Osteoid Osteoma of the Calcaneus in a Young Patient Treated With Radiofrequency Ablation: A Case Report.

Osteoid osteoma (OO) is a common benign tumor that tends to affect children and young adults. Patients typically present with nocturnal pain that is relieved with non-steroidal anti-inflammatory drugs (NSAIDs) and a unique round or oval radiolucent area with surrounding sclerotic bone on X-ray. The cortex of the diaphysis or metaphysis of long bones is the usual anatomical location, with only 4% of cases localizing to the foot and ankle. Treatment options include medical management, surgical excision, and less invasive techniques such as radiofrequency ablation (RFA). We present a case report of a 21-year-old female with an osteoid osteoma of the calcaneus, a rare presentation for this type of tumor. She was successfully treated with RFA and had an excellent functional outcome.

Occupational injuries and burn out among orthopedic oncology surgeons.

BACKGROUND: Orthopedic oncology surgeons commonly engage in prolonged and complex surgical procedures. These types of surgeries increase the risk of physical and psychological stressors, which may in turn make these physicians prone to work-related occupational injuries. AIM: The aim of this study was to explore in orthopedic oncologists, the prevalence of work-related physical injuries and psychological disturbances. METHODS: A modified version of the physical discomfort survey was developed to assess occupational injuries among orthopedic oncology surgeon members of the Musculoskeletal Tumor Society, the Canadian Orthopedic Oncology Society and European Musculoskeletal Oncology Societies. The survey was sent by email, and it explored musculoskeletal complaints, psychological disturbances, treatment required for these complaints and the requirement of time off work. RESULTS: A total of 67 surgeon responses were collected. A high number of orthopedic oncologists (84%) reported an occupational injury. Low back pain (39%) was the most prevalent musculoskeletal condition, followed by lumbar disk herniation (16%), shoulder tendinitis (15%) and lateral epicondylitis (13%). Of the cohort, 46% required surgery and 31% required time off work due to their injury. Thirty-three respondents reported a psychological disorder. Burnout (27%), anxiety (20%) and insomnia (20%) were the most commonly reported. Time required off work due to injury was associated with old age and years in practice. CONCLUSION: Orthopedic oncology surgeons report a high prevalence of work-related disorders. Lower back related injury and burnout were the most reported disorders. Improving operative room ergonomics and prevention of stress related to the work environment should be areas to explore in upcoming research.

Naproxen induces type X collagen expression in human bone-marrow-derived mesenchymal stem cells through the upregulation of 5-lipoxygenase.

Several studies have shown that type X collagen (COL X), a marker of late-stage chondrocyte hypertrophy, is expressed in mesenchymal stem cells (MSCs) from osteoarthritis (OA) patients. We recently found that Naproxen, but not other nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen, Celebrex, Diclofenac), can induce type X collagen gene (COL10A1) expression in bone-marrow-derived MSCs from healthy and OA donors. In this study we determined the effect of Naproxen on COL X protein expression and investigated the intracellular signaling pathways that mediate Naproxen-induced COL10A1 expression in normal and OA hMSCs. MSCs of OA patients were isolated from aspirates from the intramedullary canal of donors (50-80 years of age) undergoing hip replacement surgery for OA and were treated with or without Naproxen (100 µg/mL). Protein expression and phosphorylation were determined by immunoblotting using specific antibodies (COL X, p38 mitogen-activated protein kinase [p38], phosphorylated-p38, c-Jun N-terminal kinase [JNK], phosphorylated-JNK, extracellular signal-regulated kinase [ERK], and phosphorylated-ERK). Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the expression of COL10A1 and Runt-related transcription factor 2 gene (Runx2). Our results show that Naproxen significantly stimulated COL X protein expression after 72 h of exposure both in normal and OA hMSCs. The basal phosphorylation of mitogen-activated protein kinases (MAPKs) (ERK, JNK, and p38) in OA hMSCs was significantly higher than in normal. Naproxen significantly increased the MAPK phosphorylation in normal and OA hMSCs. NSAID cellular effects include cyclooxygenase, 5-lipoxygenase, and p38 MAPK signaling pathways. To investigate the involvement of these pathways in the Naproxen-induced COL10A1 expression, we incubated normal and OA hMSCs with Naproxen with and without inhibitors of ERK (U0126), JNK (BI-78D3), p38 (SB203580), and 5-lipoxygenase (MK-886). Our results showed that increased basal COL10A1 expression in OA hMSCs was significantly suppressed in the presence of JNK and p38 inhibitors, whereas Naproxen-induced COL10A1 expression was suppressed by 5-lipoxygenase inhibitor. This study shows that Naproxen induces COL X both at transcriptional and translational levels in normal and OA hMSCs. Elevated basal COL10A1 expression in OA hMSCs is probably through the activation of MAPK pathway and Naproxen-induced COL10A1 expression is through the increased 5-lipoxygenase signaling.

Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules.

INTRODUCTION: We previously showed that type X collagen, a marker of late stage chondrocyte hypertrophy (associated with endochondral ossification), is constitutively expressed by mesenchymal stem cells (MSCs) from osteoarthritis patients and this may be related to Naproxen (Npx), a nonsteroidal anti-inflammatory drug used for therapy. Hedgehog (HH) signaling plays an important role during the development of bone. We tested the hypothesis that Npx affected osteogenic differentiation of human MSCs through the expression of Indian hedgehog (IHH), Patched-1 (PTC1) and GLI family members GLI1, GLI2, GLI3 in vitro. METHODS: MSCs were cultured in osteogenic differentiation medium without (control) or with 0.5 µM Npx. The expression of collagen type X, alpha 1 (COL10A1), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OC), collagen type I, alpha 1 (COL1A1) was analyzed with real-time reverse transcription (RT) PCR, and the ALP activity was measured. The osteogenesis of MSCs was monitored by mineral staining and quantification with alizarin red S. To examine whether Npx affects osteogenic differentiation through HH signaling, the effect of Npx on the expression of IHH, GLI1, GLI2, GLI3 and PTC1 was analyzed with real-time RT PCR. The effect of cyclopamine (Cpn), a HH signaling inhibitor, on the expression of COL10A1, ALP, OC and COL1A1 was also determined. RESULTS: When MSCs were cultured in osteogenic differentiation medium, Npx supplementation led to a significant decrease in ALP gene expression as well as its activity, and had a tendency to decrease mineral deposition. It also decreased the expression of COL1A1 significantly. In contrast, the gene expression of COL10A1 and OPN were upregulated significantly by Npx. No significant effect was found on OC expression. The expression of IHH, PTC1, GLI1, and GLI2 was increased by Npx, while no significant difference was observed on GLI3 expression. Cpn reversed the effect of Npx on the expression of COL10A1, ALP, OPN and COL1A1. CONCLUSIONS: These results indicate that Npx can affect gene expression during osteogenic differentiation of MSCs, and downregulate mineral deposition in the extracellular matrix through IHH signaling. Therefore, Npx could affect MSC-mediated repair of subchondral bone in OA patients.

The effect of Link N on differentiation of human bone marrow-derived mesenchymal stem cells.

INTRODUCTION: We previously showed that Link N can stimulate extracellular matrix biosynthesis by intervertebral disc (IVD) cells, both in vitro and in vivo, and is therefore a potential stimulator of IVD repair. The purpose of the present study was to determine how Link N may influence human mesenchymal stem cell (MSC) differentiation, as a prelude to using Link N and MSC supplementation in unison for optimal repair of the degenerated disc. METHODS: MSCs isolated from the bone marrow of three osteoarthritis patients were cultured in chondrogenic or osteogenic differentiation medium without or with Link N for 21 days. Chondrogenic differentiation was monitored by proteoglycan staining and quantitation by using Alcian blue, and osteogenic differentiation was monitored by mineral staining and quantitation by using Alzarin red S. In addition, proteoglycan secretion was monitored with the sulfated glycosaminoglycan (GAG) content of the culture medium, and changes in gene expression were analyzed with real-time reverse transcription (RT) PCR. RESULTS: Link N alone did not promote MSC chondrogenesis. However, after MSCs were supplemented with Link N in chondrogenic differentiation medium, the quantity of GAG secreted into the culture medium, as well as aggrecan, COL2A1, and SOX9 gene expression, increased significantly. The gene expression of COL10A1 and osteocalcin (OC) were downregulated significantly. When MSCs were cultured in osteogenic differentiation medium, Link N supplementation led to a significant decrease in mineral deposition, and alkaline phosphatase (ALP), OC, and RUNX2 gene expression. CONCLUSIONS: Link N can enhance chondrogenic differentiation and downregulate hypertrophic and osteogenic differentiation of human MSCs. Therefore, in principle, Link N could be used to optimize MSC-mediated repair of the degenerated disc.

The relationship between sleep and wake habits and academic performance in medical students: a cross-sectional study.

BACKGROUND: The relationship between the sleep/wake habits and the academic performance of medical students is insufficiently addressed in the literature. This study aimed to assess the relationship between sleep habits and sleep duration with academic performance in medical students. METHODS: This study was conducted between December 2009 and January 2010 at the College of Medicine, King Saud University, and included a systematic random sample of healthy medical students in the first (L1), second (L2) and third (L3) academic levels. A self-administered questionnaire was distributed to assess demographics, sleep/wake schedule, sleep habits, and sleep duration. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). School performance was stratified as "excellent" (GPA ≥ 3.75/5) or "average" (GPA <3.75/5). RESULTS: The final analysis included 410 students (males: 67%). One hundred fifteen students (28%) had "excellent" performance, and 295 students (72%) had "average" performance. The "average" group had a higher ESS score and a higher percentage of students who felt sleepy during class. In contrast, the "excellent" group had an earlier bedtime and increased TST during weekdays. Subjective feeling of obtaining sufficient sleep and non-smoking were the only independent predictors of "excellent" performance. CONCLUSION: Decreased nocturnal sleep time, late bedtimes during weekdays and weekends and increased daytime sleepiness are negatively associated with academic performance in medical students.