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.

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.

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.

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.

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.

Factors Associated With Inpatient Endoscopy Delay and its Impact on Hospital Length-of-Stay and 30-Day Readmission.

BACKGROUNDS AND AIMS: Inpatient endoscopy delay (IED) negatively impacts the delivery of high-quality care. We aimed to identify factors associated with IED and evaluate its effect on hospital length-of-stay (LOS) and readmission. METHODS: This was a retrospective analysis of all inpatient endoscopies performed between November 2017 and November 2019 at a tertiary care center. IED was defined as the number of days elapsed between anticipated versus actual procedure day. Data were extracted from the endoscopy documentation software and via electronic chart review. Multivariate logistic regressions were modeled to determine variables associated with IED and hospital readmission. RESULTS: A total of 4239 inpatients (mean age, 58.3 years; 50.3% women) underwent endoscopic procedures during the study period of which 819 patients (19.3%) experienced a delay. IED resulted in a median prolonged LOS of 2 days (interquartile range, 1-2 days). Patients with IED were less likely to have an etiology identified on endoscopy (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.63-0.86; P < .001). The 2 most common causes for delays were poor bowel preparation (n = 218; 27%) and lack of endoscopy personnel/unit availability (n = 197; 24.4%). Independent predictors of IED included: older age (OR, 1.1; 95% CI, 1.01-1.03; P = .03), female sex (OR, 1.20; 95% CI, 1.03-1.40; P = .02), use of antithrombotics (OR, 1.30; 95% CI, 1.08-1.57; P = .006), opioids (OR, 1.23; 95% CI, 1.04-1.44; P = .012), being on contact isolation (OR, 1.38; 95% CI, 1.09-1.75; P = .008), and colonoscopy (OR, 1.50; 95% CI, 1.27-1.77; P < .001). Conversely, inpatients admitted to a dedicated GI medicine service were less likely to have IED (OR, 0.79; 95% CI, 0.65-0.96; P = .02). IED was the only independent predictor of 30-day readmission (OR, 1.22; 95% CI, 1.02-1.47; P = .03). CONCLUSIONS: IED occurred frequently, unfavorably prolonged LOS, and was an independent risk factor for 30-day readmission. We provide a comprehensive analysis of actionable variables associated with IED that can be targeted to improve inpatient endoscopy delivery.

Toxicology Screening Testing in Patients Undergoing Spine Surgery: A Prospective Observational Pilot Study.

BACKGROUND: Chronic opioid use and polypharmacy are commonly seen in chronic pain patients presenting for spine procedures. Substance abuse and misuse have also been reported in this patient population. Negative perioperative effects have been found in patients exposed to chronic opioid, alcohol, and recreational substances. Toxicology screening testing (TST) in the perioperative period provides useful information for adequate preoperative optimization and perioperative planning. METHODS: We designed a pilot study to understand this population's preoperative habits including accuracy of self-report and TST-detected prescribed and unprescribed medications and recreational substances. We compared the results of the TST to the self-reported medications using Spearman correlations. RESULTS: Inconsistencies between TST and self-report were found in 88% of patients. Spearman correlation was 0.509 between polypharmacy and intraoperative propofol use, suggesting that propofol requirement increased as the number of substances used increased. CONCLUSIONS: TST in patients presenting for spine surgery is a useful tool to detect substances taken by patients because self-report is often inaccurate. Discrepancies decrease the opportunity for preoperative optimization and adequate perioperative preparation.

MoS2/WSe2nanohybrids for flexible paper-based photodetectors.

Flexible photodetectors functionalized by transition metal dichalcogenides have attracted great attention due to their excellent photo-harvesting efficiency. However, the field of optoelectronics still requires advancement in the production of large-area, broad band and flexible photodetectors. Here we report a flexible, stable, broad band and fast photodetector based on a MoS2/WSe2heterostructure on ordinary photocopy paper with pencil-drawn graphite electrodes. Ultrathin MoS2/WSe2nanohybrids have been synthesized by an ultrahigh yield liquid-phase exfoliation technique. The thin sheets of WSe2, and MoS2contain two to four layers with a highly c-oriented crystalline structure. Subsequently, the photodetector was exploited under ultra-broad spectral range from 400 to 780 nm. The photodetector exhibits excellent figure of merit such as on/off ratio of the order of 103, photoresponsivity of 124 mA W-1and external quantum efficiency of 23.1%. Encouragingly, rise/decay time of about 0.1/0.3 s was realized, which is better than in previous reports on paper-based devices.

AAPM Medical Physics Practice Guideline 1.b: CT protocol management and review practice guideline.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: (a) Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. (b) Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.

Validation of new shoulder periprosthetic joint infection criteria.

BACKGROUND: A periprosthetic joint infection (PJI) in the shoulder can be difficult to diagnose. Many variables have been used to determine a PJI. Recently, the 2018 International Consensus Meeting (ICM) on orthopedic infections gave new criteria to help identify PJI in the shoulder. With the new criteria (major and minor), the PJI definition can be categorized into definite, probable, possible, and unlikely. This study was conducted to assess the new criteria for a series of consecutive first stage revision shoulder arthroplasty cases. METHODS: All patients undergoing a first stage revision shoulder arthroplasty using a prosthesis made of antibiotic-loaded acrylic cement (PROSTALAC) spacer from 2016 through 2019 were evaluated retrospectively. All cases were performed by a single surgeon. Each case was reviewed using the 2018 shoulder ICM diagnostic criteria. Secondary factors evaluated were type of organism identified, accuracy of minor criteria, and frozen vs. permanent section accuracy. RESULTS: A total of 87 first-stage revision arthroplasty cases were reviewed. Based on the 2018 ICM criteria, there were 20 definite (30.0%), 19 probable (21.8%), 6 possible (6.9%), and 42 unlikely (48.3%) infections. Cutibacterium acnes was the most common infectious organism overall (77.3% of culture positive cases) and was present in 39.1% of cases overall. Ten patients (25.6%) grew multiple organisms. Thirty-one patients (35.6%) had a loose humeral stem, with 23 of those patients (74.2%) having a definite or probable infection (odds ratio [OR] 7.2, 95% confidence interval [CI] 2.67-19.37, P = .0001). Eleven patients (91.7%) with an elevated intraoperative synovial neutrophil cell count had a definite or probable infection. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) was elevated in patients with a definite or probable infection (OR 9.4, 95% CI 2.47-35.62, P = .0010, and OR 7.7, 95% CI 2.29-25.56, P = .0009), respectively. Discordant results between frozen and permanent sections were found in 4 patients (4.6%). CONCLUSION: The 2018 ICM shoulder infection criteria gave a new scoring system to diagnose PJI. C acnes was the most common infectious organism identified. Patients who had a loose humeral stem, elevated ESR, or elevated CRP were more likely to have either a definite or probable PJI. Frozen sections were able to accurately identify definite infections. Unexpected wound drainage and positive preoperative cultures were low-yield criteria in this series. More research into determining periprosthetic shoulder infection is needed to help identify which patients are more likely to have an infection.

Strap stabilization for proximal junctional kyphosis prevention in instrumented posterior spinal fusion.

STUDY DESIGN: This is a retrospective, single-institution, cohort study. OBJECTIVES: To evaluate the association of Mersilene tape use and risk of proximal junctional kyphosis (PJK), after surgical correction of adult spinal deformity (ASD) by posterior instrumented fusion (PIF). PJK, following long spinal PIF, is a complication which often requires reoperation. Mersilene tape, strap stabilization of the supra-adjacent level to upper instrumented vertebra (UIV) seems a preventive measure. METHODS: Patients who underwent PIF for ASD with Mersilene tape stabilization (case group) or without (control group) between 2006 and 2016 were analyzed preoperatively to 2-year follow-up. Matching of potential controls to each case was performed. Radiographic sagittal Cobb angle (SCA), lumbar lordosis, pelvic tilt, sacral slope, and pelvic incidence were measured pre- and postoperatively, using a deformity measuring software program. PJK was defined as progression of postoperative junctional SCA at UIV ≥ 10°. RESULTS: Eighty patients were included: 20 cases and 60 controls. The cumulative rate of PJK ≥ 10° at 2-year follow-up was 15% in cases versus 38% of controls (OR = 0.28; P = 0.04) with higher latent period in cases, (20 vs. 7.5 months), P = 0.018. Mersilene tape decreased risk of PJK linked with the impact of the following confounders: age, ≥ 55 years old (OR = 0.19; 0.02 ≥ P ≤ 0.03); number of spinal levels fused 7-15 (OR = 0.13; 0.02 ≥ P ≤ 0.06); thoracic UIV (T12-T1) (OR = 0.13; 0.02 ≥ P ≤ 0.06); BMI ≥ 27 kg/m2 (OR = 0.22; 0.03 ≥ P ≤ 0.08); and osteoporosis (OR = 0.13; 0.02 ≥ P ≤ 0.08). CONCLUSIONS: Mersilene tape at UIV + 1 level decreases the risk of PJK following PIF for ASD. These slides can be retrieved under Electronic Supplementary Material.

Early results of reverse total shoulder arthroplasty using a patient-matched glenoid implant for severe glenoid bone deficiency.

BACKGROUND: Reverse total shoulder arthroplasty (rTSA) in the presence of significant glenoid bone loss remains a challenge. This study presents preliminary clinical and radiographic outcomes of primary and revision rTSA using a patient-matched, 3-dimensionally printed custom metal glenoid implant to address severe glenoid bone deficiency. METHODS: Between September 2017 and November 2018, 19 patients with severe glenoid bone deficiency underwent primary (n = 9) or revision rTSA (n = 10) using the Comprehensive Vault Reconstruction System (VRS) (Zimmer Biomet, Warsaw, IN, USA) at a single institution. Preoperative and postoperative values for the Disabilities of the Arm, Shoulder and Hand score, Constant score, American Shoulder and Elbow Surgeons score, Simple Shoulder Test score, Single Assessment Numeric Evaluation score, and visual analog scale pain score and active range of motion were compared using the Wilcoxon signed rank test with the level of statistical significance set at P < .05. RESULTS: Complications occurred in 4 patients (21%), including a nondisplaced greater tuberosity fracture treated conservatively in 1, intraoperative cortical perforation during humeral cement removal treated with an allograft strut in 1, and recurrent instability and hematoma formation treated with humeral component revision in 1. One patient with an early periprosthetic infection was treated with component removal and antibiotic spacer placement at an outside facility and was subsequently lost to follow-up. Eighteen patients with 1-year minimum clinical and radiographic follow-up were evaluated (mean, 18.2 months; range, 12-27 months). Significant improvements were noted in the mean Disabilities of the Arm, Shoulder and Hand score (57.4 ± 16.5 vs. 29.4 ± 19.5, P < .001), mean Constant score (24.6 ± 10.2 vs. 60.4 ± 14.5, P < .001), mean American Shoulder and Elbow Surgeons score (32 ± 18.2 vs. 79 ± 15.6, P < .001), mean Simple Shoulder Test score (4.5 ± 2.6 vs. 9.3 ± 1.8, P < .001), mean Single Assessment Numeric Evaluation score (25.4 ± 13.7 vs. 72.2 ± 17.8, P < .001), mean visual analog scale pain score (6.2 ± 2.9 vs. 0.7 ± 1.3, P < .001), mean active forward flexion (53° ± 27° vs. 124° ± 23°, P < .001), and mean active abduction (42° ± 17° to 77° ± 15°, P < .001). Mean external rotation changed from 17° ± 19° to 32° ± 24° (P = .06). No radiographic evidence of component loosening, scapular notching, or hardware failure was observed at last follow-up in any patient. CONCLUSION: The preliminary results of rTSA using the VRS to manage severe glenoid bone deficiency are promising, but longer follow-up is necessary to determine the longevity of this implant.

Mechanisms of lysophosphatidylcholine-induced demyelination: A primary lipid disrupting myelinopathy.

For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce demyelination, without a clear understanding of its mechanisms. LPC is an endogenous lysophospholipid so it may cause demyelination in certain diseases. We investigated whether known receptor systems, inflammation or nonspecific lipid disruption mediates LPC-demyelination in mice. We found that LPC nonspecifically disrupted myelin lipids. LPC integrated into cellular membranes and rapidly induced cell membrane permeability; in mice, LPC injury was phenocopied by other lipid disrupting agents. Interestingly, following its injection into white matter, LPC was cleared within 24 hr but by five days there was an elevation of endogenous LPC that was not associated with damage. This elevation of LPC in the absence of injury raises the possibility that the brain has mechanisms to buffer LPC. In support, LPC injury in culture was significantly ameliorated by albumin buffering. These results shed light on the mechanisms of LPC injury and homeostasis.

Evaluation and Prediction of Human Lumbar Vertebrae Endplate Mechanical Properties Using Indentation and Computed Tomography.

Current implant materials and designs used in spinal fusion show high rates of subsidence. There is currently a need for a method to predict the mechanical properties of the endplate using clinically available tools. The purpose of this study was to develop a predictive model of the mechanical properties of the vertebral endplate at a scale relevant to the evaluation of current medical implant designs and materials. Twenty vertebrae (10 L1 and 10 L2) from 10 cadavers were studied using dual-energy X-ray absorptiometry to define bone status (normal, osteopenic, or osteoporotic) and computed tomography (CT) to study endplate thickness (µm), density (mg/mm3), and mineral density of underlying trabecular bone (mg/mm3) at discrete sites. Apparent Oliver-Pharr modulus, stiffness, maximum tolerable pressure (MTP), and Brinell hardness were measured at each site using a 3 mm spherical indenter. Predictive models were built for each measured property using various measures obtained from CT and demographic data. Stiffness showed a strong correlation between the predictive model and experimental values (r = 0.85), a polynomial model for Brinell hardness had a stronger predictive ability compared to the linear model (r = 0.82), and the modulus model showed weak predictive ability (r = 0.44), likely due the low indentation depth and the inability to image the endplate at that depth (≈0.15 mm). Osteoporosis and osteopenia were found to be the largest confounders of the measured properties, decreasing them by approximately 50%. It was confirmed that vertebral endplate mechanical properties could be predicted using CT and demographic indices.

Interbody Spacer Material Properties and Design Conformity for Reducing Subsidence During Lumbar Interbody Fusion.

There is a need to better understand the effects of intervertebral spacer material and design on the stress distribution in vertebral bodies and endplates to help reduce complications such as subsidence and improve outcomes following lumbar interbody fusion. The main objective of this study was to investigate the effects of spacer material on the stress and strain in the lumbar spine after interbody fusion with posterior instrumentation. A standard spacer was also compared with a custom-fit spacer, which conformed to the vertebral endplates, to determine if a custom fit would reduce stress on the endplates. A finite element (FE) model of the L4-L5 motion segment was developed from computed tomography (CT) images of a cadaveric lumbar spine. An interbody spacer, pedicle screws, and posterior rods were incorporated into the image-based model. The model was loaded in axial compression, and strain and stress were determined in the vertebra, spacer, and rods. Polyetheretherketone (PEEK), titanium, poly(para-phenylene) (PPP), and porous PPP (70% by volume) were used as the spacer material to quantify the effects on stress and strain in the system. Experimental testing of a cadaveric specimen was used to validate the model's results. There were no large differences in stress levels (<3%) at the bone-spacer interfaces and the rods when PEEK was used instead of titanium. Use of the porous PPP spacer produced an 8-15% decrease of stress at the bone-spacer interfaces and posterior rods. The custom-shaped spacer significantly decreased (>37%) the stress at the bone-spacer interfaces for all materials tested. A 28% decrease in stress was found in the posterior rods with the custom spacer. Of all the spacer materials tested with the custom spacer design, 70% porous PPP resulted in the lowest stress at the bone-spacer interfaces. The results show the potential for more compliant materials to reduce stress on the vertebral endplates postsurgery. The custom spacer provided a greater contact area between the spacer and bone, which distributed the stress more evenly, highlighting a possible strategy to decrease the risk of subsidence.

An analysis of spine fusion outcomes in sheep pre-clinical models.

PURPOSE: The ovine model is often used to evaluate new spine fusion technologies prior to clinical testing. An important aspect of designing sheep surgery protocols is to select the appropriate postoperative time period for comparing fusion outcomes. Unfortunately, determining the ideal study endpoint is complicated by the fact that prior published studies have not used consistent timeframes. Thus, the primary aim of this study was to provide a reference for investigators as to the expected fusion outcomes of control groups at varying timepoints in sheep spine surgery models. METHODS: We identified published sheep fusion studies using autograft, interbody cages, and/or instrumentation. Fusion data were extracted, converted to a common scale, and analyzed across studied timepoints. RESULTS: Overall, 29 studies of 360 fusion levels were identified: 11 ALIF (158 levels), 3 PLIF/TLIF (28 levels), 8 PLF (90 levels), and 7 ACDF (84 levels). Studied timepoints ranged from 4 to 48 weeks postoperative. In general, fusion rates varied across techniques and instrumentation. The time to reach solid fusion differed by as many as 20 weeks between control groups. CONCLUSIONS: Recommended timeframes for future studies designed to show either superiority over controls or equivalent outcomes with controls were developed based on aggregate results. Designating ideal study endpoints for sheep fusion models has both ethical implications associated with responsible use of animals in research, and economic implications given the cost of animal research. The current results can guide the development of future research methods and help investigators choose appropriate study timelines for various control groups.

Utilization of CT scanning associated with complex spine surgery.

BACKGROUND: Due to the risk associated with exposure to ionizing radiation, there is an urgent need to identify areas of CT scanning overutilization. While increased use of diagnostic spinal imaging has been documented, no previous research has estimated the magnitude of follow-up imaging used to evaluate the postoperative spine. METHODS: This retrospective cohort study quantifies the association between spinal surgery and CT utilization. An insurance database (Humana, Inc.) with ≈ 19 million enrollees was employed, representing 8 consecutive years (2007-2014). Surgical and imaging procedures were captured by anatomic-specific CPT codes. Complex surgeries included all cervical, thoracic and lumbar instrumented spine fusions. Simple surgeries included discectomy and laminectomy. Imaging was restricted to CT and MRI. Postoperative imaging frequency extended to 5-years post-surgery. RESULTS: There were 140,660 complex spinal procedures and 39,943 discectomies and 49,889 laminectomies. MRI was the predominate preoperative imaging modality for all surgical procedures (median: 80%; range: 73-82%). Postoperatively, CT prevalence following complex procedures increased more than two-fold from 6 months (18%) to 5 years (≥40%), and patients having a postoperative CT averaged two scans. For simple procedures, the prevalence of postoperative CT scanning never exceeded 30%. CONCLUSIONS: CT scanning is used frequently for follow-up imaging evaluation following complex spine surgery. There is emerging evidence of an increased cancer risk due to ionizing radiation exposure with CT. In the setting of complex spine surgery, actions to mitigate this risk should be considered and include reducing nonessential scans, using the lowest possible radiation dose protocols, exerting greater selectivity in monitoring the developing fusion construct, and adopting non-ferromagnetic implant biomaterials that facilitate MRI postoperatively.