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Purpose: Spinal and lower extremity degeneration often causes pain and disability. Lower extremity osteoarthritis, eventually leading to total knee- (TKA) and -hip arthroplasty (THA), can alter posture through compensatory mechanisms, potentially causing spinal misalignment and paraspinal muscle (PM) atrophy. This study aims to evaluate the association between prior THA or TKA and PM-degeneration in patients undergoing elective lumbar surgery for degenerative conditions. Methods: A retrospective analysis of patients undergoing lumbar surgery for degenerative conditions was conducted. Patients were categorized based on prior THA, TKA, or both. Quantitative analysis of functional cross-sectional area (fCSA) and fat infiltration (FI) of psoas, multifidus (MF), and erector spinae (ES) muscles at L4-level was performed using T2-weighted MRI images. The association between the FI and fCSA of the PM and prior arthroplasty was investigated. Differences were assessed using ANOVA and multivariable linear regression. Results: Overall, 584 patients (60% female, 64 ± 12 years) were included. 66 patients (11%) had prior TKA, 36 patients (6%) THA, and 15 patients (3%) both TKA and THA. Patients with arthroplasty were mostly female (57%) and notably older (p < 0.001). The FI of the MF and the ES was significantly higher in the arthroplasty-group (both p < 0.001). Patients with prior TKA showed significantly higher FI (Est = 4.3%, p = 0.013) and lower fCSA (Est=-0.9 cm2, p = 0.012) in the MF compared to the non-arthroplasty-group. Conclusion: This study demonstrates a significant lower fCSA and higher FI in the MF among individuals with prior TKA. This highlights the complex knee-spine relationship and how these structures interact with each other. [ABSTRACT FROM AUTHOR]

Introduction: Intrawound application of vancomycin is becoming increasingly controversial for the prevention of surgical site infection (SSI). As children undergoing spinal fusion for secondary scoliosis are at high risk for SSIs, evidence regarding the impact of intraoperative vancomycin installation on SSI rates in these patients is of utmost importance. Methodology: A single surgeon cohort of patients under 18 years of age undergoing surgery for secondary scoliosis in 2017 was analyzed with regard to the development of SSIs requiring surgical revision and adverse events. Use of vancomycin was restricted to cases with higher risk of infection. Patients undergoing distraction surgery for growing devices were excluded. Results: After exclusions, 64 patients remained (vancomycin n = 39, control n = 25). The SSI rates were 12.8% in patients receiving vancomycin (n = 5/39) and 4% in the control group (n = 1/25, p = 0.785). None of the patients suffered from adverse events. Univariable logistic regression revealed younger age (p = 0.03) and meningomyelocele as predictors for SSI (p = 0.006), while the high-risk group receiving vancomycin was not at higher odds for SSI, also after adjustment for possible confounders such as age or MMC (p = 0.031; p = 0.009). Discussion: SSI rates were comparable between groups, suggesting a normalization of SSI risk in the vancomycin-treated patients with a preoperatively increased risk of SSI. Future, larger studies in these rare diseases are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Degenerative lumbar spondylolisthesis (DLS) is a prevalent spinal condition that can result in significant disability. DLS is thought to result from a combination of disc and facet joint degeneration, as well as various biological, biomechanical, and behavioral factors. One hypothesis is the progressive degeneration of segmental stabilizers, notably the paraspinal muscles, contributes to a vicious cycle of increasing slippage. To examine the correlation between paraspinal muscle status on MRI and severity of slippage in patients with symptomatic DLS. Retrospective cross-sectional study at an academic tertiary care center. Patients who underwent surgery for DLS at the L4/5 level between 2016–2018 were included. Those with multilevel DLS or insufficient imaging were excluded. The percentage of relative slippage (RS) at the L4/5 level evaluated on standing lateral radiographs. Muscle morphology measurements including functional cross-sectional area (fCSA), body height normalized functional cross-sectional area (HI) of Psoas, erector spinae (ES) and multifidus muscle (MF) and fatty infiltration (FI) of ES and MF were measured on axial MR. Disc degeneration and facet joint arthritis were classified according to Pfirrmann and Weishaupt, respectively. Descriptive and comparative statistics, univariable and multivariable linear regression models were utilized to examine the associations between RS and muscle parameters, adjusting for confounders sex, age, BMI, segmental degeneration, and back pain severity and symptom duration. The study analyzed 138 out of 183 patients screened for eligibility. The median age of all patients was 69.5 years (IQR 62 to 73), average BMI was 29.1 (SD±5.1) and average preoperative ODI was 46.4 (SD±16.3). Patients with Meyerding-Grade 2 (M2, N=25) exhibited higher Pfirrmann scores, lower MF fCSA and MF HI , and lower BMI, but significantly more fatty infiltration in the MF and ES muscles compared to those with Meyerding Grade 1 (M1). Univariable linear regression showed that each cm2 decrease in MF fCSA was associated with a 0.9%-point increase in RS (95% CI -1.4 to - 0.4, p<.001), and each cm2/m2 decrease in MF HI was associated with an increase in slippage by 2.2%-points (95% CI -3.7 to -0.7, p=.004). Each 1%-point rise in ES FI and MF FI corresponded to 0.17%- (95% CI 0.05–0.3, p=.01) and 0.20%-point (95% CI 0.1–0.3 p<.001) increases in relative slippage, respectively. Notably, after adjusting for confounders, each cm2 increase in Psoas fCSA and cm2/m2 in Psoas HI was associated with an increase in relative slippage by 0.3% (95% CI 0.1–0.6, p=.004) and 1.1%-points (95% CI 0.4–1.7, p=.001). While MF fCSA tended to be negatively associated with slippage, this did not reach statistical significance (p=.105). However, each 1%-point increase in MF FI and ES FI corresponded to increases of 0.15% points (95% CI 0.05–0.24, p=.002) and 0.14% points (95% CI 0.01–0.27, p=.03) in relative slippage, respectively. This study found a significant association between paraspinal muscle status and severity of slippage in DLS. Whereas higher degeneration of the ES and MF correlate with a higher degree of slippage, the opposite was found for the psoas. These findings suggest that progressive muscular imbalance between posterior and anterior paraspinal muscles could contribute to the progression of slippage in DLS. [ABSTRACT FROM AUTHOR]

Degenerative lumbar spondylolisthesis (DLS) is a prevalent spinal condition that can result in significant disability. DLS is thought to result from a combination of disc and facet joint degeneration, as well as various biological, biomechanical, and behavioral factors. One hypothesis is the progressive degeneration of segmental stabilizers, notably the paraspinal muscles, contributes to a vicious cycle of increasing slippage. To examine the correlation between paraspinal muscle status on MRI and severity of slippage in patients with symptomatic DLS. To examine the correlation between paraspinal muscle status on MRI and severity of slippage in patients with symptomatic DLS. Patients who underwent surgery for DLS at the L4/5 level between 2016-2018 were included. Those with multilevel DLS or insufficient imaging were excluded. The percentage of relative slippage (RS) at the L4/5 level evaluated on standing lateral radiographs. Muscle morphology measurements including functional cross-sectional area (fCSA), body height normalized functional cross-sectional area (HI) of Psoas, erector spinae (ES) and multifidus muscle (MF) and fatty infiltration (FI) of ES and MF were measured on axial MR. Disc degeneration and facet joint arthritis were classified according to Pfirrmann and Weishaupt, respectively. Descriptive and comparative statistics, univariable and multivariable linear regression models were utilized to examine the associations between RS and muscle parameters, adjusting for confounders sex, age, BMI, segmental degeneration, and back pain severity. The study analyzed 138 out of 183 patients screened for eligibility. The median age of all patients was 69.5 years (IQR 62 to 73), average BMI was 29.1 (SD ± 5.1) and average preoperative ODI was 46.4 (SD ± 16.3). Patients with Meyerding-Grade 2 (M2, N=25) exhibited higher Pfirrmann scores, lower MF fCSA and MF HI , and lower BMI, but significantly more fatty infiltration in the MF and ES muscles compared to those with Meyerding Grade 1 (M1). Univariable linear regression showed that each cm2 decrease in MF fCSA was associated with a 0.9%-point increase in RS (95%CI -1.4 to - 0.4, p<0.001), and each cm2/m2 decrease in MF HI was associated with an increase in slippage by 2.2%-points (95%CI -3.7 to -0.7, p=0.004). Each 1%-point rise in ES FI and MF FI corresponded to 0.17%- (95%CI 0.05 - 0.3, p=0.01) and 0.20%-point (95%CI 0.1 – 0.3 p<0.001) increases in relative slippage, respectively. Notably, after adjusting for confounders, each cm2 increase in Psoas fCSA and cm2/m2 in Psoas HI was associated with an increase in relative slippage by 0.3% (95%CI 0.1 - 0.6, p = 0.004) and 1.1%-points (95%CI 0.4 -1.7, p= 0.001). While MF fCSA tended to be negatively associated with slippage, this did not reach statistical significance (p = 0.086). However, each 1%-point increase in MF FI and ES FI corresponded to increases of 0.15% points (95%CI 0.05 – 0.24, p= 0.003) and 0.14% points (95%CI 0.01 - 0.27, p= 0.03) in relative slippage, respectively. This study found a significant association between paraspinal muscle status and severity of slippage in DLS. Whereas, higher degeneration of the ES and MF correlate with a higher degree of slippage, the opposite was found for the psoas. These findings suggest that progressive muscular imbalance between posterior and anterior paraspinal muscles could contribute to the progression of slippage in DLS. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury (TSCI), commonly caused by high energy trauma in young active patients, is frequently accompanied by traumatic brain injury (TBI). Although combined trauma results in inferior clinical outcomes and a higher mortality rate, the understanding of the pathophysiological interaction of co-occurring TSCI and TBI remains limited. This review provides a detailed overview of the local and systemic alterations due to TSCI and TBI, which severely affect the autonomic and sensory nervous system, immune response, the blood–brain and spinal cord barrier, local perfusion, endocrine homeostasis, posttraumatic metabolism, and circadian rhythm. Because currently developed mesenchymal stem cell (MSC)-based therapeutic strategies for TSCI provide only mild benefit, this review raises awareness of the impact of TSCI–TBI interaction on TSCI pathophysiology and MSC treatment. Therefore, we propose that unravelling the underlying pathophysiology of TSCI with concomitant TBI will reveal promising pharmacological targets and therapeutic strategies for regenerative therapies, further improving MSC therapy. [ABSTRACT FROM AUTHOR]

Purpose: The literature is scarce in exploring the role of imaging parameters like ultrasound (US) as a biomarker for surgical outcomes. The purpose of this study is to investigate the associations between skin US parameters and revision surgery following spine lumbar fusion. Methods: Posterior lumbar fusion patients with 2-years follow-up were assessed. Previous fusion or revision not due to adjacent segment disease (ASD) were excluded. Revisions were classified as cases and non-revision were classified as controls. US measurements conducted at two standardized locations on the lumbar back. Skin echogenicity of the average dermal (AD), upper 1/3 of the dermal (UD), lower 1/3 of the dermal (LD), and subcutaneous layer were measured. Echogenicity was calculated with the embedded echogenicity function of our institution's imaging platform (PACS). Statistical significance was set at p < 0.05. Results: A total of 128 patients (51% female, age 62 [54–72] years) were included in the final analysis. 17 patients required revision surgery. AD, UD, and LD echogenicity showed significantly higher results among revision cases 124.5 [IQR = 115.75,131.63], 128.5 [IQR = 125,131.63] and 125.5 [IQR = 107.91,136.50] compared to the control group 114.3 [IQR = 98.83,124.8], 118.5 [IQR = 109.28,127.50], 114 [IQR = 94.20,126.75] respectively. Conclusion: The findings of this study demonstrate a significant association between higher echogenicity values in different layers of the dermis and requiring revision surgery. The results provide insights into the potential use of skin US parameters as predictors for revision surgery. These findings may reflect underlying alterations in collagen. Further research is warranted to elucidate the mechanisms driving these associations. [ABSTRACT FROM AUTHOR]

Lumbar medial branch radiofrequency neurotomy (RFN), a common treatment for chronic low back pain due to facet joint osteoarthritis (FJOA), may amplify paraspinal muscle atrophy due to denervation. This study aimed to investigate the asymmetry of paraspinal muscle morphology change in patients undergoing unilateral lumbar medial branch RFN. Data from patients who underwent RFN between March 2016 and October 2021 were retrospectively analyzed. Lumbar foramina stenosis (LFS), FJOA, and fatty infiltration (FI) functional cross-sectional area (fCSA) of the paraspinal muscles were assessed on preinterventional and minimum 2-year postinterventional MRI. Wilcoxon signed-rank tests compared measurements between sides. A total of 51 levels of 24 patients were included in the analysis, with 102 sides compared. Baseline MRI measurements did not differ significantly between the RFN side and the contralateral side. The RFN side had a higher increase in multifidus FI (+4.2% [0.3-7.8] vs +2.0% [-2.2 to 6.2], P 5 0.005) and a higher decrease in multifidus fCSA (-60.9 mm² [-116.0 to 10.8] vs -19.6 mm² [-80.3 to 44.8], P = 0.003) compared with the contralateral side. The change in erector spinae FI and fCSA did not differ between sides. The RFN side had a higher increase in multifidus muscle atrophy compared with the contralateral side. The absence of significant preinterventional degenerative asymmetry and the specificity of the effect to the multifidus muscle suggest a link to RFN. These findings highlight the importance of considering the long-term effects of lumbar medial branch RFN on paraspinal muscle health. [ABSTRACT FROM AUTHOR]

The neuropeptide calcitonin gene-related peptide (CGRP) and its receptor, calcitonin receptor-like receptor (CLR) complexing with receptor activity-modifiying protein 1 (RAMP1), have been shown to be crucially involved in the pathogenesis of migraine. However, CGRP also plays a pivotal role in regulating bone turnover and was suggested to contribute to the development of the metabolic syndrome. Therefore, our study was designed to characterize the effects of CGRP antagonism on bone and glucose metabolism in a murine model of diet-induced obesity (DIO). A subcutaneous pellet releasing the CGRP receptor antagonist BIBN 4096 (BIBN; olcegepant) was implanted in WT mice with DIO. Metabolic effects were assessed through body- and organ-weights, oral glucose tolerance (oGT), serum lipids, and gene-expression studies. Bone turnover was assessed through histomorphometry of non-decalcified bone sections and analyses of bone turnover markers in serum samples. BIBN treatment did not alter body weight gain or the levels of serum lipids including triacylglycerol and cholesterol during DIO. BIBN led to a moderate improvement of oGT which was accompanied by an increased expression of stearoyl-CoA desaturase in the liver. In skeletal tissue, BIBN treatment resulted in reduced bone volume. This was explained by decreased parameters of bone formation whereas bone resorption was not affected. Our results indicate that inhibition of CGRP signaling only moderately affects glucose metabolism during DIO but significantly impairs bone formation. As novel agents blocking CGRP or its receptor are currently introduced clinically for the treatment of migraine disorders, their potential negative impact on bone metabolism requires further clinical studies. • A model of CGRP antagonism in mice with diet-induced obesity is presented • CGRP antagonism induces the hepatic expression of inflammatory cytokines and markers of fatty acid synthesis in this model. • CGRP antagonism does not affect systemic glucose and lipid metabolism in this model • CGRP antagonism reduces bone mass through decreasing bone formation in mice with diet-induced obesity • Patients receiving CGRP blockers may require the assessment of bone status [ABSTRACT FROM AUTHOR]

Systemic and local posttraumatic responses are often monitored on mRNA expression level using quantitative real-time PCR (qRT-PCR), which requires normalisation to adjust for confounding sources of variability. Normalisation requests reference (housekeeping) genes stable throughout time and divergent experimental conditions in the tissue of interest, which are crucial for a reliable and reproducible gene expression analysis. Although previous animal studies analysed reference genes following isolated trauma, this multiple-trauma gene expression analysis provides a notable study analysing reference genes in primarily affected (i.e. bone/fracture callus and hypothalamus) and secondarily affected organs (i.e. white adipose tissue, liver, muscle and spleen), following experimental long bone fracture and traumatic brain injury. We considered tissue-specific and commonly used top-ranked reference candidates from different functional groups that were evaluated applying the established expression stability analysis tools NormFinder, GeNorm, BestKeeper and RefFinder. In conclusion, reference gene expression in primary organs is highly time point as well as tissue-specific, and therefore requires careful evaluation for qRT-PCR analysis. Furthermore, the general application of Ppia, particularly in combination with a second reference gene, is strongly recommended for the analysis of systemic effects in the case of indirect trauma affecting secondary organs through local and systemic pathophysiological responses. [ABSTRACT FROM AUTHOR]

Spinal fusion surgery effectively improves pain and functional scores for degenerative disease of the lumbar spine. However, adjacent segment disease (ASD) is a common problem in the long-term course often necessitating revision surgery. While certain patient factors and sagittal alignment parameters are known to correlate with ASD, such imaging biomarkers remain underexplored on preoperative magnetic resonance imaging (MRI). This study aims to investigate the association and predictive value of intervertebral disc and paraspinal muscle degeneration on initial preoperative MRI and the risk of ASD revision surgery after elective lumbar fusion. Single-center retrospective analysis of prospectively enrolled patients. Patients undergoing primary lumbar fusion between 2014 - 2021 were followed-up by phone call after > 2-years. Exclusion criteria were prior fusion or laminectomy and incomplete or low-quality MRI. Of 184 prospectively enrolled patients, 105 met the inclusion criteria and were eligible for analysis. ASD revision surgery; Pfirrmann grades, Modic changes, endplate degeneration and paraspinal muscle status (fatty infiltration and functional cross-sectional area (fCSA) of multifidus, erector spinae and psoas. Demographic factors, comorbidities and surgical levels were assessed. The initial MRI prior to the primary elective lumbar fusion was assessed for disc degeneration by Pfirrmann (grade 1-5); Modic changes (0-3); and total endplate degeneration (grade 1-6). Paraspinal muscles were assessed on axial slices at the level and parallel to the upper endplate of L4. fCSA and percentage fatty infiltration of multifidus, erector spinae and psoas muscles were measured. Means ± standard deviations were used to display normally distributed parameters, and medians and interquartile ranges [IQR] for nonnormally distributed data. T-test and Mann-Whitney-U were performed, followed by ROC analysis and univariable logistic regression. Significance was set at p < 0.05. There were 12.4% of cases (n=13) that required a revision surgery for ASD (=ASD group) 30 [17-43] months after elective lumbar fusion. Age (62 [54-69] years), sex (49.5% female), BMI (29.2 [25.7-33.8]), fusion levels (1 [1-2] (range 1-4)) and follow-up time (46 [31-72] months) did not differ between the ASD group and the controls. Disc degeneration was significantly higher in the lower instrumented level with Pfirrmann 5 [4-5] in the ASD group vs 4 [4-5] in the control group (p=0.026), but Pfirrmann grades at the adjacent disc were similar between the ASD group and controls. No difference was found in Modic changes. Endplate degeneration trended to be higher at the instrumented and adjacent segments in the ASD group without reaching statistical significance at any level. Muscle measurements showed no difference in fCSA between the ASD and the control group. Whereas fatty infiltration of the psoas was similar, it trended to be higher in the ASD group, and multifidus fatty infiltration was significantly higher in the ASD group 57.3±7.8% vs the controls 49.4±14.2% (p=0.023). With ROC analysis (AUC 0.673), a cut-off value of Pfirrmann grade 5 in the lower instrumented segment (sensitivity 69%, specificity 62%) was found to be a predictor for ASD revision with OR 3.7 (CI 1.1 -12.8). A cut-off value for 53.8% in multifidus fatty infiltration (AUC 0.676; sensitivity 77%, specificity 62%) was predicting ASD revision with OR 4.7 (CI 1.2-18.4) in this cohort. This study reveals that higher preoperative degeneration in the lower instrumented level as well as fatty infiltration in the multifidus are significantly associated with revision surgery for ASD, with the latter being even more predictive. These findings underline the importance of not only assessing vertebrae and discs but also of the surrounding muscular envelope on MRI for a successful outcome after lumbar fusion surgery, with the functional status of the multifidus being a crucial factor in the prevention of ASD. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Despite significant advances in surgical techniques, treatment options for impaired bone healing are still limited. Inadequate bone regeneration is not only associated with pain, prolonged immobilization and often multiple revision surgeries, but also with high socioeconomic costs, underlining the importance of a detailed understanding of the bone healing process. In this regard, we previously showed that mice lacking the calcitonin receptor (CTR) display increased bone formation mediated through the increased osteoclastic secretion of sphingosine-1-phosphate (S1P), an osteoanabolic molecule promoting osteoblast function. Although strong evidence is now available for the crucial role of osteoclast-to-osteoblast coupling in normal bone hemostasis, the relevance of this paracrine crosstalk during bone regeneration is unknown. Therefore, our study was designed to test whether increased osteoclast-to-osteoblast coupling, as observed in CTR-deficient mice, may positively affect bone repair. In a standardized femoral osteotomy model, global CTR-deficient mice displayed no alteration in radiologic callus parameters. Likewise, static histomorphometry demonstrated moderate impairment of callus microstructure and normal osseous bridging of osteotomy ends. In conclusion, bone regeneration is not accelerated in CTR-deficient mice, and contrary to its osteoanabolic action in normal bone turnover, osteoclast-to-osteoblast coupling specifically involving the CTR-S1P axis, may only be of minor relevance during bone healing. [ABSTRACT FROM AUTHOR]