Infections in Children With Cancer: The Role of the Presence or Absence of Neutropenia.

BACKGROUND: Infections in patients with cancer are a major cause of morbidity and mortality. In most cases, the presence of neutropenia renders them prone to infections to either common or opportunistic pathogens. A wide spectrum of bacterial, viral, or fungal agents is encountered in these patients. AIM: The aim of this study was to evaluate infection types and pathogens in pediatric patients with cancer with and without neutropenia. METHODS: A total of 37 pediatric patients with cancer (median age ± 25% quartile, 6.0 ± 2.0% years) with 70 febrile episodes were evaluated at fever's onset and 48 hours later with complete blood count, C-reactive protein, cultures of biological fluids, polymerase chain reaction, and antibody titers. RESULTS: Of 70 infections, 30 (42.85%) were bacterial, 13 (18.57%) were viral, 3 (4.28%) were fungal, 16 (22.85%) were fever of unknown origin, 18 (25.71%) were opportunistic, and 12 (17.14%) were mixed infections. Neutropenia was detected in 42 (60.0%) of 70 febrile episodes, mainly in patients with hematological malignancies [odds ratio, 2.81 (0.96-8.22); P = 0.059]. Neutropenic patients had higher prevalence of mucocutaneous infections (47.6% vs 7.14%; P = 0.004). Herpes simplex virus 1 infections occurred only in the neutropenic group (14.3%). CONCLUSIONS: Patients with cancer exhibited a high prevalence of bacterial (42.85%), opportunistic (25.7%), and mixed infections (17.14%). Patients with hematological malignancies and neutropenia presented higher frequency of mucocutaneous and herpes simplex virus 1 infections than the nonneutropenic ones.

Post-transfusion changes in serum hepcidin and iron parameters in preterm infants.

BACKGROUND: Packed red blood cell transfusion is common in preterm neonates. Hepcidin acts as a negative feedback iron regulator. Iron parameters such as immature reticulocyte fraction (IRF) and high-light-scatter reticulocytes (HLR) are used to clarify iron metabolism. Very little is known about the regulation of hepcidin in preterm infants because most reports have evaluated prohepcidin. The aim of this study was therefore to evaluate serum hepcidin and establish hematological parameters in preterm infants after transfusion. METHODS: The subjects consisted of 19 newborns (10 boys) with mean gestational age 29.1 ± 2.0 weeks, who had been transfused at the chronological age of 44.84 ± 19.61 days. Blood sample was collected before the transfusion and thereafter at 5 days and at 1 month. Serum hepcidin and other iron parameters were evaluated. RESULTS: Mean serum hepcidin before and 5 days after transfusion was significantly different (5.5 ± 5.1 vs 10 ± 7.9 ng/mL respectively, P = 0.005). IRF and % HLR were also decreased significantly, 5 days after transfusion (0.4 ± 0.2 vs 0.2 ± 0.1, P = 0.009; 1.4 ± 1.5% vs 0.5 ± 0.4%, P = 0.012, respectively). Changes in hepcidin 5 days after transfusion were correlated significantly with changes in mean corpuscular hemoglobin (ß, 0.13; SE, 0.05; P = 0.017), total iron binding capacity (ß, 3.74; SE, 1.56; P = 0.016) and transferrin (ß, 2.9, SE, 1.4; P = 0.039). CONCLUSIONS: Serum hepcidin concentration, along with IRF and HLR, are potentially useful in estimating pre- and post-transfusion iron status. Larger studies are needed to evaluate the sensitivity and specificity of hepcidin compared with ordinary iron parameters in premature infants.

Plasma biomarkers for the identification of women at risk for early-onset preeclampsia.

BACKGROUND: To identify potential biomarkers in the 1st trimester of pregnancy for the identification of women destined to develop early onset preeclampsia (EOPE). METHODS: Blood samples were obtained from pregnant women at 11-13 weeks of gestation. Women were followed up until delivery. Five samples from EOPE complicated pregnancies and 5 from unaffected ones were analysed using 2-DE and MALDI-TOF-TOF MS/MS. The altered expression of selected proteins was verified by ELISA in an extended sample cohort. RESULTS: Twelve proteins were differentially expressed in the plasma of women who subsequently developed EOPE as compared to controls. Alpha-1-antitrypsin (A1AT), CD5 antigen-like molecule (CD5L) Keratin, type I cytoskeletal 9 (K1C9), Myeloid cell nuclear differentiation antigen (MNDA), Transferrin (TRFE) and Vitamin D-binding protein (VTDB) were up-regulated with fold changes 3.14, 2.18, 1.53, 1.53, 4.26 3.38 respectively, whereas Alpha-2-HS-glycoprotein (FETUA), Beta-2-glycoprotein 1 (APOH), Complement factor B (CFAB), Haptoglobin (HPT), Vitronectin (VTNC) and Zinc-alpha-2-glycoprotein (ZA2G) were down-regulated with fold changes -0.38, -0.76, -0.24, -0.47, -0.23, and -0.50 respectively. The down-regulation of APOH, VTNC and HPT was verified using ELISA. CONCLUSIONS: The differentially expressed proteins represent potential biomarkers for the early screening for EOPE. Follow-up experiments however are necessary for evaluation.

Diagnostic value of cardiac troponin I in postmortem diagnosis of myocardial infarction.

Troponin I (cTnI) is a very sensitive biochemical marker for the diagnosis of myocardial infarction (MI). Cardiac troponin (cTnI or cTnT) has nearly absolute myocardial tissue specificity, thereby reflecting even microscopic zones of myocardial necrosis. The aim of this study is to evaluate the pericardial fluid levels of cTnI in medicolegal autopsy cases where patients died of MI and compare them with cases where patients died of other causes. This study included 89 cases selected during a 1-year period from medicolegal autopsies. These were classified into 4 groups: (A) myocardial infarction (n = 28), (B) salt water drowning (n = 20), (C) death resulting from injury in the respiratory system (n = 16), and (D) other causes of death (n = 25), excluding MI. The mean concentrations of cTnI were 1067.03 mg/dL for group A, 546.98 mg/dL for group B, 398.75 mg/dL for group C, and 577.47 mg/dL for group D. In cases with MI (group A), there was a significant difference in the levels of cTnI compared with the other cases. More research needs to be done in order for a cutoff level to be determined.

Variation of serum C-reactive protein (CRP) over time in pediatric cancer patients with febrile illness and its relevance to identified pathogen.

OBJECTIVE: To evaluate the correlation of serum CRP with clinical and laboratory parameters proven to be related to the cause of infection in pediatric cancer patients. METHODS: We studied prospectively for a 12-month period, 37 pediatric cancer patients, who presented with 70 episodes of febrile illness (38 bacterial and 13 viral infections). At fever's onset and 48 h later, infection indices, such as CRP, WBC, ANC were measured in the peripheral blood. Moreover we calculated the change rate of CRP over 48 h [CRP/t=(CRP48h-initial CRP)/t (t=2 days)]. Cultures of biological fluids, PCR and antibody detection of infectious agents were also obtained. RESULTS: When comparing patients with viral vs. bacterial infections, mean CRP levels on admission (11.0 vs. 33.1mg/L, p=0.005) and at 48 h (13.4 vs. 71.9 mg/L, p=0.0007), and CRP/t (0.9 vs. 18.8 mg/L/day, p=0.030) were significantly lower in the group with viral infection. At 48 h - follow-up, patients with positive culture had higher CRP levels (57.3 vs. 43.3mg/L, p=0.048) and higher CRP/t (15.9 vs. 7.7 mg/L/day, p=0.025), compared to those without proven infection. CRP/t at 48 h was correlated with both the fever duration (r=0.27, p=0.027) and maximum temperature (Tmax) during the febrile episode (r=0.30, p=0.013). CONCLUSIONS: Single CRP values on fever initiation can differentiate between viral and bacterial infections in febrile pediatric cancer patients. Moreover the change rate of CRP over time (CRP/t) is offered as a prognostic index of bacterial infection and a marker of the total duration of fever and Tmax.

The effectiveness of a 9-month regimen of isoniazid alone versus 3- and 4-month regimens of isoniazid plus rifampin for treatment of latent tuberculosis infection in children: results of an 11-year randomized study.

BACKGROUND: A 9-month course of isoniazid monotherapy is currently recommended for the treatment of latent tuberculosis infection (LTBI) and has been shown to be effective in both children and adults. Reduced compliance with this regimen has forced physicians to explore shorter regimens. The aim of this study was to compare 3- and 4-month combination regimens of isoniazid plus rifampin with a 9-month regimen of isoniazid monotherapy for the treatment of LTBI in children. METHODS: This prospective, randomized, controlled study was conducted over an 11-year period (1995-2005). In period 1 (1995-1998), 232 patients received isoniazid therapy for 9 months (group A), and 238 patients received isoniazid and rifampin for 4 months (group B). In period 2 (1999-2002), 236 patients were treated with isoniazid and rifampin for 4 months (group C), and 220 patients received the same regimen for 3 months (group D). All patients were observed for > or = 3 years. RESULTS: Overall compliance with treatment was good, but patients who received isoniazid monotherapy were less compliant than were those who received short-course combination therapy (P=.011, for group A vs. group B; P=.510, for group C vs. group D). No patient in any group developed clinical disease during the follow-up period. New radiographic findings suggestive of possible active disease were more common in patients who received isoniazid monotherapy (24%) than in those treated with shorter regimens (11.8%, 13.6%, and 11% for groups B, C, and D, respectively; P=.001 for group A vs. group B; P=.418 for group C vs. group D). Serious drug-related adverse effects were not detected. CONCLUSIONS: Short-course treatment with isoniazid and rifampin for 3-4 months is safe and seems to be superior to a 9-month course of isoniazid monotherapy.

Interleukin-6 in preterm premature rupture of membranes as an indicator of neonatal outcome.

BACKGROUND: The aim of this study was to investigate whether the levels of interleukin-6 (IL-6) can be used as markers of adverse outcome in preterm neonates born after preterm premature rupture of membranes (PPROM). METHODS: This study involved 109 preterm neonates and their mothers. The PPROM group consisted of 58 neonates who were born after PPROM, and the control group consisted of 51 neonates. IL-6 levels were measured in umbilical cord blood, maternal blood sampled during delivery and in neonatal blood taken on the fourth day of life. RESULTS: In the PPROM group, IL-6 concentrations in maternal blood, cord blood, and neonatal blood were significantly higher in neonates with sepsis, compared with those without sepsis (P < 0.001). Choosing 108.5 pg/ml as a cut-off concentration of IL-6 in umbilical cord blood for neonatal sepsis resulted in sensitivity 95%, specificity 100%, positive predictive value 100%, and negative predictive value 97.4%. Concerning IL-6 in maternal blood, a cut-off concentration of 81 pg/ml showed sensitivity 90%, specificity 97.4%, positive predictive value 94.7%, and negative predictive value 94.9%. Eighteen of 20 neonates with early sepsis and seven of nine neonates, who died in the PPROM group, were born of mothers with IL-6 levels above the cut-off concentration in their blood during delivery. CONCLUSIONS: IL-6 in umbilical cord blood was the most significant variable for predicting early onset sepsis in preterm neonates. IL-6 in maternal blood was indicative of intrauterine environmental threats and might be used to identify pregnancies where intervention would be appropriate.

Urinary excretion of endothelin-1 in children with absorptive idiopathic hypercalciuria.

Urinary excretion of endothelin-1 (ET-1) and plasma ET-1 were measured in 21 children with absorptive idiopathic hypercalciuria (AIH) and 22 controls. The absorptive type of idiopathic hypercalciuria was determined by a calcium loading test. Daily urinary excretion of ET-1 and urinary ET-1/creatinine ratio were significantly increased ( P=0.005 and P=0.007, respectively) in patients with AIH (9274+/-6444 pg/24 h and 14.04+/-9.52 pg/mg, respectively) compared with controls (4699+/-2120 pg/24 h and 7.36+/-4.71 pg/mg, respectively). Plasma ET-1 levels were significantly lower in patients with AIH (0.84+/-0.64 pg/ml) than in controls (1.54+/-0.54 pg/ml, P=0.0001). In conclusion, patients with AIH had increased urinary ET-1 excretion and decreased plasma ET-1 levels. This is most likely due to the decreased reabsorption of ET-1 in the renal tubule and increased renal production.

Endothelin-1 in children with acute poststreptococcal glomerulonephritis and hypertension.

BACKGROUND: Endothelin-1 (ET-1), the most potent vasoconstrictor peptide, is known to play a role in arterial hypertension. In patients with acute poststreptococcal glomerulonephritis (APSGN) an increase in the production of ET-1 is suspected due to damaged endothelium, platelet activation and increased thrombin production in the glomeruli. The aim of the present study was to investigate whether the levels of plasma ET-1 are elevated in children with APSGN. Furthermore, we examined the association between plasma ET-1 levels and blood pressure levels in the same children. METHODS: We studied 18 children (14 boys) with APSGN (mean age 7.44 to approximately 2.82 years). Fourteen healthy children served as controls. The following parameters were evaluated: plasma ET-1, plasma atrial natriuretic peptide (ANP), plasma renin (Rn), serum aldosterone (Aldo), creatinine clearance (Ccr) and fractional excretion of sodium (FENa). RESULTS: The mean plasma ET-1 concentrations were higher in patients with APSGN (3.39 to approximately 1.86 pg/mL) compared to controls (1.40 to approximately 0.15 pg/mL; P=0.0001). Patients with APSGN also had higher plasma ANP concentrations (41.67 to approximately 27.99 pg/mL) than the controls (22.80 to approximately 4.24 pg/mL; P=0.011). Plasma Rn concentrations were lower in patients (24.54 to approximately 16.34 microU/mL) compared to controls (56.76 to approximately 32.36 microU/mL; P=0.027). A positive correlation was found between ET-1 plasma concentrations and the height of systolic or diastolic blood pressure (r=0.57, P=0.013 and r=0.53, P=0.023, respectively). CONCLUSIONS: Our results suggest that increased plasma ET-1 concentrations may play an important role in the pathogenesis of hypertension in children with acute poststreptococcal glomerulonephritis.