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Item A 64-Year-Old Man with Low Back Pain Due to Clostridium perfringens Lumbar Discitis(International Scientific Information, 2021-01-22) Bhatt, Harshil; Singh, Sandeep; Medicine, School of MedicineLumbar discitis caused by Clostridium perfringens is extremely rare. There have only been 7 published cases of confirmed discitis caused by Clostridium perfringens. We write this report to underscore this unusual relationship by discussing an additional case and providing a review of the previously published cases so clinicians can adequately evaluate and treat patients presenting with discitis. CASE REPORT A 64-year-old morbidly obese man presented with an acute onset of worsening back pain and generalized weakness after incurring physical trauma related to falling. Additionally, he also developed fever and chills before the presentation. Based on the clinical presentation and elevated serum levels of inflammatory markers, magnetic resonance imaging was ordered, which showed L5-S1 discitis with extension of infection into the epidural space. Fluoroscopy-guided aspiration of the L5-S1 epidural space facilitated the detection of Clostridium perfringens as the involved pathogen. Based on the antibiotic susceptibility report, the patient was treated with intravenous ampicillin for 8 weeks, after which his symptoms resolved. CONCLUSIONS Diagnosis of discitis can be very challenging due to its ambiguous clinical presentation, especially in the elderly population due to the presence of underlying degenerative changes. Even though Clostridium perfringens remains a rare cause of lumbar discitis, it should be considered as a pathogen capable of causing infection of the vertebrae and intervertebral discs, thus allowing clinicians to make necessary diagnostic evaluations to provide appropriate targeted treatment to patients presenting with discitis.Item A Case of Metastatic Basal Cell Carcinoma (BCC) With Spinal and Pulmonary Metastases Treated With Vismodegib, Sonedigib, and Radiotherapy(Springer Nature, 2022-03-17) Samia, Arthur M.; Nenow, Joseph M.; Boyer, Philip; Medicine, School of MedicineBasal cell carcinoma (BCC) is the most common malignancy worldwide and has one of the most favorable prognoses due to its tendency to remain local. Clinical presentation with rare distant metastases significantly increases morbidity and mortality. Historically, no effective therapies have existed for locally advanced or metastatic BCC. Recent research highlights the possibility of treating patients with advanced and metastatic BCC with hedgehog pathway inhibitors, such as vismodegib or sonedigib. We present the case of a 62-year-old male with a history of a large left shoulder lesion, which was diagnosed as a nodulocystic BCC following biopsy and histopathologic examination. The primary lesion was managed with surgical excision, and his ensuing metastatic disease was treated with vismodegib, sonedigib, tumor debulking, and radiation therapy. Magnetic resonance imaging and computed tomography of the chest revealed probable metastases to the apical segment of the left upper lobe and thoracic spine, leading to spinal stenosis and probable cause of the patient's ataxia and paresthesias. Due to the ability of BCCs to transform during metastasis, it is impossible to identify the nature of metastatic lesions (i.e., basaloid, squamous, or hybrid) without biopsy. In this case report, we review the etiologies, typical demographics, presentation patterns, and treatment regimens for metastatic BCC and the possibility of metastatic disease transforming to squamous or hybrid variants.Item Bone Density Changes Following Radiotherapy to Vertebral Metastases(Springer Nature, 2021-06-03) Jensen, Garrett L.; Gaddipati, Ravi; Hammonds, Kendall P.; Morrow, Andrew; Swanson, Gregory P.; Radiation Oncology, School of MedicineIntroduction: Patients have increasing longevity and time for bone healing following radiotherapy (RT) for treatment of bone metastases (BM). Attempts to assess the treatment response of bone metastases have been either limited or heavily subjective. Our goal was to try to quantitate cancer-involved bone changes after RT using changes in bone mineral density (BMD) from computer tomographic (CT) imaging. Methods: Retrospectively, 117 spinal metastases were identified that received RT with follow-up CT scans >9 months following CT simulation. Contoured volumes included: the metastasis (gross tumor volume; GTV); the involved vertebra (gross bone volume; GBV); a total lytic volume (Lyt); a dominant lytic volume (Domlyt); a control volume, and the nearest uninvolved, unirradiated vertebra (control bone volume; CBV). The Hounsfield-density calibration curve was used to measure the density of these volumes before and after treatment. Results: Whether using raw or control-adjusted changes, the absolute and percent change in density of the GBV, GTV, Lyt, and Domlyt volumes all significantly increased (each p<0.0001). The increase in the density of Domlyt volumes was greater than that of Lyt volumes (p=0.0465), which were greater than GTV (p=0.0065), which were greater than GBV (p<0.0001). On multivariate analysis, only the biologically effective dose (BED) dose significantly correlated with GTV density change (p=0.0175). K means clustering created groups by initial lesion size, GTV, or GBV density. A significant difference in GTV density change was not detected between any groups. Conclusion: Increases in BMD are associated with healing regardless of lesion size or initial density. A prospective study to determine whether long-term control is related to early density measurements is needed.Item Characterization of dendritic morphology and neurotransmitter phenotype of thoracic descending propriospinal neurons after complete spinal cord transection and GDNF treatment(Elsevier, 2016-03) Deng, Lingxiao; Ruan, Yiwen; Chen, Chen; Frye, Christian Corbin; Xiong, Wenhui; Jin, Xiaoming; Jones, Kathryn; Sengelaub, Dale; Xu, Xiao-Ming; Department of Anatomy & Cell Biology, IU School of MedicineAfter spinal cord injury (SCI), poor regeneration of damaged axons of the central nervous system (CNS) causes limited functional recovery. This limited spontaneous functional recovery has been attributed, to a large extent, to the plasticity of propriospinal neurons, especially the descending propriospinal neurons (dPSNs). Compared with the supraspinal counterparts, dPSNs have displayed significantly greater regenerative capacity, which can be further enhanced by glial cell line-derived neurotrophic factor (GDNF). In the present study, we applied a G-mutated rabies virus (G-Rabies) co-expressing green fluorescence protein (GFP) to reveal Golgi-like dendritic morphology of dPSNs. We also investigated the neurotransmitters expressed by dPSNs after labeling with a retrograde tracer Fluoro-Gold (FG). dPSNs were examined in animals with sham injuries or complete spinal transections with or without GDNF treatment. Bilateral injections of G-Rabies and FG were made into the 2nd lumbar (L2) spinal cord at 3 days prior to a spinal cord transection performed at the 11th thoracic level (T11). The lesion gap was filled with Gelfoam containing either saline or GDNF in the injury groups. Four days post-injury, the rats were sacrificed for analysis. For those animals receiving G-rabies injection, the GFP signal in the T7-9 spinal cord was visualized via 2-photon microscopy. Dendritic morphology from stack images was traced and analyzed using a Neurolucida software. We found that dPSNs in sham injured animals had a predominantly dorsal-ventral distribution of dendrites. Transection injury resulted in alterations in the dendritic distribution with dorsal-ventral retraction and lateral-medial extension. Treatment with GDNF significantly increased the terminal dendritic length of dPSNs. The density of spine-like structures was increased after injury, and treatment with GDNF enhanced this effect. For the group receiving FG injections, immunohistochemistry for glutamate, choline acetyltransferase (ChAT), glycine, and GABA was performed in the T7-9 spinal cord. We show that the majority of FG retrogradely-labeled dPSNs were located in the Rexed Lamina VII. Over 90% of FG-labeled neurons were glutamatergic, with the other three neurotransmitters contributing less than 10% of the total. To our knowledge this is the first report describing the morphologic characteristics of dPSNs and their neurotransmitter expressions, as well as the dendritic response of dPSNs after transection injury and GDNF treatment.Item Clinicopathological and Prognostic Characteristics in Spinal Chondroblastomas: A Pooled Analysis of Individual Patient Data From a Single Institute and 27 Studies(Sage, 2023) Zheng, Bo-Wen; Huang, Wei; Liu, Fu-Sheng; Zhang, Tao-Lan; Wang, Xiao-Bin; Li, Jing; Lv, Guo-Hua; Yan, Yi-Guo; Zou, Ming-Xiang; Radiation Oncology, School of MedicineStudy design: Retrospective pooled analysis of individual patient data. Objectives: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. Methods: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. Results: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. Conclusion: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.Item Compromised vertebral structural and mechanical properties associated with progressive kidney disease and the effects of traditional pharmacological interventions(Elsevier, 2015-08) Newman, Christopher L.; Chen, Neal X.; Smith, Eric; Smith, Mark; Brown, Drew; Moe, Sharon M.; Allen, Matthew R.; Department of Anatomy & Cell Biology, IU School of MedicineBACKGROUND/AIMS: Patients with chronic kidney disease mineral and bone disorder (CKD-MBD) have a significantly higher vertebral and non-vertebral fracture risk than the general population. Several preclinical models have documented altered skeletal properties in long bones, but few data exist for vertebral bone. The goal of this study was to examine the effects of progressive CKD on vertebral bone structure and mechanics and to determine the effects of treatment with either bisphosphonates or anti-sclerostin antibody in groups of animals with high or low PTH. METHODS: Animals with progressive kidney disease were left untreated, treated with calcium to lower PTH, zoledronic acid to lower remodeling without affecting PTH, anti-sclerostin antibody, or anti-sclerostin antibody plus calcium. Non-diseased, untreated littermates served as controls. Vertebral bone morphology (trabecular and cortical) and mechanical properties (structural and material-level) were assessed at 35 weeks of age by microCT and mechanical testing, respectively. RESULTS: CKD with high PTH resulted in 6-fold higher bone formation rate, significant reductions in the amount of trabecular and cortical bone, and compromised whole bone mechanical properties in the vertebra compared to normal animals. Treatments that reduced bone remodeling were effective in normalizing vertebral structure and mechanical properties only if the treatment reduced serum PTH. Similarly, treatment with anti-sclerostin antibody was effective in enhancing bone mass and mechanical properties but only if combined with PTH-suppressive treatment. CONCLUSIONS: CKD significantly altered both cortical and trabecular bone properties in the vertebra resulting in compromised mechanical properties and these changes can be normalized by interventions that involve reductions in PTH levels.Item Correction: Foley et al. Emerging Technologies within Spine Surgery. Life 2023, 13, 2028(MDPI, 2024-05-27) Foley, David; Hardacker, Pierce; McCarthy, Michael; Orthopaedic Surgery, School of MedicineIn the original publication [1], there was a mistake in Figure 1 as published. The plumb line drawn for the calculation of the cervical sagittal vertical axis should originate from the center of the C2 body. In the original figure, the line incorrectly begins at the anterior body. The corrected Figure 1 appears below. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.Item Dystrophic spinal deformities in a neurofibromatosis type 1 murine model(PLoS, 2015-03-18) Rhodes, Steven D.; Zhang, Wei; Yang, Dalong; Yang, Hao; Chen, Shi; Wu, Xiahoua; Yang, Xianlin; Mohammad, Khalid S.; Guise, Theresa A.; Bergner, Amanda L.; Stevenson, David A.; Yang, Feng-Chun; Department of Anatomy and Cell Biology, IU School of MedicineDespite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.Item Effect of Etidronate on Bone Remodeling in Dog Mandibular Condyle(1998) Cottingham, Karen L.; Garetto, Lawrence P.; Burr, David B.; Crow, Heidi; Katona, Thomas R.; Shanks, JamesBisphosphonates, drugs which inhibit bone resorption and remodeling, are currently prescribed for the treatment of osteoporosis. Previous research suggests that decreased bone turnover may lead to accumulation of microdamage, possibly increasing the risk for fracture in some sites. The effects of bisphosphonate therapy on the mandibular condyle have not been quantitatively studied. The purpose of the proposed study was to histomorphometrically quantify the effects of etidronate (a bisphosphonate) on trabecular bone sites of the dog mandibular condyle and to compare this to another trabecular bone site (vertebrae) to determine whether the two sites were affected differently. Eleven mature female dogs were treated with high- (5 mg/kg/d) and low- (0.5 mg/kg/d) dose etidronate therapy for seven months. Fluorochrome labels were used to mark sites of bone mineralization for the calculation of static and dynamic histomorphometric parameters. High-dose therapy resulted in a complete inhibition of remodeling, as shown by the reduction of mineral apposition rate (MAR), bone formation rate (BFR), and mineralizing surface (MS/BS) to zero. Low-dose therapy also decreased BFR and MS/BS. Osteoid accumulation was only significant in the high-dose therapy group, but there was no evidence of osteomalacia (osteoid volume < 5%). Etidronate treatment had no significant effect on bone volume, trabecular number, trabecular thickness, or trabecular separation. Vertebral trabeculae ranged from 5.5 to 9.5 times greater in number than mandibular trabeculae, but were 45 to 60 percent thinner and closer together. The interaction between dosage and site was insignificant for all parameters studied. Further investigation is needed to determine whether these effects will prove to be harmful to the mandibular condyle, especially over a long period of time.Item Emerging Technologies within Spine Surgery(MDPI, 2023-10-09) Foley, David; Hardacker, Pierce; McCarthy, Michael; Orthopaedic Surgery, School of MedicineNew innovations within spine surgery continue to propel the field forward. These technologies improve surgeons’ understanding of their patients and allow them to optimize treatment planning both in the operating room and clinic. Additionally, changes in the implants and surgeon practice habits continue to evolve secondary to emerging biomaterials and device design. With ongoing advancements, patients can expect enhanced preoperative decision-making, improved patient outcomes, and better intraoperative execution. Additionally, these changes may decrease many of the most common complications following spine surgery in order to reduce morbidity, mortality, and the need for reoperation. This article reviews some of these technological advancements and how they are projected to impact the field. As the field continues to advance, it is vital that practitioners remain knowledgeable of these changes in order to provide the most effective treatment possible.