Patient Education Level and Utilization of Internet Resources by Patients in Orthopedic Hip and Knee Consultations

Introduction: Internet has become an increasingly popular source of reference for patients to learn about their medical problems. It is easily accessible, and a large number of uncensored information is available online written from various sources and perspectives. However, the role of internet and its impact on patient’s care and understanding of the disease remains unclear. The purpose of this study is to evaluate the role and effect of internet use for patients seeking consultation for hip and knee arthritis. More specifically, the relationship between patient’s education level, internet use, motives for doing background readings, perception of internet information, and reactions to the available information will be studied. Method: Patients seeking orthopaedic consultation for knee or hip arthritis at the Toronto Western Hospital were identified and invited to fill out a questionnaire on their first visit. The questionnaire was designed to assess the patients’ pre-consultation reading habits, their use of internet, and their reaction to what they have read on the internet. The questionnaire also included questions about the respondent’s background.Results: In comparing patients holding college/university degree (CU) with patients having no college/university education (NoCU), the CU group were associated with increased internet use (CU vs. NoCU: 71.0% vs. 48.3%;p 0.01) and background reading (CU vs. NoCU: 82.2% vs. 17.8%;p 0.001) prior to consultation;fewer incidence of anxiety following internet use (CU vs. NoCU: 29.9% vs. 53.6%;p 0.05);and higher rates of decisions influenced by internet use (CU vs. NoCU: 20.8% vs. 3.6%, p 0.05). Internet users demonstrated a higher confidence in gathering and understanding medical information (Internet users vs. non-internet users: 6.59 ± 2.05 vs. 5.03 ± 2.78;p 0.001) and rated the accuracy of information on internet at 7.18 ± 2.01 (max = 10). Conclusion: Internet use can influence patient’s treatment decision, anxiety level, and understanding of their disease. Caregivers must recognize the growing trend of internet use and should counsel and educate their patients appropriately based on what they have read to help them accurately appreciate the nature of their disease.

Clinical application of concentrated bone marrow aspirate in orthopaedics:A systematic review

AIM To examine the evidence behind the use of concentrated bone marrow aspirate(c BMA) in cartilage, bone, and tendon repair; establish proof of concept for the use of cB MA in these biologic environments; and provide the level and quality of evidence substantiating the use of cB MA in the clinical setting.METHODS We conducted a systematic review according to PRISMA guidelines. EMBASE, MEDLINE, and Web of Knowledge databases were screened for the use of cB MA in the repair of cartilage, bone, and tendon repair. We extracted data on tissue type, cB MA preparation, cB MA concentration, study methods, outcomes, and level of evidence and reported the results in tables and text.RESULTS A total of 36 studies met inclusion/exclusion criteria and were included in this review. Thirty-one of 36(86%) studies reported the method of centrifugation and preparation of cB MA with 15(42%) studies reporting either a cell concentration or an increase from baseline. Variation of c BMA application was seen amongst the studies evaluated. Twenty-one of 36(58%) were level of evidence Ⅳ, 12/36(33%) were level of evidence Ⅲ, and 3/36(8%) were level of evidence Ⅱ. Studies evaluated full thickness chondral lesions(7 studies), osteochondral lesions(10 studies), osteoarthritis(5 studies), nonunion or fracture(9 studies), or tendon injuries(5 studies). Significant clinical improvement with the presence of hyaline-like values and lower incidence of fibrocartilage on T2 mapping was found in patients receiving cB MA in the treatment of cartilaginous lesions. Bone consolidation and time to bone union was improved in patients receiving cB MA. Enhanced healingrates, improved quality of the repair surface on ultrasound and magnetic resonance imaging, and a decreased risk of re-rupture was demonstrated in patients receiving cB MA as an adjunctive treatment in tendon repair. CONCLUSION The current literature demonstrates the potential benefits of utilizing c BMA for the repair of cartilaginous lesions, bony defects, and tendon injuries in the clinical setting. This study also demonstrates discrepancies between the literature with regards to various methods of centrifugation, variable cell count concentrations, and lack of standardized outcome measures. Future studies should attempt to examine the integral factors necessary for tissue regeneration and renewal including stem cells, growth factors and a biologic scaffold.

The Role of Microstructure of Highly Purified Beta-Tricalcium Phosphate for Osteoinduction in Canine Dorsal Muscles

Porous β-tricalcium phosphate (TCP) displays osteoinductivity in certain animals in the absence of osteoinductive agents. We evaluated whether the microstructure may be an important determinant of osteoinduction, and also investigated how bone formation was promoted using β-TCP combined with bone marrow aspirates. We prepared two types of β-TCP, namely, β-TCP A, which possessed interconnected macropores and micropores, and β-TCP B, which possessed macropores but had less detectable micropores. These were implanted with or without marrow in canine muscles. Bone formation and the resorption of each β-TCP implant were evaluated histologically. Newly formed bone began to appear at day 42 in the implants of β-TCP A alone, but the implants of β-TCP B alone did not show any bone formation by day 42. Meanwhile, bone formation was already evident on day 14 by loading with bone marrow aspirates with or without micropores. By immunohistochemistry, the number of cathepsin K-positive cells (osteoclasts) increased as time passed in the implants of β-TCP A alone, while the number of the osteoclasts did not change obviously in the implants of β-TCP B alone from day 14 to 56. Reticular fibrils were evident within the β-TCP A, and were barely observed in the β-TCP B in the silver impregnation. The present result would bring about the possible role to enhance the importance of the surface microstructure for the better osteoinductivity. Our findings suggest that the combination of porous β-TCP and bone marrow facilitates bone formation.

Integrative analysis of layers of data in hepatocellular carcinoma reveals pathway dependencies

BACKGROUND The broader use of high-throughput technologies has led to improved molecular characterization of hepatocellular carcinoma(HCC).AIM To comprehensively analyze and characterize all publicly available genomic,gene expression,methylation,miRNA and proteomic data in HCC,covering 85 studies and 3355 patient sample profiles,to identify the key dysregulated genes and pathways they affect.METHODS We collected and curated all well-annotated and publicly available highthroughput datasets from PubMed and Gene Expression Omnibus derived from human HCC tissue.Comprehensive pathway enrichment analysis was performed using pathDIP for each data type(genomic,gene expression,methylation,miRNA and proteomic),and the overlap of pathways was assessed to elucidate pathway dependencies in HCC.RESULTS We identified a total of 8733 abstracts retrieved by the search on PubMed on HCC for the different layers of data on human HCC samples,published until December 2016.The common key dysregulated pathways in HCC tissue across different layers of data included epidermal growth factor(EGFR)andβ1-integrin pathways.Genes along these pathways were significantly and consistently dysregulated across the different types of high-throughput data and had prognostic value with respect to overall survival.Using CTD database,estradiol would best modulate and revert these genes appropriately.CONCLUSION By analyzing and integrating all available high-throughput genomic,transcriptomic,miRNA,methylation and proteomic data from human HCC tissue,we identified EGFR,β1-integrin and axon guidance as pathway dependencies in HCC.These are master regulators of key pathways in HCC,such as the mTOR,Ras/Raf/MAPK and p53 pathways.The genes implicated in these pathways had prognostic value in HCC,with Netrin and Slit3 being novel proteins of prognostic importance to HCC.Based on this integrative analysis,EGFR,andβ1-integrin are master regulators that could serve as potential therapeutic targets in HCC.

Phylogenetic Analysis and Taste Cell Expression of Calpain 9 in Catfish (<i>Ictalurus punctatus</i>)

The calpains, calcium-activated neutral proteases, play important roles in calcium-regulated intra-cellular signal transduction cascades. Here we report the isolation and initial characterization of a cDNA encoding a calpain 9, digestive tract specific calpain, from catfish taste epithelium. This calpain 9 (Ip-CAPN9a) shares 61% identity with human calpain 9. Phylogenetic analysis provides evidence that catfish calpain 9 and the related enzymes from Oncorhynchus mykiss, Danio rerio, Xenopus laevis, Mus musculus, Rattus norvegicus and Homo sapiens make up a distinct clade within the tissue-specific calpain family. Northern blot analysis reveals that Ip-CAPN9a is predominantly expressed in barbell and digestive tract, but not expressed in brain. An antibody against the N-terminal segment of Ip-CAPN9a recognizes cells within the taste buds in catfish barbells.

Bradycardia and hypotension during pediatric scoliosis surgery-hypovolemia or spinal shock?

We present the case of a 13-year-old boy undergoing scoliosis repair utilizing skull-femoral traction who developed sudden, sustained bradycardia and hypotension during scoliosis repair, associated with loss of somatosensory evoked potentials and motor evoked potentials to all four limbs. A diagnosis of spinal shock and hypovolemia was made after ruling out primary cardiac causes, sepsis, anaphylaxis and intra-spinal pedicle screw placement. Acute complications of surgical scoliosis repair are reviewed along with anatomy of the sympathetic nervous system. In this case spinal shock may have been due to hypovolemia as well as spinal cord manipulation during T12 vertebral column resection that was needed to effect scoliosis correction. Treatment included volume expansion and inotropic support. Anesthesiologists caring for these patients should be mindful of the possibility of spinal shock during correction of severe scoliosis, particularly when vertebral column resection is undertaken.

Interobserver and intraobserver agreement for Letournel acetabular fracture classification system using 3-dimensional printed solid models

BACKGROUND Acetabular fractures pose diagnostic and surgical challenges.They are classified using the Judet-Letournel system,which is based solely on X-ray.However,computed tomography(CT)imaging is now more widely utilized in diagnosing these injuries.The emergence of 3-dimensional(3-D)printing technology in varying orthopedic fields has provided surgeons a solid model that improves their spatial understanding of complex fractures and ability to plan preoperatively.AIM To evaluate the reliability of the Judet-Letournel classification system of acetabular fractures,when using either CT imaging or 3-D printed models.METHODS Seven patients with acetabular fractures underwent pelvic CT imaging,which was then used to create solid,3-D printed models.Eighteen orthopaedic trauma surgeons responded to questionnaires regarding fracture classification and preferred surgical approach.The same questionnaire was completed using only CT imaging,and two weeks later,using only 3-D printed models.The inter-and intra-observer agreement rates were then analyzed.RESULTS Inter-observer agreement rates based on CT imaging or 3-D printed models were moderate for fracture classification:κ=0.44,κ=0.55,respectively(P<0.001)and fair for preferred surgical approach:κ=0.34,κ=0.29,respectively(P<0.005).Intra-observer agreement rates for fracture classification and preferred surgical approach comparing CT imaging or 3-D printed models were moderate:κ=0.48,κ=0.41,respectively.No significant difference in intra-observer agreement was detected when comparing orthopedic pelvic specialists to general orthopedic traumatologists.CONCLUSION The Judet-Letournel classification demonstrated only moderate rates of agreement.The use of 3-D printed models increased the inter-observer agreement rates with respect to fracture classification,but decreased it with respect to the preferred surgical approach.This study highlights the role of 3-D printed models in acetabular fractures by improving spatial understanding of these complex injuries,thus providing more reliable fracture diagnoses and alternative viewpoints for pre-operative planning.

Osteoinduction and Osteoconduction with Porous Beta-Tricalcium Phosphate Implanted after Fibular Resection in Humans

Osteoinductive properties of β-TCP remain unknown in humans. It is important to improve the bone grafts which have been the standard treatment for bone defect due to their biocompatibility and bone-healing properties. The purpose of this study was to radiologically clarify the bone forming property of β-TCP by evaluating the replacement of β-TCP by newly formed bone in the defect after fibular resection and to examine the histological features of a β-TCP specimen three months after grafting. Radiographs of 17 patients who underwent β-TCP grafting were evaluated. Osteoinductive and osteoconductive properties were assessed by examining bone formation from the remnant fibula, periosteum, and β-TCP alone. In one case, β-TCP was removed later because of postoperative complications and was evaluated histologically. Twenty two of 34 sites between the remnant fibula and β-TCP had achieved good bone regeneration. Five of 14 sites between the periosteum and β-TCP had achieved good bone regeneration. We found immature but evident bone formation in three cases with no osseous and periosteal sites. Histological analysis revealed bone formation on the outer macropore surface of β-TCP. Some blood vessels formed in the macropores expressed CD31 and CD34, while a few lymphatic vessels expressed CD34 and podoplanin. Thus, the osteoinductive ability of β-TCP alone was demonstrated in humans radiographically for the first time. The histological morphology of β-TCP was demonstrated at an early stage after grafting in humans.

Rheumatoid Arthritis with High Serum KL-6 Complicating Malignant Tumor: Two Case Reports

Interstitial pneumonia develops not only as a rheumatoid arthritis (RA) manifestation, but also due to the side effects of drugs for its treatment, leading to the necessity of regular examinations. Krebs von den Lungen-6 (KL-6) is often used to check the activity of interstitial pneumonia in RA patients. However, this marker is also produced by some malignant tumors, and a high level of serum KL-6 has been reported in cancer patients. We describe herein 2 cases of RA with the complication of a malignant tumor not involving the lung, although there is no lesion in the lung regardless of the high level of serum KL-6.

In vitro and in vivo study on fine-grained Mg-Zn-RE-Zr alloy as a biodegradeable orthopedic implant produced by friction stir processing

Magnesium alloys containing biocompatible components show tremendous promise for applications as temporary biomedical devices. However, to ensure their safe use as biodegradeable implants, it is essential to control their corrosion rates. In concentrated Mg alloys, a microgalvanic coupling between the α-Mg matrix and secondary precipitates exists which results in increased corrosion rate. To address this challenge, we engineered the microstructure of a biodegradable Mg-Zn-RE-Zr alloy by friction stir processing (FSP), improving its corrosion resistance and mechanical properties simultaneously. The FS processed alloy with refined grains and broken and uniformly distributed secondary precipitates showed a relatively uniform corrosion morphology accompanied with the formation of a stable passive layer on the alloy surface. In vivo corrosion evaluation of the processed alloy in a small animal model showed that the material was well-tolerated with no signs of inflammation or harmful by-products. Remarkably, the processed alloy supported bone until it healed till eight weeks with a low in vivo corrosion rate of 0.7 mm/year. Moreover, we analyzed blood and histology of the critical organs such as liver and kidney, which showed normal functionality and consistent ion and enzyme levels, throughout the 12- week study period. These results demonstrate that the processed Mg-Zn-RE-Zr alloy offers promising potential for osseointegration in bone tissue healing while also exhibiting controlled biodegradability due to its engineered microstructure. The results from the present study will have profound benefit for bone fracture management, particularly in pediatric and elderly patients.

Sox12 enhances Fbw7-mediated ubiquitination and degradation of GATA3 in Th2 cells

Allergic asthma that is caused by inhalation of house dust mites(HDMs)is mainly mediated by Th2 cells.Recently,the roles of Sox(SRY-related high-mobility-group(HMG)-box)family members in various immune responses have been investigated.However,the roles of Sox12,a member of the SoxC group,in Th2 cell differentiation and allergic airway inflammation,remain unknown.We showed that Sox12 mRNA was significantly increased during Th2 cell differentiation.In vivo,HDM-induced eosinophil infiltration into the lung and Th2 cell differentiation were exacerbated in Sox12−/−mice compared with those in control Sox12+/−mice.In vitro,Sox12−/−CD4^(+)T cells that were cultured under Th2 conditions had increased production of Th2 cytokines and GATA3 protein compared with those of control Sox12+/−CD4^(+)T cells.Importantly,forced expression of Sox12 decreased the protein levels of GATA3 in CD4^(+)T cells under Th2 conditions without affecting mRNA expression.Furthermore,Sox12 induced degradation of GATA3 through the proteasome pathway in CD4^(+)T cells.Consistently,Sox12 enhanced ubiquitination of GATA3,which was mediated by the E3 ligase Fbw7.Finally,we found that Fbw7 knockdown partly abrogated Sox12-mediated GATA3 suppression in CD4^(+)T cells.Taken together,these results suggest that Sox12 suppresses Th2 cell differentiation by accelerating Fbw7-mediated GATA3 degradation,and attenuates HDM-induced allergic inflammation.

Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success

Osteoarthritis(OA)is a degenerative multifactorial disease with concomitant structural,inflammatory,and metabolic changes that fluctuate in a temporal and patient-specific manner.This complexity has contributed to refractory responses to various treatments.MsCs have shown promise as multimodal therapeutics in mitigating OA symptoms and disease progression.Here,we evaluated 15 randomized controlled clinical trials(RCTs)and 11 nonrandomized RCTs using culture-expanded MSCs in the treatment of knee OA,and we found net positive effects of MSCs on mitigating pain and symptoms(improving function in 12/15 RCTs relative to baseline and in 11/15 RCTs relative to control groups at study endpoints)and on cartilage protection and/or repair(18/21 clinical studies).We examined MsC dose,tissue of origin,and autologous vs.allogeneic origins as well as patient clinical phenotype,endotype,age,sex and level of OA severity as key parameters in parsing MSC clinical effectiveness.The relatively small sample size of 610 patients limited the drawing of definitive conclusions.Nonetheless,we noted trends toward moderate to higher doses of MsCs in select OA patient clinical phenotypes mitigating pain and leading to structural improvements or cartilage preservation.Evidence from preclinical studies is supportive of MsC anti-inflammatory and immunomodulatory effects,but additional investigations on immunomodulatory,chondroprotective and other clinical mechanisms of action are needed.We hypothesize that MsC basal immunomodulatory"fitness"correlates with OA treatment efficacy,but this hypothesis needs to be validated in future studies.We conclude with a roadmap articulating the need to match an OA patient subset defined by molecular endotype and clinical phenotype with basally immunomodulatory"ft"or engineered-to-be-fit-for-OA MsCs in well-designed,data-intensive clinical trials to advance the field.