[Ophtalmological adverse events related to immune checkpoint inhibitors]. / Effets indésirables ophtalmologiques des inhibiteurs de points de contrôle immunitaire.

Immune checkpoint inhibitors are now an integral part of the anti-cancer therapeutic arsenal. They have revolutionized the prognosis of certain cancers at the cost of a specific spectrum of dysimmune side effects that can affect the ophthalmological sphere. Patient education associated with increased vigilance of health care providers will allow faster detection and therefore optimal care to limit morbidity, maintain the best possible visual acuity and above all to be able to continue therapy prolonging survival. In this article, we describe the main ocular side effects as well as an outline of their management.

Les inhibiteurs de point de contrôle immunitaire font désormais partie intégrante de l'arsenal thérapeutique anticancéreux. Ils ont révolutionné le pronostic de certains cancers au prix d'un spectre spécifique de manifestations indésirables d'ordre dysimmunitaires pouvant, notamment, affecter la sphère ophtalmologique. L'éducation des patients, associée à une vigilance accrue de la part des soignants, permettra une détection plus rapide afin de limiter la morbidité, de maintenir la meilleure acuité visuelle possible et, surtout, de pouvoir continuer une thérapie prolongeant la survie. Dans cet article, nous décrivons les principaux effets secondaires oculaires ainsi que les grandes lignes de leur prise en charge.

[Association between exposure to persistent organic pollutants during pregnancy and thyroid function during childhood : a pilot longitudinal study and literature review]. / Associations entre exposition aux polluants organiques persistants durant la grossesse et fonction thyroïdienne durant la petite enfance : étude longitudinale pilote et revue de la littérature.

OBJECTIVE: Perfluoroalkyl substances (PFAS) are chemicals widely employed in the industry. Long term consequences of the newborns' contamination by PFAS on thyroid function are of concern. The aim of this study is to assess the potential associations between PFAS contamination measured at birth and thyroid function assessed few months later. PFAS levels were previously determined in cord blood from a cohort of newborns recruited in Liege. METHOD: Parents of the children belonging to the first and the fifth quintiles of exposure to PFAS were contacted in order to measure the thyroid stimulating hormone (TSH) levels in their child few months after birth. Twenty-eight children participated in the study. Moreover, we performed a literature review about associations between pre- or perinatal exposure to persistent organic pollutants and thyroid function during early childhood. RESULT: No significant difference was highlighted between both groups of contamination (Mann-Whitney, p-value = 0.91). Literature review highlighted the critical need of new longitudinal data about this problematic. CONCLUSION: Our results suggest that the PFAS levels at birth are not associated with TSH levels later in life. Large scale studies are required to confirm our results.

Objectif : Notre but est d'étudier les associations potentielles entre contamination par les composés perfluorés (PFC) mesurée à la naissance et fonction thyroïdienne évaluée quelques mois plus tard. Les niveaux de PFC ont été déterminés précédemment dans le sang de cordon de nouveau-nés recrutés à Liège. Méthode : Les parents des enfants appartenant au premier et cinquième quintiles d'exposition aux PFC ont été contactés pour mesurer les niveaux de thyréostimuline (TSH) chez leurs enfants quelques mois après la naissance. Vingt-huit enfants ont été recrutés. De plus, nous avons réalisé une revue de littérature concernant les associations entre exposition pré- ou périnatale aux polluants organiques persistants (POP) et fonction thyroïdienne pendant la petite enfance. Résultat : Aucune différence significative n'a été mise en évidence entre les deux groupes de contamination (Mann-Whitney, p = 0,91). Selon, la revue de la littérature, il est indispensable de disposer de nouvelles données longitudinales relatives à la relation entre contamination par les POP et fonction thyroïdienne. Conclusion : Nos résultats suggèrent que les concentrations de PFC à la naissance ne sont pas associées aux niveaux de TSH au cours de la vie. Des études basées sur de plus grandes cohortes sont requises pour confirmer nos résultats.

[Ten years ahead in infectious diseases : AIDS/ HIV towards stopping transmission]. / Dix ans d'avancées en infectiologie : SIDA/HIV, vers l'arrêt de la transmission.

In order to end the AIDS pandemic, new infections must be avoided. This prevention can be divided into four axes depending on the risk of exposure to the HIV virus. Over the past decade, new prevention strategies supported by various studies have emerged. These are effective when they are used in combination. Some are not without risk or even controversial according to some authors.

Afin d'endiguer l'épidémie du syndrome d'immunodéficience acquise (SIDA), il faut contrôler les nouvelles acquisitions. Cette prévention peut être divisée en quatre axes en fonction du risque d'exposition au virus d'immunodéficience humaine (VIH). Lors de la dernière décennie, de nouvelles stratégies de prévention, soutenues par diverse études, ont vu le jour. Celles-ci sont efficaces à condition d'être utilisées de façon combinée. Certaines ne sont pas dénuées de risque, voire controversées par certains auteurs.

[Therapeutic progress in the control of uncomplicated Plasmodium falciparum malaria]. / Les dérivés combinés de l'artémisinine : une avancée thérapeutique dans le contrôle du paludisme non compliqué à Plasmodium falciparum.

Malaria is a worldwide public health problem. In Europe, data show an increasing trend of imported cases in the last ten years. Following an alarming observation reporting resistance to anti-malarial drugs, new effective treatments have been developed in early 21st century. These are artemisinin and its derivatives. Artemisinin-based combination therapies (ACT) are now recommended by the World Health Organisation (WHO) since 2006 as the first-line treatment for uncomplicated Plasmodium falciparum malaria. However, resistance phenomena to these new drugs have been described in South-East Asia since 2009. It is thus necessary to use them properly and to monitor their use to preserve their effectiveness in the future.

Le paludisme représente un problème majeur en termes de santé publique mondiale et l'on décèle une augmentation du nombre de cas d'importation en Europe au cours des dix dernières années. Suite au constat alarmant faisant état de phénomènes de résistance aux anciens anti-paludéens et grâce aux recherches activement menées, de nouveaux traitements extrêmement efficaces ont été développés au début du XXIème siècle. Il s'agit de l'artémisinine et de ses dérivés. L'Organisation Mondiale de la Santé (OMS) recommande depuis 2006 l'utilisation en première intention de dérivés semi-synthétiques combinés de l'artémisinine (ACT) dans le traitement des formes non sévères de paludisme à Plasmodium falciparum. Toutefois, des phénomènes de résistance partielle aux ACT sont décrits en Asie du sud-est depuis 2009. Il est donc nécessaire de les utiliser de manière judicieuse et de majorer la surveillance par le biais de programmes de monitoring standardisés afin de maintenir leur efficacité sur le long terme.

Long-term evolution and predictive factors of mild inflammatory bowel disease.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are potentially progressive diseases. Few data are available on the prevalence and the factors associated with mild inflammatory bowel diseases (IBD). AIM: Our aim was to assess the natural history of mild CD and mild UC and to identify predictive factors of mild evolution over the long term. METHODS: Retrospective study of IBD patients registered in the database of the university hospital CHU of Liège, Belgium. Mild CD was defined as an inflammatory luminal disease (no stricture, abdominal or perianal fistulae) requiring no immunomodulator (IM), anti-TNF and no surgery. Mild UC was defined as no requirement for IM, anti-TNF and no colectomy. RESULTS: Four hundred and seventy-three CD and 189 UC were included (median follow-up: 13 and 11 years respectively). At 1 year, 147 patients had mild CD. At 5 years and the maximum follow-up, 56% and 13% patients still had mild CD, respectively. At 1 year, 142 patients had mild UC. At 5 years and the maximum follow-up, 72% and 44% still had a mild UC, respectively. Factors associated with long-term mild CD and UC were older age at diagnosis and absence of corticosteroids in the first year. In UC proctitis location was associated with mild UC. CONCLUSIONS: In this cohort, 90% of CD patients and 3/4 of UC with mild disease at 1 year lost their mild disease status over time. An old age at diagnosis was predictive of the persistence of a mild CD and UC.

Utilization rates and results of long-term embryo cryopreservation before gonadotoxic treatment.

PURPOSE: The aim of this study was to evaluate long-term embryo cryopreservation, utilization, and success rate in patients subjected to gonadotoxic treatments in the context of cancer. METHODS: This is a retrospective study on patients (n = 54) undergoing ovarian stimulation and IVF for fertility preservation between January 1997 and June 2014. Embryos were slow-frozen and stored until the women were cured and able to undergo embryo transfer. RESULTS: Fifty-four women underwent 66 oocyte pick-up procedures in total, and embryos were obtained from 52 of the 54 patients. Four patients died before their frozen embryos could be thawed. Of the remaining 48, 9 women returned to use their embryos, resulting in 6 pregnancies (66% cumulative pregnancy rate), two of which ended in miscarriage. The live birth rate per patient was thus 44% (4/9). The true come-back rate, calculated after applicable exclusions, was found to be 23%. CONCLUSION: IVF followed by embryo freezing is a widely established technique for fertility preservation, but little has been published on the outcomes in cancer patients. While we found the number of good-quality embryos to be lower than in a normal population, the cumulative live birth rate was similar to that achieved with fresh embryos in non-cancer patients. The utilization rate of this fertility preservation method can be considered high.

Cross-border reproductive care in Belgium.

BACKGROUND: Cross-border reproductive care indicates the cross-border movements made by patients to obtain infertility treatment they cannot obtain at home. The problem at present is that empirical data on the extent of the phenomenon are lacking. This article presents the data on infertility patients going to Belgium for treatment. METHODS: A survey was conducted among the centres for reproductive medicine that are allowed to handle oocytes and create embryos (B-centres). Data were collected on the nationality of patients and the type of treatment for which they attended during the period 2000-2007. RESULTS: Sixteen of 18 centres responded to the questionnaire. The flow of foreign patients has stabilized since 2006 at approximately 2100 patients per year. The majority of foreign nationals seeking treatment in Belgium were French women for sperm donation. The next highest group was patients entering the country to obtain ICSI with ejaculated sperm. CONCLUSIONS: There are clear indications that numerous movements are motivated by the wish to evade legal restrictions in one's home country, either because the technology is prohibited or because the patients have characteristics, which exclude them from treatment in their own countries.

Does imidacloprid seed-treated maize have an impact on honey bee mortality?

Beekeepers suspected maize, Zea mays L., treated with imidacloprid to result in substantial loss of honey bee (Hymenoptera: Apidae) colonies in Belgium. The objective of this study was to investigate the potential impact of maize grown from imidacloprid-treated seeds on honey bee mortality. A survey of 16 apiaries was carried out, and all maize fields treated or not with imidacloprid were located within a radius of 3,000 m around the observed apiaries. Samples of honey, beeswax, and bees were collected in three colonies per apiary and analyzed for pesticide contain by liquid chromatography-tandem mass spectrometry and gas chromatography-tandem mass spectrometry. We first found a significant correlation between the number of colonies per apiary and the mortality rates in an apiary. In addition, this mortality rate was inversely correlated with the surface of maize fields treated and not with imidacloprid, suggesting that this pesticide do not interact with bees' fitness. Moreover, a very large number of our samples contained acaricides either prohibited or ineffective against Varroa destructor (Anderson & Trueman) (Acari: Varroidae), suggesting that the treatment methods used by the beekeepers to be inadequate for mite control. Our results support the hypothesis that imidacloprid seed-treated maize has no negative impact on honey bees.

Development and validation of a multi-residue method for pesticide determination in honey using on-column liquid-liquid extraction and liquid chromatography-tandem mass spectrometry.

We report on the development and validation under ISO 17025 criteria of a multi-residue confirmatory method to identify and quantify 17 widely chemically different pesticides (insecticides: Carbofuran, Methiocarb, Pirimicarb, Dimethoate, Fipronil, Imidacloprid; herbicides: Amidosulfuron, Rimsulfuron, Atrazine, Simazine, Chloroturon, Linuron, Isoxaflutole, Metosulam; fungicides: Diethofencarb) and 2 metabolites (Methiocarb sulfoxide and 2-Hydroxytertbutylazine) in honey. This method is based on an on-column liquid-liquid extraction (OCLLE) using diatomaceous earth as inert solid support and liquid chromatography (LC) coupled to mass spectrometry (MS) operating in tandem mode (MS/MS). Method specificity is ensured by checking retention time and theoretical ratio between two transitions from a single precursor ion. Linearity is demonstrated all along the range of concentration that was investigated, from 0.1 to 20 ng g(-1) raw honey, with correlation coefficients ranging from 0.921 to 0.999, depending on chemicals. Recovery rates obtained on home-made quality control samples are between 71 and 90%, well above the range defined by the EC/657/2002 document, but in the range we had fixed to ensure proper quantification, as levels found in real samples could not be corrected for recovery rates. Reproducibility is found to be between 8 and 27%. Calculated CCalpha and CCbeta (0.0002-0.943 ng g(-1) for CCalpha, and 0.0002-1.232 ng g(-1) for CCbeta) show the good sensitivity attained by this multi-residue analytical method. The robustness of the method has been tested in analyzing more than 100 raw honey samples collected from different areas in Belgium, as well as some wax and bee samples, with a slightly adapted procedure.

Livebirth after orthotopic transplantation of cryopreserved ovarian tissue.

BACKGROUND: The lifesaving treatment endured by cancer patients leads, in many women, to early menopause and subsequent infertility. In clinical situations for which chemotherapy needs to be started, ovarian tissue cryopreservation looks to be a promising option to restore fertility. In 1997, biopsy samples of ovarian cortex were taken from a woman with stage IV Hodgkin's lymphoma and cryopreserved before chemotherapy was initiated. After her cancer treatment, the patient had premature ovarian failure. METHODS: In 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy. FINDINGS: 5 months after reimplantation, basal body temperature, menstrual cycles, vaginal ultrasonography, and hormone concentrations indicated recovery of regular ovulatory cycles. Laparoscopy at 5 months confirmed the ultrasonographic data and showed the presence of a follicle at the site of reimplantation, clearly situated outside the ovaries, both of which appeared atrophic. From 5 to 9 months, the patient had menstrual bleeding and development of a follicle or corpus luteum with every cycle. 11 months after reimplantation, human chorionic gonadotrophin concentrations and vaginal echography confirmed a viable intrauterine pregnancy, which has resulted in a livebirth. INTERPRETATION: We have described a livebirth after orthotopic autotransplantation of cryopreserved ovarian tissue. Our findings suggest that cryopreservation of ovarian tissue should be offered to all young women diagnosed with cancer.

Fast clean-up for polychlorinated dibenzo-p-dioxins, dibenzofurans and coplanar polychlorinated biphenyls analysis of high-fat-content biological samples.

A fast clean-up procedure for the low level analysis of polychlorinated dibenzo-p-dioxins. polychlorinated dibenzofurans and coplanar polychlorinated biphenyls in highly fatty biological matrices using high capacity disposable multi-layer silica columns is presented. Results were compared with gel permeation chromatography for removal of lipids. Analytical criteria such as recovery rates, repeatability, reproducibility and robustness are evaluated through a broad range of biological matrices and reference materials analysis. The final proposed procedure for the complete analysis, including pressurized liquid extraction, Power-Prep system clean-up and GC-high-resolution MS analysis requires only 48 h, and allows the simultaneous preparation of up to 10 samples.

Levels of PCDDs, PCDFs and PCBs in Belgian and international fast food samples.

Congener-specific analyses of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) were performed on twenty-eight non-pooled fast food samples collected in Belgium, Switzerland, Czech Republic, United States of America and Australia. PCDD/F and PCB concentrations for the four investigated types of meals were very low. PCDD/F values ranged from non-detected to 1.40 pg WHO-TEQ/g fat and from 0.79 to 2.08 pg WHO-TEQ/g fat for lower and upper bound, respectively. Major contributors to the PCDD/F TEQ were 1,2,3,4,7,8-HxCDD, 1,2,3,6,7,8-HxCDD, 2,3,7,8-TCDF and 2,3,4,7,8-PeCDF. The relative contribution of PCBs to the total TEQ was 68%. For adults, an average estimated intake was 6.7 pg WHO-TEQ/kg bw/month, including consumption of all types of analyzed meals, representing 9.5% of the PTMI. For child, a value of 14.5 pg WHO-TEQ/kg bw/month was obtained, representing 20.6% of the PTMI.

Survey of commercial pasteurised cows' milk in Wallonia (Belgium) for the occurrence of polychlorinated dibenzo-p-dioxins, dibenzofurans and coplanar polychlorinated biphenyls.

Congener-specific analyses of 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs) and 4 non-ortho (coplanar) polychlorinated biphenyls (cPCBs) were performed on 35 samples of commercial long-life pasteurised cows' milk issued from eight different brands available in Walloon supermarkets (Belgium). The observed congener profile was characteristic of milk samples issued from industrialised countries with good inter and intra-brand reproducibility's. The PCDDs to PCDFs ratio was equal to 1.8 in concentration. The toxic equivalent (TEQ based on WHO-TEF) value for PCDD/Fs in all analysed milks was 1.09+/-0.30 pg TEQ/g fat (range 0.86-1.59), which is below the recommended EU non-commercialisation threshold value of 3 pg TEQ PCDD/Fs/g of milk fat. The mean TEQ value including cPCBs was 2.23+/-0.55 pg TEQ/g fat. These PCBs actually contributed for 49+/-8.6% of the total TEQ. Among PCDD/Fs and cPCBs, tetrachloro dibenzo-p-dioxin (TCDD), pentachloro dibenzo-p-dioxin (PeCDD), pentachloro dibenzofurans (PeCDFs) and 3,3',4,4',5-pentachloro biphenyl (PCB-126) were the most important contributors to the TEQ. Estimated daily intake (EDI) due to consumption of such milks was 0.34 pg TEQ/kg of body weight/day for PCDD/Fs and 0.69 pg TEQ/kg of body weight/day when cPCBs were included.

Levels and profiles of PCDDs, PCDFs and cPCBs in Belgian breast milk. Estimation of infant intake.

Congener-specific analyses of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho (coplanar) polychlorinated biphenyls (cPCBs) were performed on 20 non-pooled breast milk samples collected in or close to an industrial area of Wallonia (Belgium). PCDD/F concentrations ranged between 16.0 and 52.1 pg TEQ/g fat, with a mean value of 29.4 pg TEQ/g fat. If coplanar PCBs (77, 126, 169) are included in TEQ calculations, levels ranged between 22.2 and 100.2 pg TEQ/g fat, with a mean value of 40.8 pg TEQ/g fat. It appears that 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 2,3,4,7,8-PeCDF and PCB-126 account for more than 90% of the TEQ. Estimated PCDD/F dietary intake is 76 pg TEQ/kg body weight (bw)/day. This value is almost 20 times higher than the World Health Organization tolerable daily intake. A value of 103 pg TEQ/kg bw/day represents the intake of PCDDs, PCDFs and cPCBs (no mono-ortho PCBs included).

Levels and congener distributions of PCDDs, PCDFs and non-ortho PCBs in Belgian foodstuffs--assessment of dietary intake.

Congener-specific analyses of 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs) and 4 non-ortho (coplanar) polychlorinated biphenyls (cPCBs) were performed on 197 foodstuffs samples of animal origin from Belgium during years 2000 and 2001. All investigated matrices (except horse) present background levels lower than the Belgian non-commercialization value of 5 pg TEQ/g fat. Pork was the meat containing the lowest concentration of both PCDD/Fs and cPCBs. The mean background concentration of 2,3,7,8-TCDD toxicity equivalent in milk was 1.1 pg/g of fat, with a congener distribution typical of non-contaminated milk. The relative contribution of 2,3,7,8-TCDD, 2,3,7,8-TCDF, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF to the PCDD/Fs TEQ was 85+/-7.9% for all investigated matrices. The cPCBs contribution to the total TEQ was 47+/-19.0% for products of terrestrial species and 69+/-20.0% for aquatic species. Once the contribution of cPCBs was added to the TEQ, few foodstuffs such as horse, sheep, beef, eggs and cheese presented levels above the future European guidelines that currently only include PCDD/Fs but will be re-evaluated later in order to include 'dioxin-like' PCBs. Based on levels measured in the samples, the estimation of the dietary intake was 65.3 pg WHO-TEQ/day for PCDD/Fs only (1.00 pg WHO-TEQ/kg bw/day, for a 65 kg person) and 132.9 pg WHO-TEQ/day if cPCBs were included (2.04 pg WHO-TEQ/kg bw/day, for a 65 kg person). Meat (mainly beef), dairy products, and fish each account for roughly one third of the intake.

[Longitudinal melanonychia and hydroxyurea]. / Mélanonyche en bandes longitudinales et hydroxyurée.

A patient with chronic myeloid leukaemia was treated with hydroxyurea and developed longitudinal melanonychia on 10 of 20 nails. Such intense lesions are extremely rare.

[Erythropoietic protoporphyria]. / Protoporphyrie érythropoïétique.

The investigation and follow-up of three cases of EPP led us to reevaluate the signs and symptoms of the disease, the usefulness of early skin biopsies and protoporphyrin and ferrochelatase determinations. A review of the literature brought forth the salient features of this inborn error of porphyrin metabolism and stressed the value of treatment with beta-carotene and canthaxantine but also the risk of the so-called "gold dust" retinopathy.