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Objective: Maternal thyroid dysfunction during pregnancy is associated with neurodevelopmental impairment in the offspring. No data are currently available for the offspring of patients treated early for congenital hypothyroidism (CH). The aim of this study was to investigate motor and language milestones at one year of age in a population-based registry of children born to young women with CH., Design and Methods: We assessed 110 children born to mothers with CH, and 1367 children from the EDEN French population-based birth cohort study prospectively, at the age of one year, with identical questionnaires. Outcomes were assessed in terms of scores for childhood developmental milestones relating to mobility, motor coordination, communication, motricity and language skills., Results: After adjustment for confounding factors, children born to mothers with CH were found to have a higher risk of poor motor coordination than those of the EDEN cohort (OR: 4.18, 95% CI: 2.52-6.93). No differences were identified for the other four domains investigated. Children born to mothers with gestational diabetes have a higher risk of low motor coordination score than their peers (OR: 2.10, 95% CI: 1.21-3.66). Children born to mothers with TSH ≥ 10 IU/L during the first six months of pregnancy were more likely to have low motricity or communication skills scores than those born to mothers with lower TSH concentrations (56% vs 21% for each score, P  < 0.04)., Conclusions: Maternal CH may have slight adverse effects on some developmental milestones in the child at one year of age, particularly for children born to mothers with uncontrolled hypothyroidism. However, it remains unclear whether these adverse effects modify subsequent neurodevelopment., (© 2018 European Society of Endocrinology.)

Context: Untreated hypothyroidism is associated with a higher risk of adverse obstetric and neonatal outcomes. Pregnancy complications have yet to be evaluated in patients treated early for congenital hypothyroidism (CH)., Objective: This study aimed to investigate pregnancy outcomes and their determinants in a population-based registry of young adult women with CH., Setting and Design: In total, 1748 subjects were diagnosed with CH in the first 10 years after the introduction of neonatal screening in France; 1158 of these subjects completed a questionnaire on fecundity at a mean age of 25.3 years. We analyzed all declared singleton pregnancies ending after greater than 22 weeks of gestation before the initial survey (n = 207 pregnancies) and in the 3 years following the initial survey (prospective study, n = 174 pregnancies). The reference group comprised 7245 subjects from the French National Perinatal Survey., Main Outcome Measures: Pregnancy outcomes. Serum TSH concentrations and thyroid hormone requirements., Results: In both the overall and prospective analyses, CH was associated with gestational hypertension, emergency cesarean delivery, induced labor for vaginal delivery, and prematurity. For the prospective population with CH, the adjusted odds ratios (aOR) (95% confidence interval [CI]) were 2.19 (1.26-3.81), 1.88 (1.17-3.02), 1.58 (1.12-2.24), and 1.85 (1.06-3.25), respectively. TSH concentrations at least 10 mIU/l during the first 3 or 6 months of pregnancy were associated with a higher risk of preterm delivery (aOR, 5.6; 95% CI, 1.6-20.0) and fetal macrosomia (aOR, 4.5; 95% CI, 1.03-20.1), respectively, whereas no such relationship was observed for TSH concentrations of 5.0-9.9 mIU/l., Conclusion: CH may result in adverse pregnancy outcomes. These nationwide data suggest that better thyroid disease management is required, particularly during the first two trimesters of pregnancy, together with vigilant monitoring.

Background: Quinolone resistance is a major global clinical problem. It primarily emerges in microbiota under selective pressure. Studies evaluating the incidence and risk factors for carrying quinolone-resistant bacteria in hospitalized patients treated with fluoroquinolones (FQs) are lacking., Methods: We prospectively included hospitalized patients treated with FQs. Nasal, throat and rectal swabs were performed before FQ treatment, at the end of FQ treatment and 30 days later. A 'reference group' of patients not receiving FQs was also included to determine the rates of quinolone resistance acquisition not linked to FQ treatment. Prevalence and incidence of quinolone-resistant strains of nasal coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, pharyngeal α-haemolytic streptococci and faecal Escherichia coli, and risk factors for emergence of quinolone resistance in FQ-treated patients were assessed., Results: Four-hundred and fifty-one FQ-treated patients were included, as well as 119 subjects in the 'reference group'. Emergence of quinolone resistance occurred in 110/213 (51.6%), 50/336 (14.9%), 53/290 (18.3%) and 46/336 (13.7%) of FQ-treated patients for CoNS, S. aureus, α-haemolytic streptococci and E. coli, respectively, significantly more than for reference patients for CoNS (23/65; P < 0.05), S. aureus (5/91; P < 0.02) and E. coli (4/84; P < 0.05), but not for α-haemolytic streptococci (15/70; P = 0.55). Emergence of resistance was not associated with the type of FQ received, the duration of therapy or the duration of hospital stay, but was associated with host factors such as immunosuppression and altered performance status., Conclusions: FQs received during hospitalization account for high rates of emergence of resistance to FQs in clinically relevant bacteria from human microbiota, reflecting the important ecological impact of FQs. Host factors outweighed treatment or hospitalization characteristics as risk factors for carrying quinolone-resistant strains., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), may underestimate activity and does not predict survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib. This study assessed the value of alternative radiological criteria to evaluate response in HCC patients treated with sorafenib., Patients and Methods: A retrospective blinded central analysis was performed of computed tomography (CT) scans from baseline and the first tumor evaluation in consecutive patients treated with sorafenib over a 2-year period in a single institution. Four different evaluation criteria were used: Choi, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), and RECIST 1.1., Results: Among 82 HCC patients, 64 with Barcelona Clinic Liver Cancer stage B-C were evaluable with a median follow-up of 22 months. Median duration of sorafenib treatment was 5.7 months, and median overall survival was 12.8 months. At the time of the first CT scan, performed after a median of 2.1 months, Choi, EASL, mRECIST, and RECIST 1.1 identified 51%, 28%, 28%, and 3% objective responses, respectively. Responders by all criteria showed consistent overall survival >20 months. Among patients with stable disease according to RECIST 1.1, those identified as responders by Choi had significantly better overall survival than Choi nonresponders (22.4 vs. 10.6 months; hazard ratio: 0.43, 95% confidence interval: 0.15-0.86, p = .0097)., Conclusion: Choi, EASL, and mRECIST criteria appear more appropriate than RECIST 1.1 to identify responders with long survival among advanced HCC patients benefiting from sorafenib.

Background: It is not yet known whether the risk of developing atopic dermatitis (AD) is influenced by preterm birth. Moreover, AD risk has not been assessed in a large sample of extremely preterm infants (< 29 weeks' gestation)., Objectives: To determine whether the risk of AD is influenced by preterm birth., Methods: We investigated the relationship between gestational age (GA) and AD using data from two independent population-based cohorts, including a total of 2329 preterm infants, of whom 479 were born extremely preterm., Results: There was a lower percentage of children with AD in the extremely preterm group compared with those born at a greater GA (Epipage cohort, 2-year outcome: 13·3% for 24-28 weeks, 17·6% for 29-32 weeks, 21·8% for 33-34 weeks, P = 0·02; LIFT cohort, 5-year outcome: 11% for 24-28 weeks, 21·5% for 29-32 weeks, 19·6% for 33-34 weeks, P = 0·11). After adjusting for confounding variables, a lower GA (< 29 weeks) was significantly associated with decreased risk of AD in the Epipage cohort [adjusted odds ratio (aOR) 0·57, 95% confidence interval (CI) 0·37-0·87; P = 0·009] and the LIFT cohort (aOR 0·41, 95% CI 0·18-0·90; P = 0·03)., Conclusions: Very low GA (< 29 weeks) was associated with a lower risk of AD compared with higher GA (29-34 weeks) and full-term birth., (© 2013 British Association of Dermatologists.)

Context: Asymptomatic sporadic nonfunctioning, well-differentiated pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed, and their management is controversial because of their overall good but heterogeneous prognosis., Objective: The objective of the study was to assess the natural history of asymptomatic sporadic NF-PNETs smaller than 2 cm in size and the risk-benefit balance of nonoperative management., Experimental Design: From January 2000 to June 2011, 46 patients with proven asymptomatic sporadic NF-PNETs smaller than 2 cm in size were followed up for at least 18 months with serial imaging in tertiary referral centers., Results: Patients were mainly female (65%), with a median age of 60 years. Tumors were mainly located in the pancreatic head (52%), with a median lesion size of 13 mm (range 9-15). After a median follow-up of 34 months (range 24-52) and an average of four (range 3-6) serial imaging sessions, distant or nodal metastases appeared on the imaging in none of the patients. In six patients (13%), a 20% or greater increase in size was observed. Overall median tumor growth was 0.12 mm per year, and neither patients nor tumor characteristics were found to be significant predictors of tumor growth. Overall, eight patients (17%) underwent surgery after a median time from initial evaluation of 41 months (range 27-58); all resected lesions were European Neuroendocrine Tumor Society T stage 1 (n = 7) or 2 (n = 1), grade 1, node negative, with neither vascular nor peripancreatic fat invasion., Conclusions: In selected patients, nonoperative management of asymptomatic sporadic NF-PNETs smaller than 2 cm in size is safe. Larger and prospective multicentric studies with long-term follow-up are now needed to validate this wait-and-see policy.

Context: Untreated hypothyroidism is known to impair fecundity. Patients treated early for congenital hypothyroidism (CH) have yet to be evaluated in adulthood, because screening programs have been running for only the last 30 years in most industrialized countries., Objective: Our objective was to assess the fecundity of young adults treated early for CH and its determinants., Design, Setting, and Participants: Of the 1748 subjects diagnosed with CH in the first 10 yr after the introduction of neonatal screening in France, 1158 completed a questionnaire on fecundity at a mean age of 25.3 yr. This self-administered questionnaire focused on first attempts to have a child and time to pregnancy. The control group was that used in an analogous study on subjects born between 1971 and 1985., Main Outcome Measures: Fecundability hazard ratios (HR) were estimated with Cox regression models and adjusted for known fecundity confounders (age, smoking, and reproductive history)., Results: Fecundability was similar for the CH and control groups: HR = 1.14 (0.89-1.47) for women, and HR = 0.98 (0.58-1.66) for men. In women, the most severe initial forms of the disease, athyreosis, absence of bone maturation at the knee epiphyseal ossification centers, and a low serum free T(4) concentration at diagnosis (<5 pmol/liter), were associated with lower fecundity: HR = 0.68 (0.50-0.98) (P = 0.02); HR = 0.65 (0.45-0.94) (p = 0.02) and HR = 0.70 (0.50-0.97) (P = 0.03), respectively. However, fecundability was not associated with age at the start of treatment, initial levothyroxine dose, or the adequacy of hypothyroidism control., Conclusion: There is no evidence that fecundity is generally lower in young adults treated early than in the general population. However, fecundity was lower in women suffering from the most severe form of the disease.

Context: Screening programs resulting in the early treatment of patients with congenital hypothyroidism (CH) have successfully improved neurodevelopmental outcome, but little is known about long-term health., Objectives: The aim of the study was to assess health status, and socioeconomic attainment, for a population-based registry of young adult patients., Design, Setting, and Participants: All 1748 eligible patients diagnosed during the first decade after the introduction of neonatal screening in France were invited to participate in this study at a median age of 23.4 yr. Completed questionnaires were obtained from 1202 of the selected patients. The comparison group included 5817 subjects from the last French Decennial Health Survey., Main Outcome Measures: Health indicators including medical conditions, hearing and visual status, sociodemographic characteristics, and quality of life were measured., Results: Patients with CH were significantly more likely than their peers to report associated chronic diseases (5.7 vs. 2.9%), hearing impairment (9.5 vs. 2.5%), visual problems (55.4 vs. 47.9%), and being overweight with a body mass index of at least 25 kg/m(2) (22.8 vs. 15.7%) (P < 0.0001). Furthermore, fewer patients attained the highest socioeconomic category (14.6 vs. 23.1%) and were in full-time employment (39.9 vs. 44.8%) (P < 0.0001). They were more likely to still be living with their parents and had a lower health-related quality of life than their healthy peers, particularly for mental dimensions, with a mean difference for the mental summary component of 0.35 SD score (P < 0.0001). CH severity at diagnosis, treatment adequacy, and the presence of other chronic health conditions were the main determinants of educational achievement and health-related quality of life scores., Conclusion: These findings highlight the need for careful monitoring of neurosensory functioning, weight, and long-term treatment adequacy throughout childhood and adulthood.

Background: The aim was to evaluate the value of magnetic resonance imaging (MRI) findings in Crohn's disease (CD) in correlation with pathological inflammatory score using surgical pathology analysis as a reference method., Methods: CD patients who were to undergo bowel resection surgery underwent MR enterography before surgery. The CD pathological inflammatory score of the surgical specimens was classified into three grades: mild or nonactive CD, moderately active CD, and severely active CD; fibrosis was also classified into three grades: mild, moderate, and severe. Mural and extramural MRI findings were correlated with pathological inflammatory and fibrosis grades., Results: Fifty-three consecutive patients were included retrospectively. The mean delay between MRI and surgery was 24 days (range 1-90, median 14). The CD pathological inflammatory score was graded as follows: grade 0 (11 patients, 21%), grade 1 (15 patients, 28%), and grade 2 (27 patients, 51%). MRI findings significantly associated with pathological inflammatory grading were wall thickness (P < 0.0001), degree of wall enhancement on delayed phase (P < 0.0001), pattern of enhancement on both parenchymatous (P = 0.02), and delayed phase, (P = 0.008), T2 relative hypersignal wall (P < 0.0001), blurred wall enhancement (P = 0.018), comb sign (P = 0.004), fistula (P < 0.0001), and abscess (P = 0.049). The inflammation score correlated with the fibrosis score (r = 0.63, P = 0.0001)., Conclusions: Our study identified MRI findings significantly associated with surgical pathological inflammation. These lesions are considered potentially reversible and may be efficiently treated medically. We also showed that fibrosis was closely and positively related to inflammation., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

Newborns with severe congenital hypothyroidism (often defined by the absence of knee epiphyses at diagnosis) are still at risk of loss of intellectual potential despite early treatment. Although there is no significant sexual dimorphism in the age at appearance and size of the knee epiphyses in normal newborns, it was our clinical impression that these epiphyses were more often absent in hypothyroid newborn males than in affected females. Using the large French database of congenital hypothyroidism, we studied the presence or absence of knee epiphyses at diagnosis, as well as the length of gestation and the birth weight of 1827 term newborns with athyreosis or ectopic thyroid. Boys were twice as likely as girls to have absent epiphyses [odds ratio, 2.1 (95% confidence interval, 1.6-2.7), P < 0.001, after adjustment for etiology, plasma free T(4) concentration, and presence or absence of clinical signs at diagnosis, gestational age and birth weight]. Compared with the general population of French newborns, those with congenital hypothyroidism were more often born after a prolonged gestation (> or =42 wk) and with a high birth weight (9% were above the 95th centile, as opposed to the expected 5%), regardless of sex. We conclude that the impact of congenital hypothyroidism on fetal skeletal maturation is sexually dimorphic. This may result from less efficient conversion of T(4) to T(3) by growth plate chondrocytes in males.

The aim of this study was to investigate the effect of alcohol and caffeine consumption on birth weight and the possible interaction of these substances with smoking. The sample included 628 women who were interviewed at their first visit to the maternity hospital of Roubaix, France, in 1985-1986. A significant reduction in birth weight was found to be associated with an average daily alcohol consumption of three drinks or more after gestational age, infant sex, maternal age, parity, weight, and height, and cigarette smoking had been controlled for. There was no interaction between smoking and alcohol consumption on birth weight, but a significant relation between alcohol consumption and birth weight was observed among nonsmokers as well as heavy smokers. The relation observed between caffeine and birth weight disappeared after adjustment for smoking. Our results indicate that alcohol reduces birth weight, but do not support the hypothesis of an interaction between smoking and alcohol consumption.

The teratogenic effects of alcohol have been recognized in the fetal alcohol syndrome. The syndrome is associated with very high levels of maternal consumption. Studies of the relation between much lower levels of consumption and pregnancy outcome seem to indicate consistently lower birthweight among children born to mothers drinking more than 140 g absolute alcohol per week, or about two drinks a day.