Clinical Experience of Axillary Radiotherapy for Node-positive Breast Cancer.

AIMS: Patients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer. MATERIALS AND METHODS: We evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan-Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model. RESULTS: Locoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20-0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45-14.0, P = 0.009). CONCLUSION: We support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology.

Implementing Medical Student Teaching on Gynaecological Healthcare of Transgender Patients.

Introduction Transgender people have specific healthcare needs and experience difficulty in accessing health services. Medical students should receive teaching on general and gynaecological healthcare issues in this population. Our aim was to assess medical students' knowledge of healthcare needs of transgender people before and after a newly implemented teaching session on transgender healthcare. Method A mixed-method study was carried out over a three month period in a university obstetric and gynaecology hospital in Dublin. A one-hour teaching session was developed and delivered to final year medical students. Students completed a survey before and after receiving the lecture. Results Seventy-one students completed the pre-lecture survey and forty-three completed the post-lecture survey. Pre-lecture, 64 students (90%) reported some-to-no understanding of healthcare issues of transgender people, and only 13 (18%) reported understanding gynaecological issues faced by transgender people. Post-lecture, 41 (95%) had a better understanding of health issues faced by this population and 40 (93%) had a better understanding of gynaecological health issues faced. Most students (81%) wanted further teaching on the topic. Conclusion A one-hour teaching session was effective at improving student knowledge of care of transgender people. This teaching could be expanded to all Irish medical schools. Going forward, the teaching could be adapted for post-graduate obstetric and gynaecology teaching.

Repatriation of a historical North Atlantic right whale habitat during an era of rapid climate change.

Climate change is affecting species distributions in space and time. In the Gulf of Maine, one of the fastest-warming marine regions on Earth, rapid warming has caused prey-related changes in the distribution of the critically endangered North Atlantic right whale (Eubalaena glacialis). Concurrently, right whales have returned to historically important areas such as southern New England shelf waters, an area known to have been a whaling ground. We compared aerial survey data from two time periods (2013-2015; 2017-2019) to assess trends in right whale abundance in the region during winter and spring. Using distance sampling techniques, we chose a hazard rate key function to model right whale detections and used seasonal encounter rates to estimate abundance. The mean log of abundance increased by 1.40 annually between 2013 and 2019 (p = 0.004), and the mean number of individuals detected per year increased by 2.23 annually between 2013 and 2019 (R2 = 0.69, p = 0.001). These results demonstrate the current importance of this habitat and suggest that management options must continually evolve as right whales repatriate historical habitats and potentially expand to new habitats as they adapt to climate change.

The Profile of Women Attending the National Maternity Hospital Emergency Out Of Hours Service ­ Two Decades On. A Retrospective Review

Introduction This study aimed to review the profile of women attending an out of hours emergency service (OHS) in a maternity hospital and compare it to a previous study. Methods Retrospective study. Demographic information was recorded including timing of presentation, reason and outcome. Results In 2017, 9,020 women attended the OHS, a 334% increase since 1993. On detailed review of 2,143 charts, most (84.7%, n=1,815) were antenatal. The most common reason for presenting to the OHS then was first trimester bleeding. In 2017, over half of antenatal women (51%, n=1,092) presented with "other" reasons, such as vomiting, hypertension or suspected pre-eclampsia. Admission rates significantly decreased from 1993 (38% (n=1,053) in 1993 vs. 16% (n=338) in 2017; p<0.05). Discussion Numbers attending for emergency maternity care have increased in both numbers and variety of presentations. It is important that women are seen and cared for in a compassionate, kind and evidence based manner.

Characterization of large basking shark Cetorhinus maximus aggregations in the western North Atlantic Ocean.

Cetorhinus maximus aggregations recorded during extensive aerial survey efforts off the north-eastern United States between 1980 and 2013 included aggregations centring on sightings with group sizes of at least 30 individuals. These aggregations occurred in summer and autumn months and included aggregation sizes of up to 1398 individuals, the largest aggregation ever reported for this species. The aggregations were associated with sea surface temperatures of 13-24° C and chlorophyll-a concentrations of 0·4-2·6 mg m-3 and during one aggregation, a high abundance of zooplankton prey was present. Photogrammetric tools allowed for the estimation of total body lengths ranging between 4 and 8 m. Characterization of these events provides new insight into the potential biological function of large aggregations in this species.

A regional analysis of epidermal growth factor receptor (EGFR) mutated lung cancer for HSE South.

BACKGROUND: EGFR mutated lung cancer represents a subgroup with distinct clinical presentations, prognosis, and management requirements. We investigated the survival, prognostic factors, and real-world treatment of NSCLC patients with EGFR mutation in clinical practice. METHODS: A retrospective review of all specimens sent for EGFR analysis from December 2009 to September 2015 was performed. Patient demographics, specimen type, EGFR mutation status/type, stage at diagnosis, treatment, response rate, and survival data were recorded. RESULTS: 27/334 (8%) patient specimens sent for EGFR testing tested positive for a sensitising EGFR mutation. The median age was 65 years (40-85 years). Exon 19 deletion represented the most commonly detected alteration, accounting for 39% (n = 11). First-line treatment for those with Exon 18, 19, or 21 alterations (n = 24) was with an EGFR tyrosine kinase inhibitor (TKI) in 79% (n = 19). Objective response rate among these patients was 74% and median duration of response was 13 months (range 7-35 months). CONCLUSION: The incidence of EGFR mutation in our cohort of NSCLC is 9% which is consistent with mutation incidence reported in other countries. The rate of EGFR mutation in our population is slightly below that reported internationally, but treatment outcomes are consistent with published data. Real-world patient data have important contributions to make with regard to quality measurement, incorporating patient experience into guidelines and identifying safety signals.

Predicting carotid artery disease and plaque instability from cell-derived microparticles.

OBJECTIVES: Cell-derived microparticles (MPs) are small plasma membrane-derived vesicles shed from circulating blood cells and may act as novel biomarkers of vascular disease. We investigated the potential of circulating MPs to predict (a) carotid plaque instability and (b) the presence of advanced carotid disease. METHODS: This pilot study recruited carotid disease patients (aged 69.3 ± 1.2 years [mean ± SD], 69% male, 90% symptomatic) undergoing endarterectomy (n = 42) and age- and sex-matched controls (n = 73). Plaques were classified as stable (n = 25) or unstable (n = 16) post surgery using immunohistochemistry. Blood samples were analysed for MP subsets and molecular biomarkers. Odds ratios (OR) are expressed per standard deviation biomarker increase. RESULTS: Endothelial MP (EMP) subsets, but not any vascular, inflammatory, or proteolytic molecular biomarker, were higher (p < .05) in the unstable than the stable plaque patients. The area under the receiver operator characteristic curve for CD31(+)41(-) EMP in discriminating an unstable plaque was 0.73 (0.56-0.90, p < .05). CD31(+)41(-) EMP predicted plaque instability (OR = 2.19, 1.08-4.46, p < .05) and remained significant in a multivariable model that included transient ischaemic attack symptom status. Annexin V(+) MP, platelet MP (PMP) subsets, and C-reactive protein were higher (p < .05) in cases than controls. Annexin V(+) MP (OR = 3.15, 1.49-6.68), soluble vascular cell adhesion molecule-1 (OR = 1.64, 1.03-2.59), and previous smoking history (OR = 3.82, 1.38-10.60) independently (p < .05) predicted the presence of carotid disease in a multivariable model. CONCLUSIONS: EMP may have utility in predicting plaque instability in carotid patients and annexin V(+) MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers.

Technology-supported dietary and lifestyle interventions in healthy pregnant women: a systematic review.

Overweight and obesity are associated with increased risk of adverse maternal and fetal outcomes. However, the actuality of delivering effective lifestyle interventions in clinical practice is hampered by a high demand for resources. The use of technology to assist lifestyle interventions needs to be explored as a valid method of reducing strain on resources, and enhancing the effectiveness and population reach of interventions. The aim was to systematically review the literature on the use of technology-supported lifestyle interventions for healthy pregnant women and their impact on maternal outcomes. Online databases and registries were searched in March 2013. Primary outcomes of selected English language studies were fasting maternal glucose, incidence of gestational diabetes mellitus (GDM) and maternal gestational weight gain. Secondary outcomes were intervention uptake and acceptance, and dietary or physical activity modification. Studies whose subjects were diagnosed with GDM prior to intervention were excluded. The minimal number of eligible studies and varying outcomes precluded formal meta-analysis of the data. Initially, 203 articles were identified and screened. Seven articles, including five randomised controlled trials, met inclusion criteria for the current review. Results demonstrate several potential benefits associated with technology-supported interventions in pregnancy, despite minimal search results. Although communication technology holds potential as a safe therapeutic tool for the support of lifestyle interventions in pregnancy, there is a paucity of data on its effectiveness. Further RCTs examining the effectiveness of communication technology are required, particularly among those most likely to benefit from lifestyle interventions, such as overweight and obese pregnant women.

Persistent perforation in non-faeculant diverticular peritonitis--incidence and clinical significance.

BACKGROUND: Non-resectional strategies (NRS) have improved outcomes for a sub-group of patients with perforated diverticulitis. NRS are applicable to patients with non-faeculant peritonitis (Hinchey II and III). Success is dependent on the initial perforation sealing, which Hinchey estimated occurred 'most of the time'. An exact percentage remains ill-defined. OBJECTIVE: We aimed to define the percentage and clinical significance of a persistent perforation in non-faeculant diverticular peritonitis. DESIGN: A retrospective review was conducted of all patients admitted with a diagnosis of perforated diverticulitis between January 1999 and July 2010. Patients undergoing an emergency operation were analysed according to Hinchey and physiological and operative severity scores and compared with histological findings. RESULTS: One hundred fifteen patients were identified. Fifty-three patients underwent a 'resectional' procedure. At surgery, 15 patients had faeculent peritonitis, 27 patients had purulent peritonitis and 11 patients had a contained abscess. Of the patients with non-faeculant peritonitis, 2/9 (22.2 %) Hinchey II and 10/27 (37.1 %) Hinchey III patients had persistent perforation on review of histology. Persistent perforation was associated with a significant increase in morbidity, length of stay, physiological and operative severity score (p = 0.015, 0.011, 0.049 and 0.002, respectively). CONCLUSION: A proportion of patients with non-faeculant peritonitis have a persistent perforation which is associated with a poorer outcome and is likely to result in failure of a non-resectional management strategy. Updated classification systems and tailored peri-operative investigations are required to identify this sub-group of patients and improve patient outcomes.

Rapid on-site evaluation of axillary fine-needle aspiration cytology in breast cancer.

BACKGROUND: Axillary ultrasonography (AUS) and fine-needle aspiration cytology (FNAC) can establish axillary lymph node status before surgery, although this technique is hampered by poor adequacy rates. To achieve consistently high rates of FNAC adequacy, rapid on-site evaluation (ROSE) of FNAC samples was introduced. METHODS: This single-centre, retrospective observational study of patients with newly diagnosed breast cancer undergoing preoperative AUS and FNAC between February 2008 and November 2010 examined the effect of the introduction of ROSE. RESULTS: A total of 381 patients were included. AUS revealed 152 axillae with suspicious radiological features. FNAC was positive for malignant cells in 75 (49·3 per cent) of 152 samples. Sentinel lymph node mapping was avoided in 75 patients, representing 19·7 per cent of the entire study population. Adequacy rates increased from 78 per cent to 96 per cent following the introduction of ROSE (P = 0·001). The overall sensitivity and specificity of AUS and FNAC was 80·6 and 100 per cent respectively. A lymph node diameter equal to or larger than 10 mm and extranodal extension were significantly associated with positive FNAC (P < 0·001 and P = 0·012 respectively). Maximum lymph node diameter of at least 10 mm was an independent predictor of positive FNAC (odds ratio 11·2, 95 per cent confidence interval 3·32 to 37·76; P < 0·001). CONCLUSION: AUS with FNAC provided accurate preoperative staging of the axilla for metastatic breast disease and avoided unnecessary sentinel lymph node mapping. The introduction of ROSE ensured the efficiency of AUS and FNAC.

Tremorgenic neuromycotoxicosis in 2 dogs ascribed to the ingestion of penitrem A and possibly roquefortine in rice contaminated with Penicillium crustosum.

Two dogs developed alarming tremorgenic nervous stimulation shortly after ingesting discarded rice that had been forgotten in a refrigerator for an undetermined period and that was covered with a grey-green mould. Both dogs exhibited vomition followed by slight salivation, tremors and ataxia and 1 showed such severe agitation and seizures that it necessitated anaesthesia with thiopentone followed, on recovery, by xylazine. The other dog was only sedated with xylazine. They made an uneventful recovery. The rice vomitus yielded a pure culture of Penicillium crustosum. On chemical analysis it was negative for organochlorine, organophosphor and carbamate insecticides, as well as for strychnine, but contained 2.6 microg/g of the mycotoxins penitrem A as well as 34 microg/g of roquefortine as determined by LC-MS and confirmed by MS-MS. This is the 1st South African case of naturally occurring penitrem A toxicosis and also the 1st case where quantification of the levels of mycotoxins in dog vomitus is reported. The tremorgenicity of roquefortine and its contribution towards this syndrome, is questioned.

Large scale deletions in the GPC3 gene may account for a minority of cases of Simpson-Golabi-Behmel syndrome.

AIMS OF THE STUDY: To identify the proportion and type of deletions present in the glypican 3 (GPC3) gene in a group of patients with Simpson-Golabi-Behmel syndrome (SGBS). SUBJECTS AND METHODS: PCR analysis using primer pairs which amplify fragments from each of the eight exons of the GPC3 gene was carried out in a series of 18 families with SGBS (approximately half of reported cases). RESULTS: Deletions were detected in only five families (one reported previously). We found deletions in all exons of the gene except exon 3. CONCLUSIONS: Our results suggest that large scale deletions may be less common in SGBS than was originally thought. One patient, with an exon 4 and 5 deletion, lacked the characteristic facial dysmorphic features. This raises the possibility of involvement of GPC3 gene defects in a wider range of overgrowth disorders.

PPM-X: a new X-linked mental retardation syndrome with psychosis, pyramidal signs, and macroorchidism maps to Xq28.

We report a three-generation family manifesting a previously undescribed X-linked mental retardation syndrome. Four of the six moderately retarded males have had episodes of manic-depressive psychosis. The phenotype also includes pyramidal signs, Parkinsonian features, and macroorchidism, but there are no characteristic dysmorphic facial features. Affected males do not show fragile sites at distal Xq on cytogenetic analysis, nor do they have expansions of the CGG repeats at the FRAXA, FRAXE, or FRAXF loci. Linkage analyses were undertaken, and a maximal LOD score of 3.311 at theta = .0 was observed with the microsatellite marker DXS1123 in Xq28. A recombination was detected in one of the affected males with DXS1691 (Xq28), which gives the proximal boundary of the localization. No distal recombination has been detected at any of the loci tested.