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Neoplasias da Mama , COVID-19 , Humanos , Feminino , Neoplasias da Mama/epidemiologia , PandemiasRESUMO
INTRODUCTION AND IMPORTANCE: Acute appendicitis is one of the most common presentations to the emergency department, particularly in young adults. A combination of clinical suspicion, inflammatory blood markers and imaging modalities such as ultrasound and CT are used for its definitive diagnosis. Early detection and intervention are paramount to reduce morbidity and mortality. Laparoscopic appendicectomy is the current gold standard in the management of appendicitis, especially if complicated according to EAES guidelines. There are few documented cases in the literature of acute appendicitis secondary to foreign body ingestion. On account of this, there are currently no guidelines for its management. Our literature review highlights the importance of surgical management of foreign body acute appendicitis. CASE PRESENTATION: This case report describes the rare presentation of acute complicated appendicitis caused by an ingested toothpick in a 64 year old woman. The patient was admitted with a 3 day history of lower abdominal pain, localizing to the right iliac fossa with raised inflammatory markers. CT imaging reported acute complicated appendicitis. Laparoscopic appendicectomy was performed during which a toothpick was seen protruding through the appendiceal wall. Post operatively the patient was treated with IV antibiotics for 5 days prior to discharge. CLINICAL DISCUSSION: Due to the rare nature of foreign body appendicitis there are no specific guidelines on the respective surgical approach. A literature review showed that in the setting of foreign body appendicitis, surgical intervention is paramount with no scope for conservative management. CONCLUSION: Surgical approach is based on the clinical judgement and skillset of the operating surgeon.
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BACKGROUND: Centralisation of rectal cancer surgery to designated centres was a key objective of the Irish national cancer control program. A national audit of rectal cancer surgery indicated centralisation was associated with improved early surgical outcomes. This study aimed to determine the impact of implementation of the national cancer strategy on survival from rectal cancer. MATERIALS AND METHODS: Data were collected from the National Cancer Registry of Ireland to include all patients with Stage I-III rectal cancer undergoing rectal cancer surgery with curative intent between 2003 and 2012. Five-year overall survival and cancer-specific survival was compared between patients in the pre-centralisation (2003-2007) and post-centralisation period (2008-2012) and between patients receiving surgery in designated cancer centres and non-cancer centres. RESULTS: The proportion of rectal cancer surgery performed in a designated cancer centre increased from 42% during 2003-2007 to 58% during 2008-2012. Five-year overall survival increased from 66.1% in 2003-2007 to 73.5% in 2008-2012 (p < 0.001). Five-year cancer-specific survival increased from 75.3% in 2003-2007 to 81.9% in 2008-2012 (p < 0.001). Surgery in a cancer centre and surgery post-centralisation were significantly associated with overall and cancer specific survival using Cox proportional hazards regression. CONCLUSION: Survival following resection of rectal cancer was significantly improved following implementation of a national cancer strategy incorporating centralisation of rectal cancer surgery.
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Neoplasias Retais , Humanos , Irlanda/epidemiologia , Neoplasias Retais/cirurgia , Reto , Sistema de Registros , Estudos RetrospectivosRESUMO
BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.
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Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Humanos , Linfócitos , Linfócitos do Interstício Tumoral , Prognóstico , Receptor ErbB-2/genéticaRESUMO
BACKGROUND: Adequate clinical skills training is a challenge for present day medical education. Simulation Based Education (SBE) is playing an increasingly important role in healthcare education worldwide to teach invasive procedures. The impact of this teaching on students along with retention of what is taught is not fully understood. The purpose of this study was to evaluate the retention levels of practical skills taught and assessed by SBE and to explore the degree of re-training required to restore decayed performance. In exploring this aim, the study further investigates how skilled performance decays over time and which dimensions of clinical skills were more likely to decay. METHODS: Study participants were 51 final year medical students. They were provided with online pre-course videos and procedural guides asynchronously with repeatedly access. 7 of the skills taught over 2 years using task trainers were selected. Following demonstration from faculty, students practiced in small groups with faculty facilitated supervision and peer support prior to formal testing. Score sheets with itemised procedure checklists detailing the minimum passing standard (MPS) for each skill were designed. To test retention of skills, 18 months later, there was an unannounced test to demonstrate proficiency in the skills. Students were asked to complete a questionnaire indicating how many times and where they had practiced or performed the skills. RESULTS: 55% of the students were deficient in 3 or more skills and 4% were not competent in 5 or more skills. A significant number of students had never practiced some skills following the initial teaching session. A relationship was noted with the number of times students self-declared that they had practiced and their performance. Decay is evident in both psychomotor and cognitive domains of the skills. CONCLUSION: A curriculum with deliberate practice significantly increases the competence of students in defined clinical skills. Deliberate practice of clinical skills, under supervision of an engaged instructor, is a key component of the mastery model. Experiences and assessments in the clinical setting need to be augmented with focus on direct observation and focused feedback to reinforce the skills acquired in the simulated setting.
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Competência Clínica , Currículo , Educação de Graduação em Medicina/métodos , Retenção Psicológica , Treinamento por Simulação/métodos , Estudos de Coortes , Feminino , Humanos , Irlanda , Masculino , Estudos Prospectivos , Estudantes de Medicina/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: The purpose of this study was to examine hospital mortality, long-term mortality, and health service utilization among critically ill patients. We also determined whether these outcomes differed according to demographic and clinical characteristics. METHODS: We conducted a retrospective cohort study of adults (age ≥ 18 years) who survived admission to an intensive care unit (ICU) in Ontario, Canada, between 1 April 2002 and 31 March 2012, excluding isolated admissions to step-down or intermediate ICUs, coronary care ICUs, or cardiac surgery ICUs. Adults (age ≥ 18 years) who survived an acute hospitalization that did not include an ICU stay formed the comparator group. The primary outcome was mortality following hospital discharge. Secondary outcomes were healthcare utilization, including emergency room admissions and hospital readmissions during follow-up. RESULTS: Over the study interval, 500,124 patients were admitted to ICUs and 420,187 (84%) survived to hospital discharge. Median follow-up for survivors was 5.3 (interquartile range 2.5, 8.2) years. Patients admitted to an ICU were more likely to subsequently visit the emergency department, be readmitted to the hospital and ICU, receive home care support, require rehabilitation, and be admitted for long-term care. Those requiring more resources within the ICU required more resources after discharge. One-third of patients admitted to the ICU died during long-term follow-up, with overall probabilities of death of 11% and 29% at 1 year and 5 years, respectively. In the adjusted analysis, there was an increasing hazard of death with increasing age, reaching a hazard ratio of 18.08 (95 % confidence interval 16.60-19.68) for those ≥ 85 years of age compared with those aged 18-24 years. CONCLUSIONS: Healthcare utilization after hospital discharge was higher among ICU patients, and also among those requiring more healthcare resources during their ICU admission, than among all hospitalized patients as a group. One-third of ICU patients died within the 5 years following discharge, and age was the most influential determinant of outcome. These findings should help target post-ICU discharge services for high-risk groups and better inform goals-of-care discussions for elderly critically ill patients.
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Estado Terminal/mortalidade , Atenção à Saúde/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Assistência de Longa Duração/estatística & dados numéricos , Avaliação de Resultados da Assistência ao Paciente , Readmissão do Paciente/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ontário , Estudos Retrospectivos , Sobreviventes/estatística & dados numéricosRESUMO
BACKGROUND: Management of axillary disease in breast cancer has evolved significantly over the last two decades with the introduction of SLNB and a trend towards less radical surgery. Data from the American College of Surgeons Oncology Group Z0011 trial proposes that not all patients with positive axillary lymph nodes require completion axillary dissection. AIMS: The aim of this study was to determine whether there has been a change in practice patterns for axillary management in Ireland since the publication of this 'practice-changing' trial. METHODS: A review of breast cancers managed in the 12 months prior to publication of Z0011 (pre-Z0011) and comparison with those managed in the following 12 months (post-Z0011) was undertaken in three tertiary referral breast cancer centres. Patients with a positive SLNB were identified, and clinicopathologic data and subsequent management was compared between the two cohorts. RESULTS: There were 708 SLNB performed during the study period; 326 pre-Z0011 and 382 post-Z0011. There was no difference in the rate of SLN positivity between the two cohorts: 29.1 % had a positive SLN pre-Z0011 and 29.3 % were positive post-Z0011. There were a significantly lower number of axillary clearances performed in SLN-positive patients in the post-Z0011 period (71.4 %) compared to the pre-Z011 period (93.7 %, p = 0.0022 Chi-square). Of the patients with tumour characteristics meeting the Z0011 inclusion criteria in the initial 12 months of the study, 92.3 % underwent ALND compared with 65.6 % in the final 12 months of the study (p = 0.0006 Chi-square). CONCLUSIONS: There has been a change in clinical practice since the publication of the Z0011 trial, illustrated by a decrease in the rate of axillary clearance in node-positive breast cancers.
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Neoplasias da Mama/patologia , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Linfonodos/cirurgia , Padrões de Prática Médica , Adulto , Idoso , Axila , Feminino , Humanos , Análise de Séries Temporais Interrompida , Irlanda , Excisão de Linfonodo/tendências , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Biópsia de Linfonodo SentinelaRESUMO
INTRODUCTION: Major changes are occurring in surgical training in the UK and Ireland. Training time is reduced due to the introduction of run-through training and the EWTD. Streamlined training also may affect the number of trainees engaging in full-time higher degrees by research, in spite of the fact that those who do engage are more academically productive. This study assesses the attitudes of medical students towards a career in surgery and their attitudes to research, especially in the context of an intercalated degree programme. METHODS: 615 students comprising both undergraduates and postgraduates from RCSI were surveyed. The influence of a number of factors was ranked using five-point Likert scales. Students were asked to rate the importance of research to their future careers. RESULTS: 595 (97 %) of those surveyed completed the questionnaire satisfactorily. Those interested in surgery were more likely to be male, undergraduate students and younger. Factors encouraging students to pursue a surgical career were prestige, identification of a surgical mentor, financial reward and research opportunities on offer (p < 0.001 in all cases). Almost 27 % of students had already engaged with some form of research project. A significant proportion of those interested and not interested in surgery (26 and 29 % respectively) would consider taking time out to do an intercalated research degree as part of their primary medical studies. CONCLUSION: Surgical training faces significant challenges. One way to encourage the next generation of academic surgeons may be to offer some candidates intercalated research degrees while pursuing their medical qualification.
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Atitude , Pesquisa Biomédica/educação , Escolha da Profissão , Educação de Pós-Graduação em Medicina , Cirurgia Geral , Estudantes de Medicina/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Renda , Irlanda , Masculino , Mentores , Fatores Sexuais , Estudantes de Medicina/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
The key learning points of Surgical Grand Rounds (SGR) are often not accessible at times of exam revision for students. We sought to use Twitter as an online teaching repository. A SGR Twitter profile was created. 23 SGR presentations were made accessible on Twitter over a 3 month period. 93 students were invited to complete a questionnaire assessing usage of the repository. 84 (90%) in total responded, of these, 25 (80.6%) felt that the online provision of SGR through twitter was "useful". The majority (71%) felt that the online content was easily accessible. The novel use of social media is a useful adjunctive educational tool in accessing an online repository of SGR presentations.
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Cirurgia Geral/educação , Disseminação de Informação/métodos , Mídias Sociais , Estudantes de Medicina , Visitas de Preceptoria , Humanos , Inquéritos e QuestionáriosRESUMO
Laparoscopic cholecystectomy is a common procedure performed in both emergency and elective settings. Our aim was to analyse the trends in laparoscopic surgery in Ireland in the public and private healthcare systems. In particular we studied the trend in day case laparoscopic cholecystectomy. National HIPE data for the years 2010-2012 was obtained. Similar datasets were obtained from the three main health insurers. 19,214 laparoscopic cholecystectomies were carried out in Ireland over the 3-year period. More procedures were performed in the public system than the private system from 2010-2012. There was a steady increase in surgeries performed in the public sector, while the private sector remained static. Although the ALOS was significantly higher in the public sector, there was an increase in the rate of day case procedures from 416 (13%) to 762 (21.9%). The day case rates in private hospitals increased only slightly from 29 (5.1%) in 2010 to 40 (5.9%) in 2012. Day case laparoscopic cholecystectomy has been shown to be a safe procedure, however significant barriers remain in place to the implementation of successful day case units nationwide.
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Atitude do Pessoal de Saúde , Colecistectomia Laparoscópica , Cálculos Biliares/cirurgia , Hospitais Privados/estatística & dados numéricos , Hospitais Públicos , Tempo de Internação/tendências , Colecistectomia Laparoscópica/métodos , Colecistectomia Laparoscópica/estatística & dados numéricos , Colecistectomia Laparoscópica/tendências , Barreiras de Comunicação , Hospitais Públicos/métodos , Hospitais Públicos/estatística & dados numéricos , Humanos , Seguro Saúde/estatística & dados numéricos , Irlanda , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Risco AjustadoRESUMO
BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.
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Neoplasias da Mama/patologia , Carcinoma Papilar/patologia , Papiloma/patologia , Adulto , Idoso , Neoplasias da Mama/cirurgia , Carcinoma Papilar/cirurgia , Feminino , Seguimentos , Humanos , Agências Internacionais , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Papiloma/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
There are divergent opinions regarding the optimum surgical management of the axilla in patients with invasive breast cancer. Guidelines mandate axillary lymph node dissection (ALND) in the setting of positive sentinel lymph nodes. However, recent studies have questioned the true benefits of this procedure. Therefore, a meta-analysis of relevant randomized trials was performed in order to clarify the oncological benefit of axillary lymph node dissection. A comprehensive search of published randomized trials that compared patients with primary operable breast cancer with/without ALND was performed using MEDLINE, and available data were cross-referenced. Reviews of each study were conducted, and data were extracted. Primary outcomes were overall survival and recurrent axillary disease. A total of 7347 patients with operable primary breast cancer were identified from 8 randomised controlled trials comparing axillary recurrence in patients with or without ALND. Six of these trials provided data on overall survival on 6895 patients. Overall survival favours patients having ALND (OR = 1.22 (95% CI 1.03-1.44, p = 0.02). Similarly, patients undergoing ALND had increased recurrence-free survival (OR = 2.25 (95% CI 1.28-3.94, p = 0.0047). ALND appears to positively impact on overall and recurrence-free survival from breast cancer. These data highlight the enduring benefits of ALND in an era where adjuvant therapies are being promoted to manage regionally advanced/metastatic disease.
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Axila , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Excisão de Linfonodo , Neoplasias da Mama/mortalidade , Feminino , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Razão de Chances , Resultado do TratamentoRESUMO
Treatment with tyrosine kinase inhibitors (TKIs) including trastuzumab has revolutionized the management of HER2-positive breast cancer. Recent evaluation of clinical trial data suggests that a subset of HER2/ER double-positive cancers may not receive significant benefit from the TKI therapy. Here we investigate the cross talk between HER2 and ER in breast cancer and monitor the effect of trastuzumab on the tyrosine kinase effector transcription factor Myc. In HER2-positive breast cancer patients treated with neoadjuvant trastuzumab, steroid receptor-negative status (ER and PR negative) of pre-treatment biopsies predicted pathological complete response (pCR) (n=31 patients, P=0.0486), whereas elevated Myc protein inversely associated with pCR (P=0.0446). Liquid chromatography mass spectrometry identified the corepressor SMRT as a novel Myc-interacting protein. Trastuzumab treatment enhanced Myc-SMRT interactions in HER2-overexpressing breast cancer cells (LCC1) and inhibited expression of the Myc target gene survivin. In HER2-low, ER-positive steroid-dominant cells (MCF7), trastuzumab therapy repressed Myc-SMRT interactions and upregulated survivin expression. Trastuzumab treatment induced ER-CBP interactions, enhanced ER transcriptional activity and upregulated expression of the ER target gene pS2. The absence of pS2 expression in pre-treatment biopsies predicted pCR to neoadjuvant trastuzumab in breast cancer patients (n=25, P=0.0089) and pS2 expression associated with residual cancer burden (P=0.0196). Furthermore, metastatic tissues from patients who had failed trastuzumab therapy were pS2 positive. In HER2-overexpressing cells, trastuzumab treatment can repress Myc transcriptional activity and clinical response is favorable. However, with co-expression of the steroid pathway, this inhibition is lost and response to treatment is often poor.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Receptor Cross-Talk/fisiologia , Receptor ErbB-2/fisiologia , Receptores de Estrogênio/fisiologia , Neoplasias da Mama/química , Feminino , Humanos , Células MCF-7 , Correpressor 2 de Receptor Nuclear/fisiologia , Proteínas Proto-Oncogênicas c-myc/fisiologia , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Trastuzumab , Fator Trefoil-1 , Proteínas Supressoras de Tumor/análiseRESUMO
BACKGROUND: Sentinel lymph node (SLN) positivity is an important prognostic factor in cutaneous melanoma. A nomogram has been developed at Memorial Sloan-Kettering Cancer Centre (MSKCC) to predict SLN positivity and this may be useful to select patients for SLN biopsy. AIMS: We aimed to determine whether this nomogram would be of clinical use in an Irish population. METHODS: Age, Breslow thickness, Clark's level, presence of ulceration and tumour location indices were used to calculate the probability of SLN positivity with the MSKCC nomogram in 124 patients who underwent SLN biopsy in Beaumont Hospital between 2006 and 2012. Discrimination and calibration of the nomogram were evaluated. Negative predictive value (NPV) of the nomogram was calculated, using a cut-off of nomogram predicted probability of <9%. RESULTS: SLN biopsy was positive in 25 patients (20.16%). Overall predictive accuracy of the nomogram was found to be significant with an area under the curve of 0.805 (95% confidence interval 0.710-0.899). The mean predicted probability correlated well with observed risk (r = 0.887). The NPV was 92.86% with an error rate of 3.23%. This would lead to a reduction in SLN biopsy rate of 45.16%. CONCLUSIONS: This nomogram is valid and accurate at predicting SLN positivity in an Irish population. This may facilitate the clinical decision to perform a SLN biopsy in malignant melanoma.
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Melanoma/patologia , Nomogramas , Neoplasias Cutâneas/patologia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Biópsia de Linfonodo SentinelaRESUMO
INTRODUCTION: Laminar airflow (LAF) systems are thought to minimise contamination of the surgical field with airborne microbes and thus to contribute to reducing surgical site infections (SSI). However recent publications have questioned whether LAF ventilation confers any significant benefit and may indeed be harmful. METHODS: A detailed literature review was undertaken through www.Pubmed.com and Google scholar (http://scholar.google.com). Search terms used included "laminar flow". "laminar airflow", "surgical site infection prevention", "theatre ventilation" and "operating room ventilation", "orthopaedic theatre" and "ultra-clean ventilation". Peer-reviewed publications in the English language over the last 50 years were included, up to and including March 2014. RESULTS: Laminar airflow systems are predominantly used in clean prosthetic implant surgery. Several studies have demonstrated decreased air bacterial contamination with LAF using bacterial sedimentation plates placed in key areas of the operating room. However, apart from the initial Medical Research Council study, there are few clinical studies demonstrating a convincing correlation between decreased SSI rates and LAF. Moreover, recent analyses suggest increased post-operative SSI rates. CONCLUSION: It is premature to dispense with LAF as a measure to improve air quality in operating rooms where prosthetic joint surgery is being carried out. However, new multi-centre trials to assess this or the use of national prospective surveillance systems to explore other variables that might explain these findings such as poor operating room discipline are needed, to resolve this important surgical issue.
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Controle de Infecções/métodos , Salas Cirúrgicas/normas , Infecção da Ferida Cirúrgica/prevenção & controle , Ventilação/métodos , Humanos , OrtopediaRESUMO
Breast cancer resistance to endocrine therapies such as tamoxifen and aromatase inhibitors is a significant clinical problem. Steroid receptor coactivator-1 (SRC-1), a coregulatory protein of the oestrogen receptor (ER), has previously been shown to have a significant role in the progression of breast cancer. The chromatin protein high mobility group box 2 (HMGB2) was identified as an SRC-1 interacting protein in the endocrine-resistant setting. We investigated the expression of HMGB2 in a cohort of 1068 breast cancer patients and found an association with increased disease-free survival time in patients treated with endocrine therapy. However, it was also verified that HMGB2 expression could be switched on in endocrine-resistant tumours from breast cancer patients. To explore the function of this poorly characterized protein, we performed HMGB2 ChIPseq and found distinct binding patterns between the two contexts. In the resistant setting, the HMGB2, SRC-1 and ER complex are enriched at promoter regions of target genes, with bioinformatic analysis indicating a switch in binding partners between the sensitive and resistant phenotypes. Integration of binding and gene expression data reveals a concise set of target genes of this complex including the RNA helicase DDX18. Modulation of DDX18 directly affects growth of tamoxifen-resistant cells, suggesting that it may be a critical downstream effector of the HMGB2:ER complex. This study defines HMGB2 interactions with the ER complex at specific target genes in the tamoxifen-resistant setting.
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Neoplasias da Mama/metabolismo , RNA Helicases DEAD-box/metabolismo , Proteína HMGB2/metabolismo , Receptores de Estrogênio/metabolismo , Animais , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , RNA Helicases DEAD-box/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteína HMGB2/genética , Humanos , Estimativa de Kaplan-Meier , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos SCID , Coativador 1 de Receptor Nuclear/genética , Coativador 1 de Receptor Nuclear/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas/genética , Ligação Proteica , Interferência de RNA , Receptores de Estrogênio/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Centralisation of breast cancer services in Ireland has resulted in a significant increase in the number of patients attending symptomatic breast units (SBU). A considerable proportion of patients referred to SBU present with non-suspicious symptoms and fall into a "low-risk" category for breast cancer. It has been proposed that consideration be given to a primary care-delivered service for these patients. AIM: To evaluate SBU attendances and correlate with diagnosis to identify a cohort of patients who may be suitable for management in the primary care setting. METHODS: Data were collected from a prospectively maintained database on patients attending SBU at two tertiary referral centres (Beaumont Hospital and University College Hospital Galway) from January 2011 to 2012. Reasons for attendance, outcome of triple-assessment and incidence of malignancy were analysed. RESULTS: 14,325 patients underwent triple assessment at the SBU in this time period. 5,841 patients were referred with mastalgia, of whom 3,331 (57 %) reported mastalgia as the only symptom. The incidence of breast cancer in patients presenting with mastalgia alone was 1.2 %. All patients diagnosed with breast cancer in this cohort were over 35 years of age. CONCLUSION: The incidence of breast cancer in patients referred to SBU with mastalgia as an isolated symptom is extremely low. Patients under 35 years of age, with mastalgia as an isolated symptom do not require breast imaging and have a sufficiently low risk of breast cancer that they may be suitable for management in the primary care setting.
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Neoplasias da Mama/diagnóstico , Mastodinia/etiologia , Atenção Primária à Saúde , Encaminhamento e Consulta , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Feminino , Humanos , Irlanda , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Clean surgical scrubs, surgical gowns and headgear are worn by operative teams to decrease bacterial contamination and lower surgical site infection (SSI) rates. METHODS: A detailed review was undertaken of peer-reviewed publications and other sources of material in the English language over the last 50 years included. RESULTS: Surgical scrubs should be clean and made of tightly woven material. Studies investigating single-use gowns and drapes versus reusable gowns report conflicting evidence. Double gloving may reduce SSI rates in procedures where no antibiotic prophylaxis was administered. Bacterial contamination of the operative field has been shown to be decreased by the wearing of surgical headgear by the operating team. CONCLUSIONS: Further consideration and better trials are required to determine the impact of different theatre clothing on SSI rates.
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Controle de Infecções/métodos , Vestimenta Cirúrgica , Infecção da Ferida Cirúrgica/prevenção & controle , Humanos , Guias de Prática Clínica como AssuntoRESUMO
Melanocytic lesions with spitzoid differentiation represent a difficult management paradigm. Spitzoid lesions form a spectrum of distinct entities encompassing Spitz naevi, atypical Spitz naevi and spitzoid melanoma which range from benign to malignant. Differentiation between benign and malignant lesions can be challenging making surgical management difficult. In this article we highlight clinical conundrums regarding Spitz naevi. We review the literature in terms of the newer histological tools available to more explicitly classify these lesions which may have an impact on the clinical care that these patients receive. The article also examines the controversy which surrounds the role of sentinel lymph node biopsy (SLNB) and completion lymph node dissection in the management of melanocytic proliferations with Spitz differentiation.