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Objective: To test whether real-time polymerase chain reaction allows for rapid quantitative detection of Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila in bronchoalveolar lavage fluids and to determine the prevalence of these pathogens in nosocomial ventilator-associated pneumonia.Design: Prospective epidemiologic study applying a new molecular biology-based diagnostic tool during a 27-month period.Setting: Three medical intensive care units of a tertiary care university hospital.Patients: One hundred patients suffering from nosocomial ventilator-associated pneumonia, hospitalized for > or =14 days, intubated for reasons other than pneumonia, and mechanically ventilated for >48 hrs.Interventions: None.Measurements and Main Results: S. pneumoniae, M. pneumoniae, and C. pneumoniae were detected in bronchoalveolar lavage fluids of 100 patients in 20 (20%), three (3%), and two (2%) cases, respectively. There of 17 (71%) revealed no growth or no significant growth by conventional culture. In one patient, S. pneumoniae and M. pneumoniae were detected simultaneously. Corresponding colony-forming units/mL were partly up to 10 CFU/mL with Gram stainings showing signs of acute inflammation in 80%. A significant temporary correlation between the number of days on ventilator, development of nosocomial pneumonia, and the frequency of detection of these pathogens was found for day 4.Conclusions: S. pneumoniae, M. pneumoniae, and C. pneumoniae should be considered as causative agents in critically ill patients who develop early-onset nosocomial ventilator-associated pneumonia. Thus, empirical antimicrobial regimens should cover S. pneumoniae, Chlamydia, and Mycoplasma alike. Quantitative polymerase chain reaction is a fast diagnostic tool allowing for detection of these bacteria within 3 hrs in pretreated patients. [ABSTRACT FROM AUTHOR]

We describe a patient suffering from nosocomial Legionella pneumophila pneumonia with extremely high lipopolysaccharide (LPS) concentrations (peak concentration = 725 EU/ml). This unexpectedly high LPS load led to an exaggerated response of the cytokine network. Although immediate treatment with macrolides was instituted, the patient developed an adult respiratory distress syndrome. Despite application of nitric oxide and porcine natural surfactant factor, the patient died 5 days after admission to the ICU. Because of this dramatic case, we emphasize physicians to be aware of L. pneumophila and to include this organism into the diagnosis and antibiotic therapy in patients with nosocomial pneumonia. [ABSTRACT FROM PUBLISHER]

Rationale and Objective: The discharge summary (DS) is one of the most important instruments to transmit information to the treating general physician (GP). The objective of this study was to analyse important components of DS, structural characteristics as well as medical and general abbreviations., Method: One hundred randomly selected DS from five different clinics were evaluated by five independent reviewers regarding content, structure, abbreviations and conformity to the Austrian Electronic Health Records (ELGA) using a structured case report form. Abbreviations of all 100 DS were extracted. All items were scored on a 4-point Likert-type scale ranging from "strongly agree" to "strongly disagree" (or "not relevant"). Subsequently, the results were discussed among reviewers to achieve a consensus decision., Results: The mandatory fields, reason for admission and diagnosis at discharge were present in 80% and 98% of DS. The last medication was fully scored in 48% and the recommended medication in 94% of 100 DS. There were significant overall differences among clinics for nine mandatory items. In total, 750 unexplained abbreviations were found in 100 DS., Conclusions: In conclusion, DS are often lacking important items. Particularly important are a detailed medication history and recommendations for further medication that should always be listed in each DS. It is thus necessary to design and implement changes that improve the completeness of DS. An important quality improvement can be achieved by avoiding the use of ambiguous abbreviations., (© 2021 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose.

Objective: To provide a novel way to predict the likelihood that antibiotic therapy will result in prompt, adequate therapy on the basis of local microbiological data., Design and Setting: Prospective study conducted at 3 medical intensive care units at the Viennese General Hospital, a tertiary care medical university teaching hospital in Vienna, Austria., Patients: One hundred one patients who received mechanical ventilation and who met the criteria for having ventilator-associated pneumonia., Design: Fiberoptic bronchoscopic examination was performed, and bronchoalveolar samples were collected. Samples were analyzed immediately by a single technician. Minimum inhibitory concentrations were determined for imipenem, cephalosporins (cefepime and cefpirome), ciprofloxacin, and piperacillin-tazobactam, and drug resistance rates were calculated. These drug resistance rates were translated into the likelihood of inadequate therapy (LIT; the frequency of inadequately treated patients per antibiotic and drug-resistant strain), cumulative LIT (the cumulative frequency of inadequately treated patients), and syndrome-specific LIT., Results: Among the 101 bronchoalveolar samples, culture yielded significant (at least 1 x 10(4) colony-forming units per mL) polymicrobial findings for 34 and significant monomicrobial findings for 31; 36 culture results were negative. Of the isolates from patients with ventilator-associated pneumonia who had monomicrobial culture findings, 33% were gram-positive bacteria and 20% were gram-negative bacteria. LIT suggested that 1 of 2 patients was treated inadequately for Pseudomonas aeruginosa infection. The LIT for patients with ventilator-associated pneumonia revealed that the rank order of antibiotics for appropriate therapy was (1) imipenem, (2) cephalosporins, (3) ciprofloxacin, and (4) piperacillin-tazobactam. These calculations were based solely on microbiological data., Conclusions: The novel ratio LIT may help clinicians use microbiological data on drug resistance to predict which antimicrobial agents will provide adequate therapy. In daily practice, this new approach may be helpful for choosing adequate antimicrobial therapy.

Objectives: This study sought to evaluate the predictive value of copeptin over the entire spectrum of heart failure (HF) and compare it to the current benchmark markers, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)., Background: Vasopressin has been shown to increase with the severity of chronic HF. Copeptin is a fragment of pre-pro-vasopressin that is synthesized and secreted in equimolar amounts to vasopressin. Both hormones have a short lifetime in vivo, similar to BNPs, but in contrast to vasopressin, copeptin is very stable in vitro. The predictive value of copeptin has been shown in advanced HF, where it was superior to BNP for predicting 24-month mortality., Methods: This was a long-term observational study in 786 HF patients from the whole spectrum of heart failure (New York Heart Association [NYHA] functional class I to IV, BNP 688 +/- 948 pg/ml [range 3 to 8,536 pg/ml], left ventricular ejection fraction 25 +/- 10% [range 5% to 65%])., Results: The NYHA functional class was the most potent single predictor of 24-month outcome in a stepwise Cox regression model. The BNP, copeptin, and glomerular filtration rate were related to NYHA functional class (p < 0.0001 for trend). Copeptin was the most potent single predictor of mortality in patients with NYHA functional class II (p < 0.0001) and class III (p < 0.0001). In NYHA functional class IV, the outcome of patients was best predicted by serum sodium, but again, copeptin added additional independent information., Conclusions: Increased levels of copeptin are linked to excess mortality, and this link is maintained irrespective of the clinical signs of severity of the disease. Copeptin was superior to BNP or NT-proBNP in this study, but the markers seem to be closely related.

Instillation of bacillus Calmette-Guérin (BCG) into the urine bladder is an effective treatment of superficial bladder cancer. BCG-mediated anti-tumor activity appears to be a local phenomenon in which cell-mediated immunity, involving cytotoxic T cells, lymphokine-activated killer cells and natural killer cells, is important for the elimination of malignant cells. Serious side-effects of BCG therapy are rare; nevertheless, BCG is a live, attenuated strain of Mycobacterium (M.) bovis and may exhibit invasive properties. Both local and distant or generalized infections have been reported after treatment with BCG. We describe the case of a 68-year-old man who developed bone marrow infection with BCG two years after intravesical instillation of BCG for treatment of superficial bladder cancer. He presented with intermittent fever, weight loss and pronounced pancytopenia. A bone marrow biopsy specimen showed granulomatous inflammation and BCG was cultured from the urine. Anti-mycobacterial treatment with isoniazid, rifampicin and ethambutol (pyrazinamide is inactive against M. bovis) led to full clinical recovery of the patient.

Objectives: To assess efficacy and tolerability of a newly developed helmet for the delivery of non-invasive ventilation in patients with acute respiratory failure., Patients and Methods: Ten consecutive immunocompromised patients with acute respiratory failure admitted to our intensive care unit were included in the study. The patients were equipped with the helmet and non-invasive ventilation (NIV) was performed. Oxygenation and tolerability were assessed during the first 24 hours of NIV., Results: All patients tolerated the helmet well and their oxygenation improved. Two patients developed septic shock and had to be endotracheally intubated during the study period, eight patients survived to be weaned from NIV., Conclusions: NIV delivered via the helmet is effective and may serve as a better tolerated alternative to endotracheal intubation and to NIV via a standard face mask.

Tuberculostearic acid (TBSA), a mycobacterial cell wall constituent, was measured in plasma samples using a highly sensitive high-performance liquid chromatography method. Plasma TBSA concentrations in patients with active tuberculosis (20 [0.5-347] nmol/l; n = 125) were higher than in patients with a variety of non-tuberculous pulmonary and extrapulmonary inflammatory conditions (0.1 [0-29] nmol/l; n = 116) and in healthy controls (0 [0-2] nmol/l; n = 102) (p = < 0.001). The calculated sensitivity, specificity, positive and negative predictive values for tuberculosis were 95.2%, 87.9%, 89.5% and 94.4%, respectively, indicating that assay of plasma TBSA might be a valuable complementary diagnostic tool.

Objective: To determine whether local warming of the lower arm and hand facilitates peripheral venous cannulation., Design: Single blinded prospective randomised controlled trial and single blinded randomised crossover trial., Setting: Neurosurgical unit and haematology ward of university hospital., Participants: 100 neurosurgical patients and 40 patients with leukaemia who required chemotherapy., Interventions: Neurosurgical patients' hands and forearms were covered for 15 minutes with a carbon fibre heating mitt. Patients were assigned randomly to active warming at 52 degrees C or passive insulation (heater not activated). The same warming system was used for 10 minutes in patients with leukaemia. They were assigned randomly to active warming or passive insulation on day 1 and given alternative treatment during the subsequent visit., Main Outcome Measures: PRIMARY: success rate for insertion of 18 gauge cannula into vein on back of hand. SECONDARY: time required for successful cannulation., Results: In neurosurgical patients, it took 36 seconds (95% confidence interval 31 to 40 seconds) to insert a cannula in the active warming group and 62 (50 to 74) seconds in the passive insulation group (P=0.002). Three (6%) first attempts failed in the active warming group compared with 14 (28%) in the passive insulation group (P=0.008). The crossover study in patients with leukaemia showed that insertion time was reduced by 20 seconds (8 to 32, P=0.013) with active warming and that failure rates at first attempt were 6% with warming and 30% with passive insulation (P<0.001)., Conclusions: Local warming facilitates the insertion of peripheral venous cannulas, reducing both time and number of attempts required. This may decrease the time staff spend inserting cannulas, reduce supply costs, and improve patient satisfaction.

Objective: To investigate how often a prolongation of the activated partial thromboplastin time in critically ill patients is caused by lupus anticoagulants and to identify possible triggering events., Design: Prospective study., Setting: Internal medicine intensive care unit (University Hospital of Vienna, Vienna, Austria)., Patients: Fifty-one critically ill patients without severe coagulopathy, hepatopathy, or anticoagulant treatment (35 male, 16 female, median age 60 yrs, range: 22-85 yrs)., Interventions: All patients were screened daily for lupus anticoagulants with the activated partial thromboplastin time STA assay., Measurements and Main Results: Diluted Russell's viper venom time, plasma mixing studies, and confirmation assays were used to identify lupus anticoagulants at the time of an unexplained prolongation of the activated partial thromboplastin time. The influence of heparin was excluded by determination of thrombin clotting time and anti-Xa activity. In 27 of 51 patients (52.9 %) lupus anticoagulants were found after a median stay of 13 days. None of the patients had concomitant immune thrombocytopenia, hypoprothrombinemia, bleeding, or thromboembolic complications. Sepsis (p =.006) and/or catecholamine treatment (p =.002) were significantly associated with the development of lupus anticoagulants. Extracorporeal circulation, transfusion of blood products, or surgery did not increase this risk. Lupus anticoagulants resolved spontaneously in 63% of the patients after a median stay of 17 days., Conclusions: Lupus anticoagulants are frequent in critically ill patients and associated with sepsis syndrome and/or catecholamine treatment. The prolonged activated partial thromboplastin time does not warrant the administration of coagulation factors or the cessation of anticoagulant therapy or prophylaxis, inasmuch as this phenomenon is not associated with bleeding or thromboembolic complications.

Administration of interleukin-2 (IL-2) to cancer patients has been shown to transiently decrease the number of circulating hematopoietic progenitor cells, but the mechanism of this phenomenon is unknown. Recently, the interaction of vascular adhesion molecule-1 (VCAM-1) with leukocyte very late antigen-4 (VLA-4) has been demonstrated to play a crucial role in the adhesion of progenitor cells to bone marrow stromal elements. Cytokine induced upregulation of VCAM-1 leads to increased binding of progenitor cells to stromal cells in vitro, and inhibition of this interaction by monoclonal antibodies is associated with marked progenitor cell mobilisation in vivo. In the present study we serially determined peripheral blood progenitor cell numbers during IL-2 treatment (10 courses) in 6 cancer patients and determined in parallel levels of soluble VCAM-1 as a surrogate marker for the in vivo activation of this molecule. Our data indicate that continuous intravenous administration of IL-2 for 5 days leads to a marked decrease of circulating progenitor cells associated with a substantial increase of circulating VCAM-1. Circulating myeloid progenitor cells (CFU-GM) dropped from a mean value of 167 +/- 187 / ml pre IL-2 to 16 +/- 15 / ml on day 3 (p < 0.01). Similarily, mean erythroid progenitors (BFU-E) decreased from 282 +/- 204 / ml before IL-2 administration to 86 +/- 61 / ml on day 3 (p < 0.005). In contrast, soluble VCAM-1 rose from a mean value of 1814 +/- 451 ng/ml before to 4607 +/- 736 ng/ml at the end of IL-2 therapy (p < 0.0001). Sera from IL-2 treated patients did not inhibit hematopoietic colony formation from normal bone marrow. These results suggest redistribution and increased adhesion of progenitor cells to stromal and/or endothelial elements during IL-2 via the VCAM-1/VLA-4 interaction as a possible mechanism for the decrease of circulating progenitor cells during IL-2 therapy.

Immunotherapy with intravenous recombinant human interleukin-2 (rh IL-2) may be accompanied by hypotension and the emergence of capillary leak syndrome. Nitric oxide (NO) is supposed to be responsible for both side effects. The aim of the current investigation was to elucidate the relationship between pro- and anti-inflammatory cytokines and the production of NO in eight tumor patients receiving intravenous rh IL-2 continuously over a time period of 120 hours. Markers of systemic inflammation, as well as nitrate plasma levels, were consecutively determined. Significant changes in the levels of pro-inflammatory cytokines IL-6 and IL-8 were observed (p < 0.05). In contrast to the anti-inflammatory cytokine IL-10, which did not increase significantly, the serum concentrations of the soluble tumor necrosis factor receptors (sTNFr) I and II rose continuously and significantly during the observation period (p < 0.05). In parallel, a significant rise in nitrate plasma levels was observed (p < 0.05). Moreover, there were highly significant correlations between nitrate and IL-6 serum levels (p < 0.05), nitrate and sTNFr-I (p < 0.05), nitrate and sTNFr-II (p < 0.05), and between IL-6 and IL-10 (p < 0.05), respectively. We conclude that immunotherapy with IL-2 promotes a pro-inflammatory state, parallelled by an increased production of nitric oxide. Although anti-inflammatory responses accompany this process, they are not able to diminish the production of nitric oxide.

Involvement of neutrophils in the control of blood parasites in malaria has been reported. Both, mononuclear phagocytes and neutrophils are known to be stimulated by cytokines such as TNF-alpha in order to augment the defence potency against the parasites. Previously, it has been shown that serum-G-CSF concentrations are increased in patients with bacterial sepsis. In vitro studies have shown that P. falciparum - infected erythrocytes induce the release of G-CSF by several cells such as endothelial cells and monocytes, however, nothing is known about G-CSF serum concentrations during the clinical course of severe P. falciparum malaria. Thus, it was the aim of the present study to investigate the time course for G-CSF serum concentrations in patients with complicated P. falciparum malaria, and to correlate these values with other mediators of inflammation and hematopoesis. Twenty-six patients suffering from complicated P. falciparum malaria were included in the study, and 20, age and sex matched, healthy volunteers were used as the negative control group. Serum samples for determination of G-CSF were taken on day 0, 7 and 14, and measured by ELISA. We found significantly increased serum concentrations of G-CSF in patients with complicated P. falciparum malaria on day 0, values decreasing to within the normal range by day 7. A significant correlation was found between G-CSF (d0) and procalcitonin, the parasite count, erythropoietin and macrophage inflammatory protein, however no correlation could be shown for the neutrophil count. In conclusion, on the day of hospital admission, elevated serum concentrations of G-CSF were detected in patients with complicated P. falciparum malaria, which might indicate a role of G-CSF in the acute defence mechanism against the parasites.

The aim of this study was to measure plasma homocysteine and laminin concentrations in patients with nonbacteremic systemic inflammatory response syndrome (SIRS) and to compare them with those of a healthy control group. Concerning laminin, significant increased concentrations could be observed in the SIRS group compared to the control group, but for homocysteine, no significance could be observed. In summary, homocysteine and laminin levels are not useful in the prediction of a patient's outcome.

Background: Nitric oxide (NO), an endogenous product of L-arginine oxidation, seems to account for the vasodilatatory effect of the endothelium-derived relaxing factor. It was the aim of the present study to measure serum nitrate concentrations, the degradation product of nitric oxide in patients with peripheral arterial occlusive disease (PAOD)., Patients and Methods: 20 patients with PAOD in Fontaine stage IIb, 10 patients in stage III and IV respectively were included in the study. Serum samples for determination of nitrate were taken at admission after fasting overnight. Nitrate concentrations were determined using a recently developed high performance liquid chromatography which allows direct measurement of nitrate. The control group comprised 14 age and risk factor matched volunteers., Results: We found significantly increased nitrate concentrations in patients with PAOD compared to the control group [stage IIb: 6.65 +/- 1.58 mumol/l; stage III: 6.94 +/- 1.85 mumol/l, stage IV: 7.05 +/- 1.16 mumol/l; control: 4.41 +/- 1.24 mumol/l], however no significance was calculated within the different PAOD groups. There was no association of either diabetes mellitus, hypertension and smoking behaviour with increased nitrate levels., Conclusion: These data might indicate that NO might be involved in adaptive vasodilatation already in the early phase of the disease. The source of nitrate in PAOD patients, however, remains unclear.

Treatment with intravenous recombinant human interleukin-2 (rh IL-2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate more precisely the role of the endothelium in the generation of IL-2-based side-effects. In nine tumour patients receiving intravenous rh IL-2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increase of the circulating endothelial leucocyte adhesion molecule-1 (cELAM-1) and the vasoconstrictor peptide endothelin-1 (ET-1) was observed (P<0.05), indicating activation of endothelial cells. The simultaneous increase of tissue-plasminogen activator and plasminogen activator inhibitor type-1 during therapy (P<0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolongation of partial thromboplastin time, and the decrease of fibrinogen (P<0.05) suggested the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepatic failure. We concluded that activation of the endothelium mediated by IL-2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation cascade. The increased ET-1 might act as an endogenous counter-regulator of the disadvantageous haemodynamic side-effects induced by IL-2.

Unlabelled: One of the most serious complications of conventional endotracheal intubation is unidentified placement of the tube in the esophagus. The aim of our study was to evaluate four different methods for immediate detection of the tube position: auscultation, capnographic determination of ETCO2, esophageal detection method (EDM) using a self-inflating bulb, and the transillumination method using a lighted stylet (Trachlight; Laerdal, Armonk, NY). Thirty-eight endotracheally intubated patients admitted to our medical intensive care unit were enrolled in the study. A second identical tube was inserted into the esophagus under laryngoscopic control. The endotracheal tube was then disconnected from the ventilator. Two blinded examiners, one experienced, the other inexperienced, determined the tube position within 30 s using one of the four methods. The order of the tubes tested and the methods used were randomized. In 130 of 152 examinations, both examiners correctly diagnosed the position of the tube. The wrong result was obtained by both examiners 4 times; only the experienced examiner was wrong 4 times, and only the inexperienced examiner was wrong 14 times. Using ETCO2, both examiners were correct in all cases. Auscultation showed an obvious relation to the examiner's experience: the experienced examiner was correct in all cases, the inexperienced examiner was correct in only 68% of cases. Using the self-inflating bulb, there were two wrong results of the experienced examiner and one wrong result of the inexperienced examiner. The transillumination technique was associated with a high error rate by both examiners (16% and 13%, respectively). Comparing all four methods showed that capnography is superior to auscultation (P = 0.0005) and to the Trachlight detection method (P = 0.0078). EDM was not statistically superior to auscultation and transillumination. Capnography was the most reliable method for rapid evaluation of tube position, followed by EDM, whereas auscultation and Trachlight did not seem to be of comparable value. Experience was a determining factor for auscultation., Implications: To prevent unidentified esophageal intubation, a serious complication in the critical care setting, four methods for detecting tube position were tested by two examiners (one experienced, the other inexperienced) in endotracheally intubated patients after insertion of a second tube into the esophagus.