Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103.

BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.) [97/103Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 (103Ru; ß-, γ) and ruthenium-97 (97Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a. [103Ru]BOLD-100 (3 and 30 mg kg-1) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally, ex vivo autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg-1) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [103Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [97Ru]BOLD-100.

Social representations of intellectual disability; a comparison between cultures.

OBJECTIVES: People with Intellectual disability consistently appear to be one of the most looked-down upon and repressed subgroups of society in many cultures. The main aim of this study was to compare social representations of intellectual disability in its various aspects between different cultures. MATERIALS AND METHODS: The study was conducted in four different sites: Beirut-Lebanon, Algiers-Algeria, Tours-France and Namur-Belgium. Participants were asked to complete a questionnaire evaluating social representations of intellectual disability. RESULTS: A total of 755 participants consented to take part in the study. Gender only affected social representations in the Lebanese population. Overall, Algerians appeared to have the least positive social representations and Lebanon to have more positive attitudes, while France and Belgium tended to have the most favourable representations. DISCUSSION AND CONCLUSIONS: Findings highlight the imbalance between a European and a non-European country showing the importance of developing tailored interventions to improve general attitudes towards intellectual disability.

A meta-analysis assessing time for return to sport following hip resurfacing.

BACKGROUND: Hip resurfacing arthroplasty (HRA) is associated with excellent functional outcomes and return to pre-disease level of activity. The time for return to sport (RTS) following HRA remains unknown. The aim of this meta-analysis was to establish the time for RTS following HRA. METHODS: A search was performed on PUBMED, MEDLINE, EMBASE, and the Cochrane Library for trials on HRA and RTS, in the English language, published from the inception of the database to October 2020. In addition, a manual search was performed of relevant sports medicine and orthopaedic journals, and the bibliographies reviewed for eligible trials. All clinical trials reporting on time to RTS following HRA were included. Data relating to patient demographics, methodological quality, operation type, RTS, clinical outcomes, and complications were recorded by two independent reviewers. The PRISMA guidelines for reporting meta-analyses was used to undertake this study. RESULTS: The initial literature search identified 1559 studies and nine further studies were found. Of these, 11 studies with a total of 659 patients matched the inclusion criteria. Two studies involving a total of 94 patients demonstrated an overall pooled proportion of 91.8% (95% CI 71.8-100) of patients RTS by three months post-operatively. Four studies including a total of 265 patients determined a pooled proportion of 96.8% (95% CI 91.0-99.7) of patients able to RTS by the 6-month post-operative stage. Pooled proportion analysis from all 11 studies comprising 659 patients showed 90.9% (95% CI 82.2-96.9) of patients were able to RTS by final follow up of 3 years. CONCLUSION: Pooled proportion analysis showed an increasing number of patients were able to RTS after HRA over the first one year after surgery. There remains marked inter and intra-study variations in time for RTS but the pooled analysis shows that over 80% of patients were able to RTS at 6 to 12 months after HRA. The findings of this meta-analysis will enable more informed discussions between patients and healthcare professionals about time for RTS following HRA.

Tourniquet use in total knee arthroplasty and the risk of infection: a meta-analysis of randomised controlled trials.

PURPOSE: The intra-operative use of tourniquets during Total Knee Arthroplasty (TKA) is common practice. The advantages of tourniquet use include decreased operating time and the creation of a bloodless visualisation field. However, tourniquet use has recently been linked with increased post-operative pain, reduced range of motion, and slower functional recovery. Importantly, there is limited evidence of the effect of tourniquet use on infection risk. The purpose of this systematic review and meta-analysis is to fill this gap in the literature by synthesising data pertaining to the association between tourniquet use and infection risk in TKA. METHODS: A systematic literature search was performed on Pubmed, Embase, Cochrane and clinicaltrials.gov up to May 2021. Randomized control trials were included, comparing TKA outcomes with and without tourniquet use. The primary outcome was overall infection rate. Secondary outcomes included superficial and deep infection, skin necrosis, skin blistering, DVT rate, and transfusion rate. RESULTS: 14 RCTs with 1329 patients were included. The pooled incidence of infection in the tourniquet group (4.0%, 95% CI = 2.7-5.4) was significantly higher compared to the non-tourniquet group (2.0%, 95% CI = 1.1-3.1) with an OR of 1.9 (95% CI = 1.1-3.76, p = 0.03). The length of hospital stay, haemoglobin drop (0.33 95% CI =0.12-0.54), P = 0.002) and transfusion rates (OR of 2.7, 95%CI = 1.4-5.3, P = < 0.01) were higher in the tourniquet group than the non-tourniquet group. The difference in the length of inhospital stay was 0.24 days favouring the non-tourniquet group (95% CI = 0.10-0.38, P = < 0.01). The incidence of skin blistering (OR 2.6, 95% CI = 0.7-9.9, p = 0.17), skin necrosis (OR 3.0, 95% CI = 0.50-19.3, p = 0.25), and DVT rates (OR 1.5, 95% CI = 0.60-3.60, p = 0.36) did not differ between the two groups. CONCLUSION: Quantitative synthesis of the data suggested tourniquet use was associated with an increased overall risk of infection, intraoperative blood loss, need for blood transfusion and longer hospital stay. Findings of this meta-analysis do not support the routine use of tourniquet in TKA and arthroplasty surgeons should consider any potential additional risks associated with its use. LEVEL OF EVIDENCE: meta-analysis, Level II.

Debridement, antibiotics, and implant retention in non-oncological femoral megaprosthesis infections: minimum 5 year follow-up.

PURPOSE: Megaprostheses are increasingly utilised outside of the oncological setting, and remain at significant risk of periprosthetic joint infection (PJI). Debridement, antibiotic, and implant retention (DAIR) is an established treatment for PJI, however its use in non-oncological patients with femoral megaprostheses has not been widely reported. There are significant differences in patient physiology, treatment goals, and associated risks between these patient cohorts. METHODS: We identified 14 patients who underwent DAIR for a PJI of their femoral megaprostheses, between 2000 and 2014, whom had their index procedure secondary to non-oncological indications. Patients were managed as part of a multidisciplinary team, with our standardised surgical technique including exchange of all mobile parts, and subsequent antibiotic therapy for a minimum of 3 months. Patients were followed up for a minimum of 5 years. RESULTS: Patients included six proximal femoral replacements, five distal femoral replacements, and three total femoral replacements. No patients were lost to follow-up. There were six males and eight females, with a mean age of 67.2 years, and mean ASA of 2.3. Nine patients (64.3%) successfully cleared their infection following DAIR at a minimum of 5 year follow-up. Five patients (35.7%) required further revision surgery, with four patients cleared of infection. No patients who underwent DAIR alone suffered complications as a result of the procedure. CONCLUSIONS: The use of DAIR in these complex patients can lead to successful outcomes, but the risk of further revision remains high. The success rate (64.3%) remains on par with other studies evaluating DAIR in megaprostheses and in primary arthroplasty. This study indicates judicious use of DAIR can be an appropriate part of the treatment algorithm. LEVEL OF EVIDENCE: II.

Spirituality and the quality of life of cancer patients: An antidepressant effect.

OBJECTIVES: Cancer is the second leading cause of mortality in the world, and represents an economic, social and psychological burden. Scientific studies have focused on psychosocial coping mechanisms of patients and on factors improving their quality of life. Thus, the aim of the present study is to analyze the influence that spirituality would have on the quality of life of Lebanese cancer patients and to identify whether the influence on quality of life is mediated through a decreased depression. METHODS: This is a cross-sectional study targeting cancer patients in the hemato-oncology department of the Hôtel-Dieu de France Hospital (Beirut, Lebanon). It is based on a questionnaire composed of three parts: EQ-5D-5L, PHQ-9, and FACIT-Sp-12. Likewise, a control group suffering from chronic diseases and treated in the hospital was questioned. Univariate and multivariate analysis were conducted to assess the relationship between the different questionnaires for controls and for cancer patients. RESULTS: Thirty-nine cancer patients and eight control patients were questioned. In the univariate analysis, there was no relationship between depression and spirituality nor for spirituality and quality of life. After controlling for depression, an inverse correlation between quality of life and spirituality was shown. CONCLUSIONS: Our study is a pilot study which for the first time investigates the implication of depression in a "spirituality-quality of life" association. There is no clear association of spirituality with quality of life. In fact, the physical and psychological burden of chronically ill patients could exceed and render insignificant a possible impact of spirituality on quality of life.

Sclerostin and bone turnover markers response to cycling and running at the same moderate-to-vigorous exercise intensity in healthy men.

BACKGROUND: Recreational cycling is a popular activity which stimulates and improves cardiovascular fitness. The corresponding benefits for bone are unclear. PURPOSE: This study examined the effect of running (high-impact) vs. cycling (low-impact), at the same moderate-to-vigorous exercise intensity, on markers of bone formation (N-terminal propeptide of type I collagen, PINP) and bone resorption (C-telopeptide of type I collagen, CTX-1), a non-collagenous bone remodeling marker (osteocalcin), as well as bone-modulating factors, including parathyroid hormone (PTH), irisin (myokine) and sclerostin (osteokine). METHODS: Thirteen healthy men (23.7 ± 1.0 y) performed two progressive exercise tests to exhaustion (peak VO2) on a cycle ergometer (CE) and on a treadmill (TM). On subsequent separate days, in randomized order, participants performed 30-min continuous running or cycling at 70% heart rate reserve (HRR). Blood was drawn before, immediately post- and 1 h into recovery. RESULTS: PTH transiently increased (CE, 51.7%; TM, 50.6%) immediately after exercise in both exercise modes. Sclerostin levels increased following running only (27.7%). Irisin increased following both running and cycling. In both exercise modes, CTX-1 decreased immediately after exercise, with no significant change in PINP and osteocalcin. CONCLUSION: At the same moderate-to-vigorous exercise intensity, running appears to result in a greater transient sclerostin response compared with cycling, while the responses of bone markers, PTH and irisin are similar. The longer-term implications of this differential bone response need to be further examined.

Day-case unicompartmental knee arthroplasty: a literature review and development of a novel hospital pathway.

INTRODUCTION: We have seen unparalleled changes in our healthcare systems globally as a result of the COVID-19 pandemic. As we strive to regenerate our full capacity elective services in order to contest the increasing demand for lower limb arthroplasty, this pandemic has allowed us a rare opportunity to revise and develop novel elective arthroplasty pathways intended to improve patient care and advance healthcare efficiency. We present an extensive evidence-based review of the approaches used to achieve day-case unicompartmental arthroplasty (UKA) as well as the development of a day-case UKA care pathway in a UK NHS institution based on the evidence provided in the literature. METHODS: An extensive search of the literature was performed for articles that reported on readmission or complication rates ≥30 days postoperatively following day-case UKA. FINDINGS: Fifteen manuscripts reporting the results of day-case UKA, defined as discharged on the same calendar day of surgery, were included in our review. Mean reported complication rates for day-case and inpatient UKA within the follow-up periods were 4.05% and 6.52%, respectively. Mean readmission rates were 2.71% and 4.36% for day-case and inpatient UKA, respectively. The mean rate of successful same-day discharge was 92.45%. CONCLUSION: We introduce our institutional Elective Day Surgery Arthroplasty Pathway (EDSAP) founded upon the evidence presented in the literature. Stringent patient selection complimented by a well-defined day-case arthroplasty pathway is fundamental for successful commencement of day-case UKA in the NHS.

Time for return to sport following total knee arthroplasty: a meta-analysis.

INTRODUCTION: The frequency of total knee arthroplasty (TKA) is increasing, particularly in younger and more active patients. In these patients, there may be greater functional demands, with an expectation to return to sporting activities (RTS) following TKA. There is a paucity of data on the time to RTS following TKA and the aim of this meta-analysis is to determine the time to RTS following TKA. METHODS: Using the PRISMA guidelines, an electronic search of PUBMED, MEDLINE, EMBASE, and the Cochrane Library for trails was performed on TKA and RTS in English language, published since the inception of the database to 31st October 2020. Data evaluating the time to RTS and functional outcomes were recorded by two authors independently that were included in the analysis. Pooled analysis using random effect model on overall proportions at the different time intervals and at the end of the follow-up was carried out for all studies. RESULTS: In total, 1,611 studies were retrieved from literature search. Of these, nine studies met the inclusion criteria with 1,307 patients. Two studies with 148 patients demonstrated an overall pooled proportion of 18.7% (95% CI 8.2-32.3%) of patients RTS at 3 month post-TKA; Three studies reported RTS rate at 6 months 70.% (95% CI 48-88.4). Two studies with 123 patients demonstrated an overall pooled proportion of 84.0% (95% CI 77.1-89.9%) patients RTS at 12 months. 986 patients returned to sport from total of 1307, with an overall adjusted proportion return to sport of 87.9 (95% CI 80.5-93.8%) at the end of follow-up; mean 14 months (range 3-36 months). CONCLUSION: Patients undergoing TKA were found to successfully RTS, pooled proportion analysis showed an increasing rate of RTS with time, at a mean of 14 months following TKA, where 87.9% of patients had returned to sports. The findings of this study will enable more informed discussions and rehabilitation planning between patients and clinicians on RTS following TKA.

Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements.

In the frame of "precision medicine", the scandium radionuclides have recently received considerable interest, providing personalised adjustment of radiation characteristics to optimize the efficiency of medical care or therapeutic benefit for particular groups of patients. Radionuclides of scandium, namely scandium-43 and scandium-44 (43/44Sc) as positron emitters and scandium-47 (47Sc), beta-radiation emitter, seem to fit ideally into the concept of theranostic pair. This paper aims to review the work on scandium isotopes production, coordination chemistry, radiolabeling, preclinical studies and the very first clinical studies. Finally, standardized procedures for scandium-based radiopharmaceuticals have been proposed as a basis to pave the way for elaboration of the Ph.Eur. monographs for perspective scandium radionuclides.

Artificial intelligence and surgical innovation: lower limb arthroplasty.

The number of patients requiring hip and knee arthroplasty continues to rise each year. Patients are living longer and expecting to remain active into later life following joint replacement. Developments in computer-assisted surgery and robotic technology may optimise surgical outcomes and patient satisfaction following lower limb arthroplasty. The use of artificial intelligence in healthcare is rapidly growing and has gained momentum in lower limb arthroplasty. This article reviews the use of artificial intelligence and surgical innovation in lower limb arthroplasty, with a particular focus on robotic-assisted surgery in total knee arthroplasty.

Use of preoperative opioids increases duration of hospital stay following elective lower limb arthroplasty. - A snapshot of UK practice.

This study is one of the first in the UK where to assess the link between pre-operative opioid use and length of stay or complications. The primary objective was to test our hypothesis; that low dose pre-operative opioids will not lead to an increase in complications and LOS in lower limb arthroplasty patients. 640 records were found and 625 patients were included whom received elective primary or revision surgery. It was found that Pre-operative opioids >12 MED does increase LOS.