Long term follow up on treatment of hallux sesamoid fracture with temporary first metatarsal joint internal fixation.

Fracture of the hallucial sesamoids is a pathology that causes difficulty for surgeons and patients. Because of the low incidence and the fact that up to 64-90 % heal with non-operative management, there is a lack of clear guidance in the literature for the surgical treatment of sesamoid fracture in cases of failure of non-operative management. Here long term follow up of an alternative method of surgical treatment of sesamoid fracture recalcitrant to nonoperative management is presented. 32 individuals were treated with temporary surgical immobilisation of the 1st metatarsophalangeal joint using either crossed wires or two orthogonally placed two hole plates. The patients then underwent removal of the construct at 8 weeks post op after confirmation of healing on a CT scan. There was a 94 % union rate. Return to work was 61 days (15-90) return to sport 80 days (64-112) with no immediate complications and no recurrence. At last follow up mean 10 years (4-16) only 2 patients had gone on to asymptomatic non-union and one patient developed arthritis between the sesamoid and the metatarsal head. No patient has required further surgical intervention. This retrospective cohort of patients demonstrate that this method of treatment is a valuable option in the management of sesamoid fracture which does not alter the biomechanics of the foot and has none of the long term complications of sesamoidectomy or partial sesamoidectomy.

Posterior Heel Pain in Cavovarus Foot: How to Approach It.

When a patient presents with posterior heel pain on the background of a cavovarus foot, there are many different aspects to take into account. The morphology of the foot and the specific cause of the patient's pain lead the practitioner to alter the treatment appropriately. Some patients should only receive physiotherapy, but the majority should receive more invasive treatments, including calcaneal osteotomies or tendon debridement, depending on their particular presentation and pathology. This review examines the various different facets of posterior heel pain that must be dealt with and the most up-to-date treatments for the same.

Risk scoring models for patients with proximal femur fractures: Qualitative systematic review assessing 30-day mortality and ease of use.

BACKGROUND: Hip fractures are a common orthopaedic injury affecting a particularly frail and vulnerable patient cohort. They are at risk of many complications, including prolonged length of stay and mortality. Efforts to identify those at high risk may be beneficial. Over 25 risk prediction models are published for patients with hip fractures. AIM: The primary aim of this study was to assess the performance of predictor scores in predicting 30-day mortality. The secondary aim was to assess the ease of use of these systems. METHODS: A qualitative systematic review was performed. A search was conducted on online databases, including PubMed, CINAHL, Clinical Trials.gov, Cochrane, DARE, EMBASE, SCOPUS, and Web of Science.. The terms fragility hip fractures and risk prediction models were utilised while performing the search. These were then expanded using Boolean operators and similar terms. Search results were imported to Covidence. Primary observational studies using one or more hip fracture mortality prediction models and 30-day mortality as an outcome were included. Systematic reviews and studies on specific patient groups defined other medical conditions (e.g. COVID positive or dialysis patients) were excluded. RESULTS: 3,101 studies were screened following duplicate removal. 34 papers were included in the review, in which 23 scoring systems were reported. Six of these were pre-operative and reported in multiple studies. Most demonstrated appropriate fit and fair discrimination. Five of the six pre-operative scoring systems examined, displayed appropriate ease of use, allowing risk calculation at the time of admission. CONCLUSION: Nottingham Hip Fracture Score remains the most extensive reported scoring system and performs fair overall with AUROCs of 0.64-0.80 and good fit in calibration across all studies. However, new systems utilise many similar predictors. There is a need for the standardisation of publications on scoring systems to allow further systematic review and meta-analyses.

The association between weather warnings and hip fractures in the Republic of Ireland.

This study examined the relationship between hip fractures and weather warnings with the hypothesis higher rates of fractures occur during warnings. National hip fracture database and weather warning records were utilised. Higher rates of hip fractures were found with severe warnings. This has implications for planning in future severe warnings. BACKGROUND: Hip fractures represent a significant burden on the Irish Health system with 3666 in 2020. The Irish National Meteorological Service operates a colour coded warning system. Yellow being least severe, while orange represents weather with capacity to impact individuals in affected areas and red represents advice to protect themselves and property. Previous studies investigated the seasonality of hip fractures, which remains but none have investigated the relationship between weather warnings and rates of hip fractures. The hypothesis was that increasing weather warnings would be associated with increased hip fractures. The aim was to investigate the relationship between weather warnings and hip fractures in the Republic of Ireland. METHODS: Comparison of national weather warning archives from 2013 to 2019 to Fracture Database records. Reviews assessed whether fractures occurred on days a weather warning was in place in the individual's local county. A statistical analysis of warning features and their relationship to hip fractures was then performed. Fractures and weather warnings were stratified by county with both a panel and case crossover analysis performed. RESULTS: There was a tendency towards increased incidence of hip fractures with weather warnings in adjusted analysis (IRR 1.02; 95%CI 0.99-1.06; p-value 0.123). Orange warnings were associated with a statistically higher incidence of fractures (IRR 1.06; 1.01-1.12; p-value 0.026). In both panel and case crossover analysis, both orange and yellow warnings were associated with fractures. Red warnings were associated with a lower incidence of fracture on day of warning (adjusted incidence rate ratio 0.92; 0.70-1.22; p-value 0.569) but a higher incidence on the following day (adjusted incidence rate ratio 1.14; 0.88-1.46; p-value 0.313). CONCLUSION: An increased incidence of hip fractures appears to occur during weather warnings. Consideration should be given when preparing for periods of extreme weather, ensuring sufficiently resources.

Interleukin-1 blocking agents for treating COVID-19.

BACKGROUND: Interleukin-1 (IL-1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19), on the premise that their immunomodulatory effect might be beneficial in people with COVID-19. OBJECTIVES: To assess the effects of IL-1 blocking agents compared with standard care alone or with placebo on effectiveness and safety outcomes in people with COVID-19. We will update this assessment regularly. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register and the COVID-19 L-OVE Platform (search date 5 November 2021). These sources are maintained through regular searches of MEDLINE, Embase, CENTRAL, trial registers and other sources. We also checked the World Health Organization International Clinical Trials Registry Platform, regulatory agency websites, Retraction Watch (search date 3 November 2021). SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating IL-1 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity. DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two researchers independently screened and extracted data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence using the GRADE approach for the critical outcomes of clinical improvement (Day 28; ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28; ≥ D60); all-cause mortality (D28; ≥ D60); incidence of any adverse events; and incidence of serious adverse events. MAIN RESULTS: We identified four RCTs of anakinra (three published in peer-reviewed journals, one reported as a preprint) and two RCTs of canakinumab (published in peer-reviewed journals). All trials were multicentre (2 to 133 centres). Two trials stopped early (one due to futility and one as the trigger for inferiority was met). The median/mean age range varied from 58 to 68 years; the proportion of men varied from 58% to 77%. All participants were hospitalised; 67% to 100% were on oxygen at baseline but not intubated; between 0% and 33% were intubated at baseline. We identified a further 16 registered trials with no results available, of which 15 assessed anakinra (four completed, four terminated, five ongoing, three not recruiting) and one (completed) trial assessed canakinumab. Effectiveness of anakinra for people with COVID-19 Anakinra probably results in little or no increase in clinical improvement at D28 (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.97 to 1.20; 3 RCTs, 837 participants; absolute effect: 59 more per 1000 (from 22 fewer to 147 more); moderate-certainty evidence. The evidence is uncertain about an effect of anakinra on 1) the proportion of participants with a WHO Clinical Progression Score of level 7 or above at D28 (RR 0.67, 95% CI 0.36 to 1.22; 2 RCTs, 722 participants; absolute effect: 55 fewer per 1000 (from 107 fewer to 37 more); low-certainty evidence) and ≥ D60 (RR 0.54, 95% CI 0.30 to 0.96; 1 RCT, 606 participants; absolute effect: 47 fewer per 1000 (from 72 fewer to 4 fewer) low-certainty evidence); and 2) all-cause mortality at D28 (RR 0.69, 95% CI 0.34 to 1.39; 2 RCTs, 722 participants; absolute effect: 32 fewer per 1000 (from 68 fewer to 40 more); low-certainty evidence).  The evidence is very uncertain about an effect of anakinra on 1) the proportion of participants with clinical improvement at ≥ D60 (RR 0.93, 95% CI 0.78 to 1.12; 1 RCT, 115 participants; absolute effect: 59 fewer per 1000 (from 186 fewer to 102 more); very low-certainty evidence); and 2) all-cause mortality at ≥ D60 (RR 1.03, 95% CI 0.68 to 1.56; 4 RCTs, 1633 participants; absolute effect: 8 more per 1000 (from 84 fewer to 147 more); very low-certainty evidence). Safety of anakinra for people with COVID-19 Anakinra probably results in little or no increase in adverse events (RR 1.02, 95% CI 0.94 to 1.11; 2 RCTs, 722 participants; absolute effect: 14 more per 1000 (from 43 fewer to 78 more); moderate-certainty evidence).  The evidence is uncertain regarding an effect of anakinra on serious adverse events (RR 0.95, 95% CI 0.58 to 1.56; 2 RCTs, 722 participants; absolute effect: 12 fewer per 1000 (from 104 fewer to 138 more); low-certainty evidence). Effectiveness of canakinumab for people with COVID-19 Canakinumab probably results in little or no increase in clinical improvement at D28 (RR 1.05, 95% CI 0.96 to 1.14; 2 RCTs, 499 participants; absolute effect: 42 more per 1000 (from 33 fewer to 116 more); moderate-certainty evidence).  The evidence of an effect of canakinumab is uncertain on 1) the proportion of participants with a WHO Clinical Progression Score of level 7 or above at D28 (RR 0.72, 95% CI 0.44 to 1.20; 2 RCTs, 499 participants; absolute effect: 35 fewer per 1000 (from 69 fewer to 25 more); low-certainty evidence); and 2) all-cause mortality at D28 (RR:0.75; 95% CI 0.39 to 1.42); 2 RCTs, 499 participants; absolute effect: 20 fewer per 1000 (from 48 fewer to 33 more); low-certainty evidence).  The evidence is very uncertain about an effect of canakinumab on all-cause mortality at ≥ D60 (RR 0.55, 95% CI 0.16 to 1.91; 1 RCT, 45 participants; absolute effect: 112 fewer per 1000 (from 210 fewer to 227 more); very low-certainty evidence). Safety of canakinumab for people with COVID-19 Canakinumab probably results in little or no increase in adverse events (RR 1.02; 95% CI 0.86 to 1.21; 1 RCT, 454 participants; absolute effect: 11 more per 1000 (from 74 fewer to 111 more); moderate-certainty evidence). The evidence of an effect of canakinumab on serious adverse events is uncertain (RR 0.80, 95% CI 0.57 to 1.13; 2 RCTs, 499 participants; absolute effect: 44 fewer per 1000 (from 94 fewer to 28 more); low-certainty evidence). AUTHORS' CONCLUSIONS: Overall, we did not find evidence for an important beneficial effect of IL-1 blocking agents. The evidence is uncertain or very uncertain for several outcomes. Sixteen trials of anakinra and canakinumab with no results are currently registered, of which four are completed, and four terminated. The findings of this review are updated on the COVID-NMA platform (covid-nma.com).

Evaluation of a co-culture of rapidly isolated chondrocytes and stem cells seeded on tri-layered collagen-based scaffolds in a caprine osteochondral defect model.

Cartilage has poor regenerative capacity and thus damage to the joint surfaces presents a major clinical challenge. Recent research has focussed on the development of tissue-engineered and cell-based approaches for the treatment of cartilage and osteochondral injuries, with current clinically available cell-based approaches including autologous chondrocyte implantation and matrix-assisted autologous chondrocyte implantation. However, these approaches have significant disadvantages due to the requirement for a two-stage surgical procedure and an in vitro chondrocyte expansion phase which increases logistical challenges, hospital times and costs. In this study, we hypothesized that seeding biomimetic tri-layered scaffolds, with proven regenerative potential, with chondrocyte/infrapatellar fat pad stromal cell co-cultures would improve their regenerative capacity compared to scaffolds implanted cell-free. Rapid cell isolation techniques, without the requirement for long term in vitro culture, were utilised to achieve co-cultures of chondrocytes and stromal cells and thus overcome the limitations of existing cell-based techniques. Cell-free and cell-seeded scaffolds were implanted in osteochondral defects, created within the femoral condyle and trochlear ridge, in a translational large animal goat model. While analysis showed trends towards delayed subchondral bone healing in the cell-seeded scaffold group, by the 12 month timepoint the cell-free and cell-seeded groups yield cartilage and bone tissue with comparable quality and quantity. The results of the study reinforce the potential of the biomimetic tri-layered scaffold to repair joint defects but failed to demonstrate a clear benefit from the addition of the CC/FPMSC co-culture to this scaffold. Taking into consideration the additional cost and complexity associated with the cell-seeded scaffold approach, this study demonstrates that the treatment of osteochondral defects using cell-free tri-layered scaffolds may represent a more prudent clinical approach.

Layer-specific stem cell differentiation in tri-layered tissue engineering biomaterials: Towards development of a single-stage cell-based approach for osteochondral defect repair.

Successful repair of osteochondral defects is challenging, due in part to their complex gradient nature. Tissue engineering approaches have shown promise with the development of layered scaffolds that aim to promote cartilage and bone regeneration within the defect. The clinical potential of implanting these scaffolds cell-free has been demonstrated, whereby cells from the host bone marrow MSCs infiltrate the scaffolds and promote cartilage and bone regeneration within the required regions of the defect. However, seeding the cartilage layer of the scaffold with a chondrogenic cell population prior to implantation may enhance cartilage tissue regeneration, thus enabling the treatment of larger defects. Here the development of a cell seeding approach capable of enhancing articular cartilage repair without the requirement for in vitro expansion of the cell population is explored. The intrinsic ability of a tri-layered scaffold previously developed in our group to direct stem cell differentiation in each layer of the scaffold was first demonstrated. Following this, the optimal chondrogenic cell seeding approach capable of enhancing the regenerative capacity of the tri-layered scaffold was demonstrated with the highest levels of chondrogenesis achieved with a co-culture of rapidly isolated infrapatellar fat pad MSCs (FPMSCs) and chondrocytes (CCs). The addition of FPMSCs to a relatively small number of CCs led to a 7.8-fold increase in the sGAG production over chondrocytes in mono-culture. This cell seeding approach has the potential to be delivered within a single-stage approach, without the requirement for costly in vitro expansion of harvested cells, to achieve rapid repair of osteochondral defects.

Connolly Hospital Trauma Assessment Clinic (TAC): a virtual solution to patient flow.

BACKGROUND: Trauma Assessment Clinics (TAC) were pioneered by the Glasgow Royal Infirmary Group. Patients deemed for non-operative management are referred to the TAC for review by an orthopaedic consultant with multidisciplinary team (MDT) support. Connolly Hospital launched a TAC on 11 September 2018. AIMS: The goal of this study was to evaluate the effect the introduction of this initiative had on patient flow in our institution. METHODS: We performed a retrospective review of the Connolly Hospital TAC for the 6-month period since its introduction. We evaluated patient demographics, injuries and outcomes. Furthermore, we retrospectively reviewed the fracture and elective clinic attendances pre- and post-TAC introduction. RESULTS: Over the first 6 months of this initiative, there were 36 trauma assessment clinics. Two hundred forty-seven patients were reviewed with an average age of 42.3 years. 42.9% (N = 106) was reviewed directly by the physiotherapy department. 31.6% (N = 78) was scheduled directly for fracture clinic follow-up from the TAC. 8.2% (N = 45) was discharged directly to their GP from TAC. A review of fracture clinic attendances for the corresponding time period the previous year (from September 2017), highlighted a 22% decrease in new fracture clinic appointments. CONCLUSIONS: Following the introduction of the TAC, we noted a marked reduction in fracture clinic attendances. Our outcomes were consistent with results from other units. We established two injection clinics as a direct result of the time saved from the TAC. It has proven to be of benefit to both the trauma and elective patients in our institution.

Monogenic causes of chronic kidney disease in adults.

Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.

A case of Verruconis gallopava infection in a heart transplant recipient successfully treated with posaconazole.

Verruconis gallopava is an environmental dematiaceous fungus that is recognized increasingly as a cause of human disease, especially for immunocompromised persons. Infection can range from superficial and localized lesions to pulmonary involvement and disseminated disease, including central nervous system abscesses. Optimal therapy is undefined. We report a patient post cardiac transplant who had pulmonary infection with V gallopava and was treated successfully with posaconazole.

The Utility of Screening for Coccidioidomycosis in Recipients of Inhibitors of Tumor Necrosis Factor α.

BACKGROUND: Tumor necrosis factor α inhibitors (TNFi) are commonly used to treat immune-mediated disorders, but they are associated with an increased risk of mycobacterial and fungal infections. We compared the outcomes of TNFi recipients screened for asymptomatic coccidioidomycosis with those of unscreened patients to compare the development of symptomatic coccidioidomycosis and to describe its outcomes for patients with abnormal coccidioidal screenings. METHODS: We searched electronic health records from 4 September 2010 through 26 September 2016 for all patients receiving a TNFi for dermatologic, rheumatologic, or gastroenterologic diagnoses, then categorized patients by whether or not they had undergone coccidioidal serologic testing for screening or diagnostic purposes. RESULTS: A total of 2793 patients had a TNFi prescribed. Of those, 1951 met the inclusion criteria: 1025/1951 (52.5%) never had coccidioidal screening; 925/1951 (47.4%) had serologic screening either before beginning TNFi therapy or annually, or both after beginning a TNFi. Symptomatic coccidioidomycosis developed in 35/1025 (3.4%) unscreened patients. Of those screened, 861/925 (93.1%) had negative serologic tests, of which 11/861 (1.3%) subsequently developed symptomatic coccidioidomycosis; 36/925 (3.9%) had coccidioidomycosis at screening (7, probable infection; 11, possible infection; 18, asymptomatic seropositive result); and 17 had only positive findings for immunoglobulin M antibodies and did not meet the definition for coccidioidomycosis. The unscreened cohort was more likely to have symptomatic coccidioidomycosis than the screened cohort (35/1025 vs 11/861, P < .01). CONCLUSIONS: Screening for asymptomatic coccidioidomycosis within a Coccidioides-endemic area allowed for identifying and managing asymptomatic coccidioidomycosis before patients began TNFi therapy. Less symptomatic infection developed in the screened than the unscreened cohort.

Tissue-specific extracellular matrix scaffolds for the regeneration of spatially complex musculoskeletal tissues.

Biological scaffolds generated from tissue-derived extracellular matrix (ECM) are commonly used clinically for soft tissue regeneration. Such biomaterials can enhance tissue-specific differentiation of adult stem cells, suggesting that structuring different ECMs into multi-layered scaffolds can form the basis of new strategies for regenerating damaged interfacial tissues such as the osteochondral unit. In this study, mass spectrometry is used to demonstrate that growth plate (GP) and articular cartilage (AC) ECMs contain a unique array of regulatory proteins that may be particularly suited to bone and cartilage repair respectively. Applying a novel iterative freeze-drying method, porous bi-phasic scaffolds composed of GP ECM overlaid by AC ECM are fabricated, which are capable of spatially directing stem cell differentiation in vitro, promoting the development of graded tissues transitioning from calcified cartilage to hyaline-like cartilage. Evaluating repair 12-months post-implantation into critically-sized caprine osteochondral defects reveals that these scaffolds promote regeneration in a manner distinct to commercial control-scaffolds. The GP layer supports endochondral bone formation, while the AC layer stimulates the formation of an overlying layer of hyaline cartilage with a collagen fiber architecture better recapitulating the native tissue. These findings support the use of a bi-layered, tissue-specific ECM derived scaffolds for regenerating spatially complex musculoskeletal tissues.

Managing acute and chronic renal stone disease.

Nephrolithiasis, or renal stone disease, is common and the incidence is increasing globally. In the UK the lifetime risk is estimated to be 8-10%. On a population level, the increase in stone incidence, erosion of gender disparity, and younger age of onset is likely to reflect increasing prevalence of obesity and a Western diet with a high intake of animal protein and salt. Stones can be detected by a variety of imaging techniques. The gold standard is a non-contrast CT of kidneys, ureters and bladder (CT KUB) which can identify > 99% of stones. CT KUB should be the primary mode of imaging for all patients with colic unless contraindicated. In such instances, or if a CT KUB is not available, an ultrasound KUB is an alternative. This has advantages in terms of radiation exposure and cost, but is limited in sensitivity, particularly for ureteric stones. Once diagnosed, a plain film KUB can be used for follow-up of radiopaque stones. For most patients diclofenac is a reasonable first choice of analgesia, e.g. 50-100 mg rectally, or 75 mg IM. Opioid medication can worsen nausea and be less effective, but should be used if there is a contraindication to NSAIDs. A combination of diclofenac, paracetamol, and/or codeine regularly can provide adequate pain control in many cases. Failure of this analgesic combination should prompt consideration of secondary care support. If a ureteric stone < 5 mm in diameter is identified, the expectation is that this will pass without intervention. Initially medical management is still useful for stones between 5 and 10mm in diameter, but urology input is more likely to be necessary as up to 50% of these may require intervention. Stones that are >10 mm in diameter should be discussed with the urology service as they are unlikely to pass spontaneously.

The benefits and limitations of animal models for translational research in cartilage repair.

Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity. These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans. A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are required, and usually demanded by regulatory approval bodies. This review examines the in vivo models in current use for cartilage defect repair testing and the relevance of each in the context of generated results and applicability to bringing the device to clinical practice. Some of the preclinical models currently used include murine, leporine, ovine, caprine, porcine, canine, and equine models. Each of these has advantages and disadvantages in terms of animal husbandry, cartilage thickness, joint biomechanics and ethical and licencing issues. This review will examine the strengths and weaknesses of the various animal models currently in use in preclinical studies of cartilage repair.

How we implemented an integrated professionalism curriculum to 2nd year medical students at the National University of Ireland Galway Medical School, with examples from students' final output.

Since the introduction of professionalism in medical curricula worldwide, little evidence has been published to exemplify good educational practice. The Medical school at the National University of Ireland Galway teaches professionalism in an interdisciplinary manner, integrating the learning objectives of health informatics, understanding health & illness in society, medical law and ethics. Students work in small groups on clinical cases. Enquiry-based learning is used as the teaching method following a few introductory lectures on specific objectives. Students present their work in the format of a scientific essay. The latter is assessed by a board of reviewers. The purpose of this article is to demonstrate evidence of excellent professional output and illustrate the benefits to a fully integrated professionalism curriculum.