A prospective cluster trial to increase antibiotic prescription quality in seven non-ICU wards.

Aim: To evaluate general shortcomings and faculty-specific pitfalls as well as to improve antibiotic prescription quality (ABQ) in non-ICU wards, we performed a prospective cluster trial. Methods: An infectious-disease (ID) consulting service performed a prospective investigation consisting of three 12-week phases with point prevalence evaluation conducted once per week (=36 evaluations in total) at seven non-ICU wards, followed by assessment of sustainability (weeks 37-48). Baseline evaluation (phase 1) defined multifaceted interventions by identifying the main shortcomings. Then, to distinguish intervention from time effects, the interventions were performed in four wards, and the 3 remaining wards served as controls; after assessing effects (phase 2), the same interventions were performed in the remaining wards to test the generalizability of the interventions (phase 3). The prolonged responses after all interventions were then analyzed in phase 4. ABQ was evaluated by at least two ID specialists who assessed the indication for therapy, the adherence to the hospital guidelines for empirical therapy, and the overall antibiotic prescription quality. Results: In phase 1, 406 of 659 (62%) patients cases were adequately treated with antibiotics; the main reason for inappropriate prescription was the lack of an indication (107/253; 42%). The antibiotic prescription quality (ABQ) significantly increased, reaching 86% in all wards after the focused interventions (502/584; nDf=3, ddf=1,697, F=6.9, p=0.0001). In phase 2 the effect was only seen in wards that already participated in interventions (248/347; 71%). No improvement was seen in wards that received interventions only after phase 2 (189/295; 64%). A given indication significantly increased from about 80% to more than 90% (p<.0001). No carryover effects were observed. Discussion: ABQ can be improved significantly by intervention bundles with apparent sustainable effects.

Macrophage activation syndrome in a patient with pulmonary inflammatory myofibroblastic tumour.

We describe for the first time a case of macrophage activation syndrome (MAS) in a patient with a history of inflammatory myofibroblastic tumour (inflammatory pseudotumour, IPT) of the lung and thoracic spine. The patient was admitted to the intensive care unit with a history of prolonged remitting fever, hepatosplenomegaly, bilaterally enlarged thoracic lymph nodes and an acute severe inflammatory response syndrome (SIRS). Up-regulated cytokine production (e.g. IL-1ß and IL-6), increased levels of ferritin and circulating soluble interleukin-2 receptor (sIL-2R, sCD25) led to the differential diagnosis of MAS. Bone marrow aspiration, the main tool for a definite diagnosis, revealed macrophages phagocytosing haematopoietic cells. Immunosuppressive therapy with corticosteroids and cyclosporine was an effective treatment in this patient.

Littoral cell angioma of the spleen mimicking posttransplantation lymphoma in a 63-year-old renal transplant patient.

In addition to lymphomas, vascular tumors represent the most common neoplasms of the spleen. Littoral cell angiomas are benign vascular tumors originating from the littoral cells lining the splenic sinuses. In this report, we describe the case of a 63-year-old patient who developed night sweats 16 months after renal transplantation. Diagnostic workup showed multiple splenic masses believed to represent lymphoma infiltration to the spleen. Lymph nodes and bone marrow were unaffected, and diagnostic splenectomy was performed. Histological examination of the pathological specimen from the splenectomy specimen showed multiple littoral cell angiomas of the spleen. We recommend that physicians involved in the area of organ transplantation, especially kidneys, remain alert for other rarer splenic lesions in transplant recipients than posttransplantation lymphoma. More specific tools need to be developed to aid in the differential diagnosis of splenic masses to avoid splenectomy in patients with littoral cell angiomas.

Plasma endothelin-1 in hemodialysis treatment - the influence of hypertension.

In patients on chronic hemodialysis hypotensive episodes are frequently encountered during the course of treatment and the prevalence of atherosclerosis is increased. Endothelin-1 (ET-1), an endothelium-derived peptide with vasoconstrictive and mitogenic effects on smooth muscles, is involved in vascular tone regulation and in the pathogenesis of atherosclerosis. The aim of the present study was to investigate plasma ET-1 during hemodialysis treatment and to explore the probable influence of pre-existing hypertension. Forty-seven hemodialysis patients (21 females, mean age 62 +/- 12 years) were evaluated and hypertensive patients (n = 33) were compared to normotensive patients (n = 14). Relative blood volume changes (hemoglobinometry) and blood pressure were measured. Samples were taken before, every hour during and after hemodialysis. Plasma ET-1 was measured by enzyme-linked immunosorbent assay and results were corrected according to hemoconcentration. Hemodialysis with an ultrafiltration rate of 2224 +/- 933 mL was performed. Total blood volume at the end of hemodialysis was 89.4 +/- 8.2% of the pretreatment volume. The fall in blood pressure (137/74 +/- 22/11 mmHg vs 127/73 +/- 30/14 mmHg) correlated with the decrease in blood volume (mean blood pressure: r = 0.33). Plasma ET-1 increased from 1.29 +/- 0.47 pg/mL before to 1.46 +/- 0.56 pg/mL (reference range 0.3-0.9) at the end of hemodialysis (P < 0.05). This rise was more pronounced in patients with hypertension than in normotensive individuals (P < 0.05). The change in blood volume (r = 0.41) and blood pressure (mean blood pressure: r = 0.34) correlated with plasma ET-1 at the end of hemodialysis (P < 0.05). Plasma ET-1 was enhanced in hemodialysis patients compared to normal subjects. During the hemodialysis session an increase in ET-1 was encountered, which was more pronounced in hypertensive than in normotensive patients and paralleled the hemodynamic changes. Apart from pre-existing hypertension, further factors potentially influencing ET-1 include local endothelial injury (arteriovenous fistula) and generalized bioincompatibility reactions (e.g. foreign surface contact) occurring during hemodialysis.

Hemodialysis procedure does not affect the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease.

Atherosclerosis is by far the leading cause of mortality and morbidity in patients with end stage renal disease undergoing chronic hemodialysis (HD). Vascular endothelial cell adhesion molecules like the intercellular adhesion molecule-1 (ICAM-1) and the vascular cell adhesion molecule-1 (VCAM-1) are involved in the pathogenesis of atherosclerosis. Their soluble forms (sICAM-1, sVCAM-1) are considered potential serum markers of endothelial activation and atherosclerosis. The aim of this study was to clarify the influence of the HD procedure on the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease. We evaluated 35 clinically stable patients (18 males, 17 females, mean age 61 +/- 12) on chronic HD treatment. Diabetes mellitus coexisted in eight patients and arterial hypertension in 23 patients. Blood was drawn before, every hour during, and after a single HD session in each patient. Low-flux cuprophane dialyzers (GFS 12, Gambro, Lund, Sweden) were used in 22 and high-flux polysulfone dialyzers (Hemoflow F 60S, Fresenius, Oberursel, Germany) in 13 cases. At 30 min into the HD session (n=31, 20 low-flux HD, 11 high-flux HD) blood was drawn simultaneously from the entrance and the exit line of the dialyzer. From all these samples, serum concentrations of sICAM-1 and sVCAM-1 were determined by commercially available enzyme immunoassays (ELISA, R&D Systems, Minneapolis, USA). Results were corrected according to hemoconcentration, where appropriate. Plasma levels of sVCAM-1 were elevated in patients with end stage renal disease before the beginning of the dialysis session when compared to healthy controls (1449 +/- 497 ng/mL vs. 691 +/- 118 ng/mL). On the contrary, such an elevation was not found in the case of sICAM-1 (231 +/- 58.5 ng/mL vs. 236.4 +/- 96.8 ng/mL in healthy controls). These levels remained stable in all measurements throughout the dialysis procedure. Furthermore, serum sICAM-1 and sVCAM-1 levels remained unaltered after the passage of the dialyzer. The levels of sICAM-1 and sVCAM-1 were not influenced by the existence of diabetes mellitus, hypertension, or by the utilization of biocompatible, high flux dialyzers. Our study confirms that in chronic HD patients serum levels for sVCAM-1 are elevated. The levels of adhesion molecules are not affected by the HD procedure. These findings probably can be attributed to a decreased renal clearance or catabolism of sICAM-1 and sVCAM-1 and to the different sources of the two molecules. Neither coexisting diabetes mellitus nor arterial hypertension influences the circulating levels of these adhesion molecules. The functional role of sVCAM-1 and sICAM-1, the exact renal contribution to their metabolism, and their role as markers of atherosclerosis in chronic renal disease need further evaluation.

Endothelin-1 plasma levels in hemodialysis treatment--the influence of type 2 diabetes.

In patients on chronic hemodialysis the prevalence of atherosclerosis is increased and is by far the leading cause of morbidity and mortality. Endothelin-1, an endothelium-derived peptide with vasoconstrictive and mitogenic effects on vascular smooth muscles, is involved in the pathogenesis of atherosclerosis. The aim of the present study was to investigate the time course of plasma endothelin-1 levels during a hemodialysis session and to explore the influence of preexisting type 2 diabetes mellitus. Forty-five clinically stable hemodialysis patients (21 females, 24 males; mean age 62 +/- 12 years) were evaluated. Patients with type 2 diabetes (n= 11) were compared with the group of patients without diabetes (n=34). Relative blood volume (BV) changes (hemoglobinometry) and blood pressure (BP) was measured. Samples were taken before, every hour during, and after hemodialysis. Plasma endothelin-1 levels were measured by enzyme-linked immunoassay (ELISA) and results were corrected according to hemoconcentration. Hemodialysis with an ultrafiltration of 2215 +/- 952 mL was performed. Total BV at the end of hemodialysis was 89.3% +/- 8.3% of the pretreatment volume. Plasma endothelin-1 was enhanced in hemodialysis patients compared to normal subjects and increased from 1.28 +/- 0.47 before to 1.44 +/- 0.54 pg/mL (ref. 0.3-0.9) at the end of hemodialysis (p<0.05). The BV change (r=0.41) and the BP (mean BP: r=0.34) correlated with plasma endothelin-1 at the end of hemodialysis (p<0.05). The levels of endothelin-1 were significantly higher in the group of dialysis patients with type 2 diabetes compared to nondiabetics in all measurements (p<0.05). These findings suggest a potential role of endothelin-1 in the pathogenesis of vascular dysfunction in diabetes mellitus. The dialysis procedure per se, through vasoconstriction due to BV decrease, local endothelial injury (a.v. fistula), or bioincompatibility reactions (foreign surface contact) may additionally alter endothelial cell functions.

HELLP syndrome, multifactorial thrombophilia and postpartum myocardial infarction.

A case of postpartum acute myocardial infarction with intraventricular thrombus occurred in a woman with HELLP syndrome. Since coronary artery disease was ruled out angiographically, the assumed pathophysiological mechanism for myocardial malperfusion was intermittend coronary vasospasm and thrombosis. There were several thrombophilic risk factors detectable (heterozygous factor V Leiden, low levels of antithrombin III, protein S deficiency), whose possible impact in this rare but severe clinical condition is discussed.

Hyperglycemia at admission to the intensive care unit is associated with elevated serum concentrations of interleukin-6 and reduced ex vivo secretion of tumor necrosis factor-alpha.

OBJECTIVES: The aim of the study was to investigate the association between admission blood glucose concentrations and immune function variables and its correlation to mortality rate in patients of a medical intensive care unit. DESIGN: Prospective, observational study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Patients were 189 consecutive critically ill patients in the medical intensive care unit. INTERVENTIONS: At admission to the intensive care unit, serum concentrations of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-alpha were measured with immunometric assays. Additionally, ex vivo secretion of tumor necrosis factor-alpha after stimulation with lipopolysaccharide in a whole blood assay and cytometric human leukocyte antigen-DR expression on monocytes were determined in all study subjects. Simplified Acute Physiology Score II and Therapeutic Intervention Scoring System-28 were calculated for the first day in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The relationships between blood glucose concentrations and immunologic variables were analyzed using univariate and multivariate statistical methods. Overall, 75 patients (39.7%) presented with hyperglycemia. An elevated blood glucose concentration at admission was related to an increased risk of mortality in the intensive care unit (odds ratio, 2.6; p = .009). At univariate and multivariate analysis, hyperglycemia was associated with increased serum concentrations of interleukin-6 (p < .05), a reduced ex vivo production of tumor necrosis factor-alpha (p < .01), and a history of diabetes mellitus (p < .05), whereas other clinical (including Simplified Acute Physiology Score II and Therapeutic Intervention Scoring System-28) and immunologic variables were not statistically related to blood glucose. CONCLUSIONS: Our main findings show that admission hyperglycemia is statistically related to distinct changes of humoral and cellular immune functions. Furthermore, elevated glucose concentrations at admission are associated with increased intensive care unit mortality rate in a medical intensive care unit. Although these data do not explain cause and effect, our results provide a strong rationale for studying the immunologic effects of strict glycemic control in the intensive care unit during the course of critical illness.