The Fontan Pathway: Change in Dimension and Catheter-Based Intervention over Time.

An unobstructed Fontan pathway is essential for optimal hemodynamics. We hypothesize that more extracardiac conduit (ECC) Fontan pathways develop obstruction compared to lateral tunnel (LT) Fontans and that the dilation typically observed in LTs results in similar mid-term clinical outcomes. A single-center, retrospective study was done including all Fontan cardiac catheterizations from 2006 to 2019. Angiography and medical records were reviewed to define Fontan pathway dimensions, interventions, and clinical outcomes. 232 patients underwent cardiac catheterization, where 60% were ECCs and 30% LTs. The minimum cross-sectional area (CSA) of ECCs was significantly smaller than LTs and LTs dilated over time. 13% of patients had Fontan pathway stenting at a median age of 16.2 years. The minimum CSA for patients who underwent intervention was significantly smaller than patients who did not. Lower weight at Fontan surgery was associated with intervention on the Fontan pathway, with a threshold weight of 15 kg for patients with an ECC. The median follow-up was 3.3 years. Patients who had Fontan pathway intervention were not more likely to experience the composite adverse clinical outcome. LTs were more likely than ECCs to have worse clinical outcome, when liver fibrosis was included. This is the first study to describe angiographic dimensions of the Fontan pathway in a large number of patients over time. ECCs tend to become stenotic. Lower weight at Fontan surgery is a potential risk for Fontan pathway intervention. LTs may experience worse clinical outcomes in follow-up. This information can help inform the optimal timing and method of post-Fontan surveillance.

Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 -/- mouse model.

BACKGROUND: Emerging evidence implicates the gut microbiome in liver inflammation and hepatocellular carcinoma (HCC) development. We aimed to characterize the temporal evolution of gut dysbiosis, in relation to the phenotype of systemic and hepatic inflammatory responses leading to HCC development. In the present study, Mdr2 -/- mice were used as a model of inflammation-based HCC. Gut microbiome composition and function, in addition to serum LPS, serum cytokines/chemokines and intrahepatic inflammatory genes were measured throughout the course of liver injury until HCC development. RESULTS: Early stages of liver injury, inflammation and cirrhosis, were characterized by dysbiosis. Microbiome functional pathways pertaining to gut barrier dysfunction were enriched during the initial phase of liver inflammation and cirrhosis, whilst those supporting lipopolysaccharide (LPS) biosynthesis increased as cirrhosis and HCC ensued. In parallel, serum LPS progressively increased during the course of liver injury, corresponding to a shift towards a systemic Th1/Th17 proinflammatory phenotype. Alongside, the intrahepatic inflammatory gene profile transitioned from a proinflammatory phenotype in the initial phases of liver injury to an immunosuppressed one in HCC. In established HCC, a switch in microbiome function from carbohydrate to amino acid metabolism occurred. CONCLUSION: In Mdr2 -/- mice, dysbiosis precedes HCC development, with temporal evolution of microbiome function to support gut barrier dysfunction, LPS biosynthesis, and redirection of energy source utilization. A corresponding shift in systemic and intrahepatic inflammatory responses occurred supporting HCC development. These findings support the notion that gut based therapeutic interventions could be beneficial early in the course of liver disease to halt HCC development.

Extensive hepatitis A outbreak in an urban childcare facility in Ireland, associated with considerable adult morbidity.

Hepatitis A infection results in a spectrum of illness from asymptomatic disease to severe fulminant hepatitis. Since 2000, <50 cases have been reported annually in Ireland. We report on an outbreak of hepatitis A associated with a childcare facility(CCF) in 2015 in Ireland. Between January and July 2015, 12 outbreak-associated symptomatic hepatitis A cases were identified, including one delayed, retrospective diagnosis. Seven (58%) cases were adults, eight (67%) were male, six of the adults required hospitalisation. All 12 cases were confirmed on serology and the four cases that were genotyped were identical on phylogenetic analysis. Potential environmental exposures and hygiene practices at the CCF were investigated. Outbreak control measures included the provision of: hepatitis A information, infection prevention advice, hepatitis A vaccination to 554 CCF contacts, and voluntary closure of the CCF for deep-cleaning and staff education. From a healthcare perspective1, outbreak control costs were in excess of €45 000. This outbreak illustrates the considerable adult morbidity that can occur in hepatitis A outbreaks, highlights the challenges in controlling a large CCF-associated outbreak and the importance of early recognition by clinicians of hepatitis A.

In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence.

Neuroinflammation may be a critical component of the neurobiology of alcohol use disorders, yet the exact nature of this relationship is not well understood. This work compared the brain and peripheral immune profile of alcohol-dependent subjects and controls. Brain levels of 18-kDa translocator protein (TSPO), a marker of microglial activation and neuroinflammation, were measured with [11C]PBR28 positron emission tomography imaging in 15 healthy controls and 15 alcohol-dependent subjects. Alcohol-dependent subjects were imaged 1-4 days (n=14) or 24 days (n=1) after their last drink. Linear mixed modeling of partial-volume-corrected [11C]PBR28 data revealed a main effect of alcohol dependence (P=0.034), corresponding to 10% lower TSPO levels in alcohol-dependent subjects. Within this group, exploratory analyses found a negative association of TSPO levels in the hippocampus and striatum with alcohol dependence severity (P<0.035). Peripheral immune response was assessed in a subset of subjects by measuring cytokine expression from monocytes cultured both in the presence and absence of lipopolysaccharide. Peripheral monocyte response to lipopolysaccharide stimulation was lower in alcohol-dependent subjects compared with controls for the proinflammatory cytokines interleukin-6 and interleukin-8. Thus, alcohol-dependent individuals exhibited less activated microglia in the brain and a blunted peripheral proinflammatory response compared with controls. These findings suggest a role for pharmaceuticals tuning the neuroimmune system as therapeutics for alcohol dependence.

Epidemiological, clinical and genetic aspects of adult onset isolated focal dystonia in Ireland.

BACKGROUND: Adult onset idiopathic isolated focal dystonia presents with a number of phenotypes. Reported prevalence rates vary considerably; well-characterized cohorts are important to our understanding of this disorder. AIM: To perform a nationwide epidemiological study of adult onset idiopathic isolated focal dystonia in the Republic of Ireland. METHODS: Patients with adult onset idiopathic isolated focal dystonia were recruited from multiple sources. Diagnosis was based on assessment by a neurologist with an expertise in movement disorders. When consent was obtained, a number of clinical features including family history were assessed. RESULTS: On the prevalence date there were 592 individuals in Ireland with adult onset idiopathic isolated focal dystonia, a point prevalence of 17.8 per 100 000 (95% confidence interval 16.4-19.2). Phenotype numbers were cervical dystonia 410 (69.2%), blepharospasm 102 (17.2%), focal hand dystonia 39 (6.6%), spasmodic dysphonia 18 (3.0%), musician's dystonia 17 (2.9%) and oromandibular dystonia six (1.0%). Sixty-two (16.5%) of 375 consenting index cases had a relative with clinically confirmed adult onset idiopathic isolated focal dystonia (18 multiplex and 24 duplex families). Marked variations in the proportions of patients with tremor, segmental spread, sensory tricks, pain and psychiatric symptoms by phenotype were documented. CONCLUSIONS: The prevalence of adult onset idiopathic isolated focal dystonia in Ireland is higher than that recorded in many similar service-based epidemiological studies but is still likely to be an underestimate. The low proportion of individuals with blepharospasm may reflect reduced environmental exposure to sunlight in Ireland. This study will serve as a resource for international comparative studies of environmental and genetic factors in the pathogenesis of the disorder.

Catching measles in an appropriately vaccinated group: a well-circumscribed outbreak in the South East of Ireland, September-November 2013.

A measles outbreak occurred in a school in a small town in the South East of Ireland in September-November 2013. Most (and all early) cases had one dose of the measles-mumps- rubella (MMR) vaccination. All suspected cases were followed up, in order to advise on sampling and provide public health advice to them and their contacts. MMR vaccination control measures were instituted in the town. These included early second MMR in primary schools and childcare facilities, bringing forward the planned school MMR catch-up programme, early first MMR dose for children aged 6-12 months and targeted advice to unvaccinated children. There were 20 cases (17 confirmed) of measles associated with the outbreak. Fifteen cases occurred in the index school, with four in pre-school-age children (<4 years) who had clear epidemiological links with children at the school. This was a well-circumscribed outbreak occurring, unusually, in a well-vaccinated population. The outbreak came late to the attention of Department of Public Health staff but prompt action, once notified, and institution of control measures resulted in quick termination of the outbreak and prevention of cases in a neighbouring city.

Can 'Hot Spotting' Prove to be a Useful Tool to Identify Disproportionate ED Use in the Rural General Hospital Setting?

'Hot spotting' allows the identification of areas with disproportionate use of Emergency Department (ED) services. To date, 'hot spotting' has focused on large urban centres. The aim of this study was to determine if there are geographic hotspots for ED use in the rural general hospital. ED attendances were logged between 1st July 2013 and 30th June 2014. Frequent users and super users were isolated. Addresses were cross referenced against national census data to determine number of users per 500 population in geographically distinct regions. The number of frequent users ranged from 1.00/500 population to 4.88/500 population. Four out of nineteen areas had > or equals; 4 frequent users per 500 population. There was no correlation between number of users and distance from MGH (p=0.44). 77% of frequent users presented with mixed aetiologies. Nineteen percent of frequent attenders presented via GP referral only, 13% attended via self-referral only and 88% attended via GP and self-referral routes.

Declines in TBT contamination in Irish coastal waters 1987-2011, using the dogwhelk (Nucella lapillus) as a biological indicator.

Using the vas deferens sequence index (VDSI) and relative penis size index (RPSI) in dogwhelks (Nucella lapillus), imposex levels were assessed at 63 sites within 11 sea inlets during 2010/2011 and compared these with levels gathered since 1987. Sterile females (VDS>5.0) were found at 14 of the 63 sites and 47 sites (75%) met the EcoQO (VDSI<2.0). The absence of imposex in 'control' areas on the west coast is due to the lack of vessel paint applications or net dips with TBT being used as an active anti-fouling ingredient. A significant decline was observed following 2005 when comparing VDSI levels which is consistent with the decline of TBT usage. Current levels are consistent with an overall improvement towards achieving Good Environmental Status according to the requirements under the Marine Strategy Framework Directive.

Myocardial ischaemia following cocaine and adrenaline exposure in a child during an ophthalmological procedure.

We report a 23-month old girl who presented with bilateral epiphora who underwent bilateral lacrimal probing and syringing, during which a cocaine adrenaline solution was used. Two hours after the procedure she developed acute pulmonary oedema secondary to myocardial ischaemia. The patient was treated with intravenous glyceryltrinitrate and milrinone infusions; cardiac enzymes and left ventricular function normalised over the subsequent 72 hours. Topical administration of cocaine and adrenaline solution may have dangerous systemic cardiac effects and should always be used judiciously.

Application of congener based multi-matrix profiling techniques to identify potential PCDD/F sources in environmental samples from the Burrishoole Catchment in the West of Ireland.

Homologue and congener profiles of PCDD/Fs in eels, passive sampler and sediment extracts from the Burrishoole, a rural upland catchment on the western Irish seaboard were compared with potential PCDD sources. ΣPCDD/F levels in eels ranged from 2.9 to 25.9 pg g(-1) wet weight, which are elevated compared to other Irish locations. The OCDD congener dominated the pattern of ΣPCDD/Fs in all matrices from Burrishoole. Passive samplers were successfully deployed to identify for the first time the presence in the water column of PCDD/Fs and dimethoxylated octachlorodiphenyl ether (diMeOoctaCDE), impurities found in pentachlorophenol (PCP) production. Principal component analysis (PCA) identified similarities between PCDD/F profiles in technical PCP mixtures and environmental samples from the Burrishoole region. Results strongly suggest residual PCDD contamination associated with historic local use of a dioxin contaminated product in the catchment area, with pentachlorophenol a strong candidate.

Assessment of biomarkers in Mytilus edulis to determine good environmental status for implementation of MSFD in Ireland.

Candidate OSPAR/ICES recommended biomarkers at the level of the individual in Mytilus edulis for determination of good environmental status for MSFD were evaluated against contaminant levels at sites around Ireland. The sites chosen ranged from moderate to low pollution levels, but the actual ranking of the sites varied according to the contaminant levels present. At the most contaminated site, Cork, 4 out of 16 contaminants exceeded the EAC, while at Shannon, no EACs were exceeded. The SOS assay suggested that Cork was the healthiest site with a LT50 of 17.6 days, while SOS for Shannon was 15.6 days. Likewise, condition factors varied among sites and did not always correspond to contaminant-based status. There may be uncertainty in assigning status around the not good:good boundary. This raises potential difficulties not only in the biomarker/contaminant load relationship but also in the reliability of the biomarkers themselves and hence barriers meeting compliance levels.

Surgical resection for non-small cell lung cancer: clinical features and outcomes for a consecutive series at an Irish tertiary referral centre.

BACKGROUND: Few patients diagnosed with lung cancer are still alive 5 years after diagnosis. The aim of the current study was to conduct a 10-year review of a consecutive series of patients undergoing curative-intent surgical resection at the largest tertiary referral centre to identify prognostic factors. METHODS: Case records of all patients operated on for lung cancer between 1998 and 2008 were reviewed. The clinical features and outcomes of all patients with non-small cell lung cancer (NSCLC) stage I-IV were recorded. RESULTS: A total of 654 patients underwent surgical resection with curative intent during the study period. Median overall survival for the entire cohort was 37 months. The median age at operation was 66 years, with males accounting for 62.7 %. Squamous cell type was the most common histological subtype, and lobectomies were performed in 76.5 % of surgical resections. Pneumonectomy rates decreased significantly in the latter half of the study (25 vs. 16.3 %), while sub-anatomical resection more than doubled (2 vs. 5 %) (p < 0.005). Clinico-pathological characteristics associated with improved survival by univariate analysis include younger age, female sex, smaller tumour size, smoking status, lobectomy, lower T and N status and less advanced pathological stage. Age, gender, smoking status and tumour size, as well as T and N descriptors have emerged as independent prognostic factors by multivariate analysis. CONCLUSION: We identified several factors that predicted outcome for NSCLC patients undergoing curative-intent surgical resection. Survival rates in our series are comparable to those reported from other thoracic surgery centres.

Hybrid repair of a symptomatic thoracic intra-mural haematoma.

INTRODUCTION: The repair of thoracic aortic pathology by open techniques is associated with high morbidity and mortality. METHODS: We describe the first case of hybrid thoracic aortic repair performed in Ireland for a symptomatic thoracic intramural haematoma. CONCLUSION: Hybrid repair with extra-anatomical aortic visceral revascularisation and subsequent thoracic endograft exclusion offers an attractive alternative method of repair for thoracic aortic pathology.

Hybrid repair of thoracic aortic arch aneurysm.

INTRODUCTION: Aortic arch pathology requiring surgery most often affects elderly patients with multiple co-morbidities and represents a significant challenge to both patient and surgeon. MATERIALS AND METHODS: This case report describes the repair of an 8.2 cm aortic arch aneurysm arising at the origin of the left subclavian artery using a combined endovascular and open surgical approach. CONCLUSION: Hybrid techniques allow for the treatment of pathology that would otherwise not be amenable to surgery.

Herbal medicine--sets the heart racing!

The potential for pharmaceuticals to produce side effects and drug interactions is well known to medical practitioners and the lay public alike. However, the potential for alternative medicines to produce such effects is less widely known. We describe a potentially dangerous interaction between a herbal medicine and concomitant selective serotonin re-uptake inhibitor (SSRI) ingestion.

Oral health in Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED).

BACKGROUND: APECED (Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy) is a rare autosomal recessive disease characterised primarily by sequential immune-mediated destruction of endocrine tissues, chronic oral or mucocutaneous candidiasis and ectodermal disorders, including hypoplasia of dental enamel. AIM: This was to investigate the oral health and presence of enamel defects in a cohort of patients with APECED. METHODS: 16 patients with APECED (mean age of 13.9 years) were matched for age and gender with healthy controls. A comprehensive medical, dental and drug history was recorded, followed by a clinical assessment of oral health which was determined by assessing periodontal treatment needs, prevalence of dental caries, erosion, fluorosis and enamel defects. The estimated time of the development of the enamel defects and the contemporaneous medical diagnosis were recorded. RESULTS: Oral health of patients with APECED was poor compared with controls, with a higher prevalence of periodontal disease, caries and erosion. There was a significantly (P < 0.05) higher prevalence of enamel defects in the study group. The enamel defects were mostly hypoplastic in the form of pits, missing enamel and grooves. The enamel defects occurred in a chronological pattern. There was a strong association between the estimated time of defective enamel formation and a history of hypoparathyroidism. Gastrointestinal dysfunction and a history of chronic mucocutaneous candidiasis were also associated with the presence of enamel defects. CONCLUSION: The oral health of individuals with APECED was poor compared with controls with a higher prevalence of periodontal disease, caries, erosion and enamel defects. The enamel defects in the study population occurred in a chronological pattern and some were associated with a history of systemic disease during the period of tooth development.

Lack of correlation between smoking status and early postoperative outcome following valve surgery.

BACKGROUND: We sought to assess the effect of smoking on early outcome following valve surgery. METHODS: This is a retrospective review of a prospectively collected departmental database of all patients who underwent isolated aortic and/or mitral valve surgery (replacement and/or repair). Our cohort consisted of 590 patients stratified into three groups: current smokers (n = 94), ex-smokers (n = 243), and nonsmokers (n = 253). RESULTS: There were no significant differences in the in-hospital mortality between the three groups. Likewise, the length of both hospital and intensive care unit stays were similar among the three groups with a similar rate of postoperative complications. These findings remained statistically not significant, even after adjusting for potential confounders such as age, gender, etc. CONCLUSION: Smoking does not seem to be associated with an increased early postoperative risk in patients undergoing valve surgery. However, because of the known effect of smoking on the risk of cardiovascular disease and because the effect of smoking on long-term survival in patients undergoing valve surgery remains unknown, patients should still be encouraged to quit smoking.

The dental management of five paediatric patients with a history of acute intermittent porphyria.

BACKGROUND: Acute Intermittent Porphyria (AIP) is a rare autosomal dominant metabolic disorder resulting from partial deficiency of porphobobilinogen deaminase, the third enzyme of the haem synthetic pathway. Patients with AIP may be vulnerable to acute neurovisceral attacks if exposed to certain drugs, including some drugs used in dental practice. CASE REPORTS: This article outlines the dental management of 5 children with a diagnosis of latent AIP or a family history of AIP. The local analgesic agent used in all cases was bupivacaine or levobupivacaine. Nitrous oxide and oxygen inhalation sedation was used in 2 cases and general anaesthesia, using propofol, isoflurane with nitrous oxide and oxygen, was used in another case. The dental treatment undertaken included restorations, endodontics and extractions. CONCLUSION: Dental treatment using bupivacaine or levobupivacaine as local analgesic agents was successfully and safely provided for 5 children with a diagnosis of latent AIP or a family history of AIP.

Oculo-facio-cardio-dental syndrome in a mother and daughter.

Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant syndrome characterized by canine teeth with extremely large roots (radiculomegaly), congenital cataract, dysmorphic facial features and congenital heart disease. A case of mother-daughter vertical transmission of OFCD is reported. Dental findings were important in confirming the diagnosis in the mother.