[show abstract][hide abstract] ABSTRACT: There is ongoing controversy as to whether hormonal changes of the euthyroid sick syndrome are predictors of poor outcome in sepsis and critical illness. In this prospective study, the prognostic accuracy of thyroid hormone levels in 103 critically ill adult patients on admission and during follow up in a medical intensive care unit (ICU) was assessed and was compared to clinical risk scores, namely, the acute physiology and chronic health evaluation and the simplified acute physiology score. Median T3 levels on admission to the ICU were lower in the 53 septic cases [0.9 nmol/l (IQR 0.6-1.1)] as compared with the 50 patients with a systemic inflammatory response syndrome [1.2 nmol/l (IQR 0.8-1.4), P < 0.001]. The lowest T3 levels were found in patients with severe sepsis [0.8 nmol/l (IQR 0.55-0.95)] and septic shock [0.8 nmol/l (IQR 0.6-1.0)]. There was no difference in T3 and free thyroxin (fT4) levels on admission in non-survivors compared with survivors overall and in subgroups of patients with SIRS and sepsis. During the follow up, fT4 levels decreased significantly in non-survivors, while they increased in survivors [fT4 difference -1.3 (IQR -2.5 to 0.2) vs. 0.8 (IQR -0.85 to 4.1), P = 0.003]. In addition, on the day of death, non-survivors had lower T3 and fT4 levels as compared with survivors (P = 0.04 and P = 0.02). T3 and fT4 levels on admission were not prognostic in this cohort of critically ill patients. A decrease in fT4 levels in the course of disease, however, may point to adverse outcome.
[show abstract][hide abstract] ABSTRACT: Circulating levels of GH are increased during critical illness and correlate with outcome in children with meningococcal sepsis. We assessed the prognostic implications of GH on admission and during follow-up in critically ill adult patients admitted to a medical intensive care unit.
We measured GH, IGF1 and IGF-binding protein3 (IGFBP-3) plasma concentrations in 103 consecutive critically ill patients and compared it with two clinical severity scores (APACHE II, SAPS II).
Median GH levels on admission were similar in septic (n=53) and non-septic (n=50) patients and about 7-fold increased in the 24 non-survivors as compared with survivors (9.50 (interquartile ranges (IQR) 3.53-18.40) vs 1.4 (IQR 0.63-5.04), P<0.0001). GH levels increased with increasing severity of sepsis (sepsis, severe sepsis, and septic shock, P=0.019). By contrast, IGF1 and IGFBP-3 did not correlate with severity of disease or mortality. Logistic regression models showed that GH and both clinical scores were independent predictors of mortality with a similar prognostic accuracy (GH: area under the curve (AUC) 0.81 (95% confidence interval (CI), 0.71-0.92), APACHE II: AUC 0.71 (95% CI, 0.58-0.83), P=0.16, SAPS II: AUC 0.75 (95% CI, 0.63-0.86, P=0.36)). GH improved the prognostic accuracy of the APACHE II score to an AUC of 0.78 (95% CI, 0.66-090, P=0.04) and tended to improve the SAPS II score to an AUC of 0.79 (95% CI, 0.67-0.90, P=0.09).
GH plasma concentrations on admission are independent predictors for mortality in adult critically ill patients and may complement existing risk prediction scores, namely the APACHE II and the SAPS II score.
European Journal of Endocrinology 12/2008; 160(2):157-63. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: Acute respiratory tract infections are the most common reason for antibiotic therapy in primary care despite their mainly viral etiology. A laboratory test measuring procalcitonin levels in blood specimens was suggested as a tool to reduce unnecessary prescribing of antibiotics. We consider whether antibiotic therapy guided by procalcitonin reduces the use of antibiotics without increasing the restrictions experienced by patients by more than 1 day.
Fifty-three primary care physicians recruited 458 patients, each patient with an acute respiratory tract infection and, in the physician's opinion, in need of antibiotics. Patients were centrally randomized to either a procalcitonin-guided approach to antibiotic therapy or to a standard approach. For patients randomized to procalcitonin-guided therapy, the use of antibiotics was more or less strongly discouraged (procalcitonin level, < or =0.1 or < or =0.25 microg/L, respectively) or recommended (procalcitonin level, >0.25 microg/L). Follow-up data were collected at 7 days by treating physicians and at 14 and 28 days by blinded interviewers.
Adjusted for baseline characteristics, the mean increase at 14 days in days in which activities were restricted was 0.14 with procalcitonin-guided therapy (95% confidence interval [CI], -0.53 to 0.81 days), which met our criterion of an increase in days in which activities were restricted by no more than 1 day. With procalcitonin-guided therapy, the antibiotic prescription rate was 72% lower (95% CI, 66%-78%) than with standard therapy. Both approaches led to a similar proportion of patients reporting symptoms of ongoing or relapsing infection at 28 days (adjusted odds ratio, 1.0 [95% CI, 0.7-1.5]).
As an adjunct to guidelines, procalcitonin-guided therapy markedly reduces antibiotic use for acute respiratory tract infections in primary care without compromising patient outcome. In practice, this could be achieved with 1 to 2 procalcitonin measurements in patients for whom the physician intends to prescribe antibiotics.
Archives of internal medicine 10/2008; 168(18):2000-7; discussion 2007-8. · 11.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: As supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitary-adrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures.
A systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 mug) ACTH stimulation was performed in nine patients before, on the first and the last day of treatment, as well as 2, 7 and 21 days after corticosteroid withdrawal.
At baseline, all nine patients had normal responses to 1 mug ACTH. On the first day of steroid treatment, 78% had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to ACTH 2, 7, and 21 days after corticosteroid withdrawal, respectively. ROC curve analysis revealed that only basal cortisol concentrations (AUC 0.89), but not ACTH concentrations (AUC 0.49) or clinical signs (AUC 0.47) were predictive of an impaired function of the HPA axis. Basal cortisol levels of > 400 and < 150 nmol/l were 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively.
Immediate and prolonged suppression of the HPA axis is a common finding in otherwise asymptomatic patients undergoing systemic steroid treatment for acute exacerbation of chronic obstructive pulmonary disease and can reliably be assessed with the low-dose ACTH test.
BMC Pulmonary Medicine 02/2008; 8:1. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: B-type natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) are both increasingly used in the clinical management of patients with suspected coronary artery disease (CAD). Unfortunately, there is very limited data regarding the association between BNP and LVEF.
BNP and LVEF were measured in 260 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT). The correlation between BNP and LVEF was studied using Spearman's correlation test.
Median LVEF was 57% (IQR, 50 to 64), and median BNP level was 53 pg/ml (IQR, 24 to 109). LVEF and BNP levels showed a statistically significant, but overall weak correlation (r=0.274, p<0.001). The correlation seemed to depend on the presence of a myocardial scar, which was detected in 104 patients (40%), including 89 men (49% of men) and 15 women (20% of women). The correlation between BNP and LVEF was moderate in patients with a myocardial scar (r=-0.540, p<0.001), but very weak in patients without a scar (r=0.185, p=0.025). Moreover, the correlation between BNP and LVEF was moderate in men (r=-0.503, p<0.001), but not existent at all in women. In the overall cohort, BNP was not an accurate test to detect left ventricular systolic dysfunction. The area under the ROC curve was 0.643 (95% CI, 0.563-0.723).
The BNP level and LVEF show only a weak correlation in patients with suspected myocardial ischemia. Neurohormonal and morphologic assessments provide different windows to the heart.
International journal of cardiology 08/2007; 120(2):248-53. · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Community-acquired pneumonia (CAP) is the most frequent infection-related cause of death. The reference standard to diagnose CAP is a new infiltrate on chest radiograph in the presence of recently acquired respiratory signs and symptoms. This study aims to evaluate the diagnostic and prognostic accuracy of clinical signs and symptoms and laboratory biomarkers for CAP.
545 patients with suspected lower respiratory tract infection, admitted to the emergency department of a university hospital were included in a pre-planned post-hoc analysis of two controlled intervention trials. Baseline assessment included history, clinical examination, radiography and measurements of procalcitonin (PCT), highly sensitive C-reactive protein (hsCRP) and leukocyte count.
Of the 545 patients, 373 had CAP, 132 other respiratory tract infections, and 40 other final diagnoses. The AUC of a clinical model including standard clinical signs and symptoms (i.e. fever, cough, sputum production, abnormal chest auscultation and dyspnea) to diagnose CAP was 0.79 [95% CI, 0.75-0.83]. This AUC was significantly improved by including PCT and hsCRP (0.92 [0.89-0.94]; p < 0.001). PCT had a higher diagnostic accuracy (AUC, 0.88 [0.84-0.93]) in differentiating CAP from other diagnoses, as compared to hsCRP (AUC, 0.76 [0.69-0.83]; p < 0.001) and total leukocyte count (AUC, 0.69 [0.62-0.77]; p < 0.001). To predict bacteremia, PCT had a higher AUC (0.85 [0.80-0.91]) as compared to hsCRP (p = 0.01), leukocyte count (p = 0.002) and elevated body temperature (p < 0.001). PCT, in contrast to hsCRP and leukocyte count, increased with increasing severity of CAP, as assessed by the pneumonia severity index (p < 0.001).
PCT, and to a lesser degree hsCRP, improve the accuracy of currently recommended approaches for the diagnosis of CAP, thereby complementing clinical signs and symptoms. PCT is useful in the severity assessment of CAP.
[show abstract][hide abstract] ABSTRACT: Restoration of near-euglycaemia by intensive insulin therapy results in decreased serum levels of inflammatory mediators. The authors investigated whether the anti-inflammatory effect of insulin was independent of its glucose-lowering action and if this effect was intact in insulin-resistant women with the polycystic ovary syndrome (PCOS) characterized by low-grade chronic inflammation.
Blood was drawn on the third and sixth days after progestin-induced withdrawal bleeding in 20 young non-diabetic women with PCOS and once between the third and sixth days of the menstrual cycle in 21 age-matched lean healthy control women during a 75-g oral glucose tolerance test (oGTT). Serum insulin, glucose and tumour necrosis factor alpha (TNF-alpha) concentrations were measured after 0, 30, 60, 90 and 120 min.
The increase in insulin and glucose concentrations during the oGTT was significantly more pronounced in patients with PCOS (one patient with impaired fasting glucose, one patient with impaired glucose tolerance, three patients with both) compared with healthy controls. The TNF-alpha serum concentrations decreased in patients with PCOS (mean of both days, P = 0.004). In patients and in controls, there was an inverse correlation between the serum concentrations of insulin and of TNF-alpha during oGTT (for patients, a mean of both days, P = 0.009; for controls, P = 0.047), but not between the serum concentrations of glucose and TNF-alpha.
The decrease in TNF-alpha concentrations during oGTT and the inverse correlation between endogenous hyperinsulinaemia and serum TNF-alpha concentrations suggested an anti-inflammatory effect of moderately-high insulin concentrations. This occurred despite the presence of moderate hyperglycaemia. These findings also demonstrated a preserved responsiveness of inflammatory mediators to insulin in PCOS.
European Journal of Clinical Investigation 01/2007; 36(12):883-9. · 3.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Exercise electrocardiography (ECG) has high specificity but limited sensitivity for the detection of myocardial ischemia. The aim of this study was to determine whether measurement of B-type natriuretic peptide (BNP) can improve the diagnostic accuracy of exercise ECG.
A total of 256 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography were enrolled. Levels of BNP were determined before and 1 minute after maximal exercise.
Inducible myocardial ischemia on perfusion images was detected in 127 patients (49.6%). Median BNP levels at rest and after peak exercise were higher in patients with than without inducible ischemia (71 pg/mL vs 38 pg/mL, P < .001; and 88 vs 52 pg/mL, P < .001, respectively). Compared with patients in the lowest peak exercise BNP quartile, those in the highest quartile of peak exercise BNP had more than 3 times the risk of inducible ischemia (adjusted relative risk 3.3, 95% CI 1.3-8.6, P = .015). Using 110 pg/mL as a cutoff, the combination of exercise ECG and peak exercise BNP level distinguished between ischemic and nonischemic patients more accurately than the exercise ECG alone (67% vs 60%, P = .024). Although the increase in accuracy was similar for the combination of exercise ECG with baseline BNP or DeltaBNP, overall, peak exercise BNP seemed to be the preferred measurement.
B-type natriuretic peptide levels are associated with inducible myocardial ischemia. The use of BNP levels improves the diagnostic accuracy of exercise ECG.
American heart journal 06/2006; 151(6):1223-30. · 4.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cystic fibrosis (CF) is a disease characterized by weight loss and chronic low-grade inflammation.
The objective of the study was to assess changes in body composition and the serum concentrations of adiponectin, a marker of negative energy balance and insulin sensitivity, in adult patients with CF.
This was a cross-sectional study.
The study was conducted at an outpatient clinic of the University Hospital of Basel, Switzerland.
Twenty-four stable adult CF patients and 24 healthy controls, matched for body mass index, age, sex, and hormonal therapy in women participated in the study.
Changes in body composition (assessed by dual x-ray absorptiometry) and serum adiponectin levels were measured.
Body mass index, percent fat mass (in percentage of body weight), and percent lean body mass were similar in patients and controls, whereas central fat accumulation was increased [trunk to extremity fat ratio 1.2 (0.99-1.51) vs. 0.99 (0.81-1.25), P = 0.01] in patients with CF, compared with controls. Decreased lean mass and increased highly sensitive C-reactive protein levels were independently associated with worse lung function in CF patients. Despite similar insulin resistance (homeostasis model assessment) and similar SHBG serum concentrations, the serum concentrations of adiponectin were higher in CF patients, compared with controls, independent of other confounders (P = 0.01).
Central fat accumulation is increased in patients with CF. It is postulated that the energy deficit-induced increase in serum adiponectin could explain the preservation of insulin sensitivity in these patients despite the increase in central fat and in highly sensitive C-reactive protein serum concentrations and could prevent a further deterioration of protein catabolism.
[show abstract][hide abstract] ABSTRACT: To evaluate the utility of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels to detect myocardial ischemia.
We conducted a prospective observational study in 260 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography. Levels of NT-proBNP were determined before and immediately after symptom-limited bicycle ergometry.
Inducible myocardial ischemia on perfusion images was detected in 129 patients (49.6%). Baseline NT-proBNP and exercise induced increase in NT-proBNP (DeltaNT-proBNP) were significantly higher in patients with myocardial ischemia (median baseline NT-proBNP 155 pg/mL vs 91 pg/mL, P <.001; DeltaNT-proBNP 15 pg/mL vs 7 pg/mL, P = .002). Compared with patients in the lowest DeltaNT-proBNP quartile, those in the highest quartile of DeltaNT-proBNP had three times the risk of inducible ischemia (relative risk, 2.9; 95% confidence interval, 1.4 to 6.0; P = .003). Overall, the accuracy of baseline NT-proBNP and DeltaNT-proBNP in the detection of myocardial ischemia were similar to that of the exercise electrocardiogram (ECG). Combining exercise ECG and baseline NT-proBNP or DeltaNT-proBNP slightly increased the accuracy of exercise ECG only.
The NT-proBNP level at rest as well as DeltaNT-proBNP during exercise stress testing is associated with inducible myocardial ischemia. NT-proBNP levels may have incremental value in the diagnosis of myocardial ischemia.
The American journal of medicine 11/2005; 118(11):1287. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: Because of its unique storage and release mechanisms allowing a very rapid response to haemodynamic changes, pro-atrial natriuretic peptide (proANP) may be a helpful cardiac marker in the detection of myocardial ischaemia.
A total of 260 consecutive patients with suspected myocardial ischaemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT) were enrolled. Levels of plasma proANP were determined before and 1 min after maximal exercise.
Baseline proANP and peak exercise proANP were significantly higher in patients with myocardial ischaemia as compared to those without ischaemia (median, 82 [IQR, 57-112] vs. 67 [IQR, 50-106] pmol L(-1), P = 0.007; and 89 [IQR, 65-121] vs. 78 [IQR, 57-116] pmol L(-1), P = 0.033). The area under the ROC curve for baseline proANP was 0.597 (95% CI, 0.527-0.667), as compared to 0.577 (95% CI, 0.507-0.648) for peak exercise proANP. Exercise-induced changes in proANP were similar in patients with and without myocardial ischaemia, and showed no correlation with the extent of myocardial ischaemia.
Baseline proANP and peak exercise proANP are significantly higher in patients with myocardial ischaemia. However, because of considerable overlap in proANP levels between patients with and without myocardial ischaemia, neither measurement seems helpful in the detection of myocardial ischaemia in clinical practice.
European Journal of Clinical Investigation 08/2005; 35(7):450-6. · 3.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: B-type natriuretic peptide (BNP) levels are reliably elevated in patients with congestive heart failure (CHF) and therefore helpful in its diagnosis. However, kidney disease results in elevated BNP levels independently of CHF. Accordingly, the impact of kidney disease on the benefit of BNP testing needs to be scrutinized.
This study evaluated patients with and without kidney disease [glomerular filtration rate (GFR) less than 60 mL/min/1.73 m(2)) presenting with acute dyspnea. A total of 452 consecutive patients (240 with kidney disease and 212 without kidney disease) were randomly assigned to a diagnostic strategy with (BNP group) or without (control group) the use of BNP levels provided by a rapid bedside assay.
Patients with kidney disease were older, more often had CHF as the cause of acute dyspnea, and more often died in-hospital or within 30 days as compared to patients without kidney disease. In patients without kidney disease, BNP testing significantly reduced median time to discharge (from 9.5 days to 2.5 days) (P= 0.003) and total cost of treatment (from 7184 dollars to 4151 dollars) (P= 0.004). In contrast, in patients with kidney disease, time to discharge and total cost of treatment were similar in both groups.
When applying BNP cut-off values without adjustment for the presence of kidney disease, the use of BNP levels does significantly improve the management of patients without kidney disease, but not of those with kidney disease.
Kidney International 02/2005; 67(1):278-84. · 7.92 Impact Factor