Outcome and human epidermal growth factor receptor (HER) 1–4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labelling

BACKGROUND: We have shown previously that whereas overexpression of human epidermal growth factor receptor (HER)1, HER2 and HER3 is associated with poor prognosis in breast cancer, HER4 is associated with a good prognosis. Cell proliferation is a key component of aggressive cancers and is driven by growth factors. In this study, bromodeoxyuridine (BrdU)-derived proliferation indices are correlated with clinical outcome and HER1–4 status for further clarification of the differing roles for the HER family at a biological level. METHODS: Seventy-eight invasive breast cancers had BrdU labelling in vivo to determine the BrdU labelling index (BLI) and the potential tumour doubling time (T(pot)). Long-term clinical follow-up was available for these patients. We used immunohistochemistry to establish the HER1–4 status in 55 patients from the BrdU cohort. RESULTS: We demonstrate a significant correlation between high BLI values and breast cancer-specific death (P = 0.0174). Low T(pot )times were also significantly correlated with breast cancer-specific death (P = 0.0258). However, BLI did not independently predict survival in Cox's multiple regression analysis when combined with other prognostic factors such as size, grade and nodal status. Tumours found to be positive for HER1, HER2 or HER3 had significantly (P = 0.041) higher labelling indices, with HER1 also showing significantly higher indices when considered independently (P = 0.024). Conversely, HER4 positivity was significantly correlated (P = 0.013) with low BLI values, in line with previous data associating this receptor with good prognosis tumours. CONCLUSIONS: These results support the hypothesis that HER1–3 are associated with driving tumour proliferation, whereas HER4 is involved in a non-proliferative or even protective role

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

A nicotina atua como fator deletério na reparação da parede abdominal The nicotine has a deleterious effect on the healing of abdominal wall

OBJETIVO: Avaliar o efeito da nicotina na cicatrização da camada musculoaponeurótica da parede abdominal. MÉTODOS: Estudo experimental em que foram usados 16 ratos da raça Wistar pesando em média 210&plusmn; 8g, separados aleatoriamente em 2 grupos de 8. Nos animais do grupo A foi implantado disco de nicotina (Nicotinel Ò) na dose de 5mg/Kg de peso/dia no subcutâneo da região dorsal, trocado a cada dois dias, a partir do 5&ordm; dia antes da operação em que foi feita laparotomia mediana de 5 cm, até o 10º dia de observação. No grupo B (controle) foram usados discos de celulose com o mesmo diâmetro. Tubo de silicone multiperfurado foi implantado no subcutâneo a 1cm da lesão da parede abdominal. A camada musculoaponeurótica e a pele foram suturadas com fio de nylon 5-0. No 10&ordm; dia pós-operatório foi colhido 1ml de líquido seroso do tubo de silicone por punção percutânea para dosagem de pO2 e os animais receberam dose letal de anestésico. Foi ressecado um segmento da camada musculoaponeurótica com 2cm de largura para tensiometria, em seguida processado e corado em HE e tricrômico de Masson para análise quantitativa dos dados histopatológicos em sistema digitalizado. A análise estatística foi feita pelo ANOVA e teste Newman-Keuls, com significância 0,05. RESULTADOS: No grupo A a pO2 do líquido tecidual atingiu o valor 17,75&plusmn; 3,4 mmHg e no grupo B (controle) a pO2 = 40,75&plusmn; 6,4 mmHg (p<0,01). A resistência à tensão apresentou o valor de 728,5&plusmn; 161,75gf no grupo A e 1241,6&plusmn; 232gf no grupo de controle (p<0,01), coincidindo com os achados da pO2. A densidade média dos elementos histopatológicos estudados foi de 105&plusmn; 17,1 nos animais do grupo A e 146,2&plusmn; 8,8 no grupo B (p<0,01). CONCLUSÃO: após avaliação da pO2 tecidual, tensiometria e histopatologia, concluiu-se que a nicotina por via subcutânea exerce efeito deletério sobre a cicatrização de lesões da parede abdominal de ratos.<br>OBJETIVE: An experimental study was done to evaluate the effect of nicotine on the healing of abdominal wall. METHODS: Sexteen Wistar rats weighing 210&plusmn; 8g were randomly separated into two groups of eight rats each. In the group A Nicotine (Nicotinel Ò) was implanted in the back subcutaneous 5mg/Kg each two days, begining at the fifth preoperative day. A 5cm median laparotomy was done, sutured with nylon 5-0 and the rats were observed in individual cages. The group B (control) didn&rsquo;t use nicotine. A multiperfurated silicone tube was implanted subcutaneously near the abdominal sutured lesion. In the tenth postoperative day 1ml of serous liquid was harvested from the silicone tube and a pO2 dosage was done. The rats were killed with overdose of anesthetic. A 2cm width transversal segment of abdominal wall was submited to tensile strength test by a tensiometer. A biopsy of the sutured area including muscle, aporeurosis and peritoneum was processed for histopatologic analysis by a digitalised system. The data were processed by the ANOVA and Newman-Keuls tests, considering significant the differences when p<0,05. RESULTS: In the group A the pO2 on the tissue serous liquid reached 17,75&plusmn; 3,4 mmHg and in the group B (control) the pO2 = 40,75&plusmn; 6,4 mmHg (p<0,01). The tensile strength reached 728,5&plusmn; 161,75gf in the group A and 1241,6&plusmn; 232gf in the control one (p<0,01).The mean density of the histopatologic elements was 105&plusmn; 17,1 in group A and 146,2&plusmn; 8,8 in group B (p<0,01). CONCLUSION: after evaluation of tissue pO2 , tensiometry and histopatology, the data permited to conclude that the nicotine has a deleterious effect on the healing the abdominal wall of rats

Wound healing process in post-bariatric patients: an experimental evaluation

Bariatric surgery is the most effective treatment for morbid obesity. Despite this, side effects are recorded. One of them is redundant skin hanging from the patients' body causing both aesthetical and functional deformities. They can only be corrected with body contouring surgery, whose wound complication rate is very high in previously obese population. Despite several hypotheses, an adequate explanation is still awaited. The aim of our study was to evaluate the wound healing process in post-bariatric patients. Seven patients, six women and one man, were enrolled. They all were nonsmokers and nondiabetic. They all underwent biliopancreatic diversion (BPD). After 36&nbsp;months, abdominoplasty was performed. Biochemical parameters before and after bariatric surgery were evaluated. The content of total protein and hydroxyproline was assessed in multiple scar biopsies before and after BPD. Abdominoplasty horizontal scar skin samples were subjected to histological evaluation with Weigert-Van Gieson stain for elastic fibers and connectivum. All biochemical parameters analyzed were reduced post-BPD compared to the preoperative period. Tissue proteins were significantly reduced after BPD both in their totality and as hydroxyproline and hydroxyproline/total tissue protein. Histological evaluation revealed abnormal dermal elastic and collagen fibers. The cause of aberrant healing in massive weight loss body contouring is likely multifactorial. A relationship between nutritional state, wound collagen accumulation, and elastic fiber content seems to be only partially involved. The high mechanical stress of tissues before BPD probably influences the wound healing process after BPD

Evaluation and Outcomes of Women with a Breast Lump and a Normal Mammogram Result

BACKGROUND: Many women experience a breast lump. Clinical guidelines suggest that a normal mammogram result alone is not adequate to exclude a diagnosis of cancer. OBJECTIVE: To examine the characteristics of women with a breast lump and a normal mammogram that were associated with receiving further evaluation, and to examine cancer outcomes. DESIGN: Observational cohort. PARTICIPANTS: Women aged 35 to 70 years who participated in a population-based mammography registry and who did not have a history of breast cancer noted at the time of their mammogram that they had a breast lump, and had a “normal” (Breast Imaging Reporting and Data System 1 or 2) mammogram result (n=771). MEASUREMENTS: Telephone survey performed 6 months after the mammogram to ascertain information about evaluation. Cancer outcomes within 12 months of the index mammogram were confirmed through linkage with a cancer registry. RESULTS: Only 56.9% of women reported receiving an adequate evaluation for their breast lump, including a subsequent clinical breast exam, a visit to a breast specialist, an ultrasound, a biopsy, or aspiration. Latinas were less likely than white women to have received adequate evaluation, as were obese women compared with normal-weight women, and uninsured women compared with women with insurance. Among women with at least 12 months of follow-up, 1.4% were diagnosed with cancer. CONCLUSIONS: Many women do not receive adequate evaluation for a recent breast lump. Interventions should be designed to improve the follow-up of women with this common clinical problem