bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflections on Thyroid Autoimmunity: A Personal Overview from the Past into the Future
Authors: Rapoport Basil , McLachlan Sandra
Published: October 2018

After investigating thyroid autoimmunity for more than 40 years, we present a personal perspective on the field. Despite effective therapies for Graves’ hyperthyroidism and Hashimoto’s thyroiditis, cures are elusive. Novel forms of therapy are being developed, such as small molecule inhibitors of the TSH receptor (TSHR), but cure will require immunotherapy. This goal requires advances in understanding the pathogenesis of thyroid autoimmunity, the ‘keys’ for which are the thyroid antigens themselves. Presently, however, greater investigative focus is on non-thyroid specific immune cell types and molecules. Thyroid autoantigens are the drivers of the autoimmune response, a prime example being the TSHR. In our view, the TSHR is the culprit as well as the victim in Graves’ disease because of its unique structure. Unlike the closely related gonadotropin receptors, the TSHR cleaves into subunits and there is strong evidence that its shed extracellular A-subunit, not the holoreceptor, is the major antigen driving pathogenic thyroid stimulating autoantibodies (TSAb) development. There is no Graves’ disease of the gonads. Studies of potential antigen-specific immunotherapies require an animal model. Such models have been developed in which TSAb can be induced or, more importantly, arise spontaneously. Not appreciated until recently by thyroid investigators is that B cell surface autoantibodies are highly efficient ‘antigen receptors’ and the epitope to which an autoantibody binds influences antigen processing and which peptide is presented to T cells. These animal models and recombinant human autoantibodies cloned from Graves’ and Hashimoto’s B cells (plasma cells) are available for study by future generations.
StärkeR – Strukturierte Delegation ärztlicher Leistungen im Rahmen konzeptionsgeregelter Kooperation in der Versorgung von Patienten mit entzündlich rheumatischen Erkrankungen(Förderkennzeichen: 01NVF17004)
Authors: Braun Jürgen , Krause Dietmar
Published: October 2018

Patienten mit entzündlich-rheumatischen Erkrankungen sind hierzulande zumindest zum Teil nicht bestmöglich versorgt, weil es nach dem letzten Memorandum der DGRh an vielen Orten nicht genug internistische Rheumatologen gibt. Diese Situation könnte durch die Übernahme von ausgewählten Aufgaben der Patientenversorgung durch qualifizierte rheumatologische Fachassistentinnen (RFA) verbessert werden. Kernpunkt des StärkeR-Projekts ist die Evaluation der strukturierten Delegation ärztlicher Leistungen an rheumatologische Fachassistent(inn)en. Dafür werden 800 Patienten mit stabilem Verlauf einer rheumatoiden Arthritis oder einer Psoriasisarthritis in 20 Zentren in Nordrhein-Westfalen und Niedersachsen im Rahmen einer randomisierten, multizentrischen Studie entweder in der neuen Versorgungsform mit Delegation an RFAs oder mit der Standardversorgung behandelt. Beide Versorgungsformen werden mithilfe der Differenz zwischen Beginn und Ende des Evaluationszeitraumes sowohl der Krankheitsaktivität als auch der gesundheitsbezogene Lebensqualität verglichen. An dem Projekt sind folgende Einrichtungen und Kooperationspartner beteiligt: Rheumazentrum Ruhrgebiet als Krankenkasse die BARMER GEK, das Koordinierungszentrum für Klinische Studien Marburg und die Abteilung für Medizinische Informatik, Biometrie und Epidemiologie der Ruhr-Universität Bochum.
Management von Viszeralarterienaneurysmen unter besonderer Berücksichtigung der Organperfusion – Erfahrungen über mehr als 20 Jahre
Authors: Pfister Karin , Kasprzak Piotr , Oikonomou Kyriakos , Apfelbeck Hanna , Derwich Wojciech , Uller Wibke , Stehr Alexander , Schierling Wilma
Published: October 2018

Einleitung Viszeralarterienaneurysmen (VAA) sind selten und werden meist als Zufallsbefund entdeckt. Die Indikation zur Behandlung besteht bei symptomatischen Patienten, Pseudoaneurysmen sowie bei asymptomatischen Patienten bei einer Größe von mehr als 2,5 cm (Viszeralarterienaneurysmen) bzw. mehr als 3 cm (Nierenarterienaneurysmen), bei Schwangeren und vor einer Lebertransplantation. Neben der erfolgreichen, operativen oder endovaskulären Ausschaltung des Aneurysmas ist der Erhalt der Organperfusion wichtig. Die folgende Arbeit stellt das Management von Viszeralarterienaneurysmen und die Erfahrungen über einen Zeitraum von mehr als 20 Jahren dar und zeigt einen Behandlungsalgorithmus auf.

Patienten Zwischen 1995 und 2018 wurden am Universitätsklinikum Regensburg 179 VAA diagnostiziert (84 Männer, 95 Frauen, medianes Alter 62 (18 – 87) Jahre). 113-mal (63%) lag ein Milzarterien-, 21- bzw. 22-mal (je 12%) ein Nieren- und Leberarterienaneurysma vor. 14-mal (8%) fand sich ein Aneurysma der gastropankreatikoduodenalen Arkade, 9-mal (5%) der A. mesenterica superior/inferior. 110 (62%) Patienten wurden bei fehlender Behandlungsindikation nachbeobachtet, 34 (19%) offen und 35 (19%) endovaskulär behandelt. Bei allen wurde präoperativ eine Bildgebung, meist mit CT-Angiografie durchgeführt.

Ergebnisse Von den 69 therapierten Patienten mit VAA wurden 51 (74%) elektiv und 18 (26%) notfallmäßig wegen Blutung behandelt. 16 Notfallpatienten wurden endovaskulär, 2 offen chirurgisch behandelt. Postoperativ fand sich 2-mal eine partielle Minderdurchblutung der Leber, die folgenlos blieb. Einmal musste Dünndarm teilreseziert werden. 32/51 (63%) elektive VAA wurden offen, 19/51 (37%) endovaskulär therapiert. Leber und Darm blieben bei beiden Verfahren intakt. Bei den 21 Milz- und Nierenarterienaneurysmen wurde operativ 4-mal die Milz, 1-mal die Niere komplett entfernt, zusätzlich fanden sich postoperativ 3 Nierenteilinfarkte (gesamt 8/21 [38%]). Postinterventionell zeigte sich bei den 14 Milz- und Nierenarterienaneurysmen 2-mal ein Milz- und 3-mal ein Nierenteilinfarkt, 2-mal wurde die Milz später entfernt (gesamt 7/14 [50%]). Zum Nachweis der Organperfusion wurde die CT-Angiografie, vor allem aber der Kontrastmittelultraschall (CEUS) durchgeführt.

Schlussfolgerung Bei Blutung und Pseudoaneurysmen ist die endovaskuläre Therapie das Vorgehen der ersten Wahl. Bei elektiven Eingriffen spielt die sorgfältige Planung im Hinblick auf die technische Machbarkeit der Aneurysmaausschaltung, aber auch der Erhalt der Organperfusion, vor allem bei Milz- und Nierenarterienaneurysmen, eine entscheidende Rolle. Eine bildgebende Nachsorge, vorzugsweise mit Ultraschall, wird dringend empfohlen. Vor bzw. nach Splenektomie oder bei funktioneller Asplenie sind entsprechende Impfungen vorgeschrieben.
Heparanase induces tissue factor pathway inhibitor expression and extracellular accumulation in endothelial and tumor cells
Authors: Nadir Yona , Brenner Benjamin , Gingis-Velitski Sveta , Levy-Adam Flonia , Ilan Neta , Zcharia Eyal , Nadir Erez , Vlodavsky Israel
Published: October 2018

Heparanase activity is implicated in cell invasion, tumor metastasis and angiogenesis. Recently, we have reported that heparanase stimulates tissue factor (TF) expression in endothelial and cancer cells, resulting in elevation of coagulation activity. We hypothesized that heparanase regulates other coagulation modulators, and examined the expression and localization of tissue factor pathway inhibitor (TFPI) following heparanase over-expression or exogenous addition. Primary human umbilical vein endothelial cells (HUVEC) and human tumor-derived cell lines were incubated with heparanase, or were stably transfected with heparanase gene-constructs, and TFPI expression and secretion were examined. Heparanase over-expression or exogenous addition stimulated TFPI expression by 2–3 folds. TFPI accumulation in the cell culture medium exceeded in magnitude the observed induction ofTFPI gene transcription reaching 5– to 6-fold increase. Extracellular accumulation of TFPI was evident already 60 min following heparanase addition, prior toTFPI protein induction, and correlated with increased coagulation activity. This effect was found to be independent of heparanase enzymatic activity and interaction with heparan-sulfate, and correlated with reduced TFPI levels on the cell surface. Data were verified in heparanase transgenic mice tissues and plasma. Interaction between heparanase and TFPI was evident by co-immunoprecipitation. Interaction of heparanase with TFPI resulted in its displacement from the surface of the vascular endothelium and in increased pro-coagulant activity. Thus, heparanase facilitates blood coagulation on the cell surface by two independent mechanisms:dissociation ofTFPI from the vascular surface short after local elevation of heparanase levels, and subsequent induction of TF expression.
Interaction of thyroid hormone with brown adipose tissue
Authors: Hankir M. , Krause K. , Tönjes A. , Fenske W. K. , Sabri O. , Hesse S. , Steinhoff K. G.
Published: October 2018

Brown adipose tissue (BAT) plays an important role in regulating core-body temperature in various species including man. [18F]FDGPET/ CT imaging first revealed the presence of metabolically active BAT depots and that decreased BAT function is associated with various metabolic conditions. Thyroid hormone (TH) in concert with sympathetic nervous system signalling (SNS) stimulates BAT thermogenesis and thyroid disorders result in dysfunctional BAT. Currently, research is focussing not only on BAT regulation but also on browning of white adipose tissue (WAT) to BAT beige adipose tissue (BeAT) in order to develop novel treatments for human obesity and related conditions. While [18F]FDG-PET/ CT imaging is continuing to provide valuable insights into BAT and BeAT function in health and disease, there is a pressing need to develop alternative radiotracers that reliably track their activity in vivo. As a result it is expected that preclinical micro PET/CT investigations of BAT and BeAT will gain in prominence.

The aim of this short review is to i) describe fundamentals in BAT biology, ii) highlight some of the clinical and preclinical studies performed on humans and rodents with a focus on TH, BAT and PET/CT, and iii) bridge these data with our own studies within the DFG thyroid transact priority program.
Is thyroid surgery performed too often in Germany?
Authors: Verburg F. A.
Published: October 2018

Thyroid surgery is one of the more common surgical procedures in Germany. This is in contrast with the situation in some other countries, where this procedure is performed comparatively rarely. In this paper the number of thyroid surgeries in Germany is compared with other western countries (Netherlands, USA, England). In contrast to e. g. the USA and England the number of thyroid surgeries in Germany is declining, however with approximately 109/100 000/year in 2012 is still elevated (Netherlands: 16/100 000/year, USA: at least 42/100 000/year, England: at least 27/100 000/year).

Possible contributing factors to this higher number of thyroid surgeries in Germany are explored. These factors include iodine deficiency, the frequent use of advanced diagnostics such as ultrasound, insufficient use of preoperative diagnostic measures such as fine needle biopsy and the practice of “defensive medicine”. How much each of these factors contributes is however unclear.
Combined coagulation factor VIII and factor IX deficiency (CDF8F9) in a patient from Lithuania
Authors: Pezeshkpoor B. , Biswas A. , Goldmann G. , Horneff S. , Gimbutyte M. , Malciute L. , Jurgutis R. , Oldenburg J. , Ivaškevičius V.
Published: October 2018

Haemophilia A (FVIII deficiency) and haemophilia B (FIX deficiency) are X-linked inherited bleeding disorders. It is a very rare event to identify both haemophilias in the same patient. So far, only two families with such combination are reported in the literature worldwide supported by genetic background. Patients and methods: Evaluation of clinical data, determination of FVIII and FIX levels and genetic analysis of F8 and F9 genes by direct sequencing. Results: We report on a patient having severe haemophilia B (FIX:C <1 IU dl-1) and mild haemophilia A (FVIII:C 18 IU dl-1 ). FIX deficiency was known since childhood, whereas mild haemophilia A was confirmed at the age of 42 due to unexpected bleeding complications after dental extraction despite adequate substitution with plasma derived FIX concentrate. F9 gene analysis showed a point mutation in exon 2 (c.223C>T, p.R75X), whereas F8 gene analysis revealed a point mutation in exon 4 (c.545A>C, p.D182A). The mother of the patient was heterozygous for F8 mutation, but not for F9 mutation suggesting a de novo F9 mutation. Accidentally, further family from Germany with mild Haemophilia A was identified to have the same F8 mutation. F8 Haplo-type analysis revealed that the p.D182A mutation most likely represents a founder mutation with common ancestors of the German and the Lithuanian family. Conclusions: Our results confirm the rare event of Haemophilia A and haemophilia B in the same patient originating from two distinct genetic defects in F8 and F9 genes.
A novel missense mutation in the FGB gene (p.Gly302Arg) leading to afibrinogenemia
Authors: Rühl H. , Detarsio G. , Biswas A. , Gupta S. , Davoli M. , Quartara A. , Pérez S. , Raviola M. , Oldenburg J. , Ivaškevičius V.
Published: October 2018

Afibrinogenemia represents the rarest form of fibrinogen deficiency. Causative missense mutations occur rarely and may improve the understanding of fibrinogen structure and function. Patients and methods: The propositus was a 26-year-old Argentinian with afibrinogenemia. FGA, FGB and FGG exons and flanking regions were screened by sequencing and the mutant protein was analyzed in silico. Results: A novel missense mutation in the FGB gene (Bbeta Gly272Arg, p.Gly302Arg) was identified. In silico analysis revealed its location in a highly conserved region, which preserves the core fold of the C-terminal beta-chain and is important for proper secretion. A substitution by a positively charged large Arg residue in this area would most likely disturb the core fold by additional interactions with adjacent residues (p.Asp291, p.Asp297, p.Asp311), or by forming of non-native interactions with other proteins, thereby hindering the action of molecular chaperones. Both alternatives would disturb the regular secretion of the beta-chain. Conclusions: The novel mis-sense mutation in the FGB gene causes afibrinogenemia most probably by affecting the secretion of the fibrinogen beta-chain.
Interest in Health Information Exchange in Ambulatory Care: A Statewide Survey
Authors: Ross S. E. , Mellis B. K. , Beaty B. L. , Schilling L. M. , Davidson A. J. , Tham E.
Published: October 2018

Objective: Assess the interest in and preferences of ambulatory practitioners in HIE.

Background: Health information exchange (HIE) may improve the quality and efficiency of care. Identifying the value proposition for smaller ambulatory practices may help those practices engage in HIE.

Methods: Survey of primary care and specialist practitioners in the State of Colorado.

Results: Clinical data were commonly (always [2%], often [29%] or sometimes [49%]) missing during clinic visits. Of 12 data types proposed as available through HIE, ten were considered “extremely useful” by most practitioners. “Clinical notes/consultation reports,” “diagnosis or problem lists,” and “hospital discharge summaries” were considered the three most useful data types. Interest in EKG reports, diagnosis/problem lists, childhood immunizations, and discharge summaries differed among ambulatory practitioner groups (primary care, obstetrics-gynecology, and internal medicine subspecialties).

Conclusion: Practitioners express strong interest in most of the data types, but opinions differed by specialties on what types were most important. All providers felt that a system that provided all data types would be useful. These results support the potential benefit of HIE in ambulatory practices.
Determining Primary Care Physician Information Needs to Inform Ambulatory Visit Note Display
Authors: Clarke M.A. , Steege L.M. , Moore J.L. , Koopman R.J. , Belden J.L. , Kim M.S.
Published: October 2018

Citation: Erratum to: Clarke MA, Steege LM, Moore JL, Koopman RJ, Belden JL, Kim MS. Determining primary care physician information needs to inform ambulatory visit note display. Appl Clin Inf 2014; 5: 190e http://dx.doi.org/10.4338/ACI-2013-08-RA-0064e
Ambivalenz des Fortschritts – Ist weniger mehr?
Authors: Scharf R.E.
Published: October 2018

Die Ökonomisierung des Gesundheitssystems hat zu einem industrialisierten Medizinbetrieb geführt. Die Auswirkungen und Folgen sind beträchtlich und begünstigen eher eine weitere Kostenexplosion infolge auferlegter Zwänge zur Erhöhung von Fallzahlen und zur Effizienzsteigerung. Hier sind kritische Positionsbestimmung und Richtungswechsel gefragt. Mögliche Auswege aus der derzeitigen Krise werden erörtert.
7th International Congress of the Croatian Society of Nuclear Medicine
Authors: Težak S , Huic D , Poropat M , Kasal B , Schicha H , Dodig D
Published: October 2018

The Seventh International Congress of The Croatian Society of Nuclear Medicine gives an overview of present-day nuclear medicine. For the Congress 82 papers were selected: 50 for oral and 32 for poster presentation. Of 82 accepted papers 44 came from Croatia. Other papers came from Austria, Bosnia and Herzegovina, Germany, Greece, Hungary, Italy, Kosovo, Russia, Slovenia and Serbia. There were 16 lectures as part of CME programme. The congress shows that Croatian nuclear medicine follows general trends of the European nuclear medicine. This report includes a selection of abstracts that might interest the readers of Nuklearmedizin.
Versorgung von Menschen mit chronischen Wunden im Pflegeheim
Authors: Hampel-Kalthoff C.
Published: October 2018

Als Setting bietet das Pflegeheim für eine hochwertige Versorgung von Menschen mit chronischen Wunden im Grunde ein förderliches Umfeld. Betreuungsdichte, Voraussetzungen für hygienische Verbandswechsel und Ansatzpunkte für interprofessionelle Kommunikation und Zusammenarbeit bieten gute Voraussetzungen. Gleichzeitig ist das Setting Pflegeheim gekennzeichnet von besonderen Herausforderungen: Häufige Multimorbidität und vor allem Demenzerkrankungen unter den Bewohnern, aber auch fehlende spezielle Kompetenzen im Personal, vor allem aber häufig fehlende Konzepte in den Einrichtungen sind Gründe, warum bei Pflegevisiten oft Fehloder Unterversorgungen zu beobachten sind. Die im Alltag zu beobachtenden Strategien unter diesen Rahmenbedingungen bleiben meist Einzelaktionen. Hierzu zählt u.a. das Hinzuziehen von Homecare-Anbietern als Berater, die sich aber durch den Verkauf von Pflegeprodukten finanzieren müssen, und somit eher zur Fokussierung auf Materialien, insbesondere Verbandsmittel, beitragen als die Versorgungsstrukturen und -prozesse insgesamt zu betrachten. Zu den zu beobachtenden Strategien zählen auch Krankenhauseinweisungen oder Versuche von Mitarbeitern der Kostenträger externe Interventionen zu initiieren. In der Regel sind diese Strategien nur begrenzt erfolg-reich, weil sie Strukturen und Prozesse nicht beeinflussen, und weil sie Strategien individueller Akteure sind, jedoch nicht auf Konsens und Ko-operation aller Beteiligten basieren.

Für eine Verbesserung der Versorgungsqualität bei Menschen mit chronischen Wunden im Pflegeheim sind aber hausinterne und interprofessionelle Konzepte erforderlich, die den Blick auf die Strukturen und Prozesse, auf Qualifikationen, Verantwortlichkeiten und Abläufe richten. Diese Konzepte sollten von Heimleitungen, Pflegefachkräften im Haus, Ärzten und externen pflegerischen Fachexperten für die Versorgung von Menschen gemeinsam entwickelt und umgesetzt werden. Die Konzepte sollten inhaltlich Qualifikationen, Zuständigkeiten und einheitliche Abläufe vorsehen und bei Bedarf die vertragliche geregelte Hinzuziehung eines unabhängigen pflegerischen Fachexperten ermöglichen, der die Pflegefachkräfte im Hause unterstützen kann.
Discussion of “Generalized Estimating Equations: Notes on the Choice of the Working Correlation Matrix”
Authors: Breitung J. , Chaganty N. R. , Daniel R. M. , Kenward M. G. , Lechner M. , Martus P. , Sabo R. T. , Wang Y.-G. , Zorn C.
Published: October 2018

Objective: To discuss generalized estimating equations as an extension of generalized linear models by commenting on the paper of Ziegler and Vens “Generalized Estimating Equations: Notes on the Choice of the Working Correlation Matrix”.

Methods: Inviting an international group of experts to comment on this paper.

Results: Several perspectives have been taken by the discussants. Econometricians have established parallels to the generalized method of moments (GMM). Statisticians discussed model assumptions and the aspect of missing data. Applied statisticians commented on practical aspects in data analysis.

Conclusions: In general, careful modeling correlation is encouraged when considering estimation efficiency and other implications, and a comparison of choosing instruments in GMM and generalized estimating equations (GEE) would be worthwhile. Some theoretical drawbacks of GEE need to be further addressed and require careful analysis of data. This particularly applies to the situation when data are missing at random.
Health IT in Asia-Pacific Region
Authors: Kimura M.
Published: October 2018

APAMI 2009 was held in Hiroshima, Japan, on November 22–24, 2009. This issue includes two selected papers recommended by the programming committee co-chairs. They are “Lessons Learned from Data Mining of WHO Mortality Database” and “Survey on Medical Records and EHR in Asia-Pacific Region – Languages, Purposes, IDs and Regulations”. The theme of APAMI 2009 was "What are the medical records for?" A Hiroshima episode; Medical Records at Dr. Ban’s Clinic, 9 km from the Epicenter of A-Bomb, is included, which lets us think of the fundamental purpose of medical records.
On the Methodology and Scientific Fundamentals of Organizing, Representing and Analysing Data, Information and Knowledge in Biomedicine and Health Care
Authors: Haux Haux
Published: October 2018

This issue of Methods of Information in Medicine celebrates the journal‘s first 50 years. As the oldest journal in biomedical and health informatics and, being broader in its scope, as the journal dealing with the methodology and scientific fundamentals of organizing, representing and analysing data, information and knowledge in biomedicine and health care, the journal publications during the last five decades also reflect the formation of a scientific field that deals with information in biomedicine and health care. Five papers that arose from a scientific symposium on “biomedical informatics: confluence of multiple disciplines” held in Heidelberg, Germany, in June 2011 are included in this volume. The papers reflect not only the broad interdisciplinary scope of the journal, but also the broad and evolving scope of the field itself. We can also recognise that there is an ongoing need for original and relevant research. As a discipline that has an impact on many other fields and is also influenced by them, scientific exchange and collaborative research continues to be needed.
The Student Editorial Board of Methods of Information in Medicine
Authors: Haux R. , Leong T. Y. , McCray A. , Aronsky D.
Published: October 2018

Objective
: Peer review is a critical process in the publication of scientific findings; trainees and young investigators, however, have few opportunities to learn systematically how to review manuscripts. Journal editors have an opportunity to engage trainees and young investigators in the peer review process early during their career.

Methods
: Methods of Information in Medicine, an official journal of the International Medical Informatics Association, is initiating a Student Editorial Board. The journal invites applications from international graduate and post-doctoral training programs that have a focus on health informatics, biomedical informatics, or a related field.

Results
: Each year up to six trainees will be invited to join the Student Editorial Board. The trainees will go through a mentored training experience that includes an active involvement in the various aspects of peer review during their one to two-year term of appointment.

Conclusions
: The journal expects that the Student Editorial Board will benefit trainees and young investigators in becoming skilled reviewers and engaged peers who can offer professional, constructive, and informative feedback and enhance the process of scientific communication.
A Pen-based Interface for Generating Graphical Reports of Findings in Cardiac Catheterization
Authors: Igarashi T. , Haraguchi R. , Nakazawa K. , Mori Y.
Published: October 2018

Objectives
: This paper introduces a pen-based interface for the graphical reporting of findings in cardiac catheterization.

Methods
: The user can interactively draw, erase, move, and deform coronary arteries as well as record stenoses on them. The location and degree of each stenosis is represented visually and the doctor can record various treatments such as bypasses and stents on the diagram. In addition, the system automatically extracts semantic information from the graphical representation and stores it in XML format. The system can also generate a table in the format specified by the American Heart Association.

Results
: Our current implementation is a research prototype and is not yet being used in clinical practice. However, we have already demonstrated it to medical professionals and confirmed the following benefits.

Conclusions
: This system is useful not only as a tool for efficiently generating reports of findings but also as an effective explanation tool for patients.
Document Recognition and XML Generation of Tabular Form Discharge Summaries for Analogous Case Search System
Authors: Sumida T. , Yamamoto K. , Shinogi T. , Tsuruoka S. , Kawanaka H.
Published: October 2018

Objectives
: This paper discusses and develops a document image recognition, keyword extraction and automatic XML generation system to search analogous cases from paper-based documents. In this paper, we propose the document structure recognition method and automatic XML generation method for the tabular form discharge summary documents. This paper also develops the prototype system using the proposed method. Evaluation experiments using actual documents are doneto discuss the effectiveness of the developed system.

Methods
: The developed system consists of the following methods. Paper-based summary documents are scanned by a scanner using 300 dpi first. Noise and tilt of the image are reduced by pre-processing, and the table structures are identified. Characters in the table are recognized and converted to text data by the OCR engine. XML documents are automatically generated using obtained results.

Results
: In this paper, patient discharge summary documents archived at Mie University Hospital were used. The results show that XML documents can be automatically generated when standard tabular form documents are input into the developed system. In this experiment, it takes about 20 seconds to generate an XML document using the general personal computer. This paper also compares the developed system with a commercial product to discuss the effectiveness of the present system. Experimental results also show that the accuracy of table structure recognition is high and it can be used in a practical situation.

Conclusions
: This paper showed the effectiveness of the proposed method to recognize the tabular form document images to generate XML documents.
Development of a Broadband Telemedical Network Based on Internet Protocol in the Asia-Pacific Region
Authors: Shimizu S. , Okamura K. , Hahm J. S. , Kim Y. W. , Han H. S. , Torata N. , Antoku Y. , Lee Y. S. , Tanaka M. , Nakashima N.
Published: October 2018

Objectives
: To promote the exchange of knowledge and standardization of medical procedures and medical systems in the Asia-Pacific region, we established a medical networkwith high-quality moving images over broadband Internet lines in February 2003.

Methods
: Real-time teleconferences and live demonstrations with medical-qualityvideos, broadcastvia the Digital Video Transport System, have been used t teach surgical techniques and other medical procedures across national borders.

The Asia-Pacific Advanced Network (APAN) committee in August 2005 formally approved our proposal to establish a medical working group within APAN. The networkwas expanded by the launch of the Trans- Eurasia Information Network 2 in 2006. By the end of 2006, we had conducted 82 events, in 10 countries in the Asia-Pacific region. The multi-station event has increased everyyear.

Results
: There have been no serious transmission problems or ethical conflicts so far. With these experiences and current achievements, we hope to extend this advanced network system to the entire Asia-Pacific.

Conclusion
: This system is a promising and very useful tool for the standardization of medical system and procedures across national borders. Drawing upon these experiences and current achievements, we hope to extend this advanced network system to the entire Asia- Pacific region.
Einflussfaktoren auf die Kalziumkonzentration im Erstkolostrum bei Holstein-Friesian-Kühen und deren Beziehung zur postpartalen Kalziumkonzentration im Blut
Authors: Staufenbiel Rudolf , Karl Maria
Published: October 2018

Ziel: Untersuchung von Einflussfaktoren auf die Kalziumkonzentration im Erstkolostrum mit Prüfung folgender Hypothesen: Die Laktationszahl ist der entscheidende Einflussfaktor auf die Kalziumkonzentration und es besteht ein Zusammenhang zur postpartalen Blutkalziumkonzentration. Material und Methoden: Von April 2012 bis März 2013 erfolgte eine Beobachtungsstudie auf einem kommerziellen Milchviehbetrieb (2278 Holstein-Friesian-Kühe) mit Analyse folgender Variablen: Menge und Kalziumkonzentration des Kolostrums; Blutserumkonzentrationen von Kalzium, Phosphor, freien Fettsäuren (NEFA) und β-Hydroxybutyrat (BHB); Rückenfettdicke; Milchleistung; Daten zur Kalbung; Laktationszahl; Kuhvater; Trächtigkeitsdauer; Erstkalbealter; Trockenstehdauer; Fruchtbarkeitskennzahlen der Vorlaktation sowie Erkrankungen in der Trockenstehphase und bis 3 Tage post partum. Die Daten wurden mithilfe der Varianzanalyse, Korrelationsanalyse sowie der multiplen linearen Regressionsanalyse auf Zusammenhänge und Einflussfaktoren stufenweise ausgewertet. Ergebnisse: Die mittlere Kalziumkonzentration betrug 2386 mg/l (Standardabweichung = 550 mg/l), wobei der Wert bei Färsen 148,5 mg/l höher lag als bei Kühen. Als relevante Einflussfaktoren ergaben sich die mittlere Tagesmilchmenge der ersten Laktationswoche und die Rückenfettdicke zum Zeitpunkt des Trockenstellens. Der Zusammenhang zur Milchmenge war negativ, was für einen Verdünnungseffekt spricht. Eine Zunahme der Rückenfettdicke bewirkte eine Erhöhung der Kalziumkonzentration im Kolostrum. Zusammen erklärten beide Faktoren 25% der Variabilität der Kolostrumkal ziumkonzentration. Laktationszahl und Kalziumkonzentration im Blut waren keine signifikanten Einflussfaktoren. Schlussfolgerung und klinische Relevanz: Die Hypothesen wurden widerlegt. Es gibt keinen Zusammenhang zur peripartalen Serumkalziumkonzentration und die Laktationszahl ist kein relevanter Einflussfaktor. Die Kalziumkonzentration im Kolostrum hat eine große individuelle Spannweite. Eine Beeinflussung über die Milchmengeneinsatzleistung und die Rückenfettdicke ist möglich, aber im Hinblick auf die Gebärpareseprophylaxe ohne Relevanz.
Third-Generation P2Y12 Inhibitors in East Asian Acute Myocardial Infarction Patients: A Nationwide Prospective Multicentre Study
Authors: Kang Jeehoon , Han Jung-Kyu , Ahn Youngkeun , Chae Shung Chull , Kim Young Jo , Chae In-ho , Hur Seung-Ho , Seong In-Whan , Chae Jei-Keon , Cho Myeong Chan , Seung Ki-Bae , Jeong Myung Ho , Yang Han-mo , Park Kyung Woo , Kang Hyun-Jae , Koo Bon-Kwon , Kim Hyo-Soo ,   on behalf of investigators for Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH)
Published: October 2018

Third-generation P2Y12 inhibitors (prasugrel, ticagrelor) are recommended in acute myocardial infarction (AMI). We aimed to evaluate the efficacy and safety of third-generation P2Y12 inhibitors in East Asian AMI patients. From the Korean AMI Registry, 9,355 patients who received dual antiplatelet agent (aspirin with clopidogrel [AC], 6,444 [70.5%] patients; aspirin with prasugrel [AP], 1,100 [11.8%] patients; or aspirin with ticagrelor [AT], 1,811 [19.4%] patients) were analysed. In-hospital endpoints were all-cause mortality or bleeding events during admission and 1-year endpoints were major adverse cardiac and cerebrovascular events (MACCE) and major bleeding events. Regarding in-hospital events, AP and AT showed similar all-cause mortality rates but higher bleeding event rates compared with AC. This trend was extended to 1-year endpoints; Cox regression analysis showed that third-generation P2Y12 inhibitors had significantly higher bleeding risk (AP vs. AC: hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.53–2.99; p < 0.001; AT vs. AC: HR, 2.26; 95% CI, 1.73–2.95; p < 0.001). A propensity score matched triplet of 572 patients showed similar 1-year MACCE and higher bleeding events with third-generation P2Y12 inhibitors (2.1 vs. 2.6 vs. 2.1%, p = 0.790 for MACCE and 3.1 vs. 8.0 vs. 8.0%, p < 0.001 for bleeding events, in AC, AP and AT groups, respectively). Inverse probability weighted regression analysis and pooled analysis after randomly imputing missing variables showed consistent results. Collectively, prasugrel and ticagrelor showed similar rates of 1-year MACCE, but a higher rate of bleeding events, compared with clopidogrel in Korean AMI patients. Further studies are warranted to adapt Western guidelines on third-generation P2Y12 inhibitors for East Asians.
Evaluation of Biomedical Infor matics Innovations and Their Impact on Public Health
Authors: Sarkar I. N.
Published: October 2018

This issue of Methods of Information in Medicine contains four feature articles that are focused on the theme of evaluation. Evaluation approaches are increasingly essential in the assessment of determining the potential impact of contemporary informatics innovations. The featured articles offer practical perspectives to determining the impact of advancements. Internationally, there are significant advances being made across biomedical informatics and its related sub-disciplines. As with any scientific discipline, it is important for practitioners to be able to relate the potential importance of findings. To this end, it is especially important for biomedical informaticians to convey, in a quantifiable and comparable form, the significance of the informatics findings – not only to peers but also to those across the biomedical research spectrum. As such, the feature articles in this issue describe the evaluation of core infrastructure and fundamental informatics innovations as well as evaluation of informatics-based resources that are a core aspect of public health initiatives.
Web Science in Medicine and Healthcare
Authors: Brooks E. , Denecke K.
Published: October 2018

Objectives: Medical social-media provide a new source of information within information gaining contexts. Facts, experiences, opinions or information on behaviour can be found in the medical web and could support a broad range of applications. The intention of this Focus Theme is to bring the existing research together and to show the possi -bilities, challenges and technologies for Web Science in medicine and healthcare.

Methods: This editorial provides an overview on the landscape of medical social-media and their possibilities in supporting healthcare. Further, it summarizes the three papers included in this Focus Theme.

Results and Conclusions: The three papers of this Focus Theme consider different aspects of Web Science in medicine which are 1) detection of drug interactions from social media, 2) inferring community structures from online forums and 3) improving access to online videos through assignment of SNOMED CT terms. All three papers show the potential of medical social-media in support -ing health information gathering processes from the web. However, several issues still need to be addressed in future: Methods are necessary for identifying high quality information from the medical web as well as for processing the language that is used by social media users to report about their symptoms, diseases and other health issues.
Discussion of “Attitude of Physi -cians Towards Automatic Alerting in Computerized Physician Order Entry Systems”
Authors: Bates D. W. , Baysari M. T. , Dugas M. , Haefeli W. E. , Kushniruk A. W. , Lehmann C. U. , Liu J. , Mantas J. , Margolis A. , Miyo K. , Nohr C. , Peleg M. , de Quirós F. G. B. , Slight S. P. , Starmer J. , Takabayashi K. , Westbrook J. I.
Published: October 2018

With these comments on the paper “Attitude of Physicians Towards Automatic Alerting in Computerized Physician Order Entry Systems”, written by Martin Jung and co authors, with Dr. Elske Ammenwerth as senior author [1], the journal wants to stimulate a broad discussion on computerized physi cian order entry systems. An international group of experts have been invited by the editor of Methods to comment on this paper. Each of the invited commentaries forms one section of this paper.
Advances in Medical Image Computing
Authors: Deserno T. M. , Handels H. , Meinzer H.-P. , Tolxdorff T.
Published: October 2018

Objectives: Medical image computing has become a key technology in high-tech applications in medicine and an ubiquitous part of modern imaging systems and the related processes of clinical diagnosis and intervention. Over the past years significant progress has been made in the field, both on methodological and on application level. Despite this progress there are still big challenges to meet in order to establish image processing routinely in health care. In this issue, selected contributions of the German Conference on Medical Image Processing (BVM) are assembled to present latest advances in the field of medical image computing.

Methods: The winners of scientific awards of the German Conference on Medical Image Processing (BVM) 2008 were invited to submit a manuscript on their latest developments and results for possible publication in Methods of Information in Medicine. Finally, seven excellent papers were selected to describe important aspects of recent advances in the field of medical image processing.

Results: The selected papers give an impression of the breadth and heterogeneity of new developments. New methods for improved image segmentation, non-linear image registration and modeling of organs are presented together with applications of image analysis methods in different medical disciplines. Furthermore, state-of-the-art tools and techniques to support the development and evaluation of medical image processing systems in practice are described.

Conclusions: The selected articles describe different aspects of the intense development in medical image computing. The image processing methods presented enable new insights into the patient’s image data and have the future potential to improve medical diagnostics and patient treatment.
Truncation of ADAMTS13 by Plasmin Enhances Its Activity in Plasma
Authors: Clark Chantal , Mebius Mirjam , de Maat Steven , Tielens Aloysius , de Groot Philip , Urbanus Rolf , Fijnheer Rob , Hazenberg Bouke , van Hellemond Jaap , Maas Coen
Published: October 2018

ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) cleaves von Willebrand Factor (VWF) multimers to control their thrombogenicity. The fibrinolytic enzyme plasmin can cleave VWF in a similar manner. However, plasmin can also cleave ADAMTS13, which ultimately inactivates it. This leaves the overall role of plasmin in primary haemostasis uncertain.

We investigated the combined molecular effects of plasmin on VWF and ADAMTS13. We first identified that plasmin destroys FRETS-VWF73 substrate by cleaving the ADAMTS13 binding region in a buffered system. We next investigated how plasmin affects both VWF and ADAMTS13 under static conditions in plasma by western blotting. We found that globular VWF is largely protected from plasmin cleavage. However, ADAMTS13 is rapidly cleaved under these conditions, suggesting inactivation. Surprisingly, we observed that plasmin enhances ADAMTS13 activity in a modified two-stage FRETS-VWF73 assay that protects FRETS-VWF73 substrate from degradation. In direct binding studies under the same conditions, we found that plasmin generates multiple C-terminally truncated forms of ADAMTS13 with VWF-binding capacity. In an effort to seek evidence for this mechanism in vivo, we analysed plasma from patients with systemic amyloidosis, which is hallmarked by a hyperfibrinolytic state. We found that their plasma contained increased levels of C-terminally truncated forms of ADAMTS13, which correlated with their hyperfibrinolytic state.

We propose that truncation of ADAMTS13 by plasmin abolishes intramolecular self-association, which improves interaction with unfolded VWF.
Myasthenie und Thymus
Authors: Zierz S. , Jordan B.
Published: October 2018

Die Thymuspathologie bei der Myasthenia gravis (MG) umfasst sowohl die lymphofollikuläre Hyperplasie (LFH) bei der Frühmanifestation der Azetylcholinrezeptorantikörper (AChR-AK) positiven Form als auch Thymome. Die Diagnostik schließt die Erhebung des Antikörperstatus ein, um die Indikation zur Thymektomie bei der klassischen AChR-Anti-körper positiven Form prüfen zu können. Bei radiologischem Verdacht einer mediastinalen Raumforderung kann nuklearmedizinisch die Bindung von Somatostatinrezeptoren (DOTATOC-PET) bei Thymomen visualisiert werden. Die Thymektomie mit Thymomresektion ist unter onkologischem Aspekt grundsätzlich indiziert. Die Diagnose der paraneoplastischen MG besitzt somit eine besondere Indikatorfunktion für den weiteren Verlauf der Thymomerkrankung.

Wenngleich die thymomassoziierte MG sich im klinischen Verlauf nicht von der klassischen Myasthenie unterscheidet, bedarf die Betreuung dieser Patienten besonderer Sorgfalt. Meist ist die Fortführung der Immunsuppression erforderlich. Gleichzeitig sind dabei die erhöhte Infektneigung, das erhöhte Risiko eines Zweitmalignoms als auch eines Thymomrezidivs zu beachten.
Update on Direct Oral AntiCoagulants (DOACs)
Authors: Rosenthal C. , von Heymann C. , Koscielny J.
Published: October 2018

Recent findings require an update of previous recommendations for the perioperative use of Direct Oral AntiCoagulants (DOACs). A break in preoperative treatment of 24-96 hours is recommended based on the pharmacokinetic profiles of DOACs and depends on individual patient characteristics, their renal and possibly liver function, and their surgery-related risk of bleeding. In cases of renal or hepatic insufficiency, whether to extend the preoperative interruption of IIa- and Xa-inhibitors is a clinical decision that must be reached on an individual patient basis. In cases of epidural or spinal anaesthesia, more conservative pausing-intervals are recommended due to the risk of persistent neurologic deficits (e.g., paraplegia) following the development of spinal subdural and epidural haematomas. Elective surgery should be postponed according to these recommendations. Preoperative “bridging” with LMWH (more precisely referred to as “switching”) should be omitted due to a significantly increased risk of bleeding. In addition, the incidence of perioperative thromboembolic risks, such as DVT, PE, and stroke, are no different whether interruption or „switching” is undertaken. Postoperatively, the DOACs can be reinstituted within the first 24 hours. In cases of major surgery or if there is a higher risk of bleeding, resumption of DOACS should only begin after 24-72 hours. In patients with an elevated thromboembolic risk, transient postoperative LMWH administration can be recommended during this period.

Interaction of DOACs with other drugs usually occurs during the absorption, transport and elimination of these drugs. Therefore, substance-specific restrictions and recommendations should be observed during these times. In everyday clinical practice, webbased, independent information portals on drug-interactions are very helpful in providing safe and rapid information about potential interactions when DOACs are used in combination with other drugs, especially during perioperative management.

Non-adherence to medications is a worldwide problem that has dangerous and costly consequences. Present data suggest that persistence is the primary factor that supports adherence. Despite the adherence data presented in the DOACS approval studies (e.g., persistence in the treatment of acute venous thromboembolism has been reported to be between 94-99%), the first registries and meta-analyses provide sobering results regarding the incidence of persistence and the success rate of interventions designed to improve adherence with DOACs in cases of long-term usage.

Nachdruck aus und zu zitieren als: Hämostaseologie 2017; 37: 267–275 https://doi.org/10.5482/HAMO-16-10-1657856
Liver Toxicity with Cancer Checkpoint Inhibitor Therapy
Authors: Nadeau Brian , Fecher Leslie , Owens Scott , Razumilava Nataliya
Published: October 2018

Immune checkpoint inhibition targeted against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has shown clinically significant survival benefit when used to treat multiple types of advanced cancer. These drugs have gained approval by the US Food and Drug Administration and their indications continue to increase. Checkpoint inhibitor therapy is associated with a unique side-effect profile characterized as immune-related adverse events (irAEs), which can result in significant morbidity and rarely mortality. Hepatotoxicity from checkpoint inhibitors is a less common irAE and often mild, while its incidence and severity vary based on the class and dose of checkpoint inhibitor, monotherapy versus combination therapy, and the type of cancer. Histological assessment of suspected irAEs is nonspecific and can show a variety of features. Hepatic irAEs can require discontinuation of checkpoint inhibitor therapy and treatment with immunosuppressive agents.
Postoperative Management of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps: Impact of High-Dose Corticosteroid Nasal Spray
Authors: Ikeda Katsuhisa , Ito Shin , Hibiya Remi , Homma Hirotomo , Ono Noritsugu , Okada Hiroko , Kidokoro Yoshinobu , Shiozawa Akihito , Kusunoki Takeshi
Published: October 2018

Introduction Eosinophilic chronic rhinosinusitis (ECRS) is characterized by an eosinophilic inflammation driven by Th2-type cytokines. Glucocorticosteroids are the most common first-line treatment for ECRS with nasal polyps.

Objective We have evaluated the long-term treatment with double-dose intranasal corticosteroids in refractory ECRS nasal polyps resistant to the conventional dose and assessed the risk of adverse systemic effects

Methods Sixteen subjects were enrolled in this study. All subjects had ECRS after endoscopic sinus surgery that resulted in recurrent mild and moderate nasal polyps and were undergoing a postoperative follow-up application of mometasone furoate at a dose of 2 sprays (100 μg) in each nostril once a day (200 μg). All the patients were prescribed mometasone furoate, administered at a dose of 2 sprays (100 μg) in each nostril twice a day (400 μg) for 6 months.

Results The average scores of the symptoms during the regular dose of intranasal steroid treatment were 5.2 ± 2.2, but 6 months after the high-dose application, they had significantly decreased to 2.5 ± 1.4 (p < 0.05). The polyp size showed an average score of 1.38 during the regular dose which was significantly reduced to 0.43 (p < 0.01) by the double dose. Glycated hemoglobin (HbA1c) showed normal ranges in all the patients tested. The cortisol plasma concentration was also normal.

Conclusion Doubling the dose of the nasal topical spray mometasone furoate might be recommended for the treatment of recurrent nasal polyps in the postoperative follow-up of intractable ECRS.