Relative adrenal insufficiency and hemodynamic status in cardiopulmonary bypass surgery patients. A prospective cohort study.

BACKGROUND: The objectives of this study were to determine the risk factors for relative adrenal insufficiency in cardiopulmonary bypass patients and the impact on postoperative vasopressor requirements. METHODS: Prospective cohort study on cardiopulmonary bypass patients who received etomidate or not during anesthetic induction. Relative adrenal insufficiency was defined as a rise in serum cortisol

Prognostic value of inflammatory markers (notably cytokines and procalcitonin), nutritional assessment, and organ function in patients with sepsis.

OBJECTIVE: Procalcitonin is useful for the diagnosis of sepsis, but its prognostic value regarding mortality is unclear. Our objective was to determine the prognostic value of procalcitonin determined at the onset of sepsis, and to compare it with other markers of inflammatory response, malnutrition and organ dysfunction data. METHODS: We studied 253 hospitalized patients (146 men, 107 women) with a median age of 65 years. Sepsis was defined as infection, and at least two SIRS criteria. We assessed co-morbidities, nutritional status, bacteremia, procalcitonin and other inflammatory markers (PCR, TNF-alpha, IL6, TREM-1, IL-10, IL-1ra, CD14 and LBP), and organ function using the SOFA score. Mortality was assessed at 28 days after onset of sepsis. RESULTS: At day 28, 49 (19%) patients had died. Inflammatory markers showed only moderate predictive value for mortality, with IL-10 and IL-6 being the best predictors. Mortality was mainly related to organ dysfunction indicators (SOFA and Glasgow scores), serum lactate, ferritin and LDH levels, and to nutritional data such as subjective assessment, handgrip strength and serum transferrin levels. The most frequent location of sepsis was the lung, with 140 cases (55%), which showed more comorbidity, worse nutritional status, less frequent bacteremia and lower inflammatory response. When the analysis was limited to patients with non-pulmonary sepsis, organ dysfunction, nutritional status and inflammatory markers showed the best prognostic value. Of the inflammatory markers, procalcitonin showed only moderate predictive value; however it showed the highest correlation with bacteremia and the ability to discriminate non-complicated sepsis from severe forms. CONCLUSION: Procalcitonin only showed moderate predictive value for sepsis-related mortality, being surpassed by organ dysfunction, nutritional status, IL-10 and IL-6. However, it proved useful to discriminate between non-complicated and severe forms of sepsis.

Serum leptin levels in community acquired pneumonia (CAP) are related to nutritional status and not to acute phase reaction.

To determine whether leptin in patients with CAP acts as a nutritional or as an inflammatory marker and whether leptin plays any role regarding survival, we included 222 patients diagnosed of CAP, 142 men and 80 women, median age 74 years. We did not find significant differences in serum leptin levels between CAP patients and healthy controls, even after adjusting by BMI. Serum leptin levels were directly related with BMI, body fat and muscle mass and inversely related with inflammatory markers, including pro- and anti-inflammatory cytokines. Patients with positive blood cultures showed lower serum leptin and raised inflammatory markers. Although patients who died showed lower values of serum leptin, multivariate analysis showed that the prognostic value of low serum leptin levels depends on impaired nutritional status. In conclusion, we suggest that in CAP patients, leptin does not act as an inflammatory reactant but as a nutritional marker.

Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial.

INTRODUCTION: Extracorporeal circulation induces hemostatic alterations that lead to inflammatory response (IR) and postoperative bleeding. Tranexamic acid (TA) reduces fibrinolysis and blood loss after cardiopulmonary bypass (CPB). However, its effects on IR and vasoplegic shock (VS) are not well known and elucidating these effects was the main objective of this study. METHODS: A case control study was carried out to determine factors associated with IR after CPB. Patients undergoing elective CPB surgery were randomly assigned to receive 2 g of TA or placebo (0.9% saline) before and after intervention. We performed an intention-to-treat analysis, comparing the incidence of IR and VS. We also analyzed several biological parameters related to inflammation, coagulation, and fibrinolysis systems. We used SPSS version 12.2 for statistical purposes. RESULTS: In the case control study, 165 patients were studied, 20.6% fulfilled IR criteria, and the use of TA proved to be an independent protective variable (odds ratio 0.38, 95% confidence interval 0.18 to 0.81; P < 0.01). The clinical trial was interrupted. Fifty patients were randomly assigned to receive TA (24) or placebo (26). Incidence of IR was 17% in the TA group versus 42% in the placebo group (P = 0.047). In the TA group, we observed a significant reduction in the incidence of VS (P = 0.003), the use of norepinephrine (P = 0.029), and time on mechanical ventilation (P = 0.018). These patients showed significantly lower D-dimer, plasminogen activator inhibitor 1, and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB. CONCLUSION: The use of TA attenuates the development of IR and VS after CPB.

Low serum leptin levels and malnutrition in chronic alcohol misusers hospitalized by somatic complications.

AIMS: Leptin is a peptide produced by fat cells which regulates fat mass by decreasing food intake and increasing resting energy expenditure, so an increase of serum leptin could be an indicator of malnutrition. Our objective was to determine serum leptin levels (at admission and on the 15th day) in 79 male alcohol misusers, hospitalized by somatic complications, who drink more than 80 g ethanol/day, and to analyse its relationships with nutritional status assessed by anthropometry and dual-energy X-ray absortiometry (DEXA), insulin-like growth factor (IGF-1) and its binding protein (IGF1BP-3); acute phase reaction assessed by C-reactive protein (CRP), interleukin-6 (IL-6) and type II soluble receptor of tumour necrosis factor (TNF) (sTNFRII); serum oestradiol and testosterone; and the amount and duration of ethanol intake, the smoking habit and the presence of liver cirrhosis. METHODS: Patients were admitted through the emergency room, and blood for the above-mentioned determinations was taken at 08.00 on the following day, so none of the patients was acutely intoxicated at this time. The control group was composed of 32 healthy male (age-matched) subjects. RESULTS: Malnutrition was frequent among alcoholics. Serum leptin levels were closely related to total fat both in controls and in alcoholics. Serum leptin levels were decreased in alcoholics, even after adjusting for the amount of fat. Those alcoholics who reported anorexia and weight loss showed decreased leptin levels. After 15 days of hospitalization, serum leptin did not increase, in contrast with LDL cholesterol, serum albumin, prealbumin, IGF-1, IGF1BP-3 and testosterone which increased, whereas oestradiol and acute phase reactants, such as CRP, IL-6 and sTNFRII, were decreased. Serum leptin was not related to gonadal hormones at admission, but on day 15 we found a negative correlation between leptin and testosterone, and a positive one with oestradiol. CONCLUSIONS: Serum leptin levels are related to many factors, e.g. fat mass, age, smoking, serum testosterone and oestradiol levels, growth factors such as IGF-1 and CRP, and cytokines, such as IL-6 and sTNFRII. The most important of these is fat mass, as shown by multivariate analysis. Since serum leptin levels are decreased in alcohol misusers, we consider this decrease to be a consequence of a low fat mass.

Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition?

Leptin is an anorexia inductor peptide produced by adipocytes and related to fat mass. Leptin is also produced by fat under proinflammatory cytokine action. Our objective is to study serum leptin levels in relation to nutritional status and acute phase response in advanced-stage non-small cell lung cancer.Seventy-six patients newly diagnosed of non surgical non-small cell lung cancer before chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin and cholesterol levels and lymphocyte count were decreased in lung cancer patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma, and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and platelets were all raised in patients, whereas the IL-2 was decreased. We found a direct relationship between leptin and other indicators of the status of nutrition, especially total fat mass. We also found a close relationship between the status of nutrition and the performance status (Karnofsky index). However, serum leptin and nutritional status were inversely correlated with acute phase proteins and proinflammatory cytokines, suggesting a stress-type malnutrition. Although serum leptin levels, nutritional status and Karnofsky index are related to survival, at multivariate analysis they all were displaced by the acute phase reaction markers. These results suggest that cancer anorexia and cachexia are not due to a dysregulation of leptin production. Circulating leptin concentrations are not elevated in weight-losing cancer patients and are inversely related to the intensity of the inflammatory response. In advanced lung cancer patients serum leptin concentrations only depend on the total amount of fat.

Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation: a randomized placebo-controlled study.

BACKGROUND: Dietary fish oil, rich in omega-3 polyunsaturated fatty acids, decreases TNF-alpha, IL-1beta and IL-2 levels, which may benefit renal transplant recipients. To explore this possibility, we studied the effect of fish oil on the incidence of acute rejection, in situ expression of interleukins (TNF-alpha, IL-1beta and IL-2) and renal function after renal transplantation. METHODS: In a double-blind clinical trial, 86 subjects with no immunological risk randomly received either 6 g/day of fish oil (fish oil group; n=46) or soy oil (control group; n=40) during the first 3 months after transplantation. The mRNA expression of interleukins (TNF-alpha, IL-1beta and IL-2) was determined by RT-PCR using fine-needle aspiration during follow-up (at baseline and the 1st, 2nd and 3rd month after renal transplantation), as well as during acute rejection episodes and after anti-rejection therapy. The glomerular filtration rate was determined at baseline, and at 1 and 3 months post-graft by [(51)Cr]EDTA clearances. RESULTS: The incidence of acute rejection during the first post-transplant year was similar in both groups (44 vs. 47%), as was 1-year graft survival (86 vs. 89%). There were no differences between groups in overall renal expression of interleukins in patients who did not suffer rejections during the study. At rejection episodes, the fish oil group showed a trend toward a lower renal expression of TNF-alpha (3.7+/-6.8 vs. 15+/-18.6 TNF-alpha/actin, ratio of arbitrary optical units; P=0.05). In addition, a trend toward a lower IL-1beta expression after therapy was observed in the fish oil group (49.3+/-54 vs. 84.4+/-59 IL-1beta/actin, ratio of arbitrary optical units; P=0.05). However, the severity of acute rejections (Banff criteria) as well as renal function after anti-rejection treatment were similar in both groups. Finally, a greater reduction in triglyceride levels was observed in the fish oil group compared with the control group (-6.6+/-52.7 vs. 12.7+/-40.2%; P<0.05). CONCLUSIONS: Treatment with fish oil during the first 3 months post-transplantation does not influence acute rejection rate and has no beneficial effect on renal function or graft survival.