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University of California Health (UCH) provided a system-wide, rapid response to the humanitarian crisis of unaccompanied children crossing the southern U.S. border in the midst of the COVID-19 pandemic in 2021. In collaboration with multiple federal, state, and local agencies, UCH mobilized a multidisciplinary team to deliver acute general and specialty pediatric care to unaccompanied children at 2 Californian emergency intake sites (EISs). The response, which did not disrupt normal UCH operations, mobilized the capacities of the system and resulted in a safe and developmentally appropriate environment that supported the physical and mental health of migrant children during this traumatic period. The capacities of UCH's 6 academic health centers ensured access to trauma-informed medical care and culturally sensitive psychological and social support. Child life professionals provided access to exercise, play, and entertainment. Overall, 260 physicians, 42 residents and fellows, 4 nurse practitioners participated as treating clinicians and were supported by hundreds of staff across the 2 EISs. Over 5 months and across both EISs, a total of 4,911 children aged 3 to 17 years were cared for. A total of 782 children had COVID-19, most infected before arrival. Most children (3,931) were reunified with family or sponsors. Continuity of care after reunification or placement in a long-term shelter was enhanced by use of an electronic health record. The effort provided an educational experience for residents and fellows with instruction in immigrant health and trauma-informed care. The effort benefitted from UCH's recent experience of providing a system-wide response to the COVID-19 pandemic. Lessons learned are reported to encourage the alignment and integration of academic health centers' capacities with federal, state, and local plans to better prepare for and respond to the accelerating need to care for those in the wake of disasters and humanitarian crises.

Human infection caused by bacteria of the Edwardsiella genus is rare and most often presents with gastroenteritis that rarely requires antibiotics. Our case report describes a medically complex patient with chronic steroid use contributing to an immunocompromised state, who presented with fever and abdominal pain. The patient was later found to have Edwardsiella tarda (E. tarda) bacteremia and underwent paracentesis confirming E. tarda bacterial peritonitis requiring a prolonged antibiotic course. This case report aims to illustrate the presentation, diagnosis, and management of an uncommon infection that can have severe complications especially among immunocompromised patients.

BackgroundThis United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion.MethodsRSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season.ResultsEnrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 recipients were infected with vaccine (shed vaccine and/or had ≥4-fold rises in RSV antibodies). Serum RSV-neutralizing titers and anti-RSV F IgG titers increased ≥4-fold in 60% and 92% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 vaccinees, respectively. Exposure to community RSV during the subsequent winter was associated with strong anamnestic RSV-antibody responses.ConclusionsBoth vaccines had excellent infectivity and were well tolerated. RSV/276 induced an excess of mild cough. Both vaccines were immunogenic and primed for strong anamnestic responses.Clinical trials registrationNCT03227029 and NCT03422237.

BackgroundIntegrase inhibitors have been associated with excess gestational weight gain that may lead to adverse pregnancy outcomes (APOs). This post hoc analysis of NICHD P1081 compared antepartum changes in weight and body mass index (BMI) in pregnant women initiating raltegravir- or efavirenz-based combined antiretroviral therapy (cART) and examined associations between rates of weight gain and APOs.SettingNICHD P1081 enrolled antiretroviral-naive pregnant women living with HIV in the second and third trimester in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States.MethodsTwo hundred eighty-one women enrolled between 20 and 31 gestational weeks were randomized to raltegravir- or efavirenz-based cART and followed for ≥4 weeks. A low rate of weight gain was defined as 0.59 kg/wk. We compared weight gain and BMI increase between treatment arms using Kruskal-Wallis tests. Logistic regression was used to investigate the association between weight gain and APOs.ResultsRaltegravir-based cART was associated with significantly higher antepartum weight gain (median 0.36 kg/wk versus 0.29 kg/wk, P = 0.01) and BMI increase (median 0.14 kg/m 2 /wk versus 0.11 kg/m 2 /wk, P = 0.01) compared with efavirenz-based treatment. Women on raltegravir had less low weight gain (18% versus 36%) and more high weight gain (21% versus 12%) ( P = 0.001). Women with low weight gain were more likely than those with normal weight gain to have small for gestational age infants or a composite of APOs.ConclusionsA raltegravir-based antiretroviral regimen was associated with significantly higher antepartum rate of weight gain and BMI increase compared with efavirenz-based treatment in antiretroviral-naive pregnant women.

BackgroundTenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV.MethodsIMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5-9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant.ResultsTwenty-nine women were enrolled from the United States (median age 31 years and weight 84.5 kg during the third trimester; 48% Black, 45% Hispanic/Latina). TAF AUCtau did not significantly differ in the second [GMR 0.62 (90% CI: 0.29 to 1.34); P = 0.46] or third trimester [GMR 0.94 (90% CI: 0.63 to 1.39); P = 0.50] vs. postpartum and were comparable with historical data in nonpregnant adults. TAF was only quantifiable in 2/25 maternal delivery samples and below the limit of quantification in all cord blood and infant washout samples, likely because of the short half-life of TAF.ConclusionTAF AUCtau did not significantly differ between pregnancy and postpartum. These findings provide reassurance as TAF use during pregnancy continues to expand.

BackgroundSafe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed to select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar to those in adults, and was safe and well tolerated in young children.MethodsInternational Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is a phase 1-2 ongoing multicentre, open-label, non-comparative study of dolutegravir. A 5 mg dispersible tablet formulation of dolutegravir was studied in children aged 4 weeks to less than 6 years old, weighing at least 3 kg, with HIV RNA of greater than 1000 copies per mL and no previous treatment with integrase strand transfer inhibitor recruited from IMPAACT clinical research sites in Africa, the Americas, and Asia. Doses were selected on the basis of intensive pharmacokinetic evaluation on days 5-10, with safety and tolerability assessed up to 48 weeks. The primary objectives of this study are to evaluate the pharmacokinetics of dolutegravir in combination with optimised background therapy and to establish the dose of dolutegravir that achieves the targeted 24-h trough concentration and 24-h area under the curve for infants, children, and adolescents with HIV-1, to establish the safety and tolerability of dolutegravir at 24 and 48 weeks, and to select a dose that achieves similar exposure to the dolutegravir 50 mg once daily dose in adults. This analysis included participants treated with the proposed dose of dolutegravir dispersible tablets in two stages for each of three age cohorts. This trial is registered at ClinicalTrials.gov (NCT01302847) and is ongoing.FindingsWe recruited 181 participants from April 20, 2011, to Feb 19, 2020; of these, 96 received dolutegravir dispersible tablets. This analysis included 73 (35, 48% female) participants who received the final proposed dose with median (range) age of 1 year (0·1 to 6·0), weight (minimum-maximum) of 8·5 kg (3·7 to 18·5), plasma HIV-1 RNA concentration of 4·2 log10 copies per mL (2·1 to 7·0), and CD4% of 24·0% (0·3 to 49·0); 64 (87·7%) were treatment-experienced. The selected dose within each age cohort (≥2 years to

A 7-year-old cystic fibrosis patient with increased cough, new pulmonary infiltrate, and declining pulmonary function was diagnosed with clarithromycin resistant Mycobacterium abscessus infection. Treatment was initiated with clofazimine, linezolid and cefoxitin; she responded well to therapy and achieved microbiological clearance after completion of 12-month treatment. One year later, she had re-emergence of worsening symptoms and her sputum culture again grew clarithromycin resistant M. abscessus. Using a laboratory developed whole genome sequencing (WGS) test, the bacterium was determined to be the same strain with the same resistance mechanisms, indicating a relapse. This was deemed a critical element of clinical information, as the isolation of a genetically distinct organism would have indicated a new infection and would have served as evidence that a 12-month regimen was likely sufficient to achieve eradication. The confirmation of a relapse prompted the prolongation of the therapy plan to a goal of 24 months. Reinfection and relapse are great challenges in patients with cystic fibrosis who may acquire new strain of M. abscessus from the environment, may harbor multiple subpopulations of bacteria, or may have persistent infections but intermittent bacteria shedding that could not be eradicated. WGS has emerged as a powerful molecular tool to accurately differentiate re-infection from relapse thus solving this conundrum.

ObjectiveTo evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10 mg with cobicistat and 25 mg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics.DesignOpen-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery, and infant washout.MethodsPregnant women receiving TAF 10 mg with cobicistat or TAF 25 mg without boosting as part of clinical care had intensive pharmacokinetic assessments performed during the second and third trimesters, and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery, and washout pharmacokinetic samples were collected in infants. TAF concentrations were quantified using liquid chromatography/mass spectrometry. Comparisons between pregnancy and postpartum were made using geometric mean ratios (90% confidence intervals) and Wilcoxon signed-rank tests.ResultsThirty-one pregnant women receiving TAF 10 mg with cobicistat-boosting and 27 women receiving TAF 25 mg without boosting were enrolled. TAF exposures did not significantly differ between pregnancy and postpartum when administered as 10 mg with cobicistat. Antepartum TAF exposures with the 25 mg dose were 33-43% lower in comparison with postpartum, but comparable with those measured in nonpregnant adults. TAF was below the lower limit of quantitation in 43 of 44 cord blood, 41 of 45 maternal blood at delivery, and all infant washout samples.ConclusionTAF exposures were comparable or higher than those measured in nonpregnant adults during pregnancy and postpartum. These findings provide reassurance on adequate TAF exposures during pregnancy, and support efforts to expand the use of TAF in pregnant women with HIV.

In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.

BackgroundAlthough mother-to-child human immunodeficiency virus (HIV) transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180 000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission.MethodsA Phase 1 safety and pharmacokinetic study was conducted: a single subcutaneous (SC) dose of 20 or 40 mg/kg (Dose Groups 1 and 2, respectively) of the bNAb VRC01 was administered to HIV-exposed infants soon after birth. Breastfeeding infants (Dose Group 3) received 40 mg/kg SC VRC01 after birth and then 20 mg/kg/dose SC monthly. All infants received appropriate antiretroviral prophylaxis.ResultsForty infants were enrolled (21 in the United States, 19 in Africa). Subcutaneous VRC01 was safe and well tolerated with only mild-to-moderate local reactions, primarily erythema, which rapidly resolved. For multiple-dose infants, local reactions decreased with subsequent injections. VRC01 was rapidly absorbed after administration, with peak concentrations 1-6 days postdose. The 40 mg/kg dose resulted in 13 of 14 infants achieving the serum 50 micrograms (mcg)/mL target at day 28. Dose Group 3 infants maintained concentrations greater than 50 mcg/mL throughout breastfeeding.ConclusionsSubcutaneous VRC01 as single or multiple doses is safe and well tolerated in very young infants and is suitable for further study to prevent HIV transmission in infants.

The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.7 μg · h/ml) of the median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir-ritonavir at 700 mg/100 mg. Twenty-nine women were included in the analysis. The amprenavir AUC from time zero to 12 h (AUC0-12) was lower (geometric mean ratio [GMR], 0.60 [confidence interval {CI}, 0.49 to 0.72] [P

We evaluated white matter microstructure integrity in perinatally HIV-infected (PHIV) youths receiving cART compared to age- and gender-matched healthy youths through DTI metrics using voxel-based morphometry (VBM). We investigated 14 perinatally HIV-infected patients (age 17.9 ± 2.5 years) on cART and 17 healthy youths (HC) (age 18.0 ± 3.0 years) using a 3T MRI scanner. Four DTI-derived metrics were fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Statistical analysis was done with voxel-based analysis of covariance (ANCOVA), with age and gender as covariates. Region-of-interest secondary analyses in statistically significant regions were also performed. Regional increases in FA in the PHIV youths were found in left middle frontal gyrus, right precuneus, right lingual gyrus, and left supramarginal gyrus. Increased MD was found in the right precentral gyrus while decreased MD was found in the white matter of the right superior parietal lobule and right inferior temporal gyrus/fusiform gyrus. Regions of increased/decreased RD overlapped with regions of increased/decreased MD. Both increased and decreased AD were found in three to four regions respectively. The regional FA, MD, RD, and AD values were consistent with the voxel-based analysis findings. The findings are mostly consistent with previous literature, but increased FA has not been previously reported for perinatally HIV-infected youths. Potentially early and prolonged therapy in our population may have contributed to this new finding. Both toxicity of antiretroviral therapy and indolent infection must be considered as causative factors in the DTI metric changes that we have observed.

Background Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. Methods IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and nonpregnant women were calculated. Results Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9–31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35–3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. Conclusions Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy. Clinical Trials Registration NCT04582266. [ABSTRACT FROM AUTHOR]

Iron is an essential micronutrient for most microbes and their hosts. Mammalian hosts respond to infection by inducing the iron-regulatory hormone hepcidin, which causes iron sequestration and a rapid decrease in the plasma and extracellular iron concentration (hypoferremia). Previous studies showed that hepcidin regulation of iron is essential for protection from infection-associated mortality with the siderophilic pathogens Yersinia enterocolitica and Vibrio vulnificus However, the evolutionary conservation of the hypoferremic response to infection suggests that not only rare siderophilic bacteria but also common pathogens may be targeted by this mechanism. We tested 10 clinical isolates of Escherichia coli from children with sepsis and found that both genetic iron overload (by hepcidin-1 knockout [HKO]) and iatrogenic iron overload (by intravenous iron) potentiated infection with 8 out of the 10 studied isolates: after peritoneal injection of E. coli, iron-loaded mice developed sepsis with 60% to 100% mortality within 24 h, while control wild-type mice suffered 0% mortality. Using one strain for more detailed study, we show that iron overload allows rapid bacterial multiplication and dissemination. We further found that the presence of non-transferrin-bound iron (NTBI) in the circulation is more important than total plasma or tissue iron in rendering mice susceptible to infection and mortality. Postinfection treatment of HKO mice with just two doses of the hepcidin agonist PR73 abolished NTBI and completely prevented sepsis-associated mortality. We demonstrate that the siderophilic phenotype extends to clinically common pathogens. The use of hepcidin agonists promises to be an effective early intervention in patients with infections and dysregulated iron metabolism.

BackgroundInfluenza causes substantial morbidity and mortality despite available treatments. Anecdotal reports suggest that plasma with high antibody titres to influenza might be of benefit in the treatment of severe influenza.MethodsIn this randomised, open-label, multicentre, phase 2 trial, 29 academic medical centres in the USA assessed the safety and efficacy of anti-influenza plasma with haemagglutination inhibition antibody titres of 1:80 or more to the infecting strain. Hospitalised children and adults (including pregnant women) with severe influenza A or B (defined as the presence of hypoxia or tachypnoea) were randomly assigned to receive either two units (or paediatric equivalent) of anti-influenza plasma plus standard care, versus standard care alone, and were followed up for 28 days. The primary endpoint was time to normalisation of patients' respiratory status (respiratory rate of ≤20 breaths per min for adults or age-defined thresholds of 20-38 breaths per min for children) and a room air oxygen saturation of 93% or more. This study is registered with ClinicalTrials.gov, number NCT01052480.FindingsBetween Jan 13, 2011, and March 2, 2015, 113 participants were screened for eligibility and 98 were randomly assigned from 20 out of 29 participating sites. Of the participants with confirmed influenza (by PCR), 28 (67%) of 42 in the plasma plus standard care group normalised their respiratory status by day 28 compared with 24 (53%) of 45 participants on standard care alone (p=0·069). The hazard ratio (HR) comparing plasma plus standard care with standard care alone was 1·71 (95% CI 0·96-3·06). Six participants died, one (2%) from the plasma plus standard care group and five (10%) from the standard care group (HR 0·19 [95% CI 0·02-1·65], p=0·093). Participants in the plasma plus standard care group had non-significant reductions in days in hospital (median 6 days [IQR 4-16] vs 11 days [5-25], p=0·13) and days on mechanical ventilation (median 0 days [IQR 0-6] vs 3 days [0-14], p=0·14). Fewer plasma plus standard care participants had serious adverse events compared with standard care alone recipients (nine [20%] of 46 vs 20 [38%] of 52, p=0·041), the most frequent of which were acute respiratory distress syndrome (one [2%] vs two [4%] patients) and stroke (one [2%] vs two [4%] patients).InterpretationAlthough there was no significant effect of plasma treatment on the primary endpoint, the treatment seemed safe and well tolerated. A phase 3 randomised trial is now underway to further assess this intervention.FundingNational Institute of Allergy and Infectious Diseases, US National Institutes of Health.

PurposeTo measure cerebral metabolite levels in perinatally HIV-infected youths and healthy controls using the accelerated five dimensional (5D) echo planar J-resolved spectroscopic imaging (EP-JRESI) sequence, which is capable of obtaining two dimensional (2D) J-resolved spectra from three spatial dimensions (3D).Materials and methodsAfter acquisition and reconstruction of the 5D EP-JRESI data, T1-weighted MRIs were used to classify brain regions of interest for HIV patients and healthy controls: right frontal white (FW), medial frontal gray (FG), right basal ganglia (BG), right occipital white (OW), and medial occipital gray (OG). From these locations, respective J-resolved and TE-averaged spectra were extracted and fit using two different quantitation methods. The J-resolved spectra were fit using prior knowledge fitting (ProFit) while the TE-averaged spectra were fit using the advanced method for accurate robust and efficient spectral fitting (AMARES).ResultsQuantitation of the 5D EP-JRESI data using the ProFit algorithm yielded significant metabolic differences in two spatial locations of the perinatally HIV-infected youths compared to controls: elevated NAA/(Cr+Ch) in the FW and elevated Asp/(Cr+Ch) in the BG. Using the TE-averaged data quantified by AMARES, an increase of Glu/(Cr+Ch) was shown in the FW region. A strong negative correlation (r < -0.6) was shown between tCh/(Cr+Ch) quantified using ProFit in the FW and CD4 counts. Also, strong positive correlations (r > 0.6) were shown between Asp/(Cr+Ch) and CD4 counts in the FG and BG.ConclusionThe complimentary results using ProFit fitting of J-resolved spectra and AMARES fitting of TE-averaged spectra, which are a subset of the 5D EP-JRESI acquisition, demonstrate an abnormal energy metabolism in the brains of perinatally HIV-infected youths. This may be a result of the HIV pathology and long-term combinational anti-retroviral therapy (cART). Further studies of larger perinatally HIV-infected cohorts are necessary to confirm these findings.

Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

Objectives. To determine the frequency of bloodstream fungal infections in children who were admitted to our tertiary institution over an 11-year period. Methods. We conducted a retrospective cohort study of patients who were aged 0 to 21 years, had bloodstream fungal infections, and were admitted to the University of California, Los Angeles from 1991 through 2001. Patients were identified through the microbiology laboratory database. All positive fungal cultures for pediatric inpatients were reviewed. For each fungemic patient, a review of clinical course, cause, and outcome was performed. Results. Over 11 years, 1124 pediatric inpatients with 3633 positive cultures had evidence of fungal colonization or infection. The mean incidence of positive fungal cultures increased from 105 between 1991 and 1996 to 129 patients per year between 1997 and 2001. Fungal isolates were mainly Candida species (85%) obtained primarily from respiratory (41%) and urine (27%) cultures. Only 7.5% of positive fungal cultures were from blood, although 24 490 pediatric admissions prompted 72 960 bacterial and fungal blood cultures, at charges of $2.52 million. Of 14 592 fungal blood cultures, Conclusions. Episodes of fungemia increased significantly over 11 years as compared with a moderate increase in positive fungal cultures and were associated with high all-cause mortality rates. More sensitive assays for early identification of fungal bloodstream infections are warranted. Pediatrics 2005;116:61-67; fungal infections children, fungemia pediatrics, nosocomial infections, immunocompromised patients. ABBREVIATION. UCLA, University of California, Los Angeles., Fungal organisms are uncommon causes of bloodstream infections in pediatric patients who are admitted to tertiary care institutions; however, they result in significant morbidity and mortality. (1-4) A steady rise [...]