Pannexins in the musculoskeletal system: new targets for development and disease progression.

During cell differentiation, growth, and development, cells can respond to extracellular stimuli through communication channels. Pannexin (Panx) family and connexin (Cx) family are two important types of channel-forming proteins. Panx family contains three members (Panx1-3) and is expressed widely in bone, cartilage and muscle. Although there is no sequence homology between Panx family and Cx family, they exhibit similar configurations and functions. Similar to Cxs, the key roles of Panxs in the maintenance of physiological functions of the musculoskeletal system and disease progression were gradually revealed later. Here, we seek to elucidate the structure of Panxs and their roles in regulating processes such as osteogenesis, chondrogenesis, and muscle growth. We also focus on the comparison between Cx and Panx. As a new key target, Panxs expression imbalance and dysfunction in muscle and the therapeutic potentials of Panxs in joint diseases are also discussed.

Hepatocellular carcinoma and musculoskeletal system: A narrative literature review.

Musculoskeletal alterations in hepatocellular carcinoma (HCC) are less common than liver-related complications. However, they can significantly impact the quality of life and overall prognosis of patients with HCC. The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asymptomatic and unapparent during routine clinical evaluations. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to the changes in the musculoskeletal system in patients with HCC, focusing on its clinical implications and underlying etiopathogenetic mechanisms. Osteolytic bone metastases are the most common skeletal alterations associated with HCC, which could be associated with an increased risk of low-trauma bone fracture. Moreover, previous studies reported that osteopenia, sarcopenia, and myosteatosis are associated with poor clinical outcomes in patients with HCC. Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients, these complications are frequently overlooked in the clinical management of patients with HCC. Taken together, contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis. Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

Oral analgesic for musculoskeletal injuries in children: A systematic review and network meta-analysis.

OBJECTIVE: Pain in pediatric musculoskeletal (MSK) injuries can lead to increased anxiety, fear, and avoidance of medical care, making analgesic management critical. Therefore, we evaluated analgesic efficacy and adverse effects to select the optimal analgesic agent in pediatric patients with MSK injuries. METHODS: Four databases were searched from inception to March 2023 for peer-reviewed, open randomized controlled trials (RCTs). Inclusion criteria were: (1) trials with RCT design, (2) children aged 1 month-18 years with MSK injury, (3) outpatient setting, (4) interventions and control, (5) primary outcome of pain score at 60 and 120 min and secondary outcome of adverse effects, and (6) full-text and peer-reviewed articles. Two reviewers screened, extracted data, and assessed the risk of bias. A frequentist random-effects network meta-analysis (NMA) was performed. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation working group approach. RESULTS: We included eight trials comprising 1645 children. Ibuprofen was significantly associated with pain reduction at 120 min, compared with acetaminophen (SMD 0.31 [95% CI 0.11-0.51]; moderate certainty) and opioids (SMD 0.34 [95% CI 0.20-0.48]; moderate certainty). Compared with opioids alone, ibuprofen-opioid combination was significantly associated with pain reduction at 120 min (SMD 0.19 [95% CI 0.03-0.35]). No significant differences were found in pain interventions at 60 min. Ibuprofen had statistically fewer adverse events than opioids (RR, 0.54 [95% CI 0.33-0.90]; moderate certainty) and ibuprofen with opioids (RR 0.47 [95% CI 0.25-0.89]; moderate certainty). In terms of limitations, the eight RCTs included had relatively small sample sizes; only two were high-quality RCTs. CONCLUSIONS: Our NMA found ibuprofen to be the most effective and least adverse analgesic in pediatric patients with MSK injuries.

The diagnostic accuracy of 332 incisional biopsies in patients with malignant tumors in the musculoskeletal system.

BACKGROUND: It is known that specimen collection followed by histopathological workup is the core of evidence-based medical therapy of musculoskeletal tumors. There exist many controversies about how a biopsy should be performed. While some centers recommend minimal invasive biopsy procedures, mostly the core needle biopsy (CNB), others prefer the incisional biopsy. PURPOSE OF THE STUDY: This study aimed to determine the accuracy of incisional biopsy for malignant tumors in the musculoskeletal system. Moreover, advantages and disadvantages to other biopsy methods are discussed. METHODS: This retrospective, single-center study about 844 incisional biopsies (benign and malignant) analysis the diagnostic accuracy of 332 malignant tumors, concerning the final histopathological result. In addition, surgical complications are analyzed to find the best way to plan and treat patients timely and correct. Secondary endpoints are the patients age, the pure operation time, as well as the type of tumor, and the subsequent therapy. RESULTS: In summary, incisional biopsy corresponded a sensitivity of 100% for malignancy in 844 incisional biopsies and a specificity of 97.6% in 332 malignant tumors, but it features greater operative expense (incision/suture 23.5 min) and the risk of general anesthesia. CONCLUSION: The method of biopsy should be tailored to the individual patient and the experience of the center performing the procedure.

Primary Soft-Tissue Lymphomas: MRI Features Help Discriminate From Other Soft-Tissue Tumors.

OBJECTIVES: MRI presentation of extra-nodal soft-tissue lymphomas (STLs) is scarcely reported and lacks of comparison with other soft-tissue tumors (STTs) including sarcomas (STS). Yet, suggesting this diagnosis on MRI would considerably reduce diagnostic intervals. Our aim was to investigate if conventional MRI could discriminate STLs from other STTs. METHODS: MRIs of STL patients were compared with those of patients addressed to a sarcoma reference center for the diagnosis of a STT. MRI characteristics depicting the tumor (size, signal, habitats, shape, surrounding tissues) were reported. Uni- and multivariate associations with STL diagnosis were evaluated in the entire cohort, and in the subgroups of benign and malignant STTs patients. Diagnostic performances of MRI features combinations were tested. RESULTS: We included 39 patients with STLs (median age: 69 years) and 368 patients with other STTs (122 benign STTs and 246 STS; median age: 58 years). Six MRI features were independent predictors of STL compared to all other STTs: intermediate SI on T1-WI, homogeneous enhancement (without necrotic areas), no blood signal, no fibrotic signal, no peritumoral enhancement and lack of abnormal intra- and peritumoral vasculature (p-value range: <0.0001-0.0163). Their simultaneous presence had a sensitivity of 0.88 (0.71-0.96) and a specificity of 0.88 (0.84-0.91). Other relevant MRI features were: no fat signal to discriminate against STS (p = 0.0409), the infiltrative growth pattern and the vessel and nerve encasement to discriminate against benign STTs (p = 0.0016 and 0.0011, respectively). CONCLUSION: Our research demonstrates that conventional MRI can help discriminating STLs from other STTs. Indeed, radiologists can help suggesting the possible diagnosis of STL, which could speed-up the subsequent proper histopathological analysis in light of MRI findings.

Multiparametric Evaluation of Soft Tissue Sarcoma: Current Perspectives and Future Directions.

Imaging plays an essential role in diagnosing and managing musculoskeletal soft tissue masses. It provides anatomic details and aids in the characterization and prognostication of tumors. Advanced imaging is also essential for assessing treatment response and post-treatment surveillance. Several novel imaging techniques are now available that provide additional functional and metabolic information about these tumors. This additional information may be used to predict the biological behavior of the tumors and effectively assess the treatment response for optimizing their management. This article focuses on multiparametric imaging evaluation of soft tissue masses with a discussion of advancements in the domains of ultrasound, MRI, and CT imaging and how these may be helpful in pre- and post-treatment assessment of soft tissue tumors. Current perspectives on the role of diffusion imaging, perfusion imaging, and MR spectroscopy have been highlighted, and future directions of metabolic imaging are briefly outlined. As these advances hold a promising role in the multidisciplinary management of soft tissue sarcomas, it is important for the radiologist to be familiar with the latest advances and developments in imaging soft tissue tumors.

In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo: Part II: Pathology: Part II: Pathology.

It is clear from Part I of this series that extracellular vesicles (EVs) play a critical role in maintaining the homeostasis of most, if not all, normal physiological systems. However, the majority of our knowledge about EV signalling has come from studying them in disease. Indeed, EVs have consistently been associated with propagating disease pathophysiology. The analysis of EVs in biofluids, obtained in the clinic, has been an essential of the work to improve our understanding of their role in disease. However, to interfere with EV signalling for therapeutic gain, a more fundamental understanding of the mechanisms by which they contribute to pathogenic processes is required. Only by discovering how the EV populations in different biofluids change-size, number, and physicochemical composition-in clinical samples, may we then begin to unravel their functional roles in translational models in vitro and in vivo, which can then feedback to the clinic. In Part II of this review series, the functional role of EVs in pathology and disease will be discussed, with a focus on in vivo evidence and their potential to be used as both biomarkers and points of therapeutic intervention.

Treatment of skeletal and non-skeletal alterations of Mucopolysaccharidosis type IVA by AAV-mediated gene therapy.

Mucopolysaccharidosis type IVA (MPSIVA) or Morquio A disease, a lysosomal storage disorder, is caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency, resulting in keratan sulfate (KS) and chondroitin-6-sulfate accumulation. Patients develop severe skeletal dysplasia, early cartilage deterioration and life-threatening heart and tracheal complications. There is no cure and enzyme replacement therapy cannot correct skeletal abnormalities. Here, using CRISPR/Cas9 technology, we generate the first MPSIVA rat model recapitulating all skeletal and non-skeletal alterations experienced by patients. Treatment of MPSIVA rats with adeno-associated viral vector serotype 9 encoding Galns (AAV9-Galns) results in widespread transduction of bones, cartilage and peripheral tissues. This led to long-term (1 year) increase of GALNS activity and whole-body correction of KS levels, thus preventing body size reduction and severe alterations of bones, teeth, joints, trachea and heart. This study demonstrates the potential of AAV9-Galns gene therapy to correct the disabling MPSIVA pathology, providing strong rationale for future clinical translation to MPSIVA patients.

Fatty infiltration in cervical flexors and extensors in patients with degenerative cervical myelopathy using a multi-muscle segmentation model.

BACKGROUND: In patients with degenerative cervical myelopathy (DCM) that have spinal cord compression and sensorimotor deficits, surgical decompression is often performed. However, there is heterogeneity in clinical presentation and post-surgical functional recovery. OBJECTIVES: Primary: a) to assess differences in muscle fat infiltration (MFI) in patients with DCM versus controls, b) to assess association between MFI and clinical disability. Secondary: to assess association between MFI pre-surgery and post-surgical functional recovery. STUDY DESIGN: Cross-sectional case control study. METHODS: Eighteen patients with DCM (58.6 ± 14.2 years, 10 M/8F) and 25 controls (52.6 ± 11.8 years, 13M/12 F) underwent 3D Dixon fat-water imaging. A convolutional neural network (CNN) was used to segment cervical muscles (MFSS- multifidus and semispinalis cervicis, LC- longus capitis/colli) and quantify MFI. Modified Japanese Orthopedic Association (mJOA) and Nurick were collected. RESULTS: Patients with DCM had significantly higher MFI in MFSS (20.63 ± 5.43 vs 17.04 ± 5.24, p = 0.043) and LC (18.74 ± 6.7 vs 13.66 ± 4.91, p = 0.021) than controls. Patients with increased MFI in LC and MFSS had higher disability (LC: Nurick (Spearman's ρ = 0.436, p = 0.003) and mJOA (ρ = -0.399, p = 0.008)). Increased MFI in LC pre-surgery was associated with post-surgical improvement in Nurick (ρ = -0.664, p = 0.026) and mJOA (ρ = -0.603, p = 0.049). CONCLUSION: In DCM, increased muscle adiposity is significantly associated with sensorimotor deficits, clinical disability, and functional recovery after surgery. Accurate and time efficient evaluation of fat infiltration in cervical muscles may be conducted through implementation of CNN models.

The effects of spaceflight microgravity on the musculoskeletal system of humans and animals, with an emphasis on exercise as a countermeasure: a systematic scoping review.

The purpose of this systematic review is twofold: 1) to identify, evaluate, and synthesize the heretofore disparate scientific literatures regarding the effects of direct exposure to microgravity on the musculoskeletal system, taking into account for the first time both bone and muscle systems of both humans and animals; and 2) to investigate the efficacy and limitations of exercise countermeasures on the musculoskeletal system under microgravity in humans.The Framework for Scoping Studies (Arksey and O'Malley 2005) and the Cochrane Handbook for Systematic Reviews of Interventions (Higgins JPT 2011) were used to guide this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was utilized in obtaining the combined results (Moher, Liberati et al. 2009). Data sources, PubMed, Embase, Scopus, and Web of Science were searched for published articles through October 2019 using the Mesh terms of microgravity, musculoskeletal system, and exercise countermeasures. A total of 84 references were selected, including 40 animal studies and 44 studies with human participants. The heterogeneity in the study designs, methodologies, and outcomes deemed this review unsuitable for a meta-analysis. Thus, we present a narrative synthesis of the results for the key domains under five categories: 1) Skeletal muscle responses to microgravity in humans 2) Skeletal muscle responses to microgravity in animals 3) Adaptation of the skeletal system to microgravity in humans 4) Adaptation of the skeletal system to microgravity in animals 5) Effectiveness of exercise countermeasures on the human musculoskeletal system in microgravity. Existing studies have produced only limited data on the combined effects on bone and muscle of human spaceflight, despite the likelihood that the effects on these two systems are complicated due to the components of the musculoskeletal system being anatomically and functionally interconnected. Bone is directly affected by muscle atrophy as well as by changes in muscle strength, notably at muscle attachments. Given this interplay, the most effective exercise countermeasure is likely to be robust, individualized, resistive exercise, primarily targeting muscle mass and strength.

Current advances and research in ultrasound imaging to the assessment and management of musculoskeletal disorders.

Currently evidence-based practice has given scientific weight to the physical therapist profession; it is essential that all medical professional and physical therapists know the usefulness of new tools that optimize the effectiveness of their interventions and allow the growing of the scientific knowledge base. The use of ultrasound imaging (USI) by physiotherapists has evolved in recent years, consolidating as an increasingly standardized technique, low cost compared to other imaging techniques, quickly of execution, feasible and reliable tool. USI offers a wide range of opportunities in clinical practice as well as in different research areas. Therefore, ultrasound has been currently used as a diagnostic tool by physicians and in recent years there has been an expansion of the use of ultrasound equipment by non-physicians professionals such as physical therapist or physical trainers, who incorporates USI as a means of assessing musculoskeletal system architecture and composition, musculoskeletal changes in dysfunction, pain or injury conditions, as an interventional technique assisting echo-guided procedures or using the visual real-time information as a biofeedback in control motor approaches, as guiding tool in clinical decisions as well as to improve the understanding of tissue adaptations to exercise or movement. The purpose of this article is to review and provide an overview about the currently research of the USI applications and their benefits for the diagnosis and management in individuals with musculoskeletal conditions.

Óbitos pós-cirúrgicos em neonatos com malformações congênitas do aparelho digestivo ou osteomuscular / Post-surgical deaths in neonates with congenital malformations in the digestive or musculoskeletal systems / Muertes post-quirúrgicas en neonatos con malformaciones congénitas digestivas o musculoesqueléticas

Objetivo: Analisar a ocorrência de óbitos pós-cirúrgicos em recém-nascidos com malformação do aparelho digestivo ou osteomuscular em uma maternidade de referência. Método: Estudo exploratório, retrospectivo, de abordagem quantitativa, realizado em uma maternidade de referência localizada em Teresina ­ PI. Os dados foram coletados do Tabwin e de fichas de investigação de óbito infantil de neonatos nascidos em 2016 e 2017 e analisados no software Statistical Package for the Social Sciences. Resultados: O tipo de malformação mais prevalente do aparelho digestivo e osteomuscular entre os neonatos que foram a óbito após cirurgia foi o ânus imperfurado (41%) e a gastrosquise (64,2%), respectivamente. O choque séptico, seguido da insuficiência renal aguda foram os fatores determinantes dos óbitos analisados. Conclusão: O diagnóstico precoce é o fator primordial para redução da morbimortalidade de neonatos acometidos por malformações congênitas, uma vez que contribui para o direcionamento e planejamento dos cuidados imprescindíveis a esses pacientes

Objective: To analyze the occurrence of post-surgical deaths in newborns with malformation in the digestive or musculoskeletal systems in a reference maternity hospital. Method: This is an exploratory and retrospective study, with a quantitative approach, conducted in a reference maternity located in Teresina ­ PI. Data were collected from Tabwin and infant death investigation forms of neonates born in 2016 and 2017 and analyzed through the Statistical Package for the Social Sciences software. Results: The most prevalent type of malformation of the digestive and musculoskeletal systems among neonates who died after surgery was the imperforate anus (41%) and gastroschisis (64.2%), respectively. Septic shock, followed by acute kidney failure, constituted the determining factors of the analyzed deaths. Conclusion: Early diagnosis is the key factor for reducing morbidity and mortality in neonates affected by congenital malformations, as it contributes to the targeting and planning of care actions essential for these patients

Objetivo: Analizar la ocurrencia de muertes post-quirúrgicas en recién nacidos con malformación digestiva o musculoesquelética en una maternidad de referencia. Método: Estudio exploratorio, retrospectivo, con enfoque cuantitativo, realizado en una maternidad de referencia ubicada en Teresina - PI. Los datos se recopilaron de Tabwin y de registros de investigación de muerte infantil de neonatos en 2016 y 2017 y se analizaron utilizando el programa Statistical Package for the Social Sciences. Resultados: El tipo de malformación digestiva y musculoesquelética más frecuente entre los neonatos que murieron después de la cirugía fue el ano imperforado (41%) y la gastrosquisis (64,2%), respectivamente. El shock séptico, seguido de insuficiencia renal aguda, constituyeron los factores determinantes de las muertes analizadas. Conclusión: El diagnóstico temprano es el factor principal para reducir la morbimortalidad en los neonatos afectados por malformaciones congénitas, ya que contribuye a la dirección y planificación de la atención esencial para estos pacientes

Role of Scx+/Sox9+ cells as potential progenitor cells for postnatal supraspinatus enthesis formation and healing after injury in mice.

A multipotent cell population co-expressing a basic-helix-loop-helix transcription factor scleraxis (Scx) and SRY-box 9 (Sox9) has been shown to contribute to the establishment of entheses (tendon attachment sites) during mouse embryonic development. The present study aimed to investigate the involvement of Scx+/Sox9+ cells in the postnatal formation of fibrocartilaginous entheses and in the healing process after injury, using ScxGFP transgenic mice. We demonstrate that Scx+/Sox9+ cells are localized in layers at the insertion site during the postnatal formation of fibrocartilaginous entheses of supraspinatus tendon until postnatal 3 weeks. Further, these cells were rarely seen at postnatal 6 weeks, when mature fibrocartilaginous entheses were formed. Furthermore, we investigated the involvement of Scx+/Sox9+ cells in the healing process after supraspinatus tendon enthesis injury, comparing the responses of 20- and 3-week-old mice. In the healing process of 20-week-old mice with disorganized fibrovascular tissue in response to injury, a small number of Scx+/Sox9+ cells transiently appeared from 1 week after injury, but they were rarely seen at 4 weeks after injury. Meanwhile, in 3-week-old mice, a thin layer of fibrocartilaginous tissue with calcification was formed at healing enthesis at 4 weeks after injury. From 1 to 2 weeks after injury, more Scx+/Sox9+ cells, widely distributed at the injured site, were seen compared with the 20-week-old mice. At 4 weeks after injury, these cells were located near the surface of the recreated fibrocartilaginous layer. This spatiotemporal localization pattern of Scx+/Sox9+ cells at the injured enthesis in our 3-week-old mouse model was similar to that in postnatal fibrocartilaginous enthesis formation. These findings indicate that Scx+/Sox9+ cells may have a role as entheseal progenitor-like cells during postnatal maturation of fibrocartilaginous entheses and healing after injury in a manner similar to that seen in embryonic development.

Classifying and diagnosing systemic lupus erythematosus in the 21st century.

The EULAR/ACR 2019 classification criteria for SLE constitute a current and optimized clinical approach to SLE classification. Classification is still not based on molecular approaches and the results from large studies using polyomics may be interpreted as demonstrating the relevance of the genetic and environmental background rather than splitting SLE into several entities. In fact, an association study within the EULAR/ACR classification criteria project found associations between manifestations only within organ domains. This independency of various organ manifestations argues for SLE as one disease entity. The current review article will therefore concentrate on the clinical and immunological manifestations of SLE and on what we have already learned in this century. Moreover, the structure and essential rules of the EULAR/ACR 2019 classification criteria will be discussed. While classification and diagnosis are distinct concepts, which have to remain clearly separated, information derived from the process towards the classification criteria is also useful for diagnostic purposes. Therefore this article also tries to delineate what classification can teach us for diagnosis, covering a wide variety of SLE manifestations.

Hypergravity as a gravitational therapy mitigates the effects of knee osteoarthritis on the musculoskeletal system in a murine model.

Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeletal system are limited. Our goal was to analyze musculoskeletal changes in OA mice and test the efficacy of 8-week exposure to hypergravity, as a replacement of physical activity. 16-week-old male (C57BL/6J) mice allocated to sham control and OA groups not centrifuged (Ctrl 1g and OA 1g, respectively) or centrifuged at 2g acceleration (Ctrl 2g and OA 2g). OA 1g displayed decreased trabecular bone in the proximal tibia metaphysis and increased osteoclastic activity and local TNFα gene expression, all entirely prevented by 2g gravitational therapy. However, while cortical bone of tibia midshaft was preserved in OA 1g (vs. ctrl), it is thinner in OA 2g (vs. OA 1g). In the hind limb, OA at 1g increased fibers with lipid droplets by 48% in the tibialis anterior, a fact fully prevented by 2g. In Ctrl, 2g increased soleus, tibialis anterior and gastrocnemius masses. In the soleus of both Ctrl and OA, 2g induced larger fibers and a switch from type-II to type-I fiber. Catabolic (myostatin and its receptor activin RIIb and visfatine) and anabolic (FNDC5) genes dramatically increased in Ctrl 2g and OA 2g (p<0.01 vs 1g). Nevertheless, the overexpression of FNDC5 (and follistatine) was smaller in OA 2g than in Ctrl 2g. Thus, hypergravity in OA mice produced positive effects for trabecular bone and muscle typology, similar to resistance exercises, but negative effects for cortical bone.

Epidemiology and risk factors for avascular necrosis in childhood systemic lupus erythematosus in a Taiwanese population.

Childhood-onset systemic lupus erythematosus (SLE) is associated with greater disease activity, more aggressive course, and high rates of organ damage. The prolonged use of corticosteroids in childhood SLE contributes to increased morbidity, including avascular necrosis (AVN). We conducted this retrospective study using claims data from the Taiwan National Health Insurance Research Database, enrolling 1,472 children with newly-diagnosed SLE between 2005 and 2013. The mean age at the diagnosis of SLE was 15.5 ± 3.3 years, and the female to male ratio was 6.2:1. Thirty-nine patients (2.6%) developed symptomatic AVN during a mean follow-up of 4.6 ± 2.5 years. In multivariate analysis, the risk of AVN was higher in the patients with a daily prednisolone dose between 7.5 mg and 30 mg (HR 7.435, 95% CI 2.882-19.178, p < 0.001) and over 30 mg (HR 9.366, 95% CI 2.225-39.418, p = 0.002) than in those with a dose ≤ 7.5 mg/day. In addition, AVN was inversely correlated with the use of hydroxychloroquine > 627 days (HR 0.335, 95% CI 0.162-0.694, p = 0.003). In conclusion, high daily doses of prednisolone were associated with a significant risk of AVN, whereas the use of hydroxychloroquine > 627 days conferred an advantage. We suggest that the judicious use of corticosteroids combined with hydroxychloroquine might be a promising preventive strategy for AVN.

Comparison of three-dimensional soft-tissue evaluations between skeletal and pseudo-class III malocclusions.

The aim of our study was to compare soft tissue measurements with 3D imaging methods in individuals with untreated skeletal and pseudo-Class III malocclusions. The study sample consisted of 75 patients (38 males, 37 females, mean age 12.41 ± 2.35 years) with pseudo- and true skeletal Class III malocclusions and skeletal Class I malocclusions. Soft tissue evaluations of all patients were performed using 3D stereophotogrammetric facial images. In our study, 26 landmarks, 17 linear measurements, 13 angular measurements, and 5 volume measurements were made using the 3dMD Vultus software. The significance was determined to be p < 0.05 in ANOVA, Tukey tests. No significant differences were found among the groups in terms of demographic data (p > 0.05). The skeletal Class I control group had a significantly more extended upper lip and vermillion length as compared to the Class III groups. The soft tissue convexity angle and upper nasal angle were found to be wider in the Class III malocclusion group compared to those in the Class I control group. While the pseudo-Class III group had a significantly lower midface volume, chin volume was significantly higher in the skeletal class group. Upper lip volume was significantly higher in the Class I group. Using 3dMD for guiding clinicians in the differential soft and hard tissue diagnosis of pseudo-Class III malocclusions, differences were revealed in Class I patients in the middle part of the face. In the differential diagnosis of true Class III malocclusions, chin volume was found to be different from that of Class I patients.

Report of isolated epidural extra-nodal Rosai-Dorfman disease of cervicothoracic spine.

INTRODUCTION: Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a nonneoplastic lymphoproliferative disorder which commonly presents with painless massive cervical lymphadenopathy along with fever and weight loss. Isolated extra-nodal disease involvement, especially isolated central nervous system disease without lymph node involvement is rare. CASE PRESENTATION: A 35-year-old man presented with upper back pain and paraparesis of 2 months duration. Contrast-MRI revealed an enhancing epidural mass lesion from C6-T7 suggestive of a primary epidural spinal-cord tumor. The lesion was resected and posterolateral fusion C6-T8 was performed. Histopathological examination revealed an isolated extra-nodal case of RDD. He was started on chemotherapy after the healing of surgical site in 2 weeks post operatively. Complete resolution of neurological deficits with significant improvement in gait was seen at the last follow-up 2 years after surgery. Repeat MRI revealed complete resolution of the disease. DISCUSSION: RDD with spinal involvement is rare and it is often a challenge to arrive at the correct diagnosis. Histopathological characteristics and immunohistochemical findings are necessary for diagnosis. Resection of the lesion takes compression off the cord and therefore, is the primary line of management of this disease. Our case presentation serves as a reference when diagnosing and managing a patient of RDD.

The utility of fine-needle aspiration: how FNA has affected our musculoskeletal oncology practice.

Fine-needle aspiration (FNA) has been a widely accepted practice in the diagnosis of head and neck, thyroid, lung, pancreas, and many other visceral sites. This has not been the case with the diagnosis of primary bone and soft tissue lesions. FNA has been an important part of our orthopaedic oncology practice for 18 years. Our ability to efficiently and effectively care for patients dramatically improved when FNA became an option for obtaining a tissue diagnosis. We discuss the advantages and disadvantages of a pathologist-driven FNA service in orthopaedic oncology.