[Concordances and predictors of biopsies in renal tumors]. / Concordances et facteurs prédictifs des biopsies dans les tumeurs rénales.

AIM: Evaluate the concordance between the renal lesions biopsy's histology and the final histology of the surgical specimen according to histological subtype, and search for predictive factors of non-concordance. MATERIAL: We performed a monocentric retrospective study that included 156 patients suffering from a renal tumor that benefited a lesion biopsy before surgical treatment. Sensibility and specificity of the renal lesion's biopsy for histological diagnostic of the different renal tumors where calculated. RESULTS: One hundred and fifty-eight renal tumor biopsies were realized between 2001 and 2016. One hundred and forty-three renal cell carcinoma were found on the surgical piece, 135 were diagnosed on prior biopsy. Global concordance rate was 88%. For the establishment of the nuclear Fuhrmann grade, the concordance rate (low vs. high grade) was 72.9%. The cohort was divided into 2 groups according to the existence (group 1, n=139) or the absence (group 2, n=19) of concordance. Group 1 and 2 differed by the predominance of men in group 1 (66% vs. 37%, P=0.013), distance between the sinus and the tumor above 4mm (65% vs. 42%, P=0.05). CONCLUSION: In renal tumor care, renal biopsy is a reliable testing. However, some factors most likely linked to the tumor anatomy (intra-sinusal tumor) and their histological composition were involved in the lack of non-contribution to the diagnosis. LEVEL OF EVIDENCE: 4.

Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial.

AIMS: The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. METHODS: Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg-1 ; maintenance dose 12 mg kg-1 day-1 or 20 mg kg-1 day-1 , respectively, for infants <30 weeks or ≥30 weeks' corrected gestational age) or micafungin (loading dose 15 mg kg-1 day-1 ; maintenance dose 10 mg kg-1 day-1 ). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks' corrected gestational age or hospital discharge. RESULTS: Thirty-six neonates were enrolled. The median (range) gestational age was 28.2 (24.1-40.1) and 26.8 (23.5-40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h-1 kg-1 ) and volume of distribution (l kg-1 ) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported. CONCLUSION: Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration-time curve target attainment rate in neonates.

Different subsets of circulating angiogenic cells do not predict bronchopulmonary dysplasia or other diseases of prematurity in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in very and extremely preterm infants undergoing mechanical ventilation. Given the altered lung vascular growth characterizing BPD, circulating angiogenic cells could be useful biomarkers to predict the risk. The objective of the study was to determine whether the percentages of circulating angiogenic cells (CD34+VEGFR-2+, CD34+CD133+VEGFR-2+, and CD45-CD34+CD133+VEGFR-2+ cells), assessed in the peripheral blood at birth by flow cytometry, could be used as markers for the risk of BPD. In one-hundred and forty-two preterm neonates (gestational age less than 32 weeks and/or birth weight less than 1500 g) admitted to our tertiary care Neonatal Intensive Care Unit between 2006 and 2009, we evaluated the percentages of circulating angiogenic cells at birth, at 7 days, and, in a subset of infants (n=40), at 28 days of life. The main outcome was the correlation between cell counts at birth and the subsequent risk of developing BPD. In our study, all the three cell populations failed to predict the development of BPD or other diseases of prematurity. We suggest that these cells cannot be used as biomarkers in preterm infants, and that research is needed to find other early predictors of BPD.

Variation of B-type natriuretic peptide concentrations and intrauterine growth restriction: mother, fetus and newborn.

To evaluate maternal, fetal, neonatal B-type natriuretic peptide (BNP) concentrations related to Intra Uterine Growth Restriction (IUGR). BNP concentrations in 43 IUGR and 35 healthy, Appropriate for Gestational Age (AGA) infants/paired mothers have been compared, from delivery/birth to first month of life. Maternal and IUGR cord BNP concentrations were coupled to fetal ultrasonography. Neonatal echocardiography was performed too. On delivery BNP was higher in all IUGR mothers, suffering or not from gestational hypertension, than in AGA (median 37.14 vs 11.1 pg/ml p=0.002). Maternal BNP was not associated to cord/neonatal BNP or fetal ultrasonographic parameters. Cord BNP was higher in IUGR than AGA newborns (median 23.9 vs 11.4 pg/ml p=0.0007) independently of gestational age, while varied with amniotic fluid (p=0.0044) and umbilical artery flowmetry (p=0.0121). Earlier drop of BNP on day 3 was reported in IUGR neonates (p=0.0001).Ventricular mass change/body weight varied positively in AGA newborns (p<0.001), while declined in IUGR ones (p=0.003). Carrying IUGR fetus is a stress factor resulting in high maternal BNP concentration. Altered fetal ultrasonographic parameters in IUGR newborns lead to higher BNP cord levels. A rapid BNP drop and probable ventricular mass adjustment of IUGR newborns may indicate earlier post-natal cardiovascular adaptation than AGA infants.

Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Preterm newborns are provided with triggering receptor expressed on myeloid cells-1.

Triggering receptor expressed on myeloid cells-1 (TREM-1) and soluble fraction (sTREM-1) are useful markers of infection in adults. Neonates, especially preterm infants, are exposed to high risk of sepsis due to the immature immune system and few data are available regarding TREM-1, mainly focused on the soluble form. We therefore decided to investigate the baseline assessment of TREM-1, membrane and soluble receptors, in preterm newborns without clinical or microbiological evidence of infection, in order to precociously measure the possible changes due to sepsis and compare them to the obtained reference values. Fifty-nine newborns were enrolled in the study. Median and Interquartile range of TREM-1 were: in monocytes 96 percent with 71 Mean Fluorescence Intensity (50-94); in PMNs: 80 percent (68-87); soluble TREM-1: 29.1 pg/ml (14.55-103.93). Monocyte expression and soluble TREM-1 concentrations appeared comparable to healthy adults, while not all PMNs expressed this receptor, possibly due to their immaturity. Birth weight negatively correlated with sTREM-1, while there were no statistical significances with gestational age, maternal age, gender, mode of delivery, patent ductus arteriosus, intrauterine growth restriction, premature rupture of membranes and TREM-1 or sTREM-1. We also reported a statistical relationship between monocyte TREM-1 and surfactant administration and between sTREM-1 and antenatal steroid prophylaxis. Even if untrained, the neonatal immune system of preterm newborns is equipped with TREM-1 system, but further studies are needed to evaluate the functionality in newborns.

[Real-time contrast-enhanced ultrasound in the evaluation of focal liver lesions: diagnostic efficacy and economical issues from a French multicentric study]. / Echographie de contraste temps réel dans la prise en charge diagnostique des lésions nodulaires hépatiques: évaluation des performances diagnostiques et de l'impact économique sur une étude multicentrique française.

The recent introduction of high-end ultrasound equipment combined with recent contrast agents provides marked improvements in the characterization of focal liver lesions as previously reported by monocentric studies. The aim of the present study was to evaluate the diagnostic performance of Contrast-Enhanced Ultrasonography (CEUS) using SonoVue as well as its medico-economic value for characterization of focal liver lesions. These nodules were not characterized on previous CT or conventional sonography. This prospective multicentric study conducted in 15 French centres found diagnostic performances similar to those reported for CT and MRI, with a concordance rate of 84.5%, sensitivity greater than 80% and specificity greater than 90% for all types of lesions. Higher acceptance was found for CEUS compared to other imaging modalities. Economical assessment based on examination reimbursment and contrast agent cost showed a lower cost for contrast ultrasound versus CT and MRI. This French multicentric study confirmed the high diagnostic value of CEUS for focal liver lesion characterization and demonstrated a lower economical impact compared to other imaging modalities such as CT and MRI.

[The contribution of CT-guided transthoracic lung biopsy to the diagnosis of organizing pneumonia]. / Apport de la biopsie pulmonaire transthoracique dans le diagnostic de pneumonie organisée.

BACKGROUND: Organizing pneumonia is a pulmonary disease with variable clinical and radiological features and with many differential diagnoses. Diagnosis is based on histology obtained by either transbronchial or surgical lung biopsy but these techniques have several disadvantages. The aim of this study was to evaluate the diagnostic yield of CT-guided transthoracic lung biopsy in organizing pneumonia and to compare it to the usual diagnostic tools. METHODS: Six cases of organizing pneumonia diagnosed with CT-guided lung biopsy are reported and discussed. A review of literature concerning the role of CT-guided lung biopsy in the diagnosis of organizing pneumonia was performed. RESULTS: CT-guided transthoracic lung biopsies provided a higher rate of adequate samples than transbronchial biopsies (92-100% versus 77-86%). The samples were larger, which reduced the risks of misdiagnosis and increased the diagnostic yield (88-97% versus 26-55% in pulmonary nodules and 42-100% versus 66-75% in diffuse pulmonary disease). Complications were rare and generally not serious. CONCLUSION: CT-guided transthoracic lung biopsy may be considered in place of transbronchial biopsy in the diagnosis of organizing pneumonia. Surgical lung biopsy remains the reference method for diagnosis.

Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study.

BACKGROUND: Colonization by Candida species is the most important predictor of the development of invasive fungal disease in preterm neonates, and the enteric reservoir is a major site of colonization. We evaluated the effectiveness of an orally supplemented probiotic (Lactobacillus casei subspecies rhamnosus; Dicoflor [Dicofarm spa]; 6 x 10(9) cfu/day) in the prevention of gastrointestinal colonization by Candida species in preterm, very low birth weight (i.e., < 1500-g) neonates during their stay in a neonatal intensive care unit. METHODS: Over a 12-month period, a prospective, randomized, blind, clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit. During the first 3 days of life, the neonates were randomly assigned to receive either an oral probiotic added to human (maternal or pooled donors') milk (group A) or human milk alone (group B) for 6 weeks or until discharge from the NICU, if the neonate was discharged before 6 weeks. On a weekly basis, specimens obtained from various sites (i.e., oropharyngeal, stool, gastric aspirate, and rectal specimens) were collected from all patients for surveillance culture, to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract. RESULTS: The incidence of fungal enteric colonization (with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site) was significantly lower in group A than in group B (23.1% vs. 48.8%; relative risk, 0.315 [95% confidence interval, 0.120-0.826]; P = .01). The numbers of fungal isolates obtained from each neonate (P = .005) and from each colonized patient (P = .005) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001-1500 g. There were no changes in the relative proportions of the different Candida strains. No adverse effects potentially associated with the probiotic were recorded. CONCLUSIONS: Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by Candida species among very low birth weight neonates.

Fungal and bacterial sepsis and threshold ROP in preterm very low birth weight neonates.

OBJECTIVE: To determine whether an association exists between either fungal or bacterial sepsis and retinopathy of prematurity (ROP). STUDY DESIGN: Retrospective cohort study on all neonates with birth weight <1500 g admitted to a large Italian third Level Neonatal Intensive Care Unit in the years 1997-2001 and screened for ROP. Univariate analysis and multiple logistic regression were used to detect significant associations with ROP (all grades and threshold) in neonates with birth weight<1000 g (extremely low birth weight (ELBW)) and 1000-1500 g. RESULTS: Among 301 enrolled neonates, ROP (all grades), threshold ROP, fungal and bacterial sepsis occurred in 31.9, 12.9, 11.6 and 40.5% of the infants, respectively. At multivariate analysis, only gestational age (P=0.03), colonization by Candida non-albicans spp (P=0.03) and fungal sepsis (P=0.03) were independent predictors of threshold ROP, and only in ELBW neonates. CONCLUSIONS: Fungal (but not bacterial) sepsis is significantly and independently associated with ROP, but only in ELBW neonates and only with threshold ROP.

[Ganglioneuroma revealed by complicated nephritic colic]. / Ganglioneurome rétropéritonéal révélé par une colique néphrétique compliquée.

INTRODUCTION: Ganglioneuroma is a rare benign nervous tumour frequently located in the retroperitoneal area. We report the case of a 22-year-old female patient where this tumour was revealed by nephritic colic complicated by pyelitis and kidney abscess. EXEGESIS: The patient presented with brutal feverish lumbar pains and urinary signs. Abundant iconography, in particular contrasted enhanced sonography, allowed to show a massive retroperitoneal lump and a puncture-biopsy indicated a ganglioneuroma which was surgically removed by laparotomy. Signs may be varied and misleading. Biological and radiological exams are useful for the diagnosis which can only be confirmed by the thorough histological examination of the removed sample. CONCLUSION: A large retroperitoneal lump without alteration of the patient's health should point to this diagnosis, since the complete surgical removal leads to recovery without recurrence, but all the other differential diagnoses must first be dismissed.

[Pain management in bone metastasis of pulmonary origin: new interventional and metabolic techniques]. / Nouvelles techniques interventionnelles et métaboliques dans la prise en charge des métastases osseuses.

Invasion of bone by a metastatic lesion is the most common cause of pain in cancer patients. Pain management in these patients is an important and difficult task. The pain is not always properly controlled by high doses of specific medication, radiation therapy or chemotherapy. When these therapies do not provide adequate pain relief, percutaneous vertebroplasty, cementoplasty, radiofrequency ablation and internal radiotherapy appear to be elegant and efficient complementary alternative pain control methods.

[G-CSF, neutropenia and candidiasis in VLBW patients]. / G-CSF, neutropenia e candidiasi nel VLBW.

OBJECTIVES: Relationships among Early Onset Neutropenia (EON), i.e. neutropenia in the first week of life, treated with Filgrastim, and subsequent colonization by Candida spp. with eventual systemic fungal infection in ELBW patients are not clear. We tried to analyze these features in a retrospective study on a selected population of a large tertiary NICU. METHODS: By a database search, we identified a group of VLBW patients who were diagnosed a systemic fungal infection (SFI) during their stay in NICU (n=52), and divided them in two subgroups: those who had presented Early Onset Neutropenia (EON) and thus had been treated with a 3-day course of Filgrastim (n=14)(group A), and those who had not presented EON and thus had not undergone Filgrastim therapy (n=38) (group B). We investigated in both subgroups the following variables: neutrophil count monitoring during the first 2 weeks of life, colonization by Candida spp, day of onset of SFI, outcome. Statistical analysis was performed by Chi-square test, ANOVA and T-test using SPSS 8.0 for Windows. RESULTS: Absolute neutrophil number was obviously lower in group A at recruitment (354/mmc vs 2910\mmc, Chi-square = 9.776, p <0.005), but became normal at the end of G-CSF treatment, thus detecting no significant differences between the two groups at day 8 (p<0.12) and 14 (p<0.34). The onset of SFI occurred significantly earlier ( 9.6 dol vs 14.6 dol., p<0.004) in group A neonates. Fungal Colonization rate in the 2nd week of life was significantly higher in previously neutropenic patients (71% vs. 37%, p< 0.005), who had also a significantly higher number of sites involved (p<0.003). CONCLUSIONS: Neutropenia in the first days of life in VLBW neonates, even if adequately and succesfully treated, heavily influences rates and severity of colonization by fungal spp., and is associated with an earlier onset of a SFI.

Update on the management of Candida infections in preterm neonates.

Invasive fungal infections in preterm neonates in the neonatal intensive care unit are predominantly caused by Candida spp, and have a high burden of morbidity and mortality. Effective prophylactic strategies have recently become available, but the identification of the best possible strategies to manage high-risk infants is still a priority. Choice and use of appropriate antifungal drugs needs careful assessment of neonatal characteristics, the epidemiology and drug pharmacokinetics. Ideally, antifungal drugs for preterm neonates should target fungal bio-films, prevent or effectively treat end-organ localisations, be active against fluconazole-resistant Candida species, and have reliable safety and tolerability profiles. The paper reviews the state-of-the-art in the area of neonatal fungal infections, and addresses some open questions related to the best possible prophylactic and therapeutic strategies to be implemented in such unique patients.

[Congenital hemangiomas: Report on ten patients]. / Hémangiomes congénitaux : à propos de dix cas.

INTRODUCTION: Congenital hemangiomas (CHs) are rare congenital vascular tumors seldom mentioned in the literature. MATERIALS AND METHODS: We carried out a retrospective study of all the cases of CH diagnosed and treated at Besançon Hospital from 2008 to 2014. The clinical, radiological, and histological data of each case were collected. All the children were seen again in 2014. RESULTS: Ten CHs (seven rapidly involuting CHs, RICH and three non-involuting CH, NICH), predominantly full-term eutrophic male infants, were enrolled. RICHs were located on the head (n=2), trunk (n=2), and lower limbs (n=3), and NICHs were found on the hands. Diagnosis was clinical for all ten infants. All CHs resembled "tumor" congenital lesions: single, oval-shaped, nonpulsatile, and well delimited, and their size did not increase after birth. Two RICHs were warm, one had phlebolites, and two had draining veins at the first visit. The mean age of the RICH involution onset was 1.7 months and the mean time to complete involution was 10.4 months. One CH was classified as a PICH (partially involuting CH) due to partial regression, two RICHs were still in the involution process at the age of 10 and 15 months, and one regressed very quickly within 7 days. No complications were observed in the NICH. Two RICHs presented benign complications (ulcerations and bleeding). Two RICHs regressed entirely, and five regressed with sequelae: lipoatrophy (n=3), cutaneous excess (n=2), dysplastic veins (n=3), a pigmented area (n=1), and an anemic halo (n=2). DISCUSSION: The small number of patients in our cohort, in spite of the length of the study, confirms the rarity of CH. The sex-ratio in favor of male infants and the location of NICH on the hands have not been reported. The most discriminating element remained the follow-up over 1 year. The initial clinical aspect of the NICH and the progression of one RICH into a NICH suggested possible overlapping forms between RICH and NICH. Some CHs, including one PICH, presented clinical and radiological criteria similar to those of vascular malformations (warm lesion, dysplastic veins, and echo-Doppler results in favor of vascular malformation). RICH regressed with sequelae in most cases. CONCLUSION: This study reveals a polymorphous clinical presentation of CH and provides a thorough description of their progression. It underlines the existence of overlapping phenomena between RICH and NICH, and between CH and vascular malformations, thus suggesting a possible link between proliferation and malformation phenomena at the origin of these lesions.

Highly active antiretroviral-treated HIV-infected children show fat distribution changes even in absence of lipodystrophy.

BACKGROUND: Combined use of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) allows a precise estimate of regional body composition and intra-abdominal adipose tissue (IAT). Data on body composition in HIV-infected children (HIV+) receiving highly active antiretroviral therapy (HAART) with (LD+) and without (LD-) lipodystrophy are lacking. METHODS: DXA scans were performed in 34 HIV+: six LD+, 28 LD- and 34 pair-matched (age, sex and body mass index) healthy controls (HC): six for LD+ (HC+) and 28 for LD- (HC-). MRI scans were performed in 16 HIV+: six LD+, 10 LD- and 16 pair-matched (age and sex) HC. Data were analysed by analysis of variance, post hoc Fisher test and Mann-Whitney test. RESULTS: LD+ and LD- were similar for: previous exposure to zidovudine/zidovudine + didanosine, months on HAART (stavudine + lamuvidine + one protease inhibitor), CD4+ cells, patients with HIV-RNA < 50 copies/ml. In HIV+ and HC, fat mass and distribution were significantly different, whereas lean mass was comparable. Thus, LD+ and LD- as compared to HC+ and HC- respectively showed: (1) reduced fat amount and percentage; (2) lower truncal fat mass; (3) markedly reduced limbs fat mass. Within the HIV+ group, (4) LD+ showed higher fat trunk/fat total (P = 0.04) and lower fat limbs/ fat total ratios (P = 0.009) than LD-; (5) LD+ showed larger IAT areas than LD- and HC (P < 0.0003). CONCLUSIONS: Increased central fat and peripheral lipoatrophy are distinctive features of all HAART-treated children. Changes in body fat composition are detectable by DXA even in the absence of signs of Lipodystrophy. Only LD+ show true central obesity.

Peculiar body composition in patients with Prader-Labhart-Willi syndrome.

Prader-Labhart-Willi syndrome (PWS)-characterized by severe obesity, short stature, hypogonadism, and muscle hypotonia-appears to be an interesting model for body-composition abnormalities. Twenty-seven PWS patients (15 males and 12 females) aged 6-22 y underwent total-body analysis by dual-energy X-ray photon absorptiometry (DXA). For each PWS patient two age- and sex-matched control subjects were studied: one obese subject with a relative body weight (RBW > 120%) and body mass index (BMI) similar to that of the patient and one normal-weight subject (RBW < 120%). Percentage body fat was significantly greater in PWS patients than in obese subjects (47.4 +/- 7.2% compared with 41.9 +/- 9.9%, P < 0.0001) and the same difference was evident for arms and legs but not for the trunk. Lean mass was significantly lower in PWS patients (26.4 +/- 8.2 kg) than in normal-weight subjects (32.9 +/- 10.2 kg) and even more so than in obese subjects (40.3 +/- 13.2 kg) (P < 0.0001). The most affected regions were limbs; thus, the ratio of lean mass in the trunk to that in the limbs was significantly higher in PWS patients (1.19 +/- 0.15) than in obese (1.07 +/- 0.13) and normal-weight (1.07 +/- 0.09) subjects (P < 0.002). The ratio of fat mass to lean mass was significantly higher in PWS patients than in obese subjects (0.90 +/- 0.32 and 0.74 +/- 0.27, P < 0.05). Bone mineral content (BMC) was significantly lower in PWS patients (1503 +/- 46 g) than in normal-weight (1876 +/- 677 g) and obese (2322 +/- 773 g) subjects (P < 0.0001); this difference was most pronounced in the limb region. Bone mineral density (BMD) in PWS patients (0.993 +/- 0.116 g/cm2) did not differ significantly from that of normal-weight subjects (1.033 +/- 0.147 g/cm2) but was significantly lower than that of obese subjects (1.154 +/- 0.139 g/cm2). The influence of age on body composition was assessed by comparing two age subgroups (< 12 y, n = 10; and > or = 12 y, n = 17). The older PWS patients had higher adiposity, lower BMC, and dramatically lower BMD. Also, the lean mass deficit increased with age so that the ratio of fat mass to lean mass was close to 1. In conclusion, PWS patients showed a peculiar body composition, to some extent similar to that found in subjects deficient in growth hormone or even to sedentary and elderly people. These results suggest the importance of an accurate analysis of body composition in PWS patients.

Influence of body composition on bone mineral content in children and adolescents.

Excess fat and fat-free mass have been extensively described in obese children, whereas few data about bone mineral content (BMC) variations are available in children. Dual-energy X-ray absorptiometry (DXA) allows a direct and accurate measurement of three body compartments (fat, lean, and BMC), subdivided into three regions (arms, trunk, and legs). The aim of our study was to evaluate the influence of body compartments on total BMC (TBMC) and regional BMC (RBMC) in obese and normal-weight subjects. Sixty-five obese and 50 normal-weight children and adolescents (age range: 5-18 y relative body weight: 160 +/- 23% and 101 +/- 12%, respectively), matched for sex and pubertal stage underwent a DXA total-body analysis. Obese subjects had significantly greater fat and lean compartments than normal-weight subjects (P < 0.0001). TBMC was larger in obese children (1930 +/- 670 g compared with 1480 +/- 490 g, P < 0.0001) as was RBMC (arms: 182 +/- 81 g compared with 151 +/- 65 g; trunk: 560 +/- 223 g compared with 433 +/- 169 g; legs: 788 +/- 341 g compared with 539 +/- 231 g, P < 0.0001). We found lean mass to be the best correlate with TBMC (r = 0.91 in obese and 0.94 in normal-weight children). Multiple-regression analysis confirmed lean mass as one of the major determinants of TBMC and RBMC in children. However, differences in TBMC and RBMC were no longer present after correction for age, sex, and body-composition variables. There were no differences in TBMC and RBMC between obese and normal-weight children after correction for the confounding variables age and sex.

Body composition assessed on the basis of arm circumference and triceps skinfold thickness: a new index validated in children by magnetic resonance imaging.

Fat and muscle areas can be calculated from equations on the basis of upper arm circumference (C) and triceps skinfold thickness (TS). These equations assume a circular limb and muscle compartment and a symmetrically distributed fat rim: total upper arm area (TUA) = C2/(4 pi), upper arm muscle area (UMA) = [C - (TS x pi)2]/(4 pi), and upper arm fat area (UFA) = TUA - UMA. This traditional method underestimates the degree of adiposity. We propose that the unrolled fat rim is a rectangle whose length = C and width = TS/2. The following new indexes are based on this assumption: upper arm fat area estimate (UFE) = C x (TS/2), and upper arm muscle area estimate (UME) = TUA - UFE. To validate these equations, areas were measured with magnetic resonance imaging (MRI) in 28 children aged 9-15 y (17 control subjects and 11 obese subjects). Correlations between MRI and UFA and MRI and UFE were similar (r = 0.96 for both correlations in the control group and r = 0.84 and 0.82, respectively, in the obese group), but the areas assessed by MRI (13.8 cm2) were closer to UFE (12.4 cm2) than to UFA (11.2 cm2) in the control group as well as in the obese group (MRI = 48.7 cm2, UFE = 46.6 cm2, and UFA = 38.5 cm2). The limits of agreement between MRI and anthropometry were 5.7 +/- 5.8 cm2 for UFA and 0.6 +/- 5.0 cm2 for UFE, showing that UFA is not acceptable in most cases, whereas UFE measurements are close to MRI measurements. In conclusion, UFE and UME are simple and accurate indexes to assess body composition. French reference values are available from 1 mo to 17 y of age.

Relative expansion of extracellular water in obese vs. normal children.

This preliminary communication reports data regarding the distribution between intracellular (ICW) and extracellular (ECW) water compartments in a group of 21 prepubertal young obese children of both sexes in comparison with a group of 18 normal children weight matched for age. Our data indicate that obesity is associated with a highly significant relative expansion of extracellular water (ECW/ICW = 0.61 +/- 0.19 and 0.76 +/- 0.09 in control and obese subjects, respectively; P < 0.0015). This observation, which has been already reported in adult women, suggests that some disturbances of water homeostasis have an early onset and stress the need for an early control of energy imbalance in children. These findings are of great concern also in the field of human body composition, suggesting the opportunity for a critical reevaluation of the assumed constancy of some human body characteristics. Body composition methodologies developed for "normal" populations would require adjustment for use in the obese population, since a considerable error would be introduced.