Spondylolysis and Isthmic Spondylolisthesis: A Guide to Diagnosis and Management.

INTRODUCTION: Spondylolysis and isthmic spondylolisthesis are commonly implicated as organic causes of low back pain in this population. Many patients involved in sports that require repetitive hyperextension of the lumbar spine like diving, weightlifting, gymnastics and wrestling develop spondylolysis and isthmic spondylolisthesis. While patients are typically asymptomatic in mild forms, the hallmark of symptoms in more advanced disease include low back pain, radiculopathy, postural changes and rarely, neurologic deficits. METHODS: We conducted a narrative review of the literature on the clinical presentation, diagnosis, prognosis and management of spondylolysis and isthmic spondylolisthesis. RESULTS: A comprehensive physical exam and subsequent imaging including radiographs, CT and MRI play a role in the diagnosis of this disease process. While the majority of patients improve with conservative management, others require operative management due to persistent symptoms. CONCLUSION: Due to the risk of disease progression, referral to a spine surgeon is recommended for any patient suspected of having these conditions. This review provides information and guidelines for practitioners to promote an actionable awareness of spondylolysis and isthmic spondylolisthesis.

Emphysematous osteomyelitis of the spine: a case report and case based review of the literature.

Background/Objective: Emphysematous osteomyelitis (EO) of the spine is an uncommon type of osteomyelitis characterized by intraosseous gas-formation in the vertebrae. The objective of this report is to present a rare case of spine EO in a patient with emphysematous cystitis. A case-based review of the literature on spinal EO was also performed as an update to the relevant literature of this rare infection. Case Description/Methods: A 55-year-old female with diabetes mellitus and peripheral vascular disease (PVD) presented to our institution with recurrent falls, fatigue, and low back pain. Computed tomography (CT) and magnetic resonance imaging (MRI) scans confirmed emphysematous cystitis and EO at L4. Given the diffuse involvement, surgical intervention was deferred for IV antibiotic therapy. A case-based review was also conducted by searching the SCOPUS and PubMed databases for the following terms: "emphysematous osteomyelitis", "gas", and "spine". Only publications in English were included in this review. Key Content/Findings: Urine/blood cultures identified Klebsiella pneumoniae. After initial improvement with six weeks of broad-spectrum antibiotics, the patient re-presented with recurrent fevers and fatigue. Despite maximal medical therapy, the patient expired 2 months later due to multi-organ system failure. Including the present report, only 29 cases of spine EO have been described in the literature. Patients almost consistently presented with fever, elevated inflammatory markers, and localized pain. Most cases of spinal EO (89.7%) were monomicrobial. Escherichia coli (37.9%) and Klebsiella pneumoniae (27.6%) were the most causative organisms identified. Medical treatment universally consisted of broad-spectrum IV antibiotics prior to tailoring. Debridement and decompression, with or without fusion, were the main operative procedures performed for spine EO. Outcomes following spinal EO are varied with a 44.4% mortality rate. Conclusions: We present a case of EO of the spine and concomitant emphysematous cystitis with Klebsiella pneumoniae and a case-based review of the literature. Appropriate work up for this rare infection should include inflammatory markers, cultures, and CT/MRI imaging. Treatment consists of IV antibiotics with anaerobic and gram-negative coverage. However, treatment guidelines and operative indications for spinal emphysematous osteomyelitis remain unclear.

Ewing sarcoma of the pelvis: Clinical features and overall survival.

INTRODUCTION: Primary Ewing Sarcoma of Bone is a malignancy whose treatment requires both systemic chemotherapy and local control through surgical resection and/or radiation. Ewing Sarcoma of the pelvis has been noted to confer a worse prognosis relative to other anatomic sites of Ewing Sarcoma. This study explores the presenting features, treatment modalities for local control, and overall survival of primary Ewing sarcoma of the pelvis in comparison to other commonly affected anatomic sites. METHODS: The National Cancer Institute Surveillance, Epidemiology, and End-Results (SEER) database was used to identify cases of pelvic Ewing sarcoma diagnosed between years 2004 and 2015. Demographic variables including sex, race, and age at diagnosis were described for each case, as well as therapeutic modalities including surgery and radiation. Bone-specific Collaborative Staging variables, including tumor size, tumor extension, and metastasis at diagnosis, were described for the same cohort. Univariate and multivariate assessments were performed for statistical comparison between presenting factors, treatment modalities, and between anatomic locations of presentation. RESULTS: Within the database, 296 patients with Ewing sarcoma of the pelvic bones were available for review, which represented 25.7% of the 1152 cases surveyed across all anatomic sites. In the subset of patients with Ewing Sarcoma of the pelvis, 63.5% were male; the median age of diagnosis was 17 years; extra-compartmental tumor extension was noted in 82.1%; average tumor size was 9.7 cm; and metastasis at diagnosis was noted in 46.1% of the cohort. Only 28.6% of the pelvis sarcoma patients received surgical resection as part or all of their local control treatment, while 67.6% received some form of radiation therapy. When compared to the presenting features of Ewing Sarcoma from other anatomic sites, patients with pelvic tumors had larger tumors at time of diagnosis, higher rates of metastatic disease, and were less likely to undergo surgical intervention. The 2-, 5-, and 10-year overall survival rates for the patients presenting with Ewing Sarcoma of the pelvis was 70.3%, 49.7%, and 41.9%, respectively, which were significantly lower across all time-points than any other anatomic site. DISCUSSION AND CONCLUSION: Ewing Sarcoma of the pelvis is an aggressive malignancy that presents with relatively large tumors and a high rate of metastatic dissemination. Surgical intervention is less frequent when Ewing Sarcoma presents in the pelvis than when it presents in other anatomic locations. These factors may contribute to the worse overall survival of Ewing Sarcoma when compared to the same diagnosis originating in other anatomic sites. Prospective, randomized study is required to determine the true causal effects of these factors on survival.

Risk Factors for Blood Transfusions in Primary Anatomic and Reverse Total Shoulder Arthroplasty for Osteoarthritis.

Background: The purpose of this study was to determine risk factors for blood transfusion in primary anatomic and reverse total shoulder arthroplasty (TSA) performed for osteoarthritis. Methods: Patients who underwent anatomic or reverse TSA for a diagnosis of primary osteoarthritis were identified in a national surgical database from 2005 to 2018 by utilizing both CPT and ICD-9/ICD-10 codes. Univariate analysis was performed on the two transfused versus non-transfused cohorts to compare for differences in comorbidities and demographics. Independent risk factors for perioperative blood transfusions were identified via multivariate regression models. Results: 305 transfused and 18,124 nontransfused patients were identified. Female sex (p<0.001), age >85 years (p=0.001), insulin-dependent diabetes mellitus (p=0.001), dialysis dependence (p=0.001), acute renal failure (p=0.012), hematologic disorders (p=0.010), disseminated cancer (p<0.001), ASA ≥ 3 (p<0.001), and functional dependence (p=0.001) were shown to be independent risk factors for blood transfusions on multivariate logistic regression analysis. Conclusion: Several independent risk factors for blood transfusion following anatomic/reverse TSA for osteoarthritis were identified. Awareness of these risk factors can help surgeons and perioperative care teams to both identify and optimize high-risk patients to decrease both transfusion requirements and its associated complications in this patient population. Level of Evidence: III.

Extraskeletal myxoid chondrosarcoma: Clinical features and overall survival.

INTRODUCTION: Extraskeletal myxoid chondrosarcoma is a rare form of soft tissue sarcoma characterized by a unique chromosomal translocation involving the NR4A3 gene on chromosome 9. It is most frequently diagnosed in the proximal extremities of older adult males and is notable for its insidious growth with predilection for local recurrence and metastasis. Currently, extraskeletal myxoid chondrosarcoma is managed with wide resection, with recent investigations supporting the utility of adjuvant radiation and novel chemotherapeutic strategies. METHODOLOGY: A retrospective study was performed with the Surveillance, Epidemiology, and End-Results (SEER) database, which was searched for cases of extraskeletal myxoid chondrosarcoma diagnosed between years 2004 and 2015. Demographic variables were assessed, as well as Collaborative Staging variables including tumor size, metastatic disease, grade, and lymph node involvement. Cases were stratified according to the anatomic site of the primary tumor and were described by therapeutic intervention. A multivariate Cox proportional hazards model evaluated predictive factors for poor survival, and Kaplan-Meier analyses assessed effects of various staging, demographic, and therapeutic variables on overall survival. RESULTS: There were 270 cases of extraskeletal myxoid chondrosarcoma reviewed in this study, which were diagnosed most frequently in the lower limb or hip of older adult males. The 5-year overall survival was 76.5% and was worse on univariate assessment for patients with age > 60, high histologic grade, pelvic location, tumor size > 8.0 cm, metastatic or nodal spread, and in patients without surgical intervention. The Cox regression predicted significantly worse survival for older age, larger tumor size, non-surgical status, and high tumor grade. Metastasis did not significantly predict worse survival on multivariate assessment, and neither chemotherapy nor radiotherapy provided a discernable improvement in survival in this cohort. DISCUSSION AND CONCLUSION: As a rare soft tissue sarcoma, many of the presenting features and survival outcomes of extraskeletal myxoid chondrosarcoma remain poorly defined due to the limited prevalence of this disease. The findings of this study suggest the overall survival may be worse than previously reported, and poor prognostic factors are those associated with worse survival in other soft tissue sarcomas, including high histologic grade, older age, larger tumor size, and lack of wide resection. Radiation and chemotherapy did not demonstrably improve survival for patients with localized or metastatic disease.

Presenting features and overall survival of chondrosarcoma of the pelvis.

INTRODUCTION: Chondrosarcoma is the second most common sarcoma of bone. This sarcoma is generally unresponsive to chemotherapy and radiation and is primarily managed through surgical excision. Pelvic chondrosarcoma presents a distinct therapeutic challenge due the complexity of resection, frequent recurrence and metastasis, and high post-operative morbidity. METHODS: The SEER database was queried for pelvic chondrosarcoma diagnosed between 2004 and 2015. Cases were described by age, sex, tumor size, extension, grade, metastasis, and therapeutic intervention. These same variables were assessed for the upper extremities, lower extremities, skull and facial bones, thoracic bones, and vertebral column. RESULTS: In total, 472 cases of pelvic chondrosarcoma were identified, representing 18.4% out of 2571 cases of chondrosarcoma distributed throughout the skeletal system. Among pelvic cases, 288 were male and 184 were female, with a median age of diagnosis of 54. Median tumor size was 96 mm, 64.9% of tumors were considered extracompartmental, and 11.3% of tumors were metastatic at time of diagnosis. The 2, 5, and 10-year survival rates for all cases of primary chondrosarcoma of the pelvis are 76.7%, 61.8%, and 52.2%, respectively. Survival was worse for patients with metastasis, male sex, age >60, tumor size >8 cm, dedifferentiated histology, and no surgical resection. On multivariate assessment high grade and metastasis most significantly predicted worse overall survival. CONCLUSION: Pelvic chondrosarcoma commonly presents with high-risk features including larger tumor size, extracompartmental extension, and metastatic disease at diagnosis, predicting worse overall survival compared to non-pelvic tumors, and were the least amenable to surgical resection.

Osteosarcoma of the Pelvis: Clinical Presentation and Overall Survival.

INTRODUCTION: Osteosarcoma is the most common sarcoma of bone. Pelvic osteosarcoma presents a significant therapeutic challenge due to potential late symptom onset, metastatic dissemination at diagnosis, and inherent difficulties of wide surgical resection secondary to the complex and critical anatomy of the pelvis. The rates of survival are well reported for osteosarcoma of the appendicular skeleton, but specific details regarding presentation and survival are less known for osteosarcoma of the pelvis. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program was queried for primary osteosarcoma of the bony pelvis from 2004 to 2015. Cases with Collaborative Staging variables (available after 2004) were analyzed by grade, histologic subtype, surgical intervention, tumor size, tumor extension, and presence of metastasis at diagnosis. The 2-, 5-, and 10-year survival rates were assessed with respect to these variables. The SEER database was then queried for age, tumor size, surgical intervention, metastasis at time of presentation, and survivorship data for patients with primary osteosarcoma of the upper extremity, lower extremity, vertebrae, thorax, and face/skull, and rates for all anatomic locations were then compared to patients with primary pelvic osteosarcoma. RESULTS: A total of 292 cases of pelvic osteosarcoma were identified from 2004 to 2015 within the database, representing 9.8% of cases among all surveyed primary sites. The most common histologic subtype was osteoblastic osteosarcoma (69.9%), followed by chondroblastic osteosarcoma (22.3%). The majority of cases were high-grade tumors (94.3%), of size >8 cm (72.0%), and with extension beyond the originating bone (74.0%). For the entire pelvic osteosarcoma group, the 2-, 5-, 10-year survival rates were 45.6%, 26.5%, and 21.4%, respectively, which were the poorest among surveyed anatomic sites. The 5-year overall survival was an abysmal 5.3% for patients with metastatic disease at diagnosis, and 37.0% for non-metastatic pelvic osteosarcoma treated with surgery and chemotherapy. When compared to other locations, pelvic osteosarcoma had higher rates of metastatic disease at presentation (33.5%), larger median tumor size (11.0 cm), and older median age at diagnosis (47.5 years). While over 85% of patients with tumors at the extremities received surgery, only 47.4% of pelvic osteosarcomas in this cohort received surgical resection-likely influenced by larger tumor size, sacral involvement, frequency of metastasis, older age, or delayed referral to a sarcoma center. CONCLUSION: This study clarifies presenting features and clinical outcomes of pelvic osteosarcomas, which often present with large, high-grade tumors with extracompartmental extension, high likelihood of metastatic disease at diagnosis, and a potential limited ability to be addressed surgically. The survival rates of primary osteosarcoma of the pelvis are poor and are lower than osteosarcomas from other anatomic locations. While acknowledging the influence of metastasis, tumor characteristics, and advanced age on the decision to undergo surgical excision of a pelvic osteosarcoma, the rates of surgical resection are low and highlight the importance of understanding appropriate conditions for oncologic resection of pelvic sarcomas.

Matrix Metalloproteinase 13 from Satellite Cells is Required for Efficient Muscle Growth and Regeneration.

BACKGROUND/AIMS: Cell migration and extracellular matrix remodeling underlie normal mammalian development and growth as well as pathologic tumor invasion. Skeletal muscle is no exception, where satellite cell migration replenishes nuclear content in damaged tissue and extracellular matrix reforms during regeneration. A key set of enzymes that regulate these processes are matrix metalloproteinases (MMP)s. The collagenase MMP-13 is transiently upregulated during muscle regeneration, but its contribution to damage resolution is unknown. The purpose of this work was to examine the importance of MMP-13 in muscle regeneration and growth in vivo and to delineate a satellite cell specific role for this collagenase. METHODS: Mice with total and satellite cell specific Mmp13 deletion were utilized to determine the importance of MMP-13 for postnatal growth, regeneration after acute injury, and in chronic injury from a genetic cross with dystrophic (mdx) mice. We also evaluated insulin-like growth factor 1 (IGF-1) mediated hypertrophy in the presence and absence of MMP-13. We employed live-cell imaging and 3D migration measurements on primary myoblasts obtained from these animals. Outcome measures included muscle morphology and function. RESULTS: Under basal conditions, Mmp13-/- mice did not exhibit histological or functional deficits in muscle. However, following acute injury, regeneration was impaired at 11 and 14 days post injury. Muscle hypertrophy caused by increased IGF-1 was blunted with minimal satellite cell incorporation in the absence of MMP-13. Mmp13-/- primary myoblasts displayed reduced migratory capacity in 2D and 3D, while maintaining normal proliferation and differentiation. Satellite cell specific deletion of MMP-13 recapitulated the effects of global MMP-13 ablation on muscle regeneration, growth and myoblast movement. CONCLUSION: These results show that satellite cells provide an essential autocrine source of MMP-13, which not only regulates their migration, but also supports postnatal growth and resolution of acute damage.