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Introduction: Patients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis., Methods: All patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included., Results: A total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002)., Conclusion: The risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization., Competing Interests: Conflict of interest The authors declare the following conflict of interest: M.F. has received lecture/consultant fees from AbbVie, Ferring, Tillotts, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Celgene, Gilead, Boehringer, Galapagos, Janssen, and Takeda. C.D. has received consultant fees from AbbVie. N.R. has received lecture/consultant fees from AbbVie and Takeda. The other authors state that they have no competing interests regarding this work to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD., Methods: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model., Results: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment., Conclusion: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC., Competing Interests: Conflict of interest MF has received lecture/consultant fees from Abbvie, Ferring, Tillots, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Celgene, Gilead, Boehringer, Galapagos, Janssen and Takeda. CD has received consultant fees from Abbvie. PW: none DL has received lecture/consultant fees from Abbvie and Sandoz. The other authors state that they have no competing interests regarding this work to disclose., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: Although previous studies have shown a high prevalence of mental health problems among adult Ebola virus disease survivors, no studies have yet been conducted on mental health problems among children and adolescents in affected regions. Consequently, the current study aimed to examine the prevalence and factors associated with depression and post-traumatic stress disorder (PTSD) among children and adolescent survivors and orphans by utilizing a cross-sectional survey following the 2018-2020 epidemic in Eastern Democratic Republic of the Congo., Methods: A total of 146 survivors (mean age = 13.62, standard deviation [SD] = 2.50, 49.32% female), 233 orphans (mean age = 13.18, SD = 2.96, 53.32% female), and 34 orphan-survivor participants (mean age = 13.39, SD = 2.87, 44.12% female) were recruited. Participants completed measures assessing depression and PTSD symptoms, traumatic experiences, and stigma related to Ebola and COVID-19., Results: The prevalence of depression and PTSD symptoms was 87.32% and 44.42%, respectively. Results showed significant differences in depression and PTSD symptoms between orphan-survivors (100% and 97.06%), survivors (90.21% and 75.86%), and orphans (83.48% and 16.52%; χ 2 (2) = 9.02; p = .011 and χ 2 (2) = 168.85; p < .001). Experience of traumatic events, Ebola stigmatization, and COVID-19 stigmatization positively predicted depression and PTSD symptoms. The regression models explained 61%-72% of the variance of depression and PTSD., Discussion: The results reveal that the Ebola virus disease and its associated grief severely jeopardize the mental health of children and adolescents in affected regions. Despite the relative paucity of resources, intervention programs may be helpful to minimize associated stigma and promote psychological support., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction and Aims: Malnutrition is frequent in patients with idiopathic pulmonary fibrosis (IPF). We examined the relationship between malnutrition at diagnosis and all-cause hospitalization, survival, and acute exacerbation in newly diagnosed IPF patients., Methods: In this prospective cohort study, the nutritional status of 153 consecutive newly-diagnosed IPF outpatients was evaluated by measuring body mass index (BMI), fat-free mass index (FFMI) with bioelectrical impedance analysis, and food intake with the Self Evaluation of Food Intake (SEFI)®. Diagnosis was taken as the baseline date and malnutrition was defined as an FFMI below 17 (men) or 15 kg/m 2 (women). To determine the factors associated with all-cause hospitalization and mortality, univariate Cox regression analyses were performed and variables with P < 0.2 were included in a stepwise multivariable analysis., Results: A quarter (26%; 40/153) of the patients were suffering from malnutrition at baseline, which was more frequent (62%) in patients whose BMI was <25 kg/m 2 . Patients whose baseline FFMI was low were more likely to be hospitalized (Hazard Ratio (HR) = 1.98 [95% confidence interval, 1.15; 3.41], P = 0.0139) and/or die (HR = 1.79 [1.11; 2.89], P = 0.0165), but their acute exacerbation rate was similar to that of patients with normal FFMIs. Decreased food intake (SEFI®<7) at baseline was associated with all-cause hospitalization (P = 0.003) and mortality (P < 0.0001) during follow-up. Baseline higher gender-age-physiology (GAP) scores (HR = 1.24 [1.01; 1.52], P = 0.0434; HR = 1.71 [1.37; 2.14], P < 0.0001, respectively), lower BMI (HR = 0.89 [0.83; 0.96], P = 0.003; HR = 0.89 [0.82; 0.96], P = 0.003), and decreased food intake (SEFI® score) (HR = 0.81 [0.71; 0.93], P = 0.003; HR = 0.72 [0.64; 0.81], P < 0.0001), but not FFMI, were independently associated with all-cause hospitalization and mortality rates during follow-up., Conclusions: Malnutrition and decreased food intake at IPF diagnosis are associated with all-cause hospitalization and mortality. Future studies will determine whether dedicated interventions to improve food intake and nutritional status could improve outcomes for IPF patients., Competing Interests: Conflicts of interest Stéphane Jouneau has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups, and research projects over the past 5 years from Actelion, AIRB, Astra Zeneca, Bellorophon Therapeutics, Biogen, BMS, Boehringer, Chiesi, Fibrogen, Gilead, GSK, LVL, Mundipharma, Novartis, Olam Pharm, Pfizer, Pliant Therapeutics, Roche, Savara-Serendex. Mathieu Lederlin has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups and research projects over the past 5 years from Astra Zeneca, Boehringer, Fresenius-Kabi, Roche, and Siemens Healthcare. Laurent Vernhet has received funding from Boehringer-Ingelheim for research projects. Ronan Thibault has received royalties for designing the Simple Evaluation of Food Intake® (SEFI®) (Knoë, le Kremlin Bicêtre, France) tool, and consulting fees from Roche. The other authors disclose no conflict of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In the management of prostate cancer in recent years, innovative therapies have appeared requiring precise and reliable disease detection. In 2021, new generation imaging (PET/CT, multiparametric MRI, PET/MRI) have their place at all stages of the prostate cancer natural history to help target the lesion(s) and guide therapy and improve the results obtained. PSMA PET/CT is currently the leader in this type of imaging with a complete offer during the disease: both from diagnosis, to recurrence or in the oligo-metastatic and metastatic stage resistant to castration with a pivotal role in the PSMA theranostic approach. However, multiparametric MRI also has many detection advantages when the prostate is left in place, which suggests the potential major benefit of hybrid PSMA PET/MRI imaging., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Ambient air pollution is recognized as one of the leading causes of global burden of disease. Involvement of air pollution in respiratory and cardiovascular diseases was first recognized, and then cumulative data has indicated that the intestinal tract could be also damaged., Aim: To review and discuss the current epidemiological and animal data on the effects of air pollution on intestinal homeostasis., Methods: An extensive literature search was conducted using Google Scholar and Pubmed to gather relevant human and animal studies that have reported the effects of any air pollutant on the intestine., Results: Exposure to several gaseous and particulate matter components of air pollution have been associated either positively or negatively with the onset of various intestinal diseases including appendicitis, gastroenteric disorders, irritable bowel syndrome, inflammatory bowel diseases, and peptic ulcers. Several atmospheric pollutants have been associated with modifications of gut microbiota in humans. Animal studies have showed that inhalation of atmospheric particulate matter can lead to modifications of gut microbiota, impairments of oxidative and inflammatory intestinal balances, and disruption of gut epithelial permeability., Conclusions: Overall, the literature appears to indicate that the gut is an underestimated target of adverse health effects induced by air pollution. It is therefore important to develop additional studies that aim to better understand the link between air pollutants and gastro-intestinal diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction & Aims: Obstructive sleep apnea syndrome (OSAS) is a frequent complication of obesity. Intermittent chronic hypoxia which frequently results from OSAS could modulate the systemic control of iron metabolism and alter serum iron parameters, especially among obese patients., Aims: to evaluate whether serum parameters of iron bioavailability and storage (primary), as well as age, waist circumference, arterial hypertension and tobacco use (secondary) are associated with OSAS severity and/or hypoxia., Methods: design: a single-center retrospective study with prospective data collection; inclusion criteria: consecutive patients referred for initial assessment for obesity underwent nocturnal respiratory polygraphy and iron status serum assessment within a 3-month period. The adjusted analyzes were performed using ANOVA and reported as adjusted means and 95% confidence interval (95% CI)., Results: 13 men and 56 women were included. OSAS prevalence: 72% (n = 50). Ferritin (mean ± SD, 260 ± 276 vs. 111 ± 89 μg/l, p = 0.01) and transferrin saturation (31 ± 10 vs. 24 ± 9%, p = 0.002) were significantly higher in case of moderate/severe OSAS than in absent/mild OSAS, independently from gender and tobacco use. Serum iron (19.4 μg/l [CI95%, 16.5-22.3] vs. 16.2 μg/l ([14.1-18.2], p = 0.056) and transferrin saturation (31.5% [26.3-36.7]) vs. 25.3% [21.6-29.1], p = 0.043) were higher when time under oxygen saturation <90% was >15%. Age (mean ± SD, 51 ± 11 vs. 41 ± 12 yr, p = 0.001), waist circumference (136 ± 18 vs. 123 ± 12 cm, p = 0.003), arterial hypertension (59% (n = 13/22) vs. 23% (n = 11/47), p = 0.004) and tobacco use (64% (n = 14/22) vs. 32% (n = 15/47), p = 0.01) were significantly greater in moderate/severe OSAS than in absent/mild OSAS., Conclusions: Transferrin saturation was associated with OSAS severity and time under hypoxia. This suggests a relationship between OSAS-induced hypoxia and iron metabolism among obese patients., Competing Interests: Conflict of Interest The authors have no conflict of interest related to this article to declare., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: We aimed to test a repeated program of vibration sessions of the neck muscles (rNMV) on postural disturbances and spatial perception in patients with right (RBD) versus left (LBD) vascular brain damage., Methods: Thirty-two chronic stroke patients (mean age 60.9±10 yrs and mean time since stroke 4.9±4 yrs), 16 RBD and 16 LBD, underwent a program of 10 sessions of NMV over two weeks. Posturography parameters (weight-bearing asymmetry (WBA), Xm, Ym, and surface), balance rating (Berg Balance Scale (BBS), Timed Up and Go (TUG)), space representation (subjective straight ahead (SSA), longitudinal body axis (LBA), subjective visual vertical (SVV)), and post-stroke deficiencies (motricity index, sensitivity, and spasticity) were tested and the data analyzed by ANOVA or a linear rank-based model, depending on whether the data were normally distributed, with lesion side and time factor (D-15, D0, D15, D21, D45)., Results: The ANOVA revealed a significant interaction between lesion side and time for WBA (P<0.0001) with a significant shift towards the paretic lower limb in the RBD patients only (P=0.0001), whereas there was no effect in the LBD patients (P=0.98). Neither group showed a significant modification of spatial representation. Nonetheless, there was a significant improvement in motricity (P=0.02), TUG (P=0.0005), and BBS (P<0.0001) in both groups at the end of treatment and afterwards., Conclusions: rNMV appeared to correct WBA in RBD patients only. This suggests that rNMV could be effective in treating sustainable imbalance due to spatial cognition disorders., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aim: The main aim of this study was to examine the management strategies that were used and to determine the outcomes (survival and recurrence rate) of screen-detected T1-CRC., Methods: Medical records from 207 patients with T1-CRC diagnosed through the French national screening programme in one district from 2003 to 2015 were analysed. The 5-year overall, CRC-specific and CRC-free survival were calculated for the whole cohort and for the 3 groups treated by endoscopic resection (ER) alone, ER followed by subsequent surgery (ERSS), and primary surgery (PS)., Results: Of the 207 patients, 81 (39%) underwent PS, and 126 (61%) underwent primary ER, of whom 82 (64%) underwent subsequent surgery. The 5-year overall and cancer-specific survival rates were 95.5% (95% CI, 90.8; 97.9) and 98.8% (95% CI, 95.4; 99.7%), respectively. Long-term cancer-specific mortality and recurrence crude rates were 2.4% and 5.6%, respectively. The 5-year CRC-free survival rate was 96.1% (95% CI, 91.8; 98.1%) and did not differ amongst the 3 groups (ER alone, ERSS and PS)., Conclusion: This study demonstrates the good prognosis of screen-detected T1-CRC, regardless of the treatment strategy used. But, there is a room to improve the screening programme quality with regard to the management of screen-detected CRC., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Pediatric-onset Crohn's disease (CD) may represent a more severe form of disease. The aim of this study was to describe long-term outcome and identify associated risk factors of complicated behavior in a large population-based pediatric-onset CD cohort., Patients and Methods: Cases included all patients recorded in the EPIMAD registry diagnosed with definite or probable CD between January 1988 and December 2004, under the age of 17 years at the time of diagnosis, with at least two years of follow-up., Results: Five hundred and thirty-five patients were included. Median follow-up was 11.1 years [IQR, 7.3-15.0]. At the end of follow-up, 8% (n = 44) of patients had pure ileal disease (L1), 8% (n = 44) had pure colonic disease (L2), and 83% (n = 439) had ileocolonic disease (L3). L4 disease and perianal disease were observed in 42% (n = 227) and 16% (n = 85) of patients, respectively. At the end of follow-up, 58% (n = 308) of patients presented complicated disease behavior (B2, 39% and B3, 19%), and 42% (n = 163) of patients with inflammatory behavior at diagnosis had evolved to complicated behavior. During follow-up, 86% of patients (n = 466) received at least one course of corticosteroids, 67% (n = 357) of patients had been exposed to immunosuppressants and 35% (n = 187) of patients received at least one anti-TNF agent. Forty-three percent (n = 230) of patients underwent at least one intestinal resection. The overall mortality rate was 0.93% and the SMR was 1.6 [0.5-3.8] (p = 0.20). Five cancers were reported with a crude cancer incidence rate of 1.1% and an SIR of 3.3 [1.2-7.0] (p = 0.01). In a multivariate Cox model, ileal (HR, 1.87 [1.09-3.21], p = 0.022) or ileocolonic (HR, 1.54 [1.01-2.34], p = 0.042) and perianal lesions at diagnosis (HR, 1.81 [1.13- 2.89], p = 0.013) were significantly associated with complicated behavior., Conclusion: About 80% of patients with pediatric-onset CD presented extensive ileocolonic disease during follow-up. The majority of patients evolved to complicated behavior. Surgery, cancer and mortality were observed in 43%, 0.9% and 0.9% of patients, respectively., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions of the intestinal tract. IBD are believed to result from an inappropriate immune response against the intestinal flora in genetically predisposed patients. The precise etiology of these diseases is not fully understood, therefore treatments rely on the dampening of symptoms, essentially inflammation, rather than on the cure of the disease. Despite the availability of biologics, such as anti-TNF antibodies, some patients remain in therapeutic failure and new treatments are thus needed. The multiligand receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in inflammatory reactions and immune system activation. Here, we investigated the role of RAGE in intestinal inflammation and its potential as a therapeutic target in IBD. We showed that RAGE was upregulated in inflamed tissues from IBD patients compared to controls. Rage -/- mice were less susceptible to intestinal and colonic inflammation development than WT mice. WT mice treated with the RAGE-specific inhibitor FPS-ZM1 experienced less severe enteritis and colitis. We demonstrated that RAGE could induce intestinal inflammation by promoting oxidative stress and endothelial activation which were diminished by FPS-ZM1 treatment. Our results revealed the RAGE signaling pathway as a promising therapeutic target for IBD patients.

Positron Emission Tomography (PET) is a functional nuclear medicine imaging technique which clinical value in oncology has been demonstrated. PET indications are constantly evolving, thanks to the contribution of research. The use of PET in oncology has been the subject of recommendations according to the Standard-Options-Recommendations methodology from the Fédération Nationale des Centres de Lutte Contre le Cancer in 2002, updated in 2003. However, many scientific works have been published since 2003 and new tracers have also obtained a marketing authorization in France. The objective of this work was therefore to update the recommendations established in 2003. In this context, in collaboration with the Société française de médecine nucléaire, a working group was set up for the development of good clinical practice recommendations under the HAS-INCA methodological label. The present document is issued from a comprehensive review of the literature and rigorous appraisal by a panel of national experts, organ specialists, clinical oncologists, surgeons, and imaging specialists. It is intended to be used as a guide to decision-making for those oncology teams that are able to manage patients in various situations in which the AMM label is not sufficiently precise., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Multidrug-Resistant Acinetobacter baumannii (MR-AB) can cause outbreaks in burn units. We aimed to study the incidence, risk factors and outcome of MR-AB infections in a burn unit (BU)., Methods: A prospective study was conducted from April to November, 2014 during an outbreak in a BU in Paris. Weekly surveillance cultures were performed to determine MR-AB colonization. MR-AB nosocomial infections, discharge or death without MR-AB infection were considered as competing events. To identify risk factors for MR-AB infection, baseline characteristics and time-dependent variables were investigated in univariate analyses using Cox models., Results: Eighty-six patients admissions were analyzed during the study period. Among them, 15 (17%) acquired MR-AB nosocomial infection. Median time to infection was 22days (interquartile range: 10-26 days). Cumulative incidence of MR-AB infections was 15% at 28days (95% CI=8-24). Risk factors for MR-AB infection in univariate analysis were SAPS II (Hazard Ratio (HR):1.08; 95% CI:1.05-1.12; P<0.0001) and ABSI (Abbreviated Burn Severity Index) scores (HR:1.32; 95% CI:1.12-1.56; P=0.001), MR-AB colonization (HR:10.2; 95%CI:2.05-50.3; P=0.004), invasive procedures (ventilation, arterial and/or venous catheter) (P=0.0001) and ≥2 skin grafts (HR:10.2; 95% CI:1.76-59.6; P=0.010). MR-AB infection was associated with an increased risk of death (HR: 7.11; 95%CI: 1.52-33.2; P=0.013) and longer hospital stay with a median estimated increase of 10days (IQR: 6; 14)., Conclusions: Incidence of MR-AB nosocomial infection was high during this outbreak, and was associated with prolonged hospitalization and increased risk of death. High patient severity scores, prior MR-AB colonization, invasive procedures and repeated skin grafts were associated with an increased risk of nosocomial infection., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To assess prognostic factors of recurrence of phyllodes tumors (PT) of the breast., Methods: We performed a retrospective, multicentric cohort study, including all patients who underwent breast surgery for grade 1 (benign), 2 (borderline) or 3 (malignant) PT between 2000 and 2016 in five tertiary University hospitals, diagnosed according to World Health Organisation classification., Results: 230 patients were included: 144 (63%), 60 (26%) and 26 (11%) with grade 1, 2 and 3 PT, respectively. Recurrence occurred in 10 (7%), 7 (12%) and 5 (19%) patients with grade 1, 2 and 3 PT, respectively. In univariate analysis, moderate to severe nuclear stromal pleomorphism (HR 8.00 [95% CI: 1.65-38.73], p < 0.009) was correlated with recurrence in all groups including grade 1 (HR 14.3 [95% CI: 1.29-160], p = 0.031). In multivariate analysis, surgical margin >5 mm, (HR 0.20 [95% CI: 0.06-0.63], p = 0.013) were significantly correlated with less recurrence in all PT grades. For grade 1 PT, there was also significantly less recurrence with surgical margin >5 mm, (HR 0.09 [95% CI: 0.01-0.85], p = 0.047) in multivariate analysis., Conclusion: The surgical margin should be at least 5 mm whatever the grade of PT. Moderate to severe nuclear stromal pleomorphism identified a subgroup of grade 1 PT with a higher rate of recurrence. This suggests that the WHO classification could be revised with the introduction of nuclear stromal pleomorphism to tailor PT management., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Recent population-based study of elderly-onset Crohn's disease patients reported age-related differences in disease phenotype and outcome., Aims: The aim was to assess the impact of age at diagnosis on natural history of elderly-onset ulcerative colitis patients with emphasis on disease presentation, phenotype and treatment., Methods: Elderly-onset patients with ulcerative colitis (≥60 years at diagnosis) registered in a French population-based Registry EPIMAD (1988-2006) were included. Demographic and clinical data at diagnosis and at maximal follow-up were collected using predefined questionnaire., Results: Four-hundred and sixty-five elderly-onset ulcerative colitis patients were included (median follow-up 6.2 years); 276 (59%) were <70 and 189 (41%) ≥70 years at diagnosis. Patients aged <70 years presented with more rectal bleeding (86% vs. 79%, p = .06) and abdominal pain (44% vs. 34%, p = .04) while those ≥70 years had higher rate of left-sided colitis (62% vs. 49%; p = .02). Cumulative exposure to 5-ASA, corticosteroids and immunosuppressants was similar between the groups as well as surgery rate. However, patients <70 years were significantly more steroid-resistant than older individuals (12% vs. 3%, p < .05) while no significant difference in steroid-dependency was observed., Conclusion: Patients with elderly-onset ulcerative colitis differed in presentation, disease phenotype and response to medication with respect to age at diagnosis., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Fibrinogen and its functional aspects have been linked to cardiovascular disease. There is vast discrepancy between the heritability of fibrinogen concentrations observed in twin studies and the heritability uncovered by genome wide association studies. We postulate that some of the missing heritability might be explained by the pleiotropic and polygenic co-regulation of fibrinogen through multiple targeted genes, apart from the fibrinogen genes themselves. To this end we investigated single nucleotide polymorphisms (SNPs) in genes coding for phenotypes associated with total and γ' fibrinogen concentrations and clot properties. Their individual and accumulative associations with the fibrinogen variables were explored together with possible co-regulatory processes as a result of the gain and loss of transcription factor binding sites (TFBS). Seventy-eight SNPs spanning the APOB, APOE, CBS, CRP, F13A1, FGA, FGB, FGG, LDL-R, MTHFR, MTR, PCSK-9 and SERPINE-1 genes were included in the final analysis. A novel PCSK-9 SNP (rs369066144) was identified in this population, which associated significantly (p=0.04) with clot lysis time (CLT). Apart from SNPs in the fibrinogen (FGA, FGB and FGG) and FXIII (F13A1) genes, the fibrinogen phenotypes were also associated with SNPs in genes playing a role in lipid homeostasis (LDL-R, PCSK-9) together with CBS and CRP polymorphisms (particularly, CRP-rs3093068). The genetic risk scores, presenting accumulative genetic risk, were significantly associated (p≤0.007) with total and γ' fibrinogen concentrations, lag time, slope and CLT, highlighting the importance of a polygenetic approach in determining complex phenotypes. SNPs significantly associated with the fibrinogen phenotypes, resulted in a total of 75 TFBS changes, of which 35 resulted in a loss and 40 in a gain of TFBS. In terms of co-regulation, V$IRF4.02, V$E2FF and V$HIFF were of particular importance. The investigation into TFBS provided valuable insight as to how sequence divergences in seemingly unrelated genes can result in transcriptional co-regulation of the fibrinogen phenotypes. The observed associations between the identified SNPs and the fibrinogen phenotypes therefore do not imply direct effects on cardiovascular disease outcomes, but may prove useful in explaining more of the genetic regulation of the investigated fibrinogen phenotypes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Organophosphorus nerve agents, like VX, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). AChE inhibited by VX can be reactivated using powerful nucleophilic molecules, most commonly oximes, which are one major component of the emergency treatment in case of nerve agent intoxication. We present here a comparative in vivo study on Swiss mice of four reactivators: HI-6, pralidoxime and two uncharged derivatives of 3-hydroxy-2-pyridinaldoxime that should more easily cross the blood-brain barrier and display a significant central nervous system activity. The reactivability kinetic profile of the oximes is established following intraperitoneal injection in healthy mice, using an original and fast enzymatic method based on the reactivation potential of oxime-containing plasma samples. HI-6 displays the highest reactivation potential whatever the conditions, followed by pralidoxime and the two non quaternary reactivators at the dose of 50 mg/kg bw. But these three last reactivators display equivalent reactivation potential at the same dose of 100 μmol/kg bw. Maximal reactivation potential closely correlates to surviving test results of VX intoxicated mice., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Cancer may be a complication of inflammatory bowel disease (IBD) or its treatments. In older Crohn's disease and ulcerative colitis patients, the risk of malignancy is of particular concern. IBD diagnosis at an advanced age is associated with earlier development of colitis-associated colorectal cancer. Thiopurine use in older IBD patients is tied to an increased risk of non-Hodgkin's lymphoma, nonmelanoma skin cancer, and urinary tract cancers. Additionally, older age is accompanied by multimorbidity, an increased risk of malnutrition, and decreased life expectancy, factors that complicate the management of cancer in the elderly. The optimal approach to the increased risk of malignancy in older age IBD is appropriate cancer screening and medical treatment. This may include age-specific colorectal cancer screening and limiting UV radiation exposure. With a growing number of older IBD patients, further studies are necessary to delineate the risk of cancer in this population., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval [CI] 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to "not reached"). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692)., (© 2016 by The American Society of Hematology.)

The propagation of stress waves in epoxy-glass particulate composites and graded materials was studied experimentally. Materials tested in this study consisted of an epoxy matrix with various concentrations of spherical glass particles having a mean diameter of 42μm. Plate impact experiments were performed using a gas gun. Embedded within the specimens were manganin stress gauges used to record propagating compressive longitudinal stress waves through the material. High strain rate experiments using a Split Hopkinson Pressure Bar (SHPB) apparatus were also performed to evaluate the dynamic strength of the specimens, while quasi-static compression tests were undertaken to characterize their quasi-static behavior. Ultrasonic wave speed measurements were carried-out in order to obtain additional material properties and characterize the gradation in functionally graded materials (FGM). It was found that low volume fractions of particles are detrimental to the performance of the material under impact loading, while concentrations in the range of about 30 to 45% by volume exhibit characteristics of higher degrees of scattering. This suggests that materials in this latter range would be more effective in the thwarting of destructive shock waves than the homogeneous matrix material. Impact testing of FGM specimens suggests that impact loading on the stiff (high volume fraction) face results in much higher levels of scattering. Therefore, such materials would be effective for use in light weight armor or as shielding materials due to their effective attenuation of mechanical impulses., (Copyright © 2015 Elsevier B.V. All rights reserved.)

d-glucose end-capped polylactide ruthenium cyclopentadienyl complex (RuPMC) was newly synthesized by a straightforward method. RuPMC was tested against human MCF7 and MDAMB231 breast and A2780 ovarian adenocarcinoma revealing IC50 values in the micromolar range. A pH dependent hydrolysis is advanced by preliminary UV-visible spectroscopy. Cellular distribution studies showed that RuPMC is predominantly found in the nucleus and in the membrane. Data suggest potential application of RuPMC as a new drug delivery system for Ru(II)Cp compounds., (© 2013.)

Background: The role of small bowel capsule endoscopy in the management of established Crohn's disease is uncertain., Methods: A retrospective study of small bowel capsule endoscopy tests performed in a referral centre from 2008 to 2011; 77 tests were performed in patients with known Crohn's disease. Six patients were excluded due to capsule test retention. Patients were classified into 4 indication groups: unexplained anaemia (G1, n = 6); discrepancy between clinical symptoms and morphology (G2, n = 25), full assessment of Crohn's disease location (G3, n = 37) and evaluation of mucosal healing (G4, n = 3)., Results: Twenty-seven (38%) patients had no lesions, 32 (45%) moderate and 12 (17%) severe lesions. Endoscopic lesions were found in 4/6 (67%) G1 patients, 11/25 (44%) G2 and 28/37 (76%) G3 (p < 0.03). Three months after endoscopy was performed, 38/71 patients experienced a change in their treatment that was significantly associated with the severity of endoscopic lesions and with test indications; in 60%, 20% and 58% of patients from G1, G2 and G3, respectively (p < 0.01)., Conclusion: Small bowel capsule endoscopy resulted in management changes in the majority of patients with established Crohn's disease., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Most data regarding the natural history of inflammatory bowel diseases and their therapeutic management are from tertiary referral-centres. However, the patients followed in these centres represent a selected sample and extrapolation of these data to the general population is disputable. The EPIMAD Registry covers a large area of Northern France with almost 6 million inhabitants representing 9.3% of the entire French population. From 1988 to 2008, 18,170 incident patients were recorded in the registry including 8071 incident Crohn's disease, 5113 incident ulcerative colitis and 591 unclassified inflammatory bowel disease cases. The aim of this study was to review some of the most recent information obtained from this large population-based registry since its launch in 1988., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The concept of comprehensive gerontological assessment is a foundation of modern geriatrics. Our focus was to try to clarify the underlying concepts, assess the level of evidence and clarify the issues still under debate. The concept implies the definition of an interdisciplinary process for a multidimensional assessment in order to produce a coordinated plan. The central notion is that the systematization of this multidimensionality and interdisciplinarity needs the establishment of dedicated process (meeting tools, clinical information system, etc.). Following dimensions should be covered: health, social, economic, environmental and psychological. Any assessment process that could lead to forgetting one of its dimensions cannot be viewed as a comprehensive gerontological assessment. The level of evidence is higher in hospital acute inpatient unit but it is still low in all other areas of health care but the scattered data in the literature argues for qualitative benefits (improved quality of care or quality of life). The questions that remain are numerous including the choice of strategy for initial evaluation (maximum versus minimum; from the outset by many professionals versus graduated based on the minimum initial evaluation), the choice of tool, the optimal location, the required intensity of monitoring and the ideal target population., (Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Cancer stem cells are a subject of increasing interest in oncology. In particular, several data suggest that cancer stem cells are involved in the mechanisms of tumor radioresistance, and may explain the therapeutic failures after radiotherapy. Because of its poor prognosis and high recurrence rate after irradiation, glioblastoma model is often studied in the search for new radiosensitizers. There are several preclinical data suggesting that cancer stem cells could be a potential therapeutic target for improving the biological effectiveness of radiation therapy. Through the example of glioblastoma, we review the main signaling pathways involved in the mechanisms of radiation resistance of cancer stem cells and for which pharmacological targeting could potentially enhance tumor radiosensitivity.

Background: Streptococcus pneumoniae is a major cause of pneumonia and meningitis. Several genetic polymorphisms have been described to explain differences in susceptibility and severity of encapsulated pathogen-related diseases. Among them, a functional FCGR2A polymorphism leading to amino acid change of histidine (H) to arginine (R) at position 131 appears to be a major candidate in adult invasive pneumococcal diseases (IPDs). However, previous reports need confirmation in a large, well-defined population., Methods: This prospective genetic association study was carried out in a 24-bed medical ICU of a tertiary teaching hospital over 7 years. DNA from all white patients with IPD (pneumonia or meningitis) was genotyped for the FcγRIIa-R/H131 polymorphism., Results: A total of 243 patients with IPD were enrolled; 202 (82%) had pneumonia, and 55 (22%) had meningitis. Mean age was 61 years, and mean Simplified Acute Physiology Score II was 50.4. One-half of the patients had bacteremia, and 84% of the cohort received mechanical ventilation. The hospital mortality rate was 31%. In the IPD group, the distribution of the FcγRIIa-R/H131 genotypes (H/H, 25%; H/R, 53%; R/R, 22%) was comparable with that in the white control group. Comparison of the FcγRIIa-R/R131 and the FcγRIIa-R/H131 + FcγRIIa-H/H131 groups did not demonstrate any difference for age, Simplified Acute Physiology Score II, origin of sepsis, and other comorbid conditions. However, the variant FcγRIIa-R/R131 genotype was independently associated with decreased hospital mortality (OR, 0.251; 95% CI, 0.098-0.645; P = .004)., Conclusions: In a well-defined population of patients with IPD, the frequency of the variant FcγRIIa-R131 does not differ from that of other critically ill patients. However, the FcγRIIa-R/R131 genotype was independently associated with increased survival, regardless of site of infection.

Background: Our objective was to assess the global cost of the sentinel lymph node detection [axillary sentinel lymph node detection (ASLND)] compared with standard axillary lymphadenectomy [axillary lymph node dissection (ALND)] for early breast cancer patients., Patients and Methods: We conducted a prospective, multi-institutional, observational, cost comparative analysis. Cost calculations were realized with the micro-costing method from the diagnosis until 1 month after the last surgery., Results: Eight hundred and thirty nine patients were included in the ASLND group and 146 in the ALND group. The cost generated for a patient with an ASLND, with one preoperative scintigraphy, a combined method for sentinel node detection, an intraoperative pathological analysis without lymphadenectomy, was lower than the cost generated for a patient with lymphadenectomy [€ 2947 (σ = 580) versus € 3331 (σ = 902); P = 0.0001]., Conclusion: ASLND, involving expensive techniques, was finally less expensive than ALND. The length of hospital stay was the cost driver of these procedures. The current observational study points the heterogeneous practices for this validated and largely diffused technique. Several technical choices have an impact on the cost of ASLND, as intraoperative analysis allowing to reduce rehospitalization rate for secondary lymphadenectomy or preoperative scintigraphy, suggesting possible savings on hospital resources.

Aim: Clostridium difficile is the most common agent of postantibiotic and nosocomial bacterial diarrhoea. Since the emergence of the highly virulent and epidemic strain NAP1/027 in Europe, it appears necessary to isolate C. difficile strains to realize an epidemiologic follow-up by molecular typing. The aim of this work was to compare three selective culture conditions for the isolation of C. difficile., Methods: One hundred and thirty stools collected from patients hospitalized at Jean Verdier were swabbed on the commercial medium CLO (BioMérieux) and on a medium prepared at the laboratory (CCTa: Columbia, cefoxitine 8 mg/l, cycloserine 250 mg/l, horse blood 5 %, sodium taurocholate 0.1 %) with and without preliminary alcoholic shock (EtOH). C. difficile was isolated from 38 stools and colonies were counted on each medium., Results: The fluorescence intensity of C. difficile colonies is comparable on CLO and CCTa-EtOH media, however their aspect is more characteristic on CLO. This medium appears very selective contrary to the CCTa medium on which an associated flora obstructs the fluorescence reading and requires a new isolation of the suspect strains. On average 30 times more colonies of C. difficile are counted on CCTa+/-EtOH than on CLO, suggesting the presence of great proportions of spores in the stools., Conclusions: The medium CLO is successful for the isolation of C. difficile despite of its selectivity. Nevertheless, it appears interesting to associate a medium enhancing spore germination as the CCTa medium inoculated after alcoholic shock to increase the sensitivity of detection while being freed from conservation and transport conditions., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)

Introduction: Current unusual environmental sources of lead exposure mainly include traditional medicines, either ayurvedic remedies or others, traditional cosmetics (kohl, surma), and the use of traditional earthenware, for storage or cooking., Case Reports: We report two cases of lead poisoning in adults initially identified by paroxysmal abdominal pain or anemia. In both cases, the environmental investigation evidenced one main source of lead exposure, namely a lead-glazed earthenware jug in which a drink was stored, "kefir" in the first case, and "kombucha" tea in the second one., Conclusion: It is recommended to search for lead intoxication in patients with unexplained anemia. Environmental sources of lead can be multiple. Their relative importance has to be ranked during the environmental investigation and among these, lead-glazed earthenware must be considered as a source of high lead exposure when drinks are stored inside and thus can soak.

Caribbean and Filipino immigrant families in Canada have much in common: the women have often immigrated as domestic workers, first-generation children may be separated from their parents for long periods, and they must deal with negative stereotypes of their ethnic group. This transcultural study looks at the associations between family relations and adolescents' perceptions of both their own group and the host society, and analyzes how these affect their mental health. The results suggest that family cohesion plays a key role in shaping adolescents' perceptions of racism in the host country and in promoting a positive appraisal of their own community, thus highlighting the need for a systemic understanding of family and intergroup relations.

Cathodic protection by sacrificial zinc anodes is often applied to prevent immerged metallic structures from corrosion. But this technique induces the zinc anodes dissolution, which can induce marine sediments and seawater contamination. A large scale experiment, in natural seawater, was conducted during 12 months, in order to evaluate the potential environmental impact of this continuous zinc dissolution, and of some necessary cleaning operations of the anodes surfaces. The heavy metal (Cr, Cu, Pb and Zn) concentration in water and sediment samples was monitored. A sequential extraction procedure was applied on sediment samples to differentiate the zinc mobile fractions from the residual one. A significant increase of zinc concentration was observed in water as well as in the surface sediments under the specific operating conditions. Sediments then become a secondary pollution source, as the sorbed labile zinc can be remobilized to seawater.

The eukaryotic translation initiation factor eIF4E is elevated in 30% of malignancies including M4/M5 subtypes of acute myeloid leukemia (AML). The oncogenic potential of eIF4E arises from its ability to bind the 7-methyl guanosine (m(7)G) cap on mRNAs, thereby selectively enhancing eIF4E-dependent nuclear mRNA export and translation. We tested the clinical efficacy of targeting eIF4E in M4/M5 AML patients with a physical mimic of the m(7)G cap, ribavirin. Among 11 evaluable patients there were 1 complete remission (CR), 2 partial remissions (PRs), 2 blast responses (BRs), 4 stable diseases (SDs), and 2 progressive diseases (PDs). Ribavirin-induced relocalization of nuclear eIF4E to the cytoplasm and reduction of eIF4E levels were associated with clinical response. Lack of response or relapse coincided with continued or renewed nuclear localization of eIF4E. This first clinical study to target eIF4E in human malignancy demonstrates clinical activity and associated molecular responses in leukemic blasts. This trial is registered at ClinicalTrials.gov (NCT00559091).

Background: Ascorbic acid is a widely used and controversial alternative cancer treatment. In millimolar concentrations, it is selectively cytotoxic to many cancer cell lines and has in vivo anticancer activity when administered alone or together with other agents. We carried out a dose-finding phase I and pharmacokinetic study of i.v. ascorbic acid in patients with advanced malignancies., Patients and Methods: Patients with advanced cancer or hematologic malignancy were assigned to sequential cohorts infused with 0.4, 0.6, 0.9 and 1.5 g ascorbic acid/kg body weight three times weekly., Results: Adverse events and toxicity were minimal at all dose levels. No patient had an objective anticancer response., Conclusions: High-dose i.v. ascorbic acid was well tolerated but failed to demonstrate anticancer activity when administered to patients with previously treated advanced malignancies. The promise of this approach may lie in combination with cytotoxic or other redox-active molecules.

MGCD0103 is an isotype-selective inhibitor of histone deacetylases (HDACs) targeted to isoforms 1, 2, 3, and 11. In a phase 1 study in patients with leukemia or myelodysplastic syndromes (MDS), MGCD0103 was administered orally 3 times weekly without interruption. Twenty-nine patients with a median age of 62 years (range, 32-84 years) were enrolled at planned dose levels (20, 40, and 80 mg/m(2)). The majority of patients (76%) had acute myelogenous leukemia (AML). In all, 24 (83%) of 29 patients had received 1 or more prior chemotherapies (range, 0-5), and 18 (62%) of 29 patients had abnormal cytogenetics. The maximum tolerated dose was determined to be 60 mg/m(2), with dose-limiting toxicities (DLTs) of fatigue, nausea, vomiting, and diarrhea observed at higher doses. Three patients achieved a complete bone marrow response (blasts