Incidence of Tibial Tubercle Fractures in Patients With and Without Osgood-Schlatter Disease.

BACKGROUND: Patients with Osgood-Schlatter disease (OSD) may be at increased risk of tibial tubercle fractures due to an underlying weakness of the tibial tubercle apophysis relative to the patellar tendon as a result of repetitive microtrauma. HYPOTHESIS/PURPOSE: The purpose of this study is to analyze the incidence of tibial tubercle fractures in patients with and without Osgood-Schlatter disease. We hypothesized that the incidence of tibial tubercle fractures would be higher in patients with Osgood-Schlatter disease. METHODS: A retrospective cohort analysis of the PearlDiver database was performed by querying all patients diagnosed with Osgood-Schlatter disease between January 2010 and October 2022. An OSD cohort of 146,672 patients was captured using International Classification of Diseases, Ninth Revision (ICD-9), Tenth Revision (ICD-10) billing codes, and age as inclusion/exclusion criteria. The Student t test and the χ2 analyses were used to compare the demographics and obesity between the OSD and control cohorts. Multivariable logistic regressions, controlling for residual differences in age, sex, and obesity, were used to compare rates of tibial tubercle fractures. RESULTS: Patients with a recent history of OSD were found to have higher rates of tibial tubercle fractures than the control group at all measured time points (P<0.001). The 1-year rate of tibial tubercle fractures was 0.62% in the OSD group. The incidence of tibial tubercle fractures in the OSD group was 627.3 cases per 100,000 person-years compared with 42.7 cases per 100,000 person-years in the control group (P<0.001). Male sex and obesity were also associated with an increased risk of sustaining a tibial tubercle fracture within these patient populations (P<0.001). CONCLUSION: We report a significantly higher incidence of tibial tubercle fractures among patients with OSD compared with controls. This increase was most significant at 1 month following OSD diagnosis, however, held true for all measured time points. In addition, male patients and those with obesity were also noted to have increased incidence of tibial tubercle fractures regardless of an OSD diagnosis.

Osteoarthritis in the Upper Extremity.

Osteoarthritis is a common cause of morbidity in an increasingly aging population. Although the weight-bearing joints of the leg and foot are frequently affected by osteoarthritis, degenerative changes in the joints of the upper extremity are likewise common and can be both particularly debilitating for affected individuals and uniquely challenging for the health care providers managing it. The present review seeks to overview the epidemiology, anatomy, diagnosis, and management of osteoarthritis in the joints of the shoulder, elbow, and hand with the intent of providing accessible and relevant information to the range of medical professionals involved in patient care.

Recurrence of Hamstring Injuries and Risk Factors for Partial and Complete Tears in the National Football League: An Analysis From 2009-2020.

PURPOSE: To (1) characterize hamstring injury (HSI) recurrence rates across the 2009-2010 to 2019-2020 NFL seasons and (2) to identify HSI recurrence risk factors among positions and determine the weekly return to play (RTP) recurrence risk. We hypothesized that older players, skill position players, and players returning to play faster were most at risk. METHODS: Public data from the 2009-2010 to 2019-2020 seasons were reviewed to identify HSIs. Player characteristics were collected before and two seasons following injury. A week-by-week analysis of recurrence risk was evaluated with linear and logarithmic trendlines of the best fit. RESULTS: A total of 2075 HSI were identified with a mean age of 26.2 years (20.0-43.0), BMI of 29.6 (22.7-43.5), and 3.4 seasons of experience (0-17), with 1826 strains (88.0%), 236 partial tears (11.3%), and 13 complete tears (0.63%). Of the 2075 injuries, 796 (38.4%) were recurrent, with 247 (11.9%) being a same-season reinjury. Logistic regression found that fewer weeks before RTP, in-game injury, and lower BMI were risk factors for same-season recurrence. For any recurrence, logistic regression identified more recent year of injury, lower BMI, and longer playing experience as significant risk factors. Wide receivers were found to be at risk for same-season recurrence. For any-season recurrence, defensive backs, linebackers, running backs, tight ends, and wide receivers were at risk. Week-by-week recurrence analysis determined the greatest risk to be when players returned within 2 weeks (13.4%). CONCLUSIONS: There is a high rate of HSI recurrence in the NFL. Risk factors for same-season injury include shorter time to RTP, in-game injury, lower BMI, and playing wide receiver. Risk factors for any-season recurrence were more recent year of injury, lower BMI, longer playing experience, and playing defensive back, linebacker, running back, tight end, or wide receiver. The greatest risk factor for HSI recurrence was RTP within 2 weeks.

Traumatic Fibular Loss Managed with a Free Vascularized Fibular Graft: A Case Report.

CASE: A 25-year-old man involved in a jet skiing accident experienced a traumatic excision of his distal fibula in conjunction with other lower extremity injuries. He subsequently underwent a reconstruction of his lateral malleolus using an ipsilateral free vascularized fibular graft (FVFG) from his proximal fibular shaft, resulting in a preserved and stabilized ankle joint at 1 year. CONCLUSION: Traumatic distal fibular excision is a rare injury that can be successfully managed using an FVFG, with fusion of the distal syndesmosis and a symmetric ankle mortise observed at the 1-year follow-up.

Performance After Concussion in National Basketball Association Players.

Background: Concussions have received national attention in collision sports such as football, soccer, and hockey, but less focus has been placed on basketball. Purpose: To determine return-to-play (RTP) and player performance in the first and second season after concussion in National Basketball Association (NBA) players. Study Design: Descriptive epidemiology study. Methods: An online database of publicly available NBA athlete injuries was queried for instances of "concussion" between 2010 and 2018. The age at injury, team, position, height, weight, body mass index, NBA experience, date of concussion, date of return, and seasons played postconcussion was recorded for each player. Regular-season statistics (games started, games played, minutes played, and player efficiency rating [PER]) were compiled for the season before, and 2 seasons immediately after, injury. Kaplan-Meier survivorship plots were computed for athlete RTP and retirement endpoints. Results: A total of 81 injuries were identified from 2010 to 2018, with a rate of 2.0 concussions per 100 player-years. Overall RTP was 100% after concussion, with nearly all (88%) returning in the season of injury; 12% of players experienced a season-ending concussion. RTP averaged 37.3 days after injury, varying widely (range, 2-291 days). Compared with preinjury season (78.0%), athletes played in significantly fewer overall games in the season of injury (36.6%; P < .0001), as well as 1 (69.5%; P = .0229) and 2 seasons postinjury (73.2%; P = .3192). PER scores were not significantly different across the study period. Each point increase in a player's preinjury PER score was associated with a 2.4% decrease in PER from the preinjury season to season of injury (P = .0016) and a 3.1% decrease from preinjury to season after injury (P = .0053). Each increasing year of age or year of experience was associated with 5% decline in PER score at 1 season after injury. Conclusion: NBA players had a high RTP after concussion, with most returning in the same season as the injury. Players sustaining concussions played significantly fewer games for at least 2 seasons after injury. Performance via PER did not change across the entire cohort; however, players with higher preinjury PER, and older players were more likely to sustain a greater decline in performance after injury.

Lower extremity injuries in the baseball athlete.

Baseball is unique in its multiple facets: pitching, hitting, base rounding, and fielding are distinct activities that require different athletic skills to perform at a high level. Likewise, these different aspects of the game can contribute to a multitude of varying injuries. While high-velocity overhead throwing, along with batting, can produce a plethora of upper extremity injuries that often garner attention, injuries to the lower extremity can severely impact a player's performance and ability to compete. The rigors of the short, explosive sprinting required for base running, as well as the dynamic movement required for fielding, create ample opportunity for lower limb injury, and even subtle pathology can affect a pitcher's ability to perform or increase their long-term risk of injury. Chronic injury from conditions such as femoroacetabular impingement and hip labral tears can also occur. The purpose of the present review is to summarize the relevant epidemiology, pathophysiology, and treatment of lower extremity injuries in baseball athletes, with reference to current research into the prevention and management of such injuries.

Defining the contemporary epidemiology and return to play for high ankle sprains in the National Football League.

BACKGROUND: High ankle sprains and syndesmotic injuries are commonly sustained by National Football League players, yet there is apaucity of literature reporting the incidence, risk factors and return to play (RTP) rates for these injuries. The purpose of this study is to examine the epidemiology and trends in incidence of high ankle sprains across 11 NFL seasons. METHODS: Publicly available data from the 2009-2010 through 2019-20 seasons were reviewed to identify injuries and collect player characteristics and return to play. Incidence of high ankle injuries was calculated per 10,000 athlete-exposures. Linear regression was performed for incidence of injuries. Risk factors for failure to RTP were identified through multivariate logistic regression, controlling foryear of injury, player position, body mass index (BMI), age at injury, and years of experience before injury. RESULTS: A total of 533 high ankle sprains were identified in 498 players at an average age of 25.8 ± 3.1 and average BMI of 31.8 ± 4.6. The annual incidence of high ankle sprains in the NFL increased at alinear rate of 0.067per 10,000 player exposures (R2 = 0.3357) in 2009, to 1.75per 10,000 player exposures to 2.49 in 2019-20. Most injuries were in offensive players (304/533 injuries, 57.0%). Overall, 89.7% (478/533) of players returned to play; average RTP time was 80.5 ± 132.9 days. Defensive players had afaster RTP (68.1 ± 114.6 days) compared to offensive players (90.1 ± 144.8 days) (p = 0.084). Higher age at injury was found to increase the risk of failure to RTP (p = 0.0088). CONCLUSION: RTP rate was high following high ankle sprain aamongNFL players at 90%, with an average recovery period of 11 weeks. Defensive players experience RTP faster than offensive players. Future studies are needed to determine performance outcomes following RTP, along with which patients might benefit from surgery.

The Weekend Warrior: Common Shoulder and Elbow Injuries in the Recreational Athlete.

"Weekend warriors" are recreational athletes who compress their physical activity into 1-2 weekly exercise sessions. These individuals are generally older than the conventionally discussed athlete, and can live otherwise sedentary lifestyles that contribute to limited opportunities for regular exercise. The combination of high-energy physical activity with relative deconditioning, as well as older age and a potential history of competitive athletic play, can predispose these weekend warriors to a plethora of sports injuries. The shoulder and elbow are dynamically involved in a multitude of common recreational sports, such as baseball, softball, tennis, golf, and volleyball, and forms of casual exercise, such as swimming or climbing. A lack of proper conditioning and supplemental training in weekend warriors, particularly in comparison to elite athletes in these respective sports, can contribute to the development of both acute and chronic conditions of the shoulder and elbow. Inconsistency in physical activity can minimize the prominence of symptoms, leading patients to delayed presentations with injuries that severely impact their ability to engage in their exercise of choice, and therefore remain active at all. This narrative review aims to present the etiology, presentation, and management of common shoulder and elbow injuries that may afflict this patient population. Prevention strategies will also be discussed.

Orthopedic manifestations of child abuse.

Child abuse is common in the United States but is often undetected. The incidence of this form of abuse is difficult to quantify, but children with a history of abuse are at risk of chronic health conditions. Medical providers are in the unique position of triaging trauma patients and differentiating unintentional from abusive trauma, as well as having the important position of being a mandated reporter of abuse in all states. Obtaining a detailed history and screening for risk factors can help identify children at risk of abuse. Certain orthopedic injuries may be related to abuse, which may trigger clinical suspicion and lead to further workup or intervention. By increasing awareness, through medical provider education and increased screening, earlier detection of abuse may prevent more serious injuries and consequences. This review evaluates current literature regarding the orthopedic manifestations of child abuse in hopes of increasing medical provider awareness. IMPACT: Child abuse is common in the United States but often remains undetected. Medical professionals are in the unique position of evaluating trauma patients and identifying concerns for abusive injuries. Certain orthopedic injuries may raise concern for abuse triggering clinical suspicion and further workup or intervention.

Malpractice Litigation Involving Chiropractic Spinal Manipulation.

OBJECTIVE: To evaluate the relationship between chiropractic spinal manipulation and medical malpractice using a legal database. METHODS: The legal database VerdictSearch was queried using the terms "chiropractor" OR "spinal manipulation" under the classification of "Medical Malpractice" between 1988 and 2018. Cases with chiropractors as defendants were identified. Relevant medicolegal characteristics were obtained, including legal outcome (plaintiff/defense verdict, settlement), payment amount, nature of plaintiff claim, and type and location of alleged injury. RESULTS: Forty-eight cases involving chiropractic management in the United States were reported. Of these, 93.8% (n = 45) featured allegations involving spinal manipulation. The defense (practitioner) was victorious in 70.8% (n = 34) of cases, with a plaintiff (patient) victory in 20.8% (n = 10) (mean payment $658,487 ± $697,045) and settlement in 8.3% (n = 4) (mean payment $596,667 ± $402,534). Overaggressive manipulation was the most frequent allegation (33.3%; 16 cases). A majority of cases alleged neurological injury of the spine as the reason for litigation (66.7%, 32 cases) with 87.5% (28/32) requiring surgery. C5-C6 disc herniation was the most frequently alleged injury (32.4%, 11/34, 83.3% requiring surgery) followed by C6-C7 herniation (26.5%, 9/34, 88.9% requiring surgery). Claims also alleged 7 cases of stroke (14.6%) and 2 rib fractures (4.2%) from manipulation therapy. CONCLUSIONS: Litigation claims following chiropractic care predominately alleged neurological injury with consequent surgical management. Plaintiffs primarily alleged overaggressive treatment, though a majority of trials ended in defensive verdicts. Ongoing analysis of malpractice provides a unique lens through which to view this complicated topic.

Orthopedic Manifestations of Abuse.

Intimate partner violence and elder abuse are common in the United States but often remain undetected. The incidence of these forms of abuse is difficult to quantify, but those with a history of abuse are at risk of chronic health conditions. Physicians are in a unique position of triaging trauma patients and differentiating unintentional from abusive trauma in patients. Certain orthopedic injuries, in particular, may be related to abuse, which may trigger clinical suspicion and lead to further workup or intervention. By increasing awareness, through physician education and increased screening, earlier detection of abuse may prevent more serious injuries and consequences. Therefore, this review evaluates current literature regarding the orthopedic manifestations of abuse in hopes of increasing physician awareness.

Fitness habits and barriers to exercise during residency training.

While physicians advise patients on healthy lifestyle habits, physicians may struggle to abide by their own recommendations. We sought to characterize resident physician participation in exercise, their barriers to exercise, and the effect of exercise on their overall wellness. We hypothesized that residents who exercised would have less depression and greater wellbeing. Trainees at a university-based institution were surveyed. Data regarding exercise habits, hours worked, barriers to exercise, and mental health were acquired. Mental health was assessed via the Patient Health Questionnaire-2. Inter-group differences were analyzed using chi-squared testing; statistical significance was set at PÃ0.05. 129 trainees responded to the survey. 84 trainees reported exercising while 45 denied. 63 exercisers reported "living a healthy lifestyle" compared to 18 nonexercisers (PÃ0.001). Exercisers were more likely to report "Time" as their greatest barrier to exercise (PÃ0.001). Fifty-five exercisers answered "Not at all" when asked about how often they experience anhedonia compared to 23 non-exercisers. Trainees who exercise are more likely to report living a healthy lifestyle and less likely to experience anhedonia than non-exercisers, demonstrating the importance of exercise during residency.

Surgical Treatment of Meniscal Extrusion: A Biomechanical Study on the Role of the Medial Meniscotibial Ligaments With Early Clinical Validation.

BACKGROUND: Meniscal extrusion refers to meniscal displacement out of the joint space and over the tibial margin, altering knee mechanics and increasing the risk of osteoarthritis. The meniscotibial ligaments have been shown to have an important role in meniscal stability. However, it remains unclear whether an isolated lesion of the medial meniscotibial ligaments will result in meniscal extrusion and whether repairing the detached ligament will reduce extrusion. HYPOTHESIS: A lesion of the medial meniscotibial ligament will result in meniscal extrusion, and repairing the joint capsule will eliminate the extrusion by returning the meniscus back to its original position. STUDY DESIGN: Controlled laboratory study. METHODS: Fresh-frozen human cadaveric knees (N = 6) were used for biomechanical testing. The test protocol involved 100 flexion-extension cycles. In full extension, meniscal extrusion was measured using ultrasound, in both an otherwise unloaded state and while subjected to a 10-N·m varus load. Each knee was tested in its native condition (baseline), after creating a detachment of the medial meniscotibial ligament, and finally with the joint capsule repaired using 3 knotless SutureTak anchors. We also performed a retrospective review of 15 patients who underwent meniscotibial ligament repair with a minimal follow-up of 5 weeks (mean, 14 weeks; range, 5-35 weeks). RESULTS: During biomechanical testing, the mean absolute meniscal extrusion at baseline was 1.5 ± 0.6 mm. After creation of the meniscotibial ligament lesion, the mean absolute meniscal extrusion was significantly increased (3.4 ± 0.7 mm) (P < .001). After repair, the extrusion was reduced to 2.1 ± 0.4 mm (P < .001). Clinically, a reduction in absolute meniscal extrusion of approximately 48% was reached (1.2 ± 0.6 vs 2.4 ± 0.5 mm preoperatively; P < .001). CONCLUSION: This study indicates that the medial meniscotibial ligaments contribute to meniscal stability as lesions cause the meniscus to extrude and that repair of those ligaments can significantly reduce extrusion. Early clinical results using this meniscotibial ligament repair technique support our biomechanical findings, as a significant reduction in meniscal extrusion was achieved. CLINICAL RELEVANCE: Our biomechanical findings suggest that repair of medial meniscotibial ligaments reduces meniscal extrusion and clinically may improve meniscal function, with the possible long-term benefit of reducing the risk for osteoarthritis.

Internet accuracy of publicly available images of meniscal tears.

BACKGROUND: The Internet is an easily accessible resource for both providers and patients. Despite this, the Internet is not peer reviewed, leaving Internet searches subject to inaccuracies, especially with regards to medical information. The purpose of this study was to review Internet images of meniscus tears using three popular search engines: Google, Bing, and Yahoo. METHODS: A search query was performed on the aforementioned search engines for the term: 'meniscus tear'. The first 100 images found for each individual search were analyzed by two independent reviewers with different levels of orthopedic training (orthopedic surgery resident and medical student). Inter-rate reliability and accuracy was determined for each of the search engines. The images were defined based on the source that published the image as either educational (published by hospital or medical association), commercial (published by a device company), or individual (published via a physician). RESULTS: The inter-rater reliability was excellent (Cronbach's alpha = 0.91), (Cronbach's alpha = 0.94), (Cronbach's alpha >0.90) on Google, Bing, and Yahoo, respectively. When comparing the search engines for correctness, Google had 82% accuracy, compared to 81% for Bing and Yahoo. All three search engines have a similar mix of source material with educational images consisting of 86% of Google images, 84% for Yahoo, and 89% for Bing. CONCLUSION: Our study revealed that the three search engines queried displayed meniscal tear images with >80% accuracy when evaluated by two independent reviewers. Despite this, many images may still be seen as highly technical, or esoteric to an untrained individual. Ultimately, physicians should take an active role in making high quality, easy to understand medical resources, and anatomic diagrams available to their patients to avoid confusion and enhance understanding.

Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy.

A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring. A quantitative 19-gene digital RNA signature (CTC score) applied to microfluidically enriched CTCs robustly distinguishes melanoma cells, within a background of blood cells in reconstituted and in patient-derived (n = 42) blood specimens. In a prospective cohort of 49 patients treated with immune checkpoint inhibitors, a decrease in CTC score within 7 weeks of therapy correlates with marked improvement in progression-free survival [hazard ratio (HR), 0.17; P = 0.008] and overall survival (HR, 0.12; P = 0.04). Thus, digital quantitation of melanoma CTC-derived transcripts enables serial noninvasive monitoring of tumor burden, supporting the rational application of immune checkpoint inhibition therapies.

An RNA-Based Digital Circulating Tumor Cell Signature Is Predictive of Drug Response and Early Dissemination in Prostate Cancer.

Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTC) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 patients with metastatic castration-resistant prostate cancer treated with first-line abiraterone, pretreatment elevation of the digital CTCM score identifies a high-risk population with poor overall survival (HR = 6.0; P = 0.01) and short radiographic progression-free survival (HR = 3.2; P = 0.046). Expression of HOXB13 in CTCs identifies 6 of 6 patients with ≤12-month survival, with a subset also expressing the ARV7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTCL score predicts microscopic dissemination to seminal vesicles and/or lymph nodes (P < 0.001). Thus, digital quantitation of CTC-specific transcripts enables noninvasive monitoring that may guide treatment selection in both metastatic and localized prostate cancer.Significance: There is an unmet need for biomarkers to guide prostate cancer therapies, for curative treatment of localized cancer and for application of molecularly targeted agents in metastatic disease. Digital quantitation of prostate CTC-derived transcripts in blood specimens is predictive of abiraterone response in metastatic cancer and of early dissemination in localized cancer. Cancer Discov; 8(3); 288-303. ©2018 AACR.See related commentary by Heitzer and Speicher, p. 269This article is highlighted in the In This Issue feature, p. 253.

Expression of ß-globin by cancer cells promotes cell survival during blood-borne dissemination.

Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of ß-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4. Depletion of HBB in CTC-derived cultures has minimal effects on primary tumour growth, but it greatly increases apoptosis following ROS exposure, and dramatically reduces CTC-derived lung metastases. These effects are reversed by the anti-oxidant N-Acetyl Cysteine. Conversely, overexpression of HBB is sufficient to suppress intracellular ROS within CTCs. Altogether, these observations suggest that ß-globin is selectively deregulated in cancer cells, mediating a cytoprotective effect during blood-borne metastasis.

An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma.

Circulating tumor cells (CTCs) are shed into the bloodstream by invasive cancers, but the difficulty inherent in identifying these rare cells by microscopy has precluded their routine use in monitoring or screening for cancer. We recently described a high-throughput microfluidic CTC-iChip, which efficiently depletes hematopoietic cells from blood specimens and enriches for CTCs with well-preserved RNA. Application of RNA-based digital PCR to detect CTC-derived signatures may thus enable highly accurate tissue lineage-based cancer detection in blood specimens. As proof of principle, we examined hepatocellular carcinoma (HCC), a cancer that is derived from liver cells bearing a unique gene expression profile. After identifying a digital signature of 10 liver-specific transcripts, we used a cross-validated logistic regression model to identify the presence of HCC-derived CTCs in nine of 16 (56%) untreated patients with HCC versus one of 31 (3%) patients with nonmalignant liver disease at risk for developing HCC (P < 0.0001). Positive CTC scores declined in treated patients: Nine of 32 (28%) patients receiving therapy and only one of 15 (7%) patients who had undergone curative-intent ablation, surgery, or liver transplantation were positive. RNA-based digital CTC scoring was not correlated with the standard HCC serum protein marker alpha fetoprotein (P = 0.57). Modeling the sequential use of these two orthogonal markers for liver cancer screening in patients with high-risk cirrhosis generates positive and negative predictive values of 80% and 86%, respectively. Thus, digital RNA quantitation constitutes a sensitive and specific CTC readout, enabling high-throughput clinical applications, such as noninvasive screening for HCC in populations where viral hepatitis and cirrhosis are prevalent.

Spinal Cord Inflammation: Molecular Imaging after Thoracic Aortic Ischemia Reperfusion Injury.

Purpose To evaluate whether noninvasive molecular imaging technologies targeting myeloperoxidase (MPO) can reveal early inflammation associated with spinal cord injury after thoracic aortic ischemia-reperfusion (TAR) in mice. Materials and Methods The study was approved by the institutional animal care and use committee. C57BL6 mice that were 8-10 weeks old underwent TAR (n = 55) or sham (n = 26) surgery. Magnetic resonance (MR) imaging (n = 6) or single photon emission computed tomography (SPECT)/computed tomography (CT) (n = 15) studies targeting MPO activity were performed after intravenous injection of MPO sensors (bis-5-hydroxytryptamide-tetraazacyclododecane [HT]-diethyneletriaminepentaacetic acid [DTPA]-gadolinium or indium 111-bis-5-HT-DTPA, respectively). Immunohistochemistry and flow cytometry were used to identify myeloid cells and neuronal loss. Proinflammatory cytokines, keratinocyte chemoattractant (KC), and interleukin 6 (IL-6) were measured with enzyme-linked immunosorbent assay. Statistical analyses were performed by using nonparametric tests and the Pearson correlation coefficient. P < .05 was considered to indicate a significant difference. Results Myeloid cells infiltrated into the injured cord at 6 and 24 hours after TAR. MR imaging confirmed the presence of ischemic lesions associated with mild MPO-mediated enhancement in the thoracolumbar spine at 24 hours compared with the sham procedure. SPECT/CT imaging of MPO activity showed marked MPO-sensor retention at 6 hours (P = .003) that continued to increase at 24 hours after TAR (P = .0001). The number of motor neurons decreased substantially at 24 hours after TAR (P < .01), which correlated inversely with in vivo inflammatory changes detected at molecular imaging (r = 0.64, P = .0099). MPO was primarily secreted by neutrophils, followed by lymphocyte antigen 6 complexhigh monocytes and/or macrophages. There were corresponding increased levels of proinflammatory cytokines KC (P = .0001) and IL-6 (P = .0001) that mirrored changes in MPO activity. Conclusion MPO is a suitable imaging biomarker for identifying and tracking inflammatory damage in the spinal cord after TAR in a mouse model. © RSNA, 2016 Online supplemental material is available for this article.

Effect of limb demand ischemia on autophagy and morphology in mice.

BACKGROUND: Obesity is a major risk factor for diabetes and peripheral arterial disease, which frequently leads to lower limb demand ischemia. Skeletal muscle autophagy and mitochondrial biogenesis are important processes for proper oxidative capacity and energy metabolism, which are compromised in diabetes. This study compares autophagy, mitochondrial biogenesis, energy metabolism, and morphology in the hind limbs of obese diabetic mice subjected to demand or sedentary ischemia. MATERIALS AND METHODS: Unilateral hind limb demand ischemia was created in a group of diet-induced obese mice after femoral artery ligation and 4 wk of daily exercise. A parallel group of mice underwent femoral artery ligation but remained sedentary for 4 wk. Hind limb muscles were analyzed for markers of autophagy, mitochondrial biogenesis, adenosine triphosphate, and muscle tissue morphology. RESULTS: At the end of the 4-wk exercise period, demand ischemia increased the autophagy mediator Beclin-1, but it did not alter the autophagy indicator, LC3B-II/I ratio, or markers of mitochondrial biogenesis, optic atrophy/dynamin-related protein. In contrast, exercise significantly increased the level of mitochondrial protein-succinate dehydrogenase subunit-A and reduced adipocyte accumulation and the percentage of centrally nucleated myofibers in the demand ischemia limb. In addition, demand ischemia resulted in decreased uncoupling protein-3 levels without altering muscle adenosine triphosphate or pS473-Akt levels. CONCLUSIONS: Limb demand ischemia markedly decreased adipocyte accumulation and enhanced muscle regeneration in obese mice, but it did not appear to enhance autophagy, mitochondrial biogenesis, energy metabolism, or insulin sensitivity. Future studies aimed at evaluating novel therapies that enhance autophagy and mitochondrial biogenesis in diabetes with peripheral arterial disease are warranted.