• The major cause of multiple sclerosis is environmental: genetics has a minor role--commentary.

      Hutchinson, Michael; St Vincent's University Hospital. mhutchin@iol.ie (2012-02-01)
    • Management of acute diverticulitis: is less more?

      Hogan, Aisling; Winter, Des; Institute for Clinical Outcomes Research and Education, St. Vincent's University , Hospital, Dublin, Ireland. aislinghogan@yahoo.com (2012-02-01)
    • 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.
    • Management of synchronous rectal and prostate cancer.

      Kavanagh, D O; Quinlan, D M; Armstrong, J G; Hyland, J M P; O'Connell, P R; Winter, D C; Center for Colorectal Disease, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. dara_kav@hotmail.com (2012-11)
      Although well described, there is limited published data related to management on the coexistence of prostate and rectal cancer. The aim of this study was to describe a single institution's experience with this and propose a treatment algorithm based on the best available evidence.
    • Mass lesions in chronic pancreatitis: benign or malignant? An "evidence-based practice" approach.

      Gerstenmaier, Jan F; Malone, Dermot E; Department of Radiology, St. Vincent's University Hospital, Dublin, Ireland., j.gerstenmaier@svuh.ie (2012-02-01)
      The diagnosis of a pancreatic mass lesion in the presence of chronic pancreatitis can be extremely challenging. At the same time, a high level of certainty about the diagnosis is necessary for appropriate management planning. The aim of this study was to establish current best evidence about which imaging methods reliably differentiate a benign from a malignant lesion, and show how that evidence is best applied. A diagnostic algorithm based on Bayesian analysis is proposed.
    • 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.
    • Mechanical characterisation of porcine rectus sheath under uniaxial and biaxial tension.

      Lyons, Mathew; Winter, Des C; Simms, Ciaran K; Trinity Centre for Bioengineering, Department of Mechanical and Manufacturing Engineering, Parsons Building, Trinity College, Dublin 2, Ireland. Electronic address: lyonsm2@tcd.ie. (2014-06-03)
      Incisional hernia development is a significant complication after laparoscopic abdominal surgery. Intra-abdominal pressure (IAP) is known to initiate the extrusion of intestines through the abdominal wall, but there is limited data on the mechanics of IAP generation and the structural properties of rectus sheath. This paper presents an explanation of the mechanics of IAP development, a study of the uniaxial and biaxial tensile properties of porcine rectus sheath, and a simple computational investigation of the tissue. Analysis using Laplace׳s law showed a circumferential stress in the abdominal wall of approx. 1.1MPa due to an IAP of 11kPa, commonly seen during coughing. Uniaxial and biaxial tensile tests were conducted on samples of porcine rectus sheath to characterise the stress-stretch responses of the tissue. Under uniaxial tension, fibre direction samples failed on average at a stress of 4.5MPa at a stretch of 1.07 while cross-fibre samples failed at a stress of 1.6MPa under a stretch of 1.29. Under equi-biaxial tension, failure occurred at 1.6MPa with the fibre direction stretching to only 1.02 while the cross-fibre direction stretched to 1.13. Uniaxial and biaxial stress-stretch plots are presented allowing detailed modelling of the tissue either in silico or in a surrogate material. An FeBio computational model of the tissue is presented using a combination of an Ogden and an exponential power law model to represent the matrix and fibres respectively. The structural properties of porcine rectus sheath have been characterised and add to the small set of human data in the literature with which it may be possible to develop methods to reduce the incidence of incisional hernia development.
    • Mechanisms-based classifications of musculoskeletal pain: part 1 of 3: symptoms and signs of central sensitisation in patients with low back (± leg) pain.

      Smart, Keith M; Blake, Catherine; Staines, Anthony; Thacker, Mick; Doody, Catherine; Physiotherapy Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. k.smart@svuh.ie (2012-08)
      As a mechanisms-based classification of pain 'central sensitisation pain' (CSP) refers to pain arising from a dominance of neurophysiological dysfunction within the central nervous system. Symptoms and signs associated with an assumed dominance of CSP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of CSP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of three symptoms and one sign predictive of CSP, including: 'Disproportionate, non-mechanical, unpredictable pattern of pain provocation in response to multiple/non-specific aggravating/easing factors', 'Pain disproportionate to the nature and extent of injury or pathology', 'Strong association with maladaptive psychosocial factors (e.g. negative emotions, poor self-efficacy, maladaptive beliefs and pain behaviours)' and 'Diffuse/non-anatomic areas of pain/tenderness on palpation'. This cluster was found to have high levels of classification accuracy (sensitivity 91.8%, 95% confidence interval (CI): 84.5-96.4; specificity 97.7%, 95% CI: 95.6-99.0). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of CSP in patients with low back pain disorders in a way that might usefully inform their management.
    • Mechanisms-based classifications of musculoskeletal pain: part 2 of 3: symptoms and signs of peripheral neuropathic pain in patients with low back (± leg) pain.

      Smart, Keith M; Blake, Catherine; Staines, Anthony; Thacker, Mick; Doody, Catherine; Physiotherapy Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. k.smart@svuh.ie (2012-08)
      As a mechanisms-based classification of pain 'peripheral neuropathic pain' (PNP) refers to pain arising from a primary lesion or dysfunction in the peripheral nervous system. Symptoms and signs associated with an assumed dominance of PNP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of PNP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of two symptoms and one sign predictive of PNP, including: 'Pain referred in a dermatomal or cutaneous distribution', 'History of nerve injury, pathology or mechanical compromise' and 'Pain/symptom provocation with mechanical/movement tests (e.g. Active/Passive, Neurodynamic) that move/load/compress neural tissue'. This cluster was found to have high levels of classification accuracy (sensitivity 86.3%, 95% CI: 78.0-92.3; specificity 96.0%, 95% CI: 93.4-97.8; diagnostic odds ratio 150.9, 95% CI: 69.4-328.1). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of PNP mechanisms in patients with low back pain disorders in a way that might usefully inform subsequent patient management.
    • Mechanisms-based classifications of musculoskeletal pain: part 3 of 3: symptoms and signs of nociceptive pain in patients with low back (± leg) pain.

      Smart, Keith M; Blake, Catherine; Staines, Anthony; Thacker, Mick; Doody, Catherine; Physiotherapy Department, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. k.smart@svuh.ie (2012-08)
      As a mechanisms-based classification of pain 'nociceptive pain' (NP) refers to pain attributable to the activation of the peripheral receptive terminals of primary afferent neurones in response to noxious chemical, mechanical or thermal stimuli. The symptoms and signs associated with clinical classifications of NP have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of NP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol after which their pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist indicating the presence/absence of various symptoms and signs. A regression analysis identified a cluster of seven clinical criteria predictive of NP, including: 'Pain localised to the area of injury/dysfunction', 'Clear, proportionate mechanical/anatomical nature to aggravating and easing factors', 'Usually intermittent and sharp with movement/mechanical provocation; may be a more constant dull ache or throb at rest', and the absence of 'Pain in association with other dysesthesias', 'Night pain/disturbed sleep', 'Antalgic postures/movement patterns' and 'Pain variously described as burning, shooting, sharp or electric-shock-like'. This cluster was found to have high levels of classification accuracy (sensitivity 90.9%, 95% CI: 86.6-94.1; specificity 91.0%, 95% CI: 86.1-94.6). Pattern recognition of this empirically-derived cluster of symptoms and signs may help clinicians identify an assumed dominance of NP mechanisms in patients with low back pain disorders.
    • Medical Management of Patients After Atypical Femur Fractures: a Systematic Review and Recommendations From the European Calcified Tissue Society.

      van de Laarschot, Denise M; McKenna, Malachi J; Abrahamsen, Bo; Langdahl, Bente; Cohen-Solal, Martine; Guañabens, Núria; Eastell, Richard; Ralston, Stuart H; Zillikens, M Carola
      Context: Atypical femur fractures (AFFs) are serious adverse events associated with bisphosphonates and often show poor healing. Evidence acquisition: We performed a systematic review to evaluate effects of teriparatide, raloxifene, and denosumab on healing and occurrence of AFF. Evidence synthesis: We retrieved 910 references and reviewed 67 papers, including 31 case reports, 9 retrospective and 3 prospective studies on teriparatide. There were no RCTs. We pooled data on fracture union (n = 98 AFFs on teriparatide) and found that radiological healing occurred within 6 months of teriparatide in 13 of 30 (43%) conservatively managed incomplete AFFs, 9 of 10 (90%) incomplete AFFs with surgical intervention, and 44 of 58 (75%) complete AFFs. In 9 of 30 (30%) nonoperated incomplete AFFs, no union was achieved after 12 months and 4 (13%) fractures became complete on teriparatide. Eight patients had new AFFs during or after teriparatide. AFF on denosumab was reported in 22 patients, including 11 patients treated for bone metastases and 8 without bisphosphonate exposure. Denosumab after AFF was associated with recurrent incomplete AFFs in 1 patient and 2 patients of contralateral complete AFF. Eight patients had used raloxifene before AFF occurred, including 1 bisphosphonate-naïve patient. Conclusions: There is no evidence-based indication in patients with AFF for teriparatide apart from reducing the risk of typical fragility fractures, although observational data suggest that teriparatide might result in faster healing of surgically treated AFFs. Awaiting further evidence, we formulate recommendations for treatment after an AFF based on expert opinion.
    • A meta-analysis of surgical morbidity and recurrence after laparoscopic and open repair of primary unilateral inguinal hernia.

      O'Reilly, Elma A; Burke, John P; O'Connell, P Ronan; Surgical Professorial Unit, St Vincent's University Hospital, Elm Park, Dublin, Ireland. (2012-05)
      Laparoscopic inguinal hernia repair (LIHR), using a transabdominal preperitoneal (TAPP) or totally extraperitoneal (TEP) technique, is an alternative to conventional open inguinal hernia repair (OIHR). A consensus on outcomes of LIHR when compared with OIHR for primary, unilateral, inguinal hernia has not been reached.
    • Methylated genes as new cancer biomarkers.

      Duffy, M J; Napieralski, R; Martens, J W M; Span, P N; Spyratos, F; Sweep, F C G J; Brunner, N; Foekens, J A; Schmitt, M; Department of Pathology and Laboratory Medicine, Nuclear Medicine Laboratory, St., Vincent's University Hospital, Elm Park, Dublin 4, Ireland., Michael.J.Duffy@ucd.ie (2012-02-01)
      Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.
    • Microbial and viral pathogens in colorectal cancer.

      Collins, Danielle; Hogan, Aisling M; Winter, Desmond C; St Vincent's University Hospital and University College Dublin, Dublin 4, Ireland. (2011-05)
      The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.
    • Microbial and viral pathogens in colorectal cancer.

      Collins, Danielle; Hogan, Aisling M; Winter, Desmond C; St Vincent's University Hospital and University College Dublin, Dublin 4,, Ireland. (2012-02-01)
      The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.
    • Minimally invasive and surgical management strategies tailored to the severity of acute diverticulitis.

      McDermott, F D; Collins, D; Heeney, A; Winter, D C (2014-01)
      The severity of acute diverticulitis ranges from mild, simple inflammation to pericolic abscesses, or perforation with faeculent peritonitis. Treatment of diverticulitis has evolved towards more conservative and minimally invasive strategies. The aim of this review is to highlight recent concepts and advances in management.
    • Mitochondrial mutagenesis correlates with the local inflammatory environment in arthritis.

      Harty, Leonard C; Biniecka, Monika; O'Sullivan, Jacintha; Fox, Edward; Mulhall, Kevin; Veale, Douglas J; Fearon, Ursula; Translation Rheumatology Research Group, Dublin Academic Medical Centre, St Vincent’s University Hospital, Elm Park, Ireland. (2012-04)
      To examine the association between mitochondrial mutagenesis and the proinflammatory microenvironment in patients with inflammatory arthritis.
    • Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

      Gorman, Sheeona; Fox, Edward; O'Donoghue, Diarmuid; Sheahan, Kieran; Hyland, John; Mulcahy, Hugh; Loeb, Lawrence A; O'Sullivan, Jacintha; Centre for Colorectal Disease, St. Vincent's University Hospital, Elm Park,, Dublin 4, Ireland. (2012-02-01)
      The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.
    • Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

      Phelan, Dermot; Watson, Chris; Martos, Ramon; Collier, Patrick; Patle, Anil; Donnelly, Seamas; Ledwidge, Mark; Baugh, John; McDonald, Ken; Heart Failure Unit, St Vincent's University Hospital, Elm Park, Dublin, Ireland. (2012-11)
      In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.
    • Molecular detection of an atypical, highly resistant, clonal Pseudomonas aeruginosa isolate in cystic fibrosis patients.

      Keating, Deirdre; Crowe, Mary J; Kennedy, Barry; Salmon, Abigail; Britton, David; Gallagher, Charles G; McKone, Edward F; Schaffer, Kirsten (2013-03)
      The identification of Pseudomonas aeruginosa (P. aeruginosa) isolates in sputum from cystic fibrosis (CF) patients can be challenging due to the multitude of phenotypic changes isolates undergo during adaptation to the microenvironment of the CF lung.