Routine four-quadrant cavity shaving at the time of wide local excision for breast cancer reduces re-excision rate.

INTRODUCTION: Breast conservation therapy (BCT) has been shown to have comparable long-term survival outcomes when compared with mastectomy. Clearance of excision margin is one of the mainstays of the surgical treatment, which if not achieved at the first operation of BCT results in the need for subsequent surgery. METHODS: This study evaluated the impact of routinely taken cavity shavings on re-excision rates. This retrospective two-centre study describes the use of routine four-quadrant cavity shaving in 449 patients with consecutively treated with wide local excision for invasive cancer or ductal carcinoma in situ. RESULTS: The overall incomplete excision rate was 10.6%. Routine cavity shaving prevented the need for re-excision in 84 patients (18.7%) and identified the need for further re-excision in 33 patients (7.3%). Median time from surgery to radiotherapy was 50 days (range 13-209) for non-re-excised patients versus 78 days (range 47-260) for re-excised patients (p<0.001). Median time to chemotherapy (n=75) was 44 days (range 14-106) for non-re-excised patients versus 56 days (range 35-116) for re-excised patients (p=0.017). CONCLUSIONS: This study demonstrates that routine cavity shaving decreases re-excision rate in patients treated with wide local excision and prevents delays to adjuvant treatment due to incomplete excision.

The effect of postoperative complications on survival and recurrence after surgery for breast cancer: A systematic review and meta-analysis.

BACKGROUND: This systematic review investigated the impact of complications on long term outcomes for patients with primary invasive operable breast cancer. METHODS: A systematic review was performed using appropriate keywords, and meta-analysis using a random effects model completed. RESULTS: Ten retrospective cohort studies, including 37,657 patients were included. Five studies identified a relationship between wound complications, infection and pyrexia and recurrence or recurrence-free survival. Risk of recurrence, 1-year and 5-year recurrence-free survival and overall survival were related to complications, particularly for patients with poor Nottingham Prognostic Index. Five studies failed to demonstrate a relationship between complications and prognosis. Complication was found to significantly affect 5-year recurrence-free survival (HR 1.48 95 % CI 1.02-2.14, p = 0.04) but not recurrence (HR 2.39, 95 %CI 0.94-6.07, p = 0.07), with a high degree of heterogeneity amongst analysed studies (I2 = 95 %). DISCUSSION: Further research is needed to quantify the effects of postoperative complication on prognosis following surgery for breast cancer.

Importância da avaliação geriátrica ampla na decisão do tratamento da estenose aórtica grave / Importance of broad geriatric assessment in deciding treatment of severe aortic stenosis

INTRODUÇÃO: A Estenose Aórtica (EAo) é extremamente prevalente em idosos e, quando sintomática, influencia de forma significativa na qualidade e expectativa de vida. Decidir entre o tratamento clínico, percutâneo ou cirúrgico é uma árdua tarefa e deve valorizar, não apenas os aspectos cardiológicos, mas todo o contexto do idoso. O objetivo deste estudo foi utilizar a Avaliação Geriátrica Ampla (AGA) como ferramenta para decisão do tratamento de idosos portadores de EAo Grave Sintomática. MÉTODOS: Selecionados pacientes acima de 75 anos atendidos em ambulatório específico de hospital terciário de São Paulo-SP, de outubro de 2018 a janeiro de 2019, com EAo Grave (área valvar <0,8cm² e gradiente sistólico médio >40mmHg) e sintomas de angina, síncope, dispneia ou sinais de insuficiência cardíaca congestiva. A AGA englobava aspectos da Funcionalidade (Katz e Lawton), Fragilidade (FRAIL), Cognição (Mini-exame do estado mental, teste do relógio, fluência verbal), Depressão (Escala de Depressão Geriátrica) e Estado Nutricional/Sarcopenia (força de preensão palmar, circunferência de panturrilha e velocidade da marcha). Baseados nesta avaliação, integrantes do heart team (clínicos, hemodinamicistas, ecocardiografistas e cirurgiões) se reuniam e chegavam ao consenso de qual tratamento indicar. Estudo observacional, prospectivo, descritivo e aprovado pelo comitê de ética. A estratificação do risco cirúrgico foi feita pelo EuroSCORE II. As variáveis quantitativas foram apresentadas em forma de média e desvio padrão. RESULTADOS: Dos 10 pacientes portadores de EAo Grave Sintomática avaliados, a média de idade foi 83,8 anos (±3,7), sendo 55% homens. Quanto à funcionalidade, 70% eram parcialmente dependentes para atividades diárias; 30% frágeis, 40% tinham humor deprimido, 70% apresentavam boa cognição (de acordo com a escolaridade) e 20% arcopenia e risco de desnutrição. Nos pacientes com EuroSCORE II de alto risco, 20% também apresentavam fragilidade, sendo mantidos em tratamento clínico. Os classificados como risco baixo a intermediário não apresentavam fragilidade associada e foram submetidos à troca valvar aórtica, via aberta ou transcateter (TAVR). CONCLUSÃO: Os achados da AGA, somados aos aspectos clínicos e ecocardiográficos habitualmente utilizados na cardiologia atual, constituem ferramenta importante para a decisão terapêutica em idosos portadores de EAo Grave e Sintomática. (AU)

Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use.

The biocompatibility of two cyanoacrylate surgical glues (Glubran and Glubran 2), supplied by General Enterprise Marketing, Viareggio, Lucca, Italy, was tested through cytotoxicity and blood compatibility tests and the evaluation of antimicrobial activity. Cytotoxicity and blood compatibility tests were performed on the polymerized glues. Using the neutral red uptake test, the extracts from Glubran and Glubran 2 after polymerization were non-toxic to L929 cells only when diluted 1: 10 with culture medium. Glubran and Glubran 2 induced a significant decrease of activated partial thromboplastin time (APTT), which is favourable with regard to the desired haemostasis. The APTT shortening determines a haemostatic effect and therefore contribute to the tissue adhesion induced by the glues. Otherwise, no significant variation of prothrombin activity, fibrinogen, platelet number, total and differential leukocyte count was induced by the glues, which, in addition, did not show haemolytic effect. There was no difference between Glubran and Glubran 2 regarding haemocompatibility. The antimicrobial ability of the unpolymerized glues was tested onto Bacillus subtilis var. niger for 3 weeks: neither Glubran nor Glubran 2 were found effective in this respect. In conclusion, we can assume that cytotoxicity was severe with the undiluted glues, but was acceptable when glues were diluted. On the contrary, blood compatibility was acceptable for the intended use of the glues. No difference was found between Glubran and Glubran 2 after polymerization.

In vitro testing of the responses of human gingival fibroblasts and L-929 cells to nicotine.

Tobacco smoke is considered to be a major risk factor in the development of cardiac diseases and lung cancer. It has also been shown that periodontitis is more prevalent and more severe in smokers than in non-smokers. Nicotine, the major pyridine alkaloid in tobacco, has been shown to participate in periodontal disease, exerting both local and systemic effects. In the present study, the effects of nicotine (6µg/ml, 60µg/ml and 600µg/ml) on human gingival fibroblasts (HGF) were assessed by using various exposure protocols. The responses of HGF cultures obtained from smokers and non-smokers were compared to those found when using a continuous cell line (L-929). Neutral red uptake (NRU) and the measurement of DNA content with bis-benzimide dye were used to assess cell viability and cell number, respectively. NRU was the most sensitive technique for the detection of cytotoxic effects. L-929 cells were found to be affected by nicotine in the NRU assay, with a strong cytotoxic effect with 600µg/ml nicotine, and a "response" with 60µg/ml nicotine when prolonged or double challenge was applied. Non-smoker HGF and smoker HGF reacted to nicotine in different ways, depending on the concentrations and the exposure times used, but had identical reactions following double exposure. With the Hoechst DNA assay, 600µg/ml nicotine was found to affect the growth of non-smoker HGF after long or repeated exposure, while smoker HGF were affected only by repeated exposure; growth of L-929 cells was not affected. It was concluded that HGF from smokers are able to sustain higher concentrations of nicotine without adverse effects than are non-smoker HGF and L-929 cells. If this occurs in vivo, nicotine would not be considered to be a major toxicant to HGF in smokers.

Cytotoxicity testing of materials with limited in vivo exposure is affected by the duration of cell-material contact.

Silicones for dental impression largely are used to record the geometry of hard and soft dental tissues. They are considered to be medical devices, and the assessment of cytotoxicity is a necessary step in the evaluation of their biocompatibility. Extracts of six addition-type and six condensation-type silicones have been tested with L929 cells according to the ISO 10993-Part 5 standard. The cytotoxicity was evaluated by three different methods: neutral red uptake, propidium iodide (PI) staining, and amido black staining. According to the selected specific assay, contact between cells and material extracts was maintained for 24 h in the first series of experiments; then, considering that in vivo application of these materials is restricted to a few minutes, additional experiments were performed after 1 h of cell/extract contact. Analysis of the results showed that the addition-type silicones are nontoxic even when tested after prolonged exposure of the cells to the materials while the condensation-type silicones were cytotoxic at 24 h of incubation. Nevertheless, harm to the patient actually could be negligible, considering its very short time of exposure in vivo. This is supported by our finding that most are not toxic after 1 h. We suggest that the experimental conditions of cytotoxicity testing have to be relevant to the in vivo situation; accordingly, the time of exposure should be designed carefully.

Fluorescent microplate assay for respiratory burst of PMNs challenged in vitro with orthopedic metals.

This report describes a simple, rapid, automated microassay for measuring in vitro changes of oxidative burst of phagocytes following challenge with metals for orthopedic devices. The production of reactive oxygen species (ROS) by polymorphonuclear leukocytes (PMNs) was measured using 2',7'-dichlorofluorescin-diacetate (DCFH-DA) as fluorescent probe. DCFH-DA enters the cells and is oxidized by ROS to fluorescent DCF. The DCF generated was directly proportional to ROS produced intracellularly: The fluorescence intensity was read and converted to an index of ROS production by cells. In our experimental system, granulocytes (PMNs) were isolated from normal human blood and seeded in microplates. To verify if metals could influence ROS production, chromium, cobalt, nickel, molybdenum, titanium, aluminum, and vanadium prepared as aqueous extracts in phosphate-buffered saline were tested onto PMNs using phorbolmyristate acetate (PMA) as positive control. Molybdenum, aluminum, and vanadium increased ROS generation by PMNs, while signals not different from unstimulated PMNs were recorded for chromium, cobalt, nickel, and titanium. The DCFH-DA microplate-based assay provides an in vitro tool for the detection of oxygen-reactive species generated by PMNs as a response to metals.

False positive results in cytotoxicity testing due to unexpectedly volatile compounds.

We investigated the cytotoxicity of different dental materials according to the study protocol adopted by our lab for the screening of new materials. Experimental parameters used in such testing are addressed mainly in documents EN 30993 "Biological evaluation of medical devices, Part 5: Tests for cytotoxicity: in vitro methods" and "Biological evaluation of medical devices, Part 12: Sample preparation and reference materials." Cells were cultured in microplates and challenged with aqueous extracts of the materials. The assay methods were neutral red- and propidium iodide-uptake assays, both indicative of cell viability and able to provide quantitative data. The observation of contrasting results for one material using the above-mentioned methods raised some concern about the assay system used. With further experimentation, it appeared that a sustained release of volatile substances still present in one extract exerted a toxic effect in neighboring cultures. It is concluded that in the microenvironment of a microplate the distribution of samples cannot be disregarded, as it may be responsible for toxicity cross-contamination. Moreover, the use of more than one single method has to be recommended in cytotoxicity testing, in order to avoid false positive results due to experimental artifacts.

Estudo multicêntrico de idosos em ambulatórios de cardiologia e geriatria de instituiçöes brasileiras / Multicenter study of elderly patients in outpatient clinics of cardiology and geriatric brazilian institutions

OBJETIVO - Avaliar aspectos epidemiológicos, clínicos e terapêuticos de idosos com doenças cardiovasculares (DCV), no Brasil. MÉTODOS - Idosos com DCV, atendidos em 36 serviços de Cardiologia e Geriatria do Brasil, foram investigados através de questionário aplicado aos que tinham consulta marcada para o período analisado (um mês). RESULTADOS - Estudados 2196 idosos de 65 a 96 anos, sendo 60 'por cento' mulheres e analisados od fatores de risco: sedentarismo (74 'por cento'), pressão arterial (PA) elevada (53 'por cento'), LDL colesterol aumentado (33 'por cento'), colesterol total aumentado (30 'por cento'), obesidade (30 'por cento'), HDL -colesterol diminuído (15 'por cento'), diabetes (13 'por cerno') e tabagismo (6 'por cento'). Observou-se maior prevalência nas mulheres, com três ou mais fatores de risco. O principal motivo de consulta foi a PA elevada (48 'por cento'). Teste ergométrico e cinecoronariografia, foram mais solicitados para os homens. Os diagnósticos mais comuns foram hipertensão arterial sistêmica (HAS) (67 'por cento') e insuficiência coronária (iCo) (29 'por cento'). Os medicamentos mais utilizados foram diuréticos (42 'por cento'). CONCLUSÄO - Foi observada alta prevalência de fatores de risco (93 'por cento'), principalmente nas mulheres; sedentarismo, como fator de risco mais freqüente, aumentando de prevalência com a idade; HAS, como principal motivo de consulta e diagnóstico; menor investigação e diagnóstico de iCo em mulheres; diuréticos, como os fármaco mais freqüentemente prescritos; insuficiência cardíaca como principal doença associada a internação (31 'por cento') e atendimento de emergência (10 'por cento').

[Multicenter study of elderly patients assisted at outpatient cardiology and geriatrics clinics in Brazilian institutions]. / Estudo multicêntrico de idosos atendidos em ambulatórios de cardiologia e geriatria de instituições Brasileiras.

PURPOSE: To evaluate epidemiological, clinical and therapeutic aspects of elderly patients with cardiovascular disease in Brazil. METHODS: Elderly patients with cardiovascular disease treated in 36 centers of cardiology and geriatrics were investigated through a questionnaire applied to those who had an appointment during the analyzed period. RESULTS: 2196 elderly patients ranging from 65 to 96 years of age were analyzed, 60% of which were females. The main risk factors were: sedentarism (74%); high blood pressure (53%), high LDL-cholesterol (33%), high total cholesterol (30%), obesity (30%), low HDL-cholesterol (15%), diabetes (13%) and smoking (6%). A higher prevalence of females existed among those with > or = 3 risk factors. The main reason for the medical appointment was high blood pressure (48%). Stress test and coronariography were requested more often in males. The most common diagnoses were hypertension (67%), and coronary disease (29%). The most often used medications were diuretics (42%). CONCLUSION: There was high prevalence of risk factors (93%), mainly in females; sedentarism was the most common risk factor and prevalence increased with age; hypertension was the most common reason for a medical appointment. Diuretics were the most used drugs; congestive heart failure was the main disease associated to hospitalization (31%) and emergencies (10%).

Atividade física em médicos / Physical activity in physicians

Os autores chamam a atençäo para a alta incidência de sedentarismo entre médicos de Säo Paulo, Brasil. Supöe-se que isso se deva à falta de tempo livre durante o período de graduaçäo médica e mesmo após seu término. esse estilo de vida sedentário ocorre apesar do seu conhecimento sobre prevençäo das doenças e parece persistir pelo restante de suas vidas.