METHODS: The dynamics of the resting CD4 T-cell latent HIV reservoir was determined over the first 2 years of life in 17 HIV-infected infants initiating lopinavir/ritonavir-based HAART at a median age of 8.1 weeks and achieving adequate suppression of plasma viral load by 24 weeks.

RESULTS: The resting CD4 T-cell latent HIV reservoir was detected in 12 of 14 (86%) infants tested at 24 weeks of HAART [median frequency 1.88 infectious units per million (IUPM); range <0.22 to 3.25) in six of 10 (60%) children retested at 96 weeks. The reservoir declined, from 24 to 96 weeks of HAART, at an estimated mean rate of 0.028 log10 IUPM/month, corresponding to a half-life of 11 months (95% confidence interval 6-30 months]. A strong relationship was found between the frequency of latently infected CD4 T cells at 96 weeks of HAART and time to first undetectable plasma viral load (Spearman r = 0.91, P < 0.001).

CONCLUSION: Although the resting CD4 T-cell latent reservoir remains detectable over the first 2 years of HAART in a substantial proportion of infants, its size is associated with time to first undetectable viral load. To minimize HIV reservoirs in infants, rapid curtailment of viremia may limit HIV reservoirs and should be a therapeutic goal of early HAART in infants.

METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometry, we observed higher frequencies of EBV-specific CD8+ T cells and higher intensity of PD-1 expression on EBV-specific CD8+ T cells during AIM than during convalescence. PD-1 expression during AIM directly correlated with viral load and with the subsequent degree of CD8+ T cell contraction in convalescence. Consistent differences in PD-1 expression were observed between CD8+ T cells with specificity for two different EBV lytic antigen epitopes. Similar differences were observed in the degree to which PD-1 was upregulated on these epitope-specific CD8+ T cells following peptide stimulation in vitro. EBV epitope-specific CD8+ T cell proliferative responses to peptide stimulation were diminished during AIM regardless of PD-1 expression and were unaffected by blocking PD-1 interactions with PD-L1. Significant variability in PD-1 expression was observed on EBV epitope-specific CD8+ T cell subsets defined by V-beta usage.

CONCLUSIONS/SIGNIFICANCE: These observations suggest that PD-1 expression is not only dependent on the degree of antigen presentation, but also on undefined characteristics of the responding cell that segregate with epitope specificity and V-beta usage.

METHODS: A retrospective review was conducted and included mechanically ventilated children treated with isoflurane in a quaternary pediatric ICU for life-threatening bronchospasm, from 1993 to 2007. Demographic, blood gas, ventilator, and outcome data were collected.

RESULTS: Thirty-one patients, with a mean age of 9.5 years (range 0.4-23 years) were treated with isoflurane, from 1993 to 2007. Mean time to initiation of isoflurane after intubation was 13 hours (0-120 h), and the mean maximum isoflurane dose was 1.1% (0.3-2.5%). Mean duration of isoflurane administration was 54.5 hours (range 1-181 h), with a total mean duration of mechanical ventilation of 252 hours (range 16-1,444 h). Isoflurane led to significant improvement in pH and P(CO(2)) within 4 hours of initiation (P ≤ .001). Complications during isoflurane administration included hypotension requiring vasoactive infusions in 24 (77%), arrhythmia in 3 (10%), neurologic side effects in 3 (10%), and pneumothorax in 1 (3%) patient.

CONCLUSIONS: Isoflurane led to improvement in pH and P(CO(2)) within 4 hours in this series of mechanically ventilated patients with life-threatening bronchospasm. The majority of patients in this series developed hypotension, but there was a low incidence of other side effects related to isoflurane administration. Isoflurane appears to be an effective therapy in patients with life-threatening bronchospasm refractory to conventional therapy. However, further investigation is warranted, given the uncertain overall impact of isoflurane in this context.

METHODS: A retrospective study of all patients admitted from the PED to the PICU with ARI from January 2006 through December 2009. Patients admitted before the availability of HFNC (cohort 1) were compared with those admitted after the availability of HFNC but before implementation of an institution-wide guideline on pediatric HFNC usage (cohort 2) and those admitted after the implementation of a pediatric HFNC usage guideline (cohort 3).

RESULTS: After controlling for age, month of admission, type of respiratory illness, and severity of illness, there was an 83% reduction in the odds of intubation in the PED in cohort 3 compared with cohort 1 (odds ratio, 0.17; 95% confidence interval, 0.06-0.50; P = 0.001). There was no significant change in mortality or median PICU length of stay after the introduction of HFNC.

CONCLUSIONS: High-flow nasal cannula used early in the development of pediatric ARI is associated with a decreased the need for intubation and mechanical ventilation.

METHODS: The Dana-Farber Cancer Institute ALL Consortium Protocol 91-01 enrolled pediatric patients between 1991 and 1995. Newly diagnosed high-risk patients were randomly assigned to receive a total of 360 mg/m(2) of doxorubicin in 30 mg/m(2) doses every 3 weeks, by either continuous (over 48 hours) or bolus-infusion (within 15 minutes). Echocardiograms at baseline, during, and after doxorubicin therapy were blindly remeasured centrally. Primary outcomes were late left ventricular (LV) structure and function.

RESULTS: A total of 102 children were randomized to each treatment group. We analyzed 484 serial echocardiograms from 92 patients (n = 49 continuous; n = 43 bolus) with >/=1 echocardiogram >/=3 years after assignment. Both groups had similar demographics and normal baseline LV characteristics. Cardiac follow-up after randomization (median, 8 years) showed changes from baseline within the randomized groups (depressed systolic function, systolic dilation, reduced wall thickness, and reduced mass) at 3, 6, and 8 years; there were no statistically significant differences between randomized groups. Ten-year ALL event-free survival rates did not differ between the 2 groups (continuous-infusion, 83% versus bolus-infusion, 78%; P = .24).

CONCLUSIONS: In survivors of childhood high-risk ALL, continuous-infusion doxorubicin, compared with bolus-infusion, provided no long-term cardioprotection or improvement in ALL event-free survival, hence provided no benefit over bolus-infusion.

METHODS:Investigators at 6 institutions conducted a retrospective chart review of all patients aged 2 to 19 years of age for the calendar years 2007-2009. Height, weight, baseline Hb levels, demographic information, and select comorbidities were recorded from the most recent clinic visit. Overweight and obesity were defined as >/=85th and >/=95th BMI percentiles for age and gender, respectively, and underweight was defined as sample, 22.4% were overweight or obese, whereas only 6.7% were underweight. Overweight or obese status was associated with sickle genotypes other than Hb SS or Hb Sbeta0 disease, and were associated with higher baseline Hb levels. Underweight individuals were more likely to be male, older, and have had at least 1 SCD-related complication. After adjusting for demographic factors, any SCD-related complication, SCD-directed treatments, and obesity-related conditions, there was a 36% increased odds of overweight/obesity for each 1 g/dL increase in baseline Hb levels.

CONCLUSIONS:Nearly one-quarter of children and adolescents with SCD in New England are overweight or obese. Longitudinal studies are needed to determine the impact of elevated BMI on the morbidity and mortality of both children and adults with SCD.

METHODS: The plates alone were tested in four-point bending single cycle to failure. The MC3-plate constructs were created with mid-diaphyseal osteotomies with a 1 cm gap. Constructs were tested in four-point bending single cycle to failure, four-point bending cyclic fatigue, and torsion single cycle to failure.

RESULTS: There were not any significant differences in bending strength and stiffness found between the two implants. The MC3-NP-LP construct was significantly stiffer than the MC3-LC-SCP in bending. No other biomechanical differences were found in bending, yield load in torsion, or mean composite rigidity. Mean cycles to failure for bending fatigue testing were similar for both constructs.

CLINICAL SIGNIFICANCE: The NP-LP was comparable to the LC-SCP in intrinsic, as well as structural properties. The NP-LP construct was more rigid than the LC-SCP construct under four-point bending, and both constructs behaved similarly under four-point bending cyclic fatigue testing and torsion single cycle to failure. The new NP-LP implant fixation is biomechanically comparable to the LC-SCP in a simulated MC3 fracture.

OBJECTIVES: The aim of this pilot study was to assess the correlation between activation of the innate immune system and MetSyn, independent of body mass index (BMI), in a young population.

METHODS: We quantitatively measured both systemic pro-inflammatory cytokines and gene expression of Toll-like receptors (TLRs) and downstream cytokines in circulating monocytes obtained from nine adolescents with metabolic syndrome (Overwt-MetSyn) and eight BMI-matched controls (Overwt-Healthy).

RESULTS: The Overwt-MetSyn group demonstrated a significant elevation in expression of TLR2, TLR4, tumour necrosis factor-a (TNF a) and interleukin-6 (IL6) in peripheral monocytes, and increased circulating levels of TNF a and IL6 when compared with the Overwt-Healthy group. TLR2 (r = 0.78, P < 0.001), TLR4 (r = 0.57, P < 0.01) and TNF a (r = 0.61, P < 0.01) gene expression positively correlated with serum levels of TNF a.

CONCLUSIONS: Our study suggests that activation of the innate immune pathway via TLRs may be partially responsible for the increased systemic inflammation seen in adolescents with MetSyn. the Study of Obesity.

DESIGN: Multicentered retrospective cohort study.

SETTING: Five pediatric intensive care units.

PATIENTS: Mechanically ventilated children (age>/=1 month toyrs) with acute lung injury admitted in 2007-2010.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Fluid intake, output, and net fluid balance were collected on days 1-7 in 168 children with acute lung injury (median age 3 yrs, median PaO2/FIO2 138) and weight-adjusted (mL/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FIO2, and vasopressor use, increasing cumulative fluid balance (mL/kg) on day 3 was associated with fewer ventilator-free days (p=.02). Adjusted for weight, daily fluid balance on days 1-3 and cumulative fluid balance on days 1-7 were higher in these children compared to adults in the Fluid and Catheter Treatment Trial conservative arm (p<.001, each day) and was similar to adults in the liberal arm.

CONCLUSIONS: Increasing fluid balance on day 3 in children with acute lung injury at these centers is independently associated with fewer ventilator-free days. Our findings and the similarity of fluid balance patterns in our cohort to adults in the Fluid and Catheter Treatment Trial liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with acute lung injury and support a Bayesian trial mirroring the Fluid and Catheter Treatment Trial.

METHODS: We surveyed a national sample of 50 pediatric chief residents randomly selected from the 198 Accreditation Council for Graduate Medical Education-accredited residency programs from August to November 2010. The 31-item telephone survey was developed from the 2002 survey, with the addition of 10 items about electronic learning and resident quality improvement projects. The survey included 4 domains: current patient safety curriculum, chief resident knowledge, learning from medical errors, and demographics.

RESULTS: We phoned 55 chief residents and contacted 51. Fifty participated (90% participation rate). Ninety-four percent of chief residents stated that their program had a formalized curriculum to discuss medical errors, compared to only 50% (P < .001) in 2002. Ninety-six percent understood that the response to a medical error should be systemic change. The primary method for educating residents about medical error reported was informal teaching. Ninety-two percent reported never or rarely discussing medical error in an outpatient setting. Seventy-four percent of chief residents reported that they never or rarely learn from an error made by an attending physician, and 50% never or rarely learned from an error made by a fellow resident.

CONCLUSIONS: Although resident education about medical errors has improved since 2002, opportunities to model learning from mistakes are frequently missed. rights reserved.

Methods: The Wrap-ups were timely (within 48 hours of a death), consistent (conducted after each pediatric intensive care unit (PICU) death), multidisciplinary (all care providers were invited), and specifically conducted by someone trained in postdeath facilitation. The role of the conductor was focused on being inclusive, navigating the discussion, diffusing areas of conflict or angst, and managing the tone of the meeting. Resident feedback was obtained by a one-time (May 2010) anonymous internet-based survey, with both open-ended free-text questions and five-point Likert scale queries. Surveyed were all residents rotating though the PICU between 2007 and 2010. Open-ended free-text responses were analyzed using content analysis methods by combining recurrent themes and organizing by main components of the Wrap-up. Quantitative responses, via a five-point Likert scale, were averaged. Results: Between 2007 and 2010, there were 36 PICU deaths. The average age was nine years old. All deaths had an accompanying conductor-led Wrap-up occurring, on average, two days after the death. Sixty percent (27/45) of pediatric residents completed the survey. Their qualitative responses showed that the key components (timely, multidisciplinary, and specifically conducted) of the Wrap-ups were valuable. Quantitatively, they agreed or strongly agreed that the consistent Wrap-ups improved end-of-life care, teamwork, stress surrounding the death, and the ability to care for others.

Conclusion: The Wrap-up, a unique forum for debriefing after a pediatric death, was well-received by residents and assisted them with processing, understanding, and resolving their experience regarding the pediatric death. The Wrap-up was a valuable addition to residents' experience and education in pediatric critical care medicine and can be replicated in other institutions.