Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy.

PURPOSE: Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. EXPERIMENTAL DESIGN: [225Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell-derived (22Rv1, DU145), and patient-derived (LTL-545, LTL484) prostate cancer xenograft models. Biodistribution studies were carried out on 22Rv1 tumor xenograft models to confirm the targeting efficacy. Toxicity analysis of the [225Ac]DOTA-YS5 was carried out on nu/nu mice to study short-term (acute) and long-term (chronic) toxicity. RESULTS: Biodistribution study shows that [225Ac]DOTA-YS5 agent delivers high levels of radiation to the tumor tissue (11.64% ± 1.37%ID/g, 28.58% ± 10.88%ID/g, 29.35% ± 7.76%ID/g, and 31.78% ± 5.89%ID/g at 24, 96, 168, and 408 hours, respectively), compared with the healthy organs. [225Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line-derived and patient-derived xenograft models. Toxicity analysis revealed that the 0.5 µCi activity levels showed toxicity to the kidneys, likely due to redistribution of daughter isotope 213Bi. CONCLUSIONS: [225Ac]DOTA-YS5 suppressed the growth of cell-derived and patient-derived xenografts, including prostate-specific membrane antigen-positive and prostate-specific membrane antigen-deficient models. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46-targeted radioligand therapy in prostate cancer.

EGFR-dependent suppression of synaptic autophagy is required for neuronal circuit development.

The development of neuronal connectivity requires stabilization of dynamic axonal branches at sites of synapse formation. Models that explain how axonal branching is coupled to synaptogenesis postulate molecular regulators acting in a spatiotemporally restricted fashion to ensure branching toward future synaptic partners while also stabilizing the emerging synaptic contacts between such partners. We investigated this question using neuronal circuit development in the Drosophila brain as a model system. We report that epidermal growth factor receptor (EGFR) activity is required in presynaptic axonal branches during two distinct temporal intervals to regulate circuit wiring in the developing Drosophila visual system. EGFR is required early to regulate primary axonal branching. EGFR activity is then independently required at a later stage to prevent degradation of the synaptic active zone protein Bruchpilot (Brp). Inactivation of EGFR results in a local increase of autophagy in presynaptic branches and the translocation of active zone proteins into autophagic vesicles. The protection of synaptic material during this later interval of wiring ensures the stabilization of terminal branches, circuit connectivity, and appropriate visual behavior. Phenotypes of EGFR inactivation can be rescued by increasing Brp levels or downregulating autophagy. In summary, we identify a temporally restricted molecular mechanism required for coupling axonal branching and synaptic stabilization that contributes to the emergence of neuronal wiring specificity.

Comparison and calibration of dose delivered by137Cs and x-ray irradiators in mice.

Objective.The Office of Radiological Security, U.S. Department of Energy's National Nuclear Security Administration, is implementing a radiological risk reduction program which seeks to minimize or eliminate the use of high activity radiological sources, including137Cs, by replacing them with non-radioisotopic technologies, such as x-ray irradiators. The main goal of this paper is to evaluate the equivalence of the dose delivered by gamma- and x-ray irradiators in mice using experimental measurements and Monte Carlo simulations. We also propose a novel biophantom as anin situdose calibration method.Approach.We irradiated mouse carcasses and 3D-printed mouse biophantoms in a137Cs irradiator (Mark I-68) and an x-ray irradiator (X-Rad320) at three voltages (160 kVp, 225 kVp and 320 kVp) and measured the delivered radiation dose. A Geant4-based Monte Carlo model was developed and validated to provide a comprehensive picture of gamma- and x-ray irradiation in mice.Main Results.Our Monte Carlo model predicts a uniform dose delivered in soft-tissue for all the explored irradiation programs and in agreement with the absolute dose measurements. Our Monte Carlo model shows an energy-dependent difference between dose in bone and in soft tissue that decreases as photon energy increases. Dose rate depends on irradiator and photon energy. We observed a deviation of the measured dose from the target value of up to -9% for the Mark I-68, and up to 35% for the X-Rad320. The dose measured in the 3D-printed phantoms are equivalent to that in the carcasses within 6% uncertainty.Significance.Our results suggest that 320 kVp irradiation is a good candidate to substitute137Cs irradiation barring a few caveats. There is a significant difference between measured and targeted doses for x-ray irradiation that suggests a strong need forin situcalibration, which can be achieved with 3D-printed mouse biophantoms. A dose correction is necessary for bone doses, which can be provided by a Monte Carlo calculation. Finally, the biological implications of the differences in dose rates and dose per photon for the different irradiation methods should be carefully assessed for each small-animal irradiation experiment.

Small-scale (sub-organ and cellular level) alpha-particle dosimetry methods using an iQID digital autoradiography imaging system.

Targeted radiopharmaceutical therapy with alpha-particle emitters (αRPT) is advantageous in cancer treatment because the short range and high local energy deposition of alpha particles enable precise radiation delivery and efficient tumor cell killing. However, these properties create sub-organ dose deposition effects that are not easily characterized by direct gamma-ray imaging (PET or SPECT). We present a computational procedure to determine the spatial distribution of absorbed dose from alpha-emitting radionuclides in tissues using digital autoradiography activity images from an ionizing-radiation quantum imaging detector (iQID). Data from 211At-radioimmunotherapy studies for allogeneic hematopoietic cell transplantation in a canine model were used to develop these methods. Nine healthy canines were treated with 16.9-30.9 MBq 211At/mg monoclonal antibodies (mAb). Lymph node biopsies from early (2-5 h) and late (19-20 h) time points (16 total) were obtained, with 10-20 consecutive 12-µm cryosections extracted from each and imaged with an iQID device. iQID spatial activity images were registered within a 3D volume for dose-point-kernel convolution, producing dose-rate maps. The accumulated absorbed doses for high- and low-rate regions were 9 ± 4 Gy and 1.2 ± 0.8 Gy from separate dose-rate curves, respectively. We further assess uptake uniformity, co-registration with histological pathology, and requisite slice numbers to improve microscale characterization of absorbed dose inhomogeneities in αRPT.

Fracture Risk Following an Atypical Femoral Fracture.

Atypical femoral fractures (AFFs) occurring during the course of osteoporosis treatment usually lead to discontinuation of anti-resorptive (AR) drugs. However, the risk of fracture after an AFF is unknown. We conducted a follow-up study of patients with AFF matched 1:3 for age and gender with patients with a peripheral major osteoporotic fracture (pMOF), in the setting of a fracture liaison service, to investigate the incidence of subsequent low-trauma fractures. Fifty-five patients with AFF (95% women, age [mean ± standard deviation] 75 ± 10 years, 89% exposed to AR drugs), followed for 6.2 ± 3.7 years, were compared to 165 matched controls with a pMOF (hip 85%) followed for 4.3 ± 2.6 years. During the follow-up, 38% of patients in the AFF group and 16% in the pMOF group received AR therapies. Continuation of AR drugs after an AFF was associated with contralateral AFF in 27% of subjects. The risks of new low-trauma, major osteoporotic and imminent (within 2 years) fractures, were similar between the two groups: incidence rate ratio (95% confidence interval [CI]) of subsequent fracture following AFF relative to pMOF, 1.30 (95% CI, 0.82-2.04), 1.28 (95% CI, 0.74-2.15), and 1.11 (95% CI, 0.54-2.15), respectively. Moreover, the risk of sustaining multiple fractures per participant was significantly increased among patients with AFF compared to pMOF (hazard ratio 1.48 [95% CI, 1.00-2.19]; p = 0.049). When taking mortality into account, the risk of subsequent fractures tended to be higher in the AFF group (sub-hazard ratio 1.42 [95% CI, 0.95-2.12]). In conclusion, patients who sustained an AFF are at high risk of subsequent fragility fractures, at least equal or even greater to the risk observed after a pMOF. However, continuation of AR drugs increases the risk of contralateral AFF. Therefore, optimal modalities for secondary fracture prevention after AFF require further evaluation. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Short stem total hip arthroplasty with the direct anterior approach demonstrates suboptimal fixation.

PURPOSE: Short stems use has increased substantially despite variable results reported in the literature. The purpose of this study was to report the rate of complications using a short stem implanted through the direct anterior approach (DAA), and to evaluate mid-term clinical and radiological results focusing on femoral stem fixation. METHODS: Between April 2009 and November 2014, 698 elective total hip arthroplasties (THAs) were performed using a fully hydroxyapatite-coated short stem (AMIStem-H®). The mean age was 65.7 years (SD 12.6). Patients were invited for clinical and radiological evaluation, and to complete patient-reported outcomes questionnaires at two and five years after surgery. The mean follow-up was 6.2 years (range 2-9.73 years). RESULTS: During the study period, 59 (8.5%) patients died and 24 (3.4%) were lost to follow-up. There were six (0.9%) dislocations and 12 (1.7%) fractures, seven occurred intra-operatively. Twenty-nine (4.2%) THAs required revision surgery. Eleven THAs were revised for aseptic loosening of the stem at a mean 4.9 years (1.2-7.3 years). Five years after surgery, radiographs of 324 THAs (324/425 eligible = 76.2%) were available. Stem subsidence ≥ 2 mm was present in 42 cases (12.9%), proximal radiolucencies in 101 hips (31.5%), cortical thickening in 52 (16.0%), and a pedestal in 219 (67.6%). An Engh score between - 10 and 0 was associated with lower HHS pain subscore (p = 0.005), a higher risk of stem revision for aseptic loosening (18.8% vs. 2.7%; p = 0.008), and was more frequent in younger patients with ASA score 1. CONCLUSION: Patients presenting radiological alterations at five years had an increased risk of revision for aseptic stem loosening and also inferior clinical results. Our study warrants further continued scrutiny of mid- and long-term survivorship of the AMIStem-H®, with radiological results at five years indicating suboptimal fixation of the stem in younger and active patients.

The Drosophila amyloid precursor protein homologue mediates neuronal survival and neuroglial interactions.

The amyloid precursor protein (APP) is a structurally and functionally conserved transmembrane protein whose physiological role in adult brain function and health is still unclear. Because mutations in APP cause familial Alzheimer's disease (fAD), most research focuses on this aspect of APP biology. We investigated the physiological function of APP in the adult brain using the fruit fly Drosophila melanogaster, which harbors a single APP homologue called APP Like (APPL). Previous studies have provided evidence for the implication of APPL in neuronal wiring and axonal growth through the Wnt signaling pathway during development. However, like APP, APPL continues to be expressed in all neurons of the adult brain where its functions and their molecular and cellular underpinnings are unknown. We report that APPL loss of function (LOF) results in the dysregulation of endolysosomal function in neurons, with a notable enlargement of early endosomal compartments followed by neuronal cell death and the accumulation of dead neurons in the brain during a critical period at a young age. These defects can be rescued by reduction in the levels of the early endosomal regulator Rab5, indicating a causal role of endosomal function for cell death. Finally, we show that the secreted extracellular domain of APPL interacts with glia and regulates the size of their endosomes, the expression of the Draper engulfment receptor, and the clearance of neuronal debris in an axotomy model. We propose that APP proteins represent a novel family of neuroglial signaling factors required for adult brain homeostasis.

Autophagy-dependent filopodial kinetics restrict synaptic partner choice during Drosophila brain wiring.

Brain wiring is remarkably precise, yet most neurons readily form synapses with incorrect partners when given the opportunity. Dynamic axon-dendritic positioning can restrict synaptogenic encounters, but the spatiotemporal interaction kinetics and their regulation remain essentially unknown inside developing brains. Here we show that the kinetics of axonal filopodia restrict synapse formation and partner choice for neurons that are not otherwise prevented from making incorrect synapses. Using 4D imaging in developing Drosophila brains, we show that filopodial kinetics are regulated by autophagy, a prevalent degradation mechanism whose role in brain development remains poorly understood. With surprising specificity, autophagosomes form in synaptogenic filopodia, followed by filopodial collapse. Altered autophagic degradation of synaptic building material quantitatively regulates synapse formation as shown by computational modeling and genetic experiments. Increased filopodial stability enables incorrect synaptic partnerships. Hence, filopodial autophagy restricts inappropriate partner choice through a process of kinetic exclusion that critically contributes to wiring specificity.

A neurodevelopmental origin of behavioral individuality in the Drosophila visual system.

The genome versus experience dichotomy has dominated understanding of behavioral individuality. By contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using Drosophila melanogaster, we demonstrate a link between stochastic variation in brain wiring and behavioral individuality. A visual system circuit called the dorsal cluster neurons (DCN) shows nonheritable, interindividual variation in right/left wiring asymmetry and controls object orientation in freely walking flies. We show that DCN wiring asymmetry instructs an individual's object responses: The greater the asymmetry, the better the individual orients toward a visual object. Silencing DCNs abolishes correlations between anatomy and behavior, whereas inducing DCN asymmetry suffices to improve object responses.

Neuronal strategies for meeting the right partner during brain wiring.

Two neurons can only form a synapse if their axonal and dendritic projections meet at the same time and place. While spatiotemporal proximity is necessary for synapse formation, it remains unclear to what extent the underlying positional strategies are sufficient to ensure synapse formation between the right partners. Many neurons readily form synapses with wrong partners if they find themselves at the wrong place or time. Minimally, restricting spatiotemporal proximity can prevent incorrect synapses. Maximally, restricting encounters in time and space could be sufficient to ensure correct partnerships between neurons that can form synapses promiscuously. In this review we explore recent findings on positional strategies during developmental growth that contribute to precise outcomes in brain wiring.

Clinical and radiographic predictors of acute compartment syndrome in the treatment of tibial shaft fractures: a retrospective cohort study.

BACKGROUND: The purpose of this study was to evaluate the association between epidemiological, clinical and radiographic factors of patients with tibial shaft fractures and the occurrence of acute compartment syndrome. METHODS: 270 consecutive adult patients sustaining 273 tibial shaft fractures between January 2005 and December 2009 were included in this retrospective cohort study. The outcome measure was acute compartment syndrome. Patient-related (age, sex), fracture-related (high- vs. low-energy injury, isolated trauma vs. polytrauma, closed vs. open fracture) and radiological parameters (AO/OTA classification, presence or absence of a noncontiguous tibial plateau or pilon fracture, distance from the centre of the tibial fracture to the talar dome, distance between tibial and fibular fracture if associated, and angulation, translation and over-riding of main tibial fragments) were evaluated regarding their potential association with acute compartment syndrome. Univariate analysis was performed and each covariate was adjusted for age and sex. Finally, a multivariable logistic regression model was built, and odds ratios and 95% confidence intervals were obtained. Statistical significance was defined as p < 0.05. RESULTS: Acute compartment syndrome developed in 31 (11.4%) cases. In the multivariable regression model, four covariates remained statistically significantly associated with acute compartment syndrome: polytrauma, closed fracture, associated tibial plateau or pilon fracture and distance from the centre of the tibial fracture to the talar dome ≥15 cm. CONCLUSIONS: One radiological parameter related to the occurrence of acute compartment syndrome has been highlighted in this study, namely a longer distance from the centre of the tibial fracture to the talar dome, meaning a more proximal fracture. This observation may be useful when clinical findings are difficult to assess (doubtful clinical signs, obtunded, sedated or intubated patients). However, larger studies are mandatory to confirm and refine the prediction of acute compartment syndrome occurrence. Radiographic signs of significant displacement were not found to be correlated to acute compartment syndrome development. Finally, the higher rate of acute compartment syndrome occurring in tibial shaft fractures associated to other musculoskeletal, thoraco-abdominal or cranio-cerebral injuries must raise the level of suspicion of any surgeon managing multiply injured patients.

[An update for the treatment of osteoid osteoma]. / Le point sur le traitement percutané des ostéomes ostéoïdes.

Osteoid osteoma is frequent benign tumor, descripted initially by Bergstrand in 1930 followed by Jaffe in 1935. The painful feature of the osteoid osteoma explains the specific consideration by the medical community for this entity. The debate was focused on pathologic and imaging pattern as well as the treatment modalities. Currently, the treatment options are varied and percutaneous treatment is increasingly used. The radiofrequency is widely validated as efficient method without serious adverse and with low rate of recurrence. We hope through this this work to revue the current knowledge of the treatment of osteoid osteoma.

L'ostéome ostéoïde est une tumeur osseuse bénigne relativement fréquente initialement décrite par Bergstrand en 1930, puis comme une entité propre grâce aux recherches de Jaffe en 1935. Malgré sa bénignité, elle a concentré toute l'attention des radiologues comme des cliniciens car très symptomatique. Dès lors, l'ostéome ostéoïde a fait l'objet de nombreux débats dans la communauté scientifique en particulier concernant son étiologie, ses caractéristiques pathologiques, son bilan d'imagerie et son traitement. C'est sur cette dernière question que les avancées ont été les plus marquantes et c'est ainsi que les possibilités thérapeutiques bien décrites dans la littérature apparaissent variées. Toutefois, les résultats très favorables des traitements percutanés et en particulier de la radiofréquence, de même que le faible taux de récidives et de complications de ces traitements, ont amené de nombreux pays à les considérer comme le meilleur traitement en première intention. A travers cette revue de la littérature et de notre pratique clinique, nous souhaitons rapporter les connaissances actuelles thérapeutiques en perpétuelle progression grâce au progrès technique.

Femoral head subchondral impaction on CT: what does it mean in patients with acetabular fracture?

OBJECTIVE: To evaluate the prevalence of isolated femoral head impactions associated with acetabular fractures and to assess whether impactions may be predictive of the development of delayed major complications requiring total hip arthroplasty. MATERIALS AND METHODS: A total of 128 consecutive adult patients with acetabular fracture and no femoral head fracture were included. Admission CTs were re-interpreted for the presence of hip dislocation and femoral head impactions. Radiological and clinical reports were reviewed in patients in whom conservative management of the femoral head was attempted, to determine if total hip arthroplasty was eventually required over a 48-month follow-up period. Univariate and multivariate analyses were performed to assess whether impaction is an independent predictor of failure of conservative management. RESULTS: Impaction was found in 40% of all patients (51 out of 128), in 58% of those with dislocation (19 out of 33), and in 34% of those without dislocation (32 out of 95; p < 0.05). One hundred and five patients underwent conservative management of the femoral head; 12.5% of them (13 out of 105) eventually required total hip arthroplasty. An impaction was present in 77% of the latter (10 out of 13) and in 33% of patients with successful conservative management (30 out of 92; p = 0.0042). At multivariate analysis, impaction and dislocation were significantly and independently associated with a higher risk for delayed total hip arthroplasty (odds ratio of 4.8 and 4.0 respectively). CONCLUSION: Femoral head impactions are frequently seen on CT of patients with acetabular fractures; they are independent predictive factors for the need for delayed total hip arthroplasty. They should be systematically mentioned in the CT report.

Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds.

The serum and glucocorticoid-regulated kinase (SGK) family has been implicated in the regulation of many cellular processes downstream of the PI3K pathway. It plays a crucial role in PI3K-mediated tumorigenesis, making it a potential therapeutic target for cancer. SGK family consists of three isoforms (SGK1, SGK2, and SGK3), which have high sequence homology in the kinase domain and similar substrate specificity with the AKT family. In order to identify novel compounds capable of inhibiting SGK3 activity, a high-throughput screening campaign against 50,400 small molecules was conducted using a fluorescence-based kinase assay that has a Z' factor above 0.5. It identified 15 hits (including nitrogen-containing aromatic, flavone, hydrazone, and naphthalene derivatives) with IC50 values in the low micromolar to sub-micromolar range. Four compounds with a similar scaffold (i.e., a hydrazone core) were selected for structural modification and 18 derivatives were synthesized. Molecular modeling was then used to investigate the structure-activity relationship (SAR) and potential protein-ligand interactions. As a result, a series of SGK inhibitors that are active against both SGK1 and SGK3 were developed and important functional groups that control their inhibitory activity identified.

High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds.

The phosphatidylinositol 3-kinase (PI3K) pathway is involved in many cellular functions including cell growth, metabolism, and transformation. Hyperactivation of this pathway contributes to tumorigenesis, therefore, PI3K is a major target for anticancer drug discovery. Since the PI3Kα isoform is implicated mostly in cancer, we conducted a high-throughput screening (HTS) campaign using a 3-step PI3K homogenous time-resolved fluorescence assay against this isoform bearing the H1047R mutation. A total of 288,000 synthetic and natural product-derived compounds were screened and of which, we identified 124 initial hits that were further selected by considering the predicted binding mode, relationship to known pan-assay interference compounds and previous descriptions as a lipid kinase inhibitor. A total of 24 compounds were then tested for concentration-dependent responses. These hit compounds provide novel scaffolds that can potentially be optimized to create novel PI3K inhibitors.

Rab GTPases and Membrane Trafficking in Neurodegeneration.

Defects in membrane trafficking are hallmarks of neurodegeneration. Rab GTPases are key regulators of membrane trafficking. Alterations of Rab GTPases, or the membrane compartments they regulate, are associated with virtually all neuronal activities in health and disease. The observation that many Rab GTPases are associated with neurodegeneration has proven a challenge in the quest for cause and effect. Neurodegeneration can be a direct consequence of a defect in membrane trafficking. Alternatively, changes in membrane trafficking may be secondary consequences or cellular responses. The secondary consequences and cellular responses, in turn, may protect, represent inconsequential correlates or function as drivers of pathology. Here, we attempt to disentangle the different roles of membrane trafficking in neurodegeneration by focusing on selected associations with Alzheimer's disease, Parkinson's disease, Huntington's disease and selected neuropathies. We provide an overview of current knowledge on Rab GTPase functions in neurons and review the associations of Rab GTPases with neurodegeneration with respect to the following classifications: primary cause, secondary cause driving pathology or secondary correlate. This analysis is devised to aid the interpretation of frequently observed membrane trafficking defects in neurodegeneration and facilitate the identification of true causes of pathology.

Live Observation of Two Parallel Membrane Degradation Pathways at Axon Terminals.

Neurons are highly polarized cells that require continuous turnover of membrane proteins at axon terminals to develop, function, and survive. Yet, it is still unclear whether membrane protein degradation requires transport back to the cell body or whether degradation also occurs locally at the axon terminal, where live observation of sorting and degradation has remained a challenge. Here, we report direct observation of two cargo-specific membrane protein degradation mechanisms at axon terminals based on a live-imaging approach in intact Drosophila brains. We show that different acidification-sensing cargo probes are sorted into distinct classes of degradative "hub" compartments for synaptic vesicle proteins and plasma membrane proteins at axon terminals. Sorting and degradation of the two cargoes in the separate hubs are molecularly distinct. Local sorting of synaptic vesicle proteins for degradation at the axon terminal is, surprisingly, Rab7 independent, whereas sorting of plasma membrane proteins is Rab7 dependent. The cathepsin-like protease CP1 is specific to synaptic vesicle hubs, and its delivery requires the vesicle SNARE neuronal synaptobrevin. Cargo separation only occurs at the axon terminal, whereas degradative compartments at the cell body are mixed. These data show that at least two local, molecularly distinct pathways sort membrane cargo for degradation specifically at the axon terminal, whereas degradation can occur both at the terminal and en route to the cell body.

The where, what, and when of membrane protein degradation in neurons.

Membrane protein turnover and degradation are required for the function and health of all cells. Neurons may live for the entire lifetime of an organism and are highly polarized cells with spatially segregated axonal and dendritic compartments. Both longevity and morphological complexity represent challenges for regulated membrane protein degradation. To investigate how neurons cope with these challenges, an increasing number of recent studies investigated local, cargo-specific protein sorting, and degradation at axon terminals and in dendritic processes. In this review, we explore the current answers to the ensuing questions of where, what, and when membrane proteins are degraded in neurons. © 2017 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 283-297, 2018.

Comparison of dual-mobility cup and unipolar cup for prevention of dislocation after revision total hip arthroplasty.

Background and purpose - Revision total hip arthroplasty (THA) is associated with higher dislocation rates than primary THA. We compared the risk of dislocation within 6 months and all-cause re-revision during the whole study period using either the dual-mobility cup or the unipolar cup. Methods - We used a prospective hospital registry-based cohort including all total and cup-only revision THAs performed between 2003 and 2013. The cups used were either dual-mobility or unipolar; the choice was made according to the preference of the surgeon. 316 revision THAs were included. The mean age of the cohort was 69 (25-98) years and 160 THAs (51%) were performed in women. The dual-mobility group (group 1) included 150 THAs (48%) and the mean length of follow-up was 31 (0-128) months. The unipolar group (group 2) included 166 THAs (53%) and the mean length of follow-up was 52 (0-136) months. Results - The incidence of dislocation within 6 months was significantly lower with the dual-mobility cup than with the unipolar cup (2.7% vs. 7.8%). The unadjusted risk ratio (RR) was 0.34 (95% CI: 0.11-1.02) and the adjusted RR was 0.28 (95% CI: 0.09-0.87). The number of patients needed to treat with a dual-mobility cup in order to prevent 1 case of dislocation was 19. The unadjusted incidence rate ratio for all-cause re-revision in the dual-mobility group compared to the unipolar group was 0.6 (95% CI: 0.3-1.4). Interpretation - Use of a dual-mobility rather than a unipolar cup in revision THA reduced the risk of dislocation within 6 months.

Pigmented villonodular synovitis of the hip.

Pigmented villonodular synovitis (PVNS) is a rare disease that can affect any joint, bursa or tendon sheath.The hip is less frequently affected than the knee, and hence is less discussed in scientific journals.PVNS of the hip mainly occurs in young adults, requiring early diagnosis and adequate treatment to obtain good results.There is no consensus on the management of PVNS of the hip in current literature.We will discuss the options for surgical intervention in hip PVNS using a literature review of clinical, biological, etiological, histological and radiographic aspects of the disease. Cite this article: Steinmetz S, Rougemont A-L, Peter R. Pigmented villonodular synovitis of the hip. EFORT Open Rev 2016;1:260-266. DOI: 10.1302/2058-5241.1.000021.