Eu ³⁺ Sequestration by Biogenic Nano-Hydroxyapatite Synthesized at Neutral and Alkaline pH

<p>Biogenic hydroxyapatite (bio-HA) has the potential for radionuclide capture and remediation of metal-contaminated environments. Biosynthesis of bio-HA was achieved via the phosphatase activity of a <i>Serratia sp</i>. supplemented with various concentrations of CaCl₂ and glycerol 2-phosphate (G2P) provided at pH 7.0 or 8.6. Presence of hydroxyapatite (HA) was confirmed in the samples by X-ray powder diffraction analysis. When provided with limiting (1 mM) G2P and excess (5 mM) Ca²⁺ at pH 8.6, monohydrocalcite was found. This, and bio-HA with less (1 mM) Ca²⁺ accumulated Eu(III) to ∼31% and 20% of the biomineral mass, respectively, as compared to 50% of the mineral mass accumulated by commercial HA. Optimally, with bio-HA made at initial pH 7.0 from 2 mM Ca²⁺ and 5 mM G2P, Eu(III) accumulated to ∼74% of the weight of bio-HA, which was equal to the mass of the HA mineral component of the biomaterial. The implications with respect to potential bio-HA-barrier development in situ or as a remediation strategy are discussed.</p

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Ascending Tonic Clonic Seizure Syndrome after Percutaneous Vertebroplasty

Background Context. Cement leakage is not a rare complication of vertebroplasty, but ascending tonic clonic seizure syndrome is exceptionally rare. We herein report the first case to our knowledge of this complication related to vertebroplasty. Purpose. We herein report the first case of ascending tonic clonic seizure syndrome following epidural cement leakage after percutaneous vertebroplasty in a patient with multiple osteoporotic compression fractures. Study Design. Case report. Methods. A 64-year-old woman with T8, T10, L2, and L4 osteoporotic compression fractures underwent percutaneous vertebroplasty using polymethylmethacrylate. 40 minutes after the procedure the patient started suffering back and leg pain, having repetitive myoclonic jerks lasting 15 seconds of the lower extremities, spasm of the back, dyspnea, sinus tachycardia, hypoxemia, and metabolic acidosis. Results. The patient recovered completely due to a combination of early effective resuscitation and considered definitive management. Conclusions. Percutaneous vertebroplasty with polymethylmethacrylate is relatively safe but has few dangerous complications, which should be prevented by a meticulous technique and excellent image quality

Bone Mineral Density Changes Following Total Ankle Replacement With an Uncemented, Stemmed Prosthesis

Category: Ankle Arthritis Introduction/Purpose: Strong peri-prosthetic bone is mandatory for the survival of joint replacements. This has been proven in studies of total hip and knee replacement. It is hypothesised that this should be equally important in the survivorship of Total Ankle Arthroplasty (TAR). Despite observable bone preservation on postoperative radiographs, there is a paucity of literature on changes of bone mineral density (BMD) around the ankle following TAR. This prospective study used Dual Energy X-ray absorptiometry (DEXA) to quantify the BMD in different regions of the surrounding bones adjacent to the stemmed tibial and the talar components of un-cemented TAR prosthesis. Methods: We conducted a prospective cohort study in patients undergoing TAR with an uncemented, stemmed tibial component mobile bearing prosthesis in our tertiary referral centre. Patients who underwent a TAR between March 2008 and April 2009 were included and were part of a randomized controlled trial of TAR. Ethics committee approval was obtained. All operative procedures were performed by one consultant surgeon, using a standardised operative technique. DEXA scans of the ankle were assessed preoperatively and repeated at one and two years postoperatively. Ankles were scanned using a HOLOGIC DXA scanner. Seven rectangular regions of interest (ROI) were positioned on the AP view of the first post-operative image (Fig 1). The template analysing the ROI for the first post-operative scan was then used for analysis of the preoperative and subsequent post- operative scans using the HOLOGIC software. This technique produced identical areas of interest for each scan to allow the results to be compared. Results: 23 patients underwent TAR for end stage osteoarthritis. The mean age of participants was 63.3 years (SD 9, range 43 to 80). Seven female and 15 male patients were included with one male patient undergoing bilateral TAR. The mean BMD within the lateral malleolus (R2) decreased significantly from 0.5g/cm2 to 0.42g/cm2 (17%, P < 0.01), at one and two years postoperatively. There was an increase in the BMD at the medial side (R6) of the metaphysis of 0.07 g/cm2 (7%, P=0.02) and the mean BMD within medial malleolus decreased from 0.67g/cm2 to 0.64 g/cm2 (4%), but this was not statistically significant. There were small increases in BMD in the tibia, immediately proximal to the implant (R7) and at the talus (R5) which were not statistically significant. Conclusion: There was stress shielding over the lateral malleolus resulting in decrease BMD in lateral malleolus and to a lesser extent of the medial malleolus. The increase in BMD at the medial tibial metaphysis indicates an increase in mechanical stresses in that region. This may explain the occasional postoperative stress fracture of the medial malleolus or medial sided ankle pain. There was no further change in BMD from year 1 to year 2 following TAR suggesting the majority of remodelling has occurred within the first year

Topographic Pain Mapping versus Radiological Inter-observer Variation in Ankle Arthritis

Category: Ankle, Ankle Arthritis Introduction/Purpose: Topographic pain mapping has gained popularity during 20th century, providing opportunities for patients to demonstrate spatial distribution of pain. Despite this, evidence of clinical application in orthopaedics remains largely limited to spinal pathologies. We investigate how clinician interpretation of routine radiological studies compares to patient pain mapping in ankle arthritis. Methods: Between 2014 and 2016 we identified 21 patients ultimately diagnosed with ankle arthritis, who underwent comprehensive gait analysis (including topographic pain mapping) on referral to our institution. Patients were requested to map up to three pain areas, assigning a visual analogue score (VAS) of 0-10, to signify severity of pain in each area. A consultant orthopaedic foot and ankle surgeon, and orthopaedic trainees undertook blinded evaluation of relevant radiological studies, estimating patients’ mapping and VAS scores on the basis of radiological pathology. For the purpose of analysis findings were applied to five distinct regions around the ankle: three anterior (antero-medial; central; and antero-lateral), lateral and medial. Results were correlated between the different assessors, as well as to the patients’ pain mapping, using Spearman’s Rho & Kendall Tau correlation statistics, significance taken as p=0.05). Correlation to patient pain mapping was even poorer, with radiological assessment consistently over- estimating symptom severity (p=>0.05). Conclusion: There is a statistically strong correlation between topographic pain mapping and radiological evaluation of ankle arthritis. We strongly recommend that additional pathology around the ankle is excluded by use of pre-operative MRI imaging prior to surgery for ankle arthritis. Pain from ankle arthritis appears to mask additional soft tissue pathology surrounding the ankle noted on MRI scan

Preoperative Templating in Total Ankle Replacement - A Case for 3D Imaging

Category: Ankle Arthritis Introduction/Purpose: Pre-operative templating using plane radiographs is of great importance in planning arthroplasty of the hip and knee. Its role in total ankle arthroplasty (TAR) is less clear. Being able to use the best fitting implant is of paramount importance for transferring forces through the ankle joint. This contributes to the longevity of the TAR prosthesis. It is unclear whether pre-operative templating is more accurately performed using an AP radiograph or 3-Dimensional (3D) imaging using MRI or CT. We sought to compare the accuracy of pre-operative templating with an AP radiograph versus CT/MRI, in relation to the size of the implanted prosthesis. Methods: 29 patients undergoing TAR with BOX™ TAR between July 2014 and September 2015 were included in the study. Data was collected prospectively using a TAR database. Pre-operative templating of Tibial and Talar width using AP Radiographs was performed and recorded onto the database (Fig1). The implant sizes used was also recorded in the database (small, medium or large). Patients were part of an ongoing clinical trial which has ethics committee approval. 26 patients in this cohort underwent pre-operative CT or MRI assessment and were suitable for inclusion in the study (CT=6, MRI =20). These scans were reviewed retrospectively by two separate authors (AF and JR) to assess for Tibial and Talar width in the Coronal plane at the midpoint of the Tibia in the Sagittal plane (Fig2). A third author (MS), the lead surgeon, resolved any disagreements on measurements. The authors were blinded to the implant size used. Results: For templating the Tibial width the AP radiograph predicted the implant size 42.3% of the time while using CT/MRI scan predicted the implant size correctly 80.8% of the time. For templating the Talar width the AP radiograph predicted the implant size 42.3% of the time while using CT/MRI scan predicted the implant size correctly 84.6% of the time. The odds ratio for CT/MRI predicting the implant correctly over the AP radiograph was 5.72 (CI = 1.7 – 19.9) for the tibial component and 7.50 (CI = 2.0- 28.0) for the talar component. These values were statistically significant. Conclusion: For pre-operative templating we found 3D templating with an MRI or CT scan to be significantly more accurate than using an AP radiograph. We advise the use of MRI or CT as the most effective way to plan for TAR. MRI and CT are now frequently performed in orthopaedic centres as routine investigations. These modalities have the added benefit of assessing surrounding joints and soft tissues to aid accurate diagnosis. The limitations of this study lie in the small study size and the retrospective methodology

Rethinking Chemoprophylaxis for Total Ankle Replacement

Category: Ankle Arthritis Introduction/Purpose: Total ankle replacement (TAR) is a relatively uncommon joint replacement procedure. Only 631 TAR operations were performed in the UK in 2014. However, its popularity is increasing as a suitable alternative to ankle fusion in patients with end stage ankle arthritis. A rare complication of TAR surgery is the development of a Venous Thromboembolism (VTE), including Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). We sought to investigate the effectiveness of our own peri-operative management and VTE prophylaxis protocol in the prevention of symptomatic VTE, in patients undergoing TAR surgery in our tertiary referral hospital. Methods: We conducted a retrospective cohort study of prospectively collected data in patients undergoing TAR with Mobility TAR (Depuy™, Leeds, United Kingdom) between March 2006 and May 2012. All patients were treated according to a pre-defined protocol. Patients undergoing TAR were not given VTE prophylaxis unless there were specific indications of increased risk of VTE - such as cardiac risk factors or post-operative air travel. A Vacuum Assisted Closure (VAC™) device was applied post operatively to increase the speed of wound healing, creating a negative pressure environment preventing dehiscence. Patients were not immobilised post operatively but rested for 5 days with the index leg elevated, while ankle movement was encouraged. Patients were mobilised early (5-7days). We reviewed all post-operative clinical follow up for 6 months, the time chosen as a cut off for an incident of DVT to be attributable to the surgery. Results: A cohort of 200 TARs were assessed. The mean age of the cohort was 61.7 years of age (range 31.0-89.4). There were no recorded deaths. There were 125 male and 75 female patients with 85 Left and 115 Right TAR procedures performed. In total 31 patients (15.5%) were given chemoprophylaxis in the post-operative period on clinical grounds. 187 (73.4%) patients were mobilised early (5-7days) post-operatively; with 2 (0.8%) mobilised with partial weight bearing and 21 (4.6%) mobilised non-weight bearing. In the mobilised early subgroup of patients only 10 (5%) had problems and required subsequent immobilisation. The majority of post-operative problems were caused by post-operative peri-prosthetic fracture (n=8, 4%) and wound break down (n=2, 1%). Conclusion: This study highlights that there is a need for further research into the use of VTE prophylaxis in TAR. In addition we feel that chemoprophylaxis should not be considered the panacea for reducing the incidence of VTE in patients undergoing TAR. We suggest post-operative limb elevation, haematoma evacuation and use of VAC treatment should be prioritised with early mobilisation and full weight bearing. Furthermore this study suggests judicious VTE chemoprophylaxis should be given on clinicians’ judgement tailored to individual patient requirements. This will hopefully avoid unnecessary costs and possible complications of anticoagulation such as bleeding, delayed wound healing and thrombocytopenia