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1.
Article in English | MEDLINE | ID: mdl-38871629

ABSTRACT

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are common and impart a significant burden to patients, caregivers, and the health system. However, there are few pharmacological options for treating BPSD. We conducted a systematic review of clinical trials examining the efficacy of anticonvulsants in BPSD. METHODS: We searched five electronic databases through January 2023, for randomized controlled trials and systematic reviews evaluating the efficacy of non-benzodiazepine anticonvulsants for the treatment of BPSD. We used the Cochrane risk of bias tool to ascertain the risk of bias in included trials. Because statistical pooling of results using meta-analysis was not feasible, we synthesized findings using the Cochrane Synthesis Without Meta-analysis reporting guidelines. RESULTS: We identified 12 studies, including randomized controlled trials (RCTs) and 1 systematic review. Five RCTs evaluating valproic acid were synthesized by a recent Cochrane review which concluded that this drug is likely ineffective for BPSD. We extracted data from 6 trials involving 248 individuals comparing non-benzodiazepine anticonvulsants to either placebo or risperidone. Four trials (n = 97 participants) evaluated carbamazepine, only one of which demonstrated an improvement in the Brief Psychiatric Rating Scale measuring agitation, hostility, psychosis, and withdrawal/depression (effect size: 1.13; 95% confidence interval [CI]: 0.54-1.73) relative to placebo. Adverse effects were more common in patients receiving carbamazepine (20/27; 74%) relative to placebo (5/24; 21%). There is low quality evidence that oxcarbazepine is likely ineffective and that topiramate may be comparable to risperidone. CONCLUSION: Anticonvulsants are unlikely to be effective in BPSD, although the quality of existing evidence is low.

2.
Clin Spine Surg ; 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38637917

ABSTRACT

STUDY DESIGN: Case report and literature review. OBJECTIVE: To report the relatively rare complication of delayed infection after cervical disc arthroplasty (CDA). BACKGROUND: Delayed infection of the M6 device has been a rarely reported complication, with all cases described outside of the United States. The reliability of positive intraoperative cultures remains an ongoing debate. METHODS: Cases were reviewed, and findings were summarized. A literature review was performed and discussed, with special consideration to current reports of delayed M6 infection, etiology, and utility of intraoperative cultures. RESULTS: We present a case of delayed infection 6 years after primary 1-level CDA with the M6 device. At revision surgery, gross purulence was encountered. Intraoperative cultures finalized with Staphylococcus epidermidis and Cutibacterium acnes. The patient was revised with removal of the M6 and conversion to anterior cervical discectomy and fusion. A prolonged course of intravenous antibiotics was followed by an oral course for suppression. At the final follow-up, the patient's preoperative symptoms had resolved. CONCLUSION: Delayed infection after CDA is a rare complication, with ongoing debate regarding the reliability of positive cultures. We describe an infected M6 and demonstrate the utility of implant removal, conversion to anterior cervical discectomy and fusion, and long-term antibiotics as definitive treatment. LEVEL OF EVIDENCE: Level V-case report and literature review.

3.
Eur Spine J ; 33(4): 1398-1406, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38451373

ABSTRACT

PURPOSE: The following study aimed to determine the existence of blood biomarkers in symptomatic patients with or without lumbar Modic changes (MC). METHODS: A cross-sectional sub-analyses of a prospective cohort was performed. Fasting blood samples were collected from patients with and without lumbar MC who had undergone spinal fusion or microdiscectomy. An 80-plex panel and CCL5/RANTES were used to assess preoperative plasma cytokine concentrations. Patient demographics and imaging phenotypes were also assessed. RESULTS: Thirty-one subjects were analysed (n = 18 no MC; n = 13 MC). No significant differences were found in age, sex, body mass index, smoking and alcohol history, and surgical procedure (i.e. fusion, decompression) between the two groups (p > 0.05). Several statistically significant blood biomarkers in MC patients were identified, including elevated levels of C-C Motif Chemokine Ligand 5 (CCL5, p = 0.0006), while Macrophage Migration Inhibitory Factor (MIF) was significantly lower (p = 0.009). Additionally, C-X-C Motif Chemokine Ligand 5 (CXCL5, p = 0.052), Pentraxin 3 (PTX3, p = 0.06) and Galectin-3 (Gal-3, p = 0.07) showed potential relevance. Moreover, MC patients exhibited significantly higher levels of disc degeneration (p = 0.0001) and displacement severity (p = 0.020). Based on multivariate analyses and controlling for disc degeneration/displacement, CCL5 (OR 1.02; 95% CI 1.002-1.033; p = 0.028) and MIF (OR 0.60; 95% CI 0.382-0.951; p = 0.030) were independently associated with MC patients. CONCLUSION: This "proof-of-concept" study is the first to identify specific and significantly circulating blood biomarkers associated with symptomatic patients with lumbar MC, independent of disc alterations of degeneration and/or bulges/herniations. Specifically, differences in CCL5 and MIF protein levels were significantly noted in MC patients compared to those without MC.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/surgery , Prospective Studies , Cross-Sectional Studies , Ligands , Lumbar Vertebrae/surgery , Biomarkers , Magnetic Resonance Imaging , Chemokines
4.
Spine (Phila Pa 1976) ; 49(11): 763-771, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38343165

ABSTRACT

STUDY DESIGN: Prospective, case series. OBJECTIVE: To identify and characterize any differences in specific patient factors, MRI findings, features of spontaneous disc resorption, and outcomes between patients with single-level and multilevel LDH. BACKGROUND: Lumbar disc herniation (LDH) is one of the most common spinal pathologies worldwide. Though many cases of LDH resolve by spontaneous resorption, the mechanism underlying this "self-healing" phenomenon remains poorly understood, particularly in the context of multilevel herniations. METHODS: A one-year prospective study was conducted of patients presenting with acute symptomatic LDH between 2017 and 2019. Baseline demographics, herniation characteristics, and MRI phenotypes were recorded before treatment, which consisted of gabapentin, acupuncture, and the avoidance of inflammatory-modulating medications. MRIs were performed approximately every three months after the initial evaluation to determine any differences between patients with single-level and multilevel LDH. RESULTS: Ninety patients were included, 17 demonstrated multilevel LDH. Body mass index was higher among patients with multilevel LDH ( P <0.001). Patients with multilevel LDH were more likely to exhibit L3/L4 inferior endplate defects ( P =0.001), L4/L5 superior endplate defects ( P =0.012), and L4/L5 inferior endplate defects ( P =0.020) on MRI. No other differences in MRI phenotypes ( e.g. Modic changes, osteophytes, etc .) existed between groups. Resorption rate and time to resolution did not differ between those with single-level and multilevel LDH. CONCLUSIONS: Resorption rates were similar between single-level and multilevel LDH at various time points throughout one prospective assessment, providing insights that disc healing may have unique programmed signatures. Compared with those with single-level LDH, patients with multilevel herniations were more likely to have a higher BMI, lesser initial axial and sagittal disc measurements, and endplate defects at specific lumbar levels. In addition, our findings support the use of conservative management in patients with LDH, regardless of the number of levels affected. LEVEL OF EVIDENCE: Level 3.


Subject(s)
Intervertebral Disc Displacement , Lumbar Vertebrae , Magnetic Resonance Imaging , Phenotype , Humans , Intervertebral Disc Displacement/diagnostic imaging , Female , Male , Prospective Studies , Middle Aged , Lumbar Vertebrae/diagnostic imaging , Adult , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/pathology , Aged
5.
J Am Acad Orthop Surg ; 32(8): 339-345, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38320287

ABSTRACT

INTRODUCTION: Lumbar facet cysts represent a potential source of nerve root compression in elderly patients. Isolated decompression without fusion has proven to be a reasonable treatment option in properly indicated patients. However, the risk of lumbar fusion after isolated decompression and facet cyst excision has yet to be elucidated. METHODS: The PearlDiver database was reviewed for patients undergoing isolated laminectomy for lumbar facet cyst from January 2015 to December 2018 using Current Procedural Terminology coding. Patients undergoing concomitant fusion or additional decompression, as well as those diagnosed with preexisting spondylolisthesis or without a minimum of 5-year follow-up, were excluded. Rates of subsequent lumbar fusion and potential risk factors for subsequent fusion were identified. Statistical analysis included descriptive statistics, chi square test, and multivariate logistic regression. Results were considered significant at P < 0.05. RESULTS: In total, 10,707 patients were ultimately included for analysis. At 5-year follow-up, 727 (6.79%) of patients underwent subsequent lumbar fusion after initial isolated decompression. Of these, 301 (2.81% of total patients, 41.4% of fusion patients) underwent fusion within the first year after decompression. Multivariate analysis identified chronic kidney disease, hypertension, and osteoarthritis as risk factors for requiring subsequent lumbar fusion at 5 years following the index decompression procedure ( P < 0.033; all). CONCLUSION: Patients undergoing isolated decompression for lumbar facet cysts undergo subsequent lumbar fusion at a 5-year rate of 6.79%. Risk factors for subsequent decompression include chronic kidney disease, hypertension, and osteoarthritis. This study will assist spine surgeons in appropriately counseling patients on expected postoperative course and potential risks of isolated decompression.


Subject(s)
Cysts , Hypertension , Osteoarthritis , Renal Insufficiency, Chronic , Spinal Fusion , Spondylolisthesis , Humans , Aged , Decompression, Surgical/methods , Spinal Fusion/adverse effects , Spinal Fusion/methods , Cysts/complications , Cysts/surgery , Spondylolisthesis/surgery , Spondylolisthesis/complications , Osteoarthritis/surgery , Hypertension/complications , Hypertension/surgery , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/surgery , Lumbar Vertebrae/surgery , Treatment Outcome , Retrospective Studies
6.
JOR Spine ; 7(1): e1281, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38222804

ABSTRACT

Background: This systematic review and meta-analysis aimed to summarize evidence regarding the effectiveness and safety of oral antibiotic intervention for chronic low back pain (CLBP) patients with/without type-1 Modic changes (MC1). Methods: AMED, CINAHL, Cochrane Library, Embase, and Medline were searched from inception to March 3, 2023. Randomized controlled trials (RCTs) or non-RCTs that investigated the effectiveness or safety of oral antibiotics in treating CLBP patients were eligible for inclusion. Two independent reviewers screened abstracts, full-text articles, and extracted data. The methodological quality of each included article were evaluated by RoB2 and NIH quality assessment tools. The quality of evidence was appraised by GRADE. Meta-analyses were performed, where applicable. A subgroup analysis was conducted to evaluate the RCTs and case series separately, and to evaluate the effect of removing a low-quality RCT. Results: Three RCTs and four case series were included. All Amoxicillin-clavulanate/Amoxicillin treatments lasted for approximately 3 months. Moderate- and low-quality evidence suggested that antibiotic was significantly better than placebo in improving disability and quality of life in CLBP patients with MC1 at 12-month follow-up, respectively. Low-quality evidence from meta-analyses of RCTs showed that oral antibiotic was significantly better than placebo in improving pain and disability in CLBP patients with MC1 immediately post-treatment. Very low-quality evidence from the case series suggested that oral Amoxicillin-clavulanate significantly improved LBP/leg pain, and LBP-related disability. Conversely, low-quality evidence found that oral Amoxicillin alone was not significantly better than placebo in improving global perceived health in patients with CLBP at the 12-month follow-up. Additionally, oral antibiotic users had significantly more adverse effects than placebo users. Conclusions: Although oral antibiotics were statistically superior to placebo in reducing LBP-related disability in patients with CLBP and concomitant MC1, its clinical significance remains uncertain. Future large-scale high-quality RCTs are warranted to validate the effectiveness of antibiotics in individuals with CLBP.

7.
J Am Acad Orthop Surg ; 32(6): e251-e261, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38029387

ABSTRACT

Accurate and timely diagnosis of musculoskeletal conditions is an essential component of high-quality orthopaedic care. The proximity of the shoulder to the cervical spine leads to a multitude of pathologic conditions whose clinical presentations overlap, posing a diagnostic challenge to orthopaedic providers. Missed or delayed diagnosis of the etiology for patient-described 'shoulder pain' causes frustration among patients, incurs increased healthcare costs, and delays treatment. Moreover, patients with concurrent conditions of the cervical spine and shoulder require deliberate consideration for how each condition contributes to patients' symptoms. The purpose of this review was to describe a systematic approach for evaluating and differentiating pathologies of the shoulder and cervical spine.


Subject(s)
Musculoskeletal Diseases , Shoulder , Humans , Cervical Vertebrae , Musculoskeletal Diseases/diagnosis , Shoulder Pain/diagnosis , Shoulder Pain/etiology , Diagnosis, Differential
8.
J Neurosurg Spine ; 40(1): 115-120, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37877939

ABSTRACT

OBJECTIVE: Multiple studies have demonstrated the safety of outpatient spine surgery, with reports of equivalent to improved patient outcomes compared with inpatient procedures. This has resulted in the increased use of outpatient surgery over time. However, there remains a paucity of literature evaluating the difference in costs between ambulatory surgery center (ASC)- and hospital outpatient department (HOPD)-based procedures for Medicare beneficiaries. METHODS: Publicly available data from Centers for Medicare & Medicaid Services were accessed via the Medicare Procedure Price Lookup tool. Current Procedural Terminology (CPT) codes were used to identify spine-specific procedures approved for the outpatient setting by CMS. Procedures were grouped into decompression (cervical, thoracic, and lumbar), fusion/instrumentation (cervical, lumbar, and sacroiliac), and kyphoplasty/vertebroplasty cohorts, as well as an overall cohort. Data regarding total costs, facility fees, surgeon reimbursement, Medicare payments, and patient copayments were extracted for each procedure. Descriptive statistics were used to calculate means and standard deviations. Differences between ASC- and HOPD-associated costs were analyzed using the Mann-Whitney U-test. RESULTS: Twenty-one individual CPT codes approved by Medicare for the ASC and/or HOPD setting were identified. Decompression procedures were associated with a significantly lower total cost ($4183 ± $411.07 vs $7583.67 ± $410.89, p < 0.001), facility fees ($2998 ± $0 vs $6397 ± $0, p < 0.001), Medicare payments ($3345.75 ± $328.80 vs $6064.75 ± $328.80, p < 0.001), and patient payments ($835.58 ± $82.13 vs $1515.58 ± $82.13, p < 0.001) in ASCs compared with HOPDs. Fusion/instrumentation procedures had significantly lower facility fees ($10,436.6 ± $2347.51 vs $14,161 ± $2147.07, p = 0.044) and Medicare payments ($9501.2 ± $1732.42 vs $13,757 ± $2037.58, p = 0.009) in ASCs, as well as a trend toward lower total costs ($11,876.8 ± $2165.22 vs $15,601.2 ± $2016.06, p = 0.076). Patient payments in the HOPD setting were significantly lower in the fusion/instrumentation cohort ($1843.6 ± $73.42 vs $2374.4 ± $433.48, p = 0.009). In the kyphoplasty/vertebroplasty cohort, there was no statistically significant difference between ASCs and HOPDs, despite lower overall costs in the ASC for all variables. Surgeon fees were the same regardless of setting for all procedures (p > 0.99). When combining decompression, fusion/instrumentation, and kyphoplasty/vertebroplasty CPT codes into a single cohort, ASC setting was associated with significant cost savings in total cost, facility fees, Medicare payments, and patient payments. CONCLUSIONS: In general, performing spine surgeries in ASCs is associated with cost savings compared with HOPDs. This was demonstrated for decompression and fusion/instrumentation, and kyphoplasty/vertebroplasty Medicare-approved outpatient procedures.


Subject(s)
Ambulatory Surgical Procedures , Medicare , Aged , Humans , United States , Outpatients , Hospitals , Retrospective Studies
9.
J Transl Med ; 21(1): 922, 2023 12 19.
Article in English | MEDLINE | ID: mdl-38115032

ABSTRACT

BACKGROUND: Pain is a worldwide problem requiring an effective, affordable, non-addictive therapy. Using the edible plant broccoli, a growth protocol was developed to induce a concentrated combinatorial of potential anti-inflammatories in seedlings. METHODS: A growth method was utilized to produce a phenylpropanoid-rich broccoli sprout extract, referred to as Original Extract (OE). OE was concentrated and then resuspended for study of the effects on inflammation events. A rabbit disc model of inflammation and degeneration, and, a mouse model of pain behavior were used for in vivo and in vitro tests. To address aspects of mammalian metabolic processing, the OE was treated with the S9 liver microsome fraction derived from mouse, for use in a mouse in vivo study. Analytical chemistry was performed to identify major chemical species. Continuous variables were analyzed with a number of methods including ANOVA, and two-tailed t tests, as appropriate. RESULTS: In a rabbit spine (disc) injury model, inflammatory markers were reduced, and levels of regenerative markers were increased as a result of OE treatment, both in vivo and in vitro. In a mouse pain behavioral model, after treatment with S9 liver microsome fraction, the resultant extract significantly reduced early and late pain behavior in response to a pain stimulus. The OE itself reduced pain behavior in the mouse pain model, but did not achieve the level of significance observed for S9-treated extract. Analytical chemistry undertaken on the extract constituents revealed identities of the chemical species in OE, and how S9 liver microsome fraction treatment altered species identities and proportions. CONCLUSIONS: In vitro and in vivo results indicate that the OE, and S9-treated OE broccoli extracts are worthwhile materials to develop a non-opiate inflammation and pain-reducing treatment.


Subject(s)
Brassica , Mice , Animals , Rabbits , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Seedlings , Inflammation/drug therapy , Pain/drug therapy , Mammals
10.
CMAJ ; 195(38): E1326-E1328, 2023 10 03.
Article in French | MEDLINE | ID: mdl-37788841
11.
Genes (Basel) ; 14(10)2023 10 14.
Article in English | MEDLINE | ID: mdl-37895286

ABSTRACT

Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing interest in exploring potential connections between chronic MSDs and variations in the composition of gut microbiota. The human microbiota is a complex community consisting of viruses, archaea, bacteria, and eukaryotes, both inside and outside of the human body. These microorganisms play crucial roles in influencing human physiology, impacting metabolic and immunological systems in health and disease. Different body areas host specific types of microorganisms, with facultative anaerobes dominating the gastrointestinal tract (able to thrive with or without oxygen), while strict aerobes prevail in the nasal cavity, respiratory tract, and skin surfaces (requiring oxygen for development). Together with the immune system, these bacteria have coevolved throughout time, forming complex biological relationships. Changes in the microbial ecology of the gut may have a big impact on health and can help illnesses develop. These changes are frequently impacted by lifestyle choices and underlying medical disorders. The potential for safety, expenses, and efficacy of microbiota-based medicines, even with occasional delivery, has attracted interest. They are, therefore, a desirable candidate for treating MSDs that are chronic and that may have variable progression patterns. As such, the following is a narrative review to address the role of the human microbiome as it relates to MSDs.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Musculoskeletal Diseases , Humans , Gastrointestinal Tract/microbiology , Bacteria , Oxygen
12.
BMC Musculoskelet Disord ; 24(1): 669, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620847

ABSTRACT

BACKGROUND: One of the common mechanical complications following spinal fusion surgery is proximal junctional failure (PJF). The incidence of neurological deficit associated with PJF has been poorly described in the literature. Here, we report a case in which numbness in the lower extremities was recognized as the first symptom, but the discrepancy in the imaging findings made PJF difficult to diagnose. METHODS: A 71-year-old female underwent corrective fusion surgery. Three weeks later, she complained of persistent right leg numbness. Standing X-ray showed the back-out of the pedicle screws (PSs) in the upper instrumented vertebra (UIV), but there was no obvious evidence of cord compression on computed tomography (CT), which caused the delay of diagnosis. Five weeks later, magnetic resonance image (MRI) did not show cord compression on an axial view, but there were signal changes in the spinal cord. RESULTS: The first reason for the delayed diagnosis was the lack of awareness that leg numbness could occur as the first symptom of PJF. The second problem was the lack of evidence for spinal cord compression in various imaging tests. Loosened PSs were dislocated on standing, but were back to their original position on supine position. In our case, these contradictory images led to a delay in diagnosis. CONCLUSION: Loosened PSs caused dynamic cord compression due to repeated deviation and reduction. Supine and standing radiographs may be an important tool in the diagnosis of PJF induced by dynamic cord compression.


Subject(s)
Pedicle Screws , Spinal Cord Compression , Spinal Fusion , Aged , Female , Humans , Hypesthesia , Pedicle Screws/adverse effects , Spinal Cord Compression/diagnostic imaging , Spinal Cord Compression/etiology , Spinal Cord Compression/surgery , Spinal Fusion/adverse effects , Spinal Fusion/instrumentation
13.
Spine (Phila Pa 1976) ; 48(20): E355-E361, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37530119

ABSTRACT

STUDY DESIGN: This study compared hip stress among different types of lumbopelvic fusion based on finite element (FE) analysis. OBJECTIVE: We believe that the number and placement of S2 alar iliac (AI) screws and whether the screws loosen likely influence hip joint stress in the FE model. SUMMARY OF BACKGROUND DATA: Spinopelvic fixation has been shown to increase the risk of progression for hip joint osteoarthritis. The biomechanical mechanism is not well understood. We hypothesize that the rigid pelvic fixation may induce stress at adjacent joints. MATERIALS AND METHODS: A three-dimensional nonlinear FE model was constructed from the L4 vertebra to the femoral bone. From the intact model, we made four fusion models, each with different lower vertebrae instrumentation: (1) intact, (2) L4-S1 fusion, (3) L4-S2 AI screw fixation, (4) L4-S2 AI screw fixation with S2 AI screw loosening, and (5) L4-S1 and dual sacral AI screw fixation. A compressive load of 400 N was applied vertically to the L4 vertebra, followed by an additional 10 Nm bending moment about different axes to simulate either flexion, extension, left lateral bending, or right axial rotation. The distal femoral bone was completely restrained. The von Mises stress and angular motion were analyzed across the hip joints within each fusion construct model. RESULTS: Hip joint cartilage stress and range of motion increased for all postures as pelvic fixation became more rigid. The dual sacral AI screw fixation model increased stress and angular motion at the hip joint more than intact model. Our results suggest that more rigid fixation of the pelvis induces additional stress on the hip joint, which may precipitate or accelerate adjacent joint disease. CONCLUSIONS: Dual sacral AI fixation led to the highest stress while loosening of S2 AI decreased stress on the hip joint. This study illustrates that more rigid fixation among lumbosacral fusion constructs increases biomechanical stress on the hip joints.


Subject(s)
Pedicle Screws , Spinal Fusion , Humans , Finite Element Analysis , Bone Screws , Range of Motion, Articular , Pelvis , Lumbar Vertebrae/surgery , Spinal Fusion/methods , Biomechanical Phenomena , Hip Joint/surgery
14.
Int J Mol Sci ; 24(15)2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37569715

ABSTRACT

We investigated the effects of the cytokine inhibitors IL-1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor receptor-1 (sTNFR1) on the extracellular matrix metabolism of human intervertebral discs (IVDs) and the roles of IL-1ß and TNF in the homeostasis of IVD cells. The 1.2% alginate beads and the explants obtained from 35 human lumbar discs were treated with cytokine inhibitors. Extracellular matrix metabolism was evaluated by proteoglycan (PG) and collagen syntheses and IL-1ß, TNF, and IL-6 expressions after three days of culture in the presence or absence of IL-1Ra, sTNFR1, and cycloheximide. Simultaneous treatment with IL-1Ra and sTNFR1 stimulated PG and collagen syntheses in the NP and AF cells and explants. The IL-1ß concentration was significantly correlated to the relative increase in PG synthesis in AF explants after simultaneous cytokine inhibitor treatment. The relative increase in PG synthesis induced by simultaneous cytokine treatment was significantly higher in an advanced grade of MRI. Expressions of IL-1ß and TNF were upregulated by each cytokine inhibitor, and simultaneous treatment suppressed IL-1ß and TNF productions. In conclusion, IL-1Ra and sTNFR1 have the potential to increase PG and collagen synthesis in IVDs. IL-1ß and TNF have a feedback pathway to maintain optimal expression, resulting in the control of homeostasis in IVD explants.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Humans , Cytokines/metabolism , Intervertebral Disc Degeneration/metabolism , Interleukin 1 Receptor Antagonist Protein/pharmacology , Interleukin 1 Receptor Antagonist Protein/metabolism , Intervertebral Disc/metabolism , Extracellular Matrix/metabolism , Proteoglycans/metabolism , Receptors, Interleukin-1/metabolism , Collagen/metabolism
16.
Eur Spine J ; 32(11): 3846-3856, 2023 11.
Article in English | MEDLINE | ID: mdl-37644278

ABSTRACT

PURPOSE: Radiological degenerative phenotypes provide insight into a patient's overall extent of disease and can be predictive for future pathological developments as well as surgical outcomes and complications. The objective of this study was to develop a reliable method for automatically classifying sagittal MRI image stacks of cervical spinal segments with respect to these degenerative phenotypes. METHODS: We manually evaluated sagittal image data of the cervical spine of 873 patients (5182 motion segments) with respect to 5 radiological phenotypes. We then used this data set as ground truth for training a range of multi-class multi-label deep learning-based models to classify each motion segment automatically, on which we then performed hyper-parameter optimization. RESULTS: The ground truth evaluations turned out to be relatively balanced for the labels disc displacement posterior, osteophyte anterior superior, osteophyte posterior superior, and osteophyte posterior inferior. Although we could not identify a single model that worked equally well across all the labels, the 3D-convolutional approach turned out to be preferable for classifying all labels. CONCLUSIONS: Class imbalance in the training data and label noise made it difficult to achieve high predictive power for underrepresented classes. This shortcoming will be mitigated in the future versions by extending the training data set accordingly. Nevertheless, the classification performance rivals and in some cases surpasses that of human raters, while speeding up the evaluation process to only require a few seconds.


Subject(s)
Osteophyte , Humans , Cervical Vertebrae/surgery , Neck , Radiography , Magnetic Resonance Imaging/methods
17.
J Neurosurg Spine ; 39(3): 335-344, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37310033

ABSTRACT

OBJECTIVE: Total disc arthroplasty (TDA) has been established as a safe and effective alternative to anterior cervical discectomy and fusion for the treatment of cervical spine pathology. However, there remains a paucity of studies in the literature regarding the amount of disc height distraction that can be tolerated, as well as its impact on kinematic and clinical outcomes. METHODS: Patients who underwent 1- or 2-level cervical TDA with a minimum follow-up of 1 year with lateral flexion/extension and patient-reported outcome measures (PROMs) were included. Middle disc space height was measured on preoperative and 6-week postoperative lateral radiographs to quantify the magnitude of disc space distraction, and patients were grouped into < 2-mm distraction and > 2-mm distraction groups. Radiographic outcomes included operative segment lordosis, segmental range of motion (ROM) on flexion/extension, cervical (C2-7) ROM on flexion/extension, and heterotopic ossification (HO). General health and disease-specific PROMs were compared at the preoperative, 6-week, and final postoperative time points. The independent-samples t-test and chi-square test were used to compare outcomes between groups, while multivariate linear regression was used to adjust for baseline differences. RESULTS: Fifty patients who underwent cervical TDA at 59 levels were included in the analysis. Distraction < 2 mm was seen at 30 levels (50.85%), while distraction > 2 mm was observed at 29 levels (49.15%). Radiographically, after adjustment for baseline differences, C2-7 ROM was significantly greater in the patients who underwent TDA with < 2-mm disc space distraction at final follow-up (51.35° ± 13.76° vs 39.19° ± 10.52°, p = 0.002), with a trend toward significance in the early postoperative period. There were no significant postoperative differences in segmental lordosis, segmental ROM, or HO grades. After the authors controlled for baseline differences, < 2-mm distraction of the disc space led to significantly greater improvement in visual analog scale (VAS)-neck scores at 6 weeks (-3.68 ± 3.12 vs -2.24 ± 2.70, p = 0.031) and final follow-up (-4.59 ± 2.74 vs -1.70 ± 3.03, p = 0.008). CONCLUSIONS: Patients with < 2-mm disc height difference had increased C2-7 ROM at final follow-up and significantly greater improvement in neck pain after controlling for baseline differences. Limiting differences in disc space height to < 2 mm affected C2-7 ROM but not segmental ROM, suggesting that less distraction may result in more harmonious kinematics between all cervical levels.


Subject(s)
Intervertebral Disc Degeneration , Lordosis , Spinal Fusion , Total Disc Replacement , Humans , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/surgery , Treatment Outcome , Lordosis/surgery , Diskectomy , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Range of Motion, Articular , Patient Reported Outcome Measures , Follow-Up Studies , Retrospective Studies
18.
J Am Acad Orthop Surg ; 31(17): 923-930, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37192412

ABSTRACT

INTRODUCTION: Sacroiliac joint (SIJ) fusion is a surgical treatment option for SIJ pathology in select patients who have failed conservative management. More recently, minimally invasive surgical (MIS) techniques have been developed. This study aimed to determine the trends in procedure volume and reimbursement rates for SIJ fusion. METHODS: Publicly available Medicare databases were assessed using the National Summary Data Files for 2010 to 2020. Files were organized according to current procedural terminology (CPT) codes. CPT codes specific to open and MIS SI joint fusion (27279 and 27280) were identified and tracked. To track surgeon reimbursements, the CMS Medicare Physician Fee Schedule Look-Up Tool was used to extract facility prices. Descriptive statistics and linear regression were used to evaluate trends in procedure volume, utilization, and reimbursement rates. Compound annual growth rates were calculated, and discrepancies in inflation were corrected for using the Consumer Price Index. RESULTS: A total of 33,963 SIJ fusions were conducted in the Medicare population between 2010 and 2020, with an overall increase in procedure volume of 2,350.9% from 318 cases in 2010 to 7,794 in 2020. Since the introduction of the 27279 CPT code in 2015, 8,806 cases (31.5%) have been open and 19,120 (68.5%) have been MIS. Surgeon reimbursement for open fusions increased nominally by 42.8% (inflation-adjusted increase of 20%) from $998 in 2010 to $1,425 in 2020. Meanwhile, reimbursement for MIS fusion experienced a nominal increase of 58.4% (inflation-adjusted increase of 44.9%) from $582 in 2015 to $922 in 2020. CONCLUSION: SIJ fusion volume in the Medicare population has increased substantially in the past 10 years, with MIS SIJ fusion accounting for most of the procedures since the introduction of the 27279 CPT code in 2015. Reimbursement rates for surgeons have also increased for both open and MIS procedures, even after adjusting for inflation.


Subject(s)
Medicare , Spinal Diseases , Aged , Humans , United States , Sacroiliac Joint/surgery , Sacroiliac Joint/pathology , Arthrodesis , Minimally Invasive Surgical Procedures
19.
Spine Surg Relat Res ; 7(2): 161-169, 2023 Mar 27.
Article in English | MEDLINE | ID: mdl-37041866

ABSTRACT

Introduction: This study aimed to identify demographic, clinical, and operative factors associated with increased postoperative compliance of patient-reported outcome (PRO) assessments following lumbar spine surgery. Methods: A retrospective study of prospectively collected data of 1,680 consecutive adult patients who underwent elective lumbar surgery at a single institution from 2017-2020. Digital assessment questionnaires were used to assess PROs (i.e., VAS-back, VAS-leg, Oswestry Disability Index, Short Form (SF-12) mental & physical health, VR-12 mental and physical, and VR6D scores) and patient compliance, defined as the percentage of questionnaires completed preoperatively, at 3 months and 1 year after surgery. Multivariate logistic regression was used to assess the association between PRO compliance and patient characteristics. Results: A total of 1,680 patients (53.1% male, mean age: 57.7 years) had a mean PRO compliance of 64.7%. Compliance decreased continuously from initial preoperative rates (84.5%) to lower rates at 3 months (54.4%) and 12 months (45.6%), respectively, with 33.2% of patients completing zero assessment questionnaires at 12 months, postoperatively. Factors associated with significantly increased PRO compliance included being employed (preop: odds ratio [OR]=2.58, p=0.002; 3-month postop: OR=1.25, p=0.095; 12-month postop: OR=1.34, p=0.028). Factors associated with decreased compliance included preoperative smoking status (3-month postop: OR=0.63, p=0.029; 12-month postop: OR=0.60, p=0.016). Conclusions: Patients who completed greater than 50% of their PROs demonstrated significantly different rates of being employed compared with those who completed less than 50% throughout 1 year of follow-up. Preoperative smoking status was associated with decreased compliance, whereas a history of employment was associated with increased compliance throughout follow-up. To validate our findings and explore additional parameters that affect postoperative compliance of PROs, further investigation is required.

20.
Spine (Phila Pa 1976) ; 48(15): E257-E265, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37075330

ABSTRACT

STUDY DESIGN: Preclinical study. OBJECTIVE: Develop and test a drug delivery system (DDS) composed of anti-inflammatories and growth factors in the rabbit disk injury model. SUMMARY OF BACKGROUND DATA: Biological therapies that inhibit inflammation or enhance cell proliferation can alter intervertebral disk (IVD) homeostasis to favor regeneration. As biological molecules have short half-lives and one molecule may not cover multiple disease pathways, effective treatments may require a combination of growth factors and anti-inflammatory agents delivered in a sustained manner. MATERIALS AND METHODS: Biodegradable microspheres were generated separately to encapsulate tumor necrosis factor alpha (TNFα) inhibitors [etanercept (ETN)] or growth differentiation factor 5 (GDF5) and were embedded into a thermoresponsive hydrogel. Release kinetics and activity of ETN and GDF5 were measured in vitro . For in vivo testing, New Zealand White rabbits (n=12) underwent surgery for disk puncture and treatment with blank-DDS, ETN-DDS, or ETN+GDF5-DDS at levels L34, L45, and L56. Radiographic and magnetic resonance images of the spines were obtained. The IVDs were isolated for histologic and gene expression analyses. RESULTS: ETN and GDF5 were encapsulated into poly (L-lactide-co-glycolide) microspheres and had average initial bursts of 2.4±0.1 and 11.2±0.7 µg from DDS, respectively. In vitro studies confirmed that ETN-DDS inhibited TNFα-induced cytokine release and GDF5-DDS induced protein phosphorylation. In vivo studies showed that rabbit IVDs treated with ETN+GDF5-DDS had better histologic outcomes, higher levels of extracellular, and lower levels of inflammatory gene expression than IVDs treated with blank-DDS or ETN-DDS. CONCLUSIONS: This pilot study demonstrated that DDS can be fabricated to deliver sustained and therapeutic dosages of ETN and GDF5. In addition, ETN+GDF5-DDS may have greater anti-inflammatory and regenerative effects than ETN-DDS alone. Thus, intradiscal injection of controlled release TNF-α inhibitors and growth factors may be a promising treatment to reduce disk inflammation and back pain.


Subject(s)
Tumor Necrosis Factor Inhibitors , Tumor Necrosis Factor-alpha , Rabbits , Animals , Microspheres , Hydrogels , Growth Differentiation Factor 5/pharmacology , Pilot Projects , Drug Delivery Systems , Inflammation/drug therapy , Anti-Inflammatory Agents
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