Radiological evaluation of the metal-bone interface of a porous tantalum acetabular component

Introduction Porous tantalum presents a bone-matched elastic modulus and an high coefficient of friction on cancellous and cortical bone. Furthermore, its open-cell tantalum structure of repeating dodecahedrons, similar to cancellous bone, should be favourable for bone ingrowth. These physical and mechanical properties should increase primary fixation and potential osteointegration of acetabular cups and should decrease periacetabular stress shielding. The purpose of this study was to radiographically evaluate the evolution of the metal-bone interface of porous tantalum acetabular components. Materials and Methods Serial radiographic evaluation of 41porous tantalum acetabular component has been performed in 40 patients. Twelve hips underwent total hip arthroplasty using a trabecular metal monoblock acetabular component and 29 hips using a trabecular metal modular acetabular system. All patients were clinically and radiographically evaluated at four, eight, 12, 24 weeks, 12 months and then annually. All cases were available for a minimum follow-up of two years (mean 35 months). On post-operative x-rays the metal-bone interface was investigated for areas in which the porous surface of the acetabular component was not in contact with bone. These gaps were measured and classified by location according to DeLee and Charnley zones. Evolution of postoperative gaps, presence of lysis or periacetabular radiolucencies and component migration were assessed during follow-up. Results On post-operative x-rays 36 components (88%) had a gap between the outer surface and the host bone but only in 12 cases (29%) gaps were larger then 1 mm. The gaps were mostly situated in the polar region (zone II) when compared with the peripheral zones and no one was bigger then 5 mm in width. At last follow-up 23 (64%) of the initial gaps were no longer radiographically evident, 10 (28%) had a favourable evolution and appeared reduced in dimension but still present and 3 (8%) didn\u2019t fill at all and were unchanged when compared with post-operative controls. There was no progression progression of any post-operative gap and no evidence of new periacetabular radiolucent lines or lysis. No acetabular implant showed evidence of migration or needed revision for loosening. At last follow up the mean Harris Hip Score was 95. There were no dislocation or other complications. Discussion Short term results with porous tantalum acetabular component are encouraging: the bridging of the interface gaps and the absence of periacetabular radiolucencies indicate good mechanical and osteoconductive properties. Further follow-up will be required to confirm these results in the long term

Neonatal mucolipidosis 2. The spontaneous evolution of early bone lesions and the effect of vitamin D treatment. Report of two cases.

Evolution of the early bone lesions in two children with mucolipidosis 2 was followed from birth. The progression of the bone changes did not differ from healing of rickets. Low levels of 1,25-(OH)2-D3 were found in one child and he was treated with vitamin D; resolution of the rachitic changes was more rapid than in the untreated child. It is suggested that in mucolipidosis 2 bone reacts to two independent factors, one controlling calcium metabolism, the other depending on the primary lysosomal enzyme defect. Since ricket-like features are not present in the other mucolipidoses or mucopolysaccharidoses, the defect of calcium metabolism seems to be related to the specific enzyme defect of mucolipidosis 2

Acetabular revision surgery in the presence of severe bone loss: surgical technique and early results with modular porous tantalum augments and cups

Subject: In the presence of minimal acetabular bone loss most revision procedures can be done with the use of an uncemented hemispheric device with or without morselized allograft. The use of modular porous tantalum augments and cups has been recently introduced to address more severe bone deficiencies. The purpose of this study is to describe the surgical technique and early clinical results obtained with trabecular metal acetabular augments in cases of acetabular revision with severe bone loss. Materials and Methods: Since November 2003 seven acetabular revisions have been done by means of TMT\uae augments and cups: the primary indication for acetabular revision was aseptic loosening in five patients and septic loosening in two patients. According to Paprosky classification the acetabular bone defects were classified as follows: 2B in two hips, 2C in one hip, 3A in two hips and 3B in three hips. In two cases it was the first surgical hip replacement procedure. Five cases were multiple revisions. Results: At an average follow-up of 24 months no implant had evidence of loosening or migration. No dislocations occurred. Discussions and Conclusions: Augments provide mechanical support to hemispheric cups of various dimensions. This surgical technique avoids the use of structural allograft, helps to restore the center of hip rotation and increases contact area between the implant and the host bone for biological fixation. Longer follow-up is required to verify survival of these implants and potential mechanical and biologic complications related to use of this modular TMT\uae system

Suppression of Parasitic Nonlinear Processes in Spontaneous Four-Wave Mixing with Linearly Uncoupled Resonators

We report on a signal-to-noise ratio characterizing the generation of identical photon pairs of more than 4 orders of magnitude in a ring resonator system. Parasitic noise, associated with single-pump spontaneous four-wave mixing, is essentially eliminated by employing a novel system design involving two resonators that are linearly uncoupled but nonlinearly coupled. This opens the way to a new class of integrated devices exploiting the unique properties of identical photon pairs in the same optical mode

SAT0368 PREGNANCY IN WOMEN WITH SPONDYLOARTHRITIS: WHO ARE THE PATIENTS AT RISK OF DISEASE FLARE?

Background:Patients with Spondyloarthritis (SpA) can experience flares during pregnancy and postpartum even though the available data are limited and not conclusive.Objectives:To assess disease activity and treatment modification during pregnancy and postpartum in patients with SpA and to identify risk factors for disease flare.Methods:Data on SpA pregnancies prospectively-followed in a pregnancy clinic from 2010 to 2019 were retrospectively analysed. Disease activity was assessed during each trimester and postpartum using ASDAS-CRP or DAS28-CRP. Flare was defined as an increase of disease activity leading to treatment modification (introduction or increase ≥5mg/day of prednisone, introduction of cDMARD or bDMARD)1.Results:Data on 50 pregnancies in 46 patients were collected (mean age at conception 33±4.7 years; median disease duration: 60 months (IQR 24-132); 33 psoriatic arthritis, 6 axialSpA, 2 reactive arthritis, 2 IBD-related SpA; 6 undifferentiated SpA, 1 juvenile idiopathic arthritis). Six pregnancies ended in miscarriage, so they weren't considered for the analysis of flares during pregnancy (table 1). Fifteen out of 44 (34%) pregnancies had at least one flare during pregnancy (6, 7 and 4 during 1st, 2ndand 3rdtrimester respectively; 2 pregnancies had multiple flares). A higher rate of flare was observed in pregnancies of patients with axial involvement (p=0.01), on treatment with bDMARDs at preconceptional visit (p=0.03) and who stopped TNFi at positive pregnancy test (p=0.03). Peripheral involvement was associated with a lower rate of flares (p=0.02). Medications resumed during pregnancy were steroids (in 6 pregnancies), cDMARDs (2 sulfasalazine, 1 cyclosporine) and bDMARDs (4 certolizumab, 4 etanercept). During postpartum period flares were recorded in 46% of patients.Table 1.clinical features, medication and disease activity in pregnancies with flare vs without flareCLINICAL FEATURESFLARE (15)NO FLARE (29)pAxial involvement, n (%)11/15 (73)9/29 (31)0.01Peripheral arthritis, n (%)8/15 (53)26/29 (90)0.02Enthesitis, n (%)5/15 (33)14/29 (48)nsDactilitis, n (%)3/15 (20)8/29 (28)nsPsoriasis, n (%)6/15 (40)17/29 (59)nsIBD, n (%)2/15 (13)0nsUveitis, n(%)1/15 (7)3/29 (10)nsHLAB27 +7/11 (64)5/12 (42)nsMEDICATION HISTORYbDMARDs, n (%)11/15 (73)7/29 (24)0.003bDMARDs at preconception visit, n (%)8/15 (53)6/29 (21)0.04bDMARDs stopped at positive pregnancy test, n (%)7/15 (47)4/29 (14)0.03cDMARDs, n (%)12/15 (80)25/29 (86)nsDISEASE ACTIVITYACTIVE DISEASE* preconception visit, n(%)3/14 (21)4/23 (17)nsACTIVE DISEASE 1sttrimester, n(%)6/15 (40)1/29 (3)0.004ACTIVE DISEASE 2ndtrimester, n(%)8/15 (47)2/29 (7)0.001ACTIVE DISEASE 3rdtrimester, n(%)2/15 (13)1/29 (3)ns*DAS28-CRP>3.2 or ASDAS-CRP≥2.1Conclusion:In our cohort of prospectively-followed SpA pregnancies, 34% experienced a flare during pregnancy and 46% during postpartum. Flares occurred especially in those patients who discontinued TNFi early in pregnancy and with axial involvement. When resumed during pregnancy, TNFi was able to control the disease. At preconception counselling, the continuation of TNFi during pregnancy should be considered to ensure a better control of disease.References:[1]Fischer-Betz R et al.Arthritis Rheumatol. 2015; 67.Disclosure of Interests: :None declare

Y Engineering a 3D in vitro model of human skeletal muscle at the single fiber scale

The reproduction of reliable in vitro models of human skeletal muscle is made harder by the intrinsic 3D structural complexity of this tissue. Here we coupled engineered hydrogel with 3D structural cues and specific mechanical properties to derive human 3D muscle constructs (“myobundles”) at the scale of single fibers, by using primary myoblasts or myoblasts derived from embryonic stem cells. To this aim, cell culture was performed in confined, laminin-coated micrometric channels obtained inside a 3D hydrogel characterized by the optimal stiffness for skeletal muscle myogenesis. Primary myoblasts cultured in our 3D culture system were able to undergo myotube differentiation and maturation, as demonstrated by the proper expression and localization of key components of the sarcomere and sarcolemma. Such approach allowed the generation of human myobundles of ~10 mm in length and ~120 μm in diameter, showing spontaneous contraction 7 days after cell seeding. Transcriptome analyses showed higher similarity between 3D myobundles and skeletal signature, compared to that found between 2D myotubes and skeletal muscle, mainly resulting from expression in 3D myobundles of categories of genes involved in skeletal muscle maturation, including extracellular matrix organization. Moreover, imaging analyses confirmed that structured 3D culture system was conducive to differentiation/maturation also when using myoblasts derived from embryonic stem cells. In conclusion, our structured 3D model is a promising tool for modelling human skeletal muscle in healthy and diseases conditions

Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin

Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the presenilin 1 and 2 genes have been linked to early onset familial forms of Alzheimer's disease (FAD). Using the Drosophila central nervous system as a model we have investigated the role of presenilin in one of the earliest cellular defects associated with Alzheimer's disease, intracellular calcium deregulation. We show that expression of either wild type or FAD-mutant presenilin in Drosophila CNS neurons has no impact on resting calcium levels but does give rise to deficits in intracellular calcium stores. Furthermore, we show that a loss-of-function mutation in calmodulin, a key regulator of intracellular calcium, can suppress presenilin-induced deficits in calcium stores. Our data support a model whereby presenilin plays a role in regulating intracellular calcium stores and demonstrate that Drosophila can be used to study the link between presenilin and calcium deregulation

Frailty and post-operative delirium influence on functional status in patients with hip fracture: the GIOG 2.0 study

Background: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF). Methods: Multicenter prospective observational study of older patients with HF admitted to 12 Italian Orthogeriatric centers (July 2019-August 2022). POD was assessed using the 4AT. A 26-item Frailty Index (FI) was created using data collected on admission. The outcome measures were Cumulated Ambulation Score (CAS) ≤ 2 at discharge and a telephone-administered CAS ≤ 2 after 4 months. Poisson regression models were used to assess the effect of frailty and POD on outcomes. Results: 984 patients (median age 84 years, IQR = 79–89) were recruited: 480 (48.7%) were frail at admission, 311 (31.6%) developed POD, and 158 (15.6%) had both frailty and POD. In a robust Poisson regression, frailty alone (Relative Risk, RR = 1.56, 95% Confidence Intervals, CI 1.19–2.04, p = 0.001) and its combination with POD (RR = 2.57, 95% CI 2.02–3.26, p < 0.001) were associated with poor functional status at discharge. At 4-month follow-up, the combination of frailty with POD (RR 3.65, 95% CI 1.85–7.2, p < 0.001) increased the risk of poor outcome more than frailty alone (RR 2.38, 95% CI 1.21–4.66, p < 0.001). Conclusions: POD development exacerbates the negative effect that frailty exerts on functional outcomes in HF patients

Overhaul and Installation of the ICARUS-T600 Liquid Argon TPC Electronics for the FNAL Short Baseline Neutrino Program

The ICARUS T600 liquid argon (LAr) time projection chamber (TPC) underwent a major overhaul at CERN in 2016-2017 to prepare for the operation at FNAL in the Short Baseline Neutrino (SBN) program. This included a major upgrade of the photo-multiplier system and of the TPC wire read-out electronics. The full TPC wire read-out electronics together with the new wire biasing and interconnection scheme are described. The design of a new signal feed-through flange is also a fundamental piece of this overhaul whose major feature is the integration of all electronics components onto the signal flange. Initial functionality tests of the full TPC electronics chain installed in the T600 detector at FNAL are also described

Mitochondrial Ca2+ Overload Underlies Aβ Oligomers Neurotoxicity Providing an Unexpected Mechanism of Neuroprotection by NSAIDs

Dysregulation of intracellular Ca2+ homeostasis may underlie amyloid β peptide (Aβ) toxicity in Alzheimer's Disease (AD) but the mechanism is unknown. In search for this mechanism we found that Aβ1–42 oligomers, the assembly state correlating best with cognitive decline in AD, but not Aβ fibrils, induce a massive entry of Ca2+ in neurons and promote mitochondrial Ca2+ overload as shown by bioluminescence imaging of targeted aequorin in individual neurons. Aβ oligomers induce also mitochondrial permeability transition, cytochrome c release, apoptosis and cell death. Mitochondrial depolarization prevents mitochondrial Ca2+ overload, cytochrome c release and cell death. In addition, we found that a series of non-steroidal anti-inflammatory drugs (NSAIDs) including salicylate, sulindac sulfide, indomethacin, ibuprofen and R-flurbiprofen depolarize mitochondria and inhibit mitochondrial Ca2+ overload, cytochrome c release and cell death induced by Aβ oligomers. Our results indicate that i) mitochondrial Ca2+ overload underlies the neurotoxicity induced by Aβ oligomers and ii) inhibition of mitochondrial Ca2+ overload provides a novel mechanism of neuroprotection by NSAIDs against Aβ oligomers and AD