Axel Stachon

High in-hospital mortality of intensive care patients with nucleated red blood cells in blood

Abstract The detection of nucleated red blood cells (NRBCs) in blood of patients suffering from a variety of severe diseases is known to be highly associated with increased mortality. Blood analyzers to routinely measure NRBC concentrations are now available. However, the diagnostic and prognostic significance of this parameter for intensive care patients has not been evaluated. Using a Sysmex XE-2100 analyzer, NRBC concentrations were determined in blood samples from 421 patients treated in intensive care units (general and accident surgery, cardiothoracic surgery, and internal medicine) of a university hospital. NRBCs were found at least once in 19.2% of all patients. The mortality of NRBC-positive patients (n = 81) was 42.0% (n = 34); this was significantly higher (p < 0.001) than the mortality of NRBC-negative patients (5.9%, n = 340). The NRBC concentration was 115 ± 4 × 106/l (median 40 × 106/l; range 20–2930 × 106/l) at initial detection of NRBCs in the blood. Mortality increased with increasing NRBC concentration and increasing frequency of occurrence. With regard to in-hospital mortality, NRBCs in blood showed sensitivity and specificity of 63.0% and 87.2%, respectively. The detection of NRBCs is highly predictive of death, the odds ratio after adjustment for other laboratory prognostic indicators being 1.01 (p < 0.01) for each increase in the NRBC concentration of +1 × 106/l. NRBCs were detected for the first time, on average, 13 days (median 8 days) before death. The routine analysis of NRBCs in blood is of high prognostic power with regard to in-hospital mortality of critically ill patients. Therefore, this parameter may serve as an early indicator for patients at increased mortality risk.

Salivary cortisol and psychological mechanisms in patients with acute versus chronic low back pain

This study was designed to explore whether the basal adrenocortical activity is related with pain-related coping, nonverbal pain behavior, depressive mood, and fatigue in patients with acute and chronic nonspecific low back pain. 19 patients with acute low back pain (ALBP) and 24 with chronic low back pain (CLBP) participated in the study. The adrenocortical activity was assessed through the cortisol awakening response. All participants provided five saliva samples (0, 15, 30, 45, and 60min after waking) on two consecutive days off work. Pain-related coping [fear-avoidance coping (FAC) and endurance coping (EC)], nonverbal pain behavior (NPB), depressive mood, and fatigue were assessed through questionnaires. Among ALPB patients, EC was negatively associated with the cortisol release, whereas fatigue was positively associated with it. Among CLBP patients, FAC, NPB, depressive mood, and fatigue were negatively associated with the cortisol awakening response, whereas EC tended to be positively associated with it. The results indicate that pain-related coping strategies which are expected to be successful appear to lower the adrenocortical activity among ALBP patients, whereas affective distress may enhance the level of cortisol in this group. Among CLBP patients, long-term maladaptive coping strategies might contribute to hypocortisolism.

Katecholaminabhängiges hereditäres Cushing-Syndrom – Verlaufsbeobachtung nach einseitiger Adrenalektomie

Zusammenfassung.Fallbericht: Wir berichten über labormedizinische, klinische, radiologische und histologische Befunde bei einem 44-jährigen Patienten, der mit den klinischen Zeichen eines Cushing-Syndroms zur stationären Aufnahme kam. Die labormedizinischen Befunde gaben den Hinweis auf eine adrenale Genese. In der Computertomographie des Abdomens zeigte sich eine makronoduläre Hyperplasie beider Nebennieren. Die Cortisolsekretion stieg unter adrenerger Stimulation an, während ein Anstieg nach β-Blocker-Medikation ausblieb, was eine aberrante Regulation der Cortisolsekretion durch β-Rezeptoren als Ursache der vermehrten Cortisolproduktion nahe legt. Auch bei der Mutter des Patienten konnte eine ACTH-unabhängige bilaterale makronoduläre Nebennierenrindenhyperplasie nachgewiesen werden. Der Vater sowie der Bruder waren nicht von der Erkrankung betoffen. Neben einem bereits publizierten Fall, bei dem Mutter und Tochter betroffen waren, stellt die hier geschilderte Konstellation die zweite Beschreibung eines familiären Auftretens dar, erstmalig mit einer Erkrankung von Mutter und Sohn. Der Patient wurde einer linksseitigen Adrenalektomie zugeführt. Es zeigte sich eine rasche postoperative Absenkung der Serumcortisolkonzentrationen sowie der Ausscheidung des freien dU-Cortisols unter supportiver temporärer Blockade der β-Rezeptoren. Im weiteren Verlauf über inzwischen 2 1/4 Jahre zeigte sich eine niedrige basale Cortisolsekretion der rechten Nebenniere bei fehlender Supprimierbarkeit im Dexamethason-Hemmtest. Schlussfolgerung: Bei diskreten klinischen Zeichen der Nebennierenrindeninsuffizienz reicht zur Nachbildung eines physiologischen Cortisoltagesprofils mit morgendlichem Peak seit 1/2 Jahr die morgendliche Gabe von 5 mg Hydrocortison aus.Abstract.Case Report: We report on the laboratory, clinical, radiologic and histological findings of a 44-year-old male patient who was hospitalized with the clinical signs of Cushings syndrome. The laboratory findings were suggestive of an adrenal genesis. Abdominal computed tomography revealed macronodular hyperplasia of both adrenal glands. Specific endocrinological tests demonstrated an increased secretion of cortisol during adrenergic stimulation which, however, was absent following β-blocker medication. This would seem to point to an aberrant, β-receptor-mediated regulation of cortisol secretion as being the cause of increased cortisol production. ACTH-independent bilateral macronodular adrenocortical hyperplasia was also noted in the patients mother. Neither the father nor the brother were affected by the disease. Apart from one case of familial appearance involving mother and daughter previously reported in the literature, this is the second description of a familial appearance and the first case involving mother and son. The patient underwent a left-sided adrenalectomy. Quick postoperative normalization of S-cortisol day profile and excretion of free dU-cortisol were noted under supportive temporary blockade of β-receptors. In the further course, meanwhile spanning 2 1/4 years, a low basal cortisol secretion of the right adrenal gland has been observed, together with a lack of suppressibility in the dexamethasone suppression test. Conclusion: In the presence of mild clinical signs of adrenocortical insufficiency, matutinal administration of 5 mg hydrocortisone has proven sufficient for the past 6 months to reestablish a physiologic S-cortisol day profile with morning peak.

ASSOCIATION BETWEEN NUCLEATED RED BLOOD CELLS IN BLOOD AND THE LEVELS OF ERYTHROPOIETIN, INTERLEUKIN 3, INTERLEUKIN 6, AND INTERLEUKIN 12p70

The appearance of nucleated red blood cells (NRBC) in the circulation is associated with a variety of severe diseases, and indicates a relatively poor prognosis. Whether a malfunction of the bone marrow leads to this phenomenon is as unknown as the possible role that cytokines could play in this process. We analyzed erythropoietin, interleukin (IL)-3, IL-6, and IL-12p70 in the blood of 301 patients with circulating NRBCs. Two hundred fifty NRBC-negative patients served as controls. Multiple logistic regression revealed a significant association between the appearance of NRBCs in the blood and erythropoietin (odds ratio, 1.017; 95% confidence limits, 1.007-1.027; P < 0.001), IL-3 (odds ratio, 1.293; 95% confidence limits, 1.180-1.417; P < 0.001), IL-6 (odds ratio, 1.138; 95% confidence limits, 1.016-1.275; P < 0.05), and age (odds ratio, 1.019; 95% confidence limits, 1.009-1.030; P < 0.001), respectively. Gender and IL-12p70 were not significantly associated with the appearance of NRBC in the blood. To estimate the RBC production in the bone marrow, the increase in the reticulocyte concentration in blood was measured. The reticulocyte concentration in NRBC-positive patients was 69 ± 2/nL, which was significantly higher than in NRBC-negative patients (60 ± 2/nL; P < 0.01). Taken together, NRBC could be a marker that sums up hypoxic and inflammatory injuries. Thus, generally, the appearance of NRBC in blood is a valid parameter to identify patients at high mortal risk. Moreover, the increased number of reticulocytes in the blood of NRBC-positive patients may indicate that the appearance of NRBC is not associated with disturbed bone marrow function as far as the erythropoiesis is concerned.

Effectiveness of CT-Guided Percutaneous Biopsies of the Spine : An Analysis of 202 Examinations

RATIONALE AND OBJECTIVES The study goal was to retrospectively evaluate the effectiveness of computed tomography (CT)-guided spinal biopsies. MATERIAL AND METHODS Two hundred two CT-guided vertebral biopsies performed between May 1999 and June 2004 in 187 patients were retrospectively analyzed. Patient characteristics (age, sex, antibiotic therapy), technical parameters (depth and number of biopsies, needle approach), lesion features (spinal level, osteolysis, fluid collections, soft tissue tumor), and complications were documented. Furthermore, histopathological and microbiological diagnoses were considered. RESULTS There were two focal hematomas in our study group (complication rate: 1%). Histopathological diagnosis was established in 74% of examinations with spondylitis (41% of cases) being most common. In spinal tumors (27% of cases), malignant lesions were found in 52 of 54 examinations (96%). Osteolysis was diagnosed in 98% of patients with spondylitis and in 87% of patients with tumors (P < .01). Spinal tumors were most commonly seen in the sacrum (53%, P < .001), whereas spondylitis typically occurred in the lumbar spine (55%, P = .001). Neither patient age nor sex, needle approach, needle depth, or vertebral abnormalities showed a significant impact on diagnostic accuracy. Microbiological tests were performed in 98 patients (49%); 62 of 98 patients (65%) received antibiotic therapy. In 12 of 62 patients (19%) with antibiotic therapy and in 9 of 36 patients (25%) without antibiotic treatment, microbiological tests were positive (P = .153). Staphylococcus aureus was found in 9 of 21 examinations (43%). CONCLUSIONS CT-guided vertebral biopsy is a safe and effective procedure to establish final diagnosis in spinal lesions of unclear origin. Patient characteristics, lesions features, and technical considerations did not influence sample quality. In spondylitis, which was commonly caused by Staphylococcus aureus, microbiological yield was low regardless of antibiotic therapy.

A laboratory-based risk score for medical intensive care patients

Abstract Background: Established general risk score models for intensive care patients incorporate several clinical and laboratory data. However, the collection, documentation and classification of clinical data are time-consuming, incur labor-related costs, and are dependent on the experience of the examiner. Therefore, in the present study a general score for medical intensive care patients based solely on routine laboratory parameters is presented. Methods: Parameter selection was performed using stepwise logistic regression analysis. The maximum likelihood estimate of variable influence on mortality provided a relative weighting for each variable. The new score was compared to two established risk models (Acute Physiology And Chronic Health Evaluation II, APACHE II; and Simplified Acute Physiology Score II, SAPS II). Results: The study included 528 medical intensive care patients with a mean age of 65.4±0.7 years. The in-hospital mortality was 16.5% (87/528). Multiple logistic regression analysis revealed eight parameters with significant prognostic power: alanine aminotransferase, cholesterol, creatinine, leukocytes, sodium, thrombocytes, urea, and age. These parameters were used to build a new laboratory score called Critical Risk Evaluation by Early Keys (CREEK). The area under the receiver operating characteristics curve was 0.857 (0.814–0.900). Pearson correlation analysis showed significant correlation between CREEK and APACHE II (r=0.550) and SAPS II (r=0.516; p<0.001; n=387). The areas under curve of the APACHE II and the SAPS II were 0.869 and 0.874, respectively. Conclusions: We show that a general risk score for medical intensive care patients on admission based solely on routine laboratory parameters is feasible. The quality of risk estimation using CREEK is comparable to established risk models. Furthermore, this new score is based on quality controlled low-cost laboratory parameters that are routinely measured on admission to the intensive care unit. Therefore, no additional costs are involved. Clin Chem Lab Med 2008;46:855–62.

Effectiveness of CT-Guided Percutaneous Biopsies of the Spine: An Analysis of 202 Examinations1

RATIONALE AND OBJECTIVES The study goal was to retrospectively evaluate the effectiveness of computed tomography (CT)-guided spinal biopsies. MATERIAL AND METHODS Two hundred two CT-guided vertebral biopsies performed between May 1999 and June 2004 in 187 patients were retrospectively analyzed. Patient characteristics (age, sex, antibiotic therapy), technical parameters (depth and number of biopsies, needle approach), lesion features (spinal level, osteolysis, fluid collections, soft tissue tumor), and complications were documented. Furthermore, histopathological and microbiological diagnoses were considered. RESULTS There were two focal hematomas in our study group (complication rate: 1%). Histopathological diagnosis was established in 74% of examinations with spondylitis (41% of cases) being most common. In spinal tumors (27% of cases), malignant lesions were found in 52 of 54 examinations (96%). Osteolysis was diagnosed in 98% of patients with spondylitis and in 87% of patients with tumors (P < .01). Spinal tumors were most commonly seen in the sacrum (53%, P < .001), whereas spondylitis typically occurred in the lumbar spine (55%, P = .001). Neither patient age nor sex, needle approach, needle depth, or vertebral abnormalities showed a significant impact on diagnostic accuracy. Microbiological tests were performed in 98 patients (49%); 62 of 98 patients (65%) received antibiotic therapy. In 12 of 62 patients (19%) with antibiotic therapy and in 9 of 36 patients (25%) without antibiotic treatment, microbiological tests were positive (P = .153). Staphylococcus aureus was found in 9 of 21 examinations (43%). CONCLUSIONS CT-guided vertebral biopsy is a safe and effective procedure to establish final diagnosis in spinal lesions of unclear origin. Patient characteristics, lesions features, and technical considerations did not influence sample quality. In spondylitis, which was commonly caused by Staphylococcus aureus, microbiological yield was low regardless of antibiotic therapy.

Poor prognosis indicated by nucleated red blood cells in peripheral blood is not associated with organ failure of the liver or kidney

Abstract Background: The appearance of nucleated red blood cells (NRBCs) in peripheral blood is associated with a variety of severe diseases. When NRBCs are detected in blood, this is generally associated with increased mortality. Methods: In a prospective study, NRBCs and other laboratory parameters were measured daily in the peripheral blood of surgical intensive care patients. The appearance of NRBCs was analyzed in relation to laboratory indicators of organ injury. Results: A total of 284 surgical intensive care patients were included in this study. The mortality of NRBC-positive patients was 44.0% (40/91). This was significantly higher (p<0.001) than the mortality of NRBC-negative patients (4.2%, 8/193). Mortality increased with the NRBC concentration and the length of the NRBC-positive period. Multiple logistic regression analysis of several other clinical and laboratory risk indicators revealed a significant association between NRBCs and increased mortality, with an odds ratio of 1.95 (95% CI 1.35–2.82; p<0.001) for each increment in NRBC category (0, 1–40, 41–80, 81–240 and >240NRBC/μL). After the initial detection of NRBCs in blood, there were no significant increases in creatinine concentrations or alanine aminotransferase activity. However, the appearance of NRBCs coincided with increasing C-reactive protein and thrombocyte concentrations. Conclusions: The detection of NRBCs in blood of surgical intensive care patients is of prognostic power with regard to patient mortality. This prognostic significance of NRBCs was independent of some clinical and other laboratory risk parameters. The appearance of NRBCs in blood was not associated with kidney failure or lesion of the liver. Clin Chem Lab Med 2006;44:955–61.

Association of nucleated red blood cells in blood and arterial oxygen partial tension.

Abstract Background: Several studies suggest that the detection of nucleated red blood cells (NRBCs) in hospitalized patients indicates an increased risk of mortality. This study evaluates the impact of low arterial oxygen partial tension (pO2) on NRBC appearance and prognosis in NRBC positive patients. Methods: NRBCs in blood, arterial blood gases, and other laboratory parameters were monitored daily in 234 surgical intensive care patients. pO2 was assessed in relation to mortality and the detection of NRBCs. Results: NRBCs were found in 67 patients (28.6%). Mortality was significantly higher in NRBC positive patients (41.8%, 28/67) than in those that were NRBC negative (3.0%, 5/167). Multivariate logistic regression showed an increased mortality in NRBC positive patients (odds ratio 5.79; 95% confidence interval (CI) 1.07–31.33, p<0.05). NRBC positive patients showed significantly lower pO2 levels during intensive care treatment than NRBC negative patients. Prior to the initial detection of NRBCs in the peripheral blood, pO2 levels were significantly lower in patients who died than in surviving patients. After the first appearance of NRBCs, no significant difference in pO2 between these groups was found. Conclusions: The detection of NRBCs is of prognostic significance concerning patient mortality. In NRBC positive patients, hypoxemia occurs more frequently. Low-levels of pO2 seem to precede the appearance of NRBCs, especially in those patients with high risk of mortality.

The Secretion of Endothelin-1 by Microvascular Endothelial Cells from Human Benign Prostatic Hyperplasia is Inhibited by Vascular Endothelial Growth Factor

Prostate growth seems to be influenced by paracrine factors like endothelin-1 (ET-1), originating from the microvascular endothelium. Recently, we reported on the first isolation and primary culture of microvascular endothelial cells (HPEC) derived from tissue of human benign prostatic hyperplasia (BPH). Therefore, direct investigation of growth factor secretion by HPEC is now possible. BPH tissue was cut into small cubes and gently squeezed after incubation with dispase. HPEC were cultured from the resulting cell suspension after a stepwise selection by use of superparamagnetic beads coated with antibodies against endothelial specific antigens. HPEC were characterized by flow cytometry. After the incubation of HPEC either with vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNF-α), or adenosine triphosphate (ATP), the secretion of ET-1 was measured by ELISA. HPEC showed a typical endothelial morphology. They were positive for von Willebrand factor and CD31. The ET-1 secretion of HPEC was inhibited by VEGF, but was unaffected by TNF-α or ATP. Furthermore, histochemistry revealed that in vivo microvascular endothelial cells were negative for ET-1. Because of the suppression by the widespread VEGF, it is unlikely that ET-1 from the microvascular endothelium acts as a growth factor in human BPH.