Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.

The gastrointestinal tract can be deranged by ailments including sepsis, trauma and haemorrhage. Ischaemic injury provokes a common constellation of microscopic and macroscopic changes that, together with the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow, are collectively known as ischaemia-reperfusion injury (IRI). Although much of the gastrointestinal tract is normally hypoxemic, intestinal IRI results when there is inadequate oxygen availability due to poor supply (pathological hypoxia) or abnormal tissue oxygen use and metabolism (dysoxia).

Transitions from Aerobic to Anaerobic Metabolism and Oxygen Debt during Elective Major and Emergency Non-Cardiac Surgery.

Introduction: Intraoperative hemodynamic and metabolic optimization of both the high-risk surgical patients and critically ill patients remains challenging. Reductions in oxygen delivery or increases in oxygen consumption can initiate complex cellular processes precipitating oxygen debt (OXD).

Methods: This study tested the hypothesis that intraoperative changes in sublingual microcirculatory flow reflect clinically relevant transitions from aerobic to anaerobic metabolism (TRANAM).

Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study.

Background: Initial TRITON2 (NCT02952534) results demonstrated the efficacy of rucaparib 600 mg BID in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with a BRCA1 or BRCA2 (BRCA) or other DNA damage repair (DDR) gene alteration.

Objective: To present the final data from TRITON2.

Design, Setting, And Participants: TRITON2 enrolled patients with mCRPC who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy.

Response to Rucaparib in BRCA-Mutant Metastatic Castration-Resistant Prostate Cancer Identified by Genomic Testing in the TRITON2 Study.

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic or (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2.

Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a or Gene Alteration.

Purpose: or () alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study.

Methods: We enrolled patients who progressed after one to two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy for mCRPC.

Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study.

Purpose: Genomic alterations in DNA damage repair (DDR) genes other than may confer synthetic lethality with PARP inhibition in metastatic castration-resistant prostate cancer (mCRPC). To test this hypothesis, the phase II TRITON2 study of rucaparib included patients with mCRPC and deleterious non- DDR gene alterations.

Patients And Methods: TRITON2 enrolled patients who had progressed on one or two lines of next-generation androgen receptor-directed therapy and one taxane-based chemotherapy for mCRPC.

Low Dose Resistance Exercise: A Pilot Study Examining Effects on Blood Pressure and Augmentation Index Between Intensities.

Introduction: The effects of resistance exercise on vascular function are unclear.

Aim: To investigate the acute haemodynamic (blood pressure and augmentation index) and rate of perceived exertion (RPE) response to two types of resistance exercises of equal workload-a set of unilateral 35% of one repetition maximum (1RM) quadriceps extension and a set of unilateral 70% 1RM quadriceps extension.

Methods: Twenty two young healthy males completed both exercises on separate days.

Falls-Related EvEnts in the first year after StrokE in Ireland: Results of the multi-centre prospective FREESE cohort study.

Introduction: Falls are common post-stroke adverse events. This study aimed to describe the first-year falls incidence, circumstances and consequences among persons discharged home after stroke in Ireland, and to examine the association between potential risk factors and recurrent falls.

Patients And Methods: Patients with acute stroke and planned home-discharge were recruited consecutively from five hospitals.

Drip and ship versus direct to endovascular thrombectomy: The impact of treatment times on transport decision-making.

Introduction: In ischaemic stroke care, fast reperfusion is essential for disability free survival. It is unknown if bypassing thrombolysis centres in favour of endovascular thrombectomy (mothership) outweighs transport to the nearest thrombolysis centre for alteplase and then transfer for endovascular thrombectomy (drip-and-ship). We use conditional probability modelling to determine the impact of treatment times on transport decision-making for acute ischaemic stroke.

Endocrinopathies and renal outcomes in lithium therapy: impact of lithium toxicity.

Background: Lithium is the mainstay of treatment for bipolar disorder, mania and an augmentation therapy in patients with treatment resistant depression. It has a narrow therapeutic index, with recognized adverse multi-system and endocrine side effects.

Aim: To assess the impact of lithium therapy, in particular lithium toxicity, on the development of endocrine and renal disorders in a cohort of patients in a single tertiary referral centre in Ireland.

The ExPeCT (Examining Exercise, Prostate Cancer and Circulating Tumour Cells) trial: study protocol for a randomised controlled trial.

Background: Prostate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical activity programmes.

Weekend surgical handover enhances early management of acute clinical changes using a red flag system.

Introduction: Recent implementation of the European Working Time Directive in Ireland has resulted in a change from thetraditional model of patient care to a system characterised by shift work among clinicians. Effective handover ofpatient information is essential for transfer of responsibility between clinicians and maintaining continuity of care. The weekend has been identified as a particularly vulnerable transition of patient care.

Impact of visceral obesity and metabolic syndrome on the postoperative immune, inflammatory, and endocrine response following surgery for esophageal adenocarcinoma.

Visceral obesity and metabolic syndrome (MetSyn) represent a constellation of inflammation, insulin resistance, and hyperglycemia and are established risk factors for gastrointestinal cancer. However, their impact on the immune and inflammatory response after major upper gastrointestinal oncologic surgery is unknown. In 125 consecutive patients who underwent esophagectomy, C-reactive protein (CRP) and CRP:albumin levels were recorded preoperatively and on days 1, 3, 7, and 14 postoperatively.

Abnormal orthostatic blood pressure control among subjects with lacunar infarction.

Introduction: Hypertension is a recognised risk factor for lacunar stroke. However, their association has been evaluated using static blood pressure (BP) assessment in supine or sitting position alone. We hypothesised that impaired dynamic (orthostatic) BP control may associate with lacunar strokes.

Dipeptidyl peptidase-4 inhibition and narrow-band ultraviolet-B light in psoriasis (DINUP): study protocol for a randomised controlled trial.

Background: Moderate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM). Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycaemia and has a marketing authorisation for the treatment of T2DM. Non-immunosuppressive therapies that are effective for psoriasis and its associated comorbidities would be a significant advance in the treatment of this chronic disease.

The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis.

Background: Colonization by Aspergillus fumigatus in patients with cystic fibrosis (CF) can cause A fumigatus sensitization and/or allergic bronchopulmonary aspergillosis (ABPA), which affects pulmonary function and clinical outcomes. Recent studies show that specific allergens upregulate the surface-expressed basophil marker CD203c in sensitized subjects, a response that can be readily measured by using flow cytometry.

Objective: We sought to identify A fumigatus sensitization in patients with CF by using the basophil activation test (BAT).

Fasting plasma glucose as initial screening for diabetes and prediabetes in irish adults: The Diabetes Mellitus and Vascular health initiative (DMVhi).

Objective: Type 2 diabetes has a long pre clinical asymptomatic phase. Early detection may delay or arrest disease progression. The Diabetes Mellitus and Vascular health initiative (DMVhi) was initiated as a prospective longitudinal cohort study on the prevalence of undiagnosed Type 2 diabetes and prediabetes, diabetes risk and cardiovascular risk in a cohort of Irish adults aged 45-75 years.

Treatment Factors That Influence Mortality in Acromegaly.

Acromegaly is a rare condition characterized by excessive secretion of growth hormone (GH), which is almost always due to a pituitary adenoma. Acromegaly is associated with significant morbidity such as hypertension, type 2 diabetes, cardiomyopathy, obstructive sleep apnoea, malignancy and musculoskeletal abnormalities. Acromegaly has also been associated with increased mortality in several retrospective studies.

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

Background: Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied.

Methods: In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin.

Childhood adversity, depression, age and gender effects on white matter microstructure: a DTI study.

Previous diffusion tensor imaging (DTI) studies have shown that various factors can affect white matter (WM) tract diffusivity. The aim of the present study was to investigate the effects of childhood adversity (CA), age and gender on WM diffusivity in tracts that are thought to be involved in emotional regulation in individuals with major depressive disorder (MDD) and healthy controls (HC). DTI was obtained from 46 subjects with MDD and 46 HC subjects.

Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus.

Primary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age-matched controls using high-resolution magnetic resonance imaging (MRI).

Surveillance of gastric intestinal metaplasia for the prevention of gastric cancer.

Background: Adenocarcinoma of the stomach is the second leading cause of cancer related death in the world. Gastric intestinal metaplasia (GIM) is a recognised premalignant condition of the stomach. It has been described as occurring in up to one in five patients in western countries.

Treatment of Helicobacter pylori infection 2013.

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2012 up to March 2013. To begin with, the updated European Consensus Guidelines were published last year, highlighting the role of bismuth and nonbismuth quadruple regimen as first-line treatments. Cure rates for standard triple therapy remain acceptable in quite a few settings nowadays, and some reports on innovative triple therapies look promising.