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Beyond pancreatic ductal adenocarcinoma, which is by far the most frequent pancreatic neoplasm, a great variety of tumors occur in the pancreas. They include solid and cystic masses and epithelial and nonepithelial neoplasms, and they show a great diversity in their biological behavior, ranging from benign tumors to highly aggressive neoplasms. As examples of rare pancreatic tumors, clinical, morphological, and molecular aspects of acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary neoplasm, and serous cystic neoplasms are presented and discussed.

Background In the absence of rapid on‐side pathological evaluation, endoscopy staff generally “smears” endoscopic ultrasound guided fine needle aspiration (EUS‐FNA) specimens on a glass slide. As this technique is vulnerable to preparation artifacts, we assessed if its quality could be improved through a smear‐preparation‐training for endoscopy staff. Methods In this prospective pilot study, 10 endosonographers and 12 endoscopy nurses from seven regional EUS‐centers in the Netherlands were invited to participate in a EUS‐FNA smear‐preparation‐training. Subsequently, post training slides derived from solid pancreatic lesions were compared to pre‐training “control” slides. Primary outcome was to assess if the training positively affects smear quality and, consequently, diagnostic accuracy of EUS‐FNA of solid pancreatic lesions. Results Participants collected and prepared 71 cases, mostly pancreatic head lesions (48%). Sixty‐eight controls were selected from the pretraining period. The presence of artifacts was comparable for smears performed before and after training (76% vs 82%, P = .36). Likewise, smear cellularity (≥50% target cells) before and after training did not differ (44% (30/68) vs 49% (35/71), P = .48). Similar, no difference in diagnostic accuracy for malignancy was detected (P = .10). Conclusion In this pilot EUS‐FNA smear‐preparation‐training for endoscopy personnel, smear quality and diagnostic accuracy were not improved after the training. Based on these results, we plan to further study other training programs and possibilities.

Background and study aims The traditional “smear technique” for processing and assessing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is sensitive to artifacts. Processing and evaluation of specimens collected in a liquid medium, liquid-based cytology (LBC) may be a solution. We compared the diagnostic value of EUS-FNA smears to LBC in pancreatic solid lesions in the absence of rapid on-site evaluation (ROSE). Patients and methods Consecutive patients who required EUS-FNA of a solid pancreatic lesion were included in seven hospitals in the Netherlands and followed for at least 12 months. Specimens from the first pass were split into two smears and a vial for LBC (using ThinPrep and/or Cell block). Smear and LBC were compared in terms of diagnostic accuracy for malignancy, sample quality, and diagnostic agreement between three cytopathologists. Results Diagnostic accuracy for malignancy was higher for LBC (82 % (58/71)) than for smear (66 % (47/71), P = 0.04), but did not differ when smears were compared to ThinPrep (71 % (30/42), P = 0.56) or Cell block (62 % (39/63), P = 0.61) individually. Artifacts were less often present in ThinPrep (57 % (24/42), P = 0.02) or Cell block samples (40 % (25/63), P Conclusion After a single pass, LBC provides higher diagnostic accuracy than the conventional smear technique for EUS-FNA of solid pancreatic lesions in the absence of ROSE. Therefore, LBC, may be an alternative to the conventional smear technique, especially in centers lacking ROSE.

Pleistocene volcaniclastic turbidites drilled during IODP 340 (U1398B, ≤ 170 mbsf) in the Grenada basin west of Martinique (central Lesser Antilles) have been investigated for sediment provenance. U/Pb ages by ion microprobe from 323 detrital zircon grains at three U1398B levels reveal youngest population maximum ages which are interpreted to represent major eruption periods. Systematic age progression with depth defines a ~ 20 cm/ka depositional rate and provides a robust chronostratigraphic frame for the ≤167.5 mbsf (≤ 856 ± 10 ka) interval of U1398B, and confirms on-board paleomagnetic constraints for a possible late Matuyama age for the lowermost sampled parts of U1398B. The achieved chronostratigraphic frame yields sedimentation rates for carbonate ooze and of volcaniclastic sands and gravels of 8.2 and 7.6 cm/ky, respectively. Depth plots of cumulative thickness of these lithologies allow for a differentiation into periods of enhanced and reduced volcanic activity. Porphyritic lava and mineral fragments include plagioclase, diopside, augite and enstatite, as well as magnesio-hornblende and ferri-tschermakite. Geothermobarometry based on clinopyroxene and amphibole reveal the dominant role of upper crustal magma reservoirs. Ferri-tschermakite from 93 and 167.5 mbsf (~410 and 856 ka, respectively) records contributions from lower crustal, hot magma reservoirs. These temperature estimates are supported by Ti-in-zircon data. O-isotope ratios and trace elements in zircon reflect magmatic activity typical for an evolved island arc system. The bathymetry of the Grenada basin, the composition of lava clasts and minerals, scarcity of altered lava fragments, the narrow maximum age population of detrital zircon, and the O-isotope and trace element data on zircon suggest that the majority of U1398B volcaniclastic turbidites originated from the island of Dominica. The thick volcaniclastic units are most likely related to major eruption periods of andesitic magma that ascended from crustal reservoirs. Debris avalanche-related processes seem to be less important in U1398B at ≤170 mbsf. Mineral chemistry and O-isotope data obtained from plagioclase, pyroxene, amphibole, zircon and glass, separated from deep marine volcaniclastic turbidites, provide a chronostratigraphic frame for the sedimentary succession, and helps to genetically fingerprint the volcanic and magmatic evolution of the neighboring volcanic islands. While this is documented here for the well-constrained Pleistocene history of the central Lesser Antilles, the applied methods may also be used to characterize ancient marine volcaniclastic mass flow deposits and to reconstruct their volcanic source areas.

Beyond pancreatic ductal adenocarcinoma, which is by far the most frequent pancreatic neoplasm, a great variety of tumors occur in the pancreas. They include solid and cystic masses and epithelial and nonepithelial neoplasms, and they show a great diversity in their biological behavior, ranging from benign tumors to highly aggressive neoplasms. As examples of rare pancreatic tumors, clinical, morphological, and molecular aspects of acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary neoplasm, and serous cystic neoplasms are presented and discussed.Neben dem weitaus häufigsten Pankreastumor, dem duktalen Adenokarzinom des Pankreas, existieren zahlreiche solide und zystische, epitheliale und nichtepitheliale Tumoren im Pankreas, die für sich genommen jeweils selten sind und klinisch ein breites Spektrum von benignen Tumoren bis zu hochaggressiven, metastasierungs- und rezidivfreudigen Neoplasien abdecken. Exemplarisch werden in der vorliegenden Übersicht klinische, morphologische und molekulare Kriterien von Azinuszellkarzinomen, Pankreatoblastomen, solid-pseudopapillären Neoplasien und serös-zystischen Neoplasien vorgestellt, anhand derer eine differenzialdiagnostische Einordnung in der Regel leicht möglich ist.

BackgroundCurrently, real-world data on rheumatoid arthritis (RA) treatment patterns in France are limited.ObjectivesThe aim of this study was therefore to describe, between 2013 and 2017, the sequence of therapies used in the treatment of patients with RA and to characterize RA treatment patterns using real-world data.MethodsA non-interventional, longitudinal study was conducted using the Echantillon Généraliste des Bénéficiaires (EGB) between 1 January 2013 and 31 December 2017. EGB is a 1/97th representative random sample from the French National Healthcare Database (SNDS) which includes claims data covering 99% of the total French population.Treatment patterns, adherence and persistence of RA treatments were described in a cohort of patients with RA, identified between 2013 and 2017.ResultsBetween 2013 and 2017, 2,553 patients with RA were identified, including 2,314 in 2017. Of the 2,314 RA patients identified in 2017 (mean age 66.2 ± 15.4 years; 73.7% female; mean Charlson comorbidity score 4.2), 1,102 (47.6%) did not receive any disease-modifying anti-rheumatic drug (DMARD). Of these, 944 (85.7%) had received at least one symptomatic treatment, including 862 (91.3%) an analgesic, 509 (53.9%) an oral corticosteroid and 384 (40.7%) non-steroidal anti-inflammatory drugs.Of the 2,553 RA patients monitored between 2013 and 2017, 1,512 (59.2%) patients received a DMARD, of which 721 (47.7%) patients received only one treatment sequence, mainly methotrexate (n=529, 35.0%), and did not discontinue or switch treatment. Switching treatment to a targeted DMARD was reported for 144 (9.5%) patients. During follow-up, 377 (25%) patients discontinued treatment. In total, 1,142 RA treatment initiations were recorded, 62.4% of which were conventional synthetic DMARDs (csDMARDs). Persistence rates (95% confidence interval) for csDMARDs, TNF inhibitors (TNFi) and other targeted DMARDs (tDMARDs) were 63.4% (59.6–67.0), 55.9% (49.2–62.0) and 59.4% (51.2–66.6) at 12 months, respectively; Medication Possession Ratio (MPR), an adherence indicator, was 80.5%, 90.8% and 71.9%, respectively.Long-term oral corticosteroids (≥6 months) were also associated with csDMARD for 42.6% of cases (n=304/713), TNFi for 39.7% (n=100/252) and another tDMARD for 53.1% (n=94/177). The average doses of long-term oral corticosteroids were 7.5 mg, 6.5 mg and 7.8 mg of prednisone equivalent per day, respectively.ConclusionUsing data obtained from the EGB, this study estimated the number of patients with RA in France to be 307,612 in 2017. Approximately half of the patients identified in the EGB cohort were not treated with a DMARD. For a substantial proportion of patients receiving DMARDs, therapeutic escalation, a switch in treatment, or long-term corticosteroid co-therapy with an average daily dose greater than 5 mg were needed. Furthermore, median persistence for most targeted DMARDs was less than 2 years, and the early discontinuation rates of up to 46.6% suggest poor DMARD tolerance in many patients.This study highlights that the medical need for RA treatment is not covered by current therapeutic strategies.Table 1.Characteristics of DMARD treatments initiated between 2013–2017 in the EGB database (N=1,142)csDMARDTNFiOther targeted DMARDTreatments initiated, n (%)713 (62.4)252 (22.1)177 (15.5)Median duration of treatment, months26.718.514.6Rate of early treatment discontinuation (≤2 dispensations within 2 months of initiation), %15.510.711.9Mean treatment adherence (MPR), %80.590.871.9AcknowledgementsThis study was funded by Galapagos NV (Mechelen, Belgium). Publications management support was provided by Aspire Scientific Ltd (Bollington, UK) and funded by Galapagos NV (Mechelen, Belgium).Disclosure of InterestsCécile Gaujoux-Viala Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Inc., Janssen, Medac, Merck-Serono, Mylan, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Inc., Janssen, Medac, Merck-Serono, Mylan, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB, Jean-François Bergmann Consultant of: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Galapagos, Gilead, GSK, Lilly, Novartis, Roche, Sanofi, and Takeda, Mélanie Goguillot Employee of: Stève Consultants, who carried out the study on behalf of Galapagos, Asma Melaine Employee of: Stève Consultants, who carried out the study on behalf of Galapagos, Marie Guérin Employee of: Galapagos, Alban Edouard Employee of: Galapagos, Stève Benard Employee of: Stève Consultants, who carried out the study on behalf of Galapagos, Bruno Fautrel Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celltrion, Fresenius Kabi, Galapagos, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celltrion, Fresenius Kabi, Galapagos, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, and UCB, Grant/research support from: AbbVie, Lilly, MSD, and Pfizer

Background We investigated the association between socioclinical, inflammatory, and metabolic markers and weight gain in people with human immunodeficiency virus (HIV) on combination antiretroviral therapy (cART). Methods Individuals from the COPANA cohort of normal weight (body mass index [BMI], 18.5–24.9 [ calculated as weight in kilograms divided by height in meters squared) at cART initiation who achieved virological suppression (viral load, Results After 36 months of cART, 32 of 158 people with HIV (20%) became overweight or obese (21% female; 65% born in France and 23% born in sub-Saharan Africa; median BMI at cART initiation, 22 [interquartile range, 21–23]). After adjustment, higher BMI, originating from sub-Saharan Africa, living in a couple, and higher soluble tumor necrosis factor receptor 2 and lower adiponectin concentrations at cART initiation were associated with becoming overweight or obese. Conclusion Weight gain on cART is multifactorial. Special attention should be given to migrants from sub-Saharan Africa. Monocyte activation and adipocyte dysfunction at cART initiation affect weight regulation.

Venous thromboembolism (VTE) is a major cause of maternal morbidity during pregnancy and the postpartum period. Because there is a lack of adequate study data, management strategies for the prevention of VTE during pregnancy have mainly been deduced from case–control and observational studies and extrapolated from recommendations for non-pregnant patients. The decision for or against pharmacologic thromboprophylaxis must be made on an individual basis weighing the risk of VTE against the risk of adverse side effects such as severe bleeding complications. A comprehensive, multidisciplinary approach is often essential as the clinical scenario is made more complex by the specific obstetric context, especially in the peripartum period. As members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH), we summarize the evidence from the available literature and aim to establish a more uniform strategy for VTE risk assessment and thromboprophylaxis in pregnancy and the puerperium. In this document, we focus on women with hereditary thrombophilia, prior VTE and the use of anticoagulants that can safely be applied during pregnancy and the lactation period.

Despite a lot of research on antiphospholipid antibodies (aPL), standardization of test systems, and better definition of its clinical symptoms, the pathomechanism of this acquired autoimmune disease is not yet fully explained. Progress in treatment increased the live birth rate in 70 to 80% of women suffering from obstetric antiphospholipid syndrome (OAPS). However, still 20 to 30% will develop adverse pregnancy outcome. Lack of awareness of this disorder as the cause for pregnancy complications is very harmful to mothers and to their newborns. Complications can be avoided or minimized by proper treatment. The aim of this article is to increase the awareness of gynecologists and medical personal for OAPS.Trotz erheblicher Forschungsaktivität auf dem Gebiet Antiphospholipid-Antikörper (aPL) über drei Dekaden, verbesserter Standardisierung der Testsysteme und exakter Klassifikation der klinischen Kriterien als Basis aktueller Studien, ist der Pathomechanismus dieser erworbenen Autoimmunerkrankung noch nicht völlig aufgeklärt. Durch Fortschritte in der Behandlung betroffener Frauen ist die Lebendgeburtenrate bei Frauen mit gynäkologischem (obstetrical) Antiphospholipid-Syndrom (OAPS) auf 70–80% gestiegen. Trotzdem treten in 20–30% der Schwangerschaften schwere Schwangerschaftskomplikationen auf. Das fehlende Wissen um dieses Krankheitsbild als Ursache von Schwangerschaftskomplikationen bzw. das Nichterkennen der Symptome ist für betroffene Frauen und ihr Neugeborenes gefährlich. Komplikationen wären durch Prophylaxemaßnahmen vermeidbar bzw. zu reduzieren. Ziel dieser Übersichtsarbeit ist es, das Wissen um diese Erkrankung bei Gynäkologen und medizinischem Fachpersonal zu vertiefen und die Aufmerksamkeit für dieses Krankheitsbild zu schärfen.

Die manuelle Medizin ist durch ihre spezifische Diagnostik in der Lage, Funktionsstorungen fruhzeitig zu erkennen und sich anbahnende Strukturstorungen zu vermeiden. Auf dieser Grundlage konnen mit Anleitung praventive Ubungen gezielt eingesetzt und auch Selbstubungen lebensbegleitend am Arbeitsplatz oder zu Hause durchgefuhrt werden. In diesem Beitrag wird das Praventionsprogramm „Aktiv von Kopf bis Fus“ vorgestellt. Dazu wurden gezielt Ubungen unter manualmedizinischen Aspekten sowie mit unseren manualtherapeutischen Erfahrungen ausgesucht und zusammengestellt. Grundlage fur alle Ubungen bildet die Aktivierung der Rumpfstabilitat. Gleichzeitig werden damit die Korperwahrnehmung sowie die Konzentration und Entspannung gefordert. Durch das wiederholte Abfordern dieser Ausgangsstellung im Rahmen des Programms wird das Ziel einer automatisierten Verfugbarkeit verfolgt.

Glass ceramics obtained via a true glassy phase are homogeneous and pore free, which makes them interesting for electronic applications, especially in the GHz frequency range. We discuss the glass-ceramic system with Ba4Al2Ti10O27 as the main crystalline phase and show material properties, including dielectric properties measured up to 110 GHz. Application examples are shown for filters and antennas in the GHz frequency range. The extremely high material homogeneity makes very precise manufacturing possible and enables MHz accuracy and reproducibility in GHz applications. The high linearity of the material properties is shown as well and makes high power applications, e.g., in cell phone base stations, possible. Also, applications in the MHz range are discussed.

Azinuszellkarzinome des Pankreas sind biologisch aggressive Tumoren, die nur unzulanglich auf derzeit verfugbare Therapien ansprechen. Der molekulare Hintergrund von Azinuszellkarzinomen ist weitgehend unbekannt, Vorlauferlasionen wurden bislang nicht identifiziert.

Vesivirus 2117 (VV-2117) has been recently described as a contaminant of cell culture operations in several biologics manufacturing facilities. VV-2117 has been poorly studied and little information exists about its biology, pathogenicity and infectivity range in cell culture settings. In this study we evaluated the potential in vitro viral infectivity of VV-2117 using a range of established mammalian cell lines from various species, the effectiveness of virus amplification in CHO-K1 cells at differing infection levels, and the relative sensitivity of two test methods (cytopathic effect [CPE] and polymerase chain reaction [PCR]) to detect infection and viral amplification. Of eight cell culture systems studied, two originating from hamster (CHO-K1 and BHK-21) and one from canine (MDCK) were positive for CPE and also showed a marked increase of viral RNA in a reverse transcriptase quantitative PCR (RT-qPCR) test. CHO-K1 cell cultures inoculated at 10, 1 and 0.1 genome copies per cell (gc/cell) showed both CPE and amplification of VV-2117 RNA, indicating that infection had occurred in these cultures. CHO-K1 cultures inoculated at 0.01, 0.001, 0.0001 and 0.00001 gc per cell showed neither CPE nor VV-2117, indicating that infection had not occurred. Therefore, the minimum dose necessary for infection of CHO-K1 cells was approximately 0.1 genome copies per cell. At any infection level where VV-2117 amplification was observed by RT-qPCR, the cultures also showed CPE. There was no low-level infection that could be detected by RT-qPCR without developing signs of CPE. However, the RT-qPCR assay appeared more sensitive in that it detected VV-2117 infection earlier than the onset of observable CPE.

A Vigna radiata (L.) Wilczek popularmente conhecida como mungo-verde ou feijão-moyashi é um membro da família das leguminosas Fabaceae. Esta leguminosa é de fácil adaptação nos climas tropicais e subtropicais, sendo utilizada principalmente como suplemento proteico em diferentes pratos utilizando a farinha ou a leguminosa bruta, devido suas fontes de minerais, vitaminas, proteínas e baixas calorias o que o tornou popular no Brasil pela procura de alimentação saudável. Neste sentido, o objetivo do trabalho foi realizar uma avaliação química e nutricional do broto de feijão-moyashi e da farinha produzida a partir dele. Para isso o alimento adquirido da Chácara Paraíso, passou inicialmente por uma análise macroscópica e foi submetido a várias determinações como: umidade, proteínas, lipídios, fibras e minerais, obtendo os seguintes resultados: 94,89%, 1,31%, 0,038%, 1,46% e 0,266%, respectivamente para o broto de feijão e 16,10%, 25,82%, 0,74%, 28,51% e 5,20%, para a farinha. Os dados de carboidratos foram obtido por diferença, 2,03% para o broto de feijão e 23,63% para a farinha. A partir dos dados obtidos comparou-se os resultados com os estabelecidos pela tabela TACO, e ainda com outras farinhas comerciais. Os valores nutricionais encontrados para o broto de feijão se mostraram próximos aos valores estabelecidos. Já a farinha do broto de feijão-moyashi se destacou pela grande quantidade de proteínas, baixo teor lipídico e grande quantidade de fibras, sendo assim, uma opção saudável para indivíduos veganos e vegetarianos por ser muito nutritiva e economicamente acessível.

Patients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments.Between June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days.Three hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75-6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine.This study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.

Objectives HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. Methods In this cross-sectional study, 53 HIV-infected male individuals with a mean (± standard deviation) age of 49 ± 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate (DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high-resolution peripheral quantitative computed tomography (HR-p QCT). Results Volumetric trabecular bone density was 17% lower in the tibia (P < 10−4) and 16% lower in the radius (P < 10−3) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume (BV/TV) and trabecular number were each 13% lower (P < 10−4 for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/TV and trabecular thickness were each 13% lower (P < 10−3 and 10−2, respectively). Cortical thickness was not different between the two groups. Conclusions The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients.

Objective To evaluate the effectiveness of the Patient Education Programme Parkinson (PEPP) in patients with Parkinson’s disease (PD) in a randomized controlled trial and its sustainability after a 3-month follow-up. Methods Thirty-nine patients were allocated to the intervention group and participated in the 8-week PEPP. Thirty-four patients were assigned to the control group undergoing routine neurological care. Primary outcome was the Parkinson’s disease quality of life questionnaire (PDQ-39) measured at baseline, directly after the programme and at 3-month follow-up. Secondary outcomes assessed coping behavior, psychosocial strain, health-related quality of life (HrQoL), sense of coherence, self-efficacy, anxiety and depression. Results A significant effect for the intervention group on the PDQ-39 ( p = .001) and on the active problem-oriented coping subscale of the Freiburg Coping with disease questionnaire ( p = .027) was found at 3-month follow-up. Conclusion In this study the PEPP improved disease-specific HrQoL and helped patients to cope with the disease.

Resume Propos Le diagnostic differentiel entre la maladie tuberculose (granulomatose la plus frequente a l’echelle mondiale) et la sarcoidose (granulomatose rare) est important, car les traitements different completement. Methodes Nous avons evalue prospectivement la presence de granulomes epithelioides a la biopsie de glandes salivaires accessoires (BGSA), critere d’orientation habituel pour le diagnostic de sarcoidose, chez des patients atteints de tuberculose prouvee et vus consecutivement. Resultats Sur notre echantillon de 65 patients, 10,8 % des patients tuberculeux avaient des granulomes epithelioides sans necrose caseeuse sur leur BGSA, independamment de la localisation de la tuberculose, du statut VIH du patient ou du caractere bacillifere de l’infection. Conclusion La presence de granulomes epithelioides a la BGSA ne permet donc pas d’eliminer une maladie tuberculose lorsque le clinicien hesite entre cette affection et une sarcoidose.

Pankreaskarzinome bzw. Cholangiokarzinome umfassen diverse Neoplasien unterschiedlicher Differenzierung, Atiologie und Pathogenese. In dieser Arbeit soll die Atiologie und Pathogenese der jeweils haufigsten malignen Tumoren des Pankreas und der Gallengange, des duktalen Adenokarzinoms des Pankreas und der vorwiegend duktal differenzierten intra- und extrahepatischen Cholangiokarzinome charakterisiert werden. Grundlage hierfur sind die derzeit verfugbare Fachliteratur sowie eigene Erkenntnisse. Duktale Pankreaskarzinome und Cholangiokarzinome zeigen histologisch und immunhistochemisch breite Uberlappungen, konnen jedoch anhand der makroskopischen Befundausdehnung und ggf. anhand ihrer morphologisch gut charakterisierten Vorlauferlasionen als eigenstandige Tumorentitaten klassifiziert werden, wobei Cholangiokarzinome daruber hinaus in extrahepatische und intrahepatische Karzinome subklassifiziert werden. Wie sich durch neuere Untersuchungen abzeichnet, bestehen zwischen diesen Subgruppen auch deutliche molekulare Unterschiede. Trotz augenscheinlicher Ahnlichkeit der Tumorentitaten ist eine exakte Klassifikation somit essenziell, v. a. im Hinblick auf die Entwicklung innovativer, zielgerichteter Therapieansatze.

Thrombozyten besitzen wichtige Funktionen bei Blutstillung, Gefasreparatur und entzundlichen Prozessen. Im ersten Abschnitt dieses Kapitels wird auf die Physiologie und Pathophysiologie der Thrombozyten eingegangen. Thrombozytenfunktionsstorungen konnen sowohl erworben als auch angeboren sein. Bei den angeborenen Thrombozytenfunktionsstorungen werden Rezeptordefekte, Defekte des Zytoskeletts sowie Storage-Pool-Defekte der α- oder β-Granula unterschieden. Im darauffolgenden Abschnitt wird ein Uberblick uber die hereditaren Thrombozytopenien gegeben, eine Gruppe seltener Erkrankungen sehr unterschiedlicher Pathophysiologie. Kriterien zur Diagnose sind die Unterscheidung zwischen syndromalen und nicht-syndromalen Formen, Thrombozytengrose, klinische Merkmalskombinationen und krankheitsspezifische Laborparameter. Die Immunthrombozytopenie ist eine Blutungskrankheit mit vorzeitigem Abbau und defekter Produktion von Thrombozyten. Sie ist eine Ausschlussdiagnose. Die Behandlung ist von der Erfahrung des Klinikers abhangig und orientiert sich an nationalen und internationalen Richtlinien. Thrombozytosen sind im Kindesalter im Allgemeinen ohne klinische Relevanz. Hiervon abzugrenzen sind bei Symptompersistenz uber Monate und/oder Auftreten von Gefasverschlussen oder Blutungszeichen die sehr seltenen hereditaren Thrombozytosen infolge genetischer Veranderungen des TPO- oder MPL-Rezeptors oder hamatologische Erkrankungen (Thrombozythamien).

Die Sektorengrenzen zwischen ambulanten und stationaren Leistungsanbietern konnen Bruche in der Versorgungskontinuitat verursachen. Die Deutsche Gesellschaft fur Neurologie (DGN), die Berufsverbande Deutscher Nervenarzte, Neurologen und Psychiater (BVDN, BDN und BVDP) sowie die Kassenarztliche Bundesvereinigung (KBV) und das Zentralinstitut fur die kassenarztliche Versorgung in der Bundesrepublik Deutschland (ZI) haben deswegen beim IGES Institut ein Gutachten in Auftrag gegeben, um mit einer analytisch-empirischen Datengrundlage die gegenwartige sehr kontroverse gesundheitspolitische Diskussion starker daten- und faktenbasiert zu fuhren. Die Versorgung von Patienten mit Multipler Sklerose, Demenz und Schizophrenie wurden aus sektorubergreifender Perspektive analysiert. Die Grundlage der Untersuchung bildeten umfassende patientenbezogene Daten der Barmer-GEK Krankenkasse, die routinemasig dokumentiert wurden. Hier werden die Ergebnisse zur Versorgung von Patienten mit Demenz (n = 130 952 im Jahr 2010) dargestellt. Facharzte fur Neurologie, Nervenheilkunde und Psychiatrie waren im Jahr 2010 nur zu etwa 42,3 % an der Behandlung von Demenzpatienten beteiligt. Noch geringer war die Beteiligung der Facharzte bei der Erstdiagnose (25 %). Die Beteiligung von Facharzten bei der Versorgung von Patienten mit Demenz zeigt erhebliche regionale Unterschiede. Antidementiva werden haufiger von Facharzten und seltener von Hausarzten verordnet. Demenzbedingte stationare Krankenhausaufenthalte sind insgesamt selten (7 %), variieren jedoch regional teilweise deutlich. Dabei bestehen kein Zusammenhang mit dem Bettenangebot und nur ein schwacher Zusammenhang mit der Anzahl der ambulant tatigen Haus- und Facharzte einer Region. Die Ergebnisse des Gutachtens unterstreichen die Notwendigkeit einer starker sektorenubergreifenden Versorgungsplanung.

Die manuelle Medizin sollte sich verstarkt dem fruhzeitigen Erkennen von Ursachen schmerzauslosender Schadigungen durch Fehl- und Uberbelastungen am Bewegungssystem im Arbeitsprozess oder taglichen Lebensgewohnheiten widmen. Erhohte Muskelspannungen oder abweichende Bewegungsmuster haben Strukturanderungen zur Folge. Dies fuhrt zum Schmerz. Dieser fuhrt wiederum zu Veranderungen der Motorik. In beiden Fallen sprechen wir von Dysfunktionen bzw. von Bewegungskontrollstorungen, die moglicherweise durch orientierende und gezielte manuelle Untersuchungen im Entstehungsstadium erfasst werden konnen. Unter diesen Aspekten wurde ein praventiver manualmedizinischer Check-up fur Laufer entwickelt, der hier vorgestellt wird und moglicherweise beispielgebend fur andere Zielgruppen sein kann.

Background: Preoperative placement of self-expanding metal stents is used in patients with obstructing colon carcinoma to prevent an emergency operation. The perceived benefits remain the subject of discussion. The data-evaluating function and complications of stents in relation to radiological position are limited. Methods: Patients receiving a preoperative stent between 2003 and 2013 were retrospectively analysed in this single-centre study. We analysed radiological deployment, eccentricity and angulation of the stent directly after placement. Endpoints were clinical success (resolution of ileus), complications needing non-elective surgery (blow-out, perforation, persistent ileus, dislocation) and other complications (bleeding, infiltrate). Associations were corrected for other potential influences. Results: Eighty-two patients were included. In 22 patients (26.8%), the stent was placed proximal to the splenic flexure. Clinical success was present in 85.4%. Twenty-two patients (26.8%) had a complication of which 16 (19.5%) underwent urgent surgery for insufficient functioning of the stent; there were two blow-outs (2.4%). A more symmetrically placed stent was associated with clinical success (p = 0.042), with large overlap between groups. However, no association was found with non-elective surgery or complications. Also, angulation and deployment were unassociated with these outcomes. Conclusions: We could not establish an association between symmetry, angulation or deployment of self-expandable colonic stents with clinical success and complications.

Essentials In venous thromboembolism (VTE), it is uncertain if enoxaparin should be given twice or once daily. We compared the 15- and 30-day outcomes in VTE patients on enoxaparin twice vs. once daily. Patients on enoxaparin once daily had fewer major bleeds and deaths than those on twice daily. The rate of VTE recurrences was similar in both subgroups. SummaryBackground In patients with acute venous thromboembolism (VTE), it is uncertain whether enoxaparin should be administered twice or once daily. Methods We used the RIETE Registry data to compare the 15- and 30-day rates of VTE recurrence, major bleeding and death between patients receiving enoxaparin twice daily and those receiving it once daily. We used propensity score matching to adjust for confounding variables. Results The study included 4730 patients: 3786 (80%) received enoxaparin twice daily and 944 once daily. During the first 15 days, patients on enoxaparin once daily had a trend towards more VTE recurrences (odds ratio [OR], 1.79; 95% confidence interval [CI], 0.55–5.88), fewer major bleeds (OR, 0.42; 95% CI, 0.17–1.08) and fewer deaths (OR, 0.32; 95% CI, 0.13–0.78) than those on enoxaparin twice daily. At day 30, patients on enoxaparin once daily had more VTE recurrences (OR, 2.5; 95% CI, 1.03–5.88), fewer major bleeds (OR, 0.40; 95% CI, 0.17–0.94) and fewer deaths (OR, 0.58; 95% CI, 0.33–1.00). On propensity analysis, patients on enoxaparin once daily had fewer major bleeds at 15 (hazard ratio [HR], 0.30; 95% CI, 0.10–0.88) and at 30 days (HR, 0.16; 95% CI, 0.04–0.68) and also fewer deaths at 15 (HR, 0.37; 95% CI, 0.14–0.99) and at 30 days (HR, 0.19; 95% CI, 0.07–0.54) than those on enoxaparin twice daily. Conclusions Our findings confirm that enoxaparin prescribed once daily results in fewer major bleeds than enoxaparin twice daily, as suggested in a meta-analysis of controlled clinical trials.

Resume Propos Au cours d’une hospitalisation en medecine interne, les prescriptions therapeutiques des patients sont souvent modifiees. Nous avons etudie le devenir de ces modifications therapeutiques au decours de l’hospitalisation. Methodes Quatre-vingt-quatre patients ayant une prescription au long cours et un medecin traitant ont ete inclus le jour de leur sortie d’hospitalisation d’un service de medecine interne parisien. Leurs traitements d’entree et de sortie ont ete determines d’apres les comptes-rendus d’hospitalisation, et les patients ont ete contactes deux mois apres leur sortie afin d’analyser les eventuelles differences de prescriptions observees depuis la sortie de l’hopital. Resultats Les traitements a l’entree ont ete le plus souvent conserves, avec 17,7 % de traitements retires et 7 % de changement de traitement. Deux mois apres la sortie, les modifications etaient maintenues dans 85 % des cas, l’ordonnance de sortie etait renouvelee sans changement pour 77 % des patients. Les antihypertenseurs etaient la classe la plus souvent modifiee durant l’hospitalisation, avec des modifications maintenues a 65 %. Les antalgiques etaient l’autre classe la plus souvent modifiee, avec un taux de maintien global de 75 %. Les modifications therapeutiques expliquees dans les comptes-rendus d’hospitalisation avaient un taux de maintien significativement plus eleve que celles non expliquees (100 % versus 79 %, IC95 % de la difference [0,09–0,27] ; p Conclusion Les modifications de traitements decidees au cours d’une hospitalisation en medecine interne et prescrites a la sortie sont tres frequemment poursuivies en ambulatoire deux mois apres la sortie, en particulier lorsqu’elles ont ete expliquees dans le compte-rendu d’hospitalisation.

ZusammenfassungAngeborene Thrombozytopathien sind komplexe Erkrankungen. Zur optimalen Blutungsprophylaxe und -behandlung empfehlen wir eine Abklärung und Diagnose der zugrunde liegenden Funktionsstörung. Dazu steht eine interdisziplinäre Leitlinie zur Verfügung (AWMF # 86–003 S2K; Hämostaseologie 2014; 34: 201–212).Die Behandlung ist auf den Defekt, die Thrombozytenzahl, das Lebensalter und die klinischen Umstände abzustimmen. Die Transfusion von Thrombozyten allein kann wegen der damit verbundenen Risiken unangemessen sein. Empfohlen wird ein stufenweiser und individualisierter Behandlungsplan. Antifibrinolytika sind generell anwendbar, besonders bei der Quebec-Erkrankung. Desmopressin ist älteren Kindern vor behalten und vor allem zur Behandlung der Storage- Pool-Erkrankungen und nicht klassifizierter Defekte geeignet. Rekombinanter FVIIa ist zwar nur für die Behandlung der Thrombasthenie Glanzmann mit Alloantikörpern zugelassen, wird jedoch in der klinischen Praxis auch bei Thrombozytendefekten mit schwerer Blutungsneigung eingesetzt. Das Ziel dieser Leitlinie ist die Behandlung von Patienten mit angeborenen Thrombozytenfunktionsstörungen bestmöglich zu unterstützen.

Pancreatic acinar cell carcinomas are biologically aggressive neoplasms for which treatment options are very limited. The molecular mechanisms of tumor initiation and progression are largely not understood and precursor lesions have not yet been identified. In this study, pancreatic acinar cell carcinomas were cytogenetically characterized as well as by molecular and immunohistochemical analyses. Corresponding investigations were carried out on pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms augmented by functional analyses. We show that pancreatic acinar cell carcinomas display a microsatellite stable, chromosomal unstable genotype, characterized by recurrent chromosomal imbalances that clearly discriminate them from pancreatic ductal adenocarcinomas and neuroendocrine neoplasms. Based on findings obtained from comparative genomic hybridization, candidate genes could be identified, such as deleted in colorectal cancer (DCC) and c-MYC. Furthermore, several therapeutic targets were identified in acinar cell carcinomas and other pancreatic neoplasms, including epidermal growth factor receptor (EGFR), L1 cell adhesion molecule (L1CAM) and heat shock protein 90 (HSP90). Moreover, L1CAM was shown to play a significant role in the tumorigenesis of pancreatic ductal adenocarcinoma. Functional analyses in cell lines derived from pancreatic neuroendocrine neoplasms revealed promising anti-tumorigenic effects using EGFR and HSP90 inhibitors affecting the cell cycle and in the case of HSP90, regulating several other oncogenes. Finally, based on mutational analyses of mitochondrial DNA, molecular evidence is provided that acinar cell cystadenomas (or better cystic acinar transformation) represent non-clonal lesions, suggesting an inflammatory reactive non-neoplastic nature.

Relationships between species diversity and genetic diversity, the two most important elements of biodiversity, have recently attracted considerable interest in the field of community genetics. The present study contributes to this issue by addressing three questions that seem to have been ignored so far, namely whether the use of (a) different diversity measures, of (b) different components of diversity, and of (c) different genetic traits may lead to different assessements of speciesgenetic diversity relationships. For this purpose, data on species composition and genetic traits were collected from the natural regeneration of nine forest communities, which consist of three pure and six mixed tree stands located in the Thuringian forest area. The genetic traits comprised one DNA (AFLP) and five isozyme traits all of which were determined in all species. In contrast to other studies, the species diversity was determined for two components, SD (species diversity) and NeS (effective number of genetically distinct species), and the genetic diversity was determined for three components, TSGD (the transspecific genetic diversity taken over all species of a community), ISGD and NGS (each describing a special average of intraspecific genetic diversity). Each component was quantified by measures of diversity representing four orders of the Renyi/Hillfamily. The orders correspond to the degree to which prevalence of types is considered in the diversity measure (at the lowest order, known as richness, prevalence is disregarded, with increasing order, the diversity measure reports prevalent types only). In our data, the diversity measured for each genetic trait separately showed a great range of variation across traits and components of diversity even in the same stand. The choice of the diversity component thus turned out to have a substantial effect on the assessment of the level of genetic diversity within stands. This prompted more detailed studies of the relationships between species and genetic diversity. Relationships were quantified with the help of the coefficient of co-variation, and the statistical significance of the co-variations was verified through permutation tests. The co-variations between SD and TSGD were found to be generally positive and in most cases significant, but the co-variation declined with increasing orders of diversity for most of the genetic traits. In contrast, the co-variation between SD and ISGD was not consistent for the four orders of diversity. In particular, the co-variations for the highest order were found to be negative for all traits. The results of our explorative study thus demonstrate that the assessment of levels of genetic diversity within stands as well as species-genetic interrelations critically depend on the choice of the diversity component, of the order of diversity, and of the genetic trait. These observations lend support to different and even opposing hypotheses on the processes potentially generating species-genetic relationships. Therefore, strategies in the conservation of biodiversity, for example, are suggested to be related more specifically to the components and orders of diversity to be safegarded and to consider the functions of genetic traits in relation to adaptationally relevant environmental factors.

Neuroendocrine neoplasms of the pancreas and the gastrointestinal tract are heterogeneous regarding etiology (e.g. sporadic or hereditary), histomorphology, hormone expression, hormone-related functional activity and especially the malignant potential. In neuroendocrine neoplasms the biopsy-based diagnosis plays an important role for the clinical management of patients. The diagnosis most importantly relies on the differentiation (e.g. organoid versus diffuse growth patterns) and the grading of tumors. The latter is based on the proliferation activity as determined by Ki-67 immunostaining and mitotic count and results in the current tumor classification into neuroendocrine tumors G1, neuroendocrine tumors G2 or neuroendocrine carcinomas G3. Occasionally, tumors may show mixed differentiation containing a non-neuroendocrine cancer component. The neuroendocrine markers synaptophysin and chromogranin A are recommended for the immunohistochemical confirmation of the diagnosis. Furthermore, biopsy material can be used to investigate the expression of therapy-related markers, such as somatostatin receptor-2A. Moreover, if needed, the expression of transcription factors and hormones can be determined to obtain information on the possible site of origin of metastatic neuroendocrine neoplasms or to determine the syndrome-inducing hormone in functionally active neuroendocrine neoplasms. Finally, using the stomach as an example, biopsies may also be successfully used to investigate neuroendocrine precursor lesions which may harbor prognostic significance.

Resume Introduction L’hemorragie massive reste une cause importante de mortalite dans les pays developpes, particulierement en obstetrique, chez le polytraumatise et dans les chirurgies majeures. Le facteur VII active recombinant (rFVIIa) (Novoseven®) a ete developpe pour le traitement substitutif des hemophiles, mais etait actuellement utilise dans d’autres indications de saignement aigu. L’objectif de cette etude etait d’evaluer le respect des criteres d’utilisation hors AMM du rFVIIa selon les groupes definis par l’Afssaps, dans les hopitaux de l’assistance publique a Paris (AP–HP) en 2010. Patients et methodes Nous avons retrospectivement contacte les services d’anesthesie-reanimation des centres ayant une activite en obstetrique, d’accueil de polytraumatises, de chirurgie cardiaque, hepatique et pediatrique pour recuperer tous les dossiers d’utilisation hors AMM du rFVIIa en 2010. La qualite de l’indication et de son utilisation a ete analysee sur la base des recommandations francaises ou europeennes ou selon la litterature existante dans les domaines consideres. Trois categories de prescriptions ont ete etablies : conforme, acceptable et non conforme. Resultats Sur les 59 patients ayant recu du rFVIIa hors AMM en 2010, 49 prescriptions ont pu etre analysees. L’indication et le moment d’administration etaient conformes dans 100 % des prescriptions pour le polytraumatisme et 83 % des prescriptions pour les hemorragies du postpartum. Les criteres biologiques etaient remplis dans deux tiers des prescriptions. La prescription a ete jugee conforme ou acceptable dans 82 % des cas, toutes indications confondues. Conclusion Dans la grande majorite des cas, les prescriptions de rFVIIa, utilise hors AMM a l’AP–HP en 2010, respectaient les recommandations en vigueur.

ObjectiveWe evaluated the feasibility of using mobile device technology to allow students to record their own psychomotor skills so that these recordings can be used for self-reflection and formative evaluation.MethodsStudents were given the choice of using DVD recorders, zip drive video capture equipment, or their personal mobile phone, device, or digital camera to record specific psychomotor skills. During the last week of the term, they were asked to complete a 9-question survey regarding their recording experience, including details of mobile phone ownership, technology preferences, technical difficulties, and satisfaction with the recording experience and video critique process.ResultsOf those completing the survey, 83% currently owned a mobile phone with video capability. Of the mobile phone owners 62% reported having email capability on their phone and that they could transfer their video recording successfully to their computer, making it available for upload to the learning management system. Viewing the video recording of the psychomotor skill was valuable to 88% of respondents.ConclusionsOur results suggest that mobile phones are a viable technology to use for the video capture and critique of psychomotor skills, as most students own this technology and their satisfaction with this method is high.

Resume Introduction La lymphadenite histiocytaire necrosante (maladie de Kikuchi-Fujimoto) est une entite clinico-pathologique rare caracterisee par l’association d’une lymphadenopathie cervicale posterieure bien limitee et d’une fievre, touchant principalement les femmes jeunes. Observation Nous rapportons le cas d’un patient africain de 41 ans presentant une maladie de Kikuchi-Fujimoto atypique car compliquee d’un lupus cutane, d’un syndrome d’activation macrophagique et d’une meningite lymphocytaire. Une meningite tuberculeuse, initialement evoquee en raison de l’origine ethnique et de la presentation clinique, etait eliminee par l’histologie ganglionnaire caracteristique de maladie de Kikuchi-Fujimoto, la negativite des prelevements microbiologiques, l’evolution clinique et la decouverte d’une integration virale genomique d’ADN d’HHV6. Conclusion L’association d’adenopathies cervicales, d’un syndrome d’hemophagocytose, d’une meningite lymphocytaire et d’une integration genomique d’HHV-6 doit faire evoquer une maladie de Kikuchi.

We report an unusual observation of central nervous system (CNS) lymphoma in a 60-year-old woman with systemic lupus erythematosus and fatal outcome.The patient had systemic erythematosus lupus for 7 years, treated with mycophenolate mofetil and developed lymphocytic meningitis in 2015 associated to the presence of EBV in the cerebrospinal fluid and a necrotic vermis' lesion. Diagnosis of large B-cell lymphoma was histologically confirmed from stereotaxic biopsy, shortly before she died from neurological complications.Even though the current association is unusual, lymphocytic meningitis with hypoglycorrachia in patients with systemic lupus erythematosus may reveal CNS lymphoma and diagnosis confirmation requires stereotaxic biopsy in order not to delay specific therapeutic management.