Altered dNTP pools accelerate tumor formation in mice.

Alterations in deoxyribonucleoside triphosphate (dNTP) pools have been linked to increased mutation rates and genome instability in unicellular organisms and cell cultures. However, the role of dNTP pool changes in tumor development in mammals remains unclear. In this study, we present a mouse model with a point mutation at the allosteric specificity site of ribonucleotide reductase, RRM1-Y285A. This mutation reduced ribonucleotide reductase activity, impairing the synthesis of deoxyadenosine triphosphate (dATP) and deoxyguanosine triphosphate (dGTP). Heterozygous Rrm1+/Y285A mice exhibited distinct alterations in dNTP pools across various organs, shorter lifespans and earlier tumor onset compared with wild-type controls. Mutational spectrum analysis of tumors revealed two distinct signatures, one resembling a signature extracted from a human cancer harboring a mutation of the same amino acid residue in ribonucleotide reductase, RRM1Y285C. Our findings suggest that mutations in enzymes involved in dNTP metabolism can serve as drivers of cancer development.

Squatting biomechanics following physiotherapist-led care or hip arthroscopy for femoroacetabular impingement syndrome: a secondary analysis from a randomised controlled trial.

Background: Femoroacetabular impingement syndrome (FAIS) can cause hip pain and chondrolabral damage that may be managed non-operatively or surgically. Squatting motions require large degrees of hip flexion and underpin many daily and sporting tasks but may cause hip impingement and provoke pain. Differential effects of physiotherapist-led care and arthroscopy on biomechanics during squatting have not been examined previously. This study explored differences in 12-month changes in kinematics and moments during squatting between patients with FAIS treated with a physiotherapist-led intervention (Personalised Hip Therapy, PHT) and arthroscopy. Methods: A subsample (n = 36) of participants with FAIS enrolled in a multi-centre, pragmatic, two-arm superiority randomised controlled trial underwent three-dimensional motion analysis during squatting at baseline and 12-months following random allocation to PHT (n = 17) or arthroscopy (n = 19). Changes in time-series and peak trunk, pelvis, and hip biomechanics, and squat velocity and maximum depth were explored between treatment groups. Results: No significant differences in 12-month changes were detected between PHT and arthroscopy groups. Compared to baseline, the arthroscopy group squatted slower at follow-up (descent: mean difference -0.04 m∙s-1 (95%CI [-0.09 to 0.01]); ascent: -0.05 m∙s-1 [-0.11 to 0.01]%). No differences in squat depth were detected between or within groups. After adjusting for speed, trunk flexion was greater in both treatment groups at follow-up compared to baseline (descent: PHT 7.50° [-14.02 to -0.98]%; ascent: PHT 7.29° [-14.69 to 0.12]%, arthroscopy 16.32° [-32.95 to 0.30]%). Compared to baseline, both treatment groups exhibited reduced anterior pelvic tilt (descent: PHT 8.30° [0.21-16.39]%, arthroscopy -10.95° [-5.54 to 16.34]%; ascent: PHT -7.98° [-0.38 to 16.35]%, arthroscopy -10.82° [3.82-17.81]%), hip flexion (descent: PHT -11.86° [1.67-22.05]%, arthroscopy -16.78° [8.55-22.01]%; ascent: PHT -12.86° [1.30-24.42]%, arthroscopy -16.53° [6.72-26.35]%), and knee flexion (descent: PHT -6.62° [0.56- 12.67]%; ascent: PHT -8.24° [2.38-14.10]%, arthroscopy -8.00° [-0.02 to 16.03]%). Compared to baseline, the PHT group exhibited more plantarflexion during squat ascent at follow-up (-3.58° [-0.12 to 7.29]%). Compared to baseline, both groups exhibited lower external hip flexion moments at follow-up (descent: PHT -0.55 N∙m/BW∙HT[%] [0.05-1.05]%, arthroscopy -0.84 N∙m/BW∙HT[%] [0.06-1.61]%; ascent: PHT -0.464 N∙m/BW∙HT[%] [-0.002 to 0.93]%, arthroscopy -0.90 N∙m/BW∙HT[%] [0.13-1.67]%). Conclusion: Exploratory data suggest at 12-months follow-up, neither PHT or hip arthroscopy are superior at eliciting changes in trunk, pelvis, or lower-limb biomechanics. Both treatments may induce changes in kinematics and moments, however the implications of these changes are unknown. Trial registration details: Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549. Trial registered 2/11/2015.

Pancreatic metastasis of mesenchymal chondrosarcoma: a surgical case report and review of literature.

Introduction: Mesenchymal chondrosarcoma (MC) is a rapidly progressive sarcoma that predominantly impacts the bones. Making up only 3% of chondrosarcomas, about one-third of these tumours develop in extra-skeletal sites. Case presentation: The authors present a clinical case of a 42-year-old patient who was diagnosed with MC 8 years ago, now admitted to the hospital with a palpable epigastric mass. Clinical and laboratory examinations showed consistent results for MC tumours, with metastasis to the body and tail of the pancreas and invasion of the splenic vein. Surgical resection and systemic screening were performed to ensure that there were no lesions elsewhere. Regular follow-up has found no localized lesions or complications after 15 months. Clinical discussion: Metastatic extra-skeletal mesenchymal chondrosarcoma of the pancreas is exceptionally rare. To our current understanding, only 14 such cases have been documented in medical literature. The symptoms of pancreatic metastasis are diverse and the radiographic features of metastatic mesenchymal chondrosarcoma are not typically distinct. Conclusions: Although MC tumours do not frequently occur in sites other than the axial system, a tumour presenting later in a patient with a history of MC should be reviewed to confirm the diagnosis of metastatic MC. Treatment can vary between surgery, radiation therapy and systemic therapy.

The effect of 3 commonly used surgical approaches for total hip arthroplasty on mid- to long-term patient-reported outcome measures.

INTRODUCTION: The most effective surgical approach for total hip arthroplasty (THA) remains controversial. Comparisons of surgical approach based on patient-reported outcome measures (PROMs) have been limited to short- to mid-term outcomes or the comparison of only 2 approaches. The aim of this study was to compare PROMs for the 3 main approaches for THA with up to 10 years follow-up. METHODS: A total of 906 patients who underwent primary THA at a single hospital between 2009 and 2020 through an anterior (312), lateral (211) or posterior (383) approach were evaluated using the Oxford Hip Score (OHS), EuroQoL-5-Dimension (EQ-5D-5L) and visual analogue scale/verbal rating scale for pain (VAS/VRS). PROMs were prospectively collected before surgery and routinely at 6 weeks, 6 months and 1, 2, 5 and 10 years after surgery. RESULTS: There was no significant difference in demographics or comorbidities between the 3 groups. All 3 approaches resulted in a significant improvement in overall PROMs after THA, and plateaued after 6 months postoperatively, with no difference between the approaches (OHS, p < 0.01;EQ-5D-5L Index, p < 0.01;VAS/VRS, p < 0.01). The EQ-5D-5L mobility dimension showed that the lateral approach resulted in 20% more patients reporting problems with mobility than the posterior and anterior approaches at the 6-week, 6-month, 2-year and 10-year follow-up. CONCLUSIONS: This study shows that all 3 common THA approaches substantially and similarly improve the OHS, EQ-5D-5L Index and VRS between 6 months and 10 years postoperatively. However, patient-reported mobility was poorer after a lateral approach and continued to be so at long-term follow-up.

The Efficacy of Transplanting Human Umbilical Cord Mesenchymal Stem Cell Sheets in the Treatment of Myocardial Infarction in Mice.

The transplantation of mesenchymal stem cell (MSC) sheets derived from human umbilical cords (hUCs) was investigated in this study as a potential application in treating myocardial infarction (MI). Two groups of hUC-MSC sheets were formed by populating LunaGelTM, which are 3D scaffolds of photo-crosslinkable gelatin-based hydrogel with two different cell densities. An MI model was created by ligating the left anterior descending coronary artery of healthy BALB/c mice. After two weeks, the cell sheets were applied directly to the MI area and the efficacy of the treatment was evaluated over the next two weeks by monitoring the mice's weight, evaluating the left ventricle ejection fraction, and assessing the histology of the heart tissue at the end of the experiment. Higher cell density showed significantly greater efficiency in MI mice treatment in terms of weight gain and the recovery of ejection fraction. The heart tissue of the groups receiving cell sheets showed human-CD44-positive staining and reduced fibrosis and apoptosis. In conclusion, the hUC-MSC sheets ameliorated heart MI injury in mice and the efficacy of the cell sheets improved as the number of cells increased.

Effect of Aspirin vs Enoxaparin on 90-Day Mortality in Patients Undergoing Hip or Knee Arthroplasty: A Secondary Analysis of the CRISTAL Cluster Randomized Trial.

Importance: Ischemic heart disease remains the leading cause of mortality following hip and knee arthroplasty. Due to its antiplatelet and cardioprotective properties, aspirin has been proposed as an agent that could reduce mortality when used as venous thromboembolism (VTE) prophylaxis following these procedures. Objective: To compare aspirin with enoxaparin in reducing 90-day mortality for patients undergoing hip or knee arthroplasty procedures. Design, Setting, and Participants: This study was a planned secondary analysis of the CRISTAL cluster randomized, crossover, registry-nested trial performed across 31 participating hospitals in Australia between April 20, 2019, and December 18, 2020. The aim of the CRISTAL trial was to determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE following hip or knee arthroplasty. The primary study restricted the analysis to patients undergoing total hip or knee arthroplasty for a diagnosis of osteoarthritis only. This study includes all adult patients (aged ≥18 years) undergoing any hip or knee arthroplasty procedure at participating sites during the course of the trial. Data were analyzed from June 1 to September 6, 2021. Interventions: Hospitals were randomized to administer all patients oral aspirin (100 mg daily) or subcutaneous enoxaparin (40 mg daily) for 35 days after hip arthroplasty and 14 days after knee arthroplasty procedures. Main Outcomes and Measures: The primary outcome was mortality within 90 days. The between-group difference in mortality was estimated using cluster summary methods. Results: A total of 23 458 patients from 31 hospitals were included, with 14 156 patients allocated to aspirin (median [IQR] age, 69 [62-77] years; 7984 [56.4%] female) and 9302 patients allocated to enoxaparin (median [IQR] age, 70 [62-77] years; 5277 [56.7%] female). The mortality rate within 90 days of surgery was 1.67% in the aspirin group and 1.53% in the enoxaparin group (estimated difference, 0.04%; 95% CI, -0.05%-0.42%). For the subgroup of 21 148 patients with a nonfracture diagnosis, the mortality rate was 0.49% in the aspirin group and 0.41% in the enoxaparin group (estimated difference, 0.05%; 95% CI, -0.67% to 0.76%). Conclusions and Relevance: In this secondary analysis of a cluster randomized trial comparing aspirin with enoxaparin following hip or knee arthroplasty, there was no significant between-group difference in mortality within 90 days when either drug was used for VTE prophylaxis. Trial Registration: http://anzctr.org.au Identifier: ACTRN12618001879257.

Prediction of obstructive coronary artery disease in patients undergoing heart valve surgery: A cross-sectional study in a tertiary care hospital.

Introduction: Estimating the probability of obstructive coronary artery disease in patients undergoing noncoronary cardiac surgery should be considered compulsory. Our study sought to evaluate the prevalence of obstructive coronary artery disease in patients undergoing valvular heart surgery and to utilize predictive methodology of concomitant obstructive coronary artery disease in these patients. Methods: The retrospective study cohort was derived from a tertiary care hospital registry of patients undergoing coronary angiogram prior to valvular heart operations. Decision tree, logistic regression, and support vector machine models were built to predict the probability of the appearance of obstructive coronary artery disease. A total of 367 patients from 2016 to 2019 were analyzed. Results: The mean age of the study population was 57.3±9.3 years, 45.2% of the patients were male. Of 367 patients, 76 (21%) patients had obstructive coronary artery disease. The decision tree, logistics regression, and support vector machine models had an area under the curve of 72% (95% CI: 62% - 81%), 67% (95% CI: 56% - 77%), and 78% (95% CI: 68% - 87%), respectively. Multivariate analysis indicated that hypertension (OR 1.98; P=0.032), diabetes (OR 2.32; P=0.040), age (OR 1.05; P=0.006), and typical angina (OR 5.46; P<0.001) had significant role in predicting the presence of obstructive coronary artery disease. Conclusion: Our study revealed that approximately one-fifth of patients who underwent valvular heart surgery had concomitant obstructive coronary artery disease. The support vector machine model showed the highest accuracy compared to the other model.

Encapsulation of Human Umbilical Cord Mesenchymal Stem Cells in LunaGel Photocrosslinkable Extracellular Matrix and Subcutaneous Transplantation in Mice.

Stem cells have significant potential in regenerative medicines. However, a major issue with implanting stem cells in the regeneration of new tissue is the methods to implant them and cell viability and functions before and after implantation. Here we developed a simple yet effective method that used photo-crosslinkable gelatin-based hydrogel (LunaGelTM) as a scaffold for the encapsulation, expansion, and eventually, transplantation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) into mice subcutaneously. We demonstrated the proliferation and maintenance of the original expression of mesenchymal stem cell markers as well as the ability to differentiate into mesoderm-derived cells. The hydrogel was highly stable with no signs of degradation after 20 days in PBS. The hUC-MSCs remained viable after transplantation into mice's subcutaneous pockets and migrated to integrate with the surrounding tissues. We showed a collagen-rich layer surrounding the transplanted cell-laden scaffold indicating the effects of growth factors secreted by the hUC-MSCs. A connective tissue layer was found between the implanted cell-laden scaffold and the collagen layer, and immunohistochemical staining results suggested that this tissue was derived from the MSCs which migrated from within the scaffold. The results, thus, also suggested a protective effect the scaffold has on the encapsulated cells from the antibodies and cytotoxic cells of the host immune system.

Suture-tape augmentation of anterior cruciate ligament reconstruction: a prospective, randomised controlled trial (STACLR).

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction aims to restore anteroposterior and rotatory stability to the knee following ACL injury. This requires the graft to withstand the forces applied during the process of ligamentisation and the rehabilitative period. We hypothesise that the use of suture tape augmentation of single bundle ACL reconstruction (ACLR) will reduce residual knee laxity and improve patient-reported outcomes at 2-year follow-up. We will conduct a 1:1 parallel arm single-centre randomised controlled trial comparing suture tape augmented ACLR to standard ACLR technique. METHODS: The study design will be a parallel arm 1:1 allocation ratio randomised controlled trial. Sixty-six patients aged 18 and over waitlisted for primary ACLR will be randomised. Patients requiring osteotomy and extra-articular tenodesis and who have had previous contralateral ACL rupture or repair of meniscal or cartilage pathology that modifies the post-operative rehabilitation will be excluded. The primary outcome measure will be the side-to-side difference in anterior tibial translation (measured on the GNRB arthrometer) at 24 months post-surgery. GNRB arthrometer measures will also be taken preoperatively, at 3 months and 12 months post-surgery. Secondary outcomes will include patient-reported outcome measures (PROMs) collected online, including quality of life, activity and readiness to return to sport, complication rates (return to theatre, graft failure and rates of sterile effusion), examination findings and return to sport outcomes. Participants will be seen preoperatively, at 6 weeks, 3 months, 12 months and 24 months post-surgery. Participants and those taking arthrometer measures will be blinded to allocation. DISCUSSION: This will be the first randomised trial to investigate the effect of suture-tape augmentation of ACLR on either objective or subjective outcome measures. The use of suture-tape augmentation in ACLR has been associated with promising biomechanical and animal-level studies, exhibiting equivalent complication profiles to the standard technique, with initial non-comparative clinical studies establishing possible areas of advantage for the technique. The successful completion of this trial will allow for an improved understanding of the in situ validity of tape augmentation whilst potentially providing a further platform for surgical stabilisation of the ACL graft. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12621001162808. Universal Trial Number (UTN): U1111-1268-1487. Registered prospectively on 27 August 2021.

Do Certain Patient Cohorts Benefit From Different Surgical Approaches in Total Hip Arthroplasty?

BACKGROUND: Unfortunately, an important minority of total hip arthroplasty (THA) patients report unsatisfactory outcomes. We aimed to compare the patient-reported outcome measures (PROMs) for three main THA approaches and evaluate the effect of sex and body mass index (BMI) on PROMs over a 10-year period. METHODS: A total of 906 patients (535 women, mean BMI 30.7 [range, 15 to 58]; 371 men, mean BMI 31.2 [range, 17 to 56]) who underwent primary THA by an anterior (AA) (312), lateral (LA) (211), or posterior (383) approach between 2009 and 2020 at a single institution were evaluated using the Oxford Hip Score (OHS). PROMs were prospectively collected before surgery and routinely at 6 weeks, 6 months, and 1, 2, 5, and 10 years after surgery. RESULTS: All three approaches resulted in significant postoperative OHS improvement. Overall, women experienced significantly lower OHS than men (P < .01). A significant negative relationship between BMI and OHS was identified and this relationship was exacerbated with an AA (P < .01). Women who had a BMI ≤ 25 reported OHS with a difference more than 5 points in favor of the AA, while women who had a BMI ≥ 42 reported an OHS with a difference more than 5 in favor of the LA. The BMI ranges were wider when comparing the anterior and posterior approaches, 22 to 46 for women and > 50 for men. For men, an OHS difference more than 5 was only seen with BMI ≥ 45 in favor of the LA. CONCLUSION: This study demonstrated that no single THA approach is superior to another but rather that certain patient cohorts may benefit more from specific approaches. We suggest that women who have a BMI ≤ 25 should consider undergoing an anterior approach for THA, while for women who have a BMI ≥ 42, a lateral approach or for a BMI ≥ 46, a posterior approach is advised.

Moderators, Mediators, and Prognostic Indicators of Treatment With Hip Arthroscopy or Physical Therapy for Femoroacetabular Impingement Syndrome: Secondary Analyses From the Australian FASHIoN Trial.

BACKGROUND: Although randomized controlled trials comparing hip arthroscopy with physical therapy for the treatment of femoroacetabular impingement (FAI) syndrome have emerged, no studies have investigated potential moderators or mediators of change in hip-related quality of life. PURPOSE: To explore potential moderators, mediators, and prognostic indicators of the effect of hip arthroscopy and physical therapy on change in 33-item international Hip Outcome Tool (iHOT-33) score for FAI syndrome. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Overall, 99 participants were recruited from the clinics of orthopaedic surgeons and randomly allocated to treatment with hip arthroscopy or physical therapy. Change in iHOT-33 score from baseline to 12 months was the dependent outcome for analyses of moderators, mediators, and prognostic indicators. Variables investigated as potential moderators/prognostic indicators were demographic variables, symptom duration, alpha angle, lateral center-edge angle (LCEA), Hip Osteoarthritis MRI Scoring System (HOAMS) for selected magnetic resonance imaging (MRI) features, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) score. Potential mediators investigated were change in chosen bony morphology measures, HOAMS, and dGEMRIC score from baseline to 12 months. For hip arthroscopy, intraoperative procedures performed (femoral ostectomy ± acetabular ostectomy ± labral repair ± ligamentum teres debridement) and quality of surgery graded by a blinded surgical review panel were investigated for potential association with iHOT-33 change. For physical therapy, fidelity to the physical therapy program was investigated for potential association with iHOT-33 change. RESULTS: A total of 81 participants were included in the final moderator/prognostic indicator analysis and 85 participants in the final mediator analysis after exclusion of those with missing data. No significant moderators or mediators of change in iHOT-33 score from baseline to 12 months were identified. Patients with smaller baseline LCEA (ß = -0.82; P = .034), access to private health care (ß = 12.91; P = .013), and worse baseline iHOT-33 score (ß = -0.48; P < .001) had greater iHOT-33 improvement from baseline to 12 months, irrespective of treatment allocation, and thus were prognostic indicators of treatment response. Unsatisfactory treatment fidelity was associated with worse treatment response (ß = -24.27; P = .013) for physical therapy. The quality of surgery and procedures performed were not associated with iHOT-33 change for hip arthroscopy (P = .460-.665 and P = .096-.824, respectively). CONCLUSION: No moderators or mediators of change in hip-related quality of life were identified for treatment of FAI syndrome with hip arthroscopy or physical therapy in these exploratory analyses. Patients who accessed the Australian private health care system, had smaller LCEAs, and had worse baseline iHOT-33 scores, experienced greater iHOT-33 improvement, irrespective of treatment allocation.

The effect of a postoperative local anaesthetic pain pump in anterior total hip arthroplasty: a randomised control trial.

INTRODUCTION: This project aims to determine if an addition of a local anaesthetic pain pump for 48 hours postoperatively effects verbal pain scores (VRS), opioid usage and length of stay (LOS) after anterior approach total hip arthroplasty (THA). METHODS: This was a single-centre, single-surgeon, randomised, parallel-group study with balanced randomisation involving 108 patients. Randomisation and blinding were computer generated into 2 groups: local infiltration anaesthetic (LIA) only (Control Group) and LIA+ continuous postoperative infusion of local anaesthetic for 48 hours via a pain pump (Intervention Group). Postoperatively VRS (first 30 minutes, 1 hour, 2 hours and every 4 hours postoperatively up to 48 hours), opioid consumption, length of hospital admission, antiemetic and laxative usage were recorded. Statistical analysis utilised independent sample t-tests and repeated ANOVA. RESULTS: Demographics and duration of surgery were similar across both cohorts. On average, compared to the control group, the intervention group required 2 mg less of opioid consumption over 48 hours (p = 0.41). VRS between the 2 groups showed no statistically significant difference. Scores ranged from 0 to 7, with an average of 1.28 in the intervention group and 1.29 in the control group (p = 0.31). 9 patients in the intervention group and 10 in the control group required antiemetics. There was no difference in the LOS or postoperative constipation. No complications or adverse events occurred. CONCLUSIONS: Our study has shown the addition of a continuous postoperative infusion of local anaesthetic for 48 hours post an anterior THA had no effect on VRS, opioid consumption, LOS and antiemetic usage.

Comparison of Walking Biomechanics After Physical Therapist-Led Care or Hip Arthroscopy for Femoroacetabular Impingement Syndrome: A Secondary Analysis From a Randomized Controlled Trial.

BACKGROUND: Femoroacetabular impingement syndrome is characterized by chondrolabral damage and hip pain. The specific biomechanics used by people with femoroacetabular impingement syndrome during daily activities may exacerbate their symptoms. Femoroacetabular impingement syndrome can be treated nonoperatively or surgically; however, differential treatment effects on walking biomechanics have not been examined. PURPOSE: To compare the 12-month effects of physical therapist-led care or arthroscopy on trunk, pelvis, and hip kinematics as well as hip moments during walking. STUDY DESIGN: Secondary analysis of multi-centre, pragmatic, two-arm superiority randomized controlled trial subsample; Level of evidence, 1. METHODS: A subsample of 43 participants from the Australian Full randomised controlled trial of Arthroscopic Surgery for Hip Impingement versus best cONventional (FASHIoN trial) underwent gait analysis and completed the International Hip Outcome Tool (iHOT-33) at both baseline and 12 months after random allocation to physical therapist-led care (personalized hip therapy; n = 22; mean age 35; 41% female) or arthroscopy (n = 21; mean age 36; 48% female). Changes in trunk, pelvis, and hip biomechanics were compared between treatment groups across the gait cycle using statistical parametric mapping. Associations between changes in iHOT-33 and changes in hip kinematics across 3 planes of motion were examined. RESULTS: As compared with the arthroscopy group, the personalized hip therapy group increased its peak hip adduction moments (mean difference = 0.35 N·m/body weight·height [%] [95% CI, 0.05-0.65]; effect size = 0.72; P = .02). Hip adduction moments in the arthroscopy group were unchanged in response to treatment. No other between-group differences were detected. Improvements in iHOT-33 were not associated with changes in hip kinematics. CONCLUSION: Peak hip adduction moments were increased in the personalized hip therapy group and unchanged in the arthroscopy group. No biomechanical changes favoring arthroscopy were detected, suggesting that personalized hip therapy elicits greater changes in hip moments during walking at 12-month follow-up. Twelve-month changes in hip-related quality of life were not associated with changes in hip kinematics.

Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty: The CRISTAL Randomized Trial.

Importance: There remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Objective: To determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA. Design, Setting, and Participants: Cluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021. Interventions: Hospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation. Main Outcomes and Measures: The primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group. Results: Enrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years; 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin (P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group. Conclusions and Relevance: Among patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis. Trial Registration: ANZCTR Identifier: ACTRN12618001879257.

Kinesin-14 HSET may not oppose kinesin-5 Eg5 activity in RPE-1 cells.

Human retinal pigment epithelium RPE-1 cells are immortalized diploid wild-type cells. RPE-1 is increasingly used for studies of spindle assembly dynamics and chromosome segregation. Here, we imaged living RPE-1 cells using the spinning disk confocal microscope and report their complete spindle assembly dynamic parameters. Live-cell experiments enabled ascribing precise timing of function of the kinesin-5 Eg5 and kinesin-14 HSET throughout different phases of mitosis. Eg5 functions at prophase and metaphase, to assemble and maintain spindle bipolarity, respectively. Eg5 inhibition results in spindle collapse during prophase and metaphase, resulting in monoastral/monopolar spindles. HSET functions throughout mitosis to maintain spindle length. HSET degradation results in shorter spindles through all phases of mitosis. Double-inhibition of Eg5 and HSET produces only monoastral/monopolar spindles, indicating that Eg5 and HSET may not be antagonistic in wild-type RPE-1 cells, contrary to previous studies using cancer cells. In the context of spindle assembly, our results highlight potential important differences between RPE-1 and other cancer-derived cell lines.

Plating vs Closed Reduction for Fractures in the Distal Radius in Older Patients: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Distal radius fractures are common and are managed with or without surgery. Current evidence indicates surgical treatment is not superior to nonsurgical treatment at 12 months. Objective: Does surgical treatment for displaced distal radius fractures in patients 60 years or older provide better patient-reported wrist pain and function outcomes than nonsurgical treatment at 24 months? Design, Setting, and Participants: In this secondary analysis of a combined multicenter randomized clinical trial (RCT) and a parallel observational study, 300 patients were screened from 19 centers in Australia and New Zealand. Of these, 166 participants were randomized to surgical or nonsurgical treatment. Participants who declined randomization (n = 134) were included in the parallel observational group with the same treatment options and follow-up. Participants were followed up at 3, 12, and 24 months by a blinded assessor. The 24-month outcomes are reported herein. Data were collected from December 1, 2016, to December 31, 2020, and analyzed from February 4 to October 21, 2021. Interventions: Surgical treatment consisting of open reduction and internal fixation using a volar-locking plate (VLP group) and nonsurgical treatment consisting of closed reduction and cast immobilization (CR group). Main Outcomes and Measures: The primary outcome was patient-reported function using the Patient-Rated Wrist Evaluation (PRWE) questionnaire. Secondary outcomes included health-related quality of life, wrist pain, patient-reported treatment success, patient-rated bother with appearance, and posttreatment complications. Results: Among the 166 randomized and 134 observational participants (300 participants; mean [SD] age, 71.2 [7.5] years; 269 women [89.7%]), 151 (91.0%) randomized and 118 (88.1%) observational participants were followed up at 24 months. In the RCT, no clinically important difference occurred in mean PRWE scores at 24 months (13.6 [95% CI, 9.1-18.1] points for VLP fixation vs 15.8 [95% CI, 11.3-20.2] points for CR; mean difference, 2.1 [95% CI, -4.2 to 8.5]; P = .50). There were no between-group differences in all other outcomes except for patient-reported treatment success, which favored VLP fixation (33 of 74 [44.6%] in the CR group vs 54 of 72 [75.0%] in the VLP fixation group reported very successful treatment; P = .002). Rates of posttreatment complications were generally low and similar between treatment groups, including deep infection (1 of 76 [1.3%] in the CR group vs 0 of 75 in the VLP fixation group) and complex regional pain syndrome (2 of 76 [2.6%] in the CR group vs 1 of 75 [1.3%] in the VLP fixation group). The 24-month trial outcomes were consistent with 12-month outcomes and with outcomes from the observational group. Conclusions and Relevance: Consistent with previous reports, these findings suggest that VLP fixation may not be superior to CR for displaced distal radius fractures for patient-rated wrist function in persons 60 years or older during a 2-year period. Significantly higher patient-reported treatment success at 2 years in the VLP group may be attributable to other treatment outcomes not captured in this study. Trial Registration: ANZCTR.org Identifier: ACTRN12616000969460.

Can a Hip Brace Improve Short-Term Hip-Related Quality of Life for People With Femoroacetabular Impingement and Acetabular Labral Tears: An Exploratory Randomized Trial.

OBJECTIVES: To examine whether a hip brace can improve hip health quality-of-life (QoL) and is well-tolerated in people with femoroacetabular impingement syndrome (FAIS) or symptomatic labral tears after 6 weeks of wear. DESIGN: Parallel, two-arm, exploratory randomized trial. SETTING: Hospital and private clinics of orthopaedic surgeons. PARTICIPANTS: Individuals >18 years with FAIS or labral tears. INTERVENTIONS: Usual conservative care versus usual conservative care plus a hip brace. MAIN OUTCOMES: Patient-reported outcomes were assessed with the International Hip Outcome Tool (iHOT-33), and Copenhagen Hip and Groin Outcome Scores (HAGOS). Brace acceptability was measured using the Quebec User Evaluation of Satisfaction with Assistive Technology survey. Independent t-tests assessed between-group differences. RESULTS: Thirty-eight participants were recruited, 19 each group, 60% women, mean age 39.3 ± 11.8 years, body mass index 25.3 ± 4.4 kg/m2, iHOT-33 36.6 ± 24.8. Three participants dropped out (one usual care, 2 braced). The mean between-group difference for iHOT-33 was 19.4 (95% confidence interval [CI] 1.68-37.06, P = 0.03) favoring the brace. There were improvements in most HAGOS subscale scores favoring the brace. Issues with brace tolerability for some participants were perceived comfort and effectiveness. Three brace-related adverse events were reported. CONCLUSION: Between-group differences favored the braced group for hip health QoL, pain, symptoms, and function. Although these were promising results, the CIs for the estimates were wide, the small sample size likely a contributing factor. Our results suggest that further investigation of the brace is warranted, we calculated sample sizes and made recommendations for the design of a future trial.

Covalent Grafting of Ruthenium Complexes on Iron Oxide Nanoparticles: Hybrid Materials for Photocatalytic Water Oxidation.

The present environmental crisis prompts the search for renewable energy sources such as solar-driven production of hydrogen from water. Herein, we report an efficient hybrid photocatalyst for water oxidation, consisting of a ruthenium polypyridyl complex covalently grafted on core/shell Fe@FeOx nanoparticles via a phosphonic acid group. The photoelectrochemical measurements were performed under 1 sun illumination in 1 M KOH. The photocurrent density of this hybrid photoanode reached 20 µA/cm2 (applied potential of +1.0 V vs reversible hydrogen electrode), corresponding to a turnover frequency of 0.02 s-1. This performance represents a 9-fold enhancement of that achieved with a mixture of Fe@FeOx nanoparticles and a linker-free ruthenium polypyridyl photosensitizer. This increase in performance could be attributed to a more efficient electron transfer between the ruthenium photosensitizer and the Fe@FeOx catalyst as a consequence of the covalent link between these two species through the phosphonate pendant group.

Polycrystalline diamond coating on 3D printed titanium scaffolds: Surface characterisation and foreign body response.

Titanium-based implants are the leading material for orthopaedic surgery, due to their strength, versatility, fabrication via additive manufacturing and invoked biological response. However, the interface between the implant and the host tissue requires improvement to better integrate the implant material and mitigate foreign body response. The interface can be manipulated by changing the surface energy, chemistry, and topography of the Titanium-based implant. Recently, polycrystalline diamond (PCD) has emerged as an exciting coating material for 3D printed titanium scaffolds showing enhanced mammalian cell functions while inhibiting bacterial attachment in vitro. In this study, we performed in-depth characterisation of PCD coatings investigating the surface topography, thickness, surface energy, and compared its foreign body response in vivo with uncoated titanium scaffold. Coating PCD onto titanium scaffolds resulted in a similar microscale surface roughness (RMS(PCD-coated) = 24 µm; RMS(SLM-Ti) = 28 µm), increased nanoscale roughness (RMS(PCD-coated) = 35 nm; RMS(SLM-Ti) = 66 nm) and a considerable decrease in surface free energy (E(PCD-coated) = 4 mN m-1; E(SLM-Ti) = 16 mN m-1). These surface property changes were supported by X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy as corresponding to observed surface chemistry changes induced by the coating. The underlying mechanism of how the diamond coatings chemical and physical properties changes the wettability of implants was examined. In vivo, the coated scaffolds induced similar level of fibrous encapsulation with uncoated scaffolds. This study thus provides further insight into the physicochemical characteristics of PCD coatings, adding evidence to the promising potential of PCD-coatings of medical implants.