Factors Associated With Being Overweight and Obesity in People Living With Human Immunodeficiency Virus on Antiretroviral Therapy: Socioclinical, Inflammation, and Metabolic Markers.

BACKGROUND: We investigated the association between socioclinical, inflammatory, and metabolic markers and weight gain in people with human immunodeficiency virus (HIV) on combination antiretroviral therapy (cART). METHODS: Individuals from the COPANA cohort of normal weight (body mass index [BMI], 18.5-24.9 [ calculated as weight in kilograms divided by height in meters squared) at cART initiation who achieved virological suppression (viral load, <50 copies/mL) and maintained it through 36 months of treatment were selected. Clinical, immunovirological, and socioeconomic data and inflammation (high-sensitivity C-reactive protein, CXCL10, CXCL8, interleukin 6, soluble tumor necrosis factor receptors 1 and 2, soluble CD14, and soluble CD16) and serum metabolic (glucose, insulin, lipid profile, adiponectin, and leptin) markers were assessed. Factors associated with becoming overweight (BMI, 25-29.9) or obese (BMI, ≥30) at 36 months were assessed using multivariate logistic regression models. RESULTS: After 36 months of cART, 32 of 158 people with HIV (20%) became overweight or obese (21% female; 65% born in France and 23% born in sub-Saharan Africa; median BMI at cART initiation, 22 [interquartile range, 21-23]). After adjustment, higher BMI, originating from sub-Saharan Africa, living in a couple, and higher soluble tumor necrosis factor receptor 2 and lower adiponectin concentrations at cART initiation were associated with becoming overweight or obese. CONCLUSION: Weight gain on cART is multifactorial. Special attention should be given to migrants from sub-Saharan Africa. Monocyte activation and adipocyte dysfunction at cART initiation affect weight regulation.

Classic Metaphyseal Lesions among Victims of Abuse.

OBJECTIVE: To use legal statements by perpetrators to gain new insights into the causative mechanism of classic metaphyseal lesion (CML). The CML, so called "corner fracture," is considered a highly specific marker for abuse in infants. However, the precise correlation between CMLs and abusive head trauma is still unknown. STUDY DESIGN: In this retrospective observational study, we selected 67 cases with at least 1 CML from a 15-year cohort of legally prosecuted child abuse cases. Their clinical, radiologic, and forensic records were analyzed. In 27 cases, the perpetrator confessed to abusing the child and described the events. Potential associations with subdural hematoma and with confession were evaluated using 2 separate binary logistic regression models. RESULTS: All 67 infants showed other signs of abuse. Median age was 3.4 months. Over 65% had multiple CMLs. Knees and ankles were predominantly involved (64%). Only CMLs of the shoulder were significantly associated with subdural hematoma (P = .03). Different-age fractures were more common in the nonsubdural hematoma group (P = .01). In the group with confessions, perpetrators admitted inflicting violent indirect skeletal forces (torsion, traction, compression, and forced movements). The most common circumstance was diapering (44%), reported by male perpetrators only (P = .03) followed by dressing/undressing (30%). The violence was habitual in 67% of cases. CONCLUSIONS: This unique forensic case series shows that CMLs are caused by violent acts inflicted most during physical care of infants. The frequency of habitual violence responsible for CMLs deserves greater attention.

Pseudofeeders on fetal magnetic resonance imaging predict outcome in vein of Galen malformations.

OBJECTIVE: Although vein of Galen aneurysmal malformations (VGAM) can be diagnosed in the fetus, the challenge is predicting the occurrence of its 2 major complications: cardiopulmonary failure and encephalomalacia. This study attempts to determine which fetal brain magnetic resonance imaging (MRI) features might be used to predict the development of these complications at birth. METHODS: The cohort was extracted from a prospectively assembled database of VGAM cases managed at a single referral center from 2000 to 2014. Of 251 patients with VGAM, 83 cases were diagnosed prenatally. A total of 58 patient charts having at least 1 fetal MRI were reviewed. Patterns of brain parenchyma, hydrocephalus, and so-called middle cerebral artery (MCA) "pseudofeeders" were correlated with cardiac failure, pulmonary hypertension, and encephalomalacia at birth. RESULTS: The median gestational age at fetal MRI was 32.3 weeks of pregnancy (±2.3). Nine fetuses (16%) had encephalomalacia. Thirty-one fetuses (53%) had MCA pseudofeeders. Twenty-six fetuses (45%) had prenatal hydrocephalus. Prenatal MCA pseudofeeders were a risk factor for encephalomalacia at birth (p = 0.001). MCA pseudofeeders and hydrocephalus were risk factors for both severe cardiac failure (p = 0.01 and p = 0.04, respectively) and severe pulmonary hypertension (p = 0.014 and p = 0.05, respectively) at birth. INTERPRETATION: MCA pseudofeeders are the result of impaired cerebral blood flow, and are thus a risk factor for further brain melting at birth. Their presence can be used for informing parents and as an aid in management decisions. Ann Neurol 2017;81:278-286.

Polycystic Ovary Syndrome in Adolescents: Which MR Imaging-based Diagnostic Criteria?

Purpose To evaluate the validity and reproducibility of magnetic resonance (MR) imaging-based ovarian morphologic measurements for diagnosis of polycystic ovary syndrome (PCOS) in adolescents. Materials and Methods This case-control study included 110 adolescent girls (age range, 13-17 years) who underwent pelvic MR imaging in 2006-2015. The case group included girls with high (n = 40, hyperandrogenism and oligomenorrhea or amenorrhea), intermediate (n = 8, hyperandrogenism), or low (n = 7, oligomenorrhea or amenorrhea) suspicion of PCOS. Control subjects were 55 age-matched (± 2 years) girls with no clinical hyperandrogenism, oligomenorrhea, or amenorrhea. The validity (sensitivity, specificity, and area under the receiver operating characteristic curve [AUC]) of the number of follicles per ovary (FPO) measuring 9 mm or smaller (FPO-9) and FPO measuring 5 mm or smaller (FPO-5), ovarian volume (OV), sphericity index, peripheral distribution of follicles, and absence of a dominant follicle were determined, with girls who were highly suspected of having PCOS compared with control subjects as the reference. Two radiologists independently measured these criteria in 50 girls who were suspected of having PCOS to assess reproducibility (κ and intraclass correlation coefficients [ICCs]). Results All criteria except sphericity index and absence of a dominant follicle were significantly associated with the level of suspicion of PCOS (P ≤ .05). The AUCs for FPO-9 (0.78; 95% confidence interval [CI]: 0.68, 0.87), FPO-5 (0.73; 95% CI: 0.62, 0.83), and OV (0.77; 95% CI: 0.68, 0.87) were significantly greater than 0.5; that was not true for sphericity index (AUC, 0.58; 95% CI: 0.47, 0.70). Sensitivity and specificity for peripheral distribution of follicles were 33% (95% CI: 19%, 49%) and 95% (95% CI: 85%, 99%), respectively; for absence of a dominant follicle, they were 90% (95% CI: 76%, 97%) and 27% (95% CI: 16%, 41%), respectively. Reproducibility was almost perfect for OV (ICC, 0.89), substantial for absence of a dominant follicle (κ, 0.74), moderate for FPO-9 (ICC, 0.54) and FPO-5 (ICC, 0.61), and fair for peripheral distribution of follicles (κ, 0.37). Conclusion The most accurate MR imaging-based diagnostic criteria for PCOS were OV, FPO-9, and peripheral distribution of follicles; however, reproducibility of these measures was moderate, except that for OV (ICC, 0.89). © RSNA, 2017 Online supplemental material is available for this article.

Analysis of whole-body MRI artifacts in a pediatric population with a special emphasis on the effect of hands position.

PURPOSE: The purpose of this retrospective study was to determine the prevalence of artifacts on whole-body (WB) magnetic resonance imaging (MRI) examination in pediatric patients and identify their causes. MATERIALS AND METHODS: A total of 107 pediatric patients who underwent a total of 107 WB-MRI examinations, including short-tau inversion recovery (STIR) and T1-weighted sequences, were included. There were 62 girls and 45 boys with a mean age of 11 ± 3 (SD) years (age range: 2-16 years). WB-MRI examinations were analyzed for the presence of artifacts on STIR and T1-weighted sequences. Artifacts were further assigned to one of eight categories (motion, partial volume, cross-talk, phase sampling, susceptibility, equipment, noise, and "other") and 19 anatomical sites by a 4-year resident. Prevalence of artifacts were analyzed especially according to hands position during the examination for the upper limbs and patients' age. Age was expressed as a binary variable using median age (10 years) as the cut-off value. All qualitative variables were compared using chi-square test. RESULTS: A total of 3436 artifacts were found. The STIR sequences showed more "noise" artifacts (93/1038; 8.96%) and more "cross-talk" (102/1038; 9.83%) artifacts than T1-weighted sequences (12/1038 [1.16%] and 7/1038 [0.67%], respectively) (P < 0.001 for both). T1-weighted sequences showed more "equipment" (84/1038; 8.09%) and "stair-step" (a subset of "other") (41/1038; 3.95%) artifacts than the STIR sequences (39/1038 [3.76%] and 21/1038 [2.02%], respectively) (P < 0.001 and P = 0.01, respectively). T1-weighted sequences showed fewer artifacts on the wrists when the hands were under the bottom (P = 0.001). T1-weighted sequences showed less "equipment" artifacts when the hands were alongside the body (22/296; 7%) than on the abdomen (48/432; 11%) or under the bottom (14/128; 11%) (P < 0.001). STIR sequences showed more "motion" artifacts when the hands were on the abdomen (54/432; 13%) than alongside the body (30/296; 10%) or under the bottom (15/128; 12%) (P < 0.001). WB-MRI examinations had more "susceptibility" artifacts (38/960; 4%) and more "equipment" artifacts (81/960; 8.4%) in patients older than 10 years than in those under 10 years (23/752 [3.1%] and 42/752 [5.6%]) (P = 0.01 and P < 0.001, respectively). CONCLUSION: Artifacts on WB-MRI do not affect coronal STIR and T1-weighted sequences equally, so the use of both sequence types appears useful. Hands position should be considered with respect to both diagnostic benefit and safety.

Premature delivery in HIV-infected women starting protease inhibitor therapy during pregnancy: role of the ritonavir boost?

BACKGROUND: The association between combination antiretroviral (cARV) therapy use by human immunodeficiency virus (HIV)-infected women during pregnancy and risk of prematurity is still controversial. We explored this question, focusing on the initiation of ritonavir-boosted protease inhibitors (PIs) during pregnancy, which is now standard care. METHODS: Trends in prematurity (<37 gestational weeks) were studied among all singleton pregnancies in the Agence Nationale de Recherche sur le SIDA (ANRS) French Perinatal Cohort from 1990 through 2009 (n = 13 271). In-depth analysis was conducted in a more detailed substudy of the cohort, among women starting PI-based ARV therapy during pregnancy (n = 1253). Multivariable analysis adjusted for immunovirological status and known risk factors for prematurity. RESULTS: Prematurity increased from 9.2% during 1990-1993 (no therapy) and 9.6% during 1994-1996 (mostly zidovudine monotherapy) to 12.4% during 1997-1999 (dual-nucleoside analog therapy) and 14.3% during 2005-2009 (routine cARV therapy; P < .01). Prematurity was associated with cARV therapy, compared with zidovudine monotherapy, with an adjusted odds ratio of 1.69 (95% confidence interval [CI], 1.38-2.07; P < .01) when accounting for maternal age, intravenous drug use, geographic origin, and CD4 cell count. During 2005-2009, the prematurity rate was higher with boosted than with nonboosted PI therapy started during pregnancy (14.4% vs 9.1% [P = .05]; adjusted hazard ratio, 2.03 [95% CI, 1.06-3.89; P = .03] in multivariate analysis). The difference concerned mainly induced preterm delivery for maternal or fetal indications (5.6% vs 1.6%; P = .02), CONCLUSIONS: The prematurity rate among HIV-infected pregnant women was twice that in the general population in France; this was not entirely explained by sociodemographic characteristics. Prematurity was independently associated with cARV therapy and, particularly, with the initiation of ritonavir-boosted PI therapy during pregnancy.

Clinical course and cost assessment of infants with a first episode of acute bronchiolitis presenting to the emergency department: Data from the GUERANDE clinical trial.

INTRODUCTION: Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED). METHODS: Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority. RESULTS: A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756-2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France. DISCUSSION: Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.

Abusive Head Trauma in Day Care Centers.

BACKGROUND: Abusive head trauma (AHT) warrants particular attention in terms of prevention. One of the key questions asked is how often AHT occurs in infant day care centers compared with private parental or nonparental homes. To investigate this, we studied the caretaking arrangement and child's location at the time of injury in a cohort of cases involving AHT from the courts. METHODS: This multicenter retrospective study covering an 18-year period included all medical and court records of 323 children (2.5 months to 3 years) with AHT, confirmed by the authors acting as medical experts. All markers for abuse and forensic written reports were analyzed by using a standardized data collection tool. The usual child care arrangement and the child's location at the time of injury were noted. The percentage of day care centers found in the study was compared to the expected rate in the French population (19.5%) by using the χ2 test. RESULTS: In 317 AHT cases (98.5%), the assault occurred in a private home (4 in other indoor settings and 1 with missing data). In only 1 case, shaking occurred in a day care center when the nurse was alone with the infant for a few minutes. In 317 cases (98.5%), the usual child care arrangement was by a single adult in charge of 1 or more children. CONCLUSIONS: The fact that AHT is an unusual occurrence in day care centers could help social service agencies make decisions in terms of prevention. Recent government policies regarding stay-at-home orders during a pandemic have given this issue new relevance.

pCLIF-SOFA is a reliable outcome prognostication score of critically ill children with cirrhosis: an ESPNIC multicentre study.

BACKGROUND AND AIMS: Data on outcome of critically ill children with cirrhosis are scarce. We aimed to evaluate the prognostic accuracy of sequential organs scoring systems in children with cirrhosis admitted to Paediatric Intensive Care Units (PICU). METHODS: We performed a multicentre retrospective analysis of children with cirrhosis admitted into four European PICUs between 2011 and 2016. Investigators were members of the ESPNIC liver failure and support working group. Paediatric End-Stage Liver Disease (PELD) and paediatric chronic liver failure sequential organ failure assessment score (pCLIF-SOFA) diagnostic accuracy for 28- and 60-day liver transplantation, 28-day mortality and 60-day composite outcome (ie. death or liver transplantation) were tested. RESULTS: One-hundred-and-thirty children were included. The main causes for PICU admission were acute-on-chronic liver failure (ACLF), gastrointestinal bleeding and sepsis. Twenty-nine percent died and 22.3% were transplanted by day-60 after PICU admission. On multivariable analysis, pCLIF-SOFA was the only predictor of mortality at day-28 and of composite outcome. Both pCLIF-SOFA and ACLF were independently associated with emergent liver transplantation. The pCLIF-SOFA score higher than 9 well predicted a 28-day mortality with a sensitivity of 87.8% and a specificity of 77.3%. A pCLIF-SOFA score higher than 7 was independently associated with liver transplantation on day-60. Stage 3 AKI assessed with KDIGO classification was significantly associated with 28-day mortality. CONCLUSIONS: Half of critically ill cirrhotic children admitted to PICU either died or were transplanted within the initial 28-day period. On admission pCLIF-SOFA score accurately identify patients transplanted at day-28 and day-60 to those alive without LT and is associated with 28-day mortality and composite outcome at day-60.

Genomic Alterations and Complex Subclonal Architecture in Sporadic GH-Secreting Pituitary Adenomas.

Purpose: The molecular pathogenesis of growth hormone-secreting pituitary adenomas is not fully understood. Cytogenetic alterations might serve as alternative driver events in GNAS mutation-negative somatotroph tumors. Experimental Design: We performed cytogenetic profiling of pituitary adenomas obtained from 39 patients with acromegaly and four patients with sporadic gigantism by using array comparative genomic hybridization analysis. We explored intratumor DNA copy-number heterogeneity in two tumor samples by using DNA fluorescence in situ hybridization (FISH). Results: Based on copy-number profiles, we found two groups of adenomas: a low-copy-number alteration (CNA) group (<12% of genomic disruption, 63% of tumors) and a high-CNA group (24% to 45% of genomic disruption, 37% of tumors). Arm-level CNAs were the most common abnormalities. GNAS mutation-positive adenomas belonged exclusively to the low-CNA group, whereas a subgroup of GNAS mutation-negative adenomas had a high degree of genomic disruption. We detected chromothripsis-related CNA profiles in two adenoma samples from an AIP mutation-positive patient with acromegaly and a patient with sporadic gigantism. RNA sequencing of these two samples identified 17 fusion transcripts, most of which resulted from chromothripsis-related chromosomal rearrangements. DNA FISH analysis of these samples demonstrated a subclonal architecture with up to six distinct cell populations in each tumor. Conclusion: Somatotroph pituitary adenomas display substantial intertumor and intratumor DNA copy-number heterogeneity, as revealed by variable CNA profiles and complex subclonal architecture. The extensive cytogenetic burden in a subgroup of GNAS mutation-negative somatotroph adenomas points to an alternative tumorigenic pathway linked to genomic instability.