Single-cell methylation sequencing data reveal succinct metastatic migration histories and tumor progression models.

Recent studies exploring the impact of methylation in tumor evolution suggest that although the methylation status of many of the CpG sites are preserved across distinct lineages, others are altered as the cancer progresses. Because changes in methylation status of a CpG site may be retained in mitosis, they could be used to infer the progression history of a tumor via single-cell lineage tree reconstruction. In this work, we introduce the first principled distance-based computational method, Sgootr, for inferring a tumor's single-cell methylation lineage tree and for jointly identifying lineage-informative CpG sites that harbor changes in methylation status that are retained along the lineage. We apply Sgootr on single-cell bisulfite-treated whole-genome sequencing data of multiregionally sampled tumor cells from nine metastatic colorectal cancer patients, as well as multiregionally sampled single-cell reduced-representation bisulfite sequencing data from a glioblastoma patient. We show that the tumor lineages constructed reveal a simple model underlying tumor progression and metastatic seeding. A comparison of Sgootr against alternative approaches shows that Sgootr can construct lineage trees with fewer migration events and with more in concordance with the sequential-progression model of tumor evolution, with a running time a fraction of that used in prior studies. Lineage-informative CpG sites identified by Sgootr are in inter-CpG island (CGI) regions, as opposed to intra-CGIs, which have been the main regions of interest in genomic methylation-related analyses.

Efficacy and Safety of Darolutamide in Combination With Androgen-Deprivation Therapy and Docetaxel in Black Patients From the Randomized ARASENS Trial.

BACKGROUND: In the ARASENS trial (NCT02799602), darolutamide in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR, 0.68; 95% CI, 0.57-0.80; P < .0001) compared with placebo plus ADT with docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We present efficacy and safety of darolutamide versus placebo in Black patients from ARASENS. PATIENTS AND METHODS: Patients with mHSPC were randomized 1:1 to darolutamide 600 mg or placebo twice daily in combination with ADT and docetaxel. The primary endpoint was overall survival. Key secondary endpoints included time to castration-resistant prostate cancer (CRPC) and safety. RESULTS: In ARASENS, 54 Black patients received darolutamide (n = 26) or placebo (n = 28) plus ADT and docetaxel. In Black patients, overall survival favored darolutamide versus placebo (median, not reached vs. 38.7 months; stratified HR, 0.41; 95% CI, 0.17-1.02), with 4-year survival rates of 62% versus 41%. The darolutamide group also had longer time to CRPC compared with the placebo group (median, not reached vs .12.6 months; HR, 0.09; 95% CI, 0.02-0.30). The safety profile of darolutamide in Black patients was consistent with that observed for the overall ARASENS population (grade 3/4 treatment-emergent adverse events, TEAEs: 61.5% vs. 66.1%; serious TEAEs: 42.3% vs. 44.8%). CONCLUSION: In this small population of Black patients with mHSPC from the ARASENS trial, darolutamide was associated with an improvement in survival and time to CRPC and was well tolerated. Efficacy and safety findings in Black patients were consistent with the overall ARASENS population.

The role of donor type and pre-transplant immunosuppression on outcomes of hematopoietic stem cell transplantation in children and young adults with severe aplastic anemia.

BACKGROUND: The goal of this study was to assess the effect of donor type and pre-transplant immunotherapy (IST) on outcomes of hematopoietic stem cell transplantation (HSCT) for children and young adults with severe aplastic anemia (SAA). METHODS: This retrospective, multi-center study included 52 SAA patients, treated in 5 pediatric transplant programs in Florida, who received HSCT between 2010 and 2020 as the first- or second-line treatment. RESULTS: The median age at HSCT for all 52 patients was 15 years (range 1-25). The 3-year overall survival (OS) by donor type were as follows: 95% [95% CI 85.4-99] for matched related donors (MRD) (N = 24), 84% [95% CI 63.5-99] for haploidentical (N = 13), and 71% [95% CI 36-99] for matched unrelated donors (MUD) (N = 7). The 3-year OS was 81% [95% CI 69.7-99] for all patients, 90.5% [95% CI 79.5-99] for non-IST patients (N = 27), and 70% [95% CI 51-99] for IST patients (N = 24) (log-rank p = .04). Survival of haploidentical HSCT (haplo-HSCT) recipients with post-transplant cyclophosphamide (PTCy) (N = 13) was excellent for both groups: 100% for non-IST patients (N = 3) and 80% for IST patients (N = 10). The 3-year OS for patients with previous IST by donor type in groups where >5 patients were available was 78.8% [95% CI 52.3-99] for haplo-HSCT (N = 10) and 66.7% [95% CI 28.7-99] for MUD (N = 6). Although it appears that patients receiving HSCT ≥6 months after the start of IST had worse survival, the number of patients in each category was small and log-rank was not significant(p = .65). CONCLUSIONS: Patients receiving MUD and haplo-HSCT with PTCy had similar outcomes, suggesting that haplo-HSCT with PTCy could be included in randomized trials of upfront IST versus alternative donor HSCT.

Optimizing outcomes in men with prostate cancer: the cardiovascular event lowering (CaELo) pathways.

INTRODUCTION: Risk of cardiovascular disease is higher among men with prostate cancer than men without, and prostate cancer treatments (especially those that are hormonally based) are associated with increased cardiovascular risk. MATERIALS AND METHODS: An 11-member panel of urologic, medical, and radiation oncologists (along with a men's health specialist and an endocrinologist/preventive cardiologist) met to discuss current practices and challenges in the management of cardiovascular risk in prostate cancer patients who are taking androgen deprivation therapies (ADT) including LHRH analogues, alone and in combination with androgen-targeted therapies (ATTs). RESULTS: The panel developed an assessment algorithm to categorize patients by risk and deploy a risk-adapted management strategy, in collaboration with other healthcare providers (the patient's healthcare "village"), with the goal of preventing as well as reducing cardiovascular events. The panel also developed a patient questionnaire for cardiovascular risk as well as a checklist to ensure that all aspects of cardiovascular disease risk reduction are completed and monitored. CONCLUSIONS: Prostate cancer patients receiving ADT with or without ATT need to be more zealously assessed for prevention and aggressively managed to reduce cardiovascular events. This can and should include participation from the entire multidisciplinary healthcare team.

Digitally Delivered Interventions to Improve Nutrition Behaviors Among Resource-Poor and Ethnic Minority Groups With Type 2 Diabetes: Systematic Review.

BACKGROUND: Resource-poor individuals, such as those with a low income, are disproportionately affected by diabetes and unhealthy eating patterns that contribute to poor disease self-management and prognosis. Digitally delivered interventions have the potential to address some of the barriers to healthy eating experienced by this group. However, little is known about their effectiveness in disadvantaged populations. OBJECTIVE: This systematic review is conducted to assess the effectiveness of digitally delivered interventions in improving nutritional behaviors and nutrition-related health outcomes among disadvantaged people with type 2 diabetes (T2D). METHODS: MEDLINE complete, Global Health, Embase, CINAHL complete, Informit Health, IEEE Xplore, and Applied Science and Technology Source databases were searched for studies published between 1990 and 2022 on digitally delivered nutrition interventions for disadvantaged people with T2D. Two reviewers independently assessed the studies for eligibility and determined the study quality using the Cochrane Risk-of-Bias Assessment Tool. The Behavioral Change Technique Taxonomy V1 was used to identify behavior change techniques used in the design of interventions. RESULTS: Of the 2434 identified records, 10 (0.4%), comprising 947 participants, met the eligibility criteria and were included in the review. A total of 2 digital platforms, web and messaging services (eg, SMS text messaging interventions or multimedia messaging service), were used to deliver interventions. Substantial improvements in dietary behaviors were reported in 5 (50%) of the 10 studies, representing improvements in healthier food choices or increases in dietary knowledge and skills or self-efficacy. Of the 10 studies, 7 (70%) examined changes in blood glucose levels, of which 4 (57%) out of 7 achieved significant decreases in hemoglobin A1C levels ranging from 0.3% to 1.8%. The most frequently identified behavior change techniques across all studies were instruction on how to perform the behavior, information about health consequences, and social support. CONCLUSIONS: This review provided some support for the efficacy of digitally delivered interventions in improving healthy eating behaviors in disadvantaged people with T2D, an essential dietary prerequisite for changes in clinical metabolic parameters. Further research is needed into how disadvantaged people with T2D may benefit more from digital approaches and to identify the specific features of effective digital interventions for supporting healthy behaviors among disadvantaged populations. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020149844; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=149844.

Debridement, Antibiotics, and Implant Retention in Unicompartmental Knee Arthroplasty Infection.

BACKGROUND: This multicenter study sought to further investigate the method and outcome of debridement, antibiotics, and implant retention (DAIR) for the management of unicompartmental knee periprosthetic joint infection (PJI). METHODS: This retrospective study was performed on 52 patients who underwent DAIR for PJI of a unicompartmental knee arthroplasty (UKA) across 4 academic medical centers, all performed by fellowship-trained arthroplasty surgeons. Patient demographics, American Society of Anesthesiologists score, infecting organism, operative data, antibiotic data, and success in infection control at 1 year were collected. RESULTS: The average time from index surgery to diagnosis of PJI was 11.1 weeks (range, 1.4 to 48). There was no correlation between time of diagnosis and success at 1 year (R = 0.09, P = .46). There was an association between surgical synovectomy and the eradication of infection (R = 0.28, P = .04). Overall, there was an 80.8% (42 of 52) infection-controlled success rate at 1 year from the DAIR procedure. All DAIR failures went on to require another procedure, either 1-stage (2 of 10) or 2-stage (8 of 10) revision to total knee arthroplasty (TKA). Of the DAIR successes, 6 (14.3%) went on to require conversion to TKA for progression of arthritis within 5 years. CONCLUSIONS: This study demonstrates that DAIR is a safe and moderately effective procedure in the setting of acute PJI of UKA across institutions, with a success rate consistent with DAIR for TKA. The data suggest that a wide exposure and thorough synovectomy be incorporated during the DAIR UKA to improve the likelihood of successful eradication of PJI at the 1-year mark. LEVEL OF EVIDENCE: Level III.

Low Rate of Early Periprosthetic Fractures in Direct Anterior Total Hip Arthroplasty with a Triple-Tapered Wedge Stem.

INTRODUCTION: Utilization of the direct anterior approach (DAA) for total hip arthroplasty (THA) has been steadily increasing in recent years. While the DAA may offer some benefits compared to other approaches, there are still risks involved including relatively higher rates of periprosthetic femur fractures, especially when combined with cementless femoral stem use. The purpose of this study is to evaluate the early postoperative femoral complications with a short triple-wedge tapered stem used in primary THA via a DAA. MATERIALS AND METHODS: A retrospective review was conducted of the arthroplasty registry of our institution from April 2022 to August 2023 to identify patients who underwent a primary THA via a DAA with the Short Medacta Stem (SMS) (Medacta International, Castel San Pietro, Switzerland). Patients were excluded if the stem was used for a revision surgery, they were within 90 days of surgery, or they refused research consent. Inclusion criteria was met in 262 patients (302 hips). Data was collected after reviewing the chart, and reports and radiographic measurements, including Dorr type and canal fit ratios, were obtained from preoperative and postoperative radiographs, respectively. RESULTS: A total of 302 total hips were included, 161 patients were male (53.3%) and 141 were female (46.7%), with an average age of 66.5 years (27-88, +/- 10.7 years). Average follow up was 0.3 years (range, 0.05-1.71 years). The majority of patients had a Dorr B femur (81.7%). The Median stem size used was an 8 (range, 2-15), and 89.4% of those had a collar. Average canal fill ratio was 0.83 (range, 0.43-0.98, +/- 0.07). Overall, there were two Vancouver B2a periprosthetic femoral shaft fractures (0.66%) that required revision surgery to a modular stem. In addition, there were two Vancouver Ag greater trochanteric fractures (0.66%) with acceptable alignment that did not require revision surgery. Demographic information about the patients with femoral complications is summarized in Table I. Average age of patients with femoral complications was 69.5 years, with an average canal fit ratio of 0.88. CONCLUSION: We found that the triple-wedge implant had a low rate of early femoral complication in primary THA from an anterior approach and is safe for use in THA from a DAA. More follow up is needed to evaluate continuing implant survivorship and patient outcomes.

Do food-related capabilities, opportunities and motivations of adolescents mediate the association between socioeconomic position in adolescence and diet quality in early adulthood?

BACKGROUND: Socio-economic position (SEP) in adolescence may influence diet quality over the life course. However, knowledge of whether individual and environmental determinants of diet quality mediate the longitudinal association between SEP and diet quality is limited. This study examined whether and to what extent food-related capabilities, opportunities and motivations of adolescents mediated the longitudinal association between SEP in adolescence and diet quality in early adulthood overall and by sex. METHODS: Longitudinal data (annual surveys) from 774 adolescents (16.9 years at baseline; 76% female) from ProjectADAPT (T1 (baseline), T2, T3) were used. SEP in adolescence (T1) was operationalized as highest level of parental education and area-level disadvantage (based on postcode). The Capabilities, Opportunities and Motivations for Behaviour (COM-B) model was used as a framework to inform the analysis. Determinants in adolescence (T2) included food-related activities and skills (Capability), home availability of fruit and vegetables (Opportunity) and self-efficacy (Motivation). Diet quality in early adulthood (T3) was calculated using a modified version of the Australian Dietary Guidelines Index based on brief dietary questions on intake of foods from eight food groups. Structural equation modelling was used to estimate the mediating effects of adolescents' COM-B in associations between adolescent SEP and diet quality in early adulthood overall and by sex. Standardized beta coefficients (ß) and robust 95% confidence intervals (CI) were generated, adjusted for confounders (T1 age, sex, diet quality, whether still at school, and living at home) and clustering by school. RESULTS: There was evidence of an indirect effect of area-level disadvantage on diet quality via Opportunity (ß: 0.021; 95% CI: 0.003 to 0.038), but limited evidence for parental education (ß: 0.018; 95% CI: -0.003 to 0.039). Opportunity mediated 60.9% of the association between area-level disadvantage and diet quality. There was no evidence of an indirect effect via Capability or Motivation for either area-level disadvantage or parental education, or in males and females separately. CONCLUSIONS: Using the COM-B model, the home availability of fruit and vegetables (Opportunity) of adolescents explained a large proportion of the association between area-level disadvantage in adolescence and diet quality in early adulthood. Interventions to address poor diet quality among adolescents with a lower SEP should prioritize environmental determinants of diet quality.

Do 20-minute neighbourhoods moderate associations between work and commute hours with food consumption?

OBJECTIVE: To examine associations between work and commute hours with food consumption and test whether neighbourhood type (20-minute neighbourhood (20MN)/non-20MN) moderate associations. DESIGN: Cross-sectional analysis of the Places and Locations for Activity and Nutrition study (ProjectPLAN). Exposures were work hours (not working (0 h), working up to full-time (1-38 h/week), working overtime (> 38 h/week)), and among those employed, combined weekly work and commute hours (continuous). Outcomes were usual consumption of fruit, vegetables, takeaway food, snacks and soft drinks, and number of discretionary food types (takeaway, snacks and soft drinks) consumed weekly. Generalised linear models were fitted to examine associations between each exposure and outcome. The moderating role of neighbourhood type was examined through interaction terms between each exposure and neighbourhood type (20MN/non-20MN). SETTING: Melbourne and Adelaide, Australia, 2018-2019. PARTICIPANTS: Adults ≥ 18 years old (n 769). RESULTS: Although all confidence intervals contained the null, overall, patterns suggested non-workers and overtime workers have less healthy food behaviours than up-to-full-time workers. Among those employed, analysis of continuous work and commute hours data suggested longer work and commute hours were positively associated with takeaway consumption (OR = 1·014, 95 % CI 0·999, 1·030, P-value = 0·066). Patterns of better behaviours were observed across most outcomes for those in 20MN than non-20MN. However, differences in associations between work and commute hours with food consumption across neighbourhood type were negligible. CONCLUSIONS: Longer work and commute hours may induce poorer food behaviours. There was weak evidence to suggest 20MN moderate associations between work and commute hours with food consumption, although behaviours appeared healthier for those in 20MN.

Transform-Us! cluster RCT: 18-month and 30-month effects on children's physical activity, sedentary time and cardiometabolic risk markers.

OBJECTIVE: To test the efficacy of the Transform-Us! school- and home-based intervention on children's physical activity (PA), sedentary behaviour (SB) and cardiometabolic risk factor profiles. METHODS: A 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools (148 Year 3 classes) in Melbourne, Australia (2010-2012), that used pedagogical and environmental strategies to reduce and break up SB, promote PA or a combined approach, compared with usual practice. Primary outcomes (accelerometry data; n=348) were assessed at baseline, 18 and 30 months. Secondary outcomes included body mass index (BMI) and waist circumference (WC) (n=564), blood pressure (BP) (n=537) and biomarkers (minimum n=206). Generalised linear mixed models estimated the interactive effects of the PA and SB interventions on the outcomes. If there was no interaction, the main effects were assessed. RESULTS: At 18 months, there were intervention effects on children's weekday SB (-27 min, 95% CI: -47.3 to -5.3) for the PA intervention, and on children's average day PA (5.5 min, 95% CI: 0.1 to 10.8) for the SB intervention. At 30 months, there was an intervention effect for children's average day SB (-33.3 min, 95% CI: -50.6 and -16.0) for the SB intervention. Children's BMI (PA and SB groups) and systolic BP (combined group) were lower, and diastolic BP (PA group) was higher. There were positive effects on WC at both time points (SB intervention) and mixed effects on blood parameters. CONCLUSIONS: The Transform-Us! PA and SB interventions show promise as a pragmatic approach for reducing children's SB and adiposity indicators; but achieving substantial increases in PA remains challenging. TRIAL REGISTRATION: ISRCTN83725066; ACTRN12609000715279.

Impact of Proximal Tibial Varus Anatomy on Survivorship After Medial Unicondylar Knee Arthroplasty.

BACKGROUND: Precise indications for medial unicondylar knee arthroplasty (UKA) continue to be defined. It is unclear if patients who have proximal tibia vara should be considered candidates for UKA. The purpose of this study was to evaluate the impact of proximal tibial varus alignment on outcomes after UKA. METHODS: A retrospective review identified 2,416 patients (3,029 knees) who underwent mobile-bearing medial UKA with 2-year minimum follow-up or revision. Preoperative radiographs were evaluated, and medial proximal tibial angle (mPTA) was measured. Patients were grouped into two groups as follows: mPTA <80 degrees and mPTA ≥80 degrees. Analyses were performed on the impact of mPTA on clinical outcomes, all-cause revisions, and tibial failures. RESULTS: At a mean follow-up of 5 years (range, 0.5 years to 12.8 years), there was not a statistically significant difference in clinical outcomes nor increased risk for all-cause revision or tibial failure in patients who had an mPTA <80°. Mean mPTA in patients who had tibial failures was 82.5° and not significantly different than those who did not have a tibial failure (82.9°) (P = .289). Tibial failure rate in knees with an mPTA <80° was 2.2% and not significantly different than knees with an mPTA ≥80° at 1.4% (P = .211). The all-cause revision rate in knees with an mPTA <80° was 5.8% and was not significantly different than knees with an mPTA ≥80° at 4.9% (P = .492). CONCLUSION: Patients who have tibia vara are not at increased risk for tibial related or all-cause failure in medial UKA. This data may allow surgeons to increase their indications for medial UKA.

15-Year Follow-Up of Mobile Bearing Medial Unicompartmental Knee Arthroplasty.

INTRODUCTION: Medial unicompartmental knee arthroplasty (UKA) is a successful treatment for antero-medial osteoarthritis. However, there are few published studies on the long-term survival of this procedure. The purpose of this study was to review the 15-year minimum outcomes and survival of a mobile-bearing medial UKA. METHODS: A retrospective review was performed between July 2004 and December 2006 of all patients who underwent a medial UKA eligible for a minimum of 15-year follow-up. The initial query revealed 299 patients (349 knees). One hundred-seventeen patients died or were lost to follow-up, leaving 182 patients (219 knees) for analyses. Clinical outcomes and survivorship were analyzed. RESULTS: There were 59 implant-related reoperations which occurred at a mean of 10 years (range, 0 to 16 years). The most common reasons for reoperation were arthritic progression (9.1%) and aseptic loosening (9.1%). The 10-year survival with revision to TKA was 89% (95% confidence interval: 86% to 92.4%), and the 15-year survival was 84.1% (95% confidence interval: 80.3% to 88%). There were no statistically significant differences in survival between sex, body mass index, and age. Patients who were not revised had statistically significant improvements in knee range of motion and Knee Society scores. CONCLUSIONS: This study found similar long-term survival of a medial mobile-bearing UKA to published total knee arthroplasty outcomes. The implant evaluated in this study has undergone subsequent improvements in instrumentation and design. Further analyses should be performed on the long-term outcomes of the current implant platform.

The Viability of an Artificial Intelligence/Machine Learning Prediction Model to Determine Candidates for Knee Arthroplasty.

BACKGROUND: The purpose of this study is to assess the viability of a knee arthroplasty prediction model using 3-view X-rays that helps determine if patients with knee pain are candidates for total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), or are not arthroplasty candidates. METHODS: Analysis was performed using radiographic and surgical data from a high-volume joint replacement practice. The dataset included 3 different X-ray views (anterior-posterior, lateral, and sunrise) for 2,767 patients along with information of whether that patient underwent an arthroplasty surgery (UKA or TKA) or not. This resulted in a dataset including 8,301 images from 2,707 patients. This dataset was then split into a training set (70%) and holdout test set (30%). A computer vision model was trained using a transfer learning approach. The performance of the computer vision model was evaluated on the holdout test set. Accuracy and multiclass receiver operating characteristic area under curve was used to evaluate the performance of the model. RESULTS: The artificial intelligence model achieved an accuracy of 87.8% on the holdout test set and a quadratic Cohen's kappa score of 0.811. The multiclass receiver operating characteristic area under curve score for TKA was calculated to be 0.97; for UKA a score of 0.96 and for No Surgery a score of 0.98 was achieved. An accuracy of 93.8% was achieved for predicting Surgery versus No Surgery and 88% for TKA versus not TKA was achieved. CONCLUSION: The artificial intelligence/machine learning model demonstrated viability for predicting which patients are candidates for a UKA, TKA, or no surgical intervention.

Is an "Outpatient Arthroplasty Risk Assessment Score" Needed for Predicting Safe Selection of Outpatient Arthroplasty Candidates?

BACKGROUND: Total joint arthroplasty is rapidly shifting to the outpatient space. One of the challenges of same-day discharge adoption has been determining which patients are suitable candidates. Risk assessment tools have been developed, including the Outpatient Arthroplasty Risk Assessment (OARA) score. The purpose of this study was to assess its predictive utility. METHODS: A retrospective review was performed on all total joint arthroplasties performed at a single ambulatory surgery center in 2018, yielding a cohort of 1,105 patients (1,332 arthroplasties). The institution's outpatient criteria required optimization of all medical conditions; if the patient had no failing organ, they were candidates for same-day discharge. OARA scores were calculated based on preoperative histories and physical examinations. Analyses were performed on the statistical utility of the OARA score in predicting successful same-day discharge. The mean age was 59 years (range, 27-82), the mean body mass index was 33.3 kg/m2 (range, 16-66), and 51.5% were women. A total of 45% of patients had one or more major comorbidity. RESULTS: There were 81.6% of patients who had an acceptable OARA score (<60). In addition, 97% of patients who had an "unacceptable" OARA score were successfully discharged the same day. There were 23 patients who required inpatient observation; of these, 7 (30.4%) had an OARA score ≥60. CONCLUSION: The OARA score was accurate in predicting patients who successfully had same-day discharge but poor at predicting who would not. This system is time consuming and may be too restrictive on which patients are candidates for outpatient arthroplasty. Surgeons may consider a more simplified criteria for outpatient arthroplasty.

Minimum 25-Year Results of a Tapered Titanium Porous Plasma Spray Coated Femoral Component.

BACKGROUND: Previous studies have reported excellent results with tapered, titanium, porous plasma-sprayed components in patients undergoing uncemented primary total hip arthroplasty (THA). The purpose of this study was to examine survival and clinical results at a minimum 25-year follow-up. METHODS: We reviewed all patients who underwent primary THA at our center through 1995 with a specific femoral component that was essentially unchanged since its 1984 introduction, except porous coating was continued circumferentially in 1987, a hydroxyapatite-coated option was offered in 1988, and an offset option was added in 1999. There were 332 patients (396 THA) who had a minimum 25-year follow-up (range, 25 to 37). Mean age at surgery was 48 years (range, 21 to 70 years). Mean follow-up in nonfailed patients was 29 years (range, 25 to 37 years). RESULTS: There were 31 femoral revisions (7.8%): 9 infections, 3 failures of ingrowth, 5 aseptic loosening, 8 osteolysis well-fixed, 2 periprosthetic fractures, 2 polyethylene wear with trochanteric avulsion, 1 component breakage, and 1 malalignment well-fixed. Kaplan-Meier survival with the endpoint of all-cause stem revision was 94.8% (95% confidence interval: ±0.9%) at 37 years, and with the endpoint of aseptic loosening/failure of ingrowth was 98.7% (95% confidence interval: ±0.5) at 37 years. Harris hip scores improved significantly from 43 preoperatively to 76 most recently. CONCLUSION: This tapered, titanium, porous plasma spray-coated femoral component continues to demonstrate high long-term survival with a low rate of femoral component revision for any reason or aseptic loosening/failure of ingrowth.

Custom Triflange Acetabular Components For Catastrophic Bone Loss: Minimum 5-Year Results.

INTRODUCTION: Custom acetabular components are an increasingly utilized reconstructive option in total hip arthroplasty for catastrophic bone loss and acetabular failure. The purpose of this study was to determine the survivorship of such components for reconstruction due to catastrophic bone loss at a minimum 5-year follow-up. METHODS: From August 2003 to July 2016, 64 patients (66 hips) underwent acetabular reconstruction with custom triflange components. All hips were classified as Paprosky 3B or 3C. Harris hip scores were analyzed. Overall survivorship was determined by survival analysis. RESULTS: Seventeen patients (18 hips) died prior to returning for 5-year follow-up. One presumed living patient was lost to contact, yielding a cohort of 46 patients (47 hips) who had minimum 5-year follow-up. The mean age was 65 years (range, 46 to 85), mean body mass index was 29.4 (range, 18 to 45), and 72% were women. Mean follow-up was 8 years (range, 5 to 16). There were 3 revisions of the triflange device (6.4%) due to infection. Survivorship to end point of triflange removal for any reason was 94.1% (95% confidence interval: ±3.4%) at a mean of 16 years. In the overall series (n = 66), there were 9 (13.6%) additional reoperations as follows: 5 incision and debridements, one open reduction internal fixation, two stem revisions for periprosthetic femoral fracture, and one head revision. Harris hip scores improved significantly from a mean of 41 points preoperatively to 64 points postoperatively. CONCLUSIONS: Custom acetabular triflange components represent a highly effective tool in a surgeon's armamentarium. These devices are extremely helpful in managing catastrophic bone loss and have a good mean 16-year survival.

Use of a Smartphone-Based Care Platform After Primary Partial and Total Knee Arthroplasty: 1-Year Follow-Up of a Prospective Randomized Controlled Trial.

BACKGROUND: The rise in demand of knee arthroplasty has led the industry to develop methods to decrease costs of care, such as novel methods of delivering physiotherapy, including smartphone-based exercise educational platforms. The purpose of this study was to determine the noninferiority of one such system after primary knee arthroplasty as compared to traditional in-person physiotherapy. METHODS: A prospective, multicenter randomized clinical trial was conducted comparing standard of care rehabilitation to a smartphone-based care platform after primary knee arthroplasty from January 2019 to February 2020. One-year patient outcomes, satisfaction scores, and utilizations of health care resources were analyzed. A total of 401 patients was available for analysis-241 in the control and 160 in the treatment group. RESULTS: There were 194 (94.6%) patients in the control group who required 1 or more physiotherapy visits compared to only 97 (60.6%) patients in the treatment group (P < .001). Emergency department visits within 1 year occurred in 13 (5.4%) patients and 2 (1.3%) patients in the control and treatment groups, respectively (P = .03). The change in mean Knee Injury and Osteoarthritis Outcome Score for joint replacement scores at 1 year was similar between both the groups (32.1 ± 1 6.8 versus 30.1 ± 18.1, P = .32). CONCLUSION: Implementation of this smartphone/smart watch care platform showed similar outcomes to traditional care models at 1 year postoperative. Traditional physiotherapy and emergency department visits occurred at much lower rates in this cohort, which could alleviate the need for health care dollars spent by reducing postoperative costs and enhancing communication across the health care system.

A systematic review of temporal body weight and dietary intake patterns in adults: implications on future public health nutrition interventions to promote healthy weight.

PURPOSE: The global prevalence of overweight remains high; effective strategies that consider patterns of body weight changes to identify periods when adults are susceptible to weight gain are warranted. This systematic review aimed to investigate body weight patterns, and how they were associated with dietary intake and/or dietary behaviours (Prospero CRD42020161977). METHODS: Systematic literature search was conducted in the Medline, Embase, and CINAHL databases until November 2020. Observational studies in adults (18 years and over) that reported at least two measurements of weight and dietary intake in a year were included. Risk of bias was conducted using the Evidence Analysis Library by the Academy of Nutrition and Dietetics tool. This review included 16 unique studies after title, abstract, and full-text screening, and findings were narratively synthesised. RESULTS: Of the six studies conducted in the farming populations, five were conducted in countries with two seasons (dry vs. rainy seasons) and all studies observed higher body weight during the dry season (up to 3.1 kg difference between seasons). The remaining study was conducted in a sub-tropical country and did not observe temporal weight patterns. Higher dietary intake was also reported during the dry season in the tropical countries. In non-farming populations (n = 10), temporal patterns were also seen, where higher body weight and adiposity was observed during colder seasons (autumn and winter). However, the opposite was found in a study conducted in Iran, where higher weight was seen in summer. Concurrent with higher body weight, higher energy, fat, carbohydrate and soda consumption, and lower fiber and vegetable intake were observed. CONCLUSION: Temporal weight and dietary patterns exist, and they were country- and context-specific; these patterns were also related to factors such as activity levels, seasons and occupation. Future interventions should consider temporal patterns in the design and delivery of timely and tailored dietary interventions to promote optimal body weight. PROSPERO REGISTRATION: PROSPERO Registration: CRD42020161977.

Darolutamide and survival in metastatic, hormone-sensitive prostate cancer: a patient and caregiver perspective and plain language summary of the ARASENS trial.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a publication about the ARASENS trial, which was published in the New England Journal of Medicine in February 2022. The trial includes 1,306 men with a type of prostate cancer called metastatic, hormone-sensitive prostate cancer (also called mHSPC). In the trial, researchers wanted to learn if combining a treatment called darolutamide (also known by the brand name Nubeqa®) with two other medicines called androgen deprivation therapy (also called ADT) and docetaxel (brand name Taxotere®) could help treat patients with mHSPC better than placebo plus ADT and docetaxel. ADT with docetaxel is a treatment used for patients with mHSPC. Darolutamide is an approved treatment for a different type of prostate cancer called non-metastatic, castration-resistant prostate cancer (also called nmCRPC). WHAT WERE THE RESULTS?: The trial results showed that combining darolutamide with ADT and docetaxel increased the chance of survival and lowered the risk of death by 32.5% compared to combining ADT and docetaxel with placebo instead. Compared to patients who received the placebo, patients who received darolutamide had a delay in: their cancer becoming castration-resistant worsening pain having cancer-related bone fractures or related symptoms needing additional therapies for cancer The percentage of trial patients who had medical problems during the trial, also called adverse events, was similar between trial patients who received darolutamide and those who received the placebo. WHAT DO THE RESULTS OF THE STUDY MEAN?: Combining darolutamide with ADT and docetaxel helped treat trial patients with mHSPC better than placebo with ADT and docetaxel. Darolutamide in combination with ADT and docetaxel could be a treatment option for patients with mHSPC. Patients should always talk to their doctors and nurses before making any decisions about their treatment. This summary also includes perspectives on the ARASENS trial and prostate cancer from 3 members of the patient community. ClinicalTrials.gov NCT number: NCT02799602.

Origin and implications of non-radial Imbrium Sculpture on the Moon.

Rimmed grooves, lineations and elongate craters around Mare Imbrium shape much of the nearside Moon. This pattern was coined the Imbrium Sculpture, and it was originally argued that it must have been formed by a giant oblique (~30°) impact, a conclusion echoed by later studies. Some investigators, however, noticed that many elements of the Imbrium Sculpture are not radial to Imbrium, thereby implicating an endogenic or structural origin. Here we use these non-radial trends to conclude that the Imbrium impactor was a proto-planet (half the diameter of Vesta), once part of a population of large proto-planets in the asteroid belt. Such independent constraints on the sizes of the Imbrium and other basin-forming impactors markedly increase estimates for the mass in the asteroid belt before depletion caused by the orbital migration of Jupiter and Saturn. Moreover, laboratory impact experiments, shock physics codes and the groove widths indicate that multiple fragments (up to 2% of the initial diameter) from each oblique basin-forming impactor, such as the one that formed Imbrium, should have survived planetary collisions and contributed to the heavy impact bombardment between 4.3 and 3.8 billion years ago.