Hopitaux Universitaires De Geneve Research Articles

Maternal occupational exposure to endocrine-disrupting chemicals during pregnancy and semen parameters in adulthood: results of a nationwide cross-sectional study among Swiss conscripts

Study question Is there a relationship between maternal occupational exposure to endocrine-disrupting chemicals (EDCs) during pregnancy and the semen quality of their sons? Summary answer Our results suggest an association between maternal occupational exposure to potential EDCs, especially to pesticides, phthalates and heavy metals, and a decrease in several semen parameters. What is known already Sexual differentiation, development and proper functioning of the reproductive system are largely dependent on steroid hormones. Although there is some animal evidence, studies on maternal exposure to EDCs during pregnancy and its effect on the semen quality of sons are scarce and none have focused on maternal occupational exposure. Study design, size, duration A cross-sectional study aiming to evaluate semen quality was carried out among Swiss conscripts aged 18 to 22 years between 2005 and 2017. Participants/materials, setting, methods Conscript and parent questionnaires were completed prior to the collection of a semen sample. Semen parameters were categorised according to the guidelines of the World Health Organization (WHO). Data on maternal employment during pregnancy were provided by the parent questionnaire. Maternal occupational exposure to potential EDC categories was defined using a job-exposure matrix (JEM). Logistic regressions were used to analyse the relationship between maternal occupational exposure to EDCs and each semen parameter adjusted for potential confounding factors. Results are presented using odds ratios and 95% confidence intervals. Main results and the role of chance In total, 1,737 conscripts provided a conscript and parent questionnaire, as well as a semen sample; among these 1,045 of their mothers worked during pregnancy. Our study suggests an association between occupational exposure of mothers during pregnancy to potential EDCs and low semen volume and total sperm count, particularly for exposure to pesticides (OR 2.07, 95% CI 1.11-3.86 and OR 2.14, 95% CI 1.05-4.35), phthalates (OR 1.92, 95% CI 1.10-3.37 and OR 1.89, 95% CI 1.01-3.55), and heavy metals (OR 2.02, 95% CI 1.14-3.60 and OR 2.29, 95% CI 1.21-4.35). Maternal occupational exposure to heavy metals was additionally associated with a low sperm concentration (OR 1.89, 95% CI 1.06-3.37). Limitations, reasons for caution Several limitations should be noted, such as the indirect method for maternal occupational exposure assessment during the pregnancy (JEM) and the cross-sectional design of the study. Wider implications of the findings Our observations reinforce the need to inform pregnant women of potential hazards during pregnancy that could impair their child's fertility. Additional studies are needed to confirm the involvement of EDCs. Study funding/competing interest(s) This work was supported by the Swiss Centre for Applied Human Toxicology: SCAHT and the 'Fondation privee des Hopitaux Universitaires de Geneve'. The collection of human biological material used for this study was supported by the FABER Foundation, the Swiss National Science Foundation (SNSF): NFP 50 'Endocrine Disruptors: Relevance to Humans, Animals and Ecosystems', the Medical Services of the Swiss Army (DDPS) and Medisupport. The authors declare they have no competing financial interests. Trial registration number N/A.

Review of A Handbook for the Assessment of Children's Behaviours, by Jonathan Williams, and Peter Hill

[Author Affiliation]Daniel S. Schechter. Service de Psychiatrie de l'Enfant et de l'Adolescent ( SPEA) Hopitaux Universitaires de Geneve et la Faculte de Medecine de l'Universite de Geneve, Geneve, Switzerland.ISBN: 978-1-119-97589-2. Oxford: Wiley-Blackwell, 2012, 616 pages.Address correspondence to: Daniel S. Schechter, MD, CC, Service de Psychiatrie de l'Enfant et de l'Adolescent (SPEA) Hopitaux Universitaires de Geneve et la Faculte de Medecine de l'Universite de Geneve, 51 Boulevard de la Cluse, 2eme Etage, 1205 Geneve, Switzerland, E-mail: daniel.schechter@hcuge.chHave you ever wanted find a clinical reference book that is indexed by most common child and adolescent symptoms and signs rather than by Diagnostic and Statistical Manual of Mental Disorders (DSM) disorder? The new Wiley Desktop Edition of A Handbook for Assessment of Children's Behaviours by Jonathan Williams and Peter Hill is just such a volume. The authors state in Introduction, is a book about However, title states that it is a book about assessment. Therefore, we see both major advantage and major disadvantage of this particular text right at beginning.The idea of a Merck Manual style of understanding which forms of psychopathology specific symptoms and signs might be linked is in itself a welcomed addition child and adolescent psychiatry library. This practical volume is divided into a brief introductory section, a large section on problem behaviors that forms meat of book, and 250 out of 616 pages of book that are devoted eight helpful appendices, a glossary and index, and references. It is a very dense paperback that a lot of fine print, many useful tables and charts, citation of measures, laboratory tests standard normal values, and more, which obsessional clinicians can sink our teeth into.The introductory section states that this book will list individual symptoms and behaviors that are most commonly focus of complaint, and will also list factors that can contribute or cause them. The book is designed to help readers decide if symptoms merit clinical attention or not and what further assessment is indicated. The level of text and content are particularly well pitched students, interns, residents, and beginning mental health practitioners. The volume contains useful discussions such as the meaning of tears, stating that tears are an invitation meet patient with sympathy and encouragement, and then offers some model phrases of encouragement. Another passage asks When is intuition useful? and yet another recommends giving feedback during and after assessment, always starting child's and parent's points of view in mind.Following introductory section, book launches into various developmental and psychological domains in which symptoms arise, and then lists those symptoms. Although not overtly remaining wedded any particular school of thought or theory at glance, a more careful reading suggests that authors have a somewhat cognitive-behavioral bent, and that, therefore, cognition is domain in a guide meant for psychologists and psychiatrists, followed by motor, sensory, communication, and social. Thereafter, one notes categories such as breaking rules, anger, anxiety, negativeness, and languor, in of a singular emotional or affective domain. And finally, there are domains named digestive/excretory, and bizarre experiences and ideas related more specific forms of psychopathology, such as psychotic disorders.The very behavior and related Causelist in book is Poor results in school or testing. The authors state that this has in book because it needs be considered in every child, even when it is not presenting complaint. Therefore, one immediately finds focus of this volume on school-age children and academic performance be a primary indicator of functioning, which is in contrast social-emotional functioning, which might be listed as first place in other child mental health handbooks. …

Cellular swirls and cellular swirl‐like structures are not restricted to papillary thyroid carcinoma

Recently, besides the presence of papillae and typical nuclear features (e.g., grooves and pseudoinclusions), a peculiar architectural feature known as “cellular swirls” has been recognized as an additional criterion for diagnosing papillary thyroid carcinoma (PTC) in fine needle aspirates. Cellular swirls are defined as concentrically organized aggregates of tumor cells in which many of the most peripherally situated cells have ovoid rather than round nuclei that are oriented perpendicular to the radius of the swirl (Fig. 1A). Although their reported sensitivity for PTC is low (17%), they have not been found in benign thyroid lesions. Therefore, in the thyroid gland, cellular swirls appear to be highly specific to PTC. Furthermore, cellular swirl-like structures with some but not all the features of cellular swirls have also been described in PTC. They also appear to be specific for PTC, and may even more prominent in the aspiration smears than the characteristic swirls. Therefore, swirl-like structures may also be a useful feature in the diagnosis of PTC. The potential diagnostic value of cellular swirls and/or cellular swirl-like structure in other papillary lesions arising from other organs has not been investigated previously. In contrast to high grade urothelial carcinoma, the sensitivity of urinary cytology for the diagnosis of low grade papillary urothelial neoplasms (LGPUN) is very low (overall sensitivity of 26% for LGPUN versus >95% for high grade urothelial carcinoma). Although the presence of papillary fragments with fibrovascular cores is diagnostic of LGPUN, they are rare. The other architectural and cytological diagnostic criteria, including cell clusters with irregular edges, increased nuclear/cytoplasmic ratios, irregular nuclear borders, and cytoplasmic homogeneity, although specific when combined together, are also not sensitive for LGPUN. Therefore, additional diagnostic features may be helpful to recognize LGPUN on cytology. To the best of the author’s knowledge, cellular swirls or similar structures have not been described in LGPUN. Following the observation of cellular swirl-like structures (Fig. 1B) in a bladder washing specimen from a case of low-grade papillary urothelial carcinoma, the author analyzed 15 additional bladder washing specimens to evaluate if cellular swirls or similar structures could also be helpful for the diagnosis of LGPUN on cytology. For each case, the diagnosis of noninvasive low-grade papillary urothelial carcinoma was confirmed on histology. In the 15 cases subsequently analyzed, no convincing cellular swirls or cellular swirl-like structures were found. Therefore, in contrast to PTC, this peculiar architectural feature does not appear to be helpful as an additional diagnostic criterion for LGPUN on cytology. Furthermore, cellular swirls were also subsequently observed in benign mesothelial cell clusters from normal peritoneal washing specimens (Fig. 1C). This suggests, in fact that they may not be linked to tumors with a papillary architecture such as PTC, but that they may rather represent nonspecific areas of incipient infolding within flat sheets of cells, whether neoplastic or not. Division of Clinical Pathology, Geneva University Hospital, 1211 Geneva 14, Switzerland *Correspondence to: Dr. Marc Pusztaszeri, Service de Pathologie Clinique, Hopitaux Universitaires de Geneve, 1 rue Michel-Servet, 1211 Geneve 14, Switzerland. E-mail: Marc.Pusztaszeri@hcuge.ch Received 28 November 2012; Revised 11 October 2013; Accepted 9 January 2014 DOI: 10.1002/dc.23108 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).

Le projet CASSANDRE ou l’optimisation par diagnostic automatisé des documents cliniques

Abstract. In January 2007, the Hopitaux Universitaires de Geneve (HUG) went from flat rate billing day basis to flat rate billing case basis. The system used until 2012 was the All Patient Diagnosis Related Group (APDRG) system. Since 2012, the system used is the Swiss DRG. Assuming that nowadays the hospital stay billing depends on the DRG used, and that this DRG is made on a short stay resume basis, we have identified three works areas to optimize the output document and therefore the stay billing. Those three works areas, that are part of the Cassandra project, are the improvement of the completeness of the output document, the optimization of the principal diagnosis choice and finally the creation of an essential comorbidities list. For the first area, we have implemented pathology detection algorithms, especially, for the dyskaliemies detection. In this case the potential gain is almost 2’000’000 CHF. For the second area, the principal diagnosis choice has to be done by having considered the diagnosis having concretely monopolized the most resources during the patient stay, in order to have a billing as fair as possible. Finally, for the third area, we have now identified 33 diagnoses that have an impact on the DRG choice and on the medical resources that those pathologies need. For those reasons, we have initiated a meticulous study regarding their clinical documentation and possible detection algorithms. The initial results being encouraging, we believe that those three works areas will help us to create tools, that once implemented in the coding chain will improve the coding quality at the HUG and especially will achieve a more accurate billing for the patients, the insurers and our institution.

Epilepsy and electroencephalographic features in trisomy 13: A case report and review of literature

Epilepsy and electroencephalographic features in trisomy 13: A case report and review of literature

Fine‐needle aspiration biopsy for the diagnosis of metastatic type B thymoma to lymph nodes: A case report

Extrathoracic metastases of thymic neoplasms are very rare (incidence is believed to be around 3–6%), and their cytologic features have seldom been reported. The most common subtype associated with metastasis is thymic carcinoma, followed by type B thymoma. The recognition of thymic metastasis is challenging because of its rarity and because of its potency to mimic tumors from other sites. We report the case of a metastatic type B thymoma in supraclavicular and mediastinal lymph nodes in a 69-year-old male diagnosed on fine-needle aspiration biopsy (FNAB). The patient had a previous history of type B (mixed or lympho-epithelial) thymoma with myasthenia treated with corticosteroids, surgery, and radiotherapy 12 years earlier. The primary tumor, partially calcified, measured 7 3 6.5 3 3 cm and involved the pericardium and periaortic fat. Surgical margins were free of tumor. The patient developed left diaphragm and left vocal cord palsy after surgery. In 2012, he was admitted to the hospital because of recurrent bilateral bronchopneumonia due to multiresistant Pseudomonas aeruginosa. The investigations revealed mediastinal (upper and middle) and left supraclavicular lymphadenopathies with left carotid artery involvement. FNAB of lymphadenopathies from both localizations was performed and liquidbased preparations (Thinprep VR ) were made. The aspirates were cellular, composed of cohesive epithelioid to spindle cells with round regular nuclei and small nucleoli showing mild atypia and pleomorphism. These cells were admixed with small mature lymphocytes (Fig. C-1A). A cell-block from one of the aspirates was made and revealed similar cohesive clusters of epithelial cells with a squamoid appearance (Fig. C-1B). Small lymphocytes were also intermingled in the clusters or admixed in the background. Immunocytochemistry was performed: the epithelial cells were positive for keratin wide spectrum (KWS) (Fig. C-1C) and negative for neuroendocrine markers (chromogranin A and synaptophysin), CD5, and TTF-1. The lymphocytes were mostly positive for CD3 and CD5 and a fraction of them was also positive for TdT (Fig. C-1D), revealing an immature phenotype. Because of the clinical history and the presence of a dual epithelial and lymphoid population closely intermixed with immature TdT positive lymphocytes, a diagnosis of metastatic thymoma was made on cytology. Thymomas are cytologically benign neoplasms of the thymus gland accompanied by varying numbers of benign lymphocytes. The proportion of lymphocytes and epithelial cells determines the type of thymoma (A, B1, B2, B3). The epithelial cells are almost always negative for CD5. By contrast, thymic carcinomas are by definition composed of cytologically malignant cells, often positive for CD5. A peculiar feature of thymoma but not thymic Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland Center of Oncology, Geneva University Hospital, Geneva, Switzerland Cantonal Institute of Pathology, Sion, Switzerland *Correspondence to: Marc Pusztaszeri, M.D., Service de Pathologie Clinique, Hopitaux Universitaires de Geneve, 1 rue Michel-Servet, 1211 Geneve 14, Switzerland. E-mail: marc.pusztaszeri@hcuge.ch Received 9 July 2012; revised 26 November 2012; Accepted 1 January 2013 DOI: 10.1002/dc.22965 Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).

Myocardial effects of isoflurane, sevoflurane and desflurane on right ventricular function in senescent rats

Hopitaux Universitaires de Geneve, Department of Anaesthesiology and Intensive Care, Geneve, Switzerland

Micro-Structural Alterations in the Brain of Well-Treated HIV+ Patients with Mild Neurocognitive Disorders: A Multi-Contrast MRI Study at High Field (S37.001)

Objective: To investigate MRI markers of subtle HIV effects on the brain. Background Mild neurocognitive disorders (MND) affect a subset of HIV+ patients under effective highly active antiretroviral therapies (HAART). The physiopathology of MND is however not clear, as well as the reasons why some well-treated patients suffer from MND while other not. Here, we used a multi-contrast MRI based approach at high field to test the hypothesis that well-treated aviremic MND+ patients present different brain micro-structural characteristics compared to MND- HIV patients and healthy controls (HC). Design/Methods: We enrolled 17 MND+ and 19 MND- patients with undetectable viremia and 14 age-matched HC. MRI acquisitions at 3T included: MP2RAGE for T1 relaxation times as well as Magnetization Transfer (MT), T2* and Susceptibility Weighted Imaging (SWI) to probe micro-structural integrity and iron deposition. Regions of interest were automatically extracted for white and gray matter (WM, GM), thalamus, basal ganglia and hippocampus. Statistical analysis used multivariate permutation-based Hotelling tests and correction for family-wise error rate. A linear discriminant analysis between MND+ and MND- patients was performed using multi-parametric MRI data (T1, MT ratio, SWI) and cross-validated with a leave-one-out test. Results: Multivariate analysis showed significant differences between MND+ and MND- patients in WM and GM (p=0.02 respectively), and between MND+ and HC in the caudate (p=0.02). Univariate analysis revealed that MND+ patients had lower MT ratio than MND- and HC, reaching significance in WM and caudate (p=0.01). The linear discriminant analysis distinguished MND+ and MND- patients with a classification quality of 0.73% after cross-validation. Conclusions: Our findings show the presence of micro-structural brain alterations in MND+ patients as compared to MND- and HC, suggesting loss of structural integrity. In addition, they suggest that multi-contrast MRI at high field may be a powerful approach to understand the physiopathology of MND and to discriminate between patients9 sub-groups. Supported by: Centre d9Imagerie BioMedicale of the University of Lausanne, the Swiss Federal Institute of Technology Lausanne, the University of Geneve, the Centre Hospitalier Universitaire Vaudois, the Hopitaux Universitaires de Geneve, the Leenaards, the Jeantet and the Stoicescu foundations and the Swiss National Science Foundation Grant PZ00P3_131914/1. Disclosure: Dr. Granziera has nothing to disclose. Dr. Daducci has nothing to disclose. Dr. Simioni has received personal compensation for activities with Gilead and Boehringer Ingelheim as a speaker. Dr. Cavassini has nothing to disclose. Dr. Roche has received personal compensation for activities with Siemens AG as an employee. Dr. Meskaldji has nothing to disclose. Dr. Michel has nothing to disclose. Dr. Calmy has nothing to disclose. Dr. Hirschel has nothing to disclose. Dr. Krueger has received personal compensation for activities with Siemens AG as an employee. Dr. Krueger has received research support from Siemens AG. Dr. Du Pasquier has received personal compensation for activities with Merck Serono, Biogen Idec, Abbott, and ViiV.

Translating an Afro-European partnership into tangible hand hygiene action

WHO African Partnerships for Patient Safety (APPS) nurtures sustainable partnerships between African and European hospitals to improve patient safety. Through APPS, Hopitaux Universitaires de Geneve (HUG) is partnered with hospitals in Cameroon, Mali and Senegal.

Hospital patient safety situational analyses: Cameroon, Mali and Senegal

Hopitaux Universitaires de Geneve partners with hospitals in Cameroon, Mali & Senegal via African Partnerships for Patient Safety (APPS). Baseline hospital patient safety understanding is largely unknown in African settings. APPS is framed around 12 WHO AFRO action areas; prevention of health care-associated infection is a common platform.

Renal ischaemic injuries during the use of zolmitriptan for treatment of migraines in a transplanted patient under tacrolimus therapy

A 26-year-old female patient underwent kidney transplantation from a 38-year-old deceased donor in 2001. Her renal disease was a focal segmental hyalinosis secondary to congenital vesico-ureteral reflux. She was started on triple immunosuppressive therapy [tacrolimus, mycophenolate mofetil (MPM) and prednisone]. Renal transplantation was complicated by delayed graft function and a renal biopsy was performed on the day 8, showing histological signs of tubular necrosis without acute rejection. Thereafter, evolution was excellent and corticosteroids were stopped after 1 year. Creatinine at 1 year was 100 mmol/l. She had arterial hypertension which was treated with four antihypertensive drugs just after renal transplantation; the treatment was progressively decreased and 18 months after transplantation, she required no further antihypertensive therapy. A routine renal biopsy was performed after steroid withdrawal in 2002, showing no evidence of rejection but a moderate interstitial fibrosis (10–20%). Tacrolimus and MPM were continued and trough levels of tacrolimus were aimed for 6–8 mg/l. All follow-up visits between 2002 and 2005 were unremarkable, except one respiratory infection which was treated with antibiotics for 7 days. Renal function was extremely stable with values averaging 100 mmol/l (83–114 mmol/l) of creatinine during these 3 years (Figure 1). She had no proteinuria (170mg/day). Tacrolimus trough level was kept between 6 and 8 mg/l with 1.5mg b.i.d. During this period, she was also taking an oral contraception (estradiol and progesterone), magnesium and paracetamol for common migraines. She did not smoke or drink alcohol. During the summer of 2005 her common migraines became exacerbated, no longer relieved by paracetamol. In September 2005, her general practitioner prescribed zolmitriptan 2.5mg to good effect. She used this medication 3–4 times a month. In October 2005 she had a slight increase of creatinine at 120 mmol/l, but no other changes which might have raised any concerns for her renal function; a control in January was stable at 115 mmol/l. Due to an increase in her headaches, she took zolmitriptan more frequently during the following 2 months, reporting an average consumption of 10 pills per week (Figure 1). She did not complain of abdominal pains. In March 2006, a control showed a creatinine value at 161 mmol/l associated with an increase in proteinuria (500mg/day) (Figure 1). There was no clinical explanation for this rise, but tacrolimus trough levels were at the upper limit of the target (8 mg/l) during the last 4 months under the same drug regimen (1.5mg b.i.d). A renal biopsy was performed. Several cortical ischaemic scars were observed with globally sclerotic glomeruli and arteriosclerosis (Figure 2A). The cortical region without scars included eight glomeruli, four of them globally sclerosed. Two glomeruli showed severe ischaemic injury with corrugation of the basement membranes (Figure 2B). In the two other glomeruli, lesions of focal and segmental sclerosis were observed. Some intratubular calcifications were detected. Arterioles appeared unremarkable. A 99m-Tc-DMSA renal scintigraphy was done, which did not reveal renal defects compatible with large scars. Zolmitriptan and tacrolimus were suspected to be involved in this acute decline in renal function. Zolmitriptan was stopped and tacrolimus dosage was slightly decreased, to 1mg in the morning and 0.5mg in the evening. Creatinine slowly decreased to 141 umol/l and a renal biopsy was performed again in June 2006. The histology showed the same cortical scars, and moderate arteriolar lesions Correspondence to: Pierre-Yves Martin, Service de Nephrologie, Departement de Medecine Interne, Hopitaux Universitaires de Geneve, 1211 Geneve 4, Switzerland. Email: pierre-yves.martin@hcuge.ch Nephrol Dial Transplant (2007) 22: 3341–3343

Comparison of Propofol with Lidocaine Pretreatment Versus Propofol Formulated with Long- and Medium-Chain Triglycerides or Confounding Effect of Tourniquet

In Response: We would like to thank Drs. Eghtesadi-Araghi and Marashi for their interest in our randomized clinical trial. They have raised some concerns regarding tourniquet use and the potential for an interaction between ischemia/reperfusion injury and the pain triggered by the injection of propofol. First, the tourniquet used on the forearm of our patients in this trial was not a “surgical tourniquet” whereby two cuffs are inflated to a pressure of 300 mm Hg to prevent arterial flow to provide a bloodless surgical field during microsurgery, to minimize blood loss during orthopedic surgery, or to perform distal limb anesthesia with prilocaine. As is our routine practice when using standard propofol with pretreatment with lidocaine and as has been described by others (1), we used a rubber tourniquet that was held in place on the forearm for <1 min. It is most unlikely that any ischemia would result from such a procedure with low compression applied for a short time. Therefore, we do not consider that neutrophil-mediated endothelial cytotoxicity and activation or generation of free radicals and kinines provide an explanation for the increased pain observed after injection of the long- and medium-chain triglyceride propofol. Furthermore, both formulations of propofol were administered with a rubber tourniquet, so if the tourniquet were to have a confounding effect, this would have been seen in both groups. Although the solvent might be key in producing the pain (2), it is most unlikely that the different lipid contents in the two propofol formulations react in such a different way to a 30-s tourniquet application as to result in an exaggerated free radicals and cytokines release with the long- and medium-chain triglyceride formulation. Finally, a recent randomized trial comparing long- and medium-chain triglycerides with standard propofol mixed with lidocaine without using a tourniquet also described a trend towards more pain in patients receiving the long- and medium-chain triglyceride formulation (3). E. Schaub, MD C. Kern, MD Ruth Landau, MD Service d’ Anesthesiologie Hopitaux Universitaires de Geneve Geneva, Switzerland [email protected]