Antonio Milena

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

IntroductionExtracorporeal 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.MethodsA 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.ResultsIn 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.ConclusionThe use of TA attenuates the development of IR and VS after CPB.Trial registration numberISRCTN05718824.

Osteopenia assessed by body composition analysis is related to malnutrition in alcoholic patients

Osteopenia is frequent among alcoholics. Its pathogenesis seems to be multifactorial, including ethanol intake, hormonal changes, liver cirrhosis, and malnutrition. Our objective is to determine the relative role of malnutrition on bone loss. One hundred and eighty-one male alcoholic patients, drinkers of more than 80 g ethanol/day, were included, recording data on the intensity of alcoholism, liver cirrhosis, nutritional assessment based on feeding habits, body mass index (BMI), midarm anthropometrics, subjective nutritional assessment, lean and fat mass by dual energy X-ray absorptiometry (DEXA), serum proteins and insulin growth factor Type I (IGF-I), calcitropic hormones, parathyroid hormone (PTH), osteocalcin 25OHD3, and bone mass assessed by DEXA, which was also performed in 43 healthy controls. Alcoholics showed decreased serum osteocalcin, PTH, 25OHD3, IGF-I, and bone mass. Alcoholics were frequently malnourished with decreased BMI, lean, and fat mass. The loss of bone mass was not related to the alteration of calcitropic hormones, to the intensity of alcoholism, or to the existence of liver cirrhosis, but to malnutrition. For a similar BMI, bone loss was more intense in alcoholics than in controls, especially in those with irregular feeding habits. Although cross-sectional ones, our data suggest that alcoholic osteopenia may be interpreted as a form of nutritional osteoporosis, notwithstanding the influence of other factors.

High prevalence of hyperhomocysteinemia in chronic alcoholism: the importance of the thermolabile form of the enzyme methylenetetrahydrofolate reductase (MTHFR)

Alcoholism is related to malnutrition and low levels of several vitamins that take part in the metabolism of homocysteine. The objective of the study was to analyze the prevalence of hyperhomocysteinemia in patients with heavy alcohol intake and the factors on which it depends. Included in the study were 103 hospitalized heavy drinkers (i.e., patients with an intake of alcohol greater than 80 g per day). Serum homocysteine, folate, and vitamin B(12) levels, plasma vitamin B(6) levels, and CT677 polymorphisms of methylenetetrahydrofolate reductase (MTHFR) were determined. We also recorded the intensity of alcoholism, the status of nutrition, and the existence of liver cirrhosis. Determination of biochemical data was repeated after 15 days of withdrawal. Serum homocysteine levels were found to be significantly elevated, whereas serum folate and plasma B(6) levels were significantly decreased. Serum homocysteine levels were significantly higher in those heavy drinkers who showed the TT polymorphism of MTHFR, with a prevalence of hyperhomocysteinemia of 84.2% in the homozygote TT, 54.3% in the heterozygote CT, and 31.6% in the normal CC genotype. Serum homocysteine inversely correlated with serum folate, serum B(12), and plasma B(6) levels. We did not find any relation between serum homocysteine and intensity of alcoholism, nutritional status, or liver cirrhosis. Serum folate levels were significantly decreased in heavy drinkers, mainly depending on irregular feeding and malnutrition. After 15 days of withdrawal, serum homocysteine levels significantly decreased, whereas folate, B(12), and B(6) levels significantly increased. The conclusion is that heavy drinkers show a high prevalence of hyperhomocysteinemia related to low levels of folate, B(6), and B(12) and to the TT polymorphism of MTHFR.

Nutritional assessment in alcoholic patients. Its relationship with alcoholic intake, feeding habits, organic complications and social problems

To establish their ability to predict malnutrition, irregular feeding, alcoholic intake, derangement of social and familial links and organic complications (liver cirrhosis) were assessed in 181 hospitalized male alcoholic. BMI was under 18.5 kg/m(2) in 8.9%, between 18.5-20 kg/m(2) in 8.9%, 20-25 kg/m(2) in 42%, 25-30 kg/m(2) in 32.2% and over 30 kg/m(2) in 8.2% of patients. Malnutrition was related to the intensity of ethanol intake, development of social or familial problems, irregularity of feeding habits and cirrhosis with ascites. Irregularity of feeding habits was also related to heavy drinking and to social or familial derangement. By logistic regression analysis, the only variables which independently predict malnutrition were irregular feeding habits and liver cirrhosis with ascites. In a second step, irregular feeding was dependent on social or familial troubles and daily intake of ethanol. So, malnutrition related to alcoholism seems multifactorial in its pathogenesis.

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.

Alcoholic Hypogonadism: Hormonal Response to Clomiphene

To investigate the androgen, weak androgen, estrogen, and gonadotrophin response to clomiphene in alcoholics, we determined in 63 male patients (25 with and 38 without liver cirrhosis) serum testosterone, sexual hormone binding protein (SHBG), dehidroepiandrosterone, androstenedione, LH, FSH, prolactin, and estradiol levels, on the first and the sixth day after admission, and after a course of 8 days of clomiphene 200 mg/day. The same test was performed on 15 healthy volunteers. Cirrhotic patients showed decreased basal testosterone levels and a loss of the circadian rhythm with recovery after clomiphene. Although basal testosterone levels in noncirrhotic alcoholics did not differ from those of the controls, there was a significant improvement after withdrawal. SHBG levels were higher in both groups of alcoholics than in controls, pointing to a worse degree of hypogonadism, because only the free hormone is active. Before the clomiphene test, serum LH and FSH levels were nonsignificantly higher in both groups of alcoholics than in the control group. After clomiphene both LH and FSH increased. Androstenedione and estradiol showed a (parallelism) similar behavior in alcoholic and in cirrhotic groups, showing in both cases higher levels than in the control group, and an increase after clomiphene, perhaps reflecting peripheral conversion of androgens to estrogens. Because clomiphene has no effect on the adrenal cortex, the increase of androstenedione after clomiphene points to its testicular origin (directly or after testosterone conversion) and not to an adrenal one. The highest serum estradiol levels were observed in cirrhotics with ascites or gynecomastia. We have not found any relation between serum hormone levels and alcohol intake nor with nutritional status.

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

BackgroundThe 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.MethodsProspective 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 ≤ 9 μg/dl after the administration of 250 μg of consyntropin. Plasma cortisol levels were measured preoperatively, immediately before, 30, 60, and 90 minutes after the administration of cosyntropin, and at 24 hours after surgery.Results120 elective cardiopulmonary bypass patients were included. Relative adrenal insufficiency (Δcortisol ≤9 μg/dl) incidence was 77.5%. 78 patients received etomidate and 69 (88%) of them developed relative adrenal insufficiency, (P < 0.001). Controlling for clinical characteristics with a propensity analysis, etomidate was the only independent risk factor associated with relative adrenal insufficiency (OR 6.55, CI 95%: 2.47-17.4; P < 0.001). Relative adrenal insufficiency patients showed more vasopressor requirements just after surgery (P = 0.04), and at 4 hours after surgery (P = 0.01). Pre and post-test plasma cortisol levels were inversely associated with maximum norepinephrine dose (ρ = -0.22, P = 0.02; ρ = -0.18, P = 0.05; ρ = -0.21, P = 0.02; and ρ = -0.22, P = 0.02, respectively).ConclusionsRelative adrenal insufficiency in elective cardiopulmonary bypass patients may induce postoperative vasopressor dependency. Use of etomidate in these patients is a modifiable risk factor for the development of relative adrenal insufficiency that should be avoided.

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.