment options that provide long-term clinical benefit. This study hypothesized that restorative neurostimulation, a rehabilitative treatment that activates the lumbar multifidus muscles to overcome underlying dysfunction, is safe and provides relevant and durable clinical benefit to patients with this specific etiology. MATERIALS AND METHODS: In this prospective five-year longitudinal follow-up of the ReActiv8-B pivotal trial, participants (N = 204) had activity-limiting, moderate-to-severe, refractory, mechanical chronic low back pain, a positive prone instability test result indicating impaired multifidus muscle control, and no indications for spine surgery. Low back pain intensity (10-cm visual analog scale [VAS]), disability (Oswestry Disability Index), and quality of life (EuroQol's "EQ-5D-5L" index) were compared with baseline and following the intent-to-treat principle, with a supporting mixed-effects model for repeated measures that accounted for missing data. RESULTS: At five years (n = 126), low back pain VAS had improved from 7.3 to 2.4 cm (-4.9; 95% CI, -5.3 to -4.5 cm; p < 0.0001), and 71.8% of participants had a reduction of ≥50%. The Oswestry Disability Index improved from 39.1 to 16.5 (-22.7; 95% CI, -25.4 to -20.8; p < 0.0001), and 61.1% of participants had reduction of ≥20 points. The EQ-5D-5L index improved from 0.585 to 0.807 (0.231; 95% CI, 0.195-0.267; p < 0.0001). Although the mixed-effects model attenuated completed-case results, conclusions and statistical significance were maintained. Of 52 subjects who were on opioids at baseline and had a five-year visit, 46% discontinued, and 23% decreased intake. The safety profile compared favorably with neurostimulator treatments for other types of back pain. No lead migrations were observed. CONCLUSION: Over a five-year period, restorative neurostimulation provided clinically substantial and durable benefits with a favorable safety profile in patients with refractory chronic low back pain associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354; registration date: October 15, 2016; principal investigator: Christopher Gilligan, MD, Brigham and Women's Hospital, Boston, MA, USA. The study was conducted in Australia (Broadmeadow, New South Wales; Noosa Heads, Queensland; Welland, South Australia; Clayton, Victoria), Belgium (Sint-Niklaas; Wilrijk), The Netherlands (Rotterdam), UK (Leeds, London, Middlesbrough), and USA (La Jolla, CA; Santa Monica, CA; Aurora, CO; Carmel, IN; Indianapolis, IN; Kansas City, KS; Boston, MA; Royal Oak, MI; Durham, NC; Winston-Salem, NC; Cleveland, OH; Providence, RI; Spartanburg, SC; Spokane, WA; Charleston, WV).

Growth performance, meat quality and hematological parameters of broiler chickens fed safflower seed.

The aim of the current study was to determine the effects of dietary supplementation of safflower seed (SS) on the growth performance and hematological parameters of broiler birds along with the physicochemical, textural and sensory attributes of chicken meat. A total of 200 male chickens (7-days-old) were distributed into 5 groups (40 chickens in each) with 5 replicates of 8 chicks in a 42-day experiment. Each group was allocated to one of 5 dietary treatments, i.e., 0, 2.5, 5, 7.5, and 10% SS. The experimental diets were formulated for starter (7 to 21 days) and finisher (22 to 42 days) phases. Inclusion of SS in the diet improved growth performances in treatment groups between 7 and 42 days. The highest and lowest body weights were observed at the 5% SS and 0% SS levels, respectively. The physicochemical attributes of breast and thigh meat were found (P > 0.05) except for crude fat. The crude fat was significantly (P < 0.05) increased with increasing levels of SS in the diet. The inclusion of SS in the diet did not negatively impact the textural properties, i.e., hardness, cohesiveness, springiness, gumminess, chewiness, and shear force of breast and thigh meat. There was no significant difference in the sensory parameters of cooked chicken meat with increasing levels of SS in the diet. The results demonstrated a significant (P < 0.01) improvement in hematological parameters in the blood samples of broiler chickens fed diet supplemented with various levels of SS for five weeks. These findings suggest that, SS may be used as an oil seed for broiler chicken feed.

Apoptosis induction capability of silver nanoparticles capped with Acorus calamus L. and Dalbergia sissoo Roxb. Ex DC. against lung carcinoma cells.

Silver nanoparticles (AgNPs) were prepared using a one-step reduction of silver nitrate (AgNO3) with sodium borohydride (NaBH4) in the presence of polyvinylpyrrolidone (PVP) as a capping agent. Plant extracts from D. sissoo (DS) and A. calamus L. (AC) leaves were incorporated during the synthesis process. The crystalline nature of the AgNPs was confirmed through X-ray diffraction (XRD), confirming the face-centered cubic structure, with a lattice constant of 4.08 Å and a crystallite size of 18 nm. Field Emission Gun Transmission Electron Microscopy (FEG-TEM) revealed spherical AgNPs (10-20 nm) with evident PVP adsorption, leading to size changes and agglomeration. UV-Vis spectra showed a surface plasmon resonance (SPR) band at 417 nm for AgNPs and a redshift to 420 nm for PVP-coated AgNPs, indicating successful synthesis. Fourier Transform Infrared Spectroscopy (FTIR) identified functional groups and drug-loaded samples exhibited characteristic peaks, confirming effective drug loading. The anti-cancer potential of synthesized NPs was assessed by MTT assay in human adenocarcinoma lung cancer (A549) and lung normal cells (WI-38) cells. IC50 values for all three NPs (AgPVP NPs, DS@AgPVP NPs, and AC@AgPVP NPs) were 41.60 ± 2.35, 14.25 ± 1.85, and 21.75 ± 0.498 µg/ml on A549 cells, and 420.69 ± 2.87, 408.20 ± 3.41, and 391.80 ± 1.55 µg/ml respectively. Furthermore, the NPs generated Reactive Oxygen Species (ROS) and altered the mitochondrial membrane potential (MMP). Differential staining techniques were used to investigate the apoptosis-inducing properties of the three synthesized NPs. The colony formation assay indicated that nanoparticle therapy prevented cancer cell invasion. Finally, Real-Time PCR (RT-PCR) analysis predicted the expression pattern of many apoptosis-related genes (Caspase 3, 9, and 8).

Sources, variability, long-term trends, and radiative forcing of aerosols in the Arctic: implications for Arctic amplification.

Atmospheric pollution in the Arctic has been an important driver for the ongoing climate change there. Increase in the Arctic aerosols causes the phenomena of Arctic haze and Arctic amplification. Our analysis of aerosol optical depth (AOD), black carbon (BC), and dust using ground-based, satellite, and reanalysis data in the Arctic for the period 2003-2019 shows that the lowest amount of all these is found in Greenland and Central Arctic. There is high AOD, BC, and dust in the northern Eurasia and parts of North America. All aerosols show their highest values in spring. Significant positive trends in AOD (> 0.003 year-1) and BC (0.0002-0.0003 year-1) are found in the northwestern America and northern Asia. Significant negative trends are observed for dust (- 0.0001 year-1) around Central Arctic. Seasonal analysis of AOD, BC, and dust reveals an increasing trend in summer and decreasing trend in spring in the Arctic. The major sources of aerosols are the nearby Europe, Russia, and North America regions, as assessed using the potential source contribution function (PSCF). Anthropogenic emissions from the transport, energy, and household sectors along with natural sources such as wildfires contribute to the positive trends of aerosols in the Arctic. These increasing aerosols in the Arctic influence Arctic amplification through radiative effects. Here, we find that the net aerosol radiative forcing is high in Central Arctic, Greenland, Siberia, and Canadian Arctic, about 2-4 W/m2, which can influence the regional temperature. Therefore, our study can assist policy decisions for the mitigation of Arctic haze and Arctic amplification in this environmental fragile region of the Earth.

Pulsed Electromagnetic Field Stimulation in Lumbar Spine Fusion for Patients With Risk Factors for Pseudarthrosis.

BACKGROUND: Lumbar spinal fusion surgeries are increasing steadily due to an aging and ever-growing population. Patients undergoing lumbar spinal fusion surgery may present with risk factors that contribute to complications, pseudarthrosis, prolonged pain, and reduced quality of life. Pulsed electromagnetic field (PEMF) stimulation represents an adjunct noninvasive treatment intervention that has been shown to improve successful fusion and patient outcomes following spinal surgery. METHODS: A prospective, multicenter study investigated PEMF as an adjunct therapy to lumbar spinal fusion procedures in patients at risk for pseudarthrosis. Patients with at least 1 of the following risk factors were enrolled: prior failed fusion, multilevel fusion, nicotine use, osteoporosis, or diabetes. Fusion status was determined by radiographic imaging, and patient-reported outcomes were also evaluated. RESULTS: A total of 142 patients were included in the analysis. Fusion status was assessed at 12 months follow-up where 88.0% (n = 125/142) of patients demonstrated successful fusion. Fusion success for patients with 1, 2+, or 3+ risk factors was 88.5%, 87.5%, and 82.3%, respectively. Significant improvements in patient-reported outcomes using the Short Form 36, EuroQol 5 Dimension (EQ-5D) survey, Oswestry Disability Index, and visual analog scale for back and leg pain were also observed compared with baseline scores (P < 0.001). A favorable safety profile was observed. PEMF treatment showed a positive benefit-risk profile throughout the 6-month required use period. CONCLUSIONS: The addition of PEMF as an adjunct treatment in patients undergoing lumbar spinal surgery provided a high rate of successful fusion with significant improvements in pain, function, and quality of life, despite having risk factors for pseudarthrosis. CLINICAL RELEVANCE: PEMF represents a useful tool for adjunct treatment in patients who have undergone lumbar spinal surgery. Treatment with PEMF may result in improved fusion and patient-reported outcomes, regardless of risk factors. TRIAL REGISTRATION: NCT03176303.

Minimally Invasive SI Joint Fusion Procedures for Chronic SI Joint Pain: Systematic Review and Meta-Analysis of Safety and Efficacy.

BACKGROUND: Sacroiliac (SI) joint fusion is increasingly used to treat chronic SI joint pain. Multiple surgical approaches are now available. METHODS: Data abstraction and random effects meta-analysis of safety and efficacy outcomes from published patient cohorts. Patient-reported outcomes (PROs) and safety measures were stratified by surgical technique: transiliac, including lateral transiliac (LTI) and posterolateral transiliac (PLTI), and posterior interpositional (PI) procedures. RESULTS: Fifty-seven cohorts of 2851 patients were identified, including 43 cohorts (2126 patients) for LTI, 6 cohorts (228 patients) for PLTI, and 8 cohorts (497 patients) for PI procedures. Randomized trials were only available for LTI. PROs were available for pain (numeric rating scale) in 57 cohorts (2851 patients) and disability (Oswestry Disability Index [ODI]) in 37 cohorts (1978 patients).All studies with PROs showed improvement from baseline after surgery. Meta-analytic improvements in pain scores were highest for LTI (4.8 points [0-10 scale]), slightly lower for PLTI (4.2 points), and lowest for PI procedures (3.8 points, P = 0.1533). Mean improvements in ODI scores were highest for LTI (25.9 points), lowest for PLTI procedures (6.8 points), and intermediate for PI (16.3 points, P = 0.0095).For safety outcomes, acute symptomatic implant malposition was 0.43% for LTI, 0% for PLTI, and 0.2% for PI procedures. Wound infection was reported in 0.15% of LTI, 0% of PLTI, and 0% of PI procedures. Bleeding requiring surgical intervention was reported in 0.04% of LTI procedures and not reported for PLTI or PI. Breakage and migration were not reported for any device. Radiographic imaging evaluation reporting implant placement accuracy and fusion was only available for LTI. DISCUSSION: Literature support for SI joint fusion is growing. The LTI procedure contains the largest body of available evidence and shows the largest improvements in pain and ODI. Only LTI procedures have independent radiographic evidence of fusion and implant placement. The adverse event rate for all procedures was low.

Ultrasound-guided tenotomy for lateral epicondylitis with TenJet improves physical functional and decreased pain outcomes at 1 year: a case series review.

Background: Common extensor tendinopathy is a common cause of lateral elbow pain. Ultrasound-guided minimally invasive tenotomy (MIT) has been utilized successfully as a treatment for several years, but the use of TenJet device has not been well described. Purpose: To evaluate the effectiveness and safety of MIT with TenJet who failed nonsurgical management of common extensor tendinopathy in an outpatient setting. Methods: A total of 100 patients with common extensor tendinopathy who failed conservative treatment underwent ultrasound-guided MIT with TenJet device in the outpatient setting at a single institution. All 100 patients prior to MIT underwent diagnostic musculoskeletal ultrasound showing common extensor tendinosis. The findings were interpreted by a fellowship-trained and board-certified musculoskeletal radiologist. Patients were evaluated with the Oxford Elbow Score prior to the procedure and at 1-year follow-up. Exclusion criteria included prior corticosteroid injection within the past 6 weeks of the MIT intervention, active local or systemic infection, complete full thickness tear of the common extensor tendon, and pregnancy. Results: Oxford Elbow Score had a statistically significant difference in baseline to 1 year (P < .001). No complications were reported and zero patients went on to require open surgical intervention. Conclusion: MIT with TenJet is a safe, effective, and well-tolerated treatment for common extensor tendinopathy.

Synergistic Inhibitory Effect of Quercetin and Cyanidin-3O-Sophoroside on ABCB1.

The human ABCB1 (P-glycoprotein, Pgp) protein is an active exporter expressed in the plasma membrane of cells forming biological barriers. In accordance with its broad substrate spectrum and tissue expression pattern, it affects the pharmacokinetics of numerous chemotherapeutic drugs and it is involved in unwanted drug-drug interactions leading to side effects or toxicities. When expressed in tumor tissues, it contributes to the development of chemotherapy resistance in malignancies. Therefore, the understanding of the molecular details of the ligand-ABCB1 interactions is of crucial importance. In a previous study, we found that quercetin (QUR) hampers both the transport and ATPase activity of ABCB1, while cyandin-3O-sophroside (C3S) stimulates the ATPase activity and causes only a weak inhibition of substrate transport. In the current study, when QUR and C3S were applied together, both a stronger ATPase inhibition and a robust decrease in substrate transport were observed, supporting their synergistic ABCB1 inhibitory effect. Similar to cyclosporine A, a potent ABCB1 inhibitor, co-treatment with QUR and C3S shifted the conformational equilibrium to the "inward-facing" conformer of ABCB1, as it was detected by the conformation-selective UIC2 mAb. To gain deeper insight into the molecular details of ligand-ABCB1 interactions, molecular docking experiments and MD simulations were also carried out. Our in silico studies support that QUR and C3S can bind simultaneously to ABCB1. The most favourable ligand-ABCB1 interaction is obtained when C3S binds to the central substrate binding site and QUR occupies the "access tunnel". Our results also highlight that the strong ABCB1 inhibitory effect of the combined treatment with QUR and C3S may be exploited in chemotherapy protocols for the treatment of multidrug-resistant tumors or for improving drug delivery through pharmacological barriers.

Initial Validation of a Sacroiliac Joint-Specific Disability Questionnaire.

Low back pain is a multidimensional disorder that can originate from a variety of pain generators, including the sacroiliac (SI) joint. Although the Oswestry Disability Index (ODI) is often used in SI joint treatment studies, the effects of the SI joint on functional disability are likely different from those of other low back pain generators. Thus, we developed the Denver SI Joint Questionnaire (DSIJQ) and performed validation testing in patients (n=24) with SI joint-specific pain at baseline, +2 weeks, and +6 months. Psychometric analyses included test-retest reliability, internal consistency, content validity, convergent criterion validity, divergent criterion validity, and responsiveness. The DSIJQ showed good test-retest reliability (intraclass correlation coefficient=0.87), internal consistency (Cronbach's alpha=0.842), content validity (<30% floor/ceiling effects), convergent criterion validity (r=0.89; P<.001), and divergent criterion validity (r=-0.33; P=.12). The DSIJQ was correlated with performance on two physical function tests: Timed Upand-Go (r=0.53; P=.008) and 5 Minute Walk (r=-0.52; P=.009). The DSIJQ showed better responsiveness than the ODI (standardized response mean and effect size, 1.14 and 1.45 for DSIJQ and 0.75 and 0.81 for ODI). Overall, the DSIJQ performed well on all psychometrics. Importantly, we validated the DSIJQ with patients' ability to complete two tests of physical functioning. Moreover, the DSIJQ was more sensitive to changes in SI joint disability than the ODI. These psychometrics suggest the DSIJQ is appropriate for evaluating SI joint disability and detecting changes in disability after targeted SI joint treatment. [Orthopedics. 2023;46(6):345-351.].

Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) Randomized Clinical Trial.

BACKGROUND: Staphylococcus aureus is a global pathogen that is frequently responsible for healthcare-associated infections, including surgical site infections (SSIs). Current infection prevention and control approaches may be limited, with S. aureus antibiotic resistance remaining problematic. Thus, a vaccine to prevent or reduce S. aureus infection is critically needed. We evaluated the efficacy and safety of an investigational 4-antigen S. aureus vaccine (SA4Ag) in adults undergoing elective open posterior spinal fusion procedures with multilevel instrumentation. METHODS: In this multicenter, site-level, randomized, double-blind trial, patients aged 18-85 years received a single dose of SA4Ag or placebo 10-60 days before surgery. SA4Ag efficacy in preventing postoperative S. aureus bloodstream infection and/or deep incisional or organ/space SSIs was the primary end point. Safety evaluations included local reactions, systemic events, and adverse events (AEs). Immunogenicity and colonization were assessed. RESULTS: Study enrollment was halted when a prespecified interim efficacy analysis met predefined futility criteria. SA4Ag showed no efficacy (0.0%) in preventing postoperative S. aureus infection (14 cases in each group through postoperative day 90), despite inducing robust functional immune responses to each antigen compared with placebo. Colonization rates across groups were similar through postoperative day 180. Local reactions and systemic events were mostly mild or moderate in severity, with AEs reported at similar frequencies across groups. CONCLUSIONS: In patients undergoing elective spinal fusion surgical procedures, SA4Ag was safe and well tolerated but, despite eliciting substantial antibody responses that blocked key S. aureus virulence mechanisms, was not efficacious in preventing S. aureus infection. Clinical Trials Registration. NCT02388165.

Identification of liquid biopsy-based mutations in colorectal cancer by targeted sequencing assays.

Recently, liquid biopsy, as a promising approach was introduced for the analysis of different tumor-derived circulating markers including tumor DNA and cell free DNA (ct/cfDNA). Identification of mutations in cfDNA may allow the early detection of tumors, as well as predicting and monitoring treatment responses in a minimally invasive way. In the present study, we used commercially available gene panels to verify the mutation overlap between liquid biopsy and abnormalities detected in colorectal tumor tissue. The two panels (Archer®VariantPlex®Solid Tumor and LIQUIDPlexTM ctDNA) overlap in 23 genes, which enables a comprehensive view of tumor-plasma mutational status by next generation sequencing. We successfully analyzed 16 plasma and 16 tumor samples. We found that 87% of tumor tissues contained 44 mutations in 12 genes and 43.8% of cfDNA harbored 13 mutations in 5 genes. To verify whether the mutation pattern of the tumor DNA could be consistently detected in plasma cfDNA, we compared the alterations between cfDNA and matched tissue DNA in nine patients. Six of the 9 tumor tissues harbored mutations in TP53, KRAS or MET genes, those were not detectable by the ctDNA kit, even eventhough the exons of these genes overlap in both panels. Comparing the mutational patterns of the matched samples, we found that only one cfDNA had the same mutations (KRAS, SMAD4 and TP53) in the paired tissue. The results of the comparison between tumor tissue DNA and matched plasma cfDNA underline the importance of studying the paired solid tumor and plasma samples together.

Cognitive deficits after general anaesthesia in animal models: a scoping review.

BACKGROUND: It remains controversial whether general anaesthetic drugs contribute to perioperative neurocognitive disorders in adult patients. Preclinical studies have generated conflicting results, likely because of differing animal models, study protocols, and measured outcomes. This scoping review of preclinical studies addressed the question: 'Do general anaesthetic drugs cause cognitive deficits in adult animals that persist after the drugs have been eliminated from the brain?' METHODS: Reports of preclinical studies in the MEDLINE database published from 1953 to 2021 were examined. A structured review process was used to assess original studies of cognitive behaviours, which were measured after treatment (≥24 h) with commonly used general anaesthetic drugs in adult animals. RESULTS: The initial search yielded 380 articles, of which 106 were fully analysed. The most frequently studied animal model was male (81%; n=86/106) rodents (n=106/106) between 2-3 months or 18-20 months of age. Volatile anaesthetic drugs were more frequently studied than injected drugs, and common outcomes were memory behaviours assessed using the Morris water maze and fear conditioning assays. Cognitive deficits were detected in 77% of studies (n=82/106) and were more frequent in studies of older animals (89%), after inhaled anaesthetics, and longer drug treatments. Limitations of the studies included a lack of physiological monitoring, mortality data, and risk of bias attributable to the absence of randomisation and blinding. CONCLUSIONS: Most studies reported cognitive deficits after general anaesthesia, with age, use of volatile anaesthetic drugs, and duration of anaesthesia as risk factors. Recommendations to improve study design and guide future research are presented.

Alternative Uses of O-Arm and Stealth Navigation Technology Over 10 Years: The University of Colorado Experience.

Intraoperative computed tomography scanning with O-arm and use of Stealth navigation can improve surgical outcomes in a variety of orthopedic subspecialties. In spine surgery, the accuracy, precision, and safety of pedicle screw and interbody implant placement has improved. This technology is now routinely used in percutaneous pedicle screw placement and minimally invasive sacroiliac joint fusion. Other applications include, but are not limited to, isthmic pars defect repair, lumbosacral pseudoarticulation resection in Bertolotti's syndrome, radiofrequency ablation, and en bloc tumor resection. Intraoperative navigation has numerous applications, and use of this technology should continue to evolve as the technology advances. [Orthopedics. 2023;46(2):e89-e97.].

Long-Term Outcomes of Restorative Neurostimulation in Patients With Refractory Chronic Low Back Pain Secondary to Multifidus Dysfunction: Two-Year Results of the ReActiv8-B Pivotal Trial.

BACKGROUND: Impaired neuromuscular control and degeneration of the multifidus muscle have been linked to the development of refractory chronic low back pain (CLBP). An implantable restorative-neurostimulator system can override the underlying multifidus inhibition by eliciting episodic, isolated contractions. The ReActiv8-B randomized, active-sham-controlled trial provided effectiveness and safety evidence for this system, and all participants received therapeutic stimulation from four months onward. OBJECTIVE: This study aimed to evaluate the two-year effectiveness of this restorative neurostimulator in patients with disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Open-label follow-up of 204 participants implanted with a restorative neurostimulation system (ReActiv8, Mainstay Medical, Dublin, Ireland) was performed. Pain intensity (visual analog scale [VAS]), disability (Oswestry disability index [ODI]), quality-of-life (EQ-5D-5L), and opioid intake were assessed at baseline, six months, one year, and two years after activation. RESULTS: At two years (n = 156), the proportion of participants with ≥50% CLBP relief was 71%, and 65% reported CLBP resolution (VAS ≤ 2.5 cm); 61% had a reduction in ODI of ≥20 points, 76% had improvements of ≥50% in VAS and/or ≥20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 87% of participants had continued device use during the second year for a median of 43% of the maximum duration, and 60% (34 of 57) had voluntarily discontinued (39%) or reduced (21%) opioid intake. CONCLUSIONS: At two years, 76% of participants experienced substantial, clinically meaningful improvements in pain, disability, or both. These results provide evidence of long-term effectiveness and durability of restorative neurostimulation in patients with disabling CLBP, secondary to multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The study is registered on clinicaltrials.gov with identifier NCT02577354.

Catastrophic acute failure of pelvic fixation in adult spinal deformity requiring revision surgery: a multicenter review of incidence, failure mechanisms, and risk factors.

OBJECTIVE: There are few prior reports of acute pelvic instrumentation failure in spinal deformity surgery. The objective of this study was to determine if a previously identified mechanism and rate of pelvic fixation failure were present across multiple institutions, and to determine risk factors for these types of failures. METHODS: Thirteen academic medical centers performed a retrospective review of 18 months of consecutive adult spinal fusions extending 3 or more levels, which included new pelvic screws at the time of surgery. Acute pelvic fixation failure was defined as occurring within 6 months of the index surgery and requiring surgical revision. RESULTS: Failure occurred in 37 (5%) of 779 cases and consisted of either slippage of the rods or displacement of the set screws from the screw tulip head (17 cases), screw shaft fracture (9 cases), screw loosening (9 cases), and/or resultant kyphotic fracture of the sacrum (6 cases). Revision strategies involved new pelvic fixation and/or multiple rod constructs. Six patients (16%) who underwent revision with fewer than 4 rods to the pelvis sustained a second acute failure, but no secondary failures occurred when at least 4 rods were used. In the univariate analysis, the magnitude of surgical correction was higher in the failure cohort (higher preoperative T1-pelvic angle [T1PA], presence of a 3-column osteotomy; p < 0.05). Uncorrected postoperative deformity increased failure risk (pelvic incidence-lumbar lordosis mismatch > 10°, higher postoperative T1PA; p < 0.05). Use of pelvic screws less than 8.5 mm in diameter also increased the likelihood of failure (p < 0.05). In the multivariate analysis, a larger preoperative global deformity as measured by T1PA was associated with failure, male patients were more likely to experience failure than female patients, and there was a strong association with implant manufacturer (p < 0.05). Anterior column support with an L5-S1 interbody fusion was protective against failure (p < 0.05). CONCLUSIONS: Acute catastrophic failures involved large-magnitude surgical corrections and likely resulted from high mechanical strain on the pelvic instrumentation. Patients with large corrections may benefit from anterior structural support placed at the most caudal motion segment and multiple rods connecting to more than 2 pelvic fixation points. If failure occurs, salvage with a minimum of 4 rods and 4 pelvic fixation points can be successful.

Three-Year Durability of Restorative Neurostimulation Effectiveness in Patients With Chronic Low Back Pain and Multifidus Muscle Dysfunction.

BACKGROUND: Restorative neurostimulation is a rehabilitative treatment for patients with refractory chronic low back pain (CLBP) associated with dysfunction of the lumbar multifidus muscle resulting in impaired neuromuscular control. The ReActiv8-B randomized, sham-controlled trial provided evidence of the effectiveness and safety of an implanted, restorative neurostimulator. The two-year analysis previously published in this journal demonstrated accrual of clinical benefits and long-term durability. OBJECTIVE: Evaluation of three-year effectiveness and safety in patients with refractory, disabling CLBP secondary to multifidus muscle dysfunction and no indications for spine surgery. MATERIALS AND METHODS: Prospective, observational follow-up of the 204 implanted trial participants. Low back pain visual analog scale (VAS), Oswestry Disability Index (ODI), EuroQol quality of life survey, and opioid intake were assessed at baseline, six months, and one, two, and three years after activation. The mixed-effects model repeated measures approach was used to provide implicit imputations of missing data for continuous outcomes and multiple imputation for proportion estimates. RESULTS: Data were collected from 133 participants, and 16 patients missed their three-year follow-up because of coronavirus disease restrictions but remain available for future follow-up. A total of 62% of participants had a ≥ 70% VAS reduction, and 67% reported CLBP resolution (VAS ≤ 2.5cm); 63% had a reduction in ODI of ≥ 20 points; 83% had improvements of ≥ 50% in VAS and/or ≥ 20 points in ODI, and 56% had these substantial improvements in both VAS and ODI. A total of 71% (36/51) participants on opioids at baseline had voluntarily discontinued (49%) or reduced (22%) opioid intake. The attenuation of effectiveness in the imputed (N = 204) analyses was relatively small and did not affect the statistical significance and clinical relevance of these results. The safety profile remains favorable, and no lead migrations have been observed to date. CONCLUSION: At three years, 83% of participants experienced clinically substantial improvements in pain, disability, or both. The results confirm the long-term effectiveness, durability, and safety of restorative neurostimulation in patients with disabling CLBP associated with multifidus muscle dysfunction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02577354.

Biomechanical evaluation of a novel repair strategy for intervertebral disc herniation in an ovine lumbar spine model.

Following herniation of the intervertebral disc, there is a need for advanced surgical strategies to protect the diseased tissue from further herniation and to minimize further degeneration. Accordingly, a novel tissue engineered implant for annulus fibrosus (AF) repair was fabricated via three-dimensional fiber deposition and evaluated in a large animal model. Specifically, lumbar spine kinetics were assessed for eight (n = 8) cadaveric ovine lumbar spines in three pure moment loading settings (flexion-extension, lateral bending, and axial rotation) and three clinical conditions (intact, with a defect in the AF, and with the defect treated using the AF repair implant). In ex vivo testing, seven of the fifteen evaluated biomechanical measures were significantly altered by the defect. In each of these cases, the treated spine more closely approximated the intact biomechanics and four of these cases were also significantly different to the defect. The same spinal kinetics were also assessed in a preliminary in vivo study of three (n = 3) ovine lumbar spines 12 weeks post-implantation. Similar to the ex vivo results, functional efficacy of the treatment was demonstrated as compared to the defect model at 12 weeks post-implantation. These promising results motivate a future large animal study cohort which will establish statistical power of these results further elucidate the observed outcomes, and provide a platform for clinical translation of this novel AF repair patch strategy. Ultimately, the developed approach to AF repair holds the potential to maintain the long-term biomechanical function of the spine and prevent symptomatic re-herniation.