Association of polymorphism in leptin receptor gene with susceptibility of adolescent idiopathic scoliosis.

PURPOSE: Abnormal leptin bioavailability has play key roles in the etiology of adolescent idiopathic scoliosis (AIS). Both leptin and its receptor levels may be modulated by the presence of genetic polymorphisms. This study aimed to evaluate the role of polymorphisms in the leptin (LEP) and its main receptor (LEPR) genes in the AIS susceptibility in girls. METHODS: A retrospective case-control study was conducted with 189 AIS and 240 controls. LEP rs2167270 and LEPR rs2767485 polymorphisms were genotyped using a TaqMan validated assay. Associations were evaluated by odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The AIS group showed a predominance of girls under 18 years old (n = 140, 74.1%), 148 (78.3%) had low or normal BMI, 111 (58.7%) had Cobb ≥ 45º and 130 (68.7%) were skeletally mature. Minor allele frequencies of rs2167270 and rs2767485 were 35.7% and 18.3%, for AIS and 35.6% and 25.4% for controls, respectively. LEPR rs2767485 T and TC + TT were associated with higher risk of AIS (OR = 1.53; 95% CI = 1.09-2.13 and OR = 1.84; 95% CI = 1.69-2.01, respectively), since CC genotype was only present in the control group. In addition, the LEP rs2167270 GA + AA was more frequent in low weight group (BMI ≤ 24.9) of girls with AIS. There was no significant association between LEP rs2167270 and AIS susceptibility, and LEPR rs2767485 and BMI. CONCLUSION: The LEPR rs2767485 was associated with the genetic susceptibility of AIS and LEP rs2167270 with low BMI. These data can contribute to the identification of genetic biomarkers to improve the diagnosis and treatment.

Neutrophil Extracellular Trap-related Biomarkers Are Increased in the Synovial Fluid of Patients With Periprosthetic Joint Infections.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) is a major challenge in clinical practice. The role of neutrophils in fighting infection has been increasingly understood, and one mechanism of action of these cells is neutrophil extracellular traps. However, little is known about this process in PJI. QUESTIONS/PURPOSES: (1) Are the biomarkers of neutrophil extracellular trap formation (citrullinated histone H3 [H3Cit], cell-free DNA [cf-DNA], and myeloperoxidase [MPO]) increased in the synovial fluid of patients with PJI? (2) What is the diagnostic accuracy of biomarkers of neutrophil extracellular trap formation for PJI? METHODS: Between May 2020 and March 2021, 43 patients who underwent revision THA or TKA were enrolled in this study. Eleven patients were excluded and 32 patients were categorized into the PJI group (n = 16) or non-PJI group (n = 16) according to the 2018 Second International Consensus Meeting on Musculoskeletal Infection criteria. There were 15 men and 17 women in this study, with a median (range) age of 70 years (60 to 80 years). Twenty-seven patients had TKA and five had THA. We measured cf-DNA, MPO, and H3Cit in synovial fluid. The sensitivity, specificity, and receiver operating characteristic curve were calculated for each biomarker using the Musculoskeletal Infection Society criteria as the gold standard for diagnosis and considering a clinical surveillance of 2 years for patients in the non-PJI group. RESULTS: Patients with PJI had higher levels of synovial fluid cf-DNA (median [range] 130 ng/µL [18 to 179] versus 2 ng/µL [0 to 6]; p < 0.001), MPO (1436 ng/µL [55 to 3996] versus 0 ng/µL [0 to 393]; p < 0.001), and H3Cit (2115 ng/µL [5 to 2885] versus 3 ng/µL [0 to 87]; p < 0.001) than those in the non-PJI group. In receiver operating characteristic curve analyses, we observed near-perfect performance for all biomarkers evaluated, with an area under the curve of 1 (95% CI 0.9 to 1), 0.98 (95% CI 0.9 to 1), and 0.94 (95% CI 0.8 to 0.99) for cf-DNA, MPO, and H3Cit, respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 94% for MPO, and 88% for H3Cit. The specificity was 100% for cf-DNA and MPO, and 88% for H3Cit. CONCLUSION: Our results show that neutrophils in the periprosthetic microenvironment release neutrophil extracellular traps as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for identifying new biomarkers and improving the available ones. Novel studies are needed to define whether and how neutrophil extracellular trap-related biomarkers can be useful for diagnosing PJI. LEVEL OF EVIDENCE: Level II, diagnostic study.

Association of FBN1 polymorphism with susceptibility of adolescent idiopathic scoliosis: a case-control study.

BACKGROUND: Fibrillin-1 (FBN1) is an extracellular matrix glycoprotein essential to the structural component of microfibrils and FBN1 gene polymorphisms can be associated with adolescent idiopathic scoliosis (AIS) susceptibility. This study aimed to evaluate the potential role of the FBN1 rs12916536 polymorphism in AIS development or severity and the variation in Cobb angle in relation to patient's characteristics. METHODS: DNA from 563 subjects (185 AIS patients and 378 controls) were genotyped using a validated TaqMan allelic discrimination assay. A multivariate logistic regression model evaluated the association between polymorphism and AIS, using the adjusted odds ratios (OR) with their respective 95% confidence intervals (95% CI). A linear regression analysis evaluated the variation in Cobb angle according to the patient's age and body mass index (BMI). RESULTS: Among the AIS group there was a predominance of females (12:1), low or normal BMI (90%), 58% had a Cobb angle greater than 45° and 74% were skeletally mature. Age was a risk factor (4-fold) for curve progression higher than BMI (P < 0.001). The allelic frequency of the rs12916536 G > A polymorphism was 40% in controls and 31% in AIS cases; and this difference was statistically significant (P = 0.004). FBN1 rs12916536 GA + AA genotypes were associated with a lower risk of AIS susceptibility (OR = 0.58 and 95% CI = 0.35-0.98), after adjustment for age, sex and BMI. However, no significant differences were detected in polymorphism distribution with the severity of the disease (Cobb < 45° or ≥ 45°). CONCLUSION: Age was a risk factor for progression of the scoliotic curve and FBN1 rs12916536 polymorphism a protective factor for AIS susceptibility.

Predictors of hospital readmission within 30 days after surgery for thoracolumbar fractures: A mixed approach.

BACKGROUND: Readmission followed by surgery to treat spinal fractures has a substantial impact on patient care costs and reflects a hospital's quality standards. This article analyzes the factors associated with hospital readmission followed by surgery to treat spinal fractures. METHODS: This was a cross-sectional study with time-series analysis. For prediction analysis, we used Cox proportional hazards and machine-learning models, using data from the Healthcare Cost and Utilization Project, Inpatient Database from Florida (USA). RESULTS: The sample comprised 215,999 patients, 8.8% of whom were readmitted within 30 days. The factors associated with a risk of readmission were male sex (1.1 [95% confidence interval 1.06-1.13]) and >60 years of age (1.74 [95% CI: 1.69-1.8]). Surgeons with a higher annual patient volume presented a lower risk of readmission (0.61 [95% CI: 0.59-0.63]) and hospitals with an annual volume >393 presented a lower risk (0.92 [95% CI: 0.89-0.95]). CONCLUSION: Surgical procedures and other selected predictors and machine-learning models can be used to reduce 30-day readmissions after spinal surgery. Identification of patients at higher risk for readmission and complications is the first step to reducing unplanned readmissions.

Open versus minimally invasive percutaneous surgery for surgical treatment of thoracolumbar spine fractures- a multicenter randomized controlled trial: study protocol.

BACKGROUND: Thoracolumbar fractures are most frequent along the spine, and surgical treatment is indicated for unstable fractures. Percutaneous minimally invasive surgery was introduced to reduce the pain associated with the open posterior approach and reduce the morbidity of the procedure by avoiding damage and dissection of the paravertebral muscles. The goal of this study is to compare the surgical treatment of fractures of the thoracolumbar spine treated by the conventional open approach and the percutaneous minimally invasive approach using similar types of pedicle spine fixation systems. METHODS/DESIGNS: This study is designed as a multi-center, randomized controlled trial of patients aged 18-65 years who are scheduled to undergo surgical posterior fixation. Treatment by the conventional open approach or percutaneous minimally invasive approach will be randomly assigned. The primary outcome measure is postoperative pain, which will be measured using the visual analogue scale (VAS). The secondary outcome parameters are intraoperative bleeding, postoperative drainage, surgery time, length of hospital stay, SF-36, EQ-5D-5 l, HADS, pain medication, deambulation after surgery, intraoperative fluoroscopy time, vertebral segment kyphosis, fracture vertebral body height, compression of the vertebral canal, accuracy of the pedicle screws, and breakage or release of the implants. Patient will be followed up for 1, 2, 3, 6, 12 and 24 months postoperatively and evaluated according to the outcomes using clinical and radiological examinations, plain radiographs and computed tomografy (CT). DISCUSSION: Surgical treatment of thoracolumbar fractures by the open or percutaneous minimally invasive approach will be compared in a multicenter randomized study using similar types of fixation systems, and the results will be evaluated according to clinical and radiological parameters at 1, 2, 3, 6, 12 and 24 months of follow-up. TRIAL REGISTRATION: ClinicalTrial.gov approval number: 1.933.631, code: NCT03316703 in may 2017.

Does age affect surgical outcomes in patients with degenerative cervical myelopathy? Results from the prospective multicenter AOSpine International study on 479 patients.

BACKGROUND: In general, older patients with degenerative cervical myelopathy (DCM) are felt to have lower recovery potential following surgery due to increased degenerative pathology, comorbidities, reduced physiological reserves and age-related changes to the spinal cord. This study aims to determine whether age truly is an independent predictor of surgical outcome and to provide evidence to guide practice and decision-making. METHODS: A total of 479 patients with DCM were prospectively enrolled in the CSM-International study at 16 centres. Our sample was divided into a younger group (<65 years) and an elderly (≥65 years) group. A mixed model analytic approach was used to evaluate differences in the modified Japanese Orthopaedic Association (mJOA), Nurick, Short Form-36 (SF-36) and Neck Disability Index (NDI) scores between groups. We first created an unadjusted model between age and surgical outcome and then developed two adjusted models that accounted for variations in (1) baseline characteristics and (2) both baseline and surgical factors. RESULTS: Of the 479 patients, 360 (75.16%) were <65 years and 119 (24.84%) were ≥65 years. Elderly patients had a worse preoperative health status (p<0.0001) and were functionally more severe (p<0.0001). The majority of younger patients (64.96%) underwent anterior surgery, whereas the preferred approach in the elderly group was posterior (58.62%, p<0.0001). Elderly patients had a greater number of decompressed levels than younger patients (p<0.0001). At 24 months after surgery, younger patients achieved a higher postoperative mJOA (p<0.0001) and a lower Nurick score (p<0.0001) than elderly patients. After adjustments for patient and surgical characteristics, these differences in postoperative outcome scores decreased but remained significant. CONCLUSIONS: Older age is an independent predictor of functional status in patients with DCM. However, patients over 65 with DCM still achieve functionally significant improvement after surgical decompression.

Diffusion-weighted magnetic resonance (DW-MR) neurography of the lumbar plexus in the preoperative planning of lateral access lumbar surgery.

PURPOSE: Magnetic resonance (MR) neurography has been used to evaluate entire nerves and nerve bundles by providing better contrast between the nerves and the surrounding tissues. The purpose of the study was to validate diffusion-weighted MR (DW-MR) neurography in visualizing the lumbar plexus during preoperative planning of lateral transpsoas surgery. METHODS: Ninety-four (188 lumbar plexuses) spine patients underwent a DW-MR examination of the lumbar plexus in relation to the L3-4 and L4-5 disc spaces and superior third of the L5 vertebral body. Images were reconstructed in the axial plane using high-resolution Maximum Intensity projection (MIP) overlay templates at the disc space and L3-4 and L4-5 interspaces. 10 and 22 mm MIP templates were chosen to mimic the working zone of standard lateral access retractors. The positions of the L4 nerve root and femoral nerve were analyzed relative to the L4-5 disc in axial and sagittal planes. Third-party radiologists and a senior spine surgeon performed the evaluations, with inter- and intraobserver testing performed. RESULTS: In all subjects, the plexus was successfully mapped. At L3-4, in all but one case, the components of the plexus (except the genitofemoral nerve) were located in the most posterior quadrant (zone IV). The L3 and L4 roots coalesced into the femoral nerve below the L4-5 disc space in all subjects. Side-to-side variation was noted, with the plexus occurring in zone IV in 86.2 % right and only 78.7 % of left sides. At the superior third of L5, the plexus was found in zone III in 27.7 % of right and 36.2 % of left sides; and in zone II in 4.3 % right and 2.1 % left sides. Significant inter- and intraobserver agreement was found. CONCLUSIONS: By providing the surgeon with a preoperative roadmap of the lumbar plexus, DW-MR may improve the safety profile of lateral access procedures.

Strategies for Minimizing the Effects of Observer Variability on Sagittal Parameter Measurements of the Spine.

STUDY DESIGN: Exploratory-descriptive study. OBJECTIVE: Evaluate the influence of observer variability on the measurements of both thoracic kyphosis (TK) and lumbar lordosis (LL) obtained with anatomic and functional spinal segmentation methods. BACKGROUND: Parametric analysis for spinal surgery planning typically relies on anatomic parameters. However, incorporating functional parameters that consider the vertebrae orientation is important to minimizing surgical calculation errors. METHODS: The authors developed parametric analysis software that integrates traditional and functional methodologies. The proposed method included functional thoracic kyphosis and functional lumbar lordosis calculated from the lines normal to the inflection points of the spine model. Using a synthetic lateral X-ray, the observer variability was computer-simulated generating 20 landmark sets that replicate the annotations of 20 observers. The analysis also included 10 clinical X-rays, annotated twice by 3 judges with a minimum 1-week interval. The spinal curvature angles were derived using the anatomic and functional methods. Statistical analysis were performed for comparison. RESULTS: For the synthetic X-ray, the proposed method presented significantly less variability: TK (<±2.5 degrees, P=0.00023) and LL (<±5 degrees, P=0.00012). For the clinical X-rays, the interobserver reliability analysis yielded higher intraclass correlation coefficients (ICC) for functional TK (ICC>0.97) and functional LL (ICC>0.87) than for TK (ICC<0.91) and LL (ICC<0.89). Statistically significant differences were observed for both TK (P=0.001) and LL (P=0.030). Under the traditional method, observer variability led to measurement differences surpassing ±19 degrees, whereas differences with the proposed method were within ±10 degrees for both parameters. CONCLUSION: The vertebral endplate is not the most suitable place to measure spinal sagittal curvatures. Small changes in landmark position significantly alter the measured Cobb angle. The proposed method offers a substantial advantage regarding the influence of observer variability, in addition to the more individualized analysis.

Polytomous Rasch Analyses of Surgeons' Decision-Making on Choice of Procedure in Endoscopic Lumbar Spinal Stenosis Decompression Surgeries.

BACKGROUND: With the growing prevalence of lumbar spinal stenosis, endoscopic surgery, which incorporates techniques such as transforaminal, interlaminar, and unilateral biportal (UBE) endoscopy, is increasingly considered. However, the patient selection criteria are debated among spine surgeons. OBJECTIVE: This study used a polytomous Rasch analysis to evaluate the factors influencing surgeon decision-making in selecting patients for endoscopic surgical treatment of lumbar spinal stenosis. METHODS: A comprehensive survey was distributed to a representative sample of 296 spine surgeons. Questions encompassed various patient-related and clinical factors, and responses were captured on a logit scale graphically displaying person-item maps and category probability curves for each test item. Using a Rasch analysis, the data were subsequently analyzed to determine the latent traits influencing decision-making. RESULTS: The Rasch analysis revealed that surgeons' preferences for transforaminal, interlaminar, and UBE techniques were easily influenced by comfort level and experience with the endoscopic procedure and patient-related factors. Harder-to-agree items included technological aspects, favorable clinical outcomes, and postoperative functional recovery and rehabilitation. Descriptive statistics suggested interlaminar as the best endoscopic spinal stenosis decompression technique. However, logit person-item analysis integral to the Rasch methodology showed highest intensity for transforaminal followed by interlaminar endoscopic lumbar stenosis decompression. The UBE technique was the hardest to agree on with a disordered person-item analysis and thresholds in category probability curve plots. CONCLUSION: Surgeon decision-making in selecting patients for endoscopic surgery for lumbar spinal stenosis is multifaceted. While the framework of clinical guidelines remains paramount, on-the-ground experience-based factors significantly influence surgeons' selection of patients for endoscopic lumbar spinal stenosis surgeries. The Rasch methodology allows for a more granular psychometric evaluation of surgeon decision-making and accounts better for years-long experience that may be lost in standardized clinical guideline development. This new approach to assessing spine surgeons' thought processes may improve the implementation of evidence-based protocol change dictated by technological advances was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the International Society for Minimal Intervention in Spinal Surgery (ISMISS), the Mexican Spine Society (AMCICO), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Society (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS).

Comparative Analysis of Learning Curve, Complexity, Psychological Stress, and Work Relative Value Units for CPT 62380 Endoscopic Lumbar Spinal Decompression vs Traditional Lumbar Spine Surgeries: A Paired Rasch Survey Study.

BACKGROUND: Effective 1 January 2017, single-level endoscopic lumbar discectomy received a Category I Current Procedural Terminology (CPT) code 62380. However, no work relative value units (RVUs) are currently assigned to the procedure. An international team of endoscopic spine surgeons conducted a study, endorsed by several spine societies, analyzing the learning curve, difficulty, psychological intensity, and estimated work RVUs of endoscopic lumbar spinal decompression compared with other common lumbar spine surgeries. METHODS: A survey comparing CPT 62380 to 10 other comparator CPT codes reflective of common spine surgeries was developed to assess the work RVUs in terms of learning curve, difficulty, psychological intensity, and work effort using a paired Rasch method. RESULTS: The survey was sent to 542 spine specialists. Of 322 respondents, 150 completed the survey for a 43.1% completion rate. Rasch analysis of the submitted responses statistically corroborated common knowledge that the learning curve with lumbar endoscopic spinal surgery is steeper and more complex than with traditional translaminar lumbar decompression surgeries. It also showed that the psychological stress and mental and work effort with the lumbar endoscopic decompression surgery were perceived to be higher by responding spine surgeons compared with posterior comparator decompression and fusion surgeries and even posterior interbody and posterolateral fusion surgeries. The regression analysis of work effort vs procedural difficulty showed the real-world evaluation of the lumbar endoscopic decompression surgery described in CPT code 62380 with a calculated work RVU of 18.2464. CONCLUSION: The Rasch analysis suggested the valuation for the endoscopic lumbar decompression surgery should be higher than for standard lumbar surgeries: 111.1% of the laminectomy with exploration and/or decompression of spinal cord and/or cauda equina (CPT 63005), 118.71% of the laminectomy code (CPT 63047), which includes foraminotomy and facetectomy, 152.1% of the hemilaminectomy code (CPT 63030), and 259.55% of the interlaminar or interspinous process stabilization/distraction without decompression code (CPT 22869). This research methodology was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the Mexican Society of Spinal Surgeons (AMCICO), the International Society For Minimally Invasive Spine Surgery (ISMISS), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Surgery (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS). CLINICAL RELEVANCE: This study provides an updated reimbursement recommendation for endoscopic spine surgery. LEVEL OF EVIDENCE: Level 3.

Effect of pilot hole on biomechanical and in vivo pedicle screw-bone interface.

PURPOSE: To experimentally study the influence of pilot hole diameter (smaller than or equal to the internal (core) diameter of the screw) on biomechanical (insertion torque and pullout strength) and histomorphometric parameters of screw-bone interface in the acute phase and 8 weeks after pedicle screw insertion. METHODS: Fifteen sheep were operated upon and pedicle screws inserted in the L1-L3 pedicles bilaterally. The pilot hole was smaller (2.0 mm) than the internal diameter (core) of the screw on the left side pedicle and equal (2.8 mm) to the internal diameter (core) of the screw on the right side pedicle. Ten animals were sacrificed immediately (five animals were assigned to pullout strength tests and five animals were used for histomorphometric bone-screw interface evaluation). Five animals were sacrificed 8 weeks after pedicle screw insertion for histomorphometric bone-screw interface evaluation. RESULTS: The insertion torque and pullout strength were significantly greater in pedicle screws inserted into pilot holes smaller than internal (core) diameter of the screw. Histomorphometric evaluation of bone-screw interface showed that the percentage of bone-implant contact, the area of bone inside the screw thread and the area of bone outside the screw thread were significantly higher for pilot holes smaller than the internal (core) diameter of the screw immediately after insertion and after 8 weeks. CONCLUSION: A pilot diameter smaller than the internal (core) diameter of the screw improved the insertion torque and pullout strength immediately after screw insertion as well the pedicle screw-bone interface contact immediately and 8 weeks after screw placement in sheep with good bone mineral density.

Assessing the evolution of publications by Brazilian spine surgeons in the last decade.

PURPOSE: To evaluate the scientific contribution of Brazilian Spine Surgeons not only in number of publications but also in their quality between January 2000 to December 2011. METHODS: A literature search of publications by Brazilian spinal surgeons on topics concerning the spine or spinal cord was performed using an online database; Pubmed.gov. The results were limited to articles published from January 2000 to December 2011. A total of 1,778 articles were identified after a Medline search. After exclusion criteria, the study comprised 206 articles. The quality of the Journals was assessed with IF and the article quality using the Oxford classification. RESULTS: An increasing number of publications by Brazilian spine surgeons was observed in recent years: 45.1 % of those papers were published during the last 4 years (2008-2011). Clinical studies and case reports were the most frequent types of article published (37.5 vs 31.1 %). An increasing number of Brazilian publications in non-Brazilian journals has been observed in recent years (linear-by-linear association: 5.449, P = 0.020). The Arquivos de Neuro-Psiquiatria was the most frequent journal in which the papers were published (N = 67, 32 %). The IF of the publications varied from 0.021 to 8.017. The analysis of quality of the articles using the Oxford classification demonstrated that most of them provided LOE 4 (N = 113, 54.9 %) or 5 (N = 45, 21.8 %). CONCLUSIONS: There have been an increasing number of publications by Brazilian spine surgeons in recent years and the quality of the articles published has improved. Also the number of publications by Brazilians in non-Brazilian journals has increased in recent years.

Calcific discitis in an adult patient with intravertebral migration and spontaneous remission.

Symptomatic disc calcifications have been reported, especially in the pediatric population, and remain of unknown etiology. Such a condition has been very rarely reported in adults. The aim of this paper is to present a case report of calcific discitis in an adult patient with intravertebral migration and spontaneous calcification resorption. The clinical presentation was that of back pain with an abrupt onset, not related to trauma or to physical activity. No fever or neurological deficits were present. Blood count, erythrocyte sedimentation rate, routine urine, and urine culture were negative. The pain regressed in 20 days with analgesic therapy. Findings of thoracic calcific discitis are illustrated with X-rays, CT, MRI, and bone scintigraphy.

Extraforaminal Full-Endoscopic Approach for the Treatment of Lateral Compressive Diseases of the Lumbar Spine.

BACKGROUND: The authors conducted a 2-year retrospective follow-up to investigate the efficiency of an extraforaminal full-endoscopic approach with foraminoplasty used to treat lateral compressive diseases of the lumbar spine in 247 patients. METHODS: The visual analogue scale (VAS), Oswestry disability index (ODI), and MacNab scale were used to analyze the results collected during the preoperative and postoperative periods. RESULTS: The most common diagnosis was disk herniation with lateral recess stenosis, and the most common surgical level among patients was between L4 and L5 on the left side. Pain decreased over time, as determined during sessions held to evaluate pain in the lumbar, gluteal, led, and foot regions. The ODI demonstrated significant enhancement over the evaluation period and the MacNab scale classified the surgery as good or excellent. The most common complication was dysesthesia. CONCLUSIONS: An extraforaminal full-endoscopic approach with foraminoplasty can be recommended in cases of lateral herniation or stenosis for patients with symptoms of radiculopathy, and for those who have not responded to conventional rehabilitation treatment or chronic pain management. Few complications arose as a result of this approach, and most of them were treated clinically.

Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models.

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient's pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

Personalized Interventional Surgery of the Lumbar Spine: A Perspective on Minimally Invasive and Neuroendoscopic Decompression for Spinal Stenosis.

Pain generator-based lumbar spinal decompression surgery is the backbone of modern spine care. In contrast to traditional image-based medical necessity criteria for spinal surgery, assessing the severity of neural element encroachment, instability, and deformity, staged management of common painful degenerative lumbar spine conditions is likely to be more durable and cost-effective. Targeting validated pain generators can be accomplished with simplified decompression procedures associated with lower perioperative complications and long-term revision rates. In this perspective article, the authors summarize the current concepts of successful management of spinal stenosis patients with modern transforaminal endoscopic and translaminar minimally invasive spinal surgery techniques. They represent the consensus statements of 14 international surgeon societies, who have worked in collaborative teams in an open peer-review model based on a systematic review of the existing literature and grading the strength of its clinical evidence. The authors found that personalized clinical care protocols for lumbar spinal stenosis rooted in validated pain generators can successfully treat most patients with sciatica-type back and leg pain including those who fail to meet traditional image-based medical necessity criteria for surgery since nearly half of the surgically treated pain generators are not shown on the preoperative MRI scan. Common pain generators in the lumbar spine include (a) an inflamed disc, (b) an inflamed nerve, (c) a hypervascular scar, (d) a hypertrophied superior articular process (SAP) and ligamentum flavum, (e) a tender capsule, (f) an impacting facet margin, (g) a superior foraminal facet osteophyte and cyst, (h) a superior foraminal ligament impingement, (i) a hidden shoulder osteophyte. The position of the key opinion authors of the perspective article is that further clinical research will continue to validate pain generator-based treatment protocols for lumbar spinal stenosis. The endoscopic technology platform enables spine surgeons to directly visualize pain generators, forming the basis for more simplified targeted surgical pain management therapies. Limitations of this care model are dictated by appropriate patient selection and mastering the learning curve of modern MIS procedures. Decompensated deformity and instability will likely continue to be treated with open corrective surgery. Vertically integrated outpatient spine care programs are the most suitable setting for executing such pain generator-focused programs.

The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management: Perspectives from Europe, Latin America, Asia, and The United States.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work-life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur-investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus.

INTRODUCTION: The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. MATERIAL AND METHODS: Using an animal experimental model of intervertebral disc herniation and behavioral tests to evaluate mechanical (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in the hind paw of rats submitted to the surgical model, this study aimed to detect in normal intervertebral disc the cytokines known to be involved in the mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the intervertebral disc tissue to specific antibodies could affect the pain behavior (mechanical and thermal hyperalgesia) induced by the NP, and to observe the influence of the time of contact of the NP with the fifth lumbar dorsal root ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. RESULTS: The cytokines present at highest concentrations in the rat NP were TNF-α, IL-1ß and CINC-1. Rats submitted to the disc herniation experimental model, in which a NP from the sacrococcygeal region is deposited over the right L5-DRG, showed increased mechanical and thermal hyperalgesia that lasted at least 7 weeks. When the autologous NP was treated with antibodies against the three cytokines found at highest concentrations in the NP (TNF-α, IL-1ß and CINC-1), there was decrease in both mechanical and thermal hyperalgesia in different time points, suggesting that each cytokine may be important for the hyperalgesia in different steps of the inflammatory process. The surgical remotion of the NP from herniated rats 1 week after the implantation reduced the hyperalgesia to the level similar to the control group. This reduction in the hyperalgesia was also observed in the group that had the NP removed 3 weeks after the implantation, although the intensity of the hyperalgesia did not decreased totally. The removal of the NP after 5 weeks did not changed the hyperalgesia observed in the hind paw, which suggests that the longer the contact of the NP with the DRG, the greater is the possibility of development of chronic pain. CONCLUSION: Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.

Fat infiltration in the lumbar multifidus and erector spinae muscles in subjects with sway-back posture.

AIM: Decreased activity of the lumbar stabilizer muscles has been identified in individuals with sway-back posture. Disuse can predispose these muscles to atrophy, which is characterized by a reduced cross-sectional area (CSA) and by fat infiltration. The aim of this study was to evaluate the amount of fat infiltration in the lumbar multifidus and lumbar erector spinae muscles as a sign of the muscle atrophy in individuals with sway-back posture, with and without low back pain. MATERIALS AND METHODS: Forty-five sedentary individuals between 16 and 40 years old participated in this study. The sample was divided into three groups: symptomatic sway-back (SSBG) (n = 15), asymptomatic sway-back (ASBG) (n = 15), and control (CG) (n = 15). The individuals were first subjected to photographic analysis to classify their postures and were then referred for a magnetic resonance imaging (MRI) examination of the lumbar spine. The total (TCSA) and functional (FCSA) cross-sectional areas of the lumbar erector spinae together with lumbar multifidus and isolated lumbar multifidus muscles were measured from L1 to S1. The amount of fat infiltration was estimated as the difference between the TCSA and the FCSA. RESULTS: Greater fat deposition was observed in the lumbar erector spinae and lumbar multifidus muscles of the individuals in the sway-back posture groups than in the control group. Pain may have contributed to the difference in the amount of fat observed in the groups with the same postural deviation. Similarly, sway-back posture may have contributed to the tissue substitution relative to the control group independently of low back pain. CONCLUSIONS: The results of this study indicate that individuals with sway-back posture may be susceptible to morphological changes in their lumbar erector spinae and lumbar multifidus muscles, both due to the presence of pain and as a consequence of their habitual posture.

Experimental in vivo acute and chronic biomechanical and histomorphometrical comparison of self-drilling and self-tapping anterior cervical screws.

PURPOSE: Self-drilling screws (SDS) and self-tapping screws (STS) allow for quicker bone insertion and are associated with increased anchorage. This is an experimental in vivo comparison of anterior cervical SDS and STS in the post-insertion acute and chronic phases. METHODS: Thirty C2-C6 vertebrae from six Santa Inês hair sheep were used. Each screw design was randomly assigned to five of each spinal level. Insertion torque was measured using a torque device. Three animals were killed in each phase. Vertebrae were randomly assigned to pullout tests and histomorphometrical bone-screw interface evaluation (percent screw-bone contact and bone density inside and outside the threaded area). Statistical significance was set at P < 0.05. RESULTS: SDS insertion torque was greater than STS (P = 0.0001). SDS pullout strength was significantly greater than STS in the acute and chronic phases (P = 0.0001, 0.0003, respectively). SDS percent screw-bone contact and inside area bone density were significantly greater in both phases. No outside area bone density differences were observed in either phase. CONCLUSIONS: SDS had higher insertion torque and better anchorage than STS in both phases. SDS percent bone-screw contact and inside area bone density were higher in both phases.