The evolution of poller screws.

Compared to other techniques, poller screws with intramedullary nailing are technically simple, practical, and reproducible for the fixation of metaphyseal fractures. In addition, poller screws do not require special instruments or hardware and are minimally invasive. This review takes a historical perspective to evaluate poller screws holistically. A non-systematic search on PubMed was performed using 'Poller screw' or 'Blocking screw' to find early use of poller blocking screws. Relevant references from these primary studies were then followed up. In 1999, Krettek et al. first coined the term poller screws after the small metal bollards that block and direct traffic. Poller screws were introduced as an adjunct to aid the union of metaphyseal long bone fractures during intramedullary nailing. However, as more evidence was published, the true effectiveness of poller screws was not appreciated, leading to split opinions. Through our research, we have built upon our understanding of poller screws, and we present a novel classification of poller screws over the years while exploring our novel technique and what we believe to be the fourth generation of poller screws. Currently, there is a paucity of research focussing on poller screws. However, studying the original evidence regarding poller screws through the most recent articles has demonstrated a confusion of research in this field. Therefore, we suggest a more organised approach to classify the use of poller screws.

Insulin Signaling Differentially Regulates the Trafficking of Insulin and Amyloid Beta Peptides at the Blood-Brain Barrier.

The blood-brain barrier (BBB) is instrumental in clearing toxic metabolites from the brain, such as amyloid-ß (Aß) peptides, and in delivering essential nutrients to the brain, like insulin. In Alzheimer's disease (AD) brain, increased Aß levels are paralleled by decreased insulin levels, which are accompanied by insulin signaling deficits at the BBB. Thus, we investigated the impact of insulin-like growth factor and insulin receptor (IGF1R and IR) signaling on Aß and insulin trafficking at the BBB. Following intravenous infusion of an IGF1R/IR kinase inhibitor (AG1024) in wild-type mice, the BBB trafficking of 125I radiolabeled Aß peptides and insulin was assessed by dynamic SPECT/CT imaging. The brain efflux of [125I]iodo-Aß42 decreased upon AG1024 treatment. Additionally, the brain influx of [125I]iodoinsulin, [125I]iodo-Aß42, [125I]iodo-Aß40, and [125I]iodo-BSA (BBB integrity marker) was decreased, increased, unchanged, and unchanged, respectively, upon AG1024 treatment. Subsequent mechanistic studies were performed using an in vitro BBB cell model. The cell uptake of [125I]iodoinsulin, [125I]iodo-Aß42, and [125I]iodo-Aß40 was decreased, increased, and unchanged, respectively, upon AG1024 treatment. Further, AG1024 reduced the phosphorylation of insulin signaling kinases (Akt and Erk) and the membrane expression of Aß and insulin trafficking receptors (LRP-1 and IR-ß). These findings reveal that insulin signaling differentially regulates the BBB trafficking of Aß peptides and insulin. Moreover, deficits in IGF1R and IR signaling, as observed in the brains of type II diabetes and AD patients, are expected to increase Aß accumulation while decreasing insulin delivery to the brain, which has been linked to the progression of cognitive decline in AD.

The accuracy and diagnostic value of gram staining joint aspirates in suspected joint infections.

BACKGROUND: Septic arthritis is a debilitating condition with prolonged treatment and adverse outcomes. A gram stain is often performed from the joint aspirate sample, followed by a definitive culture. In our study, we assessed the accuracy of gram staining for suspected septic arthritis and explored factors associated with positive culture growth and false negatives in the gram stain. METHODS: We retrospectively reviewed joint aspirates performed from 2015-2021 at a major trauma centre. Aspirates not cultured for septic arthritis were excluded. Data collected included aspirate site, gram stain and culture result delay, patient demographics, orthopaedic/rheumatological history, and comorbidities. Outcomes measured were gram stain sensitivity and specificity. Factors influencing positive cultures and false negative gram stain results were analysed using logistic regression. RESULTS: Of 408 joint aspirates meeting the criteria, 37 did not undergo initial gram staining. Gram stain sensitivity was 30.4%, specificity was 97.6%. The delay from aspirate to definitive gram stain and culture results was 1.1 and 5.4 days, respectively Logistic regression identified that prosthetic joint(p = 0.007), past joint infections(p = 0.006), arthritis(p < 0.001), hypertension(p = 0.007), diabetes(p = 0.019) were positively associated with positive cultures. Past joint infections(p = 0.004) were positively associated with false negative gram stain results. Patients on antibiotics during the aspirate had a higher risk of false negative gram stain results (OR = 5.538, 95%CI, 2.802-10.948; p < 0.001). CONCLUSIONS: In conclusion, the initial gram stain has limited sensitivity and caution should be exercised when interpreting negative results. Vigilance is crucial when the highlighted comorbidities or antibiotic use are present, to assess patients with potential joint infections.

Adding α,α-disubstituted and ß-linked monomers to the genetic code of an organism.

The genetic code of living cells has been reprogrammed to enable the site-specific incorporation of hundreds of non-canonical amino acids into proteins, and the encoded synthesis of non-canonical polymers and macrocyclic peptides and depsipeptides1-3. Current methods for engineering orthogonal aminoacyl-tRNA synthetases to acylate new monomers, as required for the expansion and reprogramming of the genetic code, rely on translational readouts and therefore require the monomers to be ribosomal substrates4-6. Orthogonal synthetases cannot be evolved to acylate orthogonal tRNAs with non-canonical monomers (ncMs) that are poor ribosomal substrates, and ribosomes cannot be evolved to polymerize ncMs that cannot be acylated onto orthogonal tRNAs-this co-dependence creates an evolutionary deadlock that has essentially restricted the scope of translation in living cells to α-L-amino acids and closely related hydroxy acids. Here we break this deadlock by developing tRNA display, which enables direct, rapid and scalable selection for orthogonal synthetases that selectively acylate their cognate orthogonal tRNAs with ncMs in Escherichia coli, independent of whether the ncMs are ribosomal substrates. Using tRNA display, we directly select orthogonal synthetases that specifically acylate their cognate orthogonal tRNA with eight non-canonical amino acids and eight ncMs, including several ß-amino acids, α,α-disubstituted-amino acids and ß-hydroxy acids. We build on these advances to demonstrate the genetically encoded, site-specific cellular incorporation of ß-amino acids and α,α-disubstituted amino acids into a protein, and thereby expand the chemical scope of the genetic code to new classes of monomers.

Prospective Evaluation of the Clinical Benefits of a Novel Tattoo-less Workflow for Nonspine Bone Stereotactic Body Radiation Therapy: Integrating Surface-Guidance With Triggered Imaging Reduces Treatment Time and Eliminates the Need for Tattoos.

PURPOSE: Oligometastatic disease has expanded the indications for nonspine bone stereotactic body radiation therapy (NSB SBRT). We investigated whether optical surface monitoring systems (OSMS) could enable tattoo-less setup and substitute for 2-dimensional/3-dimensional or cone beam computed tomography (CBCT)-based mid-imaging in NSB SBRT. METHODS AND MATERIALS: OSMS was incorporated in parallel with an existing workflow using pretreatment CBCT and 2-dimensional/3-dimensional kV/kV mid-imaging beginning November 2019. The ability of OSMS to detect out-of-tolerance (>2 mm/>2°) and commanded couch shifts was analyzed. A workflow incorporating OSMS reference captures, CBCT for pretreatment verification, and OSMS/triggered imaging (TI) for intrafraction monitoring was developed for rib/sternum SBRT beginning November 2021 and all NSB SBRT beginning February 2022. Treatment time and CBCT-related radiation dose between the OSMS and the non-OSMS intrafraction monitoring group was analyzed pre- and post-OSMS/TI workflow adoption. All fractions were analyzed through statistical process control with use of an XmR chart of treatment time per quarter from February 2019 to February 2023. Special cause rules were based on Institute for Healthcare Improvement criteria. RESULTS: From February 2019 to February 2023, 1993 NSB SBRT fractions were delivered, including 234 rib, 109 sternum, 214 ilium, and 682 multisite. Over 20 commanded shifts, OSMS could detect 2-mm shifts to within 0.4 mm 67% of the time and 0.8 mm 95% of the time. All NSB SBRT sites showed significant reductions in treatment time, including the greatest improvement in rib total treatment (21.6-13.4 minutes; P = 1.16 × 10-17) and beam time (7.9-3.2 minutes; P = 7.32 × 10-27). Significant reductions in CBCT-related radiation were also observed for several NSB sites. These process improvements were associated with OSMS adoption. CONCLUSIONS: Adoption of a novel NSB SBRT workflow incorporating OSMS/TI for bone intrafraction motion monitoring reduced treatment time and CBCT-related radiation exposure while also allowing for more continuous intrafraction motion monitoring for NSB SBRT. OSMS/TI enabled the transition to a tattoo-less workflow.

Using Pre-Clinical Studies to Explore the Potential Clinical Uses of Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem cells.

Recent studies of exosomes derived from mesenchymal stem cells (MSCs) have indicated high potential clinical applications in many diseases. However, the limited source of MSCs impedes their clinical research and application. Most recently, induced pluripotent stem cells (iPSCs) have become a promising source of MSCs. Exosome therapy based on iPSC-derived MSCs (iMSCs) is a novel technique with much of its therapeutic potential untapped. Compared to MSCs, iMSCs have proved superior in cell proliferation, immunomodulation, generation of exosomes capable of controlling the microenvironment, and bioactive paracrine factor secretion, while also theoretically eliminating the dependence on immunosuppression drugs. The therapeutic effects of iMSC-derived exosomes are explored in many diseases and are best studied in wound healing, cardiovascular disease, and musculoskeletal pathology. It is pertinent clinicians have a strong understanding of stem cell therapy and the latest advances that will eventually translate into clinical practice. In this review, we discuss the various applications of exosomes derived from iMSCs in clinical medicine.

Identification of age- and immune-related gene signatures for clinical outcome prediction in lung adenocarcinoma.

BACKGROUND: The understanding of the factors causing decreased overall survival (OS) in older patients compared to younger patients in lung adenocarcinoma (LUAD) remains. METHODS: Gene expression profiles of LUAD were obtained from publicly available databases by Kaplan-Meier analysis was performed to determine whether age was associated with patient OS. The immune cell composition in the tumor microenvironment (TME) was evaluated using CIBERSORT. The fraction of stromal and immune cells in tumor samples were also using assessed using multiple tools including ESTIMATE, EPIC, and TIMER. Differentially expressed genes (DEGs) from the RNA-Seq data that were associated with age and immune cell composition were identified using the R package DEGseq. A 22-gene signature composed of DEGs associated with age and immune cell composition that predicted OS were constructed using Least Absolute Shrinkage and Selection Operator (LASSO). RESULTS: In The Cancer Genome Atlas (TCGA)-LUAD dataset, we found that younger patients (≤70) had a significant better OS compared to older patients (>70). In addition, older patients had significantly higher expression of immune checkpoint proteins including inhibitory T cell receptors and their ligands. Moreover, analyses using multiple bioinformatics tools showed increased immune infiltration, including CD4+ T cells, in older patients compared to younger patients. We identified a panel of genes differentially expressed between patients >70 years compared to those ≤70 years, as well as between patients with high or low immune scores and selected 84 common genes to construct a prognostic gene signature. A risk score calculated based on 22 genes selected by LASSO predicted 1, 3, and 5-year OS, with an area under the curve (AUC) of 0.72, 0.72, 0.69, receptively, in TCGA-LUAD dataset and an independent validation dataset available from the European Genome-phenome Archive (EGA). CONCLUSION: Our results demonstrate that age contributes to OS of LUAD patients atleast in part through its association with immune infiltration in the TME.

Predictors for infection severity for open tibial fractures: major trauma centre perspective.

INTRODUCTION: Open diaphyseal tibial fractures are the most common long-bone fractures and require a rapid approach to prevent devastating complications. Current literature reports the outcomes of open tibial fractures. However, there is no robust, up-to-date research on the predictive indicators of infection severity in a large open tibial fracture patient cohort. This study investigated the predictive factors of superficial infections and osteomyelitis in open tibial fractures. MATERIALS AND METHODS: A retrospective analysis of the tibial fracture database was carried out from 2014 to 2020. Criteria for inclusion was any tibial fracture including tibial plateau, shaft, pilon or ankle, with an open wound at the fracture site. Exclusion criteria included patients with a follow-up period of less than 12 months and who are deceased. A total of 235 patients were included in our study, of which 154 (65.6%), 42 (17.9%), and 39 (16.6%) developed no infection, superficial infection, or osteomyelitis, respectively. Patient demographics, injury characteristics, fracture characteristics, infection status and management details were collected for all patients. RESULTS: On multivariate modelling, patients with BMI > 30 (OR = 2.078, 95%CI [1.145-6.317], p = 0.025), Gustilo-Anderson (GA) type III (OR = 6.120, 95%CI [1.995-18.767], p = 0.001), longer time to soft tissue cover (p = 0.006) were more likely to develop a superficial infection, and patients with wound contamination (OR = 3.152, 95%CI [1.079-9.207], p = 0.036), GA-3 (OR = 3.387,95%CI [1.103-10.405], p = 0.026), longer to soft tissue cover (p = 0.007) were more likely to develop osteomyelitis. Univariate analysis also determined that risk factors for superficial infection were: BMI > 35 (OR = 6.107, 95%CI [2.283-16.332], p = 0.003) and wound contamination (OR = 2.249, 95%CI [1.015-5.135], p = 0.047); whilst currently smoking (OR = 2.298, 95%CI [1.087-4.856], p = 0.025), polytrauma (OR = 3.212, 95%CI [1.556-6.629], p = 0.001), longer time to definitive fixation (p = 0.023) were for osteomyelitis. However, none of these reached significance in multivariate analysis. CONCLUSION: Higher GA classification is a significant risk factor for developing superficial infection and osteomyelitis, with a stronger association with osteomyelitis, especially GA 3C fractures. Predictors for superficial infection included BMI and time to soft tissue closure. Time to definitive fixation, time to soft tissue closure, and wound contamination were associated with osteomyelitis.

Ankle fusion with tibiotalocalcaneal retrograde nail for fragility ankle fractures: outcomes at a major trauma centre.

PURPOSE: Fragility ankles fractures in the geriatric population are challenging to manage, due to fracture instability, soft tissue compromise, and patient co-morbidities. Traditional management options include open reduction internal fixation, or conservative treatment, both of which are fraught with high complication rates. We aimed to present functional outcomes of elderly patients with fragility ankle fractures treated with retrograde ankle fusion nails. METHODS: A retrospective observational study was performed on patients who underwent intramedullary nailing with a tibiotalocalcaneal nail. Twenty patients met the inclusion criteria of being over sixty and having multiple co-morbidities. Patient demographics, AO/OTA fracture classification, intra-operative and post-operative complications, time to mobilisation and union, AOFAS and Olerud-Molander scores, and patient mobility were recorded. RESULTS: There were seven males and thirteen females, with a mean age of 77.82 years old, five of whom are type 2 diabetics. Thirteen patients returned to their pre-operative mobility state, and the average Charlson Co-morbidity Index (CCI) was 5.05. Patients with a low CCI are more likely to return to pre-operative mobility status (p = 0.16; OR = 4.00). All patients achieved radiographical union, taking on average between 92.5 days and 144.6 days. The mean post-operative AOFAS and Olerud-Molander scores were 53.0 and 50.9, respectively. There were four cases of superficial infection, four cases of broken or loose distal locking screws. There were no deep infections, periprosthetic fractures, nail breakages, or non-unions. CONCLUSION: Tibiotalocalcaneal nailing is an effective and safe option for managing unstable ankle fractures in the elderly. This technique leads to lower complication rates and earlier mobilisation than traditional fixation methods.

A retrospective analysis of the definitive management of open talus fractures at a major trauma centre, comparing ORIF to FUSION: cohort study and audit of BOAST 4 guidelines.

PURPOSE: Open talus fractures are notoriously difficult to manage, and they are commonly associated with a high level of complications including non-union, avascular necrosis and infection. Currently, the management of such injuries is based upon BOAST 4 guidelines although there is no suggested definitive management, and thus, definitive management is based upon surgeon preference. The key principles of open talus fracture management which do not vary between surgeons are early debridement, orthoplastic wound care, anatomic reduction and definitive fixation whenever possible. However, there is much debate over whether the talus should be preserved or removed after open talus fracture/dislocation and proceeded to tibiocalcaneal fusion. METHODS: A review of electronic hospital records for open talus fractures from 2014 to 2021 returned fourteen patients with fifteen open talus fractures. Seven cases were initially managed with ORIF, and five cases were definitively managed with FUSION, while the others were managed with alternative methods. We collected patient's age, gender, surgical complications, surgical risk factors and post-treatment functional ability and pain and compliance with BOAST guidelines. The average follow-up of the cohort was 4 years and one month. EQ-5D-5L and FAAM-ADL/Sports score was used as a patient reported outcome measure. Data were analysed using the software PRISM. RESULTS: Comparison between FUSION and ORIF groups showed no statistically significant difference in EQ-5D-5L score (P = 0.13), FAAM-ADL (P = 0.20), FAAM-Sport (P = 0.34), infection rate (P = 0.55), surgical times (P = 0.91) and time to weight bearing (P = 0.39), despite a higher proportion of polytrauma and Hawkins III and IV fractures in the FUSION group. CONCLUSION: FUSION is typically used as second line to ORIF or failed ORIF. However, there is a lack of studies that directly compared outcome in open talus fracture patients definitively managed with FUSION or ORIF. Our results demonstrate for the first time that FUSION may not be inferior to ORIF in terms of patient functional outcome, infection rate and quality of life, in the management of patients with open talus fracture patients. Of note, as open talus fractures have increased risks of complications such as osteonecrosis and non-union, FUSION should be considered as a viable option to mitigate these potential complications in these patients.

Variation on a technique for the intra-muscular insertion of nerve endings to minimise neuropathic and residual pain in lower limb amputees: a retrospective cohort study.

INTRODUCTION: A major cause of morbidity in lower limb amputees is phantom limb pain (PLP) and residual limb pain (RLP). This study aimed to determine whether a variation of the surgical technique of inserting nerve endings into adjacent muscle bellies at the time of lower limb amputation can decrease the incidence and severity of PLP and RLP. METHODS: Data were retrospectively collected from January 2015 to January 2021, including eight patients that underwent nerve insertion (NI) and 36 that received standard treatment. Primary outcomes included the 11-point Numerical Rating Scale (NRS) for pain severity, and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behaviour, and interference. Secondary outcome included Neuro-QoL Lower Extremity Function assessing mobility. Cumulative scores were transformed to standardised t scores. RESULTS: Across all primary and secondary outcomes, NI patients had lower PLP and RLP. Mean 'worst pain' score was 3.5 out of 10 for PLP in the NI cohort, compared to 4.89 in the control cohort (p = 0.298), and 2.6 out of 10 for RLP in the NI cohort, compared to 4.44 in the control cohort (p = 0.035). Mean 'best pain' and 'current pain' scores were also superior in the NI cohort for PLP (p = 0.003, p = 0.022), and RLP (p = 0.018, p = 0.134). Mean PROMIS t scores were lower for the NI cohort for RLP (40.1 vs 49.4 for pain intensity; p = 0.014, 44.4 vs 48.2 for pain interference; p = 0.085, 42.5 vs 49.9 for pain behaviour; p = 0.025). Mean PROMIS t scores were also lower for the NI cohort for PLP (42.5 vs 52.7 for pain intensity; p = 0.018); 45.0 vs 51.5 for pain interference; p = 0.015, 46.3 vs 51.1 for pain behaviour; p = 0.569). Mean Neuro-QoL t score was lower in NI cohort (45.4 vs 41.9; p = 0.03). CONCLUSION: Surgical insertion of nerve endings into adjacent muscle bellies during lower limb amputation is a simple yet effective way of minimising PLP and RLP, improving patients' subsequent quality of life. Additional comparisons with targeted muscle reinnervation should be performed to determine the optimal treatment option.

The Importance of Fracture Liaison Services to the Healthcare System: A Review.

Osteoporosis is an important public health concern, with secondary fragility fractures carrying a poor prognosis. The role of a Fracture Liaison Service (FLS) is to identify fragility fracture patients via investigation and risk assessment. This serves to address the osteoporosis treatment care gap that exists where the majority of patients with a new fragility fracture over 50-years-old fail to receive a bone mass density (BMD) scan and osteoporosis treatment, ultimately receiving inadequate care. Osteoporosis medication is effective in reducing secondary fragility fractures. However, treatment adherence poses a problem. The FLS serves to prevent more serious secondary fragility fractures such as hip fractures. This minimises operative costs and the cost of postoperative care and results in fewer secondary care and care home admissions, increasing healthcare savings. Implementation of the FLS is effective in increasing investigation, treatment initiation, and adherence, with a corresponding decrease in refracture rate and mortality. This paper aims to evaluate the previous osteoporosis treatment care gap, the effectiveness of osteoporosis medications currently available, and finally, the cost and clinical effectiveness of the FLS serving as a secondary prevention tool.

Patient safety, self-injection, and B12 deficiency: a UK cross-sectional survey.

BACKGROUND: Individuals with vitamin B12 deficiency (including pernicious anaemia) often report being 'let down' or stigmatised by general practice systems and policy, and choose instead to self-medicate via injection; the association between this and perceptions of safe primary care in this group of people is unknown. AIM: To examine the association between self-medication for vitamin B12 deficiency and patient-reported safety in primary care. DESIGN AND SETTING: A UK cross-sectional online survey. METHOD: The survey consisted of the three components: demographics; the validated Primary Care Patient Measure of Safety; and questions about self-medication for vitamin B12 deficiency. Multivariable logistic regression analyses and thematic synthesis were undertaken. RESULTS: Responses from 1297 participants indicated 508 (39.2%) self-medicated via injection. Perceived primary care safety was low. Those who self-medicated via injection reported a significantly lower level of patient safety in primary care including adverse patient-related factors (odds ratio 0.82, 95% confidence interval = 0.73 to 0.92), and patients >34 years of age were significantly more likely to self-medicate via injection. Many reported that treatment under the guidance of a clinician was preferable to self-medication, but felt they had no other choice to regain quality of life. Almost half felt that the doctor did not always consider what they wanted for their care. CONCLUSION: To the authors' knowledge, this is the largest study to date examining patient safety and vitamin B12 deficiency. It found that four out of 10 patients with B12 deficiency self-medicate via injection. Patients who self-medicated perceived primary care as less safe. Providing patient-centred care and treating these patients with dignity and respect is a policy priority to reduce unsafe health behaviours.

Self-supervised learning for macromolecular structure classification based on cryo-electron tomograms.

Macromolecular structure classification from cryo-electron tomography (cryo-ET) data is important for understanding macro-molecular dynamics. It has a wide range of applications and is essential in enhancing our knowledge of the sub-cellular environment. However, a major limitation has been insufficient labelled cryo-ET data. In this work, we use Contrastive Self-supervised Learning (CSSL) to improve the previous approaches for macromolecular structure classification from cryo-ET data with limited labels. We first pretrain an encoder with unlabelled data using CSSL and then fine-tune the pretrained weights on the downstream classification task. To this end, we design a cryo-ET domain-specific data-augmentation pipeline. The benefit of augmenting cryo-ET datasets is most prominent when the original dataset is limited in size. Overall, extensive experiments performed on real and simulated cryo-ET data in the semi-supervised learning setting demonstrate the effectiveness of our approach in macromolecular labeling and classification.

Associations of physician burnout with career engagement and quality of patient care: systematic review and meta-analysis.

OBJECTIVE: To examine the association of physician burnout with the career engagement and the quality of patient care globally. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, PsycINFO, Embase, and CINAHL were searched from database inception until May 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies assessing the association of physician burnout (including a feeling of overwhelming emotional exhaustion, feelings of cynicism and detachment from job defined as depersonalisation, and a sense of ineffectiveness and little personal accomplishment) with career engagement (job satisfaction, career choice regret, turnover intention, career development, and productivity loss) and the quality of patient care (patient safety incidents, low professionalism, and patient satisfaction). Data were double extracted by independent reviewers and checked through contacting all authors, 84 (49%) of 170 of whom confirmed their data. Random-effect models were used to calculate the pooled odds ratio, prediction intervals expressed the amount of heterogeneity, and meta-regressions assessed for potential moderators with significance set using a conservative level of P<0.10. RESULTS: 4732 articles were identified, of which 170 observational studies of 239 246 physicians were included in the meta-analysis. Overall burnout in physicians was associated with an almost four times decrease in job satisfaction compared with increased job satisfaction (odds ratio 3.79, 95% confidence interval 3.24 to 4.43, I2=97%, k=73 studies, n=146 980 physicians). Career choice regret increased by more than threefold compared with being satisfied with their career choice (3.49, 2.43 to 5.00, I2=97%, k=16, n=33 871). Turnover intention also increased by more than threefold compared with retention (3.10, 2.30 to 4.17, I2=97%, k=25, n=32 271). Productivity had a small but significant effect (1.82, 1.08 to 3.07, I2=83%, k=7, n=9581) and burnout also affected career development from a pooled association of two studies (3.77, 2.77 to 5.14, I2=0%, n=3411). Overall physician burnout doubled patient safety incidents compared with no patient safety incidents (2.04, 1.69 to 2.45, I2=87%, k=35, n=41 059). Low professionalism was twice as likely compared with maintained professionalism (2.33, 1.96 to 2.70, I2=96%, k=40, n=32 321), as was patient dissatisfaction compared with patient satisfaction (2.22, 1.38 to 3.57, I2=75%, k=8, n=1002). Burnout and poorer job satisfaction was greatest in hospital settings (1.88, 0.91 to 3.86, P=0.09), physicians aged 31-50 years (2.41, 1.02 to 5.64, P=0.04), and working in emergency medicine and intensive care (2.16, 0.98 to 4.76, P=0.06); burnout was lowest in general practitioners (0.16, 0.03 to 0.88, P=0.04). However, these associations did not remain significant in the multivariable regressions. Burnout and patient safety incidents were greatest in physicians aged 20-30 years (1.88, 1.07 to 3.29, P=0.03), and people working in emergency medicine (2.10, 1.09 to 3.56, P=0.02). The association of burnout with low professionalism was smallest in physicians older than 50 years (0.36, 0.19 to 0.69, P=0.003) and greatest in physicians still in training or residency (2.27, 1.45 to 3.60, P=0.001), in those who worked in a hospital (2.16, 1.46 to 3.19, P<0.001), specifically in emergency medicine specialty (1.48, 1.01 to 2.34, P=0.042), or situated in a low to middle income country (1.68, 0.94 to 2.97, P=0.08). CONCLUSIONS: This meta-analysis provides compelling evidence that physician burnout is associated with poor function and sustainability of healthcare organisations primarily by contributing to the career disengagement and turnover of physicians and secondarily by reducing the quality of patient care. Healthcare organisations should invest more time and effort in implementing evidence-based strategies to mitigate physician burnout across specialties, and particularly in emergency medicine and for physicians in training or residency. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42021249492.

Retrograde tibiotalocalcaneal nailing for the treatment of acute ankle fractures in the elderly: a systematic review and meta-analysis.

Introduction: Fragility ankle fractures are traditionally managed conservatively or with open reduction internal fixation. Tibiotalocalcaneal (TTC) nailing is an alternative option for the geriatric patient. This meta-analysis provides the most detailed analysis of TTC nailing for fragility ankle fractures. Methods: A systematic search was performed on MEDLINE, EMBASE, Cochrane Library, and Web of Science, identifying 14 studies for inclusion. Studies including patients with a fragility ankle fracture, defined according to NICE guidelines as a low-energy fracture obtained following a fall from standing height or less, that were treated with TTC nail were included. Patients with a previous fracture of the ipsilateral limb, fibular nails, and pathological fractures were excluded. This review was registered in PROSPERO (ID: CRD42021258893). Results: A total of 312 ankle fractures were included. The mean age was 77.3 years old. In this study, 26.9% were male, and 41.9% were diabetics. The pooled proportion of superficial infection was 10% (95% CI: 0.06-0.16), deep infection 8% (95% CI: 0.06-0.11), implant failure 11% (95% CI: 0.07-0.15), malunion 11% (95% CI: 0.06-0.18), and all-cause mortality 27% (95% CI: 0.20-0.34). The pooled mean post-operative Olerud-Molander ankle score was 54.07 (95% CI: 48.98-59.16). Egger's test (P = 0.56) showed no significant publication bias. Conclusion: TTC nailing is an adequate alternative option for fragility ankle fractures. However, current evidence includes mainly case series with inconsistent post-operative rehabilitation protocols. Prospective randomised control trials with long follow-up times and large cohort sizes are needed to guide the use of TTC nailing for ankle fractures.

Investigating the links between diagnostic uncertainty, emotional exhaustion, and turnover intention in General Practitioners working in the United Kingdom.

Background: General Practitioners (GPs) report high levels of burnout, job dissatisfaction, and turnover intention. The complexity of presenting problems to general practice makes diagnostic uncertainty a common occurrence that has been linked to burnout. The interrelationship between diagnostic uncertainty with other factors such as burnout, job satisfaction and turnover intention have not been previously examined. Objectives: To examine associations between diagnostic uncertainty, emotional exhaustion (EE), depersonalization (DP), job satisfaction, and turnover intention in GPs. Methods: Seventy general practices in England were randomly selected through the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC). A total of 348 GPs within 67 these practices completed a 10-item online questionnaire which included questions on GP characteristics, work-life balance, job satisfaction, sickness presenteeism, diagnostic uncertainty, turnover intention as well as EE and DP. Associations between diagnostic uncertainty and each of EE, DP, job satisfaction, and turnover intention were evaluated in multivariate mixed-effect ordinal logistic regressions whilst adjusting for covariates, to account for the correlation in the three outcomes of interest. Results: Almost one-third of GPs (n = 101; 29%) reported experiencing >10% of diagnostic uncertainty in their day-to-day practice over the past year. GPs reporting greater diagnostic uncertainty had higher levels of EE [OR = 3.90; 95% CI = (2.54, 5.99)], job dissatisfaction [OR = 2.01; 95% CI = (1.30, 3.13)] and turnover intention [OR = 4.51; 95% CI = (2.86, 7.11)]. GPs with no sickness presenteeism had lower levels of EE [OR = 0.53; 95% CI = (0.35, 0.82)], job dissatisfaction [OR = 0.56; 95% CI = (0.35, 0.88)], and turnover intention [OR = 0.61; 95% CI = (0.41, 0.91)]. Conclusion: Diagnostic uncertainty may not only negatively impact on the wellbeing of GPs, but could also have adverse implications on workforce retention in primary care.

Fracture Related Infections and Their Risk Factors for Treatment Failure-A Major Trauma Centre Perspective.

Fracture related infections (FRI) are debilitating and costly complications of musculoskeletal trauma surgery that can result in permanent functional loss or amputation. Surgical treatment can be unsuccessful, and it is necessary to determine the predictive variables associated with FRI treatment failure, allowing one to optimise them prior to treatment and identify patients at higher risk. The clinical database at a major trauma centre was retrospectively reviewed between January 2015 and January 2021. FRI treatment failure was defined by infection recurrence or amputation. A univariable logistic regression analysis was performed, followed by a multivariable regression analysis for significant outcomes between groups on univariable analysis, to determine risk factors for treatment failure. In total, 102 patients were identified with a FRI (35 open, 67 closed fractures). FRI treatment failure occurred in 24 patients (23.5%). Risk factors determined by our multivariate logistic regression model were obesity (OR 2.522; 95% CI, 0.259-4.816; p = 0.006), Gustilo Anderson type 3c (OR 4.683; 95% CI, 2.037-9.784; p = 0.004), and implant retention (OR 2.818; 95% CI, 1.588-7.928; p = 0.041). Given that FRI treatment in 24 patients (23.5%) ended up in failure, future management need to take into account the predictive variables analysed in this study, redirect efforts to improve management and incorporate adjuvant technologies for patients at higher risk of failure, and implement a multidisciplinary team approach to optimise risk factors such as diabetes and obesity.

Risk factors for septic arthritis and multiple arthroscopic washouts: minimum 2-year follow-up at a major trauma centre.

BACKGROUND: Septic arthritis (SA) is a dangerous condition that requires emergency treatment. Managed by culture-specific antibiotics, irrigation, and debridement (I&D), some patients require repeat surgical treatment. The objectives were to determine the risk factors for SA and risk factors for repeat arthroscopic I&D in SA patients. We hypothesized that variables which directly or indirectly contributed to a larger infection burden would be associated with the development of SA and the need for repeat arthroscopic I&D. METHODS: All patients ≥ 18 years old presenting to the emergency department, orthopaedic and rheumatology clinics at our major trauma centre between January 2018 and January 2020 with a hot, swollen joint were retrospectively evaluated. Patients with previous trauma and metalwork in the affected joint, periprosthetic joint infection, previous joint arthroplasty surgery, soft tissue infection, missing data, transferred to another centre, diagnosis not concerning the joint, and < 24-month follow-up were excluded. Two hundred eleven patients were included (SA: 28; pseudogout: 32; gout: 50; others: 101). Variables of interest in the 3-month period preceding the diagnosis of SA were compared between SA and non-SA patients using univariable analysis. A multivariable logistic regression model was formed using covariates with corresponding univariable tests of p < 0.200. Similar analyses were performed to compare SA patients with multiple washouts/procedures with those with one washout/procedure. RESULTS: Multivariable analysis showed multiple risk factors for SA, namely rheumatoid arthritis (RA) (OR: 3.4; 95% CI: 1.2-10.0; p = 0.023); skin infection (OR: 3.3; 95% CI: 1.2-9.0; p = 0.017), liver disease (OR: 9.9; 95% CI: 2.2-43.9; p = 0.003), knee joint involvement (OR: 3.5; 95% CI: 1.3-9.4; p = 0.014), and use of immunosuppressive medication (OR: 3.5; 95% CI: 1.2-10.6; p = 0.027). Risk factors for multiple washouts included synovial WBC levels > 10.5 × 109 cells/L (OR: 3.0; 95% CI: 2.3-38.8; p = 0.009) and RA (OR: 3.5; 95% CI: 1.9-66.3; p = 0.017). CONCLUSIONS: These findings suggest that prophylactic actions against septic arthritis should be targeted at patients with liver disease, RA, or skin infection. Repeat arthroscopic I&D of septic joints may be needed, especially in patients with synovial WBC levels > 10.5 × 109 cells/L and RA. Key Points • The risk factors for septic arthritis determined in this study are rheumatoid arthritis, skin infection, liver disease, knee joint involvement, and immunosuppressant usage. • Some septic arthritis patients need multiple rounds of arthroscopic irrigation and debridement. The risk factors for this are a synovial WBC count > 10.5 × 109 cells/L and rheumatoid arthritis.

Open versus closed pilon fractures: Comparison of management, outcomes, and complications.

BACKGROUND: Despite the low incidence of pilon fractures amongst lower limb injuries, their high impact nature presents difficulties in surgical management and recovery. The high complication rate and long recovery times presents a challenge for surgeons and patients. Current literature is varied, with no universal treatment algorithm. We aim to highlight differences in outcomes and complications between open and closed pilon fractures, and between patients treated by open reduction internal fixation (ORIF) or fine wire fixator (FWF) for open and closed fracture subgroups. METHODS: This retrospective study was conducted at a major trauma centre including 135 patients over a 6-year period. Primary outcome was AOFAS score at 3, 6, and 12-months post-injury. Secondary outcomes included time to partial weight-bear (PWB) and full weight-bear (FWB), bone union time, and complications during the follow-up time. AO/OTA classification was used (43A: n = 23, 43B: n = 30, 43C: n = 82). Interobserver agreement was high for bone union time (kappa=0.882) and AO/OTA class (kappa=0.807). RESULTS: Higher AOFAS scores were seen in ORIF groups of both open and closed fractures, compared to FWF groups. The difference was not statistically significant apart from 12-month AOFAS score of 43C open fractures (p = 0.003) and in 43B closed fractures 3 and 6 months post-injury (p<0.001 and p<0.001, respectively). The majority of ORIF subgroups, open and closed fractures, also had shorter time to PWB, FWB, time to union, and follow-up. Statistically significant differences were seen in the following cases: ORIF-treated 43B closed fracture subgroup had shorter time to PWB and FWB (p<0.001 and p = 0.017, respectively), ORIF-treated 43C closed fractures had shorter time to union (p = 0.005). Common complications for open fractures were non-union (24%), post-traumatic arthritis (16%); for closed fractures they were post-traumatic arthritis (24%), superficial infection (21%). All occurred more frequently in FWF-treated patients. CONCLUSION: Most ORIF-treated subgroups in either open or closed pilon fractures showed better primary and secondary outcomes than FWF-treated subgroups, yet few were statistically significant. Overall, our use of a two-staged approach involving temporary external fixation, followed with ORIF or FWF achieved low complication rates and good functional recovery.