Serum levels of mannose-binding lectin and the risk of fever in neutropenia pediatric cancer patients

BACKGROUND: Fever in neutropenia (FN) is a frequent complication in pediatric oncology. Deficiency of mannose-binding lectin (MBL), an important component of innate immunity, is common due to genetic polymorphisms, but its impact on infections in oncologic patients is controversial. This study investigated whether MBL serum levels at cancer diagnosis are associated with the development of FN in pediatric cancer patients. PROCEDURE: Serum MBL was measured using ELISA. Frequency, duration, and cause of FN were assessed retrospectively. Association with MBL level was analyzed using uni- and multivariate Poisson regression taking into account both intensity and duration of chemotherapy. RESULTS: In 94 children, with a cumulative follow-up time of 81.7 years, 177 FN episodes were recorded. Patients with both very low MBL levels (<100 microg/L; risk ratio (RR), 1.93; 95% CI, 1.14-3.28; P = 0.014) and normal MBL levels (>/=1,000 microg/L; RR, P = 0.011) had significantly more frequent FN episodes than patients with low MBL levels (100-999 microg/L). Patients with very low MBL levels had significantly more episodes of FN with severe bacterial infection (bacteremia or pneumonia; RR, 4.49; 1.69 = 11.8; P = 0.003), while those with normal MBL levels had more FN episodes with no microbial etiology identified (RR, 1.85; 1.14 = 3.03; P = 0.014). CONCLUSIONS: Very low MBL levels are associated with more frequent FN episodes, mainly due to severe bacterial infections. The surprising finding that children with normal MBL levels had more frequent FN episodes than those with low MBL levels needs testing in prospective studies. Pediatr Blood Cancer (c) 2006 Wiley-Liss, Inc.

Evaluation of p24-based antiretroviral treatment monitoring in pediatric HIV-1 infection: prediction of the CD4+ T-cell changes between consecutive visits

Worldwide, 700,000 infants are infected annually by HIV-1, most of them in resource-limited settings. Care for these children requires simple, inexpensive tests. We have evaluated HIV-1 p24 antigen for antiretroviral treatment (ART) monitoring in children. p24 by boosted enzyme-linked immunosorbent assay of heated plasma and HIV-1 RNA were measured prospectively in 24 HIV-1-infected children receiving ART. p24 and HIV-1 RNA concentrations and their changes between consecutive visits were related to the respective CD4+ changes. Age at study entry was 7.6 years; follow-up was 47.2 months, yielding 18 visits at an interval of 2.8 months (medians). There were 399 complete visit data sets and 375 interval data sets. Controlling for variation between individuals, there was a positive relationship between concentrations of HIV-1 RNA and p24 (P < 0.0001). While controlling for initial CD4+ count, age, sex, days since start of ART, and days between visits, the relative change in CD4+ count between 2 successive visits was negatively related to the corresponding relative change in HIV-1 RNA (P = 0.009), but not to the initial HIV-1 RNA concentration (P = 0.94). Similarly, we found a negative relationship with the relative change in p24 over the interval (P < 0.0001), whereas the initial p24 concentration showed a trend (P = 0.08). Statistical support for the p24 model and the HIV-1 RNA model was similar. p24 may be an accurate low-cost alternative to monitor ART in pediatric HIV-1 infection.

The current and future state of interventional cardiology: a critical appraisal

After 75 years of invasive and over 50 years of interventional cardiology, cardiac catheter-based procedures have become the most frequently used interventions of modern medicine. Patients undergoing a percutaneous coronary intervention (PCI) outnumber those with coronary artery bypass surgery by a factor of 2 to 4. The default approach to PCI is the implantation of a (drug-eluting) stent, in spite of the fact that it improves the results of balloon angioplasty only in about 25% of cases. The dominance of stenting over conservative therapy or balloon angioplasty on one hand and bypass surgery on the other hand is a flagrant example of how medical research is digested an applied in real life. Apart from electrophysiological interventions, closure ot the patent foramen ovale and percutaneous replacement of the aortic valve in the elderly have the potential of becoming daily routine procedures in catheterization laboratories around the world. Stem cell regeneration of vessels or heart muscle, on the other hand, may remain a dream never to come true.

Pitfall in pediatric dialysis: malposition of a dialysis catheter mimicking azygos continuation syndrome

Central venous catheters are established as vascular access in hemodialysis therapy. Vascular catheter misdirection may occur and is a well known problem. We present a rare catheter malposition in a young dialysis patient with consequent dilatation of the azygos vein system, simulating the appearance of an azygos continuation syndrome.

8-Isoprostane in nasally exhaled breath condensate in different pediatric lung diseases

OBJECTIVE: Increased levels of 8-isoprostane were found in various human lung diseases suggesting 8-isoprostane as a marker of pulmonary oxidative stress in vivo. The exact role in pediatric lung diseases has not been defined yet. The goal of this study was to clarify the role of 8-isoprostane in nasally exhaled breath condensate as possible marker of oxidative stress in children with different lung diseases. METHODS: Levels of 8-isoprostane were measured in nasally exhaled breath condensate of 29 cystic fibrosis patients, 19 children with a history of wheezing episodes, 8 infants with acute respiratory tract infection and 53 healthy subjects using a specific enzyme immunoassay. RESULTS: Levels of 8-isoprostane did neither discriminate between different disease groups nor correlate with lung function in cystic fibrosis patients. CONCLUSIONS: Levels of 8-isoprostane in nasally exhaled breath condensate do not reflect oxidative stress in children with different lung diseases.

Deficiency of mannose-binding lectin-associated serine protease-2 associated with increased risk of fever and neutropenia in pediatric cancer patients

BACKGROUND: Mannose-binding lectin-associated serine protease-2 (MASP-2) is an essential component of the lectin pathway of complement activation. MASP-2 deficiency is common because of genetic polymorphisms, but its impact on susceptibility to infection is largely unknown. The aim of the present study was to determine whether children with cancer and MASP-2 deficiency develop more frequent or more severe episodes of fever and severe chemotherapy-induced neutropenia (FN). METHODS: Serum MASP-2 was measured by enzyme-linked immunosorbent assay at the time of diagnosis in children treated with chemotherapy for cancer. Association of FN episodes with MASP-2 concentration was analyzed using Poisson regression accounting for chemotherapy intensity and duration. RESULTS: Median MASP-2 in 94 children was 527 ng/mL (interquartile range, 367-686). Nine (10%) children had MASP-2 deficiency (<200 ng/mL). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded. MASP-2 deficient children had a significantly increased risk of developing FN (multivariate risk ratio, 2.08; 95% confidence interval, 1.31-3.21; P = 0.002), translating into significantly prolonged cumulative duration of hospitalization and of intravenous antimicrobial therapy. They experienced significantly more episodes of FN without a microbiologically defined etiology, and there was a trend toward more frequent episodes of FN with bacteremia. CONCLUSION: In this study, MASP-2 deficiency was associated with an increased risk of FN in children treated with chemotherapy for cancer. MASP-2 deficiency represents a novel risk factor for chemotherapy-related infections.

Real-time broad-range PCR versus blood culture. A prospective pilot study in pediatric cancer patients with fever and neutropenia

MATERIALS AND METHODS: In a pilot study, results of real-time broad-range (16S rRNA) polymerase chain reaction (PCR) performed on 45 blood samples of pediatric cancer patients with fever and neutropenia were compared with blood culture results. RESULTS: The PCR assay used, having proven a high sensitivity in artificially spiked blood samples, was positive in only three of ten blood culture-positive samples, and it was positive in 10 of 35 (29%) culture-negative samples. CONCLUSION: This broad-range PCR assay, which may identify not-grown bacteria potentially contributing to fever, needs improvement in sensitivity, and different reasons for positive PCR in negative blood culture samples need to be assessed before clinical application.

Quality, size, and composition of pediatric endobronchial biopsies in cystic fibrosis

BACKGROUND: Studies on airway remodeling in children with cystic fibrosis (CF) may be hampered by difficulty in obtaining evaluable endobronchial biopsy specimens because of large amounts of mucus and inflammation in the CF airway. We prospectively assessed how the quality of biopsy specimens obtained from children with CF compare with those from children with other airway diseases. METHODS: Fiberoptic bronchoscopy with endobronchial biopsy was performed in 67 CF children (age range, 0.2 to 16.8 years), 34 children with wheeze/asthma (W/A), and 64 control children with chronic respiratory symptoms. Up to three biopsy specimens were taken and stained with hematoxylin and eosin. Biopsy specimen size and structural composition were quantified using stereology. RESULTS: At least one evaluable biopsy specimen was obtained in 72% of CF children, in 79% of children with W/A, and in 72% of control subjects (difference was not significant). The use of large biopsy forceps (2.0 mm) rather than small biopsy forceps (1.0 mm) [odds ratio (OR), 5.8; 95% confidence interval (CI), 1.1 to 29.8; p = 0.037] and the number of biopsy specimens taken (odds ratio, 2.6; 95% confidence interval, 1.3 to 5.2; p = 0.006) significantly contributed to the success rate. Biopsy size and composition were similar between groups, except that CF children and those patients with W/A had a higher percentage of the biopsy specimen composed of muscle than did control subjects (median 6.2% and 9.7% vs 0.9%, respectively; p = 0.002). CONCLUSIONS: Biopsy size and quality are adequate for the study of airway remodeling in CF children as young as 2 months of age. Researchers should use large forceps when possible and take at least two biopsy specimens per patient. An increased airway smooth muscle content of the airway mucosa may contribute to the pathophysiology of CF lung disease.