Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials.

PURPOSE: Current treatment for febrile neutropenia (FN) includes hospitalization for evaluation, empiric broad-spectrum antibiotics, and other supportive care. Clinical trials have reported conflicting results when studying whether the colony-stimulating factors (CSFs) improve outcomes in patients with FN. This Cochrane Collaboration review was undertaken to further evaluate the safety and efficacy of the CSFs in patients with FN. METHODS: An exhaustive literature search was undertaken including major electronic databases (CANCERLIT, EMBASE, LILACS, MEDLINE, SCI, and the Cochrane Controlled Trials Register). All randomized controlled trials that compare CSFs plus antibiotics versus antibiotics alone for the treatment of established FN in adults and children were sought. A meta-analysis of the selected studies was performed. RESULTS: More than 8,000 references were screened, with 13 studies meeting eligibility criteria for inclusion. The overall mortality was not influenced significantly by the use of CSF (odds ratio [OR] = 0.68; 95% CI, 0.43 to 1.08; P = .1). A marginally significant result was obtained for the use of CSF in reducing infection-related mortality (OR = 0.51; 95% CI, 0.26 to 1.00; P = .05). Patients treated with CSFs had a shorter length of hospitalization (hazard ratio [HR] = 0.63; 95% CI, 0.49 to 0.82; P = .0006) and a shorter time to neutrophil recovery (HR = 0.32; 95% CI, 0.23 to 0.46; P < .00001). CONCLUSION: The use of the CSFs in patients with established FN caused by cancer chemotherapy reduces the amount of time spent in hospital and the neutrophil recovery period. The possible influence of the CSFs on infection-related mortality requires further investigation.     

A rat model of otitis media with effusion caused by eustachian tube obstruction with and without Streptococcus pneumoniae infection: methods and disease course.

OBJECTIVE: To describe the clinical and histopathologic progression of a rat model of otitis media with effusion caused by eustachian tube obstruction (ETO) with and without Streptococcus pneumoniae infection. METHODS: In 164 rats, the left, bony eustachian tube was approached via a ventral incision and obstructed with dental material. Then 108 rats were infected via an intrabullar injection with S pneumoniae. At 48 hours, the infected rats were treated for 5 days with ampicillin. All ears were evaluated by weekly otomicroscopy. On each of days 1, 2, 7, 21, 35, 56, and 112, four rats were killed for histologic study. All effusions were cultured for bacteria. RESULTS: Fourteen rats died of surgical complications; effusion resolved by 2 weeks in 9 rats. During the first few days, infected ears with ETO had bulging tympanic membranes, followed by tympanic membrane retraction, purulent effusion, and otorrhea (50%) over the next few weeks, whereas uninfected ears with ETO developed retraction and serous effusion during the same time frame. At later times, all ears with ETO presented with retraction and serous or serous-mucoid effusion. S pneumoniae was recovered only from the infected ears with ETO (days 1 and 2), with some colonization by nonpathogenic microorganisms observed equally in both groups of ears. Histology showed a typical acute inflammatory reaction in the challenged ears with ETO through day 14 and then a chronic inflammation for all ears with ETO. CONCLUSION: The experimental methods provoked reproducible pathologic signs similar to those for otitis media with effusion. Given the availability of rat-specific reagents, this model is well suited for studies of cytokine elaboration during disease pathogenesis.     

Auditive Verarbeitungsgeschwindigkeit und Sprachleistungen

ZusammenfassungHintergrund Lernstörungen werden zunehmend auf Defizite bei der Sprachwahrnehmung und diese wiederum auf eine Verlangsamung der auditiven Verarbeitungsgeschwindigkeit zurückgeführt. In der Studie wird untersucht, ob sich bei Kindern mit Schulproblemen sprachliche Leistungen durch ein Zeitverarbeitungstraining verbessern lassen.Patienten und Methoden Bei 21 Kindern mit spezifischen Lernstörungen wurden über 8 Wochen Ordnungsschwelle und Richtungshören trainiert und im Vergleich zu einer Kontrollgruppe (n=21) Sprachleistungen bis 6 Monate danach überprüft.Ergebnisse Leistungssteigerungen wurden hinsichtlich der Ordnungsschwelle, nicht aber der sprachlichen Fähigkeiten beobachtet. Die Eltern schätzten die Wirkung des Trainings eher positiv ein.Schlussfolgerungen Ein Zeitverarbeitungstraining verbessert unmittelbar geübte Leistungen, nicht aber sprachliche Fähigkeiten. Von den Eltern wahrgenommene Verbesserungen sind nicht objektivierbar und als unspezifische Effekte zu bewerten. Die Ergebnisse sprechen insgesamt gegen die Wirksamkeit eines Zeitverarbeitungstrainings bei Kindern mit Schulschwierigkeiten.     

Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy

OBJECTIVE: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. DESIGN: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. RESULTS: all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. CONCLUSIONS: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.     

Use of re-randomized data in meta-analysis

Background  

Outcomes collected in randomized clinical trials are observations of random variables that should be independent and identically distributed. However, in some trials, the patients are randomized more than once thus violating both of these assumptions. The probability of an event is not always the same when a patient is re-randomized; there is probably a non-zero covariance coming from observations on the same patient. This is of particular importance to the meta-analysts.     

Endotoxemia during supraceliac aortic crossclamping is associated with suppression of the monocyte CD14 mechanism: possible role of transforming growth factor-beta1

PURPOSE: Monocyte CD14 and its soluble form (sCD14) mediate the proinflammatory response to endotoxemia. The aim of this study was to measure the changes to these factors after major aortic surgery and the possible inhibitory role of transforming growth factor-beta(1) (TGF-beta(1)) during these procedures. METHODS: Twenty-four patients with supraceliac aortic crossclamping during thoracoabdominal aortic aneurysm (TAAA) repair and 12 patients with infrarenal aortic crossclamping as part of infrarenal aneurysm repair (AAA) were studied. Blood was collected at incision, aortic clamping, and reperfusion and at 1, 8, and 24 hours after reperfusion. Samples were assayed for endotoxin, peripheral blood monocyte CD14 expression, sCD14, tumor necrosis factor-alpha, and TGF-beta(1). RESULTS: Although there was significant endotoxemia on reperfusion in both groups of patients, peak plasma endotoxin levels were significantly higher in patients with TAAA (P =.001). Monocyte CD14 and plasma sCD14 were significantly decreased in patients with TAAA at reperfusion and 1 hour after reperfusion (P <.01, both points). In patients with AAA, a significant upregulation of CD14 was observed at 24 hours after reperfusion (P <.01), but no significant changes in sCD14 were observed. TNF-alpha showed no significant changes during the study period in both groups. In patients with TAAA, TGF-beta(1) showed significant elevation at all time points (P <.01); whereas in patients with AAA, TGF-beta(1) showed no significant changes. CONCLUSION: Splanchnic ischemia reperfusion in patients who undergo supraceliac aortic clamping is associated with peripheral blood monocyte CD14 suppression and significant elevation of TGF-beta(1). TGF-beta(1) may play an important role in modulating the immune response to endotoxemia during major aortic aneurysm surgery.