The Development of a Universally Accepted Sacral Fracture Classification: A Survey of AOSpine and AOTrauma Members.

Study Design Survey study. Objective To determine the global perspective on controversial aspects of sacral fracture classifications. Methods While developing the AOSpine Sacral Injury Classification System, a survey was sent to all members of AOSpine and AOTrauma. The survey asked four yes-or-no questions to help determine the best way to handle controversial aspects of sacral fractures in future classifications. Chi-square tests were initially used to compare surgeons\u27 answers to the four key questions of the survey, and then the data was modeled through multivariable logistic regression analysis. Results A total of 474 surgeons answered all questions in the survey. Overall 86.9% of respondents felt that the proposed hierarchical nature of injuries was appropriate, and 77.8% of respondents agreed that that the risk of neurologic injury is highest in a vertical fracture through the foramen. Almost 80% of respondents felt that the separation of injuries based on the integrity of L5-S1 facet was appropriate, and 83.8% of surgeons agreed that a nondisplaced sacral U fracture is a clinically relevant entity. Conclusion This study determines the global perspective on controversial areas in the injury patterns of sacral fractures and demonstrates that the development of a comprehensive and universally accepted sacral classification is possible

Sacral Fractures and Associated Injuries.

STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to describe the injuries associated with sacral fractures and to analyze their impact on patient outcome. METHODS: A comprehensive narrative review of the literature was performed to identify the injuries associated with sacral fractures. RESULTS: Sacral fractures are uncommon injuries that result from high-energy trauma, and that, due to their rarity, are frequently underdiagnosed and mistreated. Only 5% of sacral fractures occur in isolation. Injuries most often associated with sacral fractures include neurologic injuries (present in up to 50% of sacral fractures), pelvic ring disruptions, hip and lumbar spine fractures, active pelvic/ abdominal bleeding and the presence of an open fracture or significant soft tissue injury. Diagnosis of pelvic ring fractures and fractures extending to the lumbar spine are key factors for the appropriate management of sacral fractures. Importantly, associated systemic (cranial, thoracic, and abdominopelvic) or musculoskeletal injuries should be promptly assessed and addressed. These associated injuries often dictate the management and eventual outcome of sacral fractures and, therefore, any treatment algorithm should take them into consideration. CONCLUSIONS: Sacral fractures are complex in nature and often associated with other often-missed injuries. This review summarizes the most relevant associated injuries in sacral fractures and discusses on their appropriate management

Eradication of Metastatic Renal Cell Carcinoma after Adenovirus-Encoded TNF-Related Apoptosis-Inducing Ligand (TRAIL)/CpG Immunotherapy

Despite evidence that antitumor immunity can be protective against renal cell carcinoma (RCC), few patients respond objectively to immunotherapy and the disease is fatal once metastases develop. We asked to what extent combinatorial immunotherapy with Adenovirus-encoded murine TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus CpG oligonucleotide, given at the primary tumor site, would prove efficacious against metastatic murine RCC. To quantitate primary renal and metastatic tumor growth in mice, we developed a luciferase-expressing Renca cell line, and monitored tumor burdens via bioluminescent imaging. Orthotopic tumor challenge gave rise to aggressive primary tumors and lung metastases that were detectable by day 7. Intra-renal administration of Ad5mTRAIL+CpG on day 7 led to an influx of effector phenotype CD4 and CD8 T cells into the kidney by day 12 and regression of established primary renal tumors. Intra-renal immunotherapy also led to systemic immune responses characterized by splenomegaly, elevated serum IgG levels, increased CD4 and CD8 T cell infiltration into the lungs, and elimination of metastatic lung tumors. Tumor regression was primarily dependent upon CD8 T cells and resulted in prolonged survival of treated mice. Thus, local administration of Ad5mTRAIL+CpG at the primary tumor site can initiate CD8-dependent systemic immunity that is sufficient to cause regression of metastatic lung tumors. A similar approach may prove beneficial for patients with metastatic RCC

Ecology and genomics of an important crop wild relative as a prelude to agricultural innovation

Domesticated species are impacted in unintended ways during domestication and breeding. Changes in the nature and intensity of selection impart genetic drift, reduce diversity, and increase the frequency of deleterious alleles. Such outcomes constrain our ability to expand the cultivation of crops into environments that differ from those under which domestication occurred. We address this need in chickpea, an important pulse legume, by harnessing the diversity of wild crop relatives. We document an extreme domestication-related genetic bottleneck and decipher the genetic history of wild populations. We provide evidence of ancestral adaptations for seed coat color crypsis, estimate the impact of environment on genetic structure and trait values, and demonstrate variation between wild and cultivated accessions for agronomic properties. A resource of genotyped, association mapping progeny functionally links the wild and cultivated gene pools and is an essential resource chickpea for improvement, while our methods inform collection of other wild crop progenitor species

CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression.

Pulmonary delivery of plasmid DNA (pDNA)/cationic liposome complexes is associated with an acute unmethylated CG dinucleotide (CpG)-mediated inflammatory response and brief duration of transgene expression. We demonstrate that retention of even a single CpG in pDNA is sufficient to elicit an inflammatory response, whereas CpG-free pDNA vectors do not. Using a CpG-free pDNA expression vector, we achieved sustained (≥56 d) in vivo transgene expression in the absence of lung inflammation

Pressure and pain In Systemic sclerosis/Scleroderma - an evaluation of a simple intervention (PISCES): randomised controlled trial protocol

Background: foot problems associated with Systemic Sclerosis (SSc)/Scleroderma have been reported to be both common and disabling. There are only limited data describing specifically, the mechanical changes occurring in the foot in SSc. A pilot project conducted in preparation for this trial confirmed the previous reports of foot related impairment and reduced foot function in people with SSc and demonstrated a link to mechanical etiologies. To-date there have been no formal studies of interventions directed at the foot problems experienced by people with Systemic Sclerosis. The primary aim of this trial is to evaluate whether foot pain and foot-related health status in people with Systemic Sclerosis can be improved through the provision of a simple pressure-relieving insole. Methods: the proposed trial is a pragmatic, multicenter, randomised controlled clinical trial following a completed pilot study. In four participating centres, 140 consenting patients with SSc and plantar foot pain will be randomised to receive either a commercially available pressure relieving and thermally insulating insole, or a sham insole with no cushioning or thermal properties. The primary end point is a reduction in pain measured using the Foot Function Index Pain subscale, 12 weeks after the start of intervention. Participants will complete the primary outcome measure (Foot Function Index pain sub-scale) prior to randomisation and at 12 weeks post randomisation. Secondary outcomes include participant reported pain and disability as derived from the Manchester Foot Pain and Disability Questionnaire and plantar pressures with and without the insoles in situ. Discussion: this trial protocol proposes a rigorous and potentially significant evaluation of a simple and readily provided therapeutic approach which, if effective, could be of a great benefit for this group of patients

Systemic sclerosis in adults. Part II: Management and therapeutics

The management of systemic sclerosis (SSc) is complex, evolving and requires a multidisciplinary approach. At diagnosis and throughout the disease course, clinical assessment and monitoring of skin involvement via the modified Rodnan Skin Score, patient reported outcomes and new global composite scores (such as the CRISS, which also considers lung function), is vital. Immunomodulation is the mainstay of skin fibrosis treatment, with mycophenolate mofetil considered first line. Meanwhile vasculopathy related manifestations (Raynaud's phenomenon, digital ulcers) and calcinosis, require general measures combined with specific pharmacological (calcium channel blockers, phosphodiesterase type 5 inhibitors and prostanoids) and non-pharmacological (digital sympathectomy and botulinum toxin injections), and often multifaceted, management approaches. Patients should be specifically screened for systemic manifestations at the time of diagnosis, and regularly thereafter and treated accordingly. Numerous targeted therapeutic options for SSc, including skin fibrosis, are emerging and include B-cell depletion, anti-IL-6, JAK and TGF-β inhibition. The second article in this continuing medical education (CME) series discusses these key aspects of SSc assessment and treatment, with particular focus on skin involvement. It is vital that dermatologists play a key role in the multidisciplinary approach to SSc management

Systemic sclerosis in adults. Part I: Clinical features and pathogenesis

Systemic sclerosis (SSc; also referred to as systemic scleroderma or scleroderma), is a rare, complex immune-mediated connective tissue disease (CTD) characterized by progressive skin fibrosis and other clinically heterogenous features. The etiopathogenesis of SSc involves vasculopathy and immune system dysregulation occurring on a permissive genetic and epigenetic background, ultimately leading to fibrosis. Recent developments in our understanding of disease specific autoantibodies and bioinformatic analyses has led to reconsideration of the purely clinical classification of diffuse and limited cutaneous SSc subgroups. Autoantibody profiles are predictive of skin and internal organ involvement and disease course. Early diagnosis of SSc, with commencement of disease modifying treatment, has the potential to improve patient outcomes. Many early presenting clinical manifestations, signs of disease progression and activity in SSc are cutaneous, meaning dermatologists can and should play a key role in the diagnosis and management of this significant condition. The first article in this continuing medical education (CME) series discusses the epidemiology, clinical characteristics and pathogenesis of SSc in adults, with an emphasis on skin manifestations, the important role of dermatologists in recognising these, and their correlation with systemic features and disease course