Materials Misericordiae University Hospital

Dublin, Ireland

Materials Misericordiae University Hospital

Dublin, Ireland

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Shields C.J.,Materials Misericordiae University Hospital | Tiret E.,University Pierre and Marie Curie | Winter D.C.,St Vincents University Hospital
Annals of Surgery | Year: 2010

Objective: This study aims to describe recent experience with rectal carcinoids in European and North American centers. Background: While considered indolent, the propensity of carcinoids to metastasize can be significant. Methods: Rectal carcinoid patients were identified from prospective databases maintained at 9 institutions between 1999 and 2008. Demographic, clinical, and histologic data were collated. Median follow-up was 5 years (range, 0.5-10 years). Results: Two hundred two patients were identified. The median age was 55 years (range, 31-81 years). The majority of tumors were an incidental finding (n = 115, 56.9%). The median tumor size was 10 mm (range, 2-120 mm). Overall, 93 (49%) tumors were limited to the mucosa or submucosa, 45 (24%) involved the muscularis propria, 29 (15%) extended into the perirectal fat, and 6 (3%) reached the visceral peritoneum. The primary treatment modalities were endoscopic resection (n = 86, 43%) and surgical extirpation (n = 102, 50%). Forty-one patients (40%) underwent a high anterior resection, whereas 45 (44%) underwent anterior resection with total mesorectal excision. Seven patients (7%) underwent Hartman's procedure, 7 (7%) underwent abdomino-perineal resection, and 6 (6%) had transanal endoscopic microsurgery, whereas 4 (4%) patients underwent a transanal excision. Multiple variable logistic regression analysis demonstrated that tumor size greater than 10 mm and lymphovascular invasion were predictors of nodal involvement (P = 0.006 and < 0.001, respectively), whereas the presence of lymph node metastases and lymphovascular invasion was associated with subsequent development of distant metastases (P = 0.033 and 0.022, respectively). The presence of nodal metastases has a profound effect upon survival, with a 5-year survival rate of 70%, and 10-year survival of 60% for node positive tumors. Patients with distant metastases have a 4-year survival of 38%. Conclusion: Tumor size greater than 10 mm and lymphovascular invasion are significantly associated with the presence of nodal disease, rendering mesorectal excision advisable. Transanal excision is adequate for smaller tumors. Copyright © 2010 by Lippincott Williams & Wilkins.


Mallon P.W.G.,University College Dublin | Mallon P.W.G.,Materials Misericordiae University Hospital
Current Opinion in Infectious Diseases | Year: 2010

PURPOSE OF REVIEW: This review details the clinical aspects and pathogenesis of low bone mineral density (BMD) in HIV, discusses broad management issues and outlines areas in which our understanding of this condition is incomplete. RECENT FINDINGS: Low BMD is prevalent in HIV-infected patients, with traditional risk factors, HIV infection and exposure to antiretroviral therapy all contributing. The role of specific antiretrovirals in the development of low BMD remains controversial, but most changes arise at either antiretroviral therapy initiation or switch. SUMMARY: Further research is needed to clarify mechanisms underlying low BMD in HIV, whether low BMD will translate to increased fractures and to determine the correct therapeutic approach to low BMD in HIV, particularly in younger HIV-infected patients. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Mallon P.W.G.,University College Dublin | Mallon P.W.G.,Materials Misericordiae University Hospital
Current Opinion in HIV and AIDS | Year: 2014

PURPOSE OF REVIEW: Osteoporosis remains an important focus of contemporary research in HIV, with co-morbidities and mortality from non-AIDS illnesses now a major barrier to normal lifespan in many populations living with HIV. This review outlines the major recent advances in our understanding of osteoporosis and fractures in those living with HIV and identifies remaining gaps in our knowledge of this complex but increasingly important aspect of aging research in HIV. RECENT FINDINGS: Low bone mineral density (BMD), osteoporosis and fractures are all more common in those living with HIV, with recent data pointing for the first time to causal links between low BMD and fractures in those with HIV. The natural history and pathogenesis of osteoporosis in HIV and the epidemiology of fractures in this vulnerable population differ considerably from the general population, with both disease-related and treatment-related factors both contributing to its development through alterations in bone turnover and defects in bone architecture. SUMMARY: Only through a greater understanding of the pathogenesis can appropriate screening and preventive measures be taken in people living with HIV to preserve bone health as they age. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Cotter A.G.,University College Dublin | Mallon P.W.G.,University College Dublin | Mallon P.W.G.,Materials Misericordiae University Hospital
Current Opinion in HIV and AIDS | Year: 2014

PURPOSE OF REVIEW: Low bone mineral density (BMD) is common in those with HIV, associated with higher bone turnover and a higher prevalence of fractures. This review explores low BMD in HIV, focusing on underlying mechanisms and relationships between low BMD and HIV infection, immune dysfunction, and antiretroviral therapy (ART). RECENT FINDINGS: Greater reductions in BMD accompanying reductions in HIV viremia at initiation of first-line or second-line ART suggest an important role for immune- or viral-mediated mechanisms in its pathogenesis. SUMMARY: As bone metabolism is part-regulated by T cells and B cells, we propose that earlier initiation of ART at higher CD4 T-cell counts may attenuate BMD loss by abrogating immune- and viral-mediated disturbances in bone metabolism that accompany ART initiation. Further pathogenesis-based research is required in this field, focusing on the complex interaction between virus, immune system, ART, and bone metabolism. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Zhao J.,Materials Misericordiae University Hospital | Lawless M.W.,Materials Misericordiae University Hospital
Cytokine | Year: 2013

Liver cancer is the fifth most common cancer in the world with an estimated over half a million new cases diagnosed every year. Due to the difficulty in early diagnosis and lack of treatment options, the prevalence of liver cancer continues to climb with a 5-year survival rate of between 6% and 11%. Coinciding with the rise of liver cancer, the prevalence of obesity has rapidly increased over the past two decades. Evidence from epidemiological studies demonstrates a higher risk of hepatocellular carcinoma (HCC) in obese individuals. Obesity is recognised as a low-grade inflammatory disease, this is of particular relevance as inflammation has been proposed as the seventh hallmark of cancer development with abdominal visceral adiposity considered as an important source of pro-inflammatory stimuli. Emerging evidence points towards the direct role of visceral adipose tissue rather than generalised body fat in carcinogenesis. Cytokines such as IL-6 and TNF-α secreted from visceral adipose tissue have been demonstrated to induce a chronic inflammatory condition predisposing the liver to a protumourigenic milieu. This review focuses on excess visceral adiposity rather than simple obesity; particularly adipokines and their implications for chronic inflammation, lipid accumulation, insulin resistance, Endoplasmic Reticulum (ER) stress and angiogenesis. Evidence of molecular signalling pathways that may give rise to the onset and progression of HCC in this context are depicted. Delineation of the pro-inflammatory role of visceral adiposity in liver cancer and its targeting will provide better rational and therapeutic approaches for HCC prevention and elimination. The concept of a central role for metabolism in cancer is the culmination of an effort that began with one of the 20th century's leading biochemists and Nobel laureate of 1931, Otto Warburg. © 2013 Elsevier Ltd.


Egan J.J.,Materials Misericordiae University Hospital
European Respiratory Review | Year: 2011

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal form of diffuse interstitial lung disease. Management of IPF requires an orderly approach, with regular evaluations and implementation of both pharmacological and nonpharmacological treatments. Pulmonary rehabilitation can relieve patients from the distressing symptoms of IPF and improve quality of life. Oxygen therapy is central to treatment of all patients. Lung transplantation enhances survival in selected patients. Mechanical ventilation may be used in patients with acute exacerbations, but the prognosis is poor in these cases. Palliative care focuses on symptom management, advance directives and end-of-life planning. Patient support groups may also play an important role. Copyright©ERS 2011.


Ryan J.D.,Materials Misericordiae University Hospital
Hepatology (Baltimore, Md.) | Year: 2010

Hereditary hemochromatosis (HH) is a common inherited iron overload disorder. The vast majority of patients carry the missense Cys282Tyr mutation of the HFE gene. Hepcidin, the central regulator of iron homeostasis, is deficient in HH, leading to unchecked iron absorption and subsequent iron overload. The bone morphogenic protein (BMP)/small mothers against decapentaplegic (Smad) signaling cascade is central to the regulation of hepcidin. Recent data from HH mice models indicate that this pathway may be defective in the absence of the HFE protein. Hepatic BMP/Smad signaling has not been characterized in a human HFE-HH cohort to date. Hepatic expression of BMP/Smad-related genes was examined in 20 HFE-HH males with significant iron overload, and compared to seven male HFE wild-type controls using quantitative real-time reverse transcription polymerase chain reaction. Hepatic expression of BMP6 was appropriately elevated in HFE-HH compared to controls (P = 0.02), likely related to iron overload. Despite this, no increased expression of the BMP target genes hepcidin and Id1 was observed, and diminished phosphorylation of Smad1/Smad5/Smad8 protein relative to iron burden was found upon immunohistochemical analysis, suggesting that impaired BMP signaling occurs in HFE-HH. Furthermore, Smad6 and Smad7, inhibitors of BMP signaling, were up-regulated in HFE-HH compared to controls (P = 0.001 and P = 0.018, respectively). CONCLUSION: New data arising from this study suggest that impaired BMP signaling underlies the hepcidin deficiency of HFE-HH. Moreover, the inhibitory Smads, Smad6, and Smad7 are identified as potential disruptors of this signal and, hence, contributors to the pathogenesis of this disease.


Casey P.,Materials Misericordiae University Hospital | Bailey S.,University of Central Lancashire
World Psychiatry | Year: 2011

Adjustment disorders are common, yet under-researched mental disorders. The present classifications fail to provide specific diagnostic criteria and relegate them to sub-syndromal status. They also fail to provide guidance on distinguishing them from normal adaptive reactions to stress or from recognized mental disorders such as depressive episode or post-traumatic stress disorder. These gaps run the risk of pathologizing normal emotional reactions to stressful events on the one hand and on the other of overdiagnosing depressive disorder with the consequent unnecessary prescription of antidepressant treatments. Few of the structured interview schedules used in epidemiological studies incorporate adjustment disorders. They are generally regarded as mild, notwithstanding their prominence as a diagnosis in those dying by suicide and their poor prognosis when diagnosed in adolescents. There are very few intervention studies.


O'Donoghuea C.,Materials Misericordiae University Hospital | Kyne L.,Materials Misericordiae University Hospital
Current Opinion in Gastroenterology | Year: 2011

Purpose of review This review summarizes the most recent epidemiological data and advances in research into the pathogenesis, diagnosis and treatment of Clostridium difficile infection (CDI). Recent findings The epidemiology of CDI has changed with the emergence of hypervirulent strains. CDI rates have increased in the community, in children and in patients with inflammatory bowel disease. Although the North American pulsed-field gel electrophoresis type 1, restriction endonuclease analysis group BI, PCR ribotype 027 (NAP1/BI/027) strain remains prevalent in North America, surveillance suggests that it is decreasing in Europe. A similar strain, PCR ribotype 078, is emerging which is associated with community-associated CDI and has been isolated in animals and food products. The Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America have published new guidelines on the epidemiology, diagnosis, treatment, infection control and environmental management of C. difficile. Several novel therapies for CDI are at different stages of development. There have been promising trial results with fidaxomicin, a novel antibiotic for the treatment of CDI and monoclonal antibodies against toxins A and B, which have been shown to significantly reduce CDI recurrence rates. Summary Major advances have been made in our understanding of the spread and pathogenesis of C. difficile and new treatment options are becoming available. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Barry M.,Materials Misericordiae University Hospital | Kell M.R.,Materials Misericordiae University Hospital
Breast Cancer Research and Treatment | Year: 2011

The optimum sequencing of breast reconstruction (BR) in patients receiving postmastectomy radiation therapy (PMRT) is controversial. A comprehensive search of published studies that examined postoperative morbidity following immediate or delayed BR with combined radiotherapy was performed. Medical (MEDLINE & EMBASE) databases were searched and cross-referenced for appropriate studies where morbidity following BR was the primary outcome measured. A total of 1,105 patients were identified from 11 appropriately selected studies. Patients undergoing PMRT and BR are more likely to suffer morbidity compared with patients not receiving PMRT (OR = 4.2; 95% CI, 2.4-7.2 [no PMRT vs. PMRT]). Reconstruction technique was also examined with outcome when PMRT was delivered after BR, and this demonstrated that autologous reconstruction is associated with less morbidity in this setting (OR = 0.21; 95% CI, 0.1-0.4 [autologous vs. implant-based]). Delaying BR until after PMRT had no significant effect on outcome (OR = 0.87; 95% CI, 0.47-1.62 [delayed vs. immediate]). PMRT has a detrimental effect on BR outcome. These results suggest that where immediate reconstruction is undertaken with the necessity of PMRT, an autologous flap results in less morbidity when compared with implant-based reconstruction. © 2011 Springer Science+Business Media, LLC.

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