Non-invasive assessment of muscle compartment elasticity by pressure-related ultrasound in pediatric trauma: a prospective clinical study in 25 cases of forearm shaft fractures.

BACKGROUND: Soft-tissue swelling after limb fractures in pediatric patients is well known to be a risk factor for developing acute compartment syndrome (ACS). Clinical assessment alone is uncertain in specific cases. Recently, we proposed a non-invasive ultrasound-based method to objectify muscle compartment elasticity for monitoring. We hypothesize a strong correlation between the soft-tissue swelling after stabilization of upper limb fractures and the compartment elasticity objectified with a novel ultrasound-based approach in pediatric trauma. PATIENTS AND METHODS: In a prospective clinical study, children suffering forearm fractures but not developing an ACS were included. The muscle compartment elasticity of the m. flexor carpi ulnaris was assessed after surgical intervention by a non-invasive, ultrasound-based method resulting in a relative elasticity (RE in %) in both the control (healthy limb) and study group (fractured limb). Soft-tissue swelling was categorized in four different levels (0-3) and correlated with the resulting RE (%). RESULTS: The RE in the study group (15.67%, SD ± 3.06) showed a significantly decreased level (p < 0.001) compared with the control (22.77%, SD ± 5.4). The categorized grade of soft-tissue swelling resulted in a moderate correlation with the RE (rs = 0.474). CONCLUSIONS: The presented study appears to represent a novel approach to assess the posttraumatic pressure changes in a muscle compartment after fracture stabilization non-invasively. In this first clinical study in pediatric cases, our measurement method represents a low-cost, easy, and secure approach that has the potential to substitute invasive measurement of suspected ACS in muscle compartment conditions. Further investigations in lager cohorts are required to prove its daily clinical practicability and to confirm the expected reliability.

[How to explore... hyperandrogenism associated with insulin resistance ? An example based on the HAIR-AN syndrome.] / Comment j'explore une hyperandrogénie dans un contexte d'insulinorésistance. Un exemple basé sur le syndrome HAIR-AN.

HAIR-AN, a syndrome associating hyperandrogenism, insulin resistance and acanthosis nigricans, is currently considered as a severe form of polycystic ovary syndrome. The physiopathology of this syndrome relies on the insulin resistance which is the basis of a vicious circle : the resulting hyperinsulinism leads to an excessive production of androgens. The latter increases abdominal fat deposition which in turn worsens the insulin resistance. Hyperinsulinism is also responsible for the acanthosis nigricans by stimulating the IGF-1 receptors on keratinocytes and fibroblasts. Hyperandrogenism is clinically translated into hirsutism that can be severe. Frequently, menstrual irregularity and obesity are part of the syndrome. HAIR-AN syndrome begins soon after puberty and is currently under-diagnosed. Treatment relies on an improvement in insulin-resistance by a loss of body weight and the use of insulin sensitizers. Moreover, anti-androgenic drugs will help improving hirsutism. Although more invasive, bariatric surgery has shown a great efficacy in this syndrome : by permitting a substantial loss of weight, it often normalizes insulin-sensitivity, allowing for improvements in hyperandrogenism and acanthosis nigricans.

Considéré comme une forme sévère du syndrome des ovaires micropolykystiques, le syndrome de HAIR-AN associe une hyperandrogénie, une résistance à l'insuline et un acanthosis nigricans. La base physiopathologique du syndrome HAIR-AN est un cercle vicieux ayant pour point de départ la résistance à l'insuline : l'hyperinsulinisme qui en résulte entraîne une production excessive d'androgènes. Ces derniers, en aggravant le dépôt de graisse abdominale, majorent la résistance à l'insuline. Il s'agit donc d'un phénomène auto-entretenu. En stimulant le récepteur à l'IGF-1 des kératinocytes et des fibroblastes, l'hyperinsulinisme est également responsable de l'acanthosis nigricans. L'hyperandrogénie se traduit cliniquement par un hirsutisme pouvant être sévère. On notera fréquemment aussi une irrégularité menstruelle et une obésité. Le syndrome HAIR-AN débute tôt après la puberté et est actuellement sous-diagnostiqué. Le traitement est, avant tout, celui de la résistance à l'insuline et nécessite donc une perte de poids associée à l'utilisation de molécules insulino-sensibilisatrices. De plus, des traitements hormonaux anti-androgéniques aideront également à diminuer le hirsutisme. Plus invasive, la chirurgie bariatrique a cependant démontré une grande efficacité chez ces patientes : en permettant une perte de poids conséquente, elle normalise souvent la sensibilité à l'insuline, ce qui améliore significativement l'hyperandrogénie et l'acanthosis nigricans.

An Infundibular Unidentified Object (IUO): a new pituitary stalk marker?

PURPOSE: Measurement of the pituitary stalk (PS) diameter does not always solve the issue of minimal PS thickening. A previously undescribed image is found at the infundibular level on high resolution thin section T2W MRI in a large number of normal individuals. We speculate that this image-whose exact origin is still unknown-may serve as a marker of the normal infundibulum. METHODS: In the last 6 months, 350 consecutive adult patients suspected of sellar pathology or controlled after medical or surgical treatment prospectively underwent a pituitary MRI including a sagittal T2W high resolution sequence. One hundred twelwe patients presenting a pituitary mass with suprasellar extension or those whose PS was not entirely visible were excluded. RESULTS: A short focal annular T2 hypointense thickening of the wall of the infundibular recess of the third ventricle, more pronounced anteriorly was found in 151/238 patients. Additionally, a more or less tiny ventral extension was demonstrated on sagittal T2W sequence in 105/151 patients. These images were not identified on T1W or on T1W gadolinium enhanced sequences. The ring-like infundibular thickening and/or its ventral extension were not identified in 87/238 patients; in 43/87 of these patients the PS was found severely stretched mainly in case of primary or secondary empty sella. If patients with empty sella were excluded, our finding was observed in 194/238 cases, i.e. in 82%. CONCLUSIONS: A detailed appearance of the PS on T2W MRI is described for the first time. A previously unreported T2W hypointense annular focal image prolonged by a tiny spicular or nodular ventral bud is found at the lower part of the infundibulum in a majority of normal patients, but not if the PS is stretched such as in empty sella. This image has to be recognized as a normal anatomical landmark. The possible origin of this image is discussed but not totally elucidated. An ongoing research will demonstrate or not if this image may serve as a marker to improve the early diagnosis of PS lesions.

[Neuroendocrine neoplasms : a new era to the top of multidisciplinarity !] / Néoplasies neuroendocrines : une nouvelle ère a l'apogée de la multidisciplinarité !

Neuroendocrine neoplasms are histologically defined by a common neuroendocrine cellular phenotype. These are still considered as rare tumours even though their incidence is increasing. Heterogeneity is everywhere whether in the localization of the primitive cancer, the clinical presentation, the histological classification, the prognosis, as well as in therapeutic options, which clearly justifies specialized multidisciplinary care. Heterogeneity and scarcity explain the still fragmented nature of knowledge in this domain. Thanks to an increase in incidence, a desire for standardization of classification as well as the arrival of major therapeutic advances, such as vectorized internal radiotherapy, the future of neuroendocrine neoplasia seems more than promising and exciting. In our daily clinical practice at CHU Liège, we hope to bring our stone to the building by listing as many cases as possible in national and/or international databases, by centralizing therapeutic discussions within specific multidisciplinary concertations and by participating in multicenter study protocols.

Les néoplasies neuroendocrines sont définies histologiquement par un phénotype cellulaire neuroendocrine commun. Ces néoplasies sont toujours considérées comme des tumeurs rares, bien que leur incidence soit en constante augmentation. L'hétérogénéité est omniprésente, que ce soit dans la localisation du cancer primitif, la présentation clinique, la classification histologique, le pronostic ainsi que dans les diverses options thérapeutiques, justifiant impérativement une prise en charge pluridisciplinaire spécialisée. Cette hétérogénéité et cette rareté expliquent que les connaissances soient parcellaires. Grâce à une majoration d'incidence, une volonté d'uniformisation de classification ainsi que l'arrivée d'avancées thérapeutiques majeures, telles que la radiothérapie interne vectorisée, l'avenir des néoplasies neuroendocrines semble plus que prometteur et palpitant. En pratique clinique quotidienne au CHU de Liège, nous espérons apporter notre pierre à l'édifice en recensant un maximum de cas dans des bases de données nationales et/ou internationales, en centralisant les discussions thérapeutiques au sein de concertations multidisciplinaires dédiées et en participant à des protocoles d'études cliniques multicentriques.

[Polycystic ovary syndrome : the advantages of multidisciplinary management]. / Le syndrome des ovaires micropolykystiques : l'avantage d'une prise en charge multidisciplinaire.

The polycystic ovary syndrome is one of the most frequent endocrine disorders in women of reproductive age. The first signs and symptoms of the disease may be present as early as puberty. Diagnostic criteria include hyperandrogenism (clinical or biological), ovulatory dysfunction and polycystic ovarian morphology on ultrasound. The consequences of the syndrome are multiple. These consist of fertility issues and metabolic anomalies with increased cardiovascular risk, but also sleep disturbances, increased risk of endometrial hyperplasia and endometrial cancer and a potentially important psychological impact with decreased quality of life. The management of polycystic ovary syndrome is multidisciplinary and treatment is variable, depending on symptoms and the patient's desire for fertility. In all cases, measures aiming to improve the metabolic dysfunction are essential, going from adopting a healthy lifestyle to adequate therapy of each metabolic anomaly.

Le syndrome des ovaires micropolykystiques est une des endocrinopathies les plus fréquentes de la femme en âge de reproduction. Les premiers signes et symptômes peuvent se manifester dès la puberté. Les critères de diagnostic reposent sur une hyperandrogénie (clinique ou biologique), une anovulation chronique et un aspect d'ovaires micropolykystiques à l'échographie. Les conséquences du syndrome sont multiples, essentiellement concernant les troubles de la fertilité et les perturbations métaboliques avec un risque cardio-vasculaire augmenté, mais également des anomalies du sommeil, un risque augmenté d'hyperplasie endométriale et de cancer endométrial et un impact psychologique parfois important avec diminution de la qualité de vie. La prise en charge est multi-disciplinaire et le traitement variable, en fonction des symptômes et des souhaits de fertilité de la patiente. Dans tous les cas, une prise en charge métabolique, avec une hygiène de vie saine et des traitements visant les perturbations métaboliques individuelles, est essentielle.

[Clinical zoanthropy: a woman with the rare delusion of being an animal]. / Klinische zoantropie; een vrouw met de zeldzame waan een dier te zijn.

Clinical zoanthropy, or the conviction of having turned into an animal, is a rare delusion. There are different views about its pathogenesis. This delusion can occur with an underlying psychiatric disorder, but it can also be secondary to structural or functional disorders of the brain. Additional investigations with brain imaging and electroencephalogram are therefore advised. Treatment for the underlying disorder is recommended. In this case report we describe a 54-year-old woman who was briefly convinced she was a chicken, followed by a generalized seizure. We discuss the epidemiology, theories about pathogenesis and treatment advice for clinical zoanthropy. We also discuss the possible relevance of epilepsy to this matter. With this case report, we hope to contribute to documenting this rare, but possibly underreported phenomenon.

Discordant biological parameters of remission in acromegaly do not increase the risk of hypertension or diabetes: a study with the Liege Acromegaly Survey database.

PURPOSE: Acromegaly is a rare disease due to growth hormone (GH)-secreting pituitary adenoma. GH and IGF-1 levels are usually congruent, indicating either remission or active disease; however, a discrepancy between GH and IGF-1 may occur. We aimed to evaluate the outcome of diabetes mellitus (DM) and hypertension (HT) in acromegalic patients with congruent GH and/or IGF-1 levels vs. discordant biochemical parameters. METHODS: Retrospective analysis of the data of 3173 patients from the Liege Acromegaly Survey (LAS) allowed us to include 190 patients from 8 tertiary referral centers across Europe, treated by surgery, with available data concerning DM and HT both at diagnosis and at the last follow-up (LFU). We recorded the number of anti-HT and anti-DM drugs used at the first evaluation and at LFU for every patient. RESULTS: Ninety-nine patients belonged to the REM group (concordant parameters), 65 patients were considered as GHdis (high random GH/controlled IGF-1), and 26 patients were considered as IGF-1dis (high IGF-1/controlled random GH). At diagnosis, 72 patients (37.8%) had HT and 54 patients had DM (28.4%). There was no statistically significant difference in terms of the number of anti-HT and anti-DM drugs at diagnosis versus LFU (mean duration: 7.3 ± 4.5 years) between all three groups. CONCLUSION: The long-term outcome of DM and HT in acromegaly does not tend to be more severe in patients with biochemical discordance in comparison with patients considered as in remission on the basis of concordant biological parameters, suggesting that patients with biochemical discordance do not require a closer follow-up.

Neuroimaging of aggressive pituitary tumors.

Aggresssive pituitary tumors are defined as radiologically invasive, exhibiting a rapid growth and a poor response to the medical and surgical treatment options. The role of magnetic resonance imaging (MRI) is fundamental to assess tumor aggressiveness before surgical exploration. Distinction between cavernous sinus invasion and cavernous sinus compression is often challenging and cannot be solved always by using the Knosp criteria. Ideally, T2W images demonstrating the ruptured internal dural wall of cavernous sinus is the ultimate proof of cavernous sinus invasion. Subtle tumor volume increase in a short time can be shown when sequential MR images are rigorously replicable. A microcystic pattern observed on T2W images frequently reflects a potentially aggressive tumor as observed in silent corticotroph pituitary adenomas.

The role of AIP variants in pituitary adenomas and concomitant thyroid carcinomas in the Netherlands: a nationwide pathology registry (PALGA) study.

PURPOSE: Germline mutations in the aryl-hydrocarbon receptor interacting protein (AIP) have been identified often in the setting of familial isolated pituitary adenoma (FIPA). To date there is no strong evidence linking germline AIP mutations to other neoplasms apart from the pituitary. Our primary objective was to investigate the prevalence of AIP gene mutations and mutations in genes that have been associated with neuroendocrine tumors in series of tumors from patients presenting with both pituitary adenomas and differentiated thyroid carcinomas (DTCs). METHODS: Pathology samples were retrieved from all pituitary adenomas in patients with concomitant DTCs, including one with a known germline AIP variant. Subsequently, two additional patients with known germline AIP variants were included, of which one presented only with a follicular thyroid carcinoma (FTC). RESULTS: In total, 17 patients (14 DTCs and 15 pituitary adenomas) were investigated by targeted next generation sequencing (NGS). The pituitary tumor samples revealed no mutations, while among the thyroid tumor samples BRAF (6/14, 42.9%) was the most frequently mutated gene, followed by NRAS (3/11, 27.3%). In one AIP-mutated FIPA kindred, the AIP-variant c.853C>T; p.Q285* was confirmed in the FTC specimen, including evidence of loss of heterozygosity (LOH) at the AIP locus in the tumor DNA. CONCLUSION: Although most observed variants in pituitary adenomas and DTCs were similar to those of sporadic DTCs, we confirmed in one AIP mutation-positive case the AIP-variant and LOH at this locus in an FTC specimen, which raises the potential role of the AIP mutation as a rare initiating event.

Acromegaly in the setting of Tatton-Brown-Rahman Syndrome.

PURPOSE: Tatton-Brown-Rahman syndrome (TBRS) is a newly defined genetic entity characterized by overgrowth and intellectual disability, resulting from germline mutations in the gene encoding DNA methyltransferase 3 alpha (DNMT3A). Affected individuals with benign and malignant tumors have been reported; to our knowledge pituitary adenomas (and other tumors identified in our patient) have not yet been described in this syndrome. CASE: We report the case of a 34-year-old woman with TBRS who developed a GH-secreting pituitary macroadenoma and other benign tumors and cystic lesions involving diverse organ systems. Whole-exome sequencing revealed a heterozygous, likely pathogenic variant (c.700_709 del10, p. Gly234ArgfsX79) in exon7 of DNMT3A, and a heterozygous variant of uncertain significance (c.25 C>T, p.Arg9Trp) in exon 1 of the gene encoding aryl hydrocarbon receptor-interacting protein (AIP). The patient failed somatostatin analog treatment, and underwent surgery. The tumor retained AIP expression, and analysis of tumor DNA indicated the presence of both AIP alleles, consistent with no loss of heterozygosity. These findings suggest that the AIP variant was not the primary driver of pituitary adenoma development. CONCLUSION: Our case suggests that TBRS might be associated with pituitary adenoma and a broader spectrum of tumors than previously thought, making long-term follow up of these patients crucial to identify tumors early, and to elucidate the clinical spectrum of the disorder for optimization of management.

[Endocrine consequences of immune checkpoint inhibitors]. / Répercussions endocriniennes des immunothérapies.

Immune checkpoints inhibitors have fundamentally changed the management of oncologic patients. These treatments consist of monoclonal antibodies directed against CTLA-4 (cytotoxic T-lymphocyte antigen 4), PD-1 (programmed cell death protein-1) and PD-L1 (one of its ligands). By blocking these receptors or ligands, the antibodies reverse the immune tolerance induced by the cancerous cell on the T-lymphocyte and favour lymphocytic reactivation and anti-tumor activity. Immune tolerance to auto-antigens is maintained with the help of these checkpoints. Targeting them can lead to auto-immune side effects. These latter mostly impact the cutaneous and digestive system, but the endocrine glands are not spared. In this article, we provide monitoring and treatment algorithms for these endocrine immune side effects. An early diagnosis followed by the appropriate treatment would reduce their negative impact on the oncologic care.

Les inhibiteurs des checkpoints immunitaires ont considérablement changé la prise en charge des cancers. Ces thérapeutiques sont actuellement représentées par les anticorps monoclonaux anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4), anti-PD-1 (programmed cell death protein-1) et anti-PD-L1 (un de ses ligands). En bloquant ces récepteurs ou ligands, les anticorps contrecarrent le freinage immunitaire instauré par la cellule cancéreuse sur le lymphocyte T et favorisent, alors, la réactivation du lymphocyte et son activité anti-tumorale. Ces checkpoints sont essentiels dans le maintien de la tolérance immune aux auto-antigènes. En les ciblant, des effets secondaires de type auto-immun peuvent apparaître. S'ils privilégient principalement le système cutané et digestif, les glandes endocrines n'en sont néanmoins pas oubliées. Dans cet article, nous suggérons des algorithmes de surveillance et de prise en charge de ces manifestations indésirables endocriniennes. Le diagnostic précoce de celles-ci et leur traitement adéquat permettraient de réduire leur impact négatif sur la prise en charge de la maladie cancéreuse.

[Chronic autoimmune gastritis : a multidisciplinary management]. / La gastrite chronique auto-immune : une prise en charge multidisciplinaire.

Chronic autoimmune gastritis (CAG) is a continuum of histological changes in gastric mucosa including: atrophy, intestinal metaplasia, dysplasia and finally, the occurrence of a neoplasm (gastric Neuroendocrine Tumors -NETs- and adenocarcinoma). The association with Hashimoto and Graves-Basedow disease is known as the thyrogastric autoimmune syndrome. While Helicobacter pylori (Hp) infection may be associated with CAG, the role of the gastric microbiota is ill-defined. The gastric hypochlorhydria determines a malabsorption of different micronutrients (iron, magnesium, calcium, vitamin B12) as well as drugs (thyroxine, etc.). Pernicious anemia is favoured by the deficit of parietal intrinsic factor that contributes to B12 malabsorption. Serology for Hp, serum pepsinogen I/II, increased gastrin levels, the presence of parietal cell antibodies and intrinsic factor antibodies may reveal CAG. High definition endoscopy associated with virtual chromoendoscopy seems promising for CAG diagnosis and follow-up. NETs type 1 treatment includes: endoscopic and surgical resection, somatostatin analogues and the recent availability of netazepide, a gastrin antagonist. We review herein advances in the treatment and diagnosis of CAG and associated autoimmune disorders, which may involve, in a multidisciplinary way, all practitioners.

La gastrite chronique auto-immune (GAI) est un continuum d'altérations de la muqueuse gastrique incluant : atrophie, métaplasie intestinale, dysplasie et, enfin, la survenue d'une néoplasie (tumeurs neuroendocrines [NETs] gastriques et adénocarcinome). L'association avec la maladie de Hashimoto et de Graves-Basedow est connue comme syndrome thyrogastrique auto-immun. Alors que l'Helicobacter pylori (Hp) peut s'associer avec la GAI, le rôle du microbiote gastrique est mal défini. L'hypochlorhydrie gastrique détermine une malabsorption de micronutriments (fer, magnésium, calcium, vitamine B12) et de médicaments (thyroxine et autres). L'anémie de Biermer est favorisée par le déficit de production du facteur intrinsèque pariétal, contribuant à la malabsorption de B12. Un rapport diminué de pepsinogène I/II, une augmentation de la gastrine, la présence d'anticorps anti-cellule pariétale, les anticorps anti-facteur intrinsèque et la sérologie pour Hp contribuent à révéler précocement le diagnostic de GAI. L'endoscopie haute définition, associée à la chromoendoscopie virtuelle, semble prometteuse dans le diagnostic et dans le suivi. Le traitement des NETs gastriques de type 1, favorisées par la GAI, inclut : la résection endoscopique/chirurgicale, les analogues de la somatostatine et l'antagoniste de la gastrine nétazépide. Nous résumons ici les avancées diagnostiques et thérapeutiques dans la GAI et dans les affections associées : elles impliquent, de façon multidisciplinaire, l'ensemble des praticiens.

Surveillance of infections in long-term care facilities (LTCFs): The impact of participation during multiple years on health care-associated infection incidence.

We studied trends in the incidence of health care-associated infections (HAIs) in LTCFs between 2009 and 2015 and determined the effect of participation in our network. Elder-care physicians reported weekly the number of cases of influenza-like illness, gastroenteritis, (probable) pneumonia, urinary tract infections (UTIs) and all-cause mortality. Trends in the incidence of infection and mortality in relation to LTCF characteristics were calculated using multilevel univariate and multivariate logistic regression. Thirty LTCF participated for 3 years or more, 16 for 2 years and the remaining 12 LTCF for 1 year. During the study period, the median number of beds decreased from 158 to 139, whereas the percentage of residents with private bedrooms increased from 14% to 87%. UTIs were the most frequently reported infections, followed by (probable) pneumonia and gastroenteritis. Adjusted for calendar year and season, we observed a statistically significant decrease in the incidence of influenza-like illness (odds ratio (OR) = 0.8, P < 0.01) and (probable) pneumonia (OR = 0.8, P < 0.01) for each extra year an LTCF participated. Although there are other likely contributors, such as more private rooms and enhanced infection control measures, the decreasing trend of HAI in LTCFs participating in surveillance implies that surveillance is a valuable addition to current strategies to optimise infection control.

Plasma miRNAs as biomarkers for endometriosis.

STUDY QUESTION: Can plasma miRNAs be used for the non-invasive diagnosis of endometriosis in infertile women? SUMMARY ANSWER: miRNA-based diagnostic models for endometriosis failed the test of independent validation. WHAT IS KNOWN ALREADY: Circulating miRNAs have been described to be differentially expressed in patients with endometriosis compared with women without endometriosis, suggesting that they could be used for the non-invasive diagnosis of endometriosis. However, these studies have shown limited consistency or conflicting results, and no miRNA-based diagnostic test has been validated in an independent patient cohort. STUDY DESIGN, SIZE, DURATION: We performed genome-wide miRNA expression profiling by small RNA sequencing to identify a set of plasma miRNAs with discriminative potential between patients with and without endometriosis. Expression of this set of miRNAs was confirmed by RT-qPCR. Diagnostic models were built using multivariate logistic regression with stepwise feature selection. In a final step, the models were tested for validation in an independent patient cohort. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Plasma of all patients was available in the biobank of the Leuven Endometriosis Centre of Excellence. Biomarker discovery and model development were performed in a discovery cohort of 120 patients (controls = 38, endometriosis = 82), and models were tested for validation in an independent cohort of 90 patients (controls = 30, endometriosis = 60). RNA was extracted with the miRNeasy Plasma Kit. Genome-wide miRNA expression analysis was done by small RNA sequencing using the NEBNext small RNA library prep kit and the NextSeq 500 System. cDNA synthesis and qPCR were performed using the Qiagen miScript technology. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a set of 42 miRNAs with discriminative power between patients with and without endometriosis based on genome-wide miRNA expression profiling. Expression of 41 miRNAs was confirmed by RT-qPCR, and 3 diagnostic models were built. Only the model for minimal-mild endometriosis (Model 2: hsa-miR-125b-5p, hsa-miR-28-5p and hsa-miR-29a-3p) had diagnostic power above chance performance in the independent validation (AUC = 60%) with an acceptable sensitivity (78%) but poor specificity (37%). LIMITATIONS, REASONS FOR CAUTION: The diagnostic models were built and tested for validation in two patient cohorts from a single tertiary endometriosis centre. Further validation tests in large cohorts with patients from multiple endometriosis centres are needed. WIDER IMPLICATION OF THE FINDINGS: Our study supports a possible biological link between certain miRNAs and endometriosis, but the potential of these miRNAs as clinically useful biomarkers is questionable in women with infertility. Large studies in well-described patient cohorts, with rigorous methodology for miRNA expression analysis, sufficient statistical power and an independent validation step, are necessary to answer the question of whether miRNAs can be used as diagnostics markers for endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by a grant from the Research Foundation - Flanders (FWO). A.V., D.F.O. and D.P. are PhD fellows from the FWO. T.D. is vice president and Head of Global Medical Affairs Fertility, Research and Development, Merck KGaA, Darmstadt, Germany. He is also a professor in Reproductive Medicine and Biology at the Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven (University of Leuven), Belgium and an adjunct professor at the Department of Obstetrics and Gynecology in the University of Yale, New Haven, USA. Neither his corporate role nor his academic roles represent a conflict of interest with respect to the work done by him for this study. The other co-authors have no conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

[Cushing's syndrome during pregnancy : diagnostic and therapeutic difficulties]. / Le cas clinique du mois. Syndrome de Cushing au cours d'une grossesse : difficultés diagnostiques et thérapeutiques.

Cushing's syndrome (CS), which is often associated with infertility, exceptionally occurs in pregnancy, and markedly increases maternal and fetal morbidity and mortality. Gestational CS may be challenging. Indeed, symptoms of hypercorticism may overlap with physiological hyperactivity of the hypothalamus-pituitary-adrenal axis in normal pregnancy. This case report describes a pregnant patient that underwent a fertility treatment and developed a gestational CS due to an adrenocortical adenoma. Diagnosis of gestational CS was suspected at 13 weeks by a new onset of hypokalemia and arterial hypertension. A multidisciplinary approach was necessary during follow up. At 24 weeks, laparoscopic surgery retrieved a 4 cm adrenocortical adenoma. Cesarean surgery was successfully practiced at 31 weeks, because of preeclampsia. We discuss the differential diagnosis of hypokalemia and arterial hypertension during pregnancy and the diagnosis and management of gestational CS.

Le syndrome de Cushing (SC), déterminant fréquemment une infertilité, survient exceptionnellement au cours d´une grossesse. La présentation du SC au cours de la grossesse s'accompagne d'une plus grande morbimortalité maternelle et foetale. Son diagnostic représente un véritable défi pour le clinicien, car les symptômes de l'hypercorticisme se superposent aux modifications physiologiques induites par la stimulation de l`axe corticotrope lors de la grossesse. Nous rapportons le cas d'une patiente enceinte après une fécondation in vitro. A 13 semaines de grossesse, un SC gestationnel d'origine surrénalienne est suspecté dans le cadre d'une hypokaliémie et d'une hypertension artérielle inaugurales. Un suivi multidisciplinaire est instauré au cours de la grossesse. Une surrénalectomie gauche par voie laparoscopique est décidée à 24 semaines d'aménorrhée, avec l'exérèse complète d'un adénome cortical, de 4 cm de diamètre. La chirurgie par césarienne est pratiquée avec succès à 31 semaines de grossesse, car la patiente développait une pré-éclampsie. Nous discutons les différents diagnostics différentiels d'une hypokaliémie et d'une hypertension artérielle au cours de la grossesse et les modalités de prise en charge d´un SC gestationnel.

[A brief history of syphilis. The disease through the art and the artist]. / Une petite histoire de la syphilis. La maladie à travers l'art et l'artiste.

Considering its strong symbolic connotations and its rich history, syphilis could be regarded as the perfect example of venerian disease. It could also be seen as a representative disease of the whole medical history and the evolution of both medical ways of thinking and curing. In this work we will briefly discuss the history of the syphilitic disease and try to show how this condition has affected the life and works of some of the most famous artists of the 19th century. Moreover, we shall try to evoke the complex relationship between art and pathology.

Par ses connotations historiques et symboliques, la syphilis constitue la maladie vénérienne par excellence. Elle peut également être considérée à plus d'un titre comme une maladie représentative de l'histoire de la médecine et paradigmatique de l'évolution de la pensée médicale. Au travers de ce petit historique, nous tenterons de dresser une brève histoire de la maladie et de son traitement avant d'envisager la façon dont elle a pu influencer le parcours créatif de plusieurs figures artistiques majeures du XIXème siècle. Plus encore, nous discuterons brièvement des liens complexes que peuvent entretenir l'art et la maladie.

Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

Review article: transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome.

BACKGROUND: Abdominal pain in irritable bowel syndrome (IBS) remains challenging to treat effectively. Researchers have attempted to elucidate visceral nociceptive processes in order to guide treatment development. Transient receptor potential (TRP) channels have been implied in the generation (TRPV1, TRPV4, TRPA1) and inhibition (TRPM8) of visceral pain signals. Pathological changes in their functioning have been demonstrated in inflammatory conditions, and appear to be present in IBS as well. AIM: To provide a comprehensive review of the current literature on TRP channels involved in visceral nociception. In particular, we emphasise the clinical implications of these nociceptors in the treatment of IBS. METHODS: Evidence to support this review was obtained from an electronic database search via PubMed using the search terms "visceral nociception," "visceral hypersensitivity," "irritable bowel syndrome" and "transient receptor potential channels." After screening the abstracts the articles deemed relevant were cross-referenced for additional manuscripts. RESULTS: Recent studies have resulted in significant advances in our understanding of TRP channel mediated visceral nociception. The diversity of TRP channel sensitization pathways is increasingly recognised. Endogenous TRP agonists, including poly-unsaturated fatty acid metabolites and hydrogen sulphide, have been implied in augmented visceral pain generation in IBS. New potential targets for treatment development have been identified (TRPA1 and TRPV4,) and alternative means of affecting TRP channel signalling (partial antagonists, downstream targeting and RNA-based therapy) are currently being explored. CONCLUSIONS: The improved understanding of mechanisms involved in visceral nociception provides a solid basis for the development of new treatment strategies for abdominal pain in IBS.

Gastrointestinal disorders in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: A review for the gastroenterologist.

BACKGROUND: Joint hypermobility syndrome (JHS)/Ehlers-Danlos syndrome hypermobility type (EDS-HT) is the most common hereditary non-inflammatory disorder of connective tissue, characterized by a wide range of symptoms, mainly joint hyperextensibility and musculoskeletal symptoms. A majority of patients also experiences gastrointestinal (GI) symptoms. Furthermore, JHS/EDS-HT has specifically been shown to be highly prevalent in patients with functional GI disorders, such as functional dyspepsia and irritable bowel syndrome. PURPOSE: The aim of this review was to examine the nature of GI symptoms and their underlying pathophysiology in JHS/EDS-HT. In addition, we consider the clinical implications of the diagnosis and treatment of JHS/EDS-HT for practicing clinicians in gastroenterology. Observations summarized in this review may furthermore represent the first step toward the identification of a new pathophysiological basis for a substantial subgroup of patients with functional GI disorders.