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Biomedical subjects

Maurizio de Martino

Publications and source records attributed to Maurizio de Martino.

At least 19 recordsLinked to original sources

Cancer rates after year 2000 significantly decrease in children with perinatal HIV infection: a study by the Italian Register for HIV Infection in Children.

PURPOSE: To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. PATIENTS AND METHODS: An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. RESULTS: Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). CONCLUSION: Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

Antiretroviral Therapy, Highly Active↗

Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection.

OBJECTIVE: To investigate the impact of early versus deferred combined antiretroviral treatment (ART) in asymptomatic or moderately symptomatic [Centers for Disease Control and Prevention (CDC) category N, A or B] infants with perinatal HIV-1 infection. METHODS: A multi-centre nationwide case-control study was conducted. Data from 30 infants treated with combined ART with three or more drugs before 6 months of age were compared with data from 103 infants starting ART with three or more drugs after 6 months of age. The median follow-up time was 4.1 years (range, 1.0-6.5 years). RESULTS: No difference was evident in the first available viral load and CD4 T-lymphocyte percentage between the two groups of children. Early-treated infants showed significantly lower viral loads than infants receiving deferred treatment at all the follow-up periods. A higher proportion of early-treated infants than infants receiving deferred treatment (73.3% versus 30.1%; P < 0.0001) reached an undetectable viral load. Higher CD4 T-lymphocyte percentages were found in early-treated infants at 13-24 (P < 0.0001), 25-36 (P < 0.0001), and 37-48 (P = 0.003) months of age. No early-treated infant versus 20 of 103 (19.4%) infants receiving deferred ART (P = 0.02) showed a CD4 T-lymphocyte percentage of less than 15% at one time point during follow-up. No CDC category A, B or C clinical event occurred in early-treated infants over the follow-up period while 44 of 103 (42.7%) infants receiving deferred treatment presented a decline in the CDC category. Kaplan-Meier analyses revealed significant differences in CDC category A (P = 0.0002), B (P = 0.0003), and C (P = 0.0018) event-free survivals. CONCLUSION: The data suggest virologic, immunologic, and clinical benefits from early administration of ART.

Age Factors↗

Alanine transaminase levels in the year before pregnancy predict the risk of hepatitis C virus vertical transmission.

Vertical transmission is the most common route of hepatitis C virus (HCV) infection in children. Transmission risk factors have been described, but most risk factors can only be evaluated using expensive laboratory exams. The aim of the present study was to evaluate whether maternal alanine transaminase (ALT) levels before pregnancy correlate with HCV vertical transmission. Seventy-four transmitting and 403 nontransmitting mothers were evaluated. All mothers enrolled had two ALT determinations in the last year before pregnancy, at least 6 months apart. Mothers were divided into two groups: mothers with persistently normal serum ALT levels and mothers with abnormal ALT levels. In the second group both mothers with constantly raised or with fluctuating ALT levels (one normal and one raised determination) were included. ALT was defined as raised if higher than twice the upper limit of normal. Abnormal ALT levels were found in 39/74 (52.7%) HCV transmitting mothers and in 146/403 (32.6%) nontransmitting mothers (P = 0.008; relative risk 1.96; 95% confidence limits 1.19-3.23). The risk of transmission from mothers with constantly raised ALT levels was more evident than that from mothers with fluctuating ALT levels. Increased ALT levels may reflect a more severe liver disease and a higher viral load, factors known to be associated with vertical transmission. ALT determination, a simple, widely available and inexpensive test, may help in identifying mothers with an increased risk of HCV vertical transmission.

Alanine Transaminase↗

Lower mother-to-child HIV-1 transmission in boys is independent of type of delivery and antiretroviral prophylaxis: the Italian Register for HIV Infection in Children.

The relationship between infant's gender and rate of HIV-1 mother-to-child transmission (MTCT) was evaluated in a prospective cohort of 4151 children (2166 boys and 1985 girls) born to HIV-1-infected mothers enrolled in the Italian Register for HIV Infection in Children. Logistic regression models were performed to estimate crude odds ratios (ORs) and adjusted odds ratios (AORs) and 95% CIs for factors potentially influencing MTCT separately for the period 1985-1995 and the period 1996-2001. To evaluate rates of MTCT by gender in specific subgroups, separate logistic regression models by mode of delivery and antiretroviral prophylaxis were performed. Among children born in 1985-1995, 15.5% boys (95% CI: 13.6-17.7) and 17.9% girls (95% CI: 15.7-20.3) were infected (P = 0.1181). After 1995, a lower proportion of boys (3.1% [95% CI: 2.0-4.4]; AOR: 0.43 [95% CI: 0.26-0.71], P = 0.0008) than girls (AOR: 6.3%, 95% CI: 4.8-8.1) was infected. Lower AORs for boys persisted independently of elective cesarean delivery (AOR: 0.31, 95% CI: 0.14-0.71); other than elective cesarean (AOR: 0.38, 95% CI: 0.19-0.78) and antiretroviral prophylaxis (zidovudine monotherapy (AOR: 0.11, 95% CI: 0.03-0.38); none (AOR: 0.43, 95% CI: 0.21-0.90). No difference was observed when combined therapy in the mother was administered (AOR: 1.14, 95% CI: 0.30-4.32), but results were likely to be biased by the very low rate of infected children in this group. A lower proportion of HIV-1-infected boys in children born after 1995 was found. Factor(s) intrinsic to gender (rather than type of delivery or maternal antiretroviral prophylaxis) may be involved, because the risk of infection in boys was lower independent of interventions. A possible explanation is that, among infected fetuses, more girls survive up to the end of pregnancy and may take advantage of the benefits of preventive strategies.

Anti-HIV Agents↗

Viraemia is a common finding in immunocompetent children with rotavirus infection.

Rotavirus infection is usually localized to the intestine but involvement of extra-intestinal sites, including the respiratory tract, liver, kidney, lymph nodes, and central nervous system, has been reported. The extra-intestinal spread of the virus may occur through blood since viraemia has been documented occasionally in animals and humans. Nevertheless, the questions of how common viraemia is in immunocompetent children and whether it is associated with extra-intestinal manifestations remain unsolved. Serum samples from 54 immunocompetent children hospitalized for acute diarrhea were evaluated prospectively for the presence of rotavirus RNA by nested reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate this issue. Rotavirus antigens were detected in the stools of 14 children. A bacterial aetiology was documented in 14 cases, and in the remaining cases the aetiology remained unknown. Rotavirus RNA was detected in the blood of 9/14 (64.3%) rotavirus infected children but in no child with diarrhea of other origin. Positive RT-PCR was associated with high fever and/or evidence of extra-intestinal involvement. All positive samples were collected within 3 days of illness onset, suggesting that viraemia was detectable for only a few days. Children in whom rotavirus was detected only in stool samples had high fever but no other extra-intestinal feature. These data suggest that viraemia is common in children infected with rotavirus, which may be associated with extra-intestinal involvement.

Antigens, Viral↗

Gestational and neonatal characteristics of children with cystic fibrosis: a cohort study.

OBJECTIVE: To examine whether the birth weight (BW) and the risks of being pre-term, low birth weight (LBW), and small for gestational age (SGA) of children with cystic fibrosis (CF) are different from nonaffected children. STUDY DESIGN: Retrospective cohort study. We examined all the children with CF born in Tuscany, Italy, from 1991 to 2002 (n = 70) comparing them to the entire population of non-CF-affected children born in the same period (n = 290,059). RESULTS: The mean BW of newborns with CF was 246.2 g lower than the mean BW of the non-CF neonatal population (P = .0003). Children with CF had a higher risk of being born pre-term (RR 2.62, P = .001), LBW (RR 2.66, P = .0009), and SGA (RR = 1.74, P = .04) than the non-CF-affected children. The mean BW of term newborns with CF was 205.7 g lower than that of term non-CF-affected babies (P = .0002). CONCLUSIONS: Our data show an association between CF and reduced BW and show a greater risk of being pre-term for babies with CF.

Birth Weight↗

Persistently high IgA serum levels are a marker of immunological or virological failure of combined antiretroviral therapy in children with perinatal HIV-1 infection.

Non-expensive and low-complexity surrogate markers for monitoring the response to combined antiretroviral therapy (combined-ART) are needed in poor-resource settings where routine assessment of CD4+ T-lymphocyte count and viral load can not be afforded. We longitudinally evaluated Ig serum levels in 234 HIV-1 infected children receiving combined-ART with > or = 3 drugs. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using the mean and standard deviation of the normal population for each age period. Data from 17 (7.3%) children with immunological failure and from 54 (23.1%) children with virological failure of combined-ART were compared with data from not-failed children. At baseline children with immunological failure showed higher IgM z-scores (P = 0.042) than children without. After 3-12 months of therapy immunologically failed children displayed higher viral loads (P < 0.0001) and IgA (P = 0.043) z-scores than not-failed children. Similarly, at the same follow-up time, children with virological failure showed lower CD4(+) T-lymphocyte percentages (P = 0.005) and higher IgA z-scores (P < 0.0001) than not-failed children. No difference in IgG or IgM z-scores was evidenced between failed and not-failed children after 3-12 months of therapy. In conclusion, IgA serum level is a cheap and low-complexity marker of immunological or virological failure of combined-ART which might be adopted in poor-resource settings.

Adolescent↗

Molecular epidemiology of Pseudomonas aeruginosa, Burkholderia cepacia complex and methicillin-resistant Staphylococcus aureus in a cystic fibrosis center.

Chronic pulmonary infections caused by Pseudomonas aeruginosa, Burkholderia cepacia complex and Staphylococcus aureus are responsible for most of the morbidity and mortality of patients with cystic fibrosis (CF). Little is known about the routes of transmission of these pathogens from environmental or hospital sources to the patients. We hypothesised that strains of P. aeruginosa, B. cepacia complex and methicillin-resistant S. aureus (MRSA) are nosocomially acquired by CF patients. Bacterial isolates were obtained from 164 patients attending the CF Centre of Florence and from the hospital environment and the strains typed using restriction enzymes and pulsed-field gel electrophoresis (PFGE). Seventy (43%) of patients were colonised by P. aeruginosa, 6 (3.6%) by B. cepacia complex, and 11 (7%) by MRSA. Three P. aeruginosa strains were isolated from the sinks of the ward. All the MRSA isolates differed from each other. The analysis of 83 P. aeruginosa strains showed identical genotypes in five pairs of patients, whereas from the six patients infected with B. cepacia complex strains, two patients harboured identical genotypes. These pairs of patients had no contact with each other outside the CF centre and P. aeruginosa genotypes from the hospital environment differed from these clinical isolates, suggesting a possible common source of infection within or outside the centre. The study showed that, despite isolation precautions, a minimal risk of cross-infection still existed in the CF centre and that hygienic standards should be increased to further reduce this risk.

Adolescent↗

Changed bone status in human immunodeficiency virus type 1 (HIV-1) perinatally infected children is related to low serum free IGF-I.

INTRODUCTION: Adults and children affected by human immunodeficiency virus type-1 (HIV-1) infection show bone demineralization. Little is known about skeletal status using a quantitative high-frequency ultrasound (QUS) technique in these patients. OBJECTIVE: To evaluate the bone quality and assess the role of the IGF system in the bone metabolism and skeletal status of HIV-1 perinatally infected children. PATIENTS AND METHODS: Serum free and total IGF-I, IGFBP-3, serum osteocalcin level, urinary deoxypyridinoline concentration, spontaneous interleukin-6 (IL-6) release and broadband ultrasound attenuation (BUA) were evaluated in 44 prepubertal children who had perinatal HIV-1 infection. The patients were divided into two groups depending on the severity of their clinical condition: group 1 (23 children with no or mild clinical symptoms, mean age 8.0 +/- 2.9 years) and group 2 (21 children with severe clinical symptoms, mean age 8.58 +/- 2.47 years). Fifty-five healthy age- and sex-matched controls were analysed for comparison. RESULTS: Compared with group 1 and the controls, group 2 patients showed a significantly reduced BUA Z-score (P < 0.001), and significantly reduced concentrations of serum osteocalcin (P < 0.001) and urinary deoxypyridinoline (P < 0.001 and P < 0.05, respectively). Group 2 patients also showed significantly reduced serum free IGF-I (P < 0.001) and total IGF-I (P < 0.05) levels compared with the controls, but not with group 1. No statistically significant differences were found between the three groups with regard to IGFBP-3. Group 2 patients showed significantly higher spontaneous IL-6 release than group 1 patients and controls (P < 0.001). BUA Z-scores displayed a significant correlation with free IGF-I in group 2 (r = 0.96; P < 0.001), group 1 (r = 0.56; P = 0.005) and controls (r = 0.50; P < 0.001). CONCLUSION: Our study shows that only patients affected by perinatal HIV-1 infection with severe clinical manifestations present significant changes in bone quality and bone metabolism. Our data also show that impairment of skeletal status is related to reduction in serum total and free IGF-I. Children with perinatal HIV-1 infection, because of a considerable improvement in life expectancy, seem at great risk of not obtaining an optimal bone mass. A possible therapeutic approach should be considered in these children.

Amino Acids↗