Septic shock in children in an urban area in Western Germany--outcome, risk factors for mortality and infection epidemiology.

BACKGROUND: Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality in Western Germany. PATIENTS: Children with septic shock aged 2 months to 17 years. METHODS: In a multi-center retrospective study of 20 children's hospitals data were obtained and analyzed by chart review. Risk factors for mortality were identified and assessed by multivariate regression analysis. RESULTS: Overall mortality in 83 cases with septic shock was 25% (21 patients). Significant risk factors were high PRISM III score, low pH, low arterial systolic blood pressure, presence of disseminated intravascular coagulation and extent of multi-organ failure, but not lactate (p=0.05) and base excess (p=0.065). Mortality in hospitals which treated 10 or more patients (category 1) was 17% and increased to 22% in hospitals which treated 3-6 patients (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate was 61% (p<0.01 when compared to category 1 or 2). A stepwise increase was also seen in the severely sick patients according to PRISM III (>19): category 1: 23%, category 2: 40%, category 3: 62.5% (p<0.05 for comparison of category 1 and 3). Multivariate analysis of significant risk factors revealed low number of treated patients as the only individual risk factor for mortality. CONCLUSION: Mortality from pediatric septic shock in an urban area in Western Germany is high. Disease severity and treatment in a department with few cases were associated with increased mortality.

Putative new heat-stable cytotoxic and enterotoxic factors in culture supernatant of Escherichia coli isolated from drinking water

Enteric infections caused by the ingestion of contaminated water, especially by Escherichia coli, are important to define the virulence properties of these bacteria. Due to frequent infantile diarrhea in the city of Ouro Preto, Minas Gerais state, Brazil, the phenotypic and genotypic diarrheagenic properties of E. coli isolated from drinking water were studied. The culture supernatants of 39 (40 percent) among a total of 97 E. coli isolates from drinking water were positive by suckling mouse assay and induced cytotoxic effects on Vero cells. The enterotoxic and cytotoxic activities were present in the fraction with less than 10 kDa and were not lost when heated up to 60¨¬C and 100¨¬C for 30 minutes. PCR assays showed that among these 39 Vero cytotoxigenic E. coli, four (10.2 percent) were positive for ST II (estB) and two (5 percent) positive for ¥áHly (hlyA). Gene amplification of SLT (stx 1, stx 2), ST I (estA), LT (eltI, eltII), EAST1 (astA), EHly (enhly) and plasmid-encoded enterotoxin (pet) were not observed. This heat-stable cytotoxic enterotoxin of E. coli is probably a new putative diarrheagenic virulence factor, as a toxin presenting these characteristics has not yet been described.

Incidence and costs of osteoporosis-associated hip fractures in Austria.

This study is an investigation into the epidemiologic and socioeconomic impact of osteoporosis-associated hip fractures in Austria. We determined age- and gender-specific incidence rates of osteoporosis-associated hip fractures for all patients treated in hospitals in 1995 and calculated mortality rates, hospitalization days and direct costs of hospitalization. The data were obtained from the hospital discharge statistics for all general hospitals and for all hospitals of the General Austrian Accident Insurance. To calculate the portion of hip fractures attributable to osteoporosis in a given age-group, a basic, non-osteoporotic incidence of hip fractures was determined for ages 20-39, using gender-specific regression models. 11,379 patients with osteoporotic hip fractures underwent treatment in Austrian hospitals in 1995, accounting for 79 percent of all hip fracture patients treated. 82 percent of those were female, with the highest incidence among women aged 95 years and older with a rate of 3,000/100,000. For male patients the highest incidence was observed for the age-group of 90-94 years with 1,743/100,000. International comparisons indicate these incidence rates to be similar to those reported for the Swiss population. In 1995, 778 patients or 6.8 percent of all patients with osteoporotic hip fractures died during hospitalization. Hospital care of patients with osteoporotic hip fractures required an overall 250,268 bed-days with an age-group-specific length of stay between 8.5-27 days for female and 16-23 days for male patients. The total cost of hospital treatment of osteoporotic hip fractures in Austria was ATS 1,043,379,000 (US$ 103,509,800), with average costs per patient of ATS 91,700 (US$ 9,097). Due to the aging of the population in the years to come, an increase of osteoporotic hip fractures among individuals aged 50 years and older must be expected. The economic importance of this development and its impact on the health care system must be considered as significant.

Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial.

Recent studies suggest that low molecular weight heparin (LMW heparin) therapy in malignancy may improve cancer survival following surgical resection. We studied prospectively whether cancer mortality during follow-up in women with previously untreated breast, and pelvic cancer is reduced in those who randomly received LMW heparin (Certoparin) compared to patients given unfractionated heparin (UF heparin) for thrombosis prophylaxis during primary surgery. In a prospective, randomized, double-blind clinical trial, 160 patients received Certoparin and 164 UF heparin until post-operatively day 7. Survival estimations are based on the outcome data from a subset of 140 LMW heparin - and 147 UF heparin recipients. Long-term survival in the Certoparin group compared to the UF heparin group was significantly improved after 650 days (P=0. 0066) but not thereafter when analysis was performed on all cancer cell types combined. In the probability estimates survival benefit within this time was restricted to patients with pelvic cancer but was not observed in breast cancer. However, in breast cancer patients who received LMW heparin the impact of classical tumor prognostic markers was statistically significant after 1,050 days but not after 650 days. Thus, breast cancer patients with unfavorable prognosis seem to benefit in terms of survival advantage from LMW heparin within the 650 days after surgery. These results suggest that improvement in cancer survival can be achieved after even a short course of treatment with LMWH (compared to UFH) given for DVT prophylaxis in the post-operative period. An effect of UFH on disease outcome is not excluded. Further definitive trials of LMWH vs. placebo for cancer outcome (rather then DVT) using doses and schedules that may be more optimal are indicated.

Blood rheology during chemotherapy in patients with ovarian cancer.

The use of platinum based chemotherapy in ovarian malignancy and other cancer types is known to be associated with deep vein thrombosis. In a prospective study of 47 patients with ovarian cancer of International Federation of Gynecology and Obstetrics stage Ib-IV, serial rheological parameters were determined (plasma viscosity, red blood cell aggregation under conditions of stasis and low shear) in addition to hemoglobin, hematocrit, leukocytes, platelets, and fibrinogen. At the same time the incidence of deep vein thrombosis was recorded before, during six cycles of first line cisplatinum/epirubicin/cyclophosphamide chemotherapy, and 2 months thereafter (two-months check-up). Only six patients with previous deep vein thrombosis concomitantly received thrombosis prophylaxis once with 3000 anti Xa Units/day subcutaneously low molecular weight heparin (Certoparin, NOVARTIS) throughout chemotherapy. Before each cycle of chemotherapy impedance plethysmography was used for deep vein thrombosis screening and when this was suspected on the basis of physical examination or a pathological result of impedance plethysmography, ascending venography of both legs was performed. During chemotherapy, the venographically proven deep vein thrombosis incidence was 10.6%; (95% CI: 3.5-23.1) with no differences in occurrence between FIGO stages. Before operation mean plasma viscosity was higher in patients who developed deep vein thrombosis postoperatively (n = 5; 1.46 +/- 0.2 mPas) and during chemotherapy (n = 5; 1.49 +/- 0.1 mPas) as compared to those without deep vein thrombosis (1.38 +/- 0.2 mPas; p = 0.04). Postoperatively (before chemotherapy) none of the rheological variables were significantly different in patients with versus those without deep vein thrombosis during chemotherapy. Leukocyte and platelet counts decreased significantly during chemotherapy until the two-months check-up after chemotherapy while red blood cell aggregation (stasis & low shear), hemoglobin, and hematocrit showed a continuous but nonsignificant increase. The mean plasma viscosity, instead, declined into the normal range after the 4th cycle of chemotherapy (1.33 +/- 0.1 mPas) in patients without thrombosis. In contrast, mean plasma viscosity was increased to 1.48 +/- 0.1 mPas at the time of deep vein thrombosis diagnosis during chemotherapy. In the ovarian cancer patients of this study, the development of deep vein thrombosis postoperatively and during chemotherapy was associated with a hematocrit-independent increase in blood viscosity characterized by a high plasma viscosity and normal or low hematocrit, which was present before primary surgery as well as at the time of deep vein thrombosis diagnosis.

[Incidence of nosocomial infections as an element of cost-conscious quality management of inpatient care]. / Erhebung nosokomialer Infektionen als Element eines kostenbewussten Qualitätsmanagements im stationären Bereich.

The prevention of nosocomial infections is a result of many variables in a wide range of architectural, personal and organisational decisions taken into account in modern hospital plannings. The frequency of nosocomial infections in a given period can be used as one possible indicator of outcome quality of our hospitals. Contrary to the frequently uttered claims of many experts, who demand for a continuous hygienic monitoring in hospitals [1;2;3;4], routine procedures have not been unanimously established until now. Assessment and evaluation of nosocomial infections seem to be anything but trivial. Purpose of the described pilot study at the University of Lubeck was the development and test of a set of practicable routines to early discover and assess nosocomial infections. Methods of epidemiologic evaluation have been implemented to grant a perpetuos hygienic monitoring even on a limited base of personal, structural and financial resources. In a next step, further adaptations and improvements are planned, thus making assessment and evaluation independent of central institutions.

Hyperviscosity syndrome in patients with ovarian carcinoma.

BACKGROUND: In patients with ovarian carcinoma, an hematocrit-independent hyperviscosity syndrome is often present. The syndrome is characterized by normal or low hematocrit and hemoglobin concentration, an elevated platelet count, and an increase in clotting factor turnover. Because deep vein thrombosis (DVT) often complicates the course of ovarian carcinoma, the aim of this study was to investigate the possible association of hyperviscosity syndrome with the development of DVT. METHODS: Rheologic estimations of the blood included red blood cell (RBC) aggregation (stasis and low shear), plasma viscosity (pv), blood cell count, and fibrinogen, which were performed before primary surgery and the beginning of perioperative heparin thrombosis prophylaxis on 63 of 65 patients with Stage I-IV ovarian malignancy (according to the staging criteria of the International Federation of Gynecology and Obstetrics). Two patients who had had DVT 5-6 weeks in advance of the study were excluded from rheologic calculations. Thrombosis screening by impedance plethysmography was performed the day before primary major surgery; postoperatively on Days 1, 3, 5, 7, and 10; before each of 6 cycles of chemotherapy (once every 3 weeks); and thereafter once every 3 months during follow-up. All blood tests were also performed on 72 healthy women and 29 patients with benign ovarian tumor the day prior to surgery. RESULTS: All ovarian carcinoma patients, including 7 patients with tumors of low malignant potential, were eligible for surgery, and all except those with Stage IV disease (n = 12) were macroscopically tumor free after surgery. Before surgery, RBC aggregation, pv, and platelet and fibrinogen concentrations were significantly higher (P < 0.05) in cancer patients than in either of the control groups, whereas hemoglobin (hb) and hematocrit (hct) were significantly lower in cancer patients than in healthy women (P < 0.001). Platelet, leukocyte, and fibrinogen concentrations were significantly correlated to disease stage, whereas pv, RBC aggregation, hb, and hct were not. The preoperative pv was significantly higher in patients who later developed DVT (n = 17; 1.46+/-0.13 mPas; P = 0.01) than in those who did not (1.34+/-0.14 mPas). Of all estimated preoperative variables, only pv was a significant risk factor for postoperative and subsequent DVT (RR: 29.84; 95% CI: 1.076-827.16; P = 0.04). CONCLUSIONS: Our results confirm the presence of a hematocrit- and stage-independent hyperviscosity syndrome in untreated ovarian carcinoma patients. In addition, a high preoperative plasma viscosity was a significant risk factor for the development of DVT in the postoperative period and even thereafter.

[Specificity of "combi-effect" after xenogenic discordant heart-lung transplantation]. / Spezifität des "Combi-Effektes" nach xenogen diskordanter Herz-Lungentransplantation.

UNLABELLED: The purpose of this study was to investigate whether the "Combi-Effect" is specific for the transplanted lung tissue or not. METHOD: In a Guinea-pig to rat model we compared the heterotopic heart-lung transplantation (HLTx, n = 5) with a second heart transplantation (DHTx, n = 5) and a combined heart-kidney transplantation (HKTx, n = 5). Apart from the heart transplant survival time we determined the concentrations of histamine, CH-50, IgG, IgM, leucocytes and thrombocytes in the blood. At time of rejection all tissues were examined histologically and immunohistologically (ED-11, IgG, IgM, OX-39, W3-13, ED-1, NKR-P1, OX-19). RESULTS: We could achieve a significant prolongation of the heart transplant survival time by combined HLTx compared to HTx (25' to 12', p < 0.01). DHTx showed no effect (7' 53" to 11' 27"). But after HKTx the cardiac survival was even longer than after HTx and HLTx (62.8' to 12' and 25', p < 0.01). CH-50 showed significant lower concentrations after HLTx (180 U/l) and HKTx (178 U/l) than after HTx (260 U/l). Thrombocytes and leucocytes were lower, concentration of histamine higher than after HTx (p < 0.01). Immunohistologically C3 revealed a lower deposition in the rejected heart transplants after combined HLTx/HKTx than after isolated HTx. CONCLUSION: The "Combi-Effect" is stronger after HKTx than after HLTx. He is not specific for the lung tissue.

ProC Global: the first functional screening assay for the complete protein C pathway.

In clinical practice, venous thromboembolic complications are much more frequent than bleeding disorders. In fact, disturbances within the protein C pathway due to coagulation factor V (FV) Leiden mutation and deficiency of protein C or protein S are the most frequent abnormalities in hereditary thrombophilia. Furthermore, acquired dysfunctions of the protein C system may predispose the single individual to an increased thrombotic risk. A routine-suited screening assay that would allow the monitoring of the proper interplay of factors in the protein C pathway could add an important factor to the basic coagulation profile. This consists of the prothrombin time and of the activated partial thromboplastin time, which currently allow only a screening for increased risk for bleeding but not for venous thromboembolism. A new functional screening test for the protein C system such as the presented ProC Global should therefore facilitate detection of FV Leiden as well as deficiency of protein C and protein S. The results of the present evaluation indicate that ProC Global is highly sensitive to activated protein C resistance/FV Leiden (100%) and protein C deficiency (90%) and sensitive to protein S deficiency (63%). Furthermore, the assay gives a quantitative measure of the net potential of the protein C pathway in relation to the intrinsic procoagulant system. The use of this assay for a prospective assessment of thromboembolic risk is the subject of current studies.

Blood coagulation and thrombosis in patients with ovarian malignancy.

Ovarian cancer cells appear to be capable of both thrombin formation and induction of fibrin degradation which may be essential prerequisites for the development of deep vein thrombosis (DVT) as well as the spread of malignancy. To study further this coagulation-cancer interaction in 60 patients with untreated ovarian cancer of FIGO stage I-IV the incidence of DVT was recorded pre-operatively, post-operatively on day 1, 3, 5, 7, 10, before each of six cycles of Cisplatinum/ Epirubicin/Cyclophosphamide chemotherapy, during follow-up and in the post-operative period of second look surgery. In addition, blood coagulation tests results were determined prospectively. Two patients were excluded from these calculations due to previous DVT 5 to 6 weeks before the diagnosis of ovarian cancer but all patients were eligible for surgery and randomized to receive either daily low molecular weight heparin (LMWH) (n = 28) or unfractionated heparin (UFH) (n = 32) for perioperative thrombosis prophylaxis until the 7th post-operative day. According to the FIGO stage, patients were equally distributed in the 2 heparin treatment groups. The predictive value of pre-operative coagulation test results, clinical parameters, and type of heparin used were tested in univariate and multivariate analysis for development of post-operative DVT and overall patients survival. Impedance plethysmography for DVT screening was used. The presence of DVT was then confirmed by phlebography. Only D-dimer and fibrinogen levels were correlated significantly with the FIGO stage while antithrombin, protein C, and plasminogen activator inhibitor activity were not. The incidence of DVT was 6.7% (4/60) up to the 7th and 8.3% (5/60) between the 8th and 29th post-operative day. DVT occurred in 10.6% (5/47) during chemotherapy. Pre-operative coagulation test results, the type of heparin used, and clinical parameters were not significant risk factors for post-operative DVT development in univariate analysis. The D-dimer and fibrinogen levels were significant risk factors for reduced overall survival in univariate analysis but only the FIGO stage was an independent predictor (in multivariate analysis). After a median follow up of 26.5 months (min. 8 months, max. 41 months), 21.4% of LMWH treated and 37.5% of UFH-treated patients died of cancer (p = 0.26). Pre-operative test results were neither predictive for DVT nor the outcome of cancer but patients showed an improved though not statistically significant overall survival after LMWH treatment.

The impact of ischemic lesions in the donor kidney, donor age, recipient age and HLA (A, B, C, DR, DQ) matching on clinical course after kidney grafting.

It is generally accepted that HLA matching improves graft survival. However, there is no consensus on whether this improvement is reflected on daily clinical course. Clinical course after renal transplantation depends on many factors, such as donor age, recipient age, ischemic score in the kidney, and HLA matching. The relative contribution of these factors is unknown. Because management of the recipients in the various centers differs considerably, only a single centre study would reveal the relative contribution of all these factors. Therefore, in our centre we studied the influence of these parameters on the clinical course after renal allografting.