A Comparison of Short-Term Outcomes after Surgical Treatment of Multilevel Degenerative Cervical Myelopathy in the Geriatric Patient Population: An Analysis of the National Surgical Quality Improvement Program Database 2010-2020.

STUDY DESIGN: Retrospective review of the American College of Surgeons-National Surgical Quality Improvement Program database from 2010 to 2020. PURPOSE: To compare the short-term complication rates of anterior cervical decompression and fusion (ACDF), posterior cervical laminoplasty (LP), and posterior cervical laminectomy and fusion (PCF) in a geriatric population. OVERVIEW OF LITERATURE: The geriatric population in the United States has increased significantly. Degenerative cervical myelopathy (DCM) is caused by cervical spinal stenosis, and its prevalence increases with age. Therefore, the incidence of multilevel DCM requiring surgical intervention is likely to increase. ACDF, LP, and PCF are the most commonly used surgical techniques for treating multilevel DCM. However, there is uncertainty regarding the optimal surgical technique for the decompression of DCM in geriatric patients. METHODS: Patients aged 65 years who had undergone either multilevel ACDF, LP, or PCF for the treatment of DCM were analyzed. Additional analysis was performed by standardizing the data for the American Society of Anesthesiologists classification scores and preoperative functional status. RESULTS: A total of 23,129 patients were identified. Patients with ACDF were younger, more often female, and preoperatively healthier than those in the other two groups. The estimated postoperative mortality and morbidity, mean operation time, and length of hospital stay were the lowest for ACDF, second lowest for LP, and highest for PCF. The readmission and reoperation rates were comparable between ACDF and LP; however, both were significantly lower than PCF. CONCLUSIONS: PCF is associated with the highest risk of mortality, morbidity, unplanned reoperation, and unplanned readmission in the short-term postoperative period in patients aged 65 years. In contrast, ACDF carries the lowest risk. However, some disease-specific factors may require posterior treatment. For these cases, LP should be included in the preoperative discussion when determining the ideal surgical approach for geriatric patients.

Utility of the Modified 5-Items Frailty Index to Predict Complications and Mortality After Elective Cervical, Thoracic and Lumbar Posterior Spine Fusion Surgery: Multicentric Analysis From ACS-NSQIP Database.

STUDY DESIGN: Retrospective review of multicentric data. OBJECTIVES: The modified 5-item frailty index is a relatively new tool to assess the post-operative complication risks. It has been recently shown a good predictive value after posterior lumbar fusion. We aimed to compare the predictive value of the modified 5-item frailty index in cervical, thoracic and lumbar surgery. METHODS: The American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) Database 2015-2020 was used to identify patients who underwent elective posterior cervical, thoracic, or lumbar fusion surgeries for degenerative conditions. The mFI-5 score was calculated based on the presence of 5 co-morbidities: congestive heart failure within 30 days prior to surgery, insulin-dependent or noninsulin-dependent diabetes mellitus, chronic obstructive pulmonary disease or pneumonia, partially dependent or totally dependent functional health status at time of surgery, and hypertension requiring medication. Multivariate analysis was used to assess the independent impact of increasing mFI-5 score on the postoperative morbidity while controlling for baseline clinical characteristics. RESULTS: 53 252 patients were included with the mean age of 64.2 ± 7.2. 7946 suffered medical complications (14.9%), 1565 had surgical complications (2.9%), and 3385 were readmitted (6.3%), 363 died (.68%) within 30 days postoperative (6.3%). The mFI-5 items score was significantly associated with higher rates of complications, readmission, and mortality in cervical, thoracic, and lumbar posterior fusion surgery. CONCLUSION: The modified 5-item frailty score is a reliable tool to predict complications, readmission, and mortality in patients planned for elective posterior spinal fusion surgery.

Management of lumbar spondylolysis in the adolescent athlete: a review of over 200 cases.

BACKGROUND: Spondylolysis is a defect of the pars interarticularis of vertebrae, most commonly seen at L5 and L4. The etiology of spondylolysis and isthmic spondylolisthesis is generally considered to be a result of repetitive mechanical stress to the weak portion of the vertebrae. A higher incidence of spondylolysis is observed in young athletes. Symptomatic spondylolysis can be successfully treated conservatively, but there is currently a limited consensus on treatment modalities and a lack of large-scale clinical trials. PURPOSE: The purpose of the present study was to investigate the optimal treatment algorithm for symptomatic spondylolysis in adolescent athletes and evaluate the functional outcomes of those undergoing the nonoperative treatment. STUDY DESIGN: A retrospective review. PATIENT SAMPLE: Two hundred one adolescent patients ranging from age 10 to 19 involved in athletics OUTCOME MEASURES: Injury characteristics (age, mechanism, time), sports played, bone stimulator use, bony healing at 3 months on computed tomography (CT) scans, return to sports, corticosteroid injection use. METHODS: Two hundred one adolescent athlete patients (62 females and 139 males) diagnosed with spondylolysis between 2007 and 2019 were retrospectively reviewed. Diagnosis was based on plain radiography followed by magnetic resonance imaging. All patients were treated conservatively with cessation of sports activity, thoracolumbosacral orthosis, and external bone stimulator for three months after diagnosis. CT scans were obtained for the 3-month follow-up visits to assess bony healing. Subsequently the patients received 6 weeks of rehabilitation focused on core strengthening. Symptomatic patients after the treatment were referred for steroid injections and continued with the rehabilitation protocol. RESULTS: The most common age of injury was 15 years old, following a strong normal distribution. The most commonly played sport was football, followed by baseball/softball. The primary mechanism of injury was weight training closely followed by a football injury. The first quarter of the calendar year had the highest incidence of injuries with the most injuries occurring in March and the least occurring in December. One hundred fifty-two athletes reported using bone stimulators as prescribed, and these patients showed a significantly higher rate of bony healing on follow-up CT scans than those who did not use bone stimulators. One hundred ninety-seven patients (98%) returned to sports or similar level of activities. Thirty-seven patients (18%) received facet or epidural steroid injections due to continued pain and one patient underwent a surgical procedure. Follow-up CT scans showed 49.8% bony healing. CONCLUSIONS: Conservative treatment of spondylolysis in adolescent athletes with cessation of sports, thoracolumbosacral orthosis, and bone stimulator followed by rehabilitation was associated with excellent outcomes in terms of return to sports.

The efficacy of bactrim in reducing surgical site infections after spine surgery.

BACKGROUND: Previous studies show an increasing incidence of gram-negative organisms in surgical site infections after spine surgery. This study is looking for the association of the post-operative prophylactic use of Bactrim and the gram-negative surgical site infection after lumbar spine surgery. METHODS: Patients who underwent lumbar spine surgery between August 2010 and December 2019 at the institution were retrospectively reviewed. RESULTS: There were 11 infections out of 511 cases where no oral antibiotics were given (2.2%). There were 2 infections out of 84 cases where Bactrim was given (2.4%). This was not statistically significant (P=0.89). The organisms cultured from the no oral antibiotic group were 8 cases of methicillin sensitive Staphylococcus aureus (MSSA), 1 case of E. coli, 1 case of Pseudomonas aeruginosa, 1 case of MRSA. The organisms cultured from the Bactrim group were 1 case of MRSA, and 1 case of combined Citrobacter freundii and methicillin sensitive Staphylococcus aureus (MSSA). CONCLUSION: There was no statistically significant difference in SSIs when Bactrim was given for two weeks after surgery. However, two subjects who developed infection from the Bactrim group were paradoxically affected by gram-negative and antibiotic resistant organisms. So, clinicians should be judicious in their use of oral antibiotics after spine surgery. Level of Evidence: III.

Correlation between RUST assessments of fracture healing to structural and biomechanical properties.

Radiographic Union Score for Tibia (RUST) and modified RUST (mRUST) are radiographic tools for quantitatively evaluating fracture healing using a cortical scoring system. This tool has high intra-class correlation coefficients (ICCs); however, little evidence has evaluated the scores against the physical properties of bone healing. Closed, stabilized fractures were made in the femora of C3H/HeJ male mice (8-12 week-old) of two dietary groups: A control and a phosphate restricted diet group. Micro-computed tomography (µCT) and torsion testing were carried out at post-operative days (POD) 14, 21, 35, and 42 (n = 10-16) per group time-point. Anteroposterior and lateral radiographic views were constructed from the µCT scans and scored by five raters. The raters also indicated if the fracture were healed. ICCs were 0.71 (mRUST) and 0.63 (RUST). Both RUST scores were positively correlated with callus bone mineral density (BMD) (r = 0.85 and 0.80, p < 0.001) and bone volume fraction (BV/TV) (r = 0.86 and 0.80, p < 0.001). Both RUST scores positively correlated with callus strength (r = 0.35 and 0.26, p < 0.012) and rigidity (r = 0.50 and 0.39, p < 0.001). Radiographically healed calluses had a mRUST ≥13 and a RUST ≥10 and had excellent relationship to structural and biomechanical metrics. Effect of delayed healing due to phosphate dietary restrictions was found at later time points with all mechanical properties (p < 0.011), however no differences found in the RUST scores (p > 0.318). Clinical relevance of this study is both RUST scores showed high correlation to physical properties of healing and generally distinguished healed vs. non-healed fractures. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:945-953, 2018.

Polymer-DNA Nanoparticle-Induced CXCR4 Overexpression Improves Stem Cell Engraftment and Tissue Regeneration in a Mouse Hindlimb Ischemia Model.

Peripheral arterial disease affects nearly 202 million individuals worldwide, sometimes leading to non-healing ulcers or limb amputations in severe cases. Genetically modified stem cells offer potential advantages for therapeutically inducing angiogenesis via augmented paracrine release mechanisms and tuned dynamic responses to environmental stimuli at disease sites. Here, we report the application of nanoparticle-induced CXCR4-overexpressing stem cells in a mouse hindlimb ischemia model. We found that CXCR4 overexpression improved stem cell survival, modulated inflammation in situ, and accelerated blood reperfusion. These effects, unexpectedly, led to complete limb salvage and skeletal muscle repair, markedly outperforming the efficacy of the conventional angiogenic factor control, VEGF. Importantly, assessment of CXCR4-overexpressing stem cells in vitro revealed that CXCR4 overexpression induced changes in paracrine signaling of stem cells, promoting a therapeutically desirable pro-angiogenic and anti-inflammatory phenotype. These results suggest that nanoparticle-induced CXCR4 overexpression may promote favorable phenotypic changes and therapeutic efficacy of stem cells in response to the ischemic environment.

Predominant Activation of JAK/STAT3 Pathway by Interleukin-6 Is Implicated in Hepatocarcinogenesis.

Chronic inflammation is an important process leading to tumorigenesis. Therefore, targeting and controlling inflammation can be a promising cancer therapy. Inflammation is often caused by a variety of inflammatory cytokine such as the interleukin (IL)-6, a pleiotrophic cytokine known to be involved in the tumorigenesis. In this study, an in vivo hepatic tumorigenesis model of zebrafish was generated to demonstrate a direct consequence of the human IL6 expression causing hepatocarcinogenesis. To do this, an elevated expression of the hIL6 gene was established to specifically target the zebrafish hepatocytes by transgenesis. Interestingly, the elevated hIL6 expression caused the chronic inflammation which results in a massive infiltration of inflammatory cells. This eventually resulted in the generation of various dysplastic lesions such as clear cell, small cell, and large cell changes, and also eosinophilic and basophilic foci of hepatocellular alteration. Hepatocellular carcinoma was then developed in the transgenic zebrafish. Molecular characterization revealed upregulation of the downstream components involved in the IL6-mediated signaling pathways, especially PI3K/Akt and JAK/STAT3 pathways. Further investigation indicated that PI3K was the most reactive to the infiltrated inflammatory cells and dysplasia with large cell change, whereas STAT3 was heavily activated in the region with dysplastic foci, suggesting that the JAK/STAT3 pathway was mainly implicated in the hepatic tumorigenesis in the current model. Our present study provides an in vivo evidence of the relationship between chronic inflammation and tumorigenesis and reinforces the pivotal role of IL6 in the inflammation-associated hepatocarcinogenesis.

Paracrine release from nonviral engineered adipose-derived stem cells promotes endothelial cell survival and migration in vitro.

Stem cells hold great potential for therapeutic angiogenesis due to their ability to directly contribute to new vessel formation or secrete paracrine signals. Adipose-derived stem cells (ADSCs) are a particularly attractive autologous cell source for therapeutic angiogenesis due to their ease of isolation and relative abundance. Gene therapy may be used to further enhance the therapeutic efficacy of ADSCs by overexpressing desired therapeutic factors. Here, we developed vascular endothelial growth factor (VEGF)-overexpressing ADSCs utilizing poly(ß-amino esters) (PBAEs), a hydrolytically biodegradable polymer, and examined the effects of paracrine release from nonviral modified ADSCs on the angiogenic potential of human umbilical vein endothelial cells (HUVECs) in vitro. PBAE polymeric vectors delivered DNA into ADSCs with high efficiency and low cytotoxicity, leading to an over 3-fold increase in VEGF production by ADSCs compared with Lipofectamine 2000. Paracrine release from PBAE/VEGF-transfected ADSCs enhanced HUVEC viability and decreased HUVEC apoptosis under hypoxia. Further, paracrine release from PBAE/VEGF-transfected ADSCs significantly enhanced HUVEC migration and tube formation, two critical cellular processes for effective angiogenesis. Our results demonstrate that genetically engineered ADSCs using biodegradable polymeric nanoparticles may provide a promising autologous cell source for therapeutic angiogenesis in treating cardiovascular diseases.

Therapeutic angiogenesis for treating cardiovascular diseases.

Cardiovascular disease is the leading cause of death worldwide and is often associated with partial or full occlusion of the blood vessel network in the affected organs. Restoring blood supply is critical for the successful treatment of cardiovascular diseases. Therapeutic angiogenesis provides a valuable tool for treating cardiovascular diseases by stimulating the growth of new blood vessels from pre-existing vessels. In this review, we discuss strategies developed for therapeutic angiogenesis using single or combinations of biological signals, cells and polymeric biomaterials. Compared to direct delivery of growth factors or cells alone, polymeric biomaterials provide a three-dimensional drug-releasing depot that is capable of facilitating temporally and spatially controlled release. Biomimetic signals can also be incorporated into polymeric scaffolds to allow environmentally-responsive or cell-triggered release of biological signals for targeted angiogenesis. Recent progress in exploiting genetically engineered stem cells and endogenous cell homing mechanisms for therapeutic angiogenesis is also discussed.