Primary Peritoneal Carcinosarcoma in a Breast Cancer Patient Harboring a Germline BRCA2 Pathogenic Variant: Case Report

Malignant mixed müllerian tumor (MMMT) is a rare neoplasm, consisting of carcinomatous (epithelial) and sarcomatous (mesenchymal) components that most commonly arise in the endometrium and more infrequently in the ovaries, fallopian tube, cervix, and vagina. Primary peritoneal carcinosarcoma (PPCS) is an extremely rare extragenital presentation of MMMT. Although the occurrence of breast cancer and epithelial ovarian carcinoma in association with BRCA pathogenic variants is firmly established, the etiologic role of these genes in the development of other tumor types is less well known. Here, we present a rare case of PPCS in a 42-year-old Brazilian woman with a BRCA2 pathogenic variant, c.2808_2811del (NM_000059.3). The patient developed metastatic breast cancer at the age of 37 and underwent a risk-reducing bilateral salpingo-oophorectomy 2 years later. She was then diagnosed with PPCS 3 years after the risk-reducing surgery. She underwent treatment with surgery, chemotherapy, and targeted therapy but passed away almost 5 years after the second primary tumor diagnosis. To our knowledge, this is the first case of peritoneal carcinosarcoma described in a BRCA2 pathogenic variant carrier, and its report leads to a better understanding of the disease’s molecular features and possible therapeutic approaches

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Effects of active smoking on airway and systemic inflammation profiles in patients with chronic obstructive pulmonary disease

Background: The markers that characterize local and systemic inflammation in chronic obstructive pulmonary disease (COPD) remain unclear, as do their correlations with smoking status and presence of disease. The aim of this study was to assess markers of inflammation in the peripheral blood and airways of current smokers without COPD, of current smokers with COPD and of ex-smokers with COPD. METHODS: In this study, 17 current smokers with COPD (mean age: 58.2 ± 9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 ± 15.9%), 35 ex-smokers with COPD (mean age: 66.3 ± 7.3 years; mean FEV1: 47.9 ± 17.2%) and 20 current smokers without COPD (mean age: 49.1 ± 6.2 years; mean FEV1: 106.5 ± 15.8%) were evaluated. Spirometry findings, body composition and serum/induced sputum concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP) levels, were assessed. RESULTS: Serum TNF-α concentration was higher in all current smokers than in ex-smokers with COPD. In current smokers without COPD, serum CRP level was lower than in ex-smokers with COPD and significantly lower than in current smokers with COPD. Sputum TNF-α concentration was higher in current and ex-smokers with COPD than in current smokers without COPD. Multiple regression analyses showed that serum TNF-α was associated with active smoking, and serum CRP and sputum TNF-α were associated with COPD diagnosis. CONCLUSIONS: Smoking is associated with higher systemic inflammation in patients with COPD. Current findings also support the hypothesis that smoking and COPD have different effects on the regulation of airway and systemic inflammatory processes. © 2013 Lippincott Williams and Wilkins

Redox imbalance is related to HIV and pregnancy.

Redox imbalance may compromise the homeostasis of physiological processes indispensable to gestational development in HIV-infected women. The present study aims to evaluate markers of the redox system in the development of pregnancy of these women. HIV-positive pregnant women, HIV-negative pregnant women and non-pregnant were studied. Redox markers superoxide dismutase (SOD), catalase (CAT), protein carbonylation and malondialdehyde (MDA) were assessed at first or second trimester, third trimester and postpartum from pregnant and from non-pregnant women. According to the longitudinal analysis model, CAT activity was increased in the postpartum in HIV-positive women and before delivery in HIV-negative women. Increased carbonylation was observed in the pre-delivery period of HIV-negative pregnant women and MDA concentrations were higher in HIV-positive pregnant women compared to those non-infected by HIV at all times. According to the factorial model, higher SOD and CAT activities were observed in HIV-positive women in the initial months of pregnancy and in non-pregnant women. Carbonylation at third trimester was more evident in HIV-negative pregnant women. MDA levels were higher in HIV-positive pregnant women. Increased oxidative stress may occur in HIV-infected pregnant women. Nevertheless, the HIV virus is not solely responsible for this process; instead, mechanisms inherent to the pregnancy seem to play a role in this imbalance

Influence of ozonated water sanitation on postharvest quality of conventionally and organically cultivated mangoes after postharvest storage

We investigated the alterations on bioactive compounds after treatments with ozonated water during the storage of organically and conventionally cultivated mangoes, cv. Palmer. Mangoes were stored in a cold chamber (14 ± 2 °C) for 15 d and evaluated after the harvest and sanitization treatments (chlorine and ozonated water—10 and 20 min) at 7 and 15 d. To simulate the market, after 7 d, mangoes were removed from cold storage and kept at room temperature (27 ± 2 °C) to be analyzed following 4 (7 + 4) and 8 (7 + 8) d at room temperature. The conventionally mango showed higher firmness, regardless of the sanitization system used. Ozonated water did not alter the levels of β-carotene, ascorbic acid, dehydroascorbic acid and phenol in organically or conventionally cultivated mangoes during storage, but when the mangoes, cv. Palmer were transferred to room temperature, the β-carotene level increased. Organically cultivated mangoes showed higher levels of antioxidant activity. Ozonated water can be used as an alternative to chlorine sanitizer without causing damage to mango, cv. Palmer fruit or inducing a decrease in the various compounds and the treatment using ozonated water was efficient for maintaining fruit without microorganisms, preventing the reduction of quality and avoiding the generation of organic waste