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author:("Yin, waning")
1.  CD4/CD8 T-cell ratio predicts HIV infection in infants: The National Heart, Lung, and Blood Institute P2C2 Study 
In resource-poor regions of the world, HIV virologic testing is not available.
We sought to evaluate the diagnostic usefulness of the CD4/CD8 T-cell ratio in predicting HIV infection in infants.
Data from the 3- and 9-month visits for non–breastfed infants born to HIV-infected mothers enrolled (1990–1994) in the Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study (mother-to-child transmission of HIV, 17%) were analyzed. Data from the 3-month visit for infants enrolled (1985–1996) in the Perinatal AIDS Collaborative Transmission Study (mother-to-child transmission of HIV, 18%) were used for validation.
At 3 months of age, data were available on 79 HIV-infected and 409 uninfected non–breast-fed infants in the Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study. The area under the curve (AUC) of the receiver operating characteristic curve at 3 months was higher for the CD4/CD8 ratio compared with the CD4+ T-cell count (AUC, 0.83 and 0.75; P = .03). The mean CD4/CD8 ratio at the 3-month visit was 1.7 for HIV-infected infants and 3.0 for uninfected infants. A CD4/CD8 ratio of 2.4 at 3 months of age was almost 2.5 times more likely to occur in an HIV-infected infant compared with an uninfected infant (test sensitivity, 81%; posttest probability of HIV, 33%). Model performance in the Centers for Disease Control and Prevention Perinatal AIDS Collaborative Transmission Study validation test (224 HIV-infected and 1015 uninfected 3-month-old infants) was equally good (AUC, 0.78 for CD4/CD8 ratio).
The CD4/CD8 T-cell ratio is a more sensitive predictor of HIV infection in infants than the CD4+ T-cell count.
Clinical implications
The CD4/CD8 T-cell ratio can be used with caution to predict HIV infection in children.
PMCID: PMC4271194  PMID: 17920669
CD4/CD8 T-cell ratio; mother-to-child transmission of HIV; HIV infection
2.  Long-Term Linear Growth and Puberty in Pediatric Liver Transplant Recipients 
The Journal of pediatrics  2013;163(5):1354-60.e1-7.
To explore linear growth, puberty, and predictors of linear growth impairment among pubertal liver transplant recipients.
Study design
Review of data collected prospectively through the Studies of Pediatric Liver Transplantation registry. Thirty-one variables were tested as risk factors for linear growth impairment, and factors significant at P < .1 were included in a logistic regression model. Risk factor analysis was limited to 512 patients who had complete demographic and medical data.
A total of 892 patients surviving their first liver transplant by >1 year, with ≥1 height recorded, who were between 8 and 18 years old between the years 2005 and 2009 were included. Median follow-up was 70.2 ± 38.6 months, mean age was 12.9 ± 3.3 years, and mean height z-score (zH) was –0.5 ±1.4 SD. Twenty percent had linear growth impairment at last follow-up. Of 353 subjects with Tanner stage data, 39% of girls and 42% of boys ages 16-18 years were not yet Tanner 5. Growth impairment rates were higher among boys than girls (30% vs 7%, P < .05) at Tanner stage 4, and occurred in 8/72 (11 %) of Tanner 5 subjects. Among patients with parental height data, zH were lower than calculated mid-parental zH (P< .005). Independent predictors of growth impairment included linear growth impairment at transplant (OR 11.53, P ≤ .0001), re-transplantation (OR 4.37, P = .001), non-white race (P = .0026), and primary diagnosis other than biliary atresia (P = .0105).
Linear growth impairment and delayed puberty are common in pubertal liver transplant recipients, with pre-transplant growth impairment identified as a potentially modifiable risk factor. Catch-up growth by the end of puberty may be incomplete.
PMCID: PMC4155930  PMID: 23916225
3.  Risk Factors for Osteonecrosis of the Jaws 
Journal of Dental Research  2011;90(4):439-444.
Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with three dental Practice-based Research Networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95%CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased four-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment > 2 years; suppuration and dental extractions were independent risk factors for ONJ.
PMCID: PMC3144129  PMID: 21317246
osteonecrosis; jaws; bisphosphonates; risk factors
4.  Outcomes in Children Transplanted for Autoimmune Hepatitis 
The outcomes of 113 children with autoimmune hepatitis (AIH), registered with Studies of Pediatric Liver Transplantation and transplanted between 1995 and 2006, were compared with those transplanted for other diagnoses (non-AIH). 4.9% of liver transplants were for AIH. 81% had AIH type 1 and most were transplanted for complications of chronic disease (60%), the majority in females (72%). Transplantation for fulminant AIH was more common in males (52.5% vs. 47.5% chronic, p=0.042). AIH patients differed from non-AIH by: age (13.0±0.4 vs. 4.6±0.1 years, p<0.0001), sex (64.6% female vs.52.9%, p=0.016), ethnicity (48.7% white vs. 58.2%, p<0.0001), initial immunosuppression (tacrolimus based: 72.6% vs. 62.6%, p=0.045; MMF use: 31.0% vs. 21.6 %, p=0.02) and immunosuppression at two years post-transplant (monotherapy: 51.9% vs.17.3%, p<0.0001). Late (>3 months), but not steroid-resistant or chronic rejection, was more common in AIH (log-rank p=0.0015). 5-year post-transplant survival for AIH was 86% (95%CI 73–93). Patient and graft survival, infectious and metabolic complications and re-transplantation rates did not differ between AIH and non-AIH groups. In conclusion, the higher risk for late acute rejection and greater degree of immunosuppression does not compromise outcomes of liver transplantation for AIH. Children transplanted for AIH in North America are typically female adolescents with complications of chronic AIH type 1 and include more children of African-American or Latino-American origin compared to the overall liver transplant population. These observations may inform detection, treatment and surveillance strategies designed to reduce the progression of autoimmune hepatitis and subsequently, the need for transplantation.
PMCID: PMC3078725  PMID: 21445922
Liver transplantation; Pediatrics; Late rejection; Outcome
Immunoreconstitution of HIV-infected (HIV+) patients after treatment with highly antiretroviral therapy (HAART) appears to provoke inflammatory diseases.
Determine whether HIV+ children on HAART (HIV+ HAART+) have a higher incidence of asthma than HIV+ children not on HAART (HIV+ HAART−).
To investigate this possibility, 2,664 children (193 HIV+, 2,471 HIV−) born to HIV+ women were evaluated for the incidence and prevalence of asthma (i.e., asthma medication use), and change of CD4+ T cell percentage with time.
The HIV+ HAART+ children had higher CD4+ T cell percentages, lower CD8+ T cell percentages, and lower viral burdens than the HIV+ HAART− children (P≤0.05 to P≤0.01). The cumulative incidence of asthma medication use in HIV+ HAART+ children at 13.5 year rose to 33.5% vs. 11.5% in HIV+ HAART− children (hazard ratio=3.34, P=0.01) and was equal to that in the HIV− children. In children born prior to the HAART era, the prevalence of asthma medication use for HIV+ HAART+ children at 11 years of age was 10.4% vs. 3.8% for HIV+ HAART− children (odds ratio=3.38, P=0.02) and was equal to that of the HIV− children. The rate of change of CD4+ T cells (percent/year) around the time of first asthma medication for HIV+ HAART+ vs. HIV+ HAART− children was 0.81 vs. −1.43 (P=0.01).
The increased incidence of asthma in HIV+ HAART+ children may be driven by immunoreconstitution of CD4+ T cells.
This HIV model of pediatric asthma may yield clues to help explain the epidemic of asthma in the general pediatric population.
PMCID: PMC3246282  PMID: 18547627
pediatric HIV infection; CD4+ T cell mediated induction of asthma; HAART-produced immunoreconstitution
6.  School outcomes in children registered in the Studies for Pediatric Liver Transplant (SPLIT) consortium 
School performance is an important aspect of functional outcomes for pediatric liver transplant (LT) recipients. This longitudinal analysis conducted through the Studies of Pediatric Liver Transplantation (SPLIT) research consortium examines several indicators of school function in these patients. Thirty-nine centers participated in data collection using a semi-structured questionnaire designed specifically for this study. The survey queried school attendance, performance and educational outcomes including the need for special educational services. Participants included 823/1133 (73%) of eligible patients, mean age 11.34±3.84, 53% female, median age at LT 4.6 (range 0.05-17.8) years, and mean interval from transplant was 5.42±2.79. Overall, 34% of patients were receiving special educational services and 20% had repeated a grade, with older participants more likely to have been held back (p=0.0007). Missing more than 10 days of school per year was reported by one third of the group with this level of absence being more common in older participants (p=0.0024) and children with shorter intervals from LT (<0.0001). Multivariate analysis revealed the following factors were associated with the need for special educational services; type of immunosuppression at six months post-LT, CSA (OR 1.8, CI:1.1-3.1), or other (OR 4.9, CI:1.4-17.6) versus tacrolimus, symptomatic CMV infection within 6 months of LT (OR 3.1:CI 1.6-6.1), and pre-transplant special educational services (OR 22.5, CI:8.6-58.4).
PMCID: PMC2936718  PMID: 20818741
Liver transplantation; special education; health outcomes; learning disabilities

Results 1-6 (6)