Galactomannan antigen detection using bronchial wash and bronchoalveolar lavage in patients with hematologic malignancies.

BACKGROUND: The diagnosis of invasive pulmonary aspergillosis is challenging. It is unclear whether galactomannan (GM) results from bronchial wash (BW) and bronchoalveolar lavage (BAL) samples differ in a clinically meaningful way. RESULTS: Ninety-six paired (BAL and BW) samples from 85 patients were included. The average age was 53 years, 61 % of the patients were male, and 74.1 % had an underlying diagnosis of AML/MDS (ALL 7.1 %, other hematologic malignancy 18.8 %). 57 (67.1 %) patients were neutropenic, and 56 (65.9 %) patients were receiving mold-active drugs at least 48 h prior to bronchoscopy. The overall agreement between GM detection from BW and BAL was 63.5 % (K = 0.152; 95 % CI 0.008-0.311) and 73 % (K = 0.149; 95 % CI 0.048-0.348) at cut off ≥0.5 and ≥1.0, respectively. Among 43 positive samples, using a GM cut-off of 0.5, 39 (90.5 %) were positive in BW samples whereas 12 (29.3 %) were positive in BAL samples. The median level of GM in BW (0.28) samples was significantly higher than in BAL (0.20) samples among 53 samples with negative results (P = 0.001). There was no statistically significant difference in the median GM values between the BW and BAL samples with positive results (P = 0.08). There was no significant difference in GM detection between samples with positive and negative results with regard to antifungal, beta lactam antibacterial treatment or neutropenia (60.5 vs 56.6 %; 53.9 vs 46 %; 65.1 vs 54.7 %, respectively). CONCLUSION: This retrospective study examining two collection techniques suggests that BW may have higher diagnostic yield compared to bronchoalveolar lavage for GM detection.

Hybrid III Lower Leg Injury Assessment Reference Curves Under Axial Impacts Using Matched-Pair Tests.

The objective of the present study was to derive injury probability curves applicable to the Hybrid III dummy (also termed the Anthropomorphic Test Device, ATD) lower leg under axial impacts for military applications. A matched-pair approach was used. Axial impacts were delivered to below knee foot-ankle complex preparations of the lower leg of the ATD using pendulum and custom vertical accelerator devices. Military boot was used in some tests. Post mortem human surrogate (PMHS) preparations were used as matched-pair tests for injury outcomes. The alignment was such that the foot-ankle complex was orthogonal to the leg (below knee tibia-fibula complex), termed as the normal 90-90 posture. Injury outcomes from the biological surrogate focused on calcaneus and or distal tibia fractures with or without the involvement of articular surfaces. Peak lower tibia load cell forces were obtained from matched-pair dummy tests. Injury and force data were paired, censoring was assigned based on injury outcomes and survival analysis was done using the Weibull distribution to derive dummy-based probability curves. Mean peak forces were extracted at 5, 10, 20 and 50% probability levels. Normalized confidence interval sizes (NCIS) at ± 95% level were computed to determine the tightness-of-fit of the confidence bands. The NCIS data ranged from 0.34 to 0.78 and a peak force of 8.2 kN was associated at the ten percent injury probability level. Other data and curves are given in the body of the paper. The present Injury Assessment Reference Curves and Values (IARC and IARV) may be used in future tests for advancing safety in military environments. These survival analysis processes and IARC and IARV data may also be used in other applications.

Prior colonization is associated with increased risk of antibiotic-resistant Gram-negative bacteremia in cancer patients.

We hypothesized that prior colonization with antibiotic-resistant Gram-negative bacteria is associated with increased risk of subsequent antibiotic-resistant Gram-negative bacteremia among cancer patients. We performed a matched case-control study. Cases were cancer patients with a blood culture positive for antibiotic-resistant Gram-negative bacteria. Controls were cancer patients with a blood culture not positive for antibiotic-resistant Gram-negative bacteria. Prior colonization was defined as any antibiotic-resistant Gram-negative bacteria in surveillance or non-sterile-site cultures obtained 2-365 days before the bacteremia. Thirty-two (37%) of 86 cases and 27 (8%) of 323 matched controls were previously colonized by any antibiotic-resistant Gram-negative bacteria. Prior colonization was strongly associated with antibiotic-resistant Gram-negative bacteremia (odds ratio [OR] 7.2, 95% confidence interval [CI] 3.5-14.7) after controlling for recent treatment with piperacillin-tazobactam (OR 2.5, 95% CI 1.3-4.8). In these patients with suspected bacteremia, prior cultures may predict increased risk of antibiotic-resistant Gram-negative bacteremia.

Infection prevention in the cancer center.

Cancer patients are frequently immunosuppressed and at risk for a wide range of opportunistic and healthcare-associated infections. A good infection prevention program is extremely important to reduce risk of infection. This review focuses on infection prevention measures specific to patients, healthcare personnel, and visitors in the cancer center.

Counterpoint: routine anti-bacterial prophylaxis is not indicated in neutropenic patients with hematological malignancies.

Preventing bacterial infections by prescribing prophylactic antibiotics is seen by many as an important strategy for decreasing infectious mortality in the most profoundly immunosuppressed patients with hematologic malignancies. Comparative studies show consistently that neutropenic patients treated with prophylactic fluoroquinolone antibiotics develop fewer bacteremias than patients treated with placebo or less-potent antibacterials. However, these same studies fail to show increased survival rates in fluoroquinolone-treated patients. This repeated observation is the basis for the continued controversy concerning universal antibacterial prophylaxis of neutropenic patients, namely, the inability to translate the observed reduction in culture-proven bacterial infections with prophylaxis into improved clinical outcomes. The answer to this controversy lies in the effectiveness of empiric antibacterial therapy in response to neutropenic fevers. Mortality from bacterial infections is 1% or less for patients enrolled in empiric treatment trials who do not receive prophylactic antibacterials. Therefore, routine fluoroquinolone prophylaxis offers essentially no potential survival benefit to neutropenic patients with hematologic malignancies. In fact, the increasing potential for fluoroquinolones to select for resistant bacterial pathogens should give pause to the practice of routine prophylaxis of neutropenic patients.

Recruitment of murine neutrophils in vivo through endogenous sialidase activity.

Upon activation with various noncytokine stimuli, polymorphonuclear leukocytes (PMNs) mobilize intracellular sialidase to the plasma membrane, where the sialidase releases sialic acid from the cell surface. This desialylation enhances PMN adherence, spreading, deformability, and motility, functions critical to diapedesis. We now have examined the role of sialidase activity in PMN adhesion to and migration across the endothelium in vivo. A polyclonal antibody prepared against Clostridium perfringens neuraminidase 1) detected surface expression of sialidase on human PMNs stimulated with IL-8 in vitro and on murine PMNs stimulated in vivo, but not on that of unstimulated cells, 2) recognized proteins in human PMN lysates and granule preparations that were not detected by preimmune antibody, 3) inhibited bacterial neuraminidase and human PMN sialidase activities in vitro, and 4) inhibited both pulmonary leukostasis in mice systemically infused with cobra venom factor and intrapulmonary transendothelial migration of PMNs into the bronchoalveolar compartment of mice intranasally challenged with interleukin-8. We conclude that the chemokine interleukin-8, like other PMN agonists, induces the translocation of sialidase to the PMN surface and that surface expression of this sialidase is a prerequisite to PMN recruitment in vivo. The ability of antibodies raised against a prokaryotic neuraminidase to recognize eukaryotic sialidase extends the concept of the neuraminidase superfamily to mammalian enzymes. Inhibition of mobilized endogenous sialidase may provide a novel strategy for limiting the inflammatory response.

A 29-kDa protein associated with p67phox expresses both peroxiredoxin and phospholipase A2 activity and enhances superoxide anion production by a cell-free system of NADPH oxidase activity.

Production of toxic oxygen metabolites provides a mechanism for microbicidal activity of the neutrophil. The NADPH oxidase enzyme system initiates the production of oxygen metabolites by reducing oxygen to form superoxide anion (O(2)()). With stimulation of the respiratory burst, cytosolic oxidase components, p47(phox), p67(phox), and Rac, translocate to the phagolysomal and plasma membranes where they form a complex with cytochrome b(558) and express enzyme activity. A 29-kDa neutrophil protein (p29) was identified by co-immunoprecipitation with p67(phox). N-terminal sequence analysis of p29 revealed homology to an open reading frame gene described in a myeloid leukemia cell line. A cDNA for p29 identical to the open reading frame protein was amplified from RNA of neutrophils. Significant interaction between p29 and p67(phox) was demonstrated using a yeast two-hybrid system. A recombinant (rh) p29 was expressed in Sf9 cells resulting in a protein with an apparent molecular weight of 34,000. The rh-p29 showed immunoreactivity with the original rabbit antiserum that detected p47(phox) and p67(phox). In addition, rh-p29 exhibited PLA(2) activity, which was Ca(2+) independent, optimal at low pH, and preferential for phosphatidylcholine substrates. The recombinant protein protected glutathione synthetase and directly inactivated H(2)O(2). By activity and sequence homology, rh-p29 can be classified as a peroxiredoxin. Finally, O(2)() production by plasma membrane and recombinant cytosolic oxidase components in the SDS-activated, cell-free NADPH oxidase system were enhanced by rh-p29. This effect was not inhibited by PLA(2) inhibitors. Thus, p29 is a novel protein that associates with p67 and has peroxiredoxin activity. This protein has a potential role in protecting the NADPH oxidase by inactivating H(2)O(2) or altering signaling pathways affected by H(2)O(2).