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Brain death (BD) affects organs by multiple mechanisms related to hemodynamic effects, hormonal changes, and the systemic inflammatory response, which reduce organ function and viability. BD reduces microcirculatory perfusion in rat mesentery; this disturbance is also observed in the pancreas and lungs. Sex hormones can affect microcirculatory function, altering tissue perfusion and influencing the inflammatory process. Here, we present differences between sexes in the microcirculatory alterations generated by BD and in inflammatory infiltrate. Male, female, and ovariectomized-female Wistar rats were submitted to BD by intracranial balloon catheter sudden inflation. BD was confirmed by maximally dilated and fixed pupils, apnea, absence of reflexes, and a drop in mean arterial pressure. Perfusion and flow of the mesenteric microcirculation were analyzed. Intestinal myeloperoxidase activity and leukocyte infiltration were quantified. ELISA quantified serum estradiol, corticosterone, and inflammatory mediators, whereas expression of eNOS, endothelin, and endothelial adhesion molecule was measured by immunohistochemistry. Male rats presented lower percentages of mesenteric perfused microvessels and reduced blood flow compared to females. The female group presented higher eNOS and endothelin expression. Leukocyte infiltration into intestinal walls was higher in females in comparison to that in males. Moreover, the female group showed higher mesenteric vessel ICAM-1 expression than males, whereas serum TNF-α, IL-1β, and IL-10 levels did not differ between sexes. The high estradiol concentration before BD and high eNOS expression apparently favored the maintenance of microvascular perfusion/flow; however, BD caused an acute reduction of female sex hormone concentration and higher ICAM-1 level; thus, the proinflammatory organ status after BD is favored.

Brazil. CNPq Researcher, level 1D. Scientific and intellectual content of the study; conception and design of the study; analysis and interpretation of data; statistical analysis; manuscript preparation and writing; critical revision; final approval. ABSTRACT PURPOSE:To investigate gender differences in the evolution of the inflammatory process in rats subjected to brain death (BD). METHODS:Adult Wistar rats were divided into three groups: female; ovariectomized female; and male rats. BD was induced using intracranial balloon inflation and confirmed by maximal pupil dilatation, apnea, absence of reflex, and drop of mean arterial pressure. Six hours after BD, histological evaluation was performed in lungs, heart, liver and kidneys, and levels of inflammatory proteins, estrogen, progesterone, and corticosterone were determined in plasma. RESULTS:In the lungs, females presented more leukocyte infiltration compared to males (p<0.01). Ovariectomized female rat lungs were more hemorrhagic compared to other groups (p<0.001). In the heart, females had higher leukocyte infiltration and tissue edema compared to males (p<0.05). In the liver and kidneys, there were no differences among groups. In female group estradiol and progesterone were sharply reduced 6 hours after BD (p<0.001) to values observed in ovariectomized females and males. Corticosterone levels were similar. CONCLUSIONS:Sex hormones influence the development of inflammation and the status of organs. The increased inflammation in lungs and heart of female rats might be associated with the acute reduction in female hormones triggered by BD.

PurposeLimited data are available about the tolerability and clinical outcomes of elderly patients with metastatic castration-resistant prostate cancer (mCRPC) who are treated with docetaxel. We evaluated the efficacy and safety of docetaxel as first-line chemotherapy for patients with mCRPC who were treated in our institution.Materials and MethodsWe retrospectively identified patients with mCRPC and a Karnosfky performance status of 60% or greater treated with docetaxel on any schedule as first-line chemotherapy between 2008 and 2013. The primary end point was a comparison of median overall survival (OS) according to age in this population. Secondary end points were comparisons of the rates of severe toxicities, prostate-specific antigen (PSA) decline of 50% or greater, and time to progression (TTP). Results were stratified by three age groups: younger than 65 years, 65 to 74 years, and 75 years or older.ResultsAmong the 197 patients included, 68 (34%) were younger than 65 years, 85 (43%) were 65 to 74 years, and 44 (22%) were 75 years or older. The mean number of comorbidities was not different among groups (1.19 v 1.32 v 1.43; P = .54). Patients younger than 65 years received a higher cumulative dose of docetaxel (450 mg/m2 v 382 mg/m2 v 300 mg/m2; P = .004). The rates of PSA decline of 50% or greater (41% v 47% v 36.4%; P = .51) and the median TTP (5.13 v 5.13 v 4.7 months; P = .15) were comparable among all groups. The median OS was longer in the group of patients younger than age 65 years (19.6 v 12.4 v 12.3 months; P = .012). Rates of any grade 3 or higher adverse event were not different among groups (63.2% v 71.8% v 54.5%; P = .14).ConclusionAdministration of docetaxel in elderly patients who had good performance status was well tolerated. Rates of PSA decline and TTP were similar to those of younger patients, but median survival was lower.

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Introduction: Failure to accurately estimate energy requirements may result in an impaired recovery. Overfeeding has been associated with increased carbon dioxide production, respiratory failure, hyperglycemia and fat deposits in the liver, while underfeeding can lead to malnutrition, muscle weakness and impaired immunity. Objective: This study aimed to determine the metabolic profile of infant and preschool children submitted to mechanical ventilation in the ICU. Methods: A prospective study was carried out in a pediatric ICU in Rio de Janeiro that included children aged from 1 month to 6 years submitted to mechanical ventilation from June 2013 to May 2015. Indirect calorimetry was used to obtain resting energy expenditure (REE) and oxygen consumption (VO 2) in the first 48 hours of admission. The predicted basal metabolic rate (PBMR) was calculated using the Schofield equation. The metabolic state of each patient was assigned as hypermetabolic (REE/PBMR >110%), hypometabolic (REE/PBMR <90%) or normal (REE/PBMR 90-110%). The ratio of caloric intake to REE was also calculated and ratios of >1.5 and <0.5 were classified as overfeeding and underfeeding respectively. Results: A total of 35 infants and 17 preschool children were included. The male/female ratio was 34/18. In respect of severity of sepsis, 19 patients had septic shock, 24 had sepsis, five had severe sepsis and four had systemic inflammatory response syndrome. We observed a high incidence of hypometabolism (88.5%) and a low incidence of normal metabolism (7.7%) and hypermetabolism (3.8%). A low value of VO 2 was observed in 46.1% of the patients (VO 2 ≤120 ml/minute/m 2), a normal value in 40.4% (VO 2 >120 to ≤160 ml/minute/m 2) and a high value in only 13.5% of the patients (VO 2 > 160 ml/minute/m 2). Among the 52 included patients, 18 were fasting at the moment of the examination. The ratio of caloric intake to REE for the remaining 34 patients showed 38.2% overfeeding, 11.8% underfeeding and 50.0% normal feeding. Conclusion: Predictive equations do not accurately predict REE in critically ill infants and preschool children, resulting in inadequate feeding. Although hypermetabolism and enhanced energy expenditure are the main clinical features of critical illness in adults, the majority of our patients were found to be hypometabolic which reinforces the need for a different approach between adult and pediatric critically ill patients.