Hepatoportal Sclerosis and Extrahepatic Portal Venous Obstruction Associated with Anti-phospholipid Antibody Syndrome in Child

We report a 2-year-old child with extrahepatic portal venous obstruction, hepatoportal sclerosis and pulmonary thromboembolism whose sole hypercoagulability factor was the presence of anti-phospholipid antibodies.

Benefits of the Intermittent Use of 6-Mercaptopurine and Methotrexate in Maintenance Treatment for Low-Risk Acute Lymphoblastic Leukemia in Children: Randomized Trial From the Brazilian Childhood Cooperative Group Protocol ALL-99

Purpose To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MIX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. Patients and Methods Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n=544) were randomly allocated to receive either continuous 6-ME/MIX (group 1, n 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MIX (200 mg/m(2) every 3 weeks; group 2, n = 272). Results The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P=.28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P=.089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P=027), while no difference was seen for girls (87.0% v 88.8% SE; P=.78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P=.002), and 772 and 636 for hematologic episodes (P=.005). Deaths on maintenance were: seven (group 1) and one (group 2). Conclusion The intermittent use of 6-MP and MIX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

Pain and distress reactivity and recovery as early predictors of temperament in toddlers born preterm

Background: Pain reactivity may reflect underlying mechanisms of constitutional aspects of temperament. Aim: To examine whether the neonatal biobehavioral reactivity and recovery responses from pain and distress, as well as the gestational age, the illness severity and the amount of painful procedures undergone the Neonatal Intensive Care Unit (NICU) stay, predict temperament later in toddlerhood, in vulnerable children born preterm. Study design: Prospective-longitudinal study. Subjects: Twenty-six preterm and very low birth weight infants followed from birth to toddlerhood. Outcome measures: Illness severity was assessed with the Clinical Risk Index for Babies (CRIB) score. The medical charts were reviewed prospectively for obtaining the amount of pain exposure in NICU. For assessing the behavioral and cardiac reactivity and recovery from pain and distress, the neonates were evaluated during routine blood collection in the NICU in the first 10 days of life. Pain and distress reactivity and recovery was measured using the Neonatal Facial Coding System score, the duration of crying. and the magnitude of average heart rate. At toddlerhood, mothers answered the Early Childhood Behavior Questionnaire. Results: Higher biobehavioral reactivity to pain and distress predicted higher temperamental Negative Affect, above and beyond gestational age, illness severity and amount of pain exposure in NICU. However, we did not find a predictive relation between gestational age, CRIB score and number of painful procedures undergone NICU and toddler`s temperament. Conclusions: The findings highlight the relevance of the neonatal individual characteristics of reactivity for identifying more vulnerable infants for future problems in biobehavioral regulation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study

Objective To evaluate if two different measures of synovial activation, baseline Hoffa synovitis and effusion synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis of the knee. Methods Non-contrast-enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a short tau inversion recovery sequence in the coronal plane. Hoffa synovitis, effusion synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic osteoarthritis nor MRI-detected tibiofemoral cartilage damage at the baseline visit. The presence of Hoffa synovitis was defined as any grade = 2 (range 0-3) and effusion synovitis as any grade = 2 (range 0-3). Logistic regression was performed to examine the relation of the presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders. Results Of 514 knees included in the analysis, the prevalence of Hoffa synovitis and effusion synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion synovitis was associated with an increased risk of cartilage loss. No such association was observed for baseline Hoffa synovitis. Conclusions Baseline effusion synovitis, but not Hoffa synovitis, predicted cartilage loss. The findings suggest that effusion synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in the future development of cartilage lesions in knees without osteoarthritis.

Prevalence and risk factors of metabolic syndrome in Brazilian and Italian obese adolescents: a comparison study

Background: Metabolic syndrome (MS) prevalence between different populations in obese adolescents is scanty to date. Objective: To compare the MS prevalence and related risk factors in Brazilian and Italian obese adolescents. Methods: A total of 509 adolescents (110 Brazilian, 399 Italian), aged 15-19 years. Anthropometric characteristics, triglycerides (TG), total, low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-cholesterol, fasting plasma glucose (FPG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood pressure were measured. Results: Age, body mass index (BMI) and BMI z-score were not significantly different between the two subgroups. BMI z-score, TG, FPG, HOMA-IR and systolic blood pressure (SBP) were significantly higher in boys than in girls both in Brazilian and Italian adolescents, while HDL-cholesterol levels were lower in boys than in girls. No significant differences were observed in BMI, LDL and total-cholesterol and DBP in two genders and groups. Insulin, FPG, HOMA-IR and TG were significantly higher, while LDL-cholesterol and SBP were significantly lower in Brazilian than in Italian subjects, both in males and females. HDL and total-cholesterol and diastolic blood pressure (DBP) were not significantly different between the two subgroups and genders. MS prevalence was higher in Brazilian than in Italian obese boys (34.8 vs. 23.6%, p < 0.001) and girls (15.6 vs. 12.5%, p < 0.01). The most frequently altered parameter was HOMA-IR both in subjects with MS (100% in Brazilian and 81.8% in Italian) and without MS (42.9% and 11.7%). Conclusion: Metabolic syndrome represents a worldwide emerging health problem in different ethnical populations, the alterations of the risk factors related to MS (different in their prevalence between different subgroups) being strictly linked to the degree of obesity.

Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study)

Purpose: To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab on best corrected visual acuity (BCVA) and total area of fluorescein leakage from active new vessels (NVs) in patients with high-risk proliferative diabetic retinopathy (PDR). Methods: We carried out a prospective study of patients with high-risk PDR and no prior laser treatment who were randomly assigned to receive PRP (PRP group) or PRP plus intravitreal injection of 1.5 mg of bevacizumab (PRP-plus group). In all patients, the PRP was administered at two time-points (weeks 1 and 3), with the intravitreal bevacizumab delivered at the end of the second laser episode in the PRP-plus group. Standardized ophthalmic evaluation including Early Treatment Diabetic Retinopathy Study BCVA as well as stereoscopic fundus photography and fluorescein angiography were performed at baseline and at weeks 4, 9 (+/- 1) and 16 (+/- 2). Main outcome measures included changes in BCVA and in total area of fluorescein leakage from active NVs. Results: Twenty-two (n = 30 eyes) consecutive patients completed the 16-week follow-up. There was no significant difference between the PRP and PRP-plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active NVs or BCVA. No significant difference in BCVA was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-plus group compared with the PRP group at weeks 4, 9 and 16 (p < 0.001). No major adverse events were identified. Conclusions: In the short-term, the adjunctive use of intravitreal bevacizumab with PRP was associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR.

Sensitivity and uncertainty analyses for burden of disease and risk factor estimates

Epidemiological studies report confidence or uncertainty intervals around their estimates. Estimates of the burden of diseases and risk factors are subject to a broader range of uncertainty because of the combination of multiple data sources and value choices. Sensitivity analysis can be used to examine the effects of social values that have been incorporated into the design of the disability–adjusted life year (DALY). Age weight, where a year of healthy life lived at one age is valued differently from at another age, is the most controversial value built into the DALY. The discount rate, which addresses the difference in value of current versus future health benefits, also has been criticized. The distribution of the global disease burden and rankings of various conditions are largely insensitive to alternate assumptions about the discount rate and age weighting. The major effects of discounting and age weighting are to enhance the importance of neuropsychiatric conditions and sexually transmitted infections. The Global Burden of Disease study also has been criticized for estimating mortality and disease burden for regions using incomplete and uncertain data. Including uncertain results, with uncertainty quantified to the extent possible, is preferable, however, to leaving blank cells in tables intended to provide policy makers with an overall assessment of burden of disease. No estimate is generally interpreted as no problem. Greater investment in getting the descriptive epidemiology of diseases and injuries correct in poor countries will do vastly more to reduce uncertainty in disease burden assessments than a philosophical debate about the appropriateness of social value

Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study

Objectives To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI. Methods Multicenter Osteoarthritis Study (MOST) is a cohort study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (< 2 mm), grade 1 (2-4 mm) and grade 2 (> 4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter-and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed. Results 400 subjects were included (mean age 58.8 +/- 7.0 years, body mass index 29.5 +/- 4.9 kg/m(2), 46% women). For individual sites, intrareader reliability (weighted kappa) was 0.67-1.00 for reader 1 and 0.60-1.00 for reader 2. Inter-reader agreement (kappa) was 0.67-0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient (ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively). Conclusions A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.

Subchondral Cystlike Lesions Develop Longitudinally in Areas of Bone Marrow Edema-like Lesions in Patients with or at Risk for Knee Osteoarthritis: Detection with MR Imaging-The MOST Study

Purpose: To assess the association of prevalent bone marrow edema-like lesions (BMLs) and full-thickness cartilage loss with incident subchondral cyst-like lesions (SCs) in the knee to evaluate the bone contusion versus synovial fluid intrusion theories of SC formation. Materials and Methods: The Multicenter Osteoarthritis study is a longitudinal study of individuals who have or are at risk for knee osteoarthritis. The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all participants. Magnetic resonance images were acquired at baseline and 30-month follow-up and read semiquantitatively by using the Whole-Organ Magnetic Resonance Imaging Score system. The tibiofemoral and patellofemoral joints were subdivided into 14 subregions. BMLs and SCs were scored from 0 to 3. Cartilage morphology was scored from 0 to 6. The association of prevalent BMLs and full-thickness cartilage loss with incident SCs in the same subregion was assessed by using logistic regression with mutual adjustment for both predictors. Results: A total of 1283 knees were included. After adjustment for full-thickness cartilage loss, prevalent BMLs showed a strong and significant association with incident SCs in the same subregion, with an odds ratio of 12.9 (95% confidence interval [CI]: 8.9, 18.6). After adjustment for BMLs, prevalent full-thickness cartilage loss showed a significant but much less important association with incident SCs in the same subregion (odds ratio, 1.4; 95% CI: 1.0, 2.0). There was no apparent relationship between severity of full-thickness cartilage loss at baseline and incident SCs. Conclusion: Prevalent BMLs strongly predict incident SCs in the same subregion, even after adjustment for full-thickness cartilage loss, which supports the bone contusion theory of SC formation. (C) RSNA, 2010

Lower respiratory tract infections among human immunodeficiency virus-exposed, uninfected infants

Objectives: To evaluate whether maternal HIV disease severity during pregnancy is associated with an increased likelihood of lower respiratory tract infections (LRTIs) in HIV-exposed, uninfected infants. Methods: HIV-exposed, uninfected, singleton, term infants enrolled in the NISDI Perinatal Study, with birth weight >2500 g were followed from birth until 6 months of age. LRTI diagnoses, hospitalizations, and associated factors were assessed. Results: Of 547 infants, 103 (18.8%) experienced 116 episodes of LRTI (incidence = 0.84 LRTIs/100 child-weeks). Most (81%) episodes were bronchiolitis. Forty-nine (9.0%) infants were hospitalized at least once with an LRTI. There were 53 hospitalizations (45.7%) for 116 LRTI episodes. None of these infants were breastfed. The odds of LRTI in infants whose mothers had CD4% <14 at enrollment were 4.4 times those of infants whose mothers had CD4% >= 29 (p = 0.003). The odds of LRTI in infants with a CD4+ count (cells/ mm(3)) <750 at hospital discharge were 16.0 times those of infants with CD4+ >= 750 (p = 0.002). Maternal CD4+ decline and infant hemoglobin at the 6-12 week visit were associated with infant LRTIs after 6-12 weeks and before 6 months of age. Conclusions: Acute bronchiolitis is common and frequently severe among HIV-exposed, uninfected infants aged 6 months or less. Lower maternal and infant CD4+ values were associated with a higher risk of infant LRTIs. Further understanding of the immunological mechanisms of severe LRTIs is needed. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Low-grade astrocytoma in a child with encephalocraniocutaneous lipomatosis

Encephalocutaneous lipomatosis (ECCL), or Haberland syndrome, is an uncommon congenital disorder with unique cutaneous, ocular and neurological features. In the present article, we describe a 3-year-old boy with ECCL who developed an extensive and recurring intraventricular low-grade glioma with atypical pathological features and elevated mitotic index. Cytogenetic analysis from tumor sample was also performed. This is the first report of a low-grade astrocytoma occurring in a child with ECCL. Whether or not the origin of the tumor is associated to the pathogenesis of the underlying syndrome is a matter for further investigation.