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The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test new therapies in vivo. Here the authors present a tissue bioengineering strategy for the study of a rare kidney tumor called angiomyolipoma, in vitro and in vivo, using patient-derived hiPSCs.

Chemical dynamics in molecules involve particle migration and bond rearrangement. Here the authors show single and double hydrogen migration in ethanol cations and dications that are generated by using intense laser pulse interaction with a jet of ethanol molecules.

Cell transplantation therapies for central nervous system (CNS) deficits such as spinal cord injury (SCI) have been shown to be effective in several animal models. One cell type that has been transplanted is neural precursor cells (NPCs), for which there are several possible sources. We have studied NPCs derived from human embryonic stem cells (hESCs) and human fetal CNS tissue (hfNPCs), cultured as neurospheres, and the expression of pluripotency and neural genes during neural induction and in vitro differentiation. mRNA for the pluripotency markers Nanog , Oct-4 , Gdf3 , and DNMT3b were downregulated during neural differentiation of hESCs. mRNA for these markers was found in nonpluripotent hfNPC at higher levels compared to hESC-NPCs. However, Oct-4 protein was found in hESC-NPCs after 8 weeks of culture, but not in hfNPCs. Similarly, SSEA-4 and CD326 were only found in hESC-NPCs. NPCs from both sources differentiated as expected to cells with typical features of neurons and astrocytes. The expressions of neuronal markers in hESC-NPCs were affected by the composition of cell culture medium, while this did not affect hfNPCs. Transplantation of hESC-NPC or hfNPC neurospheres into immunodeficient mouse testis or subcutaneous tissue did not result in tumor formation. In contrast, typical teratomas appeared in all animals after transplantation of hESC-NPCs to injured or noninjured spinal cords of immunodeficient rats. Our data show that transplantation to the subcutaneous tissue or the testes of immunodeficient mice is not a reliable method for evaluation of the tumor risk of remaining pluripotent cells in grafts.

AbstractSpinal cord injury (SCI) results in immediate disruption of the spinal vascular network, triggering an ischemic environment and initiating secondary degeneration. Promoting angiogenesis and vascular stability through the induction of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), respectively, provides a possible therapeutic approach in treating SCI. We examined whether supplementing the injured environment with these two factors, which are significantly reduced following injury, has an effect on lesion size and functional outcome. Sustained delivery of both VEGF165and Ang-1 was realized using viral vectors based on the adeno-associated virus (AAV), which were injected directly into the lesion epicenter immediately after injury. Our results indicate that the combined treatment with VEGF and Ang-1 resulted in both reduced hyperintense lesion volume and vascular stabilization, as determined by magnetic resonance imaging (MRI). Western blot analysis indicated that the viral vector expression was maintained into the chronic phase of injury, and that the use of the AAV vectors did not exacerbate infiltration of microglia into the lesion epicenter. The combined treatment with AAV-VEGF and AAV-Ang-1 improved locomotor recovery in the chronic phase of injury. These results indicate that combining angiogenesis with vascular stabilization may have potential therapeutic applications following SCI. [ABSTRACT FROM AUTHOR]

AbstractComprehensive in vivolongitudinal studies that include multi-modal magnetic resonance imaging (MRI) and a battery of behavioral assays to assess functional outcome were performed at multiple time points up to 56 days post-traumatic spinal cord injury (SCI) in rodents. The MRI studies included high-resolution structural imaging for lesion volumetry, and diffusion tensor imaging (DTI) for probing the white matter integrity. The behavioral assays included open-field locomotion, grid walking, inclined plane, computerized activity box performance, and von Frey filament tests. Additionally, end-point histology was assessed for correlation with both the MRI and behavioral data. The temporal patterns of the lesions were documented on structural MRI. DTI studies showed significant changes in white matter that is proximal to the injury epicenter and persisted to day 56. White matter in regions up to 1 cm away from the injury epicenter that appeared normal on conventional MRI also exhibited changes that were indicative of tissue damage, suggesting that DTI is a more sensitive measure of the evolving injury. Correlations between DTI and histology after SCI could not be firmly established, suggesting that injury causes complex pathological changes in multiple tissue components that affect the DTI measures. Histological evidence confirmed a significant decrease in myelin and oligodendrocyte presence 56 days post-SCI. Multiple assays to evaluate aspects of functional recovery correlated with histology and DTI measures, suggesting that damage to specific white matter tracts can be assessed and tracked longitudinally after SCI. [ABSTRACT FROM AUTHOR]

AbstractVascular endothelial growth factor (VEGF)-A mRNA was previously identified as one of the significantly upregulated transcripts in spinal cord injured tissue from adult rats that developed allodynia. To characterize the role of VEGF-A in the development of pain in spinal cord injury (SCI), we analyzed mechanical allodynia in SCI rats that were treated with either vehicle, VEGF-A isoform 165 (VEGF165), or neutralizing VEGF165-specific antibody. We have observed that exogenous administration of VEGF165increased both the number of SCI rats that develop persistent mechanical allodynia, and the level of hypersensitivity to mechanical stimuli. Our analysis identified excessive and aberrant growth of myelinated axons in dorsal horns and dorsal columns of chronically injured spinal cords as possible mechanisms for both SCI pain and VEGF165-induced amplification of SCI pain, suggesting that elevated endogenous VEGF165may have a role in the development of allodynia after SCI. However, the neutralizing VEGF165antibody showed no effect on allodynia or axonal sprouting after SCI. It is possible that another endogenous VEGF isoform activates the same signaling pathway as the exogenously-administered 165 isoform and contributes to SCI pain. Our transcriptional analysis revealed that endogenous VEGF188is likely to be the isoform involved in the development of allodynia after SCI. To the best of our knowledge, this is the first study to suggest a possible link between VEGF, nonspecific sprouting of myelinated axons, and mechanical allodynia following SCI. [ABSTRACT FROM AUTHOR]

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas nucleases and human induced pluripotent stem cell (iPSC) technology can reveal deep insight into the genetic and molecular bases of human biology and disease. Undesired editing outcomes, both on-target (at the edited locus) and off-target (at other genomic loci) hinder the application of CRISPR-Cas nucleases. We developed Off-flow, a Nextflow-coded bioinformatic workflow that takes a specific guide sequence and Cas protein input to call four separate off-target prediction programs (CHOPCHOP, Cas-Offinder, CRISPRitz, CRISPR-Offinder) to output a comprehensive list of predicted off-target sites. We applied it to whole genome sequencing (WGS) data to investigate the occurrence of unintended effects in human iPSCs that underwent repair or insertion of disease-related variants by homology-directed repair. Off-flow identified a 3-base-pair-substitution and a mono-allelic genomic deletion at the target loci, KCNQ2 , in 2 clones. Unbiased WGS analysis further identified off-target missense variants and a mono-allelic genomic deletion at the targeted locus, GNAQ, in 10 clones. On-target substitution and deletions had escaped standard PCR and Sanger sequencing analysis, while missense variants at other genomic loci were not detected by Off-flow. We used these results to filter out iPSC clones for subsequent functional experiments. Off-flow, which we make publicly available, works for human and mouse genomes currently and can be adapted for other genomes. Off-flow and WGS analysis can improve the integrity of studies using CRISPR/Cas-edited cells and animal models., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Despite high prevalence of cardiovascular disease (CVD) and CVD risk factors among American Indian or Alaska Native adults (AI/AN), there is little information on aspirin use in this population. This survey-based study seeks to understand prevalence of aspirin use in a sample of AI/AN adults in the Upper Midwestern United States. In-person and telephone based surveys were conducted querying self-reported CVD and CVD risk factors, aspirin use, and aspirin related discussion with clinicians. A total of 237 AI/AN participants were included: mean age (SD) was 60.8 (8.4) years; 143 (60 %) were women; 59 (25 %) reported CVD history. CVD risk factors were common particularly smoking (37 %) and diabetes (37 %). Aspirin use was much higher among those with CVD (secondary prevention, 76 %) than those without (primary prevention, 33 %). Primary prevention aspirin use was significantly associated with age and all CVD risk factors in unadjusted analyses. After adjustment for demographics and CVD risk factors, only age (aRR 1.13 per 5 years, 95 % CI 1.02, 1.25) and diabetes (aRR 2.44, 95 % CI 1.52, 3.92) remained significantly associated with aspirin. Regardless of CVD status, a higher proportion of those taking aspirin reported a conversation about aspirin with their doctor compared to those not taking aspirin. Among participants with no CVD, those who had such a conversation were 2.6 times more likely to use aspirin than those who did not have a conversation (aRR 2.64, 95 % CI 1.58, 4.44). The findings of this study emphasize the importance of the patient-provider relationship for preventive therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. TSC is caused by mutations in the TSC1 or TSC2 genes, which encode the hamartin/tuberin proteins respectively. These proteins function as a heterodimer that negatively regulates the mechanistic Target of Rapamycin Complex 1 (mTORC1). TSC research has focused on the effects of mTORC1, a critical signaling hub, on regulation of diverse cell processes including metabolism, cell growth, translation, and neurogenesis. However, non-canonical functions of TSC2 are not well studied, and the potential disease-relevant biological mechanisms of mutations affecting these functions are not well understood. We observed aberrant multipolar mitotic division, a novel phenotype, in TSC2 mutant iPSCs. The multipolar phenotype is not meaningfully affected by treatment with the inhibitor rapamycin. We further observed dominant negative activity of the mutant form of TSC2 in producing the multipolar division phenotype. These data expand the knowledge of TSC2 function and pathophysiology which will be highly relevant to future treatments for patients with TSC., Competing Interests: MS reports grant support from Novartis, Biogen, Astellas, Aeovian, Bridgebio, and Aucta. He has served on Scientific Advisory Boards for Novartis, Roche, Regenxbio, SpringWorks Therapeutics, Jaguar Therapeutics and Alkermes. The other authors have no competing interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Chalkley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Mentorship increases trainee productivity, promotes career satisfaction and reduces burnout. Beginning in 2016, our Medicine-Paediatrics residency program developed and implemented a longitudinal mentorship curriculum among trainees. We report initial experiences with that program and discuss potential future directions., Curriculum Structure and Method of Implementation: We implemented and adapted a peer mentorship model and expanded it to include guest lectures and workshops centred around 13 core topics. Our expanded model included five longitudinal components: (1) peer mentorship; (2) virtual check-ins with residency leadership; (3) focussed didactics and workshops; (4) small-group dinners highlighting different career paths; and (5) dedicated faculty who pair residents with mentors based on common interests. We compared annual survey results on resident satisfaction with program mentorship, using chi-square and fisher's exact tests to assess statistically significant differences pre- (2012-2016) and post-intervention (2016-2020)., Results: We analysed 112 responses with annual response rate varying between 41.2% and 100%. Overall satisfaction with mentorship improved from 57.6% to 73.4% ( p  = .53), satisfaction with emotional support improved from 63.1% to 71.6% ( p  = .21), and satisfaction with career-specific mentorship improved from 48.5% to 59.5% ( p  = .70). Residents reported consistently high satisfaction with peer mentorship (77.8%-100%). The percent of residents reporting they had identified a career mentor increased from 60.0% in 2017 to 88.9% in 2019, which was sustained at 90.0% in 2020., Conclusion: We report our experience in implementing and adapting a mentorship curriculum for resident physicians in a single training program, including transitioning to a primarily online-based platform at the outset of the SARS-CoV-2 pandemic. Our results showed a trend towards improvement in resident satisfaction with overall and career-specific mentorship, as well as improved emotional support. Future work is needed using more objective outcome markers among a larger and more diverse group of residents. KEY MESSAGESAmong resident physicians in a single training program, a mix of mentor-mentee dyads, group-based peer mentoring and a structured curriculum has shown promise in improving resident-reported satisfaction with programmatic mentorshipWhile we attempted to adapt the mentorship curriculum to an online platform with the development of the SARS-CoV-2 pandemic, reported satisfaction in overall mentorship and emotional support decreased in comparison to the prior year, an important focus for future work.

Background and purpose - Vitamin E infused highly cross-linked polyethylene (VEPE) was introduced in order to enhance oxidative resistance in highly cross-linked polyethylene cups in total hip arthroplasty (THA). We have, with a follow-up of 5 years, evaluated wear characteristics of 2 identically designed cemented cups with the only difference being the material, VEPE or ultra-high molecular weight polyethylene (UHMWPE). Furthermore, we report cup migration and clinical outcome. Patients and methods - 48 patients with primary osteoarthritis were randomized to either UHMWPE or VEPE cups. Patients were followed with radiostereometric analysis (RSA) from the first postoperative day, at 3 months, 1, 2, and 5 years as well as with hip-specific outcome questionnaires. Results - At 3 months the mean proximal head penetration for UHMWPE was 0.07 mm (95% CI 0.03-0.11) and for VEPE 0.06 mm (-0.01 to 0.13). Thereafter, there was a continuous annual wear of 0.08 mm/year, up to 0.46 mm (0.36-0.57) at 5 years, for the UHMWPE cup. The VEPE cup showed low annual wear of 0.01 mm/year, up to 0.09 mm (0.02-0.16) at 5 years. In the first 3 months the UHMWPE cup migrated cranially 0.08 mm (0.03-0.13) whereas the VEPE cup migrated 0.17 mm (0.10-0.24), Thereafter, they showed similar migration patterns with stabilization between 2 and 5 years up to 0.21 mm (0.04-0.39) and 0.24 mm (0.13-0.36) respectively. The HOOS remained good up to 5 years, and no cup was revised. Interpretation - Compared with otherwise identical UHMWPE cups the cemented VEPE cup shows statistically significant reduction of wear up to 5 years and both cup types stabilize well with good clinical outcome.

Purpose: The purpose of this article is to highlight the paradigm shift away from the typical model of direct service delivery of consistent frequency and duration in the school setting to accommodate an intensive progressive resistive exercise intervention. School-based physical therapists describe how they applied an evidence-based intensive intervention with multiple students in an urban public school district., Summary of Key Points: The school-based physical therapists had to modify the typical service delivery model and overcome other challenges to implement this intensive intervention approach. Substantial improvements in strength and functional activities were observed in multiple students and measured across several months., Conclusions and Recommendations for Clinical Practice: An intensive intervention model appears effective and feasible in the school setting. Evidence-based intervention approaches should be considered when the student could benefit., Video Abstract: For more insights from the authors, see Supplemental Digital Content 1, available at: http://links.lww.com/PPT/A339., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2 -/- hiPSCs but not from isogenic TSC2 +/- or TSC2 +/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2 -/- renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo., (© 2021. The Author(s).)

Background and purpose - Cup wear in total hip arthroplasty (THA) can be affected by different manufacturing processes of the polyethylene (PE). We report the long-term wear pattern differences, as well as early creep behavior, between conventional PE and highly cross-linked PE (HXLPE) liners, as measured with radiostereometry (RSA) up to 10 years. We also compare migration and clinical outcome of 2 similar uncemented cups with different backside surface roughness.Patients and methods - We included 45 patients with primary osteoarthritis. 23 received a conventional liner and 22 an HXLPE liner in a similar uncemented cup, but with a slightly rougher surface. The patients were followed up with RSA and hip-specific outcome questionnaire (HOOS) at 3 months, 1, 2, 5, and 10 years.Results - During the first 3 months both liners showed expected deformation with mean proximal head penetration of 0.39 mm (conventional PE) and 0.21 mm (HXLPE). Between 3 months and 10 years there was a difference in annual wear with 0.12 mm/year for the conventional liner and 0.02 mm/year for the HXLPE liner. The cup with rougher surface had less initial migration but both types had stabilized after 3 months. The HOOS scores improved after surgery and remained high for both groups throughout the study period.Interpretation - Up to 10 years the HXLPE has consistent lower annual wear, possibly contributing to longer survival of the THA, compared with conventional PE. All patients reported good results regardless of liner type.

Tuberous sclerosis complex (TSC) is a genetic disorder that is associated with multiple neurological manifestations. Previously, we demonstrated that Tsc1 loss in cerebellar Purkinje cells (PCs) can cause altered social behavior in mice. Here, we performed detailed transcriptional and translational analyses of Tsc1 -deficient PCs to understand the molecular alterations in these cells. We found that target transcripts of the Fragile X Mental Retardation Protein (FMRP) are reduced in mutant PCs with evidence of increased degradation. Surprisingly, we observed unchanged ribosomal binding for many of these genes using translating ribosome affinity purification. Finally, we found that multiple FMRP targets, including SHANK2, were reduced, suggesting that compensatory increases in ribosomal binding efficiency may be unable to overcome reduced transcript levels. These data further implicate dysfunction of FMRP and its targets in TSC and suggest that treatments aimed at restoring the function of these pathways may be beneficial., Competing Interests: JD, KW, CS, MS, AS, TP, PZ, WP No competing interests declared, MM Meghan T. Miller is affiliated with Roche Pharma Research and Early Development, Neuroscience and Rare Diseases and Skyhawk Therapeutics. The author has no financial interests to declare, MTM is now an employee of Skyhawk Therapeutics. MS Mustafa Sahin reports grant support from Novartis, Roche, Biogen, Astellas, Aeovian, Bridgebio, Aucta and Quadrant Biosciences. He has served on Scientific Advisory Boards for Novartis, Roche, Celgene, Regenxbio, Alkermes and Takeda., (© 2021, Dalal et al.)

Reciprocal copy number variations (CNVs) of 16p11.2 are associated with a wide spectrum of neuropsychiatric and neurodevelopmental disorders. Here, we use human induced pluripotent stem cells (iPSCs)-derived dopaminergic (DA) neurons carrying CNVs of 16p11.2 duplication (16pdup) and 16p11.2 deletion (16pdel), engineered using CRISPR-Cas9. We show that 16pdel iPSC-derived DA neurons have increased soma size and synaptic marker expression compared to isogenic control lines, while 16pdup iPSC-derived DA neurons show deficits in neuronal differentiation and reduced synaptic marker expression. The 16pdel iPSC-derived DA neurons have impaired neurophysiological properties. The 16pdel iPSC-derived DA neuronal networks are hyperactive and have increased bursting in culture compared to controls. We also show that the expression of RHOA is increased in the 16pdel iPSC-derived DA neurons and that treatment with a specific RHOA-inhibitor, Rhosin, rescues the network activity of the 16pdel iPSC-derived DA neurons. Our data suggest that 16p11.2 deletion-associated iPSC-derived DA neuron hyperactivation can be rescued by RHOA inhibition.

Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation., Methods: Data were collected from the Swedish Hip and Knee Arthroplasty Registers (SHAR and SKAR), including 67,913 THR and 59,268 TKR operations from 2011 to 2015 on patients with osteoarthritis. Operations from 2011 to 2015 Revision and mortality in the fast-track group were compared with non-fast-track using Kaplan-Meier survival analysis and Cox regression analysis with adjustments., Results: The hazard ratio (HR) for revision within 2 years after THR with fast-track was 1.19 (CI: 1.03-1.39), indicating increased risk, whereas no increased risk was found in TKR (HR 0.91; CI: 0.79-1.06). The risk of death within 2 years was estimated with a HR of 0.85 (CI: 0.74-0.97) for TKR and 0.96 (CI: 0.85-1.09) for THR in fast-track hospitals compared to non-fast-track., Conclusions: Fast-track programs at Swedish hospitals were associated with an increased risk of revision in THR but not in TKR, while we found the mortality to be lower (TKR) or similar (THR) as compared to non-fast track.

We present a novel metric for measuring relative connection between parts of a city using geotagged Twitter data as a proxy for co-occurrence of city residents. We find that socioeconomic similarity is a significant predictor of this connectivity metric, which we call "linkage strength": neighborhoods that are similar to one another in terms of residents' median income, education level, and (to a lesser extent) immigration history are more strongly connected in terms of the of people who spend time there, indicating some level of homophily in the way that individuals choose to move throughout a city's districts., Competing Interests: We have received funding from three commercial sources: Dover Corporation, Teck Resources, and Ford. They have not participated in this project in any way, including the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author MN, an employee of Stockholm Stads, assisted with data collection and reviewed this manuscript before submission. This funding source and employment relationship, respectively, do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and purpose - Modular-neck hip stems have been identified with corrosion-related problems from the neck-stem junction. We report an ongoing varus deformity of modular-neck hip stems with simultaneous metal ion release observed during a study comparing the migration of modular vs. standard hip stems.Patients and methods - We followed 50 patients with modular and 25 with standard neck stems using radiostereometry (RSA). At 5-year follow-up, we noted a compromised integrity of the modular stem with varus deformity in the neck-stem interface. Changes in head-tip distance as well as whole-blood ion concentration and MRI findings were analyzed. The modular stems were followed further up to 8 years.Results - The head-tip distance decreased continuously by 0.15 mm per year resulting in 1.2 (95% CI 1.0-1.4) mm at 8 years for modular stems, while for the standard stems at 5 years, the decrease was 0.09 (CI 0.0-0.2) mm or 0.02 mm/year. For the modular stems, the reduction in head-tip distance correlated to the increase in whole-blood cobalt concentration at 8 years but not to the MRI grading of tissue reactions. At 5 years, cobalt levels were 4.9 µg/L for modular stems and at 8 years 4.8 µg/L, whereas for standard stems this was 1.0 µg/L. After 8 years, 9 of 72 stems had been revised for different reasons, but only 1 with obvious adverse local tissue reaction (ALTR).Interpretation - We present a surprisingly large progressive deformation at the modular neck-stem junction, but so far without a definite clinical problem. Even the femoral head seems to show slight compression onto the taper over time. A high rate of revisions for the modular type of this stem has raised general concerns, and it has been recalled from the market.

Background: Restoration of a correct biomechanical situation after total hip arthroplasty is important., Purpose: To evaluate proximal femoral symmetry of acetabular and femoral offset and femoral neck anteversion pre- and postoperatively in hip arthroplasty by semi-automated 3D-CT and to validate the software measurements by inter- and intraobserver agreement calculations., Material and Methods: In low-dose CT on 71 patients before and after unilateral total hip arthroplasty, two observers used a digital 3D templating software to measure acetabular offset, true and functional femoral offset, and femoral neck anteversion. Observer agreements were calculated using intraclass correlation. Hip measurements were compared in each patient and between pre- and postoperative measurements., Results: Preoperatively, acetabular offset (2.4 mm), true (2.2 mm), and functional global offset (2.7 mm) were significantly larger on the osteoarthritic side without side-to-side differences for true and functional femoral offset or femoral neck anteversion. Postoperatively, acetabular offset was significantly smaller on the operated side (2.1 mm) with a concomitantly increased true (2.5 mm) and functional femoral offset (1.5 mm), resulting in symmetric true and functional global offsets. There were no differences in postoperative femoral neck anteversion. Inter- and intraobserver agreements were near-perfect, ranging between 0.92 and 0.98 with narrow confidence intervals (0.77-0.98 to 0.94-0.99)., Conclusion: Acetabular and concomitantly global offset are generally increased in hip osteoarthritis. Postoperative acetabular offset was reduced, and femoral offset increased to maintain global offset. 3D measurements were reproducible with near-perfect observer agreements. 3D data sets should be used for pre- and postoperative measurements in hip arthroplasty., (© The Foundation Acta Radiologica 2020.)

Background and purpose - Rates of knee replacement (KR) are increasing worldwide. Based on population and practice changes, there are forecasts of a further exponential increase in primary knee replacement through to 2030, and a corresponding increase in revision knee replacement. We used registry data to document changes in KR over the past 15 years, comparing practice changes across Sweden, Australia, and the United States. This may improve accuracy of future predictions.Patients and methods - Aggregated data from the Swedish Knee Arthroplasty Register (SKAR), the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), and the Kaiser Permanente Joint Replacement Registry (KPJRR) were used to compare surgical volume of primary and revision KR from 2003 to 2017. Incidence was calculated using population census statistics from Statistics Sweden and the Australian Bureau of Statistics, as well as the yearly active membership numbers from Kaiser Permanente. Further analysis of KR by age < 65 and ≥ 65 years was carried out.Results - All registries recorded an increase in primary and revision KR, with a greater increase seen in the KPJRR. The rate of increase slowed during the study period. In Sweden and Australia, there was a smaller increase in revision surgery compared with primary procedures. There was consistency in the mean age at surgery, with a steady small decrease in the proportion of women having primary KR. The incidence of KR in the younger age group remained low in all 3 registries, but the proportional increases were greater than those seen in the ≥ 65 years of age group.Interpretation - There has been a generalized deceleration in the rate of increase of primary and revision KR. While there are regional differences in KR incidence, and rates of change, the rate of increase does not seem to be as great as previously predicted.

Background: Inferior placement of a femoral stem is predictive for early loosening and failure, but does restoration of the original hip anatomy benefit the function and survival of a total hip replacement?, Methods: Seventy-five patients with primary unilateral hip osteoarthritis operated with an uncemented anatomical stem were randomized for either standard or modular stems. We used 50 ABG II stems with modular necks and 25 standard stems (control group). We measured the symmetry in hip anatomy between healthy and operated side. The anatomical restoration variables were anteversion, global offset, and femoral offset/acetabular offset (FO/AO) quota. We performed measurements using a CT-based 3D templating and measuring software. Migratory behavior of the stems was then measured postoperatively with repeated radiostereometry (RSA) examinations over 5 years., Results: Both stem types showed an early (within 3 months) good stabilization after an initial slight rotation into retroversion and subsidence. There were no significant differences in RSA migration between modular and standard stems. Postoperative anteversion and FO/AO quota had no impact on stem migration. The standard stem tended to result in insufficient global offset (GO), whereas the modular stem did not., Conclusions: The modular stem gave good symmetrical anatomical restoration and, like the standard version, a benign migratory behavior. Anteversion, GO, and FO/AO quota had no significant impact on stem migration. It therefore seems to be of no importance whether we choose a modular or a standard stem with regard to postoperative stem migration for this stem type. We overestimated the effect anatomical parameters have on stem movement; hence, we believe the study to be underpowered., Trial Registration: ClinicalTrials.gov identifier: NCT01512550. Registered 19 January 2012-retrospectively registered.

Background and purpose - Fast-track care programs have been broadly introduced at Swedish hospitals in elective total hip and knee replacement (THR/TKR). We studied the influence of fast-track programs on patient-reported outcomes (PROs) 1 year after surgery, by exploring outcome measures registered in the Swedish arthroplasty registers.Patients and methods - Data were obtained from the Swedish Knee and Hip Arthroplasty Registers and included TKR and THR operations 2011-2015 on patients with osteoarthritis. Based on questionnaires concerning the clinical pathway and care programs at Swedish hospitals, the patients were divided in 2 groups depending on whether they had been operated in a fast-track program or not. PROs of the fast-track group were compared with not fast-track using regression analysis. EQ-5D, EQ VAS, Pain VAS, and Satisfaction VAS were analyzed for both THR and TKR operations. The PROMs for TKR also included KOOS.Results - The differences of EQ-5D, EQ VAS, Pain VAS, and Satisfaction VAS 1 year after surgery were small but all in favor of fast-track for both THR and TKR, also in subscales of KOOS for TKR except KOOS QoL. However, the effect sizes as measured by Cohens' d formula were < 0.2 for all PROs, in both THR and TKR.Interpretation - Our results indicate that the fast-track programs may be at least as good as conventional care from the perspective of PROs 1-year postoperatively.