Now showing items 1-20 of 472

    • Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis.

      Wade, Sarah M; Canavan, Mary; McGarry, Trudy; Low, Candice; Wade, Siobhan C; Mullan, Ronan H; Veale, Douglas J; Fearon, Ursula (2019-01-09)
      PsA synovial tissue infiltrating CD4+ T-cells expressed higher levels of interleukin (IL)-17A, interferon gamma (IFN-γ), GM-CSF and CD161, with parallel enrichment of Th1, Th17 and exTh17 T-helper subsets (all p<0.05). Interestingly, a significant proportion of synovial T-cell subsets were triple-positive for GM-CSF, tumour necrosis factor (-TNF), -IL-17 or IFN-γ compared with matched blood (all p<0.05). Importantly, frequencies of polyfunctional T-cells correlated with DAPSA: Th1-GM-CSF+/TNF+/IFN-γ+ (r=0.7, p<0.01), Th17-GM-CSF+/TNF+/IL-17+ (r=0.6, p<0.057) and exTh17-GM-CSF+/TNF+/IFN-γ+ (r=0.7, p=0.0096), with no associations observed for single cytokine-producing T-cells. Following ex vivo culture of PsA synovial tissue cell suspensions, polyfunctional GM-CSF+TNFα+IL-17A+ or/IFN-γ+-producing T-cells (p<0.05), but not single cytokine-producing T-cells, were inhibited with a PDE4 inhibitor. Conclusion: These data demonstrate enrichment of polyfunctional T-cells in PsA synovial tissue which were strongly associated with DAPSA and ex vivo therapeutic response.
    • Adipose tissue as a key player in obstructive sleep apnoea.

      Ryan, Silke; Arnaud, Claire; Fitzpatrick, Susan F; Gaucher, Jonathan; Tamisier, Renaud; Pépin, Jean-Louis (2019-06-26)
      Obstructive sleep apnoea (OSA) is a major health concern worldwide and adversely affects multiple organs and systems. OSA is associated with obesity in >60% of cases and is independently linked with the development of numerous comorbidities including hypertension, arrhythmia, stroke, coronary heart disease and metabolic dysfunction. The complex interaction between these conditions has a significant impact on patient care and mortality. The pathophysiology of cardiometabolic complications in OSA is still incompletely understood; however, the particular form of intermittent hypoxia (IH) observed in OSA, with repetitive short cycles of desaturation and re-oxygenation, probably plays a pivotal role. There is fast growing evidence that IH mediates some of its detrimental effects through adipose tissue inflammation and dysfunction. This article aims to summarise the effects of IH on adipose tissue in experimental models in a comprehensive way. Data from well-designed controlled trials are also reported with the final goal of proposing new avenues for improving phenotyping and personalised care in OSA.
    • The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis.

      Veale, Douglas J; McGonagle, Dennis; McInnes, Iain B; Krueger, James G; Ritchlin, Christopher T; Elewaut, Dirk; Kanik, Keith S; Hendrikx, Thijs; Berstein, Gabriel; Hodge, Jennifer; et al.
      The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS.
    • A Temporal Comparative Study of Women’s Rugby Injuries Presenting to an Emergency Department

      Gilmartin, S.; Ryan, J. (Irish Medical Journal, 2019-10)
      We aimed to examine the change in injury patterns, diagnostics and treatments provided to female rugby players in an emergency department between two separate seasons ten years apart.
    • The Role of Interventional Radiology in the Management of Obstetric and Gynaecological Haemorrhage

      O’Brien, C.; Healy, G.M.; Anglim, B.C.; O’Brien, A.; Duignan, J.; Patel, A.; Cheung, M.; Cantwell, C.P. (Irish Medical Journal, 2019-07)
      Aim We will review our experience of emergent arterial embolization used to treat haemodynamically unstable patients with obstetric and gynaecological haemorrhage. Methods This is a retrospective study of patients with haemodynamically unstable obstetric and gynaecological haemorrhage treated with emergent arterial embolization from 2010 to 2015. Results 22 patients (average age 41 (SD +/-9) years) had emergent arterial embolization. 63% had post-partum haemorrhage(PPH). 82% of cases were performed with conscious sedation and local anaesthesia. Embolization was technically successful in all cases. Embolization was clinically successful in 95% (21/22). In one case of PPH the patient represented six days later with recurrent bleeding and was treated with surgical suturing of the cervix. There were no complications or deaths. Conclusion Arterial embolization is a highly successful treatment of obstetric and gynaecological haemorrhage in unstable patients.
    • Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium.

      Bryant, Josephine M; Grogono, Dorothy M; Rodriguez-Rincon, Daniela; Everall, Isobel; Brown, Karen P; Moreno, Pablo; Verma, Deepshikha; Hill, Emily; Drijkoningen, Judith; Gilligan, Peter; et al. (2016-11-11)
      Lung infections with Mycobacterium abscessus, a species of multidrug resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF) where they accelerate inflammatory lung damage leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
    • Physiotherapist-Led Triage at a Rheumatology-Based Musculoskeletal Assessment Clinic: an 18-Month Service Evaluation of Activity and Outcomes

      Caffrey, Aoife; Smart, Keith M.; Fitzgerald, Oliver (American College of Rheumatology, 2019)
      Physiotherapist-led musculoskeletal triage clinics are an effective and efficient means of managing patients presenting with musculoskeletal disorders in primary and secondary care. Data regarding the activity and outcomes of physiotherapist-led triage in hospital-based outpatient rheumatology clinics are scarce. Thus, the aim of this study was to undertake a service evaluation of activity and outcomes of a physiotherapist-led rheumatologybased Musculoskeletal Assessment Clinic (MAC). The primary objective was to quantify the proportion of patients independently managed by the clinical specialist physiotherapists (CSPs).
    • Oxygen Therapy in Ireland: A Nationwide Review of Delivery, Monitoring and Cost Implications

      O’Donnell, C; Davis, P (Irish Medical Journal, 2019-05)
      Our aim was to establish which hospitals in Ireland are running oxygen clinics and to compare oxygen prescription in hospitals to a guideline standard. Long term oxygen therapy is known to be of benefit to a specific cohort of patients but is not without risk.
    • An Under-Recognised Cause of Iatrogenic, Severe Metabolic Acidosis

      Spring, A; Owens, R; Fratita, M; O’Dwyer, M (Irish Medical Journal, 2019-04)
      Pyroglutamic acidosis is an uncommonly diagnosed but important cause of a high anion gap metabolic acidosis. Our case report concerns an elderly male admitted to the Intensive Care Unit (ICU) following the acute onset of coma which developed during treatment of a prosthetic joint infection. A diagnosis of pyroglutamic acidosis was ultimately made and later confirmed with laboratory testing. Blood gas analysis revealed a profound high anion gap metabolic acidosis.
    • The Management of Incidental Prostate Cancer Following TURP

      Matanhelia, D.M; Croghan, S.; Nason, G.J; O’Connell, C.; Galvin, D.J.; 1. St Vincent’s University Hospital 2. Mater Misericordiae University Hospital (Irish Medical Journal, 2019-02)
      Prostate cancer (CaP) is the most common non-cutaneous cancer diagnosed in Ireland with a cumulative lifetime risk of 1 in 7 men1. At autopsy, up to 60% of 80 years olds have latent CaP2 while up to 80% have benign prostatic hyperplasia (BPH) 3. The detection of CaP incidentally has fallen in the post prostate specific antigen (PSA) era from ~ 20% to ~5%4. Incidental CaP detected at transurethral resection of prostate (TURP) can be sub-classified into pT1a (<5% of prostate chips) and pT1b (>5% of prostate chips) and the management subsequently stratified.
    • Preclinical validation of the small molecule drug quininib as a novel therapeutic for colorectal cancer.

      Murphy, Adrian G; Casey, Rory; Maguire, Aoife; Tosetto, Miriam; Butler, Clare T; Conroy, Emer; Reynolds, Alison L; Sheahan, Kieran; O'donoghue, Diarmuid; Gallagher, William M; et al. (Nature Publishing Group, 2016-10-14)
      Colorectal cancer (CRC) is a leading cause of cancer deaths. Molecularly targeted therapies (e.g. bevacizumab) have improved survival rates but drug resistance ultimately develops and newer therapies are required. We identified quininib as a small molecule drug with anti-angiogenic activity using in vitro, ex vivo and in vivo screening models. Quininib (2-[(E)-2-(Quinolin-2-yl) vinyl] phenol), is a small molecule drug (molecular weight 283.75 g/mol), which significantly inhibited blood vessel development in zebrafish embryos (p < 0.001). In vitro, quininib reduced endothelial tubule formation (p < 0.001), cell migration was unaffected by quininib and cell survival was reduced by quininib (p < 0.001). Using ex vivo human CRC explants, quininib significantly reduced the secretions of IL-6, IL-8, VEGF, ENA-78, GRO-α, TNF, IL-1β and MCP-1 ex vivo (all values p < 0.01). Quininib is well tolerated in mice when administered at 50 mg/kg intraperitoneally every 3 days and significantly reduced tumour growth of HT-29-luc2 CRC tumour xenografts compared to vehicle control. In addition, quininib reduced the signal from a α
    • Canis Caveat (Beware of the Dog) - Septic Shock Due To Capnocytophaga Canimorsus Contracted From A Dog Bite

      O’Shaughnessy, SM; Broderick, L; Walsh, J; Schaffer, K; Westbrook, A; St. Vincent’s University Hospital (Irish Medical Journal, 2018-11)
      We describe the case of a 61-year-old immunocompetent male who developed septic shock and multiorgan failure due to Capnocytophaga canimorsus (C. canimorsus) bloodstream infection, sustained from a dog bite. Unusually, this patient developed acute liver failure and splenic infarction in addition to many of the better-known clinical sequelae of C. canimorsus infection.
    • Ankylosing Spondylitis Response to TNF Inhibition Is Gender Specific: A 6-Year Cohort Study

      Murray, C; Fearon, C; Dockery, M; Moran, D; Heffernan, E; Fitzgerald, O; Veale, D.J; Harty, L; St. Vincent's University Hospital (Irish Medical Journal, 2018-10)
      Recent studies have suggested gender-specific differences with respect to both baseline disease activity and severity in ankylosing spondylitis (AS). Tumour necrosis factor inhibitors (TNFi) have shown significant benefit in AS but there may be gender-specific differences regarding responses to TNFi therapy.
    • A Life-Saving Palsy: Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) Presenting As Hand Weakness during Cardiopulmonary Resuscitation (CPR) Training

      Hughes, H; Tubridy, N; Connolly, S; St. Vincent’s University Hospital, Dublin (Irish Medical Journal, 2018-09)
      Hereditary neuropathy with liability to pressure palsies (HNPP), is an uncommon condition characterised by recurrent episodes of painless, focal motor and sensory peripheral neuropathies, often preceded by nerve compression 1, 2. Despite the rarity of the condition, HNPP should form part of the differential diagnosis in patients presenting with this picture.
    • St Vincent’s University Hospital Make Bold Move by Banning Soap

      Murphy, Lisa (St Vincent's University Hospital, 2017)
    • Maternal Early Warning Scores (MEWS)

      Nair, Shrijit; Dockrell, Lucy; Mac Colgain, Siaghal; St. Vincent’s University Hospital (World Federation of Societies of Anesthesiologists, 2018-07)
      According to Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries in the UK (MBRRACE-UK) report 2016, maternal mortality rate is 8.5 per 100,000 maternities. More than 50% of maternal deaths are potentially preventable.Nine pregnant women develop severe maternal morbidity for every maternal death. Evolving morbidity can be difficult to recognise in the obstetric population because of the normal changes in peripartum physiology. Delays in recognition of patient deterioration and initiation of treatment lead to worse outcomes.2 Early Warning Systems (EWS) have been used since 1999 in the general patient population to identify clinical deterioration. The Maternal Early Warning System (MEWS) has been advocated with the aim to reduce maternal morbidity and mortality, and improve clinical outcomes. The MEWS tracks physiological parameters and evolving morbidity and once a predetermined threshold has been reached, it triggers evaluation by a healthcare professional.
    • Quality Improvement of Clinical Handover in a Liaison Psychiatry Department: A Three-Phase Audit

      Alexander, L; Bechan, N; Brady, S; Douglas, L; Moore, S; Shelley, R (Irish Medical Journal, 2018-06)
      Clinical handover has been identified as a period of high risk in healthcare, with increased incidence of adverse outcomes and near-misses. The purpose of handover is to communicate relevant information between medical professionals, with emphasis on completing management tasks and preventing patients from ‘falling through the cracks’1. Poor handover practices contribute to catastrophic but avoidable adverse events in healthcare. In Ireland, one such high profile incident has been a particular catalyst in the development of comprehensive handover guidelines in maternity settings2. Other specialities have yet to follow suit and there remains a dearth of guidance on handover practices, particularly guidance that can be applied to highly specialised and logistically unique areas, such as psychiatry
    • Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

      Guo, Yanxia; Walsh, Alice M; Canavan, Mary; Wechalekar, Mihir D; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; et al. (PLoS One, 2018)
      Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.
    • Isolation and gene expression profiling of intestinal epithelial cells: crypt isolation by calcium chelation from in vivo samples.

      Balfe, Aine; Lennon, Grainne; Lavelle, Aonghus; Docherty, Neil G; Coffey, J Calvin; Sheahan, Kieran; Winter, Desmond C; O'Connell, P Ronan (Clinical and Experimental Gastroenterology, 2018)
      The epithelial layer within the colon represents a physical barrier between the luminal contents and its underlying mucosa. It plays a pivotal role in mucosal homeostasis, and both tolerance and anti-pathogenic immune responses. Identifying signals of inflammation initiation and responses to stimuli from within the epithelial layer is critical to understanding the molecular pathways underlying disease pathology. This study validated a method to isolate and analyze epithelial populations, enabling investigations of epithelial function and response in a variety of disease setting.
    • Overnight Emergency CT Imaging: A 10-Year Experience at an Irish Tertiary Referral Hospital.

      Hynes J; Redmond CE; Healy GM; Cronin, J; Heffernan, EJ (Irish Medical Journal, 2018-01)
      In recent years there has been increased utilisation of computed tomography (CT) imaging in developed countries, however there is a paucity of data regarding the utilisation of CT in the emergency overnight setting. We retrospectively analysed trends in ‘overnight’ (midnight to 8am) CT utilisation over a ten-year period at a single Irish tertiary referral hospital. Over the study period, we observed a significant increase in the proportion of CT imaging that was carried out overnight. There was no significant variation in the yield of pathological findings over the study period, which remained low (64% of CT studies were normal or had non-critical findings). The multiple factors which have contributed to the increased utilization of overnight emergency CT in recent years, the potential for reporting errors overnight and the implications therein for patient safety warrant consideration.