bluuebunny/crossref_metadata_2025_split huggingface dataset:
A META-ANALYSIS OF OSTEOARTHRITIS SYNOVIAL BIOMARKERS
Authors: Sharp V.J. , Scott C.E.H. , Hing C.B. , Masieri F.F. 
Published: July 2023

Establishing disease biomarkers has been a long-sought after goal to improve Osteoarthritis (OA) diagnosis, prognosis, clinical and pharmaceutical interventions. Given the role of the synovium in contributing to OA, a meta-analysis was performed to determine significant synovial biomarkers in human OA tissue, compared to non-OA patients. Outcomes will direct future research on marker panels for OA disease modelling in vitro/in vivo, aiding clinical research into OA disease targets.A PRISMA compliant search of databases was performed to identify potential biomarker studies analysing human, OA, synovial samples compared to non-OA/healthy participants. The Risk of Bias In Non-Randomised Studies of Interventions (ROBINS-I) tool assessed methodological quality, with outcome analysed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were conducted for individual biomarkers using fixed or random effect models, as appropriate. Where three or more studies included a specific biomarker, Forest Plot comparisons were generated.3230 studies were screened, resulting in 34 studies encompassing 25 potential biomarkers (1581 OA patients and 695 controls). Significant outcomes were identified for thirteen comparisons. Eleven favoured OA (IL-6, IL-10, IL-13, IP-10, IL-8, CCL4, CCL5, PIICP, TIMP1, Leptin and VEGF), two favoured non-OA controls (BMP-2 and HA). Notably, PIICP showed the largest effect (SMD 6.11 [3.50, 8.72], p <0.00001, I2 99%), and TIMP1 resulted critically important (0.95 [0.65, 1.25], p <0.00001, I2 82%). Leptin and CCL4 showed lower effects (SMD 0.81 [0.33, 1.28], p =0.0009; 0.59 [0.32, 0.86], p <0.0001, respectively).Thirteen significant synovial biomarkers showed links with OA bioprocesses including collagen turnover, inflammatory mediators and ECM components. Limitations arose due to bias risk from incomplete or missing data, publication bias of inconclusive results, and confounding factors from patient criteria. These findings suggest markers of potential clinical viability for OA diagnosis and prognosis that could be correlated with specific disease stages.
EPISOMAL VECTOR-BASED GENERATION OF IPSC LINES FROM HEALTHY AND OSTEOARTHRITIS (OA) PATIENT SYNOVIOCYTES FOR OA MODELLING IN VITRO
Authors: Sharp V.J. , Bury N.R. , Masieri F.F. 
Published: July 2023

The development of a representative human, in vitro OA model could deepen understanding of disease mechanisms. Our research aimed to reprogram healthy and OA-derived synoviocytes to induced pluripotent stem cells (iPSCs), thereby generating a novel OA in vitro model. Comparison between the two models shall enable research into underlying processes with potential for clinical translation.A meta-analysis of OA synovial biomarkers was conducted, identifying up to thirteen relevant pathophysiology-related factors, including, amongst others, IL-13, IL-10, IL-6, PIICP, and HA, with PIICP demonstrating the largest effect (SMD 6.11 [3.50, 8.72], p <0.00001). With these findings in mind, human fibroblast-like synoviocytes (HFLS) from healthy and OA patients were transduced using Sendai viral reprogramming. Two clones for each of the resulting iPSC lines were expanded and preliminarily analysed in triplicate by ICC and RT-qPCR for pluripotency characteristics.Healthy HFLS-derived and OA-HFLS-derived iPSC (UoS-B and UoS-C lines, respectively) were generated, indicating successful reprogramming. Morphological observations demonstrated typical iPSC appearance, and ICC confirmed presence of pluripotency markers Tra-1-60, Oct3/4 and Nanog. Expression of Oct3/4, Nanog and Sox2 were confirmed by RT-qPCR with OA-iPSC lines expressing higher levels of all markers compared to non-OA iPSC. In particular, expression of Oct3/4 and Sox2 was 3.5 fold and 4.6 fold higher (p <0.001) in OA-iPSCs (UoS-C) vs. non-OA iPSCs (UoS-B), respectively. Sendai virus clearance was confirmed by passage 4.The successfully obtained OA and non-OA iPSCs can be differentiated towards mesenchymal lineages, including chondrocyte and bone progenitor cells, enabling phenotypic comparison and biomarker analysis as identified in meta-analysis. Cell bank dissemination of these cell lines could deepen further in vitro OA research, with potential impact for clinical translation via the identification of novel cellular and molecular targets.
GIRDLESTONE RESECTION ARTHROPLASTY OF THE HIP (GRA): OUTDATED PROCEDURE OR ACCEPTABLE OUTCOME?
Authors: Condell R. , Flanagan C. , Kearns S. , Murphy C. 
Published: July 2023

Despite considerable legacy issues, Girdlestone's Resection Arthroplasty (GRA) remains a valuable tool in the armoury of the arthroplasty surgeon. When reserved for massive lysis in the context of extensive medical comorbidities which preclude staged or significant surgical interventions, and / or the presence of pelvic discontinuity, GRA as a salvage procedure can have satisfactory outcomes. These outcomes include infection control, pain control and post-op function. We describe a case series of 13 cases of GRA and comment of the indications, peri, and post-operative outcomes.We reviewed all cases of GRA performed in our unit during an 8 year period, reviewing the demographics, indications, and information pertaining to previous surgeries, and post op outcome for each. Satisfaction was based on a binary summation (happy/unhappy) of the patients’ sentiments at the post-operative outpatient consultations.13 cases were reviewed. They had a mean age of 75. The most common indication was PJI, with 10 cases having this indication. The other three cases were performed for avascular necrosis, pelvic osteonecrosis secondary to radiation therapy and end stage arthritis on a background of profound learning disability in a non-ambulatory patient. The average number of previous operations was 5 (1-10). All 13 patients were still alive post girdlestone. 7 (54%) were satisfied, 6 were not. 3 patients were diabetic. 5 patients developed a sinus tract following surgery.With sufficient pre-op patient education, early intensive physiotherapy, and timely orthotic input, we feel this procedure remains an important and underrated and even compassionate option in the context of massive lysis and / or the presence of pelvic discontinuity / refractory PJI. GRA should be considered not a marker of failure but as a definitive procedure that gives predictability to patients and surgeon in challenging situations.
A BIOMECHANICAL ASSESSMENT OF ZIMMER BIOMET'S NEXGEN TOTAL KNEE ARTHROPLASTY AS COMPARED WITH HEALTHY OLDER ADULTS
Authors: Tawy G. , McNicholas M. , Biant L. 
Published: July 2023

Total knee arthroplasty (TKA) aims to alleviate pain and restore joint biomechanics to an equivalent degree to age-matched peers.Zimmer Biomet's Nexgen TKA was the most common implant in the UK between 2003 and 2016. This study compared the biomechanical outcomes of the Nexgen implant against a cohort of healthy older adults to determine whether knee biomechanics is restored post-TKA.Patients with a primary Nexgen TKA and healthy adults >55 years old with no musculoskeletal deficits or diagnosis of arthritis were recruited locally.Eligible participants attended one research appointment. Bilateral knee range of motion (RoM) was assessed with a goniometer. A motorised arthrometer (GENOUROB) was then used to quantify the anterior-posterior laxity of each knee. Finally, gait patterns were analysed on a treadmill. An 8-camera Vicon motion capture system generated the biomechanical model.Preliminary statistical analyses were performed in SPSS (α = 0.05; required sample size for ongoing study: n=21 per group).The patient cohort (n=21) was older and had a greater BMI than the comparative group (n=13). Patients also had significantly poorer RoM than healthy older adults. However, there were no inter-group differences in knee laxity, walking speed or cadence. Gait kinematics were comparable in the sagittal plane during stance phase. Peak knee flexion during swing phase was lower in the patient group, however (49.0° vs 41.1°).Preliminary results suggest that knee laxity and some spatiotemporal and kinematic parameters of gait are restored in Nexgen TKA patients.While knee RoM remains significantly poorer in the patient cohort, an average RoM of >110° was achieved. This suggests the implant provides sufficient RoM for most activities of daily living. Further improvements to knee kinematics may necessitate additional rehabilitation.Future recruitment drives will concentrate on adults over the age of 70 for improved inter-group comparability.
THE POTENTIAL OF MAGNETIC CELL SHEET PATCHES IN TENDON REGENERATION
Authors: Gonçalves A. , Rodrigues M. , Gomes M. 
Published: July 2023

Tissue engineering and regenerative medicine (TERM) hold the promise to provide therapies for injured tendons despite the challenging cues of tendon niche and the lack of specific factors to guide regeneration. The emerging potential of magnetic responsiveness and magnetic nanoparticles (MNPs) functionalities offers new perspectives to tackle TERM challenges. Moreover, pulsed electromagnetic field (PEMF) is FDA approved for orthopaedics with potential to control inflammation upon injury. We previously demonstrated that magnetic cell-sheets assisted by PEMF trigger the inflammation resolution by modulating cytokine-enriched environments [1]. To further understand the potential of magnetically assisted living patches, we have recently conducted in vivo studies using a rat patellar defect model.After labeling of human adipose stem cells with iron oxide MNPs for 16h, magCSs were cultured up to 3 days in α-MEM medium under non-magnetic or PEMF conditions. MagCSs were evaluated by immunocytochemistry, and real time RT-PCR for tendon markers. Cell metabolic activity was also assessed by MTS and ECM proteins quantified by Sirius Red/Fast Green.The MagCSs effect in ameliorating healing was assessed after implantation in window defects created in the patellar tendon of rats. PEMF was externally applied (3mT, 70Hz) 3d/week for 1h (magnetotherapy). After 4 and 8w, tendons were histologically characterized for immune-detection of tendon and inflammatory markers, and for Perls van Gieson and HE stains. Blood and detoxification organs were screened for inflammatory mediators and biodistribution of MNPs, respectively.In vitro results suggest that PEMF stimulates cellular metabolic activity, influences protein synthesis and the deposition of collagen and non-collagenous proteins is significantly increased compared to non-magnetic conditions. No adverse reactions, as infection or swelling, were observed after surgery or during follow-up. After 8w, magCSs remained at the implantation site and no MNPs were detected on detoxification organs. Plasma levels of IL1α, β, IL6 and TNFα assessed by multiplex assay were below detectable values (<12.5pg/ml).Thus, the combination of cell sheets and magnetic technologies hold promise for the development of living tendon substitutes.Acknowledgement to ERC-COG MagTendon772817, H2020 Achilles 810850, FCT - 2020.01157.CEECIND.
IMPROVED MECHANICAL ANCHORAGE OF GAMMA NAIL LAG SCREW IN OSTEOPOROTIC BONE: A BIOMECHANICAL STUDY
Authors: Raina D. , Mrkonjic F. , Tägil M. , Lidgren L. 
Published: July 2023

A number of techniques have been developed to improve the immediate mechanical anchorage of implants for enhancing implant longevity. This issue becomes even more relevant in patients with osteoporosis who have fragile bone. We have previously shown that a dynamic hip screw (DHS) can be augmented with a calcium sulphate/hydroxyapatite (CaS/HA) based injectable biomaterial to increase the immediate mechanical anchorage of the DHS system to saw bones with a 400% increase in peak extraction force compared to un-augmented DHS. The results were also at par with bone cement (PMMA). The aim of this study was to investigate the effect of CaS/HA augmentation on the integration of a different fracture fixation device (gamma nail lag-screw) with osteoporotic saw bones.Osteoporotic saw bones (bone volume fraction = 15%) were instrumented with a gamma nail without augmentation (n=8) or augmented (n=8) with a CaS/HA biomaterial (Cerament BVF, Bonesupport AB, Sweden) using a newly developed augmentation method described earlier. The lag-screws from both groups were then pulled out at a displacement rate of 0.5 mm/s until failure. Peak extraction force was recorded for each specimen along with photographs of the screws post-extraction. A non-parametric t-test was used to compare the two groups.CaS/HA augmentation of the lag-screw led to a 650% increase in the peak extraction force compared with the controls (p<0.01). Photographs of the augmented samples shows failure of the saw-bones further away from the implant-bone interface indicating a protective effect of the CaS/HA material.We present a novel method to enhance the immediate mechanical anchorage of a lag-screw to osteoporotic bone and it is also envisaged that CaS/HA augmentation combined with systemic bisphosphonate treatment can lead to new bone formation and aid in the reduction of implant failures and re-operations.
HIP PRECAUTIONS ON DISCHARGE FOLLOWING HEMIARTHROPLASTY FOR NECK OF FEMUR FRACTURES: A SURVEY
Authors: Gupta P. , Butt S. , Dasari K. , Mallick E. , Nandhara G. 
Published: July 2023

Hip precautions are currently practiced in three-quarters of trauma hospitals in the UK, despite national recommendations from the ‘Blue Book’ not stating it as a requirement. Valuable therapist time is utilised alongside the need for specialised equipment, which can potentially delay discharge whilst it is being arranged.
Objective of this study was to explore the current practice of the use of hip precautions on discharge following hemiarthroplasty for hip fractures. To also explore whether they are necessary and to identify areas for improvement to benefit patient care overall.Online survey distributed to various Trauma and Orthopaedic Departments across the UK. Survey was available over a 4-month period, collecting 55 responses overall.Majority of responses were from trauma and orthopaedic consultants who were aware of the ‘Blue Book’ recommendations. The majority of trusts who responded did not practice hip precautions and did not feel this increased the risk of dislocations on discharge. Recommendations included integration of hip precautions in the post-op advice in coordination with the physiotherapist and information leaflets on discharge regarding hip precautions.
Hip precautions were not commonly practiced, for reasons including patient compliance and the inherently stable procedure of a hemiarthroplasty compared to a THR, reducing the need for hip precautions.Hip precautions are not widely regarded as a useful practice for post-hip hemiarthroplasty, viewed as utilising more resources and increasing costs and risk due to increased hospital stay. Thus, this potentially delays discharge overall. A consistent approach should be implemented in treating patients post-hip hemiarthroplasty.
NOVEL TECHNIQUE OF SHORT-ACTING SPINAL ANAESTHESIA FOR FRACTURE NECK OF FEMUR SURGERY ALLOWING EARLY MOBILIZATION, REDUCING MORBIDITY AND MORTALITY, AND IMPROVING OVERALL FUNCTIONAL OUTCOME
Authors: Gupta P. , Butt S. , Mahajan R. , Galhoum A. , Lakdawala A. 
Published: July 2023

Prompt mobilisation after the Fracture neck of femur surgery is one of the important key performance index (‘KPI caterpillar charts’ 2021) affecting the overall functional outcome and mortality. Better control of peri-operative blood pressure and minimal alteration of renal profile as a result of surgery and anaesthesia may have an implication on early post-operative mobilisation.Aim was to evaluate perioperative blood pressure measurements (duration of fall of systolic BP below the critical level of 90mmHg) and effect on the post-operative renal profile with the newer short acting spinal anaesthetic agent (prilocaine and chlorprocaine) used alongside the commonly used regional nerve block. 20 patients were randomly selected who were given the newer short acting spinal anaesthetic agent along with a regional nerve block between May 2019 and February 2020. Anaesthetic charts were reviewed from all patients for data collection. The assessment criteria for perioperative hypotension: Duration of systolic blood pressure less than 90 mm of Hg and change of pre and post operative renal functions.Only one patient had a significant drop in systolic BP less than 90mmHg (25 minutes). 3 other patients had a momentary fall of systolic BP of less than 5 minutes. None of the above patients had mortality and had negligible change in pre and post op renal function. Only one patient in this cohort had elevation of post-operative creatinine levels but did not have any mortality. Only 1 patient died on day 3 post operatively who had multiple comorbidities and was under evaluation for GI cancer. Even in this patient the peri-operative blood pressure was well maintained (never below 90mmHg systolic) and post-operative renal function was also shown to have improved (309 pre-operatively to 150 post-operatively) in this patient.The use of short-acting spinal anaesthesia has shown to be associated with a better control of blood pressure and end organ perfusion, less adverse effects on renal function leading to early mobilisation and a more favourable patient outcome with reduced mortality, earlier mobilisation, shorter hospital stay and earlier discharge in this elderly patient cohort.
Ethical considerations in the prehospital treatment of out-of-hospital cardiac arrest: A multi-centre, qualitative study
Authors: Milling Louise , Nielsen Dorthe Susanne , Kjær Jeannett , Binderup Lars Grassmé , de Muckadell Caroline Schaffalitzky , Christensen Helle Collatz , Christensen Erika Frischknecht , Lassen Annmarie Touborg , Mikkelsen Søren 
Published: July 2023

Background
Prehospital emergency physicians have to navigate complex decision-making in out-of-hospital cardiac arrest (OHCA) treatment that includes ethical considerations. This study explores Danish prehospital physicians’ experiences of ethical issues influencing their decision-making during OHCA.

Methods
We conducted a multisite ethnographic study. Through convenience sampling, we included 17 individual interviews with prehospital physicians and performed 22 structured observations on the actions of the prehospital personnel during OHCAs. We collected data during more than 800 observation hours in the Danish prehospital setting between December 2019 and April 2022. Data were analysed with thematic analysis.

Results
All physicians experienced ethical considerations that influenced their decision-making in a complex interrelated process. We identified three overarching themes in the ethical considerations: Expectations towards patient prognosis and expectations from relatives, bystanders, and colleagues involved in the cardiac arrest; the values and beliefs of the physician and values and beliefs of others involved in the cardiac arrest treatment; and dilemmas encountered in decision-making such as conflicting values.

Conclusion
This extensive qualitative study provides an in-depth look at aspects of ethical considerations in decision-making in prehospital resuscitation and found aspects of ethical decision-making that could be harmful to both physicians and patients, such as difficulties in handling advance directives and potential unequal outcomes of the decision-making. The results call for multifaceted interventions on a wider societal level with a focus on advance care planning, education of patients and relatives, and interventions towards prehospital clinicians for a better understanding and awareness of ethical aspects of decision-making.
Acceptance of and hesitancy about COVID-19 vaccination among nursing students in clinical practice
Authors: Kim Saeryun , Lee Jisuk , Yang Hyunju , Kim Hyunkyun 
Published: July 2023

Background
Although vaccination of nursing students in clinical practice is important due to the possibility of COVID-19 infection and subsequent transmission to patients, some nursing students are hesitant to get vaccinated. Thus, it is necessary to identify the actual intentions and motivations of nursing students who have been vaccinated for COVID-19, even if their decisions were driven by clinical practice policy. The purpose of this study was to understand the nature of COVID-19 vaccine hesitancy among vaccinated nursing students in clinical practice and to examine their reasons for getting vaccinated despite such hesitancy.

Method
A cross-sectional, descriptive study was conducted at two tertiary hospitals in South Korea from November 20, 2021, to December 17, 2021. The study recruited a convenience sample of 125 nursing students who were vaccinated for COVID-19. Data were analyzed using the chi-square test, Fisher’s exact test, and independent t-test.

Results
Of the 125 nursing students, 51 (40.8%) reported vaccine hesitancy, among whom 88.2% reported that their hesitancy was due to the adverse effects and instability of the vaccine. It was also found that 70.6% of nursing students in the vaccine-hesitant group were eventually vaccinated due to clinical practice policy, whereas 67.6% of nursing students in the non-hesitant group were vaccinated to protect their health.

Conclusions
COVID-19 vaccine hesitancy is prevalent among nursing students. Therefore, specific efforts should be made to provide education focusing on the safety, benefits, and efficacy of COVID-19 vaccines, implement mandatory vaccination policies for clinical practice, and give priority to vaccination opportunities to nursing students in order to reduce the hesitancy of nursing students to vaccines.
Educational outcomes in childhood cancer survivors: A Scotland-wide record-linkage study of 766,217 schoolchildren
Authors: Baughan Nicholas , Pell Jill P. , Mackay Daniel F. , Clark David , King Albert , Fleming Michael 
Published: July 2023

Background
A cancer diagnosis during childhood greatly disrupts the lives of those affected, causing physical and psychological challenges. We aim to investigate educational outcomes among schoolchildren with a previous cancer diagnosis compared to their peers.

Methods
Individual records from four national education databases and three national health databases were linked to construct a cohort of all singleton schoolchildren born in Scotland attending Scottish local-authority schools between 2009–2013. Pupils previously diagnosed with any cancer, haematological cancers, and central nervous system (CNS) cancers, were compared to their unaffected peers with respect to five educational outcomes: special educational need (SEN), absenteeism, school exclusion, academic attainment, and unemployment. Analyses were adjusted for sociodemographic and maternity factors and chronic conditions.

Results
Of 766,217 pupils, 1,313 (0.17%) had a previous cancer diagnosis. Children with any cancer had increased odds of SEN (OR 3.26, 95% CI 2.86–3.71), absenteeism (IRR 1.82, 95% CI 1.70–1.94), and low attainment (OR 2.15, 95% CI 1.52–3.03) compared to their peers. Similar findings were observed for haematological (SEN OR 2.62, 95% CI 2.12–3.24; absenteeism IRR 2.04, 95% CI 1.85–2.25; low attainment OR 2.17, 95% CI 1.31–3.61) and CNS (SEN OR 6.44, 95% CI 4.91–8.46; absenteeism IRR 1.75, 95% CI 1.51–2.04; low attainment OR 3.33, 95% CI 1.52–7.30) cancers. Lower exclusions were observed among children with any cancer (IRR 0.51, 95% CI 0.31–0.83) and CNS cancer (IRR 0.20, 95% CI 0.06–0.61). No associations were observed with unemployment.

Conclusions
This study highlights the wider impacts of childhood cancer on educational outcomes. These children need to be supported, as poor educational outcomes can further impact later health.