Marinella Tzanela

High prevalence of decreased cortisol reserve in brain-dead potential organ donors.

ObjectiveTo investigate the adrenocortical function in brain-dead patients, potential organ donors. DesignProspective study. SettingIntensive care units in two teaching hospitals. PatientsA total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42 ± 18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death. InterventionsIn all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 &mgr;g of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n = 10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 &mgr;g/dL after the administration of adrenocorticotropic hormone were defined as responders. Measurements and Main ResultsAfter the occurrence of brain death, group B patients had significantly lower values for baseline (8.5 ± 6.2 vs. 17.0 ± 6.6 &mgr;g/dL, p < .001) and stimulated (16.9 ± 6.3 vs. 23.9 ± 5.7 &mgr;g/dL, p = .001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p < .001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r = .71, p = .001), whereas there was no correlation between baseline cortisol and the increment in cortisol (r = −.37, p = .15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5 ± 11.4 vs. 6.8 ± 4.2 &mgr;g/dL, p = .003) and stimulated serum cortisol (28.8 ± 9.9 vs. 16.3 ± 4.3 &mgr;g/dL, p = .008). ConclusionsAdrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors.

Novel concept of antisurvival factor (ASF) therapy produces an objective clinical response in four patients with hormone-refractory prostate cancer: case report.

Osteoblasts and osteoblast‐derived survival growth factors, such as insulin‐like growth factor I (IGF I), inhibit chemotherapy apoptosis of prostate cancer cells, thereby producing cytotoxic drug‐resistant tumor growth, in vitro.

Prognostic importance of increased plasma amino-terminal pro-brain natriuretic peptide levels in a large noncardiac, general intensive care unit population.

The present study aimed to determine whether amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) predicts intensive care unit (ICU) mortality in a cohort of general, noncardiac, critically ill patients. To this end, a total of 233 consecutive mechanically ventilated patients (109 men) having a median age of 60 years and a wide range in admitting diagnoses, including medical (n = 118), surgical (n = 83), and multiple trauma (n = 32) cases were prospectively studied. Median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores on ICU admission were 16 and 9, respectively. The study end point was ICU outcome. Blood samples were drawn on admission in the ICU and on postadmission days 1 and 2 to determine NT-pro-BNP levels. In a subgroup (n = 77), admission proinflammatory and anti-inflammatory cytokine levels, including TNF-&agr;, IL-6, and IL-10, were also measured. Nonsurvivors (n = 98) had significantly higher NT-pro-BNP levels than survivors (n = 135) on admission in the ICU (2,074 vs. 283 pg/mL; P < 0.001), on day 1 (2,197 vs. 221 pg/mL; P < 0.001), and on day 2 (2,726 vs. 139 pg/mL; P < 0.001). Median values for TNF-&agr;, IL-6, and IL-10 were 3.70, 131.57, and 111.88 pg/mL, respectively. Receiver operating characteristic analysis showed that the area under the receiver operating characteristic curve in predicting ICU mortality was 0.70 for APACHE II and 0.77 for admission NT-pro-BNP (P = 0.08). The cutoff in admission NT-pro-BNP that best predicted outcome was 941 pg/mL. Multiple logistic regression analysis revealed that APACHE II score (odds ratio, 1.06; P = 0.007) and the best cutoff point in admission NT-pro-BNP (odds ratio, 7.74; P < 0.001) independently predicted ICU mortality, even if cytokines were entered in the analysis. In conclusion, plasma NT-pro-BNP is frequently raised in noncardiac, mixed, critically ill patients, and nonsurvivors have consistently higher levels than survivors. Elevated admission NT-pro-BNP represents an independent predictor for poor ICU outcome in the presence of clinical severity scores.

Association of left ventricular diastolic dysfunction with elevated NT-pro-BNP in general intensive care unit patients with preserved ejection fraction: a complementary role of tissue Doppler imaging parameters and NT-pro-BNP levels for adverse outcome.

The mechanisms of the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) release in intensive care unit (ICU) patients with preserved ejection fraction (EF) are unclear. We investigated whether left ventricular (LV) dysfunction, as assessed by tissue Doppler imaging (TDI), is related to NT-pro-BNP levels in ICU patients with preserved EF and has a complementary value to NT-pro-BNP in the determination of in-hospital mortality. We examined 58 mechanically ventilated patients with no history of heart failure (age, 60 ± 18 years; EF, 63% ± 7%). The systolic (S) and early diastolic (E&vprime;) velocity of the mitral annulus by TDI and the E/E&vprime; as well as NT-pro-BNP, troponin, lactate acid, blood oxygen (PO2/FiO2), sepsis, and ICU mortality were assessed. Systolic, E&vprime;, and E/E&vprime; correlated with age, PO2/FiO2, lactate acid, NT-pro-BNP, troponin, history of arterial hypertension, and diabetes (P < 0.05). By multivariate analysis, the determinants of NT-pro-BNP were S (P = 0.024), E/E&vprime; (P = 0.017), and sepsis (P = 0.015). An NT-pro-BNP greater than 941 pg/mL was a reliable predictor of LV diastolic dysfunction defined as a composite of E&vprime; less than or equal to 8 cm/s and/or mean E/E greater than or equal to 13 (area under the curve, 75%; P = 0.03). Patients with combined NT-pro-BNP greater than 941 pg/mL and abnormal TDI markers had increased creatinine levels and a lower MAP, PO2/FiO2, and survival rate than those with abnormal TDI or NT-pro-BNP alone or patients with normal TDI markers and NT-pro-BNP (25%, 60%, 70%, and 84%, respectively; P < 0.05). The addition of abnormal TDI in a model including NT-pro-BNP and sepsis increased the models value for in-hospital mortality (P for change = 0.01). In ICU patients with preserved EF, LV diastolic dysfunction and sepsis determine NT-pro-BNP levels. Tissue Doppler imaging markers and NT-pro-BNP have a complementary value for in-hospital mortality.

Assessment of GH reserve before and after successful treatment of adult patients with Cushing's syndrome

objective  Several studies have demonstrated impaired GH secretion in patients with active Cushings syndrome (CS). It has been suggested that persistence of GH deficiency, despite treatment of cortisol excess, may delay the recovery of these patients and therefore temporary treatment with GH may have some benefit. However, the time course of restoration of GH secretion after successful treatment of CS has only been investigated in a limited number of mostly paediatric reports. The aim of the present study was the evaluation of GH reserve in adult patients with CS before and after correction of cortisol excess.

Serial changes in adiponectin and resistin in critically ill patients with sepsis: Associations with sepsis phase, severity, and circulating cytokine levels☆☆☆

PURPOSE The aim of the present study was to describe the variation in adiponectin and resistin levels, 2 adipokines with opposing effects on metabolism, in mechanically ventilated patients with sepsis and their relationships to disease severity and cytokine levels. MATERIALS AND METHODS An observational prospective study was conducted in a secondary/tertiary unit. Forty-one mechanically ventilated patients diagnosed as having sepsis were included in the study. The Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were estimated. Adiponectin, resistin, and cytokines were measured upon sepsis diagnosis and every 3 to 4 days thereafter until day 30. Adiponectin and resistin were also measured in 40 controls. RESULTS The patients had higher adiponectin (10.9 ± 6.1 μg/mL vs 6.0 ± 2.9 μg/mL, P < .001) and resistin (24.7 ng/mL vs 3.8 ng/mL, P < .001) levels compared with the controls. Adiponectin increased and resistin decreased significantly over time in the entire cohort. Resistin correlated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, interleukin (IL)-6, IL-8, and IL-10 and was significantly higher in severe sepsis/septic shock compared with sepsis. No correlations between adiponectin and clinical scores were noted. CONCLUSIONS Adiponectin and resistin change reciprocally during the course of sepsis. Resistin relates to the severity of sepsis and the degree of inflammatory response. Adiponectin and resistin may play a critical role in the metabolic adaptations observed in sepsis.

Endocrine alterations in critically ill patients with stroke during the early recovery period.

Introduction: Endocrine abnormalities in critically ill patients with stroke during the early recovery period have not been well characterized.Methods: To investigate this issue, 33 consecutive mechanically ventilated patients (27 men) with hemorrhagic (n=21) or ischemic (n=12) stroke having a mean age of 57 ± 12 years were studied. Glasgow Coma Scale score on admission in the hospital was 8 ± 3. The following basal hormones were measured within 72 hours postextubation: cortisol, corticotropin (ACTH), free thyroxine, tri-iodothyronine, thyroid-stimulating hormone, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, growth hormone, and insulin-like growth factor (IGF)-1. Subsequently, a low-dose (1 µg) ACTH stimulation test was performed.Results: Twenty-six (79%) patients showed endocrine alterations. The most common change was low IGF-1 levels compatible with growth hormone deficiency (45%), followed by hypogonadism (39%), thyroid dysfunction (36%), and cortisol hyporesponsiveness (33%).Conclusion: Neuroendocrine changes occur with high frequency in critically ill patients with stroke during the early recovery period. It remains to be determined whether these changes have implications for functional and/or clinical outcome.

Glucose homeostasis in patients with acromegaly treated with surgery or somatostatin analogues

Objective  Long‐acting somatostatin analogues (SSA) are widely used for the treatment of acromegaly; however, they also alter β‐cell function by inhibiting insulin secretion. In this study, we assess the effect of SSA on glucose homeostasis in patients with acromegaly treated with SSAs, compared to patients treated with surgery.

Role of [18F]FDG-PET/CT in the detection of occult recurrent medullary thyroid cancer

PurposeMany patients with medullary thyroid carcinoma (MTC) have persistently elevated calcitonin levels after initial treatment, indicating disease recurrence. Conventional imaging is often negative or shows equivocal findings. In this study we report our experience with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) in the evaluation of this specific group. MethodsBetween February 2007 and May 2009, 38 [18F]FDG-PET/CT scans were performed on 32 patients with MTC and elevated calcitonin levels for localization of recurrent disease. Six of these patients had a second [18F]FDG-PET/CT scan. ResultsAmong the 38 [18F]FDG-PET/CT scans there were 18 positive and 20 negative scans. Out of the 18 positive scans, 17 were true positive and one false positive. These findings suggest that [18F]FDG-PET/CT provides additional information in almost half of all cases (overall per patient sensitivity of 47.4%) but using a serum calcitonin cut-off of 1000 pg/ml this rate is increased to 80%. An interesting finding of the study was that none of the six patients with multiple endocrine neoplasia type IIA syndrome had a positive [18F]FDG-PET/CT scan for MTC. When these patients were excluded, the overall per patient sensitivity rose to 60% and in patients with calcitonin levels >1000 pg/ml this rate increased to 100%. The mean SUVmax of all lesions showing [18F]FDG uptake was 3.96±1.61 (range, 2–7). Conclusion[18F]FDG-PET/CT seems to be valuable for the detection of recurrence in patients with highly elevated calcitonin levels and negative conventional imaging findings. In addition, it seems that the sensitivity of [18F]FDG-PET/CT may be higher in patients with sporadic or familial MTC than in patients with MTC as part of multiple endocrine neoplasia type IIA syndrome.

Early serum levels of soluble triggering receptor expressed on myeloid cells–1 in septic patients: Correlation with monocyte gene expression☆

PURPOSE To define early kinetics of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and of TREM-1 monocyte gene expression in critically ill patients with sepsis. METHODS Blood was sampled at regular time intervals from 105 patients with sepsis. Concentrations of tumour necrosis factor α (TNFα), interleukin (IL)-6, IL-8 and IL-10 and IL-12p70 and sTREM-1 were measured by an enzyme immunoassay. Blood mononuclear cells were isolated on day 0 from 20 patients and 10 healthy volunteers; RNA was extracted and gene expression of TREM-1 and TNFα were assessed by reverse transcriptase polymerase chain reaction. RESULTS Early serum concentrations of sTREM-1 were greater among patients with severe sepsis/shock than among patients with sepsis; those of TNFα, IL-6, IL-8 and IL-10 were pronounced among patients with septic shock. Gene transcripts of TNFα were lower among patients with severe sepsis/shock than among patients with sepsis; that was not the case for TREM-1. Early serum levels of sTREM-1 greater than 180 pg/mL were predictors of shorter duration of mechanical ventilation. CONCLUSIONS Although serum levels of sTREM-1 are increased early upon advent of severe sepsis/shock, gene expression of TREM-1 on monocytes in severe sepsis/shock is not increased. These findings add considerably to our knowledge on the pathophysiology of sepsis.