The Developmental Rules of Neural Superposition in Drosophila.

Complicated neuronal circuits can be genetically encoded, but the underlying developmental algorithms remain largely unknown. Here, we describe a developmental algorithm for the specification of synaptic partner cells through axonal sorting in the Drosophila visual map. Our approach combines intravital imaging of growth cone dynamics in developing brains of intact pupae and data-driven computational modeling. These analyses suggest that three simple rules are sufficient to generate the seemingly complex neural superposition wiring of the fly visual map without an elaborate molecular matchmaking code. Our computational model explains robust and precise wiring in a crowded brain region despite extensive growth cone overlaps and provides a framework for matching molecular mechanisms with the rules they execute. Finally, ordered geometric axon terminal arrangements that are not required for neural superposition are a side product of the developmental algorithm, thus elucidating neural circuit connectivity that remained unexplained based on adult structure and function alone.

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.

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.

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.

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.

[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.

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.

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.

Increased risk of joint failure in hip prostheses infected with Staphylococcus aureus treated with debridement, antibiotics and implant retention compared to Streptococcus.

PURPOSE: The debridement, antibiotic and implant retention (DAIR) procedure is an option for patients with prosthetic hip joint infections for whom arthroplasty removal is problematic. Unfortunately, some of the guidelines proposed for deciding on DAIR management of arthroplasty infections fail to take into consideration the role of the infecting pathogen. While Staphylococcus aureus and streptococci are major contributors to infected hip arthroplasties, their respective contributions to treatment success or failure rates with the DAIR procedure have not been thoroughly analysed from a microbiological perspective. METHODS: This retrospective study included all patients who were hospitalised in Geneva University Hospitals between 1996 and 2012 and were initially treated with DAIR for prosthetic hip joint monomicrobial infection due to S. aureus or Streptococcus spp. The outcome of DAIR treatment was evaluated after a minimal follow-up of two years. A literature search was also performed to retrieve data from additional DAIR-treated cases in other institutions. RESULTS: In our institution, 38 DAIR-treated patients with hip arthroplasty monomicrobial infections underwent at least one surgical debridement (median two, range one to five), exchange of mobile parts and concomitant targeted antibiotic therapy for several weeks or months. A literature search identified outcome data in other institutions from 52 additional DAIR-treated cases according to our study criteria. After merging our own data with those retrieved from other reports, we found a failure rate of 21 % instead of 24 % for S. aureus-infected, DAIR-treated patients, but no failure in 14 streptococcal-infected patients. In the pooled data, the failure rate linked with S. aureus infections was significantly higher than that with Streptococcus ssp. (19/90 vs 0/14 episodes; Fisher's exact test, P = 0.07). CONCLUSIONS: DAIR-treated patients with prosthetic hip joint infections due to S. aureus tended to have worse outcomes than those infected with Streptococcus spp. The specific influence of the infecting pathogen should be considered in future guidelines and recommendations.

The evolution and development of neural superposition.

Visual systems have a rich history as model systems for the discovery and understanding of basic principles underlying neuronal connectivity. The compound eyes of insects consist of up to thousands of small unit eyes that are connected by photoreceptor axons to set up a visual map in the brain. The photoreceptor axon terminals thereby represent neighboring points seen in the environment in neighboring synaptic units in the brain. Neural superposition is a special case of such a wiring principle, where photoreceptors from different unit eyes that receive the same input converge upon the same synaptic units in the brain. This wiring principle is remarkable, because each photoreceptor in a single unit eye receives different input and each individual axon, among thousands others in the brain, must be sorted together with those few axons that have the same input. Key aspects of neural superposition have been described as early as 1907. Since then neuroscientists, evolutionary and developmental biologists have been fascinated by how such a complicated wiring principle could evolve, how it is genetically encoded, and how it is developmentally realized. In this review article, we will discuss current ideas about the evolutionary origin and developmental program of neural superposition. Our goal is to identify in what way the special case of neural superposition can help us answer more general questions about the evolution and development of genetically "hard-wired" synaptic connectivity in the brain.

Pathogen-driven decision for implant retention in the management of infected total knee prostheses.

PURPOSE: In prosthetic joint infections (PJIs) of the knee, debridement with implant retention is associated with a high risk of recurrence. METHODS: A single-centre cohort study was performed with extensive analysis of the literature covering 1980-2012. RESULTS: In 21 patients (mean age 80.4 years, 19 immunosuppressed), in association with 1.5-three months of antibiotic treatment, an attempt was made to salvage the prosthesis by open (11 patients) or arthroscopic (ten patients) debridement. After a mean follow-up of seven years (range four-20 years), patients were in remission in seven cases (33 %). Remission was achieved in 0 % of all methicillin-resistant Staphylococcus aureus (MRSA) infections (zero/three), in 0 % (zero/three) of methicillin-resistant coagulase-negative staphylococcal infections, in 29 % (two/seven) of methicillin-sensitive S. aureus infections and in 75 % (three/four) of infections due to streptococci. The literature review focused on implant preserving approaches yielded 599 cases with an overall success rate of 47 % (284/599) and significantly more remissions in streptococcal vs staphylococcal knee PJIs (43/54 vs 144/324; p < 0.01, odds ratio 4.9, 95 % confidence interval 2.4-10.9). CONCLUSIONS: In addition to established indications for explantation such as implant loosening, sinus tract or methicillin resistance, the decision for debridement and retention of knee PJIs should also depend on the pathogen. Implant preservation is futile with methicillin-resistant staphylococci, but seems to be a valid option for streptococcal PJIs.

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.

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.

[Atypical femoral fracture associated with the use of bisphosphonates, an adverse drug reaction not to be missed]. / Fracture atypique du fémur sous bisphosphonates, un effet indésirable a ne pas manquer.

Atypical femur fractures represent a new disease entity associated with the use of oral bisphosphonates. This review summarizes the current understanding of this phenomenon. These fractures are usually transverse, affecting the proximal third of the femoral shaft. They occur after minor or no trauma, include a thickening of the lateral femoral cortex, a delayed consolidation time and prodromal symptoms. In this context, the risk/benefit ratio of bisphosphonates remains favorable if the indication is adequate. In case of fracture, indication to treatment should be reevaluated. Pain or discomfort in the thigh in a patient receiving bisphosphonate should lead to radiological investigations in order to detect the possible occurrence of a stress fracture.

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.

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).

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.

Cup size and risk of dislocation after primary total hip arthroplasty.

We evaluated the relationship between cup diameter and dislocation risk in patients undergoing primary total hip arthroplasty (THA) with a 28-mm head. There were 50 dislocations, 28 of which occurred in 2221 (1.3%) THAs with a cup diameter smaller than 56 mm and 22 in 513 (4.3%) with a cup diameter of 56 mm or larger. Dislocation risk varied between 0.6% and 2.4% in the smaller cup group and between 4.1% and 5.2% in the larger cup group. The risk was substantially higher in the large cup group (unadjusted odds ratio, 3.5; 95% confidence interval, 2.0-6.2). Multivariable logistic regression revealed an adjusted odds ratio of 2.4 (95% confidence interval, 1.2-4.9). Patients with THA (28-mm head) had more than twice the risk of dislocation with cup size of 56 mm or higher compared to patients with smaller cups.

Ten-year results with the Morscher press-fit cup: an uncemented, non-modular, porous-coated cup inserted without screws.

Total hip arthroplasty (THA) with well designed cementless acetabular implants has shown excellent results. The purpose of this study was to assess our clinical and radiological outcomes using an uncemented cup. We conducted a prospective cohort study including all consecutive primary THAs performed with the Morscher press-fit cup, an uncemented non-modular acetabular component, between March 1996 and December 1998. Patients were evaluated at ten years with clinical and radiological follow-up, patient satisfaction and questionnaire assessment using the Harris hip score (HHS), Merle d'Aubigné and Postel score, the UCLA score, the 12-item short-form health survey (SF-12) and a visual analog scale. Five hundred sixty-one THAs were performed in 518 patients. At 120 months (± 7.3 months), 303 patients with 335 THAs were still available for follow-up. None of the patients had required cup revision for aseptic loosening. At ten years, the cup survivorship was 98.8% (95% CI 97.4-99.5) with cup revision for any cause as an endpoint. No radiolucencies were seen around the cups, but osteolytic defects involved 21 stems (8.3%). Mean total linear polyethylene wear was 0.9 mm. The Morscher acetabular replacement cup provides excellent results at ten years. There were no revisions for aseptic loosening of the cup, and no osteolytic defects were found around the cup. Patient satisfaction was high and the clinical results were very good.