South Infirmary Victoria University Hospital

Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear. In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding. These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.

BACKGROUND: Obesity during pregnancy is associated with increased risk of gestational diabetes mellitus (GDM) and other complications. Physical activity is a modifiable lifestyle factor that may help to prevent these complications but many women reduce their physical activity levels during pregnancy. Interventions targeting physical activity in pregnancy are on-going but few identify the underlying behaviour change mechanisms by which the intervention is expected to work. To enhance intervention effectiveness, recent tools in behavioural science such as the Theoretical Domains Framework (TDF) and COM-B model (capability, opportunity, motivation and behaviour) have been employed to understand behaviours for intervention development. Using these behaviour change methods, this study aimed to identify the enablers and barriers to physical activity in overweight and obese pregnant women. METHODS: Semi-structured interviews were conducted with a purposive sample of overweight and obese women at different stages of pregnancy attending a public antenatal clinic in a large academic maternity hospital in Cork, Ireland. Interviews were recorded and transcribed into NVivo V.10 software. Data analysis followed the framework approach, drawing on the TDF and the COM-B model. RESULTS: Twenty one themes were identified and these mapped directly on to the COM-B model of behaviour change and ten of the TDF domains. Having the social opportunity to engage in physical activity was identified as an enabler; pregnant women suggested being active was easier when supported by their partners. Knowledge was a commonly reported barrier with women lacking information on safe activities during pregnancy and describing the information received from their midwife as 'limited'. Having the physical capability and physical opportunity to carry out physical activity were also identified as barriers; experiencing pain, a lack of time, having other children, and working prevented women from being active. CONCLUSION: A wide range of barriers and enablers were identified which influenced women's capability, motivation and opportunity to engage in physical activity with "knowledge" as the most commonly reported barrier. This study is a theoretical starting point in making a 'behavioural diagnoses' and the results will be used to inform the development of an intervention to increase physical activity levels among overweight and obese pregnant women.

BACKGROUND: Seventeen patients presenting with a cystic cervical metastasis were identified after either having undergone excision of a cyst, initially diagnosed as a branchial cyst but subsequently found to be malignant, or after having had fluid aspirated from a neck mass that ultimately proved to be malignant while undergoing fine needle aspiration biopsy. METHODS: Patients had primary cancer documented at a variety of primary sites, including hypopharynx (3 patients), oropharynx (2 patients), lower lip (2 patients), nasopharynx, supraglottis, oral cavity, and prostate (1 patient each). Six cases (35%) remained occult. RESULTS: In nearly half of the cases (8 of 17), there was no evidence of the primary cancer at presentation. In the same period, 25 branchial cysts were encountered, giving an incidence of unsuspected carcinoma in cervical cysts of 24% (8 of 33). CONCLUSION: In contrast to previous studies in which smaller numbers of patients underwent the procedure, we found fine needle aspiration to be very helpful in the assessment of these lesions, having a sensitivity of 73% in diagnosing malignancy.

These guidelines for management of contact dermatitis have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for investigation and treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, including details of relevant epidemiological aspects, diagnosis and investigation.

Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. Gene or cell therapies have emerged as realistic prospects for the treatment of cancer, and involve the delivery of genetic information to a tumor to facilitate the production of therapeutic proteins. However, there is still much to be done before an efficient and safe gene medicine is achieved, primarily developing the means of targeting genes to tumors safely and efficiently. An emerging family of vectors involves bacteria of various genera. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally. Furthermore, invasive species can deliver heterologous genes intra-cellularly for tumor cell expression. Here, we review the use of bacteria as vehicles for gene therapy of cancer, detailing the mechanisms of action and successes at preclinical and clinical levels.

“Duirt bean liom go nduirt bean lei—a woman told me that a woman told her”—Irish proverb. The general public has been overwhelmed with information related to the novel coronavirus.1 In Ireland the medical community has noted a trend of messages containing incorrect information about covid-19 spreading rapidly through social media and messaging apps. Misinformation is defined as false information that is communicated without deliberate malice; disinformation is false information that is communicated with the intent to deceive.2 The …

Hypogonadism, usually hypogonadotropic in origin, is the most common nondiabetic endocrinopathy in hereditary hemochromatosis (HH). Early studies, usually evaluating small numbers of patients with advanced HH, report prevalence rates of 10-100%. The clinical presentation of HH has changed in recent years as a result of increased awareness and screening. We assessed the prevalence of hypogonadism in a large group of patients with HH diagnosed in a single center over the past 20 yr, the period of follow-up spanning the time before and after widespread screening was introduced and the HFE gene was recognized. Abnormally low plasma testosterone levels, with low LH and FSH levels, were found in nine of 141 (6.4%) male patients tested. Eight of nine (89%) had associated hepatic cirrhosis; three of nine (33%) had diabetes. Inappropriately low LH and FSH levels were found in two of 38 females (5.2%) in whom the pituitary-gonadal axis could be assessed. This is the largest detailed study of hypogonadism reported in HH. The lower prevalence of hypogonadism compared with other reported series reflects the earlier diagnosis of HH in an unselected group of patients attending a single center. Patients with lesser degrees of hepatic siderosis at diagnosis are unlikely to develop hypogonadism.

INTRODUCTION: Human Immunodeficiency Virus (HIV) has an estimated prevalence of 0.9% in India (5.2 million). Anti-retroviral drugs (ARV) are the treatments of choice and non-adherence is an important factor in treatment failure and development of resistance, as well as being a powerful predictor of survival. This study assesses adherence to ARV in HIV positive patients in Bangalore, India, a country where only 10% of those who need therapy are receiving it. METHODS: A cross-sectional anonymous questionnaire survey of 60 HIV antibody positive patients was carried out with patients attending HIV outpatient services at two centres: The Chest and Maternity Centre, Rajajinagar, and Wockhardt Hospital and Heart Institute, Bangalore. Consent was obtained. Translation was done by a translator and doctors where required. Data was analysed using SPSS statistical analysis. RESULTS: A response rate of 88% (53/60) was achieved. The mean patient age was 39.98 years, with 50% aged 30-40, and 73.6% of participants being male. Mean family size was 4.8 (1-13). 21% lived less than 50 kms and 21% greater than 400 kms from clinic.60% reported they were fully adherent. Adherence was statistically significantly linked to regular follow-up attendance (70.5%, p = 0.002). No other results were statistically significant but trends were found. "100% adherence" trends were seen in older patients, male gender, those from larger families, those who had a previous AIDS defining illness, those taking fewer tablets, and without food restrictions. Commonest side-effects causing non-adherence were metabolic reasons (66%) and GI symptoms (50%). No trends were seen for education level, family income, distance travelled to clinic, time since diagnosis, or time on ART. CONCLUSION: Regular attendance for follow up was statistically significant for 100% lifetime adherence. Positive trends were seen in those in larger families, older, those who had AIDS defining illness, simple regimes, and without side-effects. Education, income, distance travelled and length of time diagnosed or treated had no effect on adherence.

We describe the clinical course of three patients who developed spontaneous coronary artery dissection. All patients were young women, one 9 weeks pregnant. All presented with chest pain; one died suddenly proving refractory to resuscitation, another developed unstable angina culminating in myocardial infarction, cardiogenic shock and death, and the third patient underwent coronary artery bypass grafting following diagnosis of a spontaneous coronary dissection of the left anterior descending artery at angiography. Pathological findings in the two fatal cases are reported. This condition, although rare, is a prominent cause of ischaemic coronary events in young women, when it is frequently associated with pregnancy or the puerperium. Most patients die suddenly, but a clinical spectrum is seen including stable and unstable angina, myocardial infarction and cardiogenic shock. The left anterior descending artery is most frequently affected. The classical histological finding is that of a large haematoma occupying the outer third of the media resulting in complete compression of the true lumen. The cause of spontaneous dissection remains unclear but theories of aetiology include a medial eosinophilic angiitis, pregnancy-induced degeneration of collagen in conjunction with the stresses of parturition, and rupture of the vasal vasorum. The diagnosis must be considered when a patient presents with a suggestive clinical profile. Urgent angiography should be undertaken to establish the diagnosis and consideration given to the need for coronary artery bypass grafting, which has been successfully employed in a number of patients. The uneventful long-term survival of cases treated conservatively has been reported.

BACKGROUND: The density and phenotype of tumour-associated macrophages have been linked with prognosis in a range of solid tumours. While there is strong preclinical evidence that tumour-associated macrophages promote aspects of tumour progression, it can be challenging to infer clinical activity from surface markers and ex vivo behaviour. We investigated the association of macrophage infiltration with prognosis and functional changes in the tumour microenvironment in primary human melanoma. METHODS: Fifty-seven formalin-fixed, paraffin-embedded primary melanomas were analysed by immunohistochemical analysis of CD68, CD163, inducible nitric oxide synthase (iNOS) and arginase expression. RNA sequencing was performed on serial sections of 20 of the stained tumours to determine the influence of macrophage infiltration on gene expression. RESULTS: macrophages in larger tumours, these cells are comparatively inactive, with no association with the level of iNOS or arginase staining, and no effect on gene expression within the tumour. The infiltration of either subset of macrophages did not correlate to overall survival. CONCLUSIONS: Thus, melanomas contain distinct macrophage populations with diverse phenotypes, but with no observable prognostic role.

BACKGROUND: Possible exacerbating factors are a major concern of parents of children with atopic eczema (AE). However, there is minimal evidence for their direct role in leading to disease flares. OBJECTIVES: To assess the association between 'trigger factors' and disease flares in AE. METHODS: Twenty-five children with AE were recruited. Participants completed diaries, recording severity and exposure to potential exacerbating factors (18 variables) over 28 days. Severity was assessed at baseline and study completion. The relationship between severity and exposures was assessed. RESULTS: At episode level, on the day of exposure (lag 0), hot weather correlated to increased scratch scores (P=0.043). At a lag of 2 days after exposure, damp weather was associated with raised scratch scores (P=0.027). At lag 3 days, elevated scratch scores were associated with sweating and stress (P=0.029 and 0.019, respectively). Outside damp was associated with elevated scores (P=0.001) at lag 4. Multivariate analysis of all significant variables showed that only damp at lag 4 was significantly associated with flares (P=0.039). CONCLUSIONS: This study suggests association between stress, damp and heat and disease flares. These findings need to be studied over a longer period, using objective exposure measures.

BACKGROUND: Endoscopic skull base reconstruction (ESBR) is an important advance in the management of skull base defects. Large dural defects usually require the use of pedicled mucosal flaps for successful repair and prevention of cerebral spinal fluid leak. Planning for pedicled flaps is important because raising the flap is often required before tumor removal or initial surgical access. The potential utility of the inferior turbinate pedicled flap (ITPF) in ESBR is assessed. METHODS: The ITPF was raised in nine cadaver heads. The most anterior extent reached on the anterior cranial fossa (ACF) and inferior limit on the posterior cranial fossa (PCF) were recorded with image-guided surgery. Measurements were calculated as a percentage of ACF or PCF length from easily reproducible measurements from preoperative radiology. The width was defined as the widest measurement in the distal third. The length-to-height ratio of the skull base was also assessed as a confounding factor. RESULTS: Mean length for the ITPF was 54.0+/-4.9 mm with a width of 22.1+/-3.7 mm. The mean reach was 112+/-21% (range, 90-150%) of the PCF. The ACF was less accessible with a mean reach of 67+/-9.9% (range, 52-84%). The skull base proportions did not have a strong association on utility (p=0.74 and 0.29). CONCLUSION: ITPF presents one option for ESBR of larger skull base defects. It has several limitations with access to the anterior ACF. The ITPF may be an excellent salvage flap when previous septectomy has been performed or with septal involvement by tumor. Careful preoperative assessment of potential defect can estimate the reach of the ITPF.

OBJECTIVES/HYPOTHESIS: Routine identification of all four parathyroid glands has been advocated as a means of reducing rates of postoperative hypocalcemia and inadvertent parathyroidectomy. The object of the present study was to investigate whether identification of more parathyroid glands during thyroidectomy performed by capsular dissection technique had any impact on incidence of postoperative hypocalcemia and unintentional parathyroid resection. STUDY DESIGN: Prospective cohort study of consecutive patients undergoing total thyroidectomy by capsular dissection technique over a 3-year period. Exclusion criteria included performance of concomitant central neck dissection, hyperparathyroidism, revision surgery, and invasive cancer. METHODS: The number of parathyroid glands identified intraoperatively was recorded. No effort was made to find glands that were not obviously apparent during the course of dissection. Patients were not placed on routine calcium supplementation. RESULTS: The final study population consisted of 126 patients. The mean number of parathyroid glands identified was 2.3. The incidence of biochemical (any postoperative calcium <2 mmol/L) and clinical hypocalcemia was 22.2% and 10.3%, respectively. Patients in group A (0-2 parathyroids identified) had a significantly lower incidence of clinical hypocalcemia than patients in group B (3-4 parathyroids identified) (3.2% vs. 17.1%, P = .02). The differences in biochemical hypocalcemia were not significant (16.1% vs. 28.1%, P = .13). The incidence of inadvertent parathyroidectomy was 9.5%. There was no difference between the groups in incidence of inadvertent parathyroidectomy (9.7% vs. 9.4%, P = 1.0). CONCLUSIONS: Routine identification of all four parathyroid glands is not necessary in thyroidectomy performed using capsular dissection technique.

BACKGROUND: Pharyngocutaneous fistula is a serious complication of total laryngectomy. The purpose of this study was to examine predisposing factors at our institution. METHODS: We conducted a retrospective review of 94 consecutive patients undergoing total laryngectomy. Cases with hypopharyngeal primary tumors or undergoing extended hypopharyngeal resection with flap augmentation of the pharynx were excluded. RESULTS: Seventy-four cases met inclusion criteria. A total of 25.7% patients developed a pharyngocutaneous fistula. The fistula rate was higher after salvage laryngectomy than after primary surgery (34.0% vs 11.1%; p = .05). Among salvage laryngectomies, performance of laryngectomy within 1 year of completion of radiotherapy (p = .006) and performance of concomitant bilateral neck dissection (p = .02) were significant risk factors for development of a fistula. Radiation dose, addition of chemotherapy, use of pectoralis major myofascial flap, preoperative tracheostomy, primary puncture, primary tumor subsite, and initial T classification were not significant. CONCLUSION: Interval between completion of radiotherapy and surgery is significantly associated with pharyngocutaneous fistula after salvage total laryngectomy.

COVID-19 healthcare workers (HCWs) require frequent handwashing and use of personal protective equipment (PPE) to prevent infection. However, evidence is emerging that these practices are causing adverse effects on their skin integrity. A single-centre, cross-sectional study of HCWs from an Irish hospital was undertaken to evaluate the degree of COVID-19-related irritant contact dermatitis (ICD) between April and May 2020. Of 270 participants surveyed, 223 (82.6%) reported symptoms of ICD. The hands were the most commonly affected site (76.47%) and the most frequently reported symptom was dry skin (75.37%). Nearly all (268; 99.26%) HCWs had increased hand-washing frequency, but 122 (45.35%) did not use emollients. In the ICD group, 24.7% cited a history of dermatitis compared with 4.3% of unaffected staff (P < 0.001). The ICD group recorded PPE usage for an average of 3.15 h compared with the non-ICD group at 1.97 h (P = 0.21). Promoting awareness of COVID-19-related ICD is vital to highlight prevention and treatment for frontline staff.

BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment and rehabilitation in different European countries. METHODS: A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks (synonyms: insurance against work accidents and occupational injuries; statutory social accident insurance)]. Legal standards for the assessment of occupationally triggered diseases with a genetic background differ between different countries, however, in most European member states recognition as OSD is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. CONCLUSION: OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness of this fact and further efforts for standardization are necessary.

IMPORTANCE: Optimum management of the clinically negative neck in the presence of primary site recurrence of laryngeal or hypopharyngeal cancer remains unclear. OBJECTIVE: To examine the incidence of occult cervical nodal metastatic disease in patients undergoing salvage laryngectomy with necks clinically staged as N0 at the time of recurrence and to define the role of elective neck dissection in this population with regard to risk of complications and oncologic outcomes. DESIGN: Retrospective study of patients treated from 1996 through 2011. SETTING: Academic teaching hospital. PARTICIPANTS: All patients undergoing salvage total laryngectomy for squamous cell carcinoma of larynx or hypopharynx after failed initial radiotherapy or chemoradiotherapy with radiographically N0 neck at time of recurrence. MAIN OUTCOMES AND MEASURES: Primary outcome measure was incidence of cervical nodal metastases detected by means of pathological examination of elective neck dissection specimens. Secondary outcome measures were incidence of major postoperative complications and regional cancer control. RESULTS: Forty-five patients were included. Thirty-eight underwent elective unilateral (20) or bilateral (18) ND at the time of laryngectomy. Three patients (8%) had occult metastases (3 of 56 dissected heminecks [5%]). The incidence of major wound complications was significantly greater in patients undergoing bilateral ND (12 of 18 [67%]) than in patients undergoing unilateral or no ND (8 of 27 [30%]) (P = .03). There was no significant difference in regional control according to whether bilateral, unilateral, or no ND was performed. CONCLUSIONS AND RELEVANCE: The incidence of occult metastatic disease in N0 necks in patients undergoing salvage surgery after radiotherapy is low. Neck dissection in this population does not seem to have a significant impact on regional cancer control. The need for elective ND, particularly bilateral ND, should be balanced against possible increased risk of morbidity in this group.

BACKGROUND: Cryotherapy is a standard treatment for viral warts. Although textbooks recommend treating until there is a halo of ice around the wart (traditional freeze), many authors advocate more aggressive cryotherapy. There are no previously published studies assessing the efficacy of longer freezing times. OBJECTIVES: To compare the efficacy of the traditional freeze and a sustained 10-s freeze in the treatment of common viral warts with liquid nitrogen. METHODS: Patients attending a dedicated wart clinic were randomized to receive either a traditional freeze or a 10-s sustained freeze with liquid nitrogen delivered by a spray gun. Two hundred patients were recruited, 100 in each group. RESULTS: After five treatments, 49 patients in the 10-s freeze group were clear of warts (64% of non-defaulters) as compared with 31 (39%) of those in the traditional freeze group (chi2 = 6.7; P = 0.009). Seventy-four patients in the 10-s freeze group as compared with 59 in the traditional freeze group had either improved or cleared after five treatments (chi2 = 5.0; P = 0.02). Morbidity was significantly greater in the 10-s freeze group. Sixty-four patients suffered pain or blistering as compared with 44 in the traditional freeze group (chi2 = 10.8; P = 0.0045). Five patients were withdrawn from the 10-s freeze group because of pain as compared with one patient in the traditional freeze group. CONCLUSIONS: A 10-s sustained freeze is more effective in the cryotherapy of viral warts but carries a significantly greater morbidity in terms of pain and blistering.

BACKGROUND: Hidradenitis suppurativa (HS), a chronic inflammatory disease that affects apocrine gland-bearing skin, has a significant impact on patients' quality of life. Estimates of the epidemiologic prevalence of HS are highly variable, and clinical data on disease characteristics and patient burden of disease remain limited. OBJECTIVE: The primary objective of this study was to determine the number of patients with HS attending dermatology clinics in a hospital setting in Ireland (within a 6-month time period). Secondary objectives included the assessment of disease characteristics and the collection of patient responses on disease burden and work productivity. METHODS: This was an epidemiologic, non-interventional, cross-sectional study across four dermatology clinics in Ireland over a 6-month time period. The disease prevalence was estimated by calculating the percentage of total patients with a diagnosis of HS (the primary population) across the selected sites. Secondary analyses were performed using the full analysis set, which consisted of eligible adults (≥18 years of age) from the primary population who provided informed consent. Data from these analyses are presented as descriptive summary statistics, with the use of an analysis of covariance for continuous endpoints. RESULTS: , 81.8%). Most patients for whom data were available presented with Hurley stage II (50.4%), and more than a third of the full analysis set had a relative with HS (34.7%). Questionnaire responses revealed a profound impact on quality of life, including diminished work productivity and various psychological comorbidities. CONCLUSION: This study offers insight into the clinical features and disease burden of hidradenitis suppurativa in an Irish population.