Tomosynthesis: A new radiologic technique for rapid diagnosis of scaphoid fractures.

Scaphoid fractures constitute 71% of all carpal bone fractures.1 Early diagnosis and treatment has significant bearing on fracture union rates and better clinical outcomes. While displaced fractures can be readily seen on plain radiograph, undisplaced fractures can require advanced imaging modalities to confirm that diagnosis. Advanced imaging such as Magnetic Resonance Imaging (MRI), Computerised tomography (CT) and bone scintigraphy are routinely used for the diagnosis of scaphoid fractures but require significant radiation exposure, increased cost and can be difficult to access.2 Tomosynthesis is an emerging imaging modality which uses conventional x-ray systems to produce cross-sectional images. There has yet to be extensive research carried out investigating the diagnostic value of tomosynthesis in scaphoid fractures. The aim of this study is to optimise patient positioning for the diagnosis of scaphoid fractures in a cadaveric model and compare the diagnostic yield of tomography to conventional CT. Using four cadaveric specimens, three limb positions were examined in unfractured and fractured scaphoids to determine the optimal limb positions required for visualisation of the scaphoid. As a result of this study, the optimal position for visualisation of the scaphoid and diagnosis of scaphoid fractures has been determined. The results demonstrate that tomosynthesis is as effective as CT scanning in identifying scaphoid fractures in both sensitivity and specificity. By comparison to CT, tomosynthesis is cheaper, has lower radiation exposure, requires fewer hospital resources and can be performed quickly. Tomosynthesis is a valid diagnostic tool for the diagnosis of scaphoid fractures.

The aetiology of rickets-like lower limb deformities in Malawian children.

UNLABELLED: Debilitating rickets-like lower limb deformities are common in children throughout the world, particularly in Malawi, Africa where the causes are unknown. We have identified that Blount disease and calcium deficiency rickets are the likely causes of these deformities and propose calcium supplementation as a potential treatment of Malawian rickets. INTRODUCTION: Surgical correction of rickets-like lower limb deformities is the most common paediatric operation performed at Beit Cure Orthopaedic Hospital, Malawi. The aim of this study was to investigate the aetiology of these deformities. METHODS: Children with a tibio-femoral angle of deformity >20° were enrolled (n = 42, 3.0-15.0 years). Anthropometric and early life and well-being data were collected. Early morning serum and urine samples were collected on the morning of the operation for markers of calcium and phosphate homeostasis. Knee radiographs were obtained, and the children were diagnosed with either Blount (BD, n = 22) or evidence of rickets disease (RD, n = 20). As BD is a mechanical rather than metabolic disease, BD were assumed to be biochemically representative of the local population and thus used as a local reference for RD. RESULTS: There were no differences in anthropometry or early life experiences between BD and RD. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, total alkaline phosphatase and urinary phosphate were significantly higher and serum phosphate, 25-hydroxyvitamin D (25OHD) and tubular maximal reabsorption of phosphate significantly lower in RD than BD. There was no difference in serum calcium, fibroblast growth factor 23 or markers of iron status between groups. All children had 25OHD > 25 nmol/L. CONCLUSIONS: Vitamin D deficiency is not implicated in the aetiology of RD or BD in Malawian children. The cause of RD in Malawi is likely to be dietary calcium deficiency leading to elevated PTH resulting in increased losses of phosphate from the bone and glomerular filtrate. The causes of BD remain unclear; there was no evidence in support of previously suggested risk factors such as being overweight or starting to walk early. Prior to surgical intervention, supplementation with calcium should be considered for children with RD.

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.

Evaluation in vitro of synthetic curcumins as agents promoting monocytic gene expression related to ß-amyloid clearance.

Accumulation of amyloid-beta (Aß) is one of the hallmarks of Alzheimer's disease (AD), and efficient clearance of Aß by cells of the innate immune system may be an important mechanism for controlling or preventing disease onset. It was reported that peripheral blood mononuclear cells (PBMCs) of most AD patients are defective in the phagocytosis of soluble Aß. Natural curcumins were shown to restore Aß phagocytosis by AD PBMCs and to up-regulate the expression of key genes including MGAT3 and those encoding Toll-like receptors (TLRs). Bisdemethoxycurcumin (BDC), a minor component of natural curcumin, was shown to have the greatest potency for stimulating AD PBMCs. Because natural curcumins have inherent limitations with regard to physicochemical properties, synthetic curcumin analogues were developed that showed improved solubility, stability, and bioavailability. An in vitro system using human monocytic cell lines (U-937, THP-1) was used to evaluate analogues for the potency of innate immune cell stimulation. These cell lines showed responses to curcuminoids and to 1α,25-dihydroxyvitamin D3 (VD3) resembling those seen in human PBMCs. From more than 45 curcuminoids analyzed, the most potent compounds possessing enhanced pharmaceutical properties were identified. The most promising candidates included prodrug versions containing water solubility-enhancing amino acids and stability-increasing modifications near the central diketone. In vivo studies showed compound (5) substantially increased bioavailability by combining several promising structural modifications. Studies examining ex vivo phagocytosis of Aß and bead particles in mouse microglia showed that BDC and several water-soluble analogues were quite effective compared to curcumin or an unnatural analogue. In vitro studies using monocytic cell lines reported herein complement those using human PBMCs and represent a routinely accessible and uniform cellular resource allowing direct comparisons between compounds.

Curcumins promote monocytic gene expression related to ß-amyloid and superoxide dismutase clearance.

Neurodegenerative diseases are associated with accumulation of modified proteins or peptides including amyloid-ß (Aß) in Alzheimer's disease (AD), and misfolded superoxide dismutase-1 (SOD-1) in amyotrophic lateral sclerosis (ALS). Clearance of Aß or SOD-1 by the innate immune system may be important for controlling or preventing disease onset. Curcumins restore Aß phagocytosis by peripheral blood mononuclear cells (PBMCs) from AD patients and Aß clearance with upregulation of key genes including MGAT3, vitamin D receptor (VDR) and Toll-like receptors (TLRs). Certain curcumins inhibit inflammatory processes of PBMCs from ALS patients. We developed an in vitro system using human monocytes from patients and monocytic cell lines (i.e. U-937, THP-1) for evaluating curcuminoid potency of innate immune cell stimulation. Bisdemethoxycurcumin and certain analogs potentiated MGAT3,VDR and TLR gene expression 3- to 300-fold in U-937 cells. The effect of curcumins on inflammation in monocytes from patients with ALS was examined. Recursive medicinal chemistry was applied to identify compounds that stimulate the innate immune system for use in the clearance of Aß in AD and the reversal of neuroinflammation and defective SOD-1 accumulation in ALS.

Development and Service Evaluation of an ad hoc Virtual Arthroplasty Clinic during COVID-19: Experiences from Irish National Orthopaedic Hospital.

Introduction: COVID-19 has had a significant impact on healthcare. It has forced orthopaedic surgeons to limit face-to-face patient contact. This resulted in the ad hoc creation of a virtual arthroplasty clinic (VAC) in Irish National Orthopaedic Hospital. We aimed to assess this new VAC and ascertain its effectiveness as an alternative to physical appointments during and following the pandemic. Materials and methods: Patients were followed-up in this VAC six weeks post-operatively. A service evaluation of this virtual arthroplasty clinic was carried out using a questionnaire created by the orthopaedic department. Results: A total of 30 patients requiring 6-week follow-up after the arrival of COVID-19 in Ireland were included. Average pre- and post-operative visual analogue scale score (VAS) was 8.1 and 2.3, respectively. Average pre- and postoperative Oxford hip and knee score was 19.1 and 39.2, respectively. Twenty-one patients (70%) were happy to have their six weeks post-operative e-outpatient consultation virtually. Twenty-six patients (86%) were happy with future virtual follow-up. Twenty-eight patients (93%) would be happy experiencing the whole process again. Eleven patients would be interested in having future joint replacement surgery, though ten of them (91%) stated COVID-19 would impact that decision. Conclusion: Most patients were happy to have their six-week appointment and future appointments virtually. Functional outcome scores had improved and pain scores had reduced at six-week follow-up, supporting the idea that virtual clinics are not inferior to physical clinics. Patients expressed concern about having a further joint replacement in the context of COVID-19.

A prevalence study of errors in opioid prescribing in a large teaching hospital.

AIM: In 2007, the National Patient Safety Agency performed a study demonstrating that errors in prescribing led to nearly 12,000 adverse clinical incidents a year. The following year, they issued a rapid response report entitled 'Reducing Dosing Errors with Opioid Medicines' designed to be implemented by all NHS trusts. We performed a prevalence study to assess opioid prescribing errors in our large multi-speciality teaching hospital prior to implementation of these recommendations. METHODOLOGY: We conducted a 1 day snapshot of opioid prescriptions on inpatient drug charts. For every chart, all opioid information was entered into the study proforma. All data were reviewed by consensus group and errors categorised by quality and whether they were potentially lethal, serious, significant or minor. RESULTS: A total of 330/722 (46%) charts were found to have opioid prescriptions. On the study day, there were 74 charts with errors and on expert review another 16 erroneous charts were found giving a total of 90/330 (27.2%). The largest quality statement error group was 'unclear prescription, missing information'. There were 4 potentially lethal, 26 serious, 38 significant and 22 minor errors. DISCUSSION: Previous studies have reported opioid prescription error rates of 51.2-70%. Compared with the opioid literature, our trust fares well with an error rate of 27%- four of these errors being potentially lethal. This study has identified where there are weaknesses in our hospital opioid prescribing practice and has aided us in rewriting our acute and chronic pain guidelines with the explicit inclusion of the National Patient Safety Agency recommendations. We have also disseminated the study results at the Trust academic meeting and developed an opioid e-learning package which will be mandatory for all new staff.

Changes in the proliferative activity of human hematopoietic stem cells in NOD/SCID mice and enhancement of their transplantability after in vivo treatment with cell cycle inhibitors.

Human hematopoietic tissue contains rare stem cells with multilineage reconstituting ability demonstrable in receptive xenogeneic hosts. We now show that within 3 wk nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice transplanted with human fetal liver cells regenerate near maximum levels of daughter human hematopoietic stem cells (HSCs) able to repopulate secondary NOD/SCID mice. At this time, most of the human HSCs (and other primitive progenitors) are actively proliferating as shown by their sensitivity to treatments that kill cycling cells selectively (e.g., exposure to high specific-activity [(3)H]thymidine in vitro or 5-fluorouracil in vivo). Interestingly, the proliferating human HSCs were rapidly forced into quiescence by in vivo administration of stromal-derived factor-1 (SDF-1) and this was accompanied by a marked increase in the numbers of human HSCs detectable. A similar result was obtained when transforming growth factor-beta was injected, consistent with a reversible change in HSCs engrafting potential linked to changes in their cell cycle status. By 12 wk after transplant, most of the human HSCs had already entered G(o) and treatment with SDF-1 had no effect on their engrafting activity. These findings point to the existence of novel mechanisms by which inhibitors of HSC cycling can regulate the engrafting ability of human HSCs executing self-renewal divisions in vivo.

Irish (Republic) versus British (North West) orthopaedic trainees: what are the differences?

British Trainees have gradually had their working week curtained over the last 8 years. The Republic of Ireland Trainees have not been subjected to the European Working Time Directive prior to 2009 and have therefore worked on average, more hours than their British counterparts. We wanted to see if the differing schemes had an impact on recruiting and training orthopaedic surgeons. We surveyed Republic of Ireland orthopaedic specialist registrars (SpRs) and North West (NW) British SpRs/specialist trainees (ST3 and above) to see if there were any discernable differences in working patterns and subsequent training exposure. A standard proforma was given to Irish Trainees and to NW SpRs/STs at their National or regional teaching (January/February 2009). 62% of Irish and 47% of British NW Trainees responded. Irish trainees were more likely to have obtained a post-graduate degree (p = 0.03). The Irish worked more hours per week (p < 0.001) doing more trauma operative lists (p = 0.003) and more total cases per 6 months than the NW British (p = 0.003). This study suggests that more hours worked, equals more operative exposure, without detriment to the academic side of training. Obviously it is not possible to say whether fewer operations make for a poorer surgeon, but the evidence suggests that it may be true.