Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention.

PURPOSE: Patients with coronary artery disease have increased fracture risks. P2Y12 inhibitors may impact fracture risks. We compared the fracture risks associated with ticagrelor and clopidogrel in dual anti-platelet therapy (DAPT). METHODS: We identified all adults who underwent first-ever percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) between 2010 and 2017 from a territory-wide PCI registry in Hong Kong. Following 1:1 propensity-score matching for baseline characteristics, patients were followed up till event occurrence, death, or 30 June 2022. Outcomes of interest were major osteoporotic fractures (MOF) identified by validated ICD-9-CM codes. Cox proportional hazards regression was used to compute the hazard ratio (HR) for MOF associated with ticagrelor versus clopidogrel use. RESULTS: 3018 ticagrelor users and 3018 clopidogrel users were identified after propensity-score matching (mean age: 61.4 years; 84.1% men). Upon median follow-up of 6.5 years, 59 ticagrelor users and 119 clopidogrel users sustained MOF (annualized fracture risks: 0.34% and 0.56%, respectively). Ticagrelor use was associated with lower risks of MOF (HR 0.60, 95%CI 0.44-0.83; p = 0.002). Consistent HRs were observed for fractures over vertebrae, hip and upper limbs. Subgroup analyses showed no interaction according to age, sex, presence of diabetes, presence of chronic kidney disease and prior fracture history. CONCLUSION: Among adults who underwent first-ever PCI for ACS, ticagrelor use in the DAPT was associated with a lower risk of MOF compared with clopidogrel. Our results support the use of ticagrelor in the DAPT from the perspective of bone health.

Thoracolumbar spine trauma: a guide for the FRCS examination.

Thoracolumbar spine injuries are commonly seen in trauma settings and have a high risk of causing serious morbidity. There can be controversy when it comes to classifying thoracolumbar injuries within the spinal community, but there remains a need to classify, evaluate and manage thoracolumbar fractures. This article aims to provide a guide on classification of thoracolumbar spine injuries using the AO Spine Thoracolumbar Injury Classification System (AO TLICS).

Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.

PURPOSE: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients. METHODS: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria. RESULTS: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients. CONCLUSION: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients.

Potential role of fibroblast growth factor 21 in the deterioration of bone quality in impaired glucose tolerance.

PURPOSE: Findings on trabecular bone score (TBS), an index of bone quality, have been reported in prediabetes defined by impaired fasting glucose or HbA1c. Here, we assessed the bone mineral density (BMD) and TBS in prediabetes individuals with impaired glucose tolerance (IGT), and investigated the association of these bone parameters with serum levels of fibroblast growth factor 21 (FGF21), a hormone implicated in bone metabolism and with higher levels in IGT. METHODS: Chinese postmenopausal women aged 55-80 years, without diabetes, were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study in 2016-2018. Normal glucose tolerance (NGT) was defined by fasting glucose < 5.6 mmol/L and 2-h plasma glucose (2hG) < 7.8 mmol/L, and IGT by 2hG 7.8-11 mmol/L. Serum levels of FGF21 and other bone metabolism regulators were measured. Insulin sensitivity was assessed by the Matsuda index. Independent determinants of TBS were evaluated using multivariable stepwise linear regression. RESULTS: 173 individuals with NGT and 73 with IGT were included. TBS was lower in those with IGT compared to those with NGT, while BMD was comparable. Individuals with IGT had significantly higher serum FGF21 levels, which in turn showed an independent inverse relationship with TBS, attenuated after inclusion of the Matsuda index. Serum FGF21 levels, however, did not correlate with BMD. CONCLUSION: Among Chinese postmenopausal women, bone quality was worse in IGT, despite comparable bone density. FGF21 levels showed a significant independent inverse relationship with TBS, partly attributed to insulin resistance. Whether FGF21 contributes to the impaired bone quality in IGT remains speculative.

HbA1c variability, in addition to mean HbA1c, predicts incident hip fractures in Chinese people with type 2 diabetes.

Type 2 diabetes is associated with an increased risk of hip fractures. We hypothesize that long-term glycemic variability predicts incident hip fractures. We demonstrated that HbA1c variability predicted incident hip fractures independent of mean HbA1c, suggesting the potential benefits of minimizing glycemic variability in addition to optimizing mean glycemia for bone health. INTRODUCTION: Type 2 diabetes is associated with an increased risk of hip fractures, and a linear relationship between HbA1c levels and hip fracture incidence has been observed. We hypothesize that HbA1c variability also predicts incident hip fractures in type 2 diabetes. METHODS: Chinese individuals with type 2 diabetes aged ≥ 60 years were identified from electronic health records in Hong Kong between 2008 and 2012 and observed for incident hip fractures. Hip fracture was defined by the International Classification of Diseases (Ninth Revision) code 820. HbA1c variability was determined using standard deviation, adjusted standard deviation, and coefficient of variation of HbA1c measurements in the 5 years preceding the entry date. Multivariable Cox regression analysis was used to evaluate associations between HbA1c variability and incident hip fractures. RESULTS: A total of 83,282 participants were included. Their mean age was 71.3 ± 7.5 years, duration of diabetes 11.7 ± 7.7 years, baseline HbA1c 56.6 ± 13.5 mmol/mol (7.33 ± 1.23%), and median follow-up 6.8 years. All indices of HbA1c variability were significant independent predictors of incident hip fractures, with an adjusted hazard ratio of up to 1.29 (all p < 0.001), and remained to be independent predictors across groups of different intensity of glycemic control. Mean HbA1c ≥ 64 mmol/mol (8.0%) was associated with a 25% increase in incident hip fractures compared with mean HbA1c < 53 mmol/mol (7.0%). CONCLUSION: HbA1c variability is an independent positive predictor of hip fracture in type 2 diabetes, across the spectrum of varying degree of glycemic control, while a high HbA1c is also not advisable from the perspective of bone health.

Post operative complications in a dedicated elective orthopaedic hospital: transfers requiring specialist critical care support.

We aim to report our experience with out of hospital transfers for postoperative complications in a stand-alone elective orthopaedic hospital. We aim to describe the cohort of patients transferred, the rate of transfer and assess the risk factors for transfer. Patients were identified who were transferred out of the hospital to another acute hospital for management of non-routine medical problems. Patient data was collected relating to age, BMI, ASA, type of surgery, nature of the complication, timing and the outcome of transfer. In 2012, 2,853 inpatient surgical procedures were carried out, 51 patients (1.8%) developed a postoperative complication that required out of hospital transfer. Mean age of patients transferred was 67 (12-86) years, mean age of the overall case mix 58 years (0-96) (p = 0.01). 37.7% of the overall case mix of surgeries was made up of primary hip and knee arthroplasty procedures, these patients made up 63.7% of patients transferred out (p = 0.001). Mean BMI recorded was 31.7 (22-48) compared to the mean BMI of the total arthroplasty case mix of 28.8 (20-44) (p = 0.02). 59% of all patients at our institution were ASA category II or III. 76% of patients transferred were ASA category II or III (p = 0.005). We can conclude that patients requiring transfer are typically older. Arthroplasty patients are more likely to require transfer than patients undergoing other orthopaedic procedures. Among the arthroplasty cohort transferred patients will typically have a higher BMI than average. Patients with ASA category II or III make up nearly three quarters of those patients transferred. The mean age of patients transferred is typically older by 9 years.

Reducing radiation exposure and cancer risk for children with scoliosis: EOS the new gold standard.

PURPOSE: Children are exposed to significant radiation doses during the investigation and treatment phases of scoliosis. EOS is a new form of low-dose radiation scan which also yields great image quality. However, currently its use is discouraged in the UK due to higher costs. We aimed to quantify the additional radiation dose and cancer risk. METHODS: We retrospectively reviewed all paediatric cases who received both standing whole spine roentgenograms and EOS scans as part of their investigations for scoliosis during a six-month period. We compared the radiation doses between the two modalities and estimated the additional mean lifetime cancer risk per study. RESULTS: We identified 206 children (mean age 14.4) who met the criteria of having both scans. Dose area products (dGycm2) were converted to estimated effective doses (mSv). The total mean doses were 0.68 mSv (PA 0.49 + Lat 0.19) for plain films, and 0.13 mSv (PA 0.08 + Lat 0.04) for EOS scans (p < 0.001). Additional lifetime cancer risk of a plain film was 543% greater than EOS for both sexes (1/10727 versus 1/5827 in males, 1/34483 versus 1/6350 in females). CONCLUSION: There is approximately 5.4-fold increase in risk of cancer for both boys and girls with roentgenograms over EOS, with girls being the most impacted. This carries a significant impact when considering the need for repeat imaging on additional lifetime malignancy risk in children. In our opinion, EOS dual planar scanning is the new gold standard when X-ray of the whole spine is required. LEVEL OF EVIDENCE: III.

Pelvic and acetabular fractures.

Patients that sustain pelvic and/or acetabular trauma in Ireland and require surgical intervention are treated at the Adelaide and Meath National Children's Hospital (AMNCH). For this study an audit was conducted of all pelvic and acetabular fractures referred to the AMNCH over a 12 month period from July 2010 to June 2011. This study was conducted with the purpose of recording the different fracture patterns, methods of injury and surgical procedures performed over this time frame. The results demonstrate that 109 patients were referred to the AMNCH with the majority of these fractures being sustained as the result of an RTA (43) or a fall from a height (45). Seventy one patients suffered an acetabular fracture while 43 patients suffered a fracture of their pelvic ring with some patients suffering both. There were 129 surgical procedures performed with 25 patients having more than one surgical procedure.

Bisindolylmaleimide VIII facilitates Fas-mediated apoptosis and inhibits T cell-mediated autoimmune diseases.

Fas-mediated apoptosis is essential for the elimination of cells, and impaired apoptosis can have severe detrimental consequences. Bisindolylmaleimide VIII potentiated Fas-mediated apoptosis in human astrocytoma 1321N1 cells and in Molt-4T cells, both of which were devoid of apoptosis induced by anti-Fas antibody in the absence of bisindolylmaleimide VIII, and in Jurkat and CEM-6 T cells, which showed slight and moderate apoptotic responses, respectively, to low levels of Fas stimulation. Potentiation of Fas-mediated apoptosis by bisindolylmaleimide VIII was selective for activated, rather than non-activated, T cells, and was Fas-dependent, as it was not observed in T cells from Fas-deficient lpr/lpr mice. Administration of bisindolylmaleimide VIII to rats during autoantigen stimulation prevented the development of symptoms of T cell-mediated autoimmune diseases in two models, the Lewis rat model of experimental allergic encephalitis and the Lewis adjuvant arthritis model. Thus, the use of agents such as bisindolylmaleimide VIII may be therapeutically useful for supporting more effective elimination of detrimental cells through enhancement of Fas-dependent apoptosis signaling.

The management and outcome of lateral process fracture of the talus.

BACKGROUND: Lateral process fractures of the talus are a rare injury with significant associated morbidity when missed. Only a small number of case series' and reports are available and the appropriate management of these fractures is not really known. METHODS: We reviewed available English language literature for reports and series of lateral process fractures of talus. Only papers in which the classification of fracture, management and outcome were clear were included in our analyses. RESULTS: 109 Cases in total were identified including four cases from a personal series. 50 Type I, 17 type II and 29 type III fractures were analysed. A significant number of patients required late surgery when the diagnosis was initially missed. CONCLUSION: Type I fractures are best treated with ORIF, type II with excision and type III with casting. Fractures presenting late that are not united should be excised if small and internally fixed if large.

The effect of body mass index on outcomes after total ankle replacement.

Total ankle replacement is an established alternative to ankle fusion in selected patients. One of the possible exclusions used is the presence of a high BMI. This is based on our experience with hip and knee replacements where poor outcomes have been associated with obesity, however little work has been done on this subject in the ankle. We report the first series solely focussing on the impact of BMI on TAR. Forty five consecutive patients were identified and followed up using the SF-36 and VAS-FA. All patients had their BMI collected prospectively and BMI at latest follow-up was calculated. There was an average 5-year follow-up with just 9 (20%) lost to follow-up. At final follow-up 8 (17.7%) patients were deceased, none of the deaths were attributable to their previous ankle surgery. We did not find an association between high BMI and reduced outcomes or need for secondary surgery. In addition there was no significant change in BMI after surgery.

The challenge of differentiating vaso-occlusive crises from osteomyelitis in children with sickle cell disease and bone pain: A 15-year retrospective review.

PURPOSE: The paediatric sickle cell disease (SCD) osteomyelitis (OM) incidence is 0.3% to 12%. Differentiating vaso-occlusive crises (VOC) from OM is a diagnostic challenge, with limited evidence guiding management. We present a 15-year review of a paediatric sickle cell cohort. We aim to identify OM incidence and provide a management protocol for these children presenting with bone pain. METHODS: A prospective database of children with haemoglobinopathies (2002 to 2017) was analyzed for temperature, C-reactive protein (CRP) and white cell count (WCC) on admission as well as imaging, treatment and cultures. OM diagnosis was supported by imaging and blood cultures. VOC was defined as bone pain that improved without antibiotics. RESULTS: Over 15 years, 96 children with SCD presented 358 times to hospital. Empirical antibiotics were given in 308 presentations. There were five cases of OM (1.4%); two acute and three chronic. In all, 50 presentations of VOC were identified. No significant differences in age were noted between the OM and VOC group. Temperature and CRP were significantly elevated in the OM group with no significant difference in WCC. Cultures were only positive in the chronic OM admissions. There were no cases of septic arthritis. No surgical intervention was required. CONCLUSION: In children with SCD presenting with persistent bone pain, fever, elevated CRP and WCC, OM should be suspected and prompt antibiotic treatment started. Our treatment pathway was successful avoiding OM in 98.6% and septic arthritis in 100%. Further research on novel biological markers distinguishing OM from VOC should be investigated. LEVEL OF EVIDENCE: III.

Contemporary engagement with social media amongst hernia surgery specialists.

PURPOSE: Healthcare professional engagement is increasing. This study aims to identify levels of adoption and engagement of several social media platforms by a large international cohort of hernia surgery specialists. METHODS: Hernia specialists attending the 38th International Congress of the European Hernia Society were identified. A manual search was then performed on Twitter, ResearchGate, and LinkedIn to identify those who had named accounts. Where accounts were identified, data on markers of utilisation were assessed. RESULTS: 759 surgeons (88.5% male) from 57 countries were identified. 334 surgeons (44%) engaged with a social media platform. 39 (5.1%) had Twitter accounts, 189 (24.9%) had ResearchGate accounts and 265 (34.9%) had LinkedIn accounts. 137 surgeons (18.1%) had accounts on 2 or more social media platforms. There was no gender association with social media account ownership (p > 0.05). Engagement in one social media platform was associated with increased engagement and utilisation on other platforms; LinkedIn users were more likely to have Twitter accounts (p < 0.001) and ResearchGate profiles (p < 0.001). Surgeons on all three SM platforms were more likely to have high markers of engagement across all SM platforms (multiple outcomes, p < 0.05). Geographical variation was noted with UK and South American Surgeons being more likely to be present on Twitter than their counterparts (p = 0.031). CONCLUSIONS: The level of engagement with social media amongst Hernia surgeons is similar to other surgical specialities. Geographical variation in SM engagement is seen. Engagement with one SM platform is associated with presence on multiple platforms.

Fluorescence microscopy image noise reduction using a stochastically-connected random field model.

Fluorescence microscopy is an essential part of a biologist's toolkit, allowing assaying of many parameters like subcellular localization of proteins, changes in cytoskeletal dynamics, protein-protein interactions, and the concentration of specific cellular ions. A fundamental challenge with using fluorescence microscopy is the presence of noise. This study introduces a novel approach to reducing noise in fluorescence microscopy images. The noise reduction problem is posed as a Maximum A Posteriori estimation problem, and solved using a novel random field model called stochastically-connected random field (SRF), which combines random graph and field theory. Experimental results using synthetic and real fluorescence microscopy data show the proposed approach achieving strong noise reduction performance when compared to several other noise reduction algorithms, using quantitative metrics. The proposed SRF approach was able to achieve strong performance in terms of signal-to-noise ratio in the synthetic results, high signal to noise ratio and contrast to noise ratio in the real fluorescence microscopy data results, and was able to maintain cell structure and subtle details while reducing background and intra-cellular noise.

Samarium-153-particulate hydroxyapatite radiation synovectomy: biodistribution data for chronic knee synovitis.

UNLABELLED: Biodistribution data for the radiation synovectomy agent samarium-153-particulate hydroxyapatite (153Sm-PHYP) are reported. METHODS: Mean extra-articular activity accumulation calculated from serial whole-body scans in 13 patients treated for chronic knee synovitis was 0.74% of injected activity (range 0%-3%). RESULTS: In four patients (31%), activity was noted in the lung (mean 0.68% of injected activity). In six patients (46%), 0.29% of injected activity accumulated in the regional lymph nodes and in three patients (23%), 0.62% of injected dose accumulated in the liver. Absorbed dose estimates were lung: 14 mGy, regional lymph nodes; 50 mGy, liver; 4 mGy. SPECT demonstrated good distribution of 153Sm-PHYP throughout the anterior knee compartments, although distribution to the posterior compartment was variable. CONCLUSION: Distribution is dependent on adequate knee flexion immediately following injection and may be influenced by the size range of labeled particles. Favorable biodistribution data suggest that 153Sm-PHYP is a potentially useful radiation synovectomy agent.

Functional imaging of the brain.

The radionuclide tracer method is unique amongst all other imaging methodologies in its ability to trace organ or tissue function and metabolism. It derives this advantage from the nature of the signal used for image generation, and its single interaction with the organ or system under examination. Physical processes such as electron or proton density assessment or resonance, edge identification, electrical or ultrasonic impedence, do not pertain to the image generation process in nuclear medicine, and if so, only in a rather secondary manner. The nuclear medicine imaging study is primarily a study of the chemical nature, distribution and interaction of the tracer/radiopharmaceutical utilised with the cellular system which requires investigation: the thyroid cells with sodium iodide, the recticular endothelial cells with colloidal particles, the adrenal medulla cells with metaiodobenzylguanidine, and so on. In the two most recent areas of nuclear medicine expansion, oncology (with labelled monoclonal antibodies) and neurology and psychiatry (with a whole new series of lipid soluble radiopharmaceuticals), specific cell systems can also be targeted and hence imaged and investigated. The study of structure as masterly performed by Virchow and all his successors over more than a century, is now definitely the prerogative of such imaging systems which excel with spatial and contrast resolution (x-ray computed transmission tomography, nuclear magnetic resonance imaging, diagnostic ultrasound). However the investigation of function and metabolism (as performed by Claude Bernard, Georg von Hevesy, and so many others), has clearly passed from the laboratory animal protocol and experiment to the direct investigation in man, this being the achievement of the radionuclide tracer methodology. In this article, we review present interest and developments in that part of nuclear medicine activity which is aimed at the study of the neurological or psychiatric patient.

The mechanism of diarrhoea resulting from pelvic and abdominal radiotherapy; a prospective study using selenium-75 labelled conjugated bile acid and cobalt-58 labelled cyanocobalamin.

An attempt was made to elucidate the mechanism of diarrhoea resulting from pelvic and abdominal radiotherapy in a prospective study of 10 patients undergoing treatment for curable pelvic malignant tumours using the synthetic trihydroxy 75Se-labelled conjugated bile acid, SeHcat and 58Co-labelled cyanocobalamin (58Co Vit B12). Evidence of malabsorption of vitamin B12 measured as a significant fall in whole body percentage retention of 58Co Vit B12 from baseline levels was found in all nine patients who developed diarrhoea during radiotherapy. Only four out of these nine patients also had malabsorption of the trihydroxy conjugated bile acid, cholic acid, measured as a significant fall in SeHcat whole body percentage retention and these patients had the most severe diarrhoea. The findings are discussed in the light of what is known about the pathophysiology of diarrhoea during pelvic and abdominal radiotherapy and lend support to previous work which implicated increased bowel motility in the pathogenesis of radiation-induced diarrhoea. The hypothesis that local neuroendocrine mechanisms in the gut may be involved is put forward, with possible implications for treatment.