12 research outputs found
Ablation Difficulty Score: Proposal of a new tool to predict success rate of percutaneous ablation for hepatocarcinoma
Purpose: Identify the factors related to failure ablation after percutaneous ultrasound guided single electrode radiofrequency ablation (RFA) for hepatocarcinoma (HCC) and propose a score for improving patient selection and treatment allocation. Methods: From 2010 to 2020 585 HCC nodules treated with RFA were prospectively collected. Ablation Difficulty Score (ADS) was built-up according to clinical and radiological factors related to failure ablation identified by Cox-logistic regression analysis. The study population was stratified in low risk (ADS 0), intermediate risk (ADS 1), and high risk (ADS ≥ 2) of failure ablation. Results: Overall ablation success rate was 85.5%. Morbidity and mortality rates were 3.5% and 0.0%. According to per nodule analysis the following factors resulted related to failure ablation: size > 20 mm (p = 0.002), sub-capsular location (p = 0.008), perivascular location (p = 0.024), isoechoic appearance (p = 0.008), and non-cirrhotic liver (p = 0.009). The ablation success rate was 93.5% in ADS 0, 85.8% in ADS 1 and 71.3% in ADS ≥ 2 (p < 0.001). The 1-year local tumor progression (LTP) free survival was 90.2% in ADS 0, 80.6% in ADS 1, and 72.3% in ADS ≥ 2 (p = 0.009). Nodule's size > 20 mm (p = 0.014), isoechoic appearance (p = 0.012), perivascular location (p = 0.012) resulted related to lower LTP free survival. Conclusion: Ablation Difficulty Score could be a simple and useful tool for guiding the treatment decision making of HCC. RFA in high risk nodules (ADS ≥ 2) should be carefully evaluated and reserved for patients not suitable for surgery or liver transplantation
Use of Post-Natal Antiretroviral Prophylaxis for Prevention of Mother-to-Child Transmission of HIV Is Increasing in Italy
Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy
Objective: To investigate the outcome in children perinatally infected with HIV-1 whose mothers received zidovudine (ZDV) monotherapy in pregnancy.
Design: Observational retrospective study of a prospectively recruited cohort.
Setting: Italian Register for HIV Infection in Children.
Patients: A group of 216 children perinatally infected with HIV-1, born in 1992-1997 and derived prospectively from birth: 38 children had mothers receiving ZDV monotherapy and for 178 children the mothers received no antiretroviral treatment during pregnancy.
Main outcome measures: The estimated probability of developing severe disease or severe immune suppression, survival probability [95% confidence interval (CI)] within 3 years, and the hazard ratio (95% CI), adjusted for year of birth, maternal clinical condition at delivery, birthweight and treatments (Pneumocystis carinii pneumonia chemoprophylaxis and/or antiretroviral therapy before the onset of severe disease, severe immune suppression or death) were compared.
Results: Comparison of HIV-1-infected children whose mothers were treated with ZDV with children whose mothers were not treated showed that the former group had a higher probability of developing severe disease [57.3% (95% CI 40.9-74.3) versus 37.2% (95% CI 30.0-45.4); log-rank test 7.83, P = 0.005; adjusted hazard ratio 1.8 (95% CI 1.1-3.1)] or severe immune suppression [53.9% (95% CI 36.3-73.5) versus 37.5% (95% CI 30.0-46.2); log-rank test 5.58, P = 0.018; adjusted hazard ratio 2.4, (95% CI: 1.3-4.3)] and a lower survival [72.2% (95% CI 50.4-85.7) versus 81.0% (95% CI 73.7-86.5); log-rank test 4.23, P = 0.039; adjusted hazard ratio of death 1.9 (95% CI 1.1-3.6)].
Conclusions: This epidemiological observation could stimulate virologic studies to elucidate whether this rapid progression depends on in utero infection or transmission of resistant virus. Findings may suggest a need to hasten HIV-1 diagnosis in infants of ZDV-treated mothers and undertake an aggressive antiretroviral therapy in those found to be infected
Human immunodeficiency virus-related cancer in children: Incidence and treatment outcome - Report of the Italian Register
Purpose: to outline the incidence, presenting features, treatment response, and outcome of human immunodeficiency virus (HIV)-associated malignancies in infancy and childhood, together with the estimated risk of HIV-associated cancer in children born to mothers infected with HIV.
Patients and Methods: The Italian Register for HN Infection in Children collected data by specific registration and follow-up forms. By March 1999, 5,060 children were recruited, including 4,889 with perinatal exposure to HIV-1. Overall, 1,331 infected children were enrolled onto the Register and classified according to current Centers for Disease Control criteria; of them, 1,163 were vertically infected (24% of those with perinatal exposure). Of these 1,163, 569 (49%) were considered to have been prospectively followed-up since they had been registered at birth or within the first 3 months of age.
Results: Of the 1,331 children observed for a median time of 6.5 years, 35 developed 36 malignancies, four of which occurred in patients with blood-borne risk. For the 1,163 vertically infected children, the cumulative number of years of observation was 7,178 child-years and the cumulative incidence of HIV-associated tumors was 4. 18 per 1,000 children/yr (95% confidence interval [CI], 2.92 to 5.98). When only the 569 vertically infected children prospectively followed up since birth were considered, the cumulative number of years of observation was 2,803 child-years. In this group, 10 rumors were observed, with a cumulative incidence of HIV-associated tumors of 3.57 per 1,000 children per year (95% CI, 1.92 to 6.63).
Conclusion: The risk of cancer was significantly higher but nor restricted to symptomatic and/or immune-compromised children. Cancer-directed treatment should be given promptly to these patients, who have ct fair chance to survive their tumor in view of potential highly aggressive antiretroviral therapy-associated improvement in survival and quality of life
The second generation of HIV-1 vertically exposed infants: a case series from the Italian Register for paediatric HIV infection
Background: In the Highly Active Antiretroviral Therapy (HAART) era, the prognosis of children perinatally infected with HIV-1 has significantly improved, so the number of perinatally-infected females entering child-bearing age and experiencing motherhood is increasing.Methods: A description of the medical history and pregnancy outcomes of women with perinatal acquired HIV-1 infection enrolled in the Italian Register for HIV infection in Children.Results: Twenty-three women had 29 pregnancies. They had started an antiretroviral therapy at a median of 7.7 years (interquartile range, IQR 2.3 - 11.4), and had experienced a median of 4 therapeutic regimens (IQR 2-6). Twenty women (87%) had taken zidovudine (AZT) before pregnancy, in 14 cases as a starting monotherapy. In 21 pregnancies a protease inhibitor-based regimen was used. At delivery, the median of CD4+ T lymphocytes was 450/μL (IQR 275-522), and no viral load was detectable in 15 cases (reported in 21 pregnancies). Twenty-eight children were delivered through caesarean section (median gestational age: 38 weeks, IQR 36-38, median birth weight: 2550 grams, IQR 2270 - 3000). Intravenous AZT was administered during delivery in 26 cases. All children received oral AZT (median: 42 days, IQR 31 - 42), with no adverse events reported. No child acquired HIV-1 infection.Conclusions: Despite a long history of maternal infection, multiple antiretroviral regimens and, perhaps, the development of drug-resistant viruses, the risk of mother-to-child transmission does not seem to have increased among the second-generation of HIV-1 exposed infants. © 2014 Calitri et al.; licensee BioMed Central Ltd
Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children
Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2-12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13-5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063-7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children
LOW PREVALENCE OF SELECTIVE IgA DEFICIENCY IN INFECTED CHILDREN BORN TO HIV-SEROPOSITIVE MOTHERS: AN IN VIVO MODEL FOR SPECULATION ON SELECTIVE IgA DEFICIENCY PATHOGENESIS
Anecdotal reports of restored immunoglobulin production in individuals with common variable immunodeficiency after acquiring HIV infection suggest that perturbation of the immune system occurring during HIV infection may force some underlying functional defects. These findings raise intriguing questions about the pathogenesis of common variable immunodeficiency. No study has investigated the possible influence of HIV infection on the development: of selective IgA deficiency, a primary immunologic defect genetically related to common variable immunodeficiency. IgA serum levels were evaluated in a large cohort of children born to HIV-infected mothers from 1985 to 2006. To avoid differences possibly due to different follow-up durations we considered only infected and noninfected children aged over 4 years at last-follow-up. The study included 1,157 non-infected children and 964 infected children, aged >= 4 years at last-follow-up and with availability of two or more serum IgA determinations over six months of age. No child displayed immunoglobulin values compatible with diagnosis of common variable immunodeficiency. However, 0/964 infected children vs. 5/1157 noninfected children had selective IgA deficiency (P=0.048). It may be speculated that several immunological alterations, occurring simultaneously in perinatal HIV infection, surpass the functional defect exhibited in some children with selective IgA deficiency. Our data may shed light on the pathogenesis of selective IgA deficiency
Identifying Neurobiological Markers in Obsessive–Compulsive Disorder: A Study Protocol for a Cross-Sectional Study in Subgroups of Differing Phenotype
Obsessive–compulsive disorder (OCD) represents a frequent and highly disabling mental disorder. Past attempts to characterize different disease subgroups focused on the time of onset (late vs. early onset), presence of insight (poor insight), and post-infectious forms (pediatric acute-onset neuropsychiatric syndrome, PANS). Each subgroup may be associated with a differing impact on cognition, functioning, sleep quality, and treatment response profile. Certain lines of evidence suggest brain-derived neurotrophic factor (BDNF) levels may differ between individuals living with OCD as compared with controls, but there is a lack of evidence on the variation of BDNF levels in OCD subgroups. Lastly, the potential of assessing inflammatory states, electroencephalogram, and polysomnography to characterize these subtypes has been hardly explored. Estimates of drug-resistance rates indicate that 20% and up to 65% of affected adults and up to 35% of the pediatric population may not benefit from pharmacological treatments. At least part of the variability in treatment response could depend on the underlying biological heterogeneity. In the present project, we aim to increase the accuracy in characterizing the phenotypical and biological signature for the different OCD subtypes through clinical, cognitive, and sleep markers, along with other possible markers that may be biologically plausible
Discordance between CD4 cell count and CD4 cell percentage : implications for when to start antiretroviral therapy in HIV-1 infected children
Antiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one marker is below the threshold, whereas the other is above
Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy
Background: Early highly active antiretroviral therapy ( HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking.
Methods: We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]: 4.21-7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided.
Results: Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71-5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4(+) T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4(+) T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001).
Conclusion: Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed
