Particular exosomal micro-RNAs and gastrointestinal (GI) cancer cells' roles: Current theories.

A diverse range of gastrointestinal tract disorders are called gastrointestinal (GI) malignancies. The transformation of normal cells into precursor cells, precursor cells into premalignant cells, and premalignant cells into cancerous cells is facilitated by the interaction of many modifiable and non-modifiable risk factors. Developing relevant therapy alternatives based on a better knowledge of the illness's aetiology is essential to enhance patient outcomes. The exosome is crucial in regulating intercellular interaction because it may send molecular signals to nearby or distant cells. Exosomes produced from cancer can introduce a variety of chemicals and vast concentrations of microRNA (miRNA) into the tumour microenvironment. These miRNAs significantly impact immunological evasion, metastasis, apoptosis resistance, and cell growth. Exosomal miRNAs, or exosomal miRNAs, are essential for controlling cancer resistance to apoptosis, according to mounting data. Exosomal miRNAs function as an interaction hub between cancerous cells and the milieu around them, regulating gene expression and various signalling pathways. Our research examines the regulatory function of exosomal miRNAs in mediating interactions between cancer cells and the stromal and immunological cells that make up the surrounding milieu.

Circulating tumor DNA (ctDNA) application in investigation of cancer: Bench to bedside.

Now, genomics forms the core of the precision medicine concept. Comprehensive investigations of tumor genomes have made it possible to characterize tumors at the molecular level and, specifically, to identify the fundamental processes that cause condition. A variety of kinds of tumors have seen better outcomes for patients as a result of the development of novel medicines to tackle these genetic-driving processes. Since therapy may exert selective pressure on cancers, non-invasive methods such as liquid biopsies can provide the opportunity for rich reservoirs of crucial and real-time genetic data. Liquid biopsies depend on the identification of circulating cells from tumors, circulating tumor DNA (ctDNA), RNA, proteins, lipids, and metabolites found in patient biofluids, as well as cell-free DNA (cfDNA), which exists in those with cancer. Although it is theoretically possible to examine biological fluids other than plasma, such as pleural fluid, urine, saliva, stool, cerebrospinal fluid, and ascites, we will limit our discussion to blood and solely cfDNA here for the sake of conciseness. Yet, the pace of wider clinical acceptance has been gradual, partly due to the increased difficulty of choosing the best analysis for the given clinical issue, interpreting the findings, and delaying proof of value from clinical trials. Our goal in this review is to discuss the current clinical value of ctDNA in cancers and how clinical oncology systems might incorporate procedures for ctDNA testing.

Hemp Seed Oil Inhibits the Adipogenicity of the Differentiation-Induced Human Mesenchymal Stem Cells through Suppressing the Cannabinoid Type 1 (CB1).

Central and peripheral mechanisms of the endocannabinoid system (ECS) favor energy intake and storage. The ECS, especially cannabidiol (CBD) receptors, controls adipocyte differentiation (hyperplasia) and lipid accumulation (hypertrophy) in adipose tissue. In white adipose tissue, cannabidiol receptor 1 (CB1) stimulation increases lipogenesis and inhibits lipolysis; in brown adipose tissue, it decreases mitochondrial thermogenesis and biogenesis. This study compared the availability of phytocannabinoids [CBD and Δ9-tetrahydrocannabinol (THC)] and polyunsaturated fatty acids [omega 3 (ω3) and omega 6 (ω6)] in different hemp seed oils (HSO). The study also examined the effect of HSO on adipocyte lipid accumulation by suppressing cannabinoid receptors in adipogenesis-stimulated human mesenchymal stem cells (hMSCs). Most importantly, Oil-Red-O' and Nile red tests showed that HSO induced adipogenic hMSC differentiation without differentiation agents. Additionally, HSO-treated cells showed increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to controls (hMSC). HSO reduced PPARγ mRNA expression after differentiation media (DM) treatment. After treatment with HSO, DM-hMSCs had significantly lower CB1 mRNA and protein expressions than normal hMSCs. HSO treatment also decreased transient receptor potential vanilloid 1 (TRPV1), fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase (MGL) mRNAs in hMSC and DM-hMSCs. HSO treatment significantly decreased CB1, CB2, TRPV1, and G-protein-coupled receptor 55 (GPCR55) protein levels in DM-hMSC compared to hMSC in western blot analysis. In this study, HSO initiated adipogenic differentiation in hMSC without DM, but it suppressed CB1 gene and protein expression, potentially decreasing adipocyte lipid accumulation and lipogenic enzymes.

Investigating the Impact of the Number of Medication Use on Depression Among Hypertensive Patients: Results from the National Health and Nutrition Examination Survey Database.

Background and Objective: Hypertension is a prevalent chronic condition often treated with multiple medications, leading to polypharmacy, which can heighten the risk of adverse drug reactions and contribute to psychological issues like depression. This study aimed to investigate the relationship between polypharmacy and depressive symptoms in hypertensive patients using data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Materials and Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2017 and March 2020. Results: Among 2543 hypertensive participants, 12.3% met the criteria for depression. The findings revealed that patients using 11 or more medications were ten times more likely to experience depressive symptoms compared to those taking 1 to 2 medications (OR = 10.06, p < 0.001). Additionally, younger age (18 to 45 years), female gender, and lower educational attainment were significantly associated with higher rates of depressive symptoms. Specifically, females were 1.47 times more likely to experience depression compared to males (p = 0.032). Conclusions: This research highlights the substantial impact of medication burden on mental health among hypertensive patients, emphasizing the need for tailored clinical interventions for this vulnerable population.

The utility of serum glucose potassium ratio as a predictive factor for haemorrhagic transformation, stroke recurrence, and mortality among ischemic stroke patients.

Background and Objective: Glucose-Potassium Ratio (GPR) has emerged as a biomarker in several pathophysiological conditions. However, the association between GPR and long-term outcomes in stroke patients has not been investigated. Our study evaluated the applicability of baseline GPR as a predictive prognostic tool for clinical outcomes in ischemic stroke patients. Methods: The multicenter retrospective cohort study included acute-subacute adult ischemic stroke patients who had their baseline serum GPR levels measured. Eligible patients were categorized into two sub-cohorts based on the baseline GPR levels (<1.67 vs. ≥ 1.67). The primary outcome was the incidence of 30-day hemorrhagic transformation, while stroke recurrence, and all-cause mortality within twelve months, were considered secondary. Results: Among 4083 patients screened, 1047 were included in the current study. In comparison with GPR < 1.67 group, patients with ≥ 1.67 GPR had a significantly higher ratio of all-cause mortality within twelve months (aHR 2.07 [95 % CI 1.21-3.75] p = 0.01), and higher ratio of 30-day hemorrhagic transformation but failed to reach the statistical significance (aHR 1.60 [95 % CI 0.95-2.79], p = 0.08). Conclusion: Overall, baseline GPR serum is an independent predictor of all-cause mortality within twelve months in patients with acute and subacute ischemic stroke. Further clinical studies are necessary to validate these findings.

New Succinimide-Thiazolidinedione Hybrids as Multitarget Antidiabetic Agents: Design, Synthesis, Bioevaluation, and Molecular Modelling Studies.

Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue's resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide-thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (10a-e). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound 10d was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound 10d was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound 10d was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents.

Optimal entry point for antegrade and retrograde femoral intramedullary nails.

Surgical management of femoral shaft fractures with intramedullary nails has become the standard of care, with multiple options for entry point described, including piriformis entry, trochanter entry and retrograde femoral nails. Our present review describes the surgical anatomy of the proximal and distal femur and its relation to different entry points for intramedullary femoral nails. In addition, we reviewed relative indications for each technique, difficulties associated and possible complications.

Vedolizumab does not increase risk of clostridium difficile infection in patients with inflammatory bowel disease using vedolizumab: A retrospective cohort study.

Introduction: Several studies have shown increased incidence, recurrence, and severity of Clostridium difficile infection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies. Methods: This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI. Result: There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model. Conclusion: Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.

High contribution and impact of resistant gram negative pathogens causing surgical site infections at a multi-hospital healthcare system in Saudi Arabia, 2007-2016.

BACKGROUND: Despite being largely preventable, surgical site infections (SSIs) are still one of the most frequent healthcare-associated infections. The presence of resistant pathogens can further augment their clinical and economic impacts. The objective was to estimate the distribution and resistance in SSI pathogens in Saudi Arabia and to compare them to the US National Healthcare Safety Network (NHSN) hospitals. METHODS: Targeted SSI surveillance was prospectively conducted on several surgical procedures done between 2007 and 2016 in four hospitals of Ministry of National Guard Health Affairs. Definitions and methodology of SSI and bacterial resistance were based on NHSN. RESULTS: A total 492 pathogens causing 403 SSI events were included. The most frequent pathogens were Staphylococcus aureus (22.8%), Pseudomonas aeruginosa (20.1%), Klebsiella spp. (12.2%), and Escherichia coli (12.2%), with marked variability between surgeries. Approximately 30.3% of Staphylococcus aureus was methicillin-resistant (MRSA), 13.0% of Enterococcus spp. was vancomycin-resistant (VRE), and 5.5% of Enterobacteriaceae were carbapenem resistant (CRE). The highest multidrug-resistant (MDR) GNPs were Acinetobacter spp. (58.3%), Klebsiella spp. (20.4%) and Escherichia coli (16.3%). MRSA was significantly less frequent while cephalosporin-resistant Klebsiella spp., MDR Klebsiella spp., and MDR Escherichia coli were significantly more frequent in our hospitals compared with NHSN hospitals. CONCLUSION: GNPs in a tertiary care setting in Saudi Arabia are responsible for more than 60% of SSI with more resistant patterns than Western countries. This information may be critical to secure resources and ensure support for caregivers and healthcare leaders in implementing antimicrobial stewardship programs and evidence-based SSI preventive practices.

Machine Learning Algorithms and Fault Detection for Improved Belief Function Based Decision Fusion in Wireless Sensor Networks.

Decision fusion is used to fuse classification results and improve the classification accuracy in order to reduce the consumption of energy and bandwidth demand for data transmission. The decentralized classification fusion problem was the reason to use the belief function-based decision fusion approach in Wireless Sensor Networks (WSNs). With the consideration of improving the belief function fusion approach, we have proposed four classification techniques, namely Enhanced K-Nearest Neighbor (EKNN), Enhanced Extreme Learning Machine (EELM), Enhanced Support Vector Machine (ESVM), and Enhanced Recurrent Extreme Learning Machine (ERELM). In addition, WSNs are prone to errors and faults because of their different software, hardware failures, and their deployment in diverse fields. Because of these challenges, efficient fault detection methods must be used to detect faults in a WSN in a timely manner. We have induced four types of faults: offset fault, gain fault, stuck-at fault, and out of bounds fault, and used enhanced classification methods to solve the sensor failure issues. Experimental results show that ERELM gave the first best result for the improvement of the belief function fusion approach. The other three proposed techniques ESVM, EELM, and EKNN provided the second, third, and fourth best results, respectively. The proposed enhanced classifiers are used for fault detection and are evaluated using three performance metrics, i.e., Detection Accuracy (DA), True Positive Rate (TPR), and Error Rate (ER). Simulations show that the proposed methods outperform the existing techniques and give better results for the belief function and fault detection in WSNs.

Fault Detection in Wireless Sensor Networks through the Random Forest Classifier.

Wireless Sensor Networks (WSNs) are vulnerable to faults because of their deployment in unpredictable and hazardous environments. This makes WSN prone to failures such as software, hardware, and communication failures. Due to the sensor's limited resources and diverse deployment fields, fault detection in WSNs has become a daunting task. To solve this problem, Support Vector Machine (SVM), Convolutional Neural Network (CNN), Stochastic Gradient Descent (SGD), Multilayer Perceptron (MLP), Random Forest (RF), and Probabilistic Neural Network (PNN) classifiers are used for classification of gain, offset, spike, data loss, out of bounds, and stuck-at faults at the sensor level. Out of six faults, two of them are induced in the datasets, i.e., spike and data loss faults. The results are compared on the basis of their Detection Accuracy (DA), True Positive Rate (TPR), Matthews Correlation Coefficients (MCC), and F1-score. In this paper, a comparative analysis is performed among the classifiers mentioned previously on real-world datasets. Simulations show that the RF algorithm secures a better fault detection rate than the rest of the classifiers.

Use of the Corail stem for revision total hip arthroplasty: evaluation of clinical outcomes and cost

Background: With the growing number of total hip arthroplasty (THA) procedures performed, revision surgery is also proportionately increasing, resulting in greater health care expenditures. The purpose of this study was to assess clinical outcomes and cost when using a collared, fully hydroxyapatite-coated primary femoral stem for revision THA compared to commonly used revision femoral stems. Methods: We retrospectively identified patients who underwent revision THA with a primary stem between 2011 and 2016 and matched them on demographic variables and reason for revision to a similar cohort who underwent revision THA. We extracted operative data and information on in-hospital resource use from the patients' charts to calculate average cost per procedure. Patient-reported outcomes were recorded preoperatively and 1 year postoperatively. Results: We included 20 patients in our analysis, of whom 10 received a primary stem and 10, a typical revision stem. There were no significant between-group differences in mean Western Ontario and McMaster Universities Osteoarthritis Index score, Harris Hip Score, 12-Item Short Form Health Survey (SF-12) Mental Composite Scale score or Physical Composite Scale score at 1 year. Operative time was significantly shorter and total cost was significantly lower (mean difference ­3707.64, 95% confidence interval ­5532.85 to ­1882.43) with a primary stem than with other revision femoral stems. Conclusion: We found similar clinical outcomes and significant institutional cost savings with a primary femoral stem in revision THA. This suggests a role for a primary femoral stem such as a collared, fully hydroxyapatite-coated stem for revision THA.

Contexte: Avec le nombre croissant d'interventions pour prothèse de hanche (PTH) effectuées, la chirurgie de révision est aussi proportionnellement en hausse, ce qui entraîne des coûts supérieurs pour le système de santé. Le but de cette étude était d'évaluer les résultats cliniques et le coût associés à l'emploi d'une prothèse fémorale primaire à collerette entièrement recouverte d'hydroxyapatite pour la révision de PTH, comparativement à d'autres prothèses d'usage courant utilisées pour les révisions. Méthodes: Nous avons identifié rétrospectivement les patients ayant subi une révision de PTH avec une prothèse primaire entre 2011 et 2016 et nous les avons assortis selon les caractéristiques démographiques et le motif de la révision à une cohorte similaire soumise à une révision de PTH. Nous avons extrait les données sur l'opération et sur l'utilisation des ressources hospitalières à partir des dossiers des patients pour calculer le coût par intervention. Les résultats déclarés par les patients ont été notés avant l'intervention et 1 an après. Résultats: Nous avons inclus 20 patients dans notre analyse, dont 10 ont reçu une prothèse primaire et 10, une révision de prothèse typique. On n'a noté aucune différence significative entre les groupes pour ce qui est du score WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) moyen pour l'arthrose, du score de Harris pour la hanche, ou des sous-échelles santé mentale ou santé physique à 1 an du questionnaire SF-12 (12-Item Short Form Health Survey). L'intervention a duré significativement moins longtemps et le coût a été significativement moindre (différence moyenne ­3707,64, intervalle de confiance de 95 % ­5532,85 à ­1882,43) avec une prothèse primaire qu'avec les autres prothèses de révision. Conclusion: Nous avons observé des résultats cliniques similaires et des économies significatives pour l'établissement avec la prothèse primaire utilisée pour la révision de PTH. Cela donne à penser que la prothèse fémorale primaire, par exemple, à collerette et entièrement recouverte d'hydroxyapatite, aurait un rôle à jouer pour la révision de PTH.

Strategies of enhancing bone regenerate formation in distraction osteogenesis.

Distraction osteogenesis (DO) is a commonly used technique in multiple orthopedic sub-specialties, including trauma, oncology and pediatrics. This technique aims to produce new bone formation in the distraction gap in a controlled manner. The issue with this technique has been the high risk of complications, one of which is poor regenerate formation during the distraction process. Although several factors (including patient and operative factors) and techniques (including surgical, mechanical and pharmacological) have been described to ensure successful regenerate formation during the process of DO, these factors are sometimes difficult to control clinically. Our aim from this review is to highlight the different factors that affect DO, modalities to assess the regenerate and review treatment options for poor regenerate in the distraction gap. In addition, we propose a management protocol derived from the available literature that can be used to facilitate the management of inadequate regenerate formation.

Assessment of the effect of systemic delivery of sclerostin antibodies on Wnt signaling in distraction osteogenesis.

Sclerostin is a known inhibitor of the Wnt signaling pathway which is involved in osteogenesis and, when inactivated, stimulates bone formation. To our knowledge, this effect has not been studied in the context of distraction osteogenesis (DO). Tibial DO was conducted on a total of 24 wild-type mice, which were then divided into 2 groups-a saline injection group (control) and an anti-sclerostin (Scl-Ab) injection group (treatment). The mice in the treatment group received 100 mg/kg intravenous injections of the antibody weekly until killing. The 12 mice in each group were subdivided into four time points according to post-osteotomy time of killing-11 days (mid-distraction), 17 days (late distraction), 34 days (mid-consolidation) and 51 days (late consolidation), with 3 mice per subgroup. After killing, the tibia specimens were collected for immunohistochemical analysis. Our results show that the group injected with anti-sclerostin had an earlier peak (day 11) in the distraction phase of the osteogenic molecules involved in the Wnt signaling pathway in comparison to the placebo group. In addition, downregulation of the inhibitors of this pathway was noted in the treatment group when compared with the placebo group. Furthermore, LRP-5 showed a significant increase in expression in the treatment group. Sclerostin inhibition has a significant effect on the DO process through its effect on the Wnt pathway. This effect was evident through the decreased effect of sclerostin on LRP-5 and earlier upregulation of the osteogenic molecules involved in this pathway.

Are clinical outcomes affected by type of plate used for management of mid-shaft clavicle fractures?

BACKGROUND: Open reduction and internal fixation (ORIF) using plate osteosynthesis for midshaft clavicle fractures is often complicated by the prominence of the implant due to the subcutaneous position of the clavicle. Reoperation rates for symptomatic clavicle plate removal have been reported to be as high as 53%. We sought to determine to which degree do clinical outcomes (all cause reoperation rate and rate of fracture union) differ between types of clavicle plates. MATERIALS AND METHODS: A retrospective chart review was performed using our hospital database for patients treated with ORIF for mid-shaft clavicle fractures (OTA/AO type 15-B). Implants included in this review were 2.7 mm reconstruction plates, 3.5 mm reconstruction plates, 3.5 mm precontoured clavicle plates and 3.5 mm locking compression plates. The primary outcome measure was the all cause reoperation rate. Secondary outcomes compared the rate fracture union, documented infection, hardware failures and clinical symptoms at the surgical site among the various plate types. Data was collected and descriptive statistics were analyzed. p values < 0.05 were considered statistically significant. RESULTS: A total of 102 midshaft clavicle fractures treated with ORIF were included in this study. The majority of patients were ≤ 50 years old (83.3%) and male (72.5%). The overall union rate for all plating constructs was 97.1%. We found that age, sex and smoking were not associated with the rate of re-operation. In addition, the fracture classification, type of implant used and number of screws used didn't increase the risk of revision surgery. In addition, more than 50% of patients complaining of pain at 6 weeks post-operatively required a second surgery for removal of hardware. Moreover, there was no association between age, sex, smoking, fracture classification or plate type and the rate of union. Interestingly, clavicle fractures fixed with 3.5 mm reconstruction plates were more likely to have hardware failure due to plastic deformation, whereas 2.7 mm plates were more likely to fail by plate breakage. CONCLUSION: Although different types of implants have different biomechanical properties, no difference in reoperation, union and plate removal rates were found between the various plate types. Future studies with a larger sample size are required to further examine these outcomes. LEVEL OF EVIDENCE: Level III.

Resveratrol treatment attenuates chemokine receptor expression in the BTBR T+tf/J mouse model of autism.

Autism is a neurodevelopmental disorder categorized by qualitative impairments in social interaction, communication, and repetitive stereotypic behavior. Emerging evidence increasingly suggests that chemokine receptors have a pivotal role in the central nervous system and are involved in the pathogenesis of numerous neuroinflammatory diseases. Resveratrol is widely used to treat neurodegenerative diseases, but its effect on autism has not been investigated. We investigated the effect of resveratrol (20 and 40mg/kg) in the spleen and brain tissues of BTBR T+tf/J (BTBR) and C57BL/6J (B6) mice as well as on the C-C chemokine receptor (CCR) and C-X-C motif chemokine receptor (CXCR) (CCR3+, CCR5+, CCR7+ and CCR9+, CXCR3+ and CXCR5+) in cluster of differentiation 4-positive (CD4+) T cells in the spleen. We also assessed the mRNA expression of CCR and CXCR receptors in the spleen and brain tissues. Our study revealed that the BTBR and B6 control mice showed different immune profiles. The BTBR mice showed characteristic higher levels of both CCR and CXCR production and expression in CD4+ T cells than the B6 control mice did. Treatment of B6 and BTBR mice with resveratrol (20 and 40mg/kg) induced a substantial decrease in the CCR and CXCR production and expression in CD4+ T cells compared with the respective untreated control groups. Moreover, resveratrol treatment decreased the mRNA expression levels of CCR and CXCR in the spleen and brain tissues. Resveratrol downregulated the chemokine receptor levels, which might provide unique targets for future therapies for autism.

Does Sclerostin Depletion Stimulate Fracture Healing in a Mouse Model?

BACKGROUND: Sclerostin is a secreted glycoprotein that inhibits the intracellular Wnt signaling pathway, which, when inactivated, stimulates bone formation. This has been seen in fracture studies, which have shown larger and stronger calluses with accelerated fracture healing in sclerostin knockout and sclerostin antibody injection models. However, the effects of these two mechanisms have not been compared in the context of fracture healing. QUESTIONS/PURPOSES: We sought to determine the degree to which sclerostin inhibition (Scl-Ab injection) and complete sclerostin depletion inhibit fracture healing in a mouse model as evaluated by (1) morphometric trabecular bone measures at the fracture site, and (2) fracture site structural strength. METHODS: Ten-week-old male sclerostin knockout (n = 20) and wild type (n = 40) mice underwent insertion of a tibial intramedullary pin after which a midshaft tibial osteotomy was performed. The mice were divided in three groups: sclerostin knockout (n = 20), wild type with sclerostin antibody injection (intravenous dose of 100 mg/kg weekly) (n = 20), and wild type with saline injection (n = 20). The mice for each group where subdivided and euthanized at 14, 21, 28, and 35 days after surgery, at which time the fractured tibias were assessed with microCT (to assess morphometric trabecular bone measures: bone volume to total volume (BV/TV), trabecular thickness, trabecular number, and structural model index at the fracture site. Biomechanical testing in the form of three-point bending also was done to assess fracture site structural strength. A difference greater than 3.7% in our primary outcome (BV/TV) would be required to detect a difference between groups with a power of 80%, as per our power analysis. RESULTS: The wild type with sclerostin antibody and the sclerostin knockout groups showed increased trabecular BV/TV at the fracture site compared with the wild type group with saline at all times, however no difference was seen between the treatment groups with the numbers available, except at 28 days postoperatively when the sclerostin knockout group showed greater BV/TV than the wild type sclerostin antibody group (47.0 ± 3.5 vs 40.1 ± 2.1; p < 0.05). On biomechanical testing the wild type sclerostin antibody showed increased stiffness at Days 14 and 28 compared with the wild type with saline group (70.9 ± 6.4 vs 14.8 ± 8.1; p = 0.001), (106.8 ± 24.3 vs 74.9 ± 16.0; p = 0.004); respectively. However, with the numbers available, no differences were detected between the wild type with sclerostin antibody and the sclerostin knockout groups in terms of whole-bone structural strength. CONCLUSIONS: Sclerostin antibody injections showed promising results, which were not different with the numbers available, from results achieved with complete depletion of sclerostin, especially at earlier stages of the healing process, and therefore completed the healing process at an earlier time. CLINICAL RELEVANCE: Sclerostin antibody injections appear to enhance fracture healing to a degree that is not different than complete sclerostin depletion, but larger animal studies are required to assess the accurate dosage and timing of administration in the fracture healing process to further evaluate its potential clinical utility to enhance fracture healing.

Adult Reconstructive Surgery: A High-Risk Profession for Work-Related Injuries.

BACKGROUND: Adult reconstructive surgery is an orthopedic subspecialty characterized by surgical tasks that are physical, repetitive, and require some degree of stamina from the surgeon. This can result strain and/or injury of the surgeon's musculoskeletal system. This study investigates the prevalence of work-related injuries among arthroplasty surgeons. METHODS: A modified version of the physical discomfort survey was sent to surgeon members of the Hip Society, the International Hip Society, and the Canadian Orthopedic Arthroplasty via email. One hundred and eighty-three surgeons completed the survey. RESULTS: Overall, 66.1% of the arthroplasty surgeons reported that they had experienced a work-related injury. The most common injuries that occurred were low back pain (28%), lateral epicondylitis of the elbow (14%), shoulder tendonitis (14%), lumbar disc herniation (13%), and wrist arthritis (12%). Overall, 27% of surgeons took time off from work because of the injury. As the number of disorders diagnosed increased, there was a significant increase in the incidence of requiring time off work because of the disorder (P < .001) and also exacerbation of a previously diagnosed disorder (P < .01). Factors that significantly increased the risk of the surgeon requiring time off because of the disorder were age >55 years, practicing for more than >20 years, and performing >100 total hip arthroplasty procedures per year (P < .05). In addition, 31% of the orthopedic surgeons surveyed required surgery for their injury. CONCLUSION: Although most studies concentrate on the importance of patient safety and thus the quality of the health care system, the surgeon's safety is also considered an integral part of this system's quality. This study highlights a high prevalence of musculoskeletal work-related injuries among arthroplasty surgeons and indicates the need for the identification of preventive measures directed toward improving the operative surgical environment and work ergonomics for the surgeons.

Prevalence of musculoskeletal disorders among orthopedic trauma surgeons: an OTA survey.

BACKGROUND: Occupational injuries and hazards have gained increased attention in the surgical community in general and in the orthopedic literature specifically. The aim of this study was to assess prevalence and characteristics of musculoskeletal disorders among orthopedic trauma surgeons and the impact of these injuries on the surgeons' practices. METHODS: We sent a modified version of the physical discomfort survey to surgeon members of the Orthopaedic Trauma Association (OTA) via email. Data were collected and descriptive statistics were analyzed. RESULTS: A total of 86 surgeons completed the survey during the period of data collection; 84.9% were men, more than half were 45 years or older and 40.6% were in practice for 10 years or more. More than 66% of respondents reported a musculoskeletal disorder that was related to work; the most common was low back pain (29.3%). The number of body regions involved and disorders diagnosed was associated with increasing age and number of years in practice (p = 0.033). Time off work owing to these disorders was associated with working in a private setting (p = 0.045) and working in more than 1 institute (p = 0.009). CONCLUSION: To our knowledge, our study is the first to report a high percentage of orthopedic trauma surgeons sustaining occupational injuries some time in their careers. The high cost of management and rehabilitation of these injuries in addition to the related number of missed work days indicate the need for increased awareness and implementation of preventive measures.

CONTEXTE: Les blessures et les risques professionnels font l'objet d'une attention croissante dans le milieu chirurgical, plus précisément dans les articles scientifiques en orthopédie. Cette étude visait à évaluer la prévalence et les particularités des troubles musculosquelettiques chez les praticiens en chirurgie orthopédique et traumatologique ainsi que les répercussions de ces blessures sur la pratique des chirurgiens touchés. MÉTHODES: Nous avons envoyé par courriel une version modifiée du sondage sur l'inconfort physique à des chirurgiens membres de l'Orthopaedic Trauma Association, ce qui nous a permis de recueillir des données et d'analyser des statistiques descriptives. RÉSULTATS: En tout, 86 chirurgiens ont répondu au questionnaire pendant la période de collecte de données. Parmi les répondants, 84,9 % étaient des hommes, plus de la moitié étaient âgés de 45 ans ou plus, et 40,6 % exerçaient depuis 10 ans ou plus. Plus de 66 % ont indiqué souffrir d'un trouble musculosquelettique lié à leur travail, le plus courant étant la lombalgie (29,3 %). Le nombre de parties du corps touchées et de troubles diagnostiqués était corrélé à l'âge et au nombre d'années d'exercice (p = 0,033). Les congés attribuables à ces troubles étaient associés au travail dans le privé (p = 0,045) et au travail dans plusieurs établissements (p = 0,009). CONCLUSION: À notre connaissance, notre étude est la première à faire état du pourcentage élevé de praticiens en chirurgie orthopédique et traumatologique atteints de lésions professionnelles à un moment ou à un autre de leur carrière. Compte tenu du coût élevé de la prise en charge et de la réadaptation ainsi que du nombre de jours de congé de maladie associés à ces blessures, il semble nécessaire d'accroître la sensibilisation à ce sujet et d'entreprendre des mesures préventives.

Bilateral Hallux Valgus: A Utility Outcome Score Assessment.

Hallux valgus is the most common forefoot problem in adults. Although it can cause considerable disability and affect the quality of life of those affected, many patients seek medical attention because of cosmetic concerns. Our aim was to objectively measure the perceived health burden of living with bilateral hallux valgus. Previously validated utility outcome measures, including the visual analog scale, time trade-off, and standard gamble tests, were used to quantify the health burden for single-eye blindness, double-eye blindness, and bilateral hallux valgus in 103 healthy subjects using an online survey. The Student t test and linear regression analysis were used for statistical analysis. The mean visual analog scale, time trade-off, and standard gamble scores for bilateral hallux valgus were 0.86 ± 1.6, 0.95 ± 0.5, and 0.95 ± 0.14, respectively. These were significantly greater than the utility scores for single-eye and double-eye blindness (p < .05). Age, gender, race, income, and education were not statistically significant independent predictors of the utility scores for hallux valgus. In conclusion, we have objectively demonstrated the effect of living with bilateral hallux valgus deformities. Our sample population reported being willing to undergo a procedure with a 5% mortality rate and sacrifice 1.8 years of life to attain perfect health and avoid the bilateral hallux valgus health state. Our findings will guide us in counseling our patients and understanding how they perceive their foot deformity.