bluuebunny/crossref_metadata_2025 huggingface dataset:
Trainee colonoscopy quality is influenced by the independent and unobserved performance characteristics of supervising physicians
Authors: Mahadev Srihari , Jin Zhezhen , Lebwohl Benjamin , Rosenberg Richard , Garcia-Carrasquillo Reuben , Ramirez Ivonne , Freedberg Daniel
Published: January 2019

Background Endoscopy training remains an apprenticeship, and the characteristics that facilitate transfer of high quality procedural skills from role models to trainees are unknown. We sought to determine whether unobserved supervisor performance influences the quality of colonoscopy performed by trainees, by studying how supervisors perform alone and how trainees perform while under those same supervisors.

Methods This was a retrospective cross-sectional study conducted among ambulatory adults ≥ 50 years old who underwent colonoscopy for cancer screening or polyp surveillance from 2006 to 2015 at one academic medical center. The primary exposures were the colonoscopy withdrawal time (WT) and adenoma detection rate (ADR) of supervisors while performing colonoscopies alone. The primary outcomes were the WT and ADR of trainees performing colonoscopies under supervision.

Results Data were included from 22 attending gastroenterologist supervisors, 56 gastroenterology fellow trainees, and 2777 adults undergoing 3094 colonoscopy procedures. Among all supervised colonoscopies, mean trainee WT was 12.7 minutes (SD 4.9) and trainee ADR was 33.5 %. The trainee WT was 0.42 minutes longer (standard error = 0.16, P = 0.01) per minute increase in supervisor WT. Similarly, trainee ADR was higher under a high ADR supervisor, and the odds ratio of high compared to low supervisor ADR category was 1.28 (95 %CI 1.01 – 1.62, P = 0.04) after adjusting for other factors.

Conclusions The unobserved performance characteristics of supervising endoscopists may influence the quality of colonoscopy performed by trainees.
Bacterial and Fungal Keratitis: A Retrospective Analysis at a University Hospital in Switzerland
Authors: Bograd Alexandra , Seiler Theo , Droz Sara , Zimmerli Stefan , Früh Beatrice , Tappeiner Christoph
Published: January 2019

Background Infectious keratitis is a serious corneal disease and may lead to permanent visual deterioration if not treated rapidly and effectively. In order to determine possible changes in the spectrum of pathogens over time, we evaluated the pathogenic organisms of keratitis at a university hospital in Switzerland, comparing two time periods within a decade.

Methods In this retrospective study, 417 patients with the clinical diagnosis of bacterial or fungal keratitis in 2006/07 and 2015/16 were enrolled. In an additional analysis, all cases of fungal keratitis between 2006 and 2016 were evaluated. Collected parameters were age, gender, side, use of contact lenses, systemic, neurological and ocular diseases, trauma, previous surgery, and systemic and topical therapy before presentation. In each patient, microbiological results of corneal smears such as growth and antibiotic resistance were analysed.

Results A total of 163 and 254 eyes were included in 2006/07 and 2015/16, respectively. In 2006/07, a culture of smears revealed a bacterial cause in 70 eyes (42.9%) and a fungal cause in 4 eyes (2.5%), whereas in 2015/16, bacterial growth was found in 115 eyes (45.3%) and fungal growth in 6 eyes (2.4%). The most common bacteria in 2006/07 and 2015/16 were coagulase-negative Staphylococci (44.3 vs. 49.6%), Pseudomonas aeruginosa (18.6 vs. 13.9%), Staphylococcus aureus (10 vs. 16.5%), Corynebacterium spp. (8.6 vs. 5.2%), and Moraxella spp. (7.1 vs. 9.6%). Candida parapsilosis was the most common fungal isolate in both groups (25 vs. 33.3%). Between 2006 and 2016, fungal keratitis was found in 37 eyes (Candida spp. n = 11, Fusarium spp. n = 11, Aspergillus spp. n = 5, others n = 10). All patients with Fusarium spp. keratitis had a history of wearing contact lenses.

Conclusion The most commonly isolated bacterial organisms were Staphylococci and Pseudomonas spp., whereas fungal keratitis was mainly due to Candida spp. or Fusarium spp. No relevant variation in causative pathogens was observed between the two time periods.
Update on Failure Analysis of Implants in ACL Surgery: Technical Failure or Fate?
Authors: Münch Lukas , Herbst Elmar , Dyrna Felix , Imhoff Florian B. , Imhoff Andreas B. , Beitzel Knut
Published: January 2019

Die Ursachen für das Versagen von Rekonstruktionen des vorderen Kreuzbandes (VKB) sind vielfältig und erfordern einen multifaktoriellen Erklärungsansatz. Neben technischen operativen Fehlern müssen bei der Versagensanalyse auch die vielen für eine erneute VKB-Verletzung prädisponierenden Risikofaktoren berücksichtigt werden. Technische Fehler beinhalten vor allem die nicht anatomische Platzierung der tibialen und femoralen Bohrkanäle. Eine anatomische Position des femoralen Tunnels kann nur durch eine vom tibialen Bohrkanal unabhängige Anlagetechnik erreicht werden. Bei den Risikofaktoren lassen sich nicht modifizierbare und modifizierbare Risikofaktoren unterscheiden, wobei eine Kombination von mehr als einem Risikofaktor das Verletzungsrisiko erheblich steigert. Zu den nicht modifizierbaren Faktoren gehören die genetische Prädisposition, weibliches Geschlecht, junges Alter und eine allgemeine Hyperlaxität. Ein junges Patientenalter bei erstmaliger Verletzung stellt vor allem in Zusammenhang mit Hochrisikosportarten einen wesentlichen Risikofaktor für ein Transplantatversagen dar. Zu den modifizierbaren Faktoren gehören ein hoher Body-Mass-Index, Defizite im Sprunglandungsmechanismus, ein steiler posteriorer tibialer Slope und eine schmale Notchweite. Diese lassen sich durch neuromuskuläres Training oder zusätzliche operative Eingriffe verändern, sodass das Risiko einer weiteren Verletzung reduziert werden kann. Das operative Verfahren der Wahl zur Reduktion des tibialen Slopes ist die hohe tibiale Osteotomie. Hierdurch kann die anteriore Tibiatranslation verringert werden. Bei einem tibialen Slope von über 12° sollte ein derartiges Verfahren in Betracht gezogen werden. Eine zusätzliche laterale extraartikuläre Stabilisierung sollte vor allem bei Revisionsplastiken des VKB mit einer verbliebenen anterolateralen Rotationsstabilität erwogen werden. Auch bei Patienten, die durch Risikosportarten, begleitende Hyperlaxität oder zusätzliche Beteiligung der peripheren Strukturen bei VKB-Insuffizienz zur Hochrisikogruppe gezählt werden, sollte ein derartiger Eingriff diskutiert werden. Zudem kann der Belag des Sportfeldes modifiziert und somit Einfluss auf das Verletzungsrisiko genommen werden. Zusammenfassend kann man sagen, dass nicht nur im Falle einer VKB-Reruptur eine fundierte Versagensanalyse erfolgen muss, sondern die genannten Faktoren schon bei der Risikoabschätzung in der Patientenaufklärung berücksichtigt werden sollten. Nur so kann eine gezielte und individualisierte Therapie durchgeführt werden.
Sealed endoscopic full-thickness resection for gastric cancer: a pilot study in an ex vivo and in vivo porcine model
Authors: Kitakata Hidekazu , Itoh Tohru , Kinami Shinichi , Kawaura Ken , Hamada Kazu , Azukisawa Sadafumi , Kobayashi Rika , Kamai Junji , Kosaka Takeo
Published: January 2019

Background and study aims Endoscopic full-thickness resection (EFTR) is a useful procedure that allows minimal resection of the gastric wall because the tumor can be located endoscopically. However, the procedure carries a risk of peritoneal infection or dissemination. Thus, we devised a new EFTR technique in which the serosa is sealed using a silicone sheet to prevent the escape of gastric juice.

Materials and methods Three whole stomachs were harvested from pigs for an ex vivo experiment, and seven pigs were used for an in vivo experiment. In both experiments, silicone sheets and gauze were pasted to the serosa using a fibrinogen-thrombin solution. A seromuscular incision was then made endoscopically using a HookKnife. We then evaluated whether stomach collapse could be prevented using this technique. Furthermore, the method was compared with conventional laparoscopic-assisted EFTR (LA-EFTR) in terms of resection time and quality of endoscopic view.

Results In the ex vivo experiment, stomach collapse was suppressed and the seromuscular layer could be incised layer by layer. In the in vivo experiment, the time required for seromuscular incision with the new EFTR technique was significantly shorter than that with the conventional method. All layers of the stomach were smoothly resected under good endoscopic view.

Conclusions Sealed EFTR is a potentially useful technique for the minimally invasive resection of gastric tumor. All layers of the stomach could be incised while confirming the incision line from the inside of the stomach and avoiding exposure of the tumor to the abdominal cavity.
Aufbruch in der Fastentherapie
Authors: Michalsen Andreas
Published: January 2019

Alternierende Phasen des Nahrungsüberangebots und des Hungerns waren bei den Frühmenschen vermutlich der Regelfall. Es scheint naheliegend, dass der menschliche Körper evolutionsbedingt Phasen des Fastens sehr gut bewältigen kann und sich die genetische Ausstattung, der Körpermetabolismus und die Ernährungsphysiologie gut darauf eingestellt haben. Im Gegensatz dazu ist anzunehmen, dass die mehrmals tägliche, regelmäßige Nahrungszufuhr mit Snacks, Zwischenmahlzeiten und energiehaltigen Getränken, die Hormon- und Stoffwechselsysteme überfordert. Die günstigen metabolischen Wirkungen des Fastens sind in physiologischen Arbeiten beschrieben. Der Artikel gibt einen Überblick zu den verschiedenen Formen des Fastens und dessen mögliche Effekte.
Isolation and Identification of Phenylethanoid Glycosides from Aloysia polystachya and Its Activity as Inhibitors of Monoamine Oxidase-A
Authors: Pereira Ana , Guimarães Camila , Pereira Sarazete , Crevelin Eduardo , Pinto Gustavo , Morel Lucas , Bertoni Bianca , França Suzelei , Taleb-Contini Silvia
Published: January 2019

Aloysia polystachya is used as a sedative and antidepressant by the indigenous populations of Argentina and Paraguay, but the compounds associated with these activities have not been determined. We have separated and identified the main constituents of the hydroethanolic extract of A. polystachya by ultra-performance liquid chromatography-mass spectrometry and confirmed the presence of acteoside, isoacteoside, 6'-acetylacteoside, and 4’,4’’’,5,5’’-tetrahydroxy-6,6’’,3’’’-trimethoxy-[C7–O–C7’’]-biflavone by NMR spectroscopy. Inhibitory activities of the hydroethanolic extract and purified phenylethanoid glycosides against monoamine oxidase-A were assessed using a standard fluorometric assay. The hydroethanolic extract inhibited monoamine oxidase-A activity in a dose-dependent manner with an IC50 of 9.2 µg/mL, while the selective monoamine oxidase inhibitor clorgyline exhibited an IC50 of 0.06 µg/mL (0.22 µM). Acteoside was the strongest inhibitor of monoamine oxidase-A (IC50 value of 5 µM), whereas isoacteoside and 6'-acetylacteoside showed IC50 values of around 10 µM. The results showed that phenylethanoids from a hydroethanolic extract of A. polystachya have been found to have inhibitory activity against monoamine oxidase-A. It is likely that the mode of action of the acteosides is multi-targeted, involving the downregulation of inflammatory molecules and neutralization of oxidation reactions as well as inhibition of monoamine oxidase-A.
Gibt es einen Zusammenhang zwischen den Auditergebnissen und den Patientinnenerfahrungen in Brustzentren in Nordrhein-Westfalen?
Authors: Barteldrees Kirsten , Pfaff Holger , Groß Sophie Elisabeth , Ansmann Lena
Published: January 2019

Ziel der Studie In Nordrhein-Westfalen soll Brustkrebs zur Wahrung und Verbesserung der Versorgungsqualität nur in ÄKzert-zertifizierten Brustzentren operiert werden. Dafür müssen sich alle Zentren 3-jährlich einem Auditprozess unterziehen und jährlich an einer Patient*innenbefragung teilnehmen. Während es zum Nutzen von zertifizierten Zentren bezüglich der Behandlungsqualität schon einige Studien gibt, soll nun untersucht werden, ob sich das Ergebnis des Auditierungsprozesses in den Erfahrungen der Patientinnen widerspiegelt.

Methodik Die quantitativen Ergebnisse aller Zertifizierungsauditberichte der Jahre 2014–2016 von Brustzentren in Nordrhein-Westfalen wurden mittels Mehrebenenanalysen mit verschiedenen Skalen einer jährlichen, poststationären, postalischen Befragung von Patient*innen mit primärem Mammakarzinom verknüpft.

Ergebnisse Es wurden Auditberichte und Befragungsdaten von 3016 Patientinnen aus 33 Brustzentren untersucht, dabei wurden nach Korrektur für multiples Testen keine statistisch signifikanten Zusammenhänge gefunden.

Schlussfolgerung Insgesamt zeigen sich keine Zusammenhänge zwischen den Ergebnissen eines Zentrums im Audit und den Patientinnenerfahrungen. Die Patientinnen scheinen ein spezifisches subjektives Erleben zu haben, das trotz der ausdrücklichen Forderung nach Patient*innenorientierung im Anforderungskatalog so nicht durch die Auditbesuche abgebildet werden kann. Das Ergebnis unterstreicht den Nutzen der jährlichen verpflichtenden Patient*innenbefragung, da sie weitergehende Informationen liefert, an die man durch andere Informationsquellen wie z. B. Zertifizierungsaudits offensichtlich nicht gelangt.
Stillen mit HIV – eine schwierige Entscheidungsfindung
Authors: Haberl Annette
Published: January 2019

Müttern, die mit HIV leben, wird in den westlichen Industrieländern immer noch vom Stillen abgeraten. Allerdings ist in vielen Leitlinien zumindest eine Veränderung in den Formulierungen zu beobachten. Es werden für den Einzelfall Lösungsansätze empfohlen, die auf individueller Ebene eine gute medizinische Betreuung HIV-positiver stillender Mütter und ihrer Kinder ermöglichen.
Point-of-Care Ultraschall in Notfallzentren
Authors: Schmid Mathias , Dodt Christoph
Published: January 2019

Akut- und Notfallmediziner müssen mit wenigen diagnostischen Mitteln rasche und
weitreichende Entscheidungen treffen. Im Rahmen einer Notfallversorgung ist der
Point-of-Care Ultraschall (POCUS) als immer verfügbares, bettseitiges
diagnostisches Hilfsmittel nicht mehr wegzudenken. Dabei geht es um eine
fokussierte und symptomorientierte Untersuchung – klar definierte
Fragestellungen sollten durch den Notfallmediziner möglichst mit ja oder nein
beantwortet werden. Durch immer kleinere „Handheld“-Ultraschallgeräte weitet
sich der Einsatz des POCUS inner- und auch präklinisch aus.
Multicenter prospective study on the histological diagnosis of gastric cancer by narrow band imaging-magnified endoscopy with and without acetic acid
Authors: Kishino Takaaki , Oyama Tsuneo , Funakawa Keita , Ishii Eiji , Yamazato Tetsuro , Shibagaki Kotaro , Miike Tadashi , Tanuma Tokuma , Kuwayama Yasuharu , Takeuchi Manabu , Kitamura Yoko
Published: January 2019

Background and study aims The usefulness of endoscopy for diagnosing histological type remains unclear. This study aimed to examine the diagnostic accuracy of white light endoscopy (WLE), magnified endoscopy with narrow band imaging (NBI-ME), and NBI-ME with acetic acid enhancement (NBI-AA) for histological type of gastric cancer.

Patients and methods Patients with depressed-type gastric cancers resected by endoscopic submucosal dissection were prospectively enrolled, and 221 cases were analyzed. Histological type was diagnosed by WLE, followed by NBI-ME and NBI-AA. Histological type was classified into differentiated adenocarcinoma and undifferentiated adenocarcinoma. Histological type was diagnosed based on lesion color in WLE, surface patterns (pit, villi, and unclear) and vascular irregularities in NBI-ME, and surface patterns in NBI-AA.

Results Histological types of target areas were differentiated adenocarcinoma and undifferentiated adenocarcinoma in 206 and 15 cases, respectively. Diagnostic accuracy of WLE, NBI-ME, and NBI-AA for the histological type was 96.4 % (213/221), 96.8 % (214/221), and 95.5 % (211/221), respectively. No significant differences were observed among modalities. Positive predictive value based on endoscopic findings in NBI-ME was 98.0 % (149/152) for the villi pattern, 100 % (19/19) for the irregular pit pattern, 100 % (9/9) for the unclear surface pattern with a vascular network, 90.3 % (28/31) for the unclear surface pattern with mild vascular irregularity, and 88.9 % (8/9) for the unclear surface pattern with severe vascular irregularity.

Conclusions NBI-ME and NBI-AA did not show any advantages over WLE for diagnostic accuracy. Villi pattern, irregular pit pattern, and vascular network may be useful for identifying differentiated adenocarcinoma.
Interdisziplinäres Management bei Anastomoseninsuffizienz nach Ösophagusresektion zur Vermeidung der Ösophagektomie
Authors: Herrmann Dominik , Mahoozi Hamid Reza , Kemen Matthias , Kompa Dirk , Volmerig Jan , Hecker Erich
Published: January 2019

Hintergrund Die Anastomoseninsuffizienz nach Ösophagusresektion ist eine schwere Komplikation und mit einer hohen Letalität assoziiert. Ein konservatives Vorgehen, mittels Stentimplantation oder Endo-VAC-Therapie stellt den initialen Therapieansatz dar. Diese Arbeit beschreibt eine Kombination aus konservativem und chirurgischem Management nach einem frustranen initialen Therapieversuch zur Vermeidung einer Ösophagektomie.

Material und Methoden Es wurden alle Patienten eingeschlossen, die zwischen Mai 2008 und Dezember 2016 aufgrund einer Anastomoseninsuffizienz nach Ösophagusresektion in unserer Klinik für Thoraxchirurgie behandelt wurden. Nach initialem Therapieversagen erhielten die Patienten eine konservativ-chirurgische Kombinationstherapie. Ein Ösophagusstent wurde implantiert und mittels transmuraler, resorbierbarer Naht fixiert. Nachfolgend wurde ein radikales mediastinales und pleurales Débridement durchgeführt und der Defekt mittels Muskellappenplastik gedeckt. Bei postoperativem Keimnachweis wurde zusätzlich eine diskontinuierliche Spültherapie der Pleurahöhle durchgeführt. Wir analysierten die Faktoren, die einen Einfluss auf die Letalität nach Therapie einer Anastomoseninsuffizienz nach Ösophagusresektion hatten.

Ergebnisse 18 Patienten wurden nach erfolgloser konservativer Therapie einer Anastomoseninsuffizienz nach Ösophagusresektion in unserer Klinik vorgestellt. 15 Patienten wurden innerhalb von 20 Tagen nach Detektion der Anastomoseninsuffizienz überwiesen, 3 Fälle mehr als 20 Tage nach Auftreten erster Symptome einer Anastomoseninsuffizienz. Alle Patienten präsentierten sich mit einem rechtsseitigen Pleuraempyem, Pneumonie, Mediastinitis und Sepsis. In 3 Fällen lag ein beidseitiges Pleuraempyem vor. Die erfolgreiche chirurgische Therapie der Anastomoseninsuffizienz gelang in 100% der Fälle. Die 90-Tages-Mortalität lag bei 20% (3 Patienten).

Zusammenfassung Insgesamt hat das kombinierte Management der Anastomoseninsuffizienz nach Ösophagusresektion eine sehr hohe Erfolgsrate. Einzig das Fortführen einer konservativen Therapie für mehr als 20 Tage hat einen signifikanten Einfluss auf die Letalität.
Digitale Gesundheit
Authors: Opalka Markus
Published: January 2019

Digitale Gesundheitssysteme wie Trainings-Apps und Symptomchecker haben Hochkonjunktur und revolutionieren den Gesundheitsmarkt. Als Folge der Digitalisierung ist eine Patientengruppe entstanden, die mithilfe von Gesundheitsanwendungen ihre Gesundheit gestalten und optimieren will. Der digitale Gesundheitsmarkt stellt alle Heilberufe vor neue Herausforderungen zu Themen wie Datensicherheit, Konkurrenz oder Vernetzung.
Die Rolle der lokalen Therapie des Primärtumors bei der
Behandlung des oligometastasierten Prostatakarzinoms
Authors: Jentzmik Florian
Published: January 2019

Die bisherige Studienlage lässt es nicht zu, eine generelle Empfehlung zur
lokalen Therapie bei oligometastasierten Prostatakarzinompatienten
auszusprechen. Die Datenlage vornehmlich klinischer retrospektiver Studien
deutet darauf hin, dass bezüglich des karzinomspezifischen – wie auch des
Gesamtüberlebens einzelne Patienten profitieren können. Die zytoreduktive
Prostatektomie ist an erfahrenen Zentren mit vergleichbarer Komplikationsrate
zur Standardindikation durchführbar. Einzelne Patienten können von der
Vermeidung von lokoregionären Sekundärkomplikationen profitieren.
Multizentrische prospektive Studien laufen, die Ergebnisse sind noch
ausstehend.
Facetten des Arzt-Patienten-Gesprächs in der Urologischen Praxis – Handlungsempfehlungen aus der Psychoonkologie
Authors: Kendel Friederike , Hilger Caren
Published: January 2019

Tumorerkrankungen werden von vielschichtigen Ängsten und psychischen Belastungen begleitet, mit denen der behandelnde Urologe konfrontiert wird. Dieser Beitrag beleuchtet Facetten des Arzt-Patienten-Gesprächs aus einer psychoonkologischen Perspektive. Dazu gehören die Risikowahrnehmung, subjektive Krankheitsvorstellungen, Lebensstiländerungen, Sexualität und ganz zentral der Umgang mit der Angst. Auf der Grundlage von neueren Forschungsergebnissen werden Anregungen für die Gesprächsführung gegeben. Der Beitrag zeigt aber auch Grenzen des Arzt-Patienten-Gesprächs. Eine professionelle psychoonkologische Unterstützung ist indiziert, wenn durch die Krebserkrankung psychische Krisen ausgelöst oder tieferliegende Konflikte wieder aktiviert werden. Sie kann auch hilfreich sein, wenn manche Probleme einfach mehr Zeit und Ruhe erfordern, als im Praxisalltag verfügbar ist. Deshalb erfolgt abschließend ein Überblick über weiterführende psychoonkologische Interventionen und Unterstützungsangebote für Krebspatienten.
2–Benzylidene–1–Indanone Analogues as Dual Adenosine A1/A2a Receptor Antagonists for the Potential Treatment of Neurological Conditions
Authors: van Rensburg HelenaDorathea Janse , Legoabe LesetjaJ. , Terre’Blanche Gisella , Van der Walt MiethaM.
Published: January 2019

Previous studies explored 2-benzylidine-1-tetralone derivatives as innovative adenosine A1 and A2A receptor antagonists for alternative non-dopaminergic treatment of Parkinson’s disease. This study’s aim is to investigate structurally related 2-benzylidene-1-indanones with substitutions on ring A and B as novel, potent and selective adenosine A1 and A2A receptor blockers. 2-Benzylidene-1-indanone derivatives were synthesised via acid catalysed aldol condensation reactions and evaluated via radioligand binding assays to ascertain structure activity relationships to govern A1 and A2A AR affinity. The results indicated that hydroxy substitution at C4 of ring A and meta (3’), or para (4’) substitution on ring B of the 2-benzylidene-1-indanone scaffold (2c) is preferred over substitution at C5 (2d) or C6 (2e) of ring A for adenosine A1 receptor activity and selectivity in the micromolar range. Furthermore, substitution at the meta (3’) position of ring B with chlorine lead to the highly potent and selective adenosine A2A receptor antagonist, compound 2 h. Compound 2c and the 2q behaved as adenosine A1 receptor antagonists in the performed GTP shift assays. In view of these findings, compounds 2c, 2 h, 2q and 2p are potent and selective adenosine A1 and A2A receptor antagonists for the potential treatment of neurological conditions.
Therapie des chronischen Rückenschmerzes unter Berücksichtigung psychosozialer Faktoren
Authors: Henn Lea , Hardt Jochen
Published: January 2019

Chronische Schmerzen, darunter v. a. Rückenschmerz als häufigste Lokalisation, zählen zu den bedeutsamsten medizinischen Leiden weltweit. Die Kosten für das Gesundheitssystem sind dabei erheblich. Zugleich sind die derzeit noch häufig angewendeten Therapieansätze, die oftmals aus einer alleinigen symptomatischen Behandlung bestehen, wenig erfolgversprechend. In 80–85% der Fälle lassen sich keine morphologischen Anhaltspunkte für eine mögliche Ätiologie finden, sodass in diesem Fall von „nicht-spezifischen“ Rückenschmerzen gesprochen wird. Insgesamt betrachtet lässt sich die Genese chronischer Rückenschmerzen am besten durch einen multifaktoriellen Entstehungsmechanismus erklären, in den eine Kombination aus biopsychosozialen, biographischen, neurobiologischen, genetischen und kognitiven Faktoren mit einbezogen wird. Aus diesem Grund zeigt eine multimodal ausgerichtete Therapie die beste Wirksamkeit, weil sie die verschiedenen Aspekte der Schmerzentstehung berücksichtigen kann.
Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU): Technical Background and Overview of Current Clinical Applications (Part 1)
Authors: Siedek Florian , Yeo Sin Yuin , Heijman Edwin , Grinstein Olga , Bratke Grischa , Heneweer Carola , Puesken Michael , Persigehl Thorsten , Maintz David , Grüll Holger
Published: January 2019

Background Extracorporeal high-intensity focused ultrasound (HIFU) is a promising method for the noninvasive thermal ablation of benign and malignant tissue. Current HIFU treatments are performed under ultrasound (US-HIFU) or magnetic resonance (MR-HIFU) image guidance offering integrated therapy planning, real-time control (spatial and temperature guidance) and evaluation.

Methods This review is based on publications in peer-reviewed journals addressing thermal ablation using HIFU and includes our own clinical results as well. The technical background of HIFU is explained with an emphasis on MR-HIFU applications. A brief overview of the most commonly performed CE-approved clinical applications for MR-HIFU is given.

Results Over the last decade, several HIFU-based applications have received clinical approval in various countries. In particular, MR-HIFU is now approved for the clinical treatment of uterine fibroids, palliation of bone pain, ablation of the prostate and treatment of essential tremor as a first neurological application.

Conclusion MR-HIFU is a patient-friendly noninvasive method for thermal ablation which has received clinical approval for several applications. Overall, clinical data demonstrate treatment efficacy, safety and cost efficiency.

Key Points: 

Citation Format
Catalpol Ameliorates Neointimal Hyperplasia in Diabetic Rats
Authors: Lin Chiu-Mei , Wang Bao-Wei , Fang Wei-Jen , Pan Chun-Ming , Shyu Kou-Gi , Hou Sheng-Wen
Published: January 2019

Catalpol, an iridoid glycoside, is an isolated natural product of Rehmannia glutinosa, which has been reported to have antidiabetic properties. This study investigated the vascular protective effects of catalpol in hyperglycemic rats with balloon-injured carotid arteries. Balloon injury stress led to the upregulation of monocyte chemoattractant protein-1 expression in rats with streptozotocin-induced diabetes. Western blotting and real-time PCR were performed. In situ hybridization, immunohistochemistry, and confocal analyses were employed. Monocyte chemoattractant protein-1 levels were increased through streptozotocin induction or balloon injury. After treatment with catalpol, the neointimal hyperplasia area was reduced 2 weeks after balloon injury in hyperglycemic rats. Real-time PCR and immunohistochemical analysis demonstrated reduced levels of monocyte chemoattractant protein-1 2 weeks after the balloon injury. Monocyte chemoattractant protein-1 expression was significantly increased in balloon-injured rats compared with the control groups. Thus, treatment with catalpol affected monocyte chemoattractant protein-1 expression. This study demonstrated that catalpol downregulated monocyte chemoattractant protein-1 expression in carotid arteries and ameliorated neointimal hyperplasia in hyperglycemic rats. The suppressive effect of monocyte chemoattractant protein-1 suggests that it plays a key role in neointimal hyperplasia. The results imply that catalpol is potentially effective for preventing hyperglycemia-related ischemic cardiac diseases.
Deutsches Hepatitis C-Register (DHC-R) – eine Zwischenbilanz 4 Jahre nach Zulassung direkt antiviraler Substanzen (DAAs)
Authors: Hüppe Dietrich , Serfert Yvonne , Buggisch Peter , Mauss Stefan , Böker Klaus , Müller Tobias , Klinker Hartwig , Günther Rainer , Berg Thomas , Cornberg Markus , Niederau Claus , Sarrazin Christoph , Simon Karl-Georg , Zeuzem Stefan , Manns Michael , Wedemeyer Heiner
Published: January 2019

Einleitung In Deutschland sind mehr als 250 000 Patienten an einer chronischen Hepatitis C (CHC) erkrankt. Seit 2014 sind zahlreiche potente direkt antivirale Substanzen gegen HCV zugelassen worden. Ziel des Deutschen Hepatitis-C-Registers (DHC-R) ist es, die Epidemiologie und Versorgung von Patienten mit CHC abzubilden und die Effektivität und Sicherheit der neuen Behandlungsmöglichkeiten im Praxisalltag zu untersuchen.

Methoden Das DHC-R ist eine prospektive, multizentrische, nicht interventionelle Registerstudie. Bundesweit sind 327 Zentren für die Dokumentation freigeschaltet. Alle in Deutschland zugelassenen Medikamente wurden im DHC-R dokumentiert. Für die aktuelle Auswertung wurden 4 Phasen unterschieden: 2/2014 bis 12/2014, 1/2015 bis 12/2015, 1/2016 bis 7/2017 und 8/2017 bis 7/2018.

Ergebnisse Zwischen Februar 2014 und Juli 2018 wurden 12 170 Patienten in das Register eingeschlossen (61,3 % Männer), eine antivirale Therapie erhielten 11 268. Das Behandlungsalter sank von 52,3 (Phase 1) auf 49,3 Jahre (Phase 4), der Anteil der Behandelten mit einer Drogenanamnese nahm zu (von 26,9 auf 43,1 %). 2014 wurden viele Patienten mit Leberzirrhose (35,1 %) behandelt, deren Anteil im Verlauf deutlich abnahm (Phase 4: 16,5 %). Die HCV-Genotypenverteilung änderte sich im Zeitverlauf deutlich, zuletzt stieg der Anteil des HCV-Genotyps 3 (30 % in Phase 4). Die Ausheilungsrate (PP-Analyse) steigerte sich von 92,8 % im Jahre 2014 auf zuletzt 97,4 % bei sehr guter Verträglichkeit.

Zusammenfassung Das DHC-R beschreibt die Versorgungssituation der Patienten mit CHC in Deutschland, zeigt epidemiologische Tendenzen auf und belegt die ausgezeichneten Behandlungsmöglichkeiten.
Zusammenhang zwischen beruflichen Traumata, posttraumatischer Belastungsstörung und Depression – eine Beurteilung von systematischen Reviews
Authors: Bolm-Audorff Ulrich , Petereit-Haack Gabriela , Seidler Andreas
Published: January 2019

In einem Meta-Review wurden 35 systematische Reviews zum Thema mit AMSTAR, ein Instrument zur Qualitätsbewertung von systematischen Reviews, beurteilt. 31 Reviews wiesen eine niedrige Qualität auf und hatten überwiegend Studien ohne eigene Kontrollgruppe einbezogen. Die 4 systematischen Reviews mit zumindest mittelgradiger Qualität zeigten ein signifikant erhöhtes Risiko von Soldaten nach Entsendung in einen Krieg für die Entwicklung einer posttraumatischen Belastungsstörung (PTBS) und einer Depression. Ferner zeigten sich Hinweise für ein deutlich erhöhtes PTBS-Risiko von Feuerwehrleuten und Rettungssanitätern.
Inhibitory Effects of Pterocarpus santalinus Extract against IgE/Antigen-Sensitized Mast Cells and Atopic Dermatitis-Like Skin Lesions
Authors: Ham Baknoon , Kim Myungsuk , Son Yang-Ju , Chang Sungyul , Jung Sang Hoon , Nho Chu Won , Kwon Man Jae
Published: January 2019

Pterocarpus santalinus has been traditionally used as a medicinal plant owing to its anti-inflammatory, anthelmintic, tonic, antihyperglycemic, and diaphoretic properties. We hypothesized that P. santalinus might have therapeutic potential in alleviating allergy and atopic dermatitis. Thus, we investigated the inhibitory effects of P. santalinus extract against allergic responses and 2,4-dinitrochlorobenzene-induced atopic dermatitis-like dorsal skin lesions using immunoglobulin E-sensitized rat basophilic leukemia-2H3 mast cells and NC/Nga mice. Degranulation and enzyme-linked immunosorbent assays were conducted to measure degranulation, proinflammatory cytokine levels, and prostaglandin E2 concentrations in immunoglobulin E/antigen-sensitized RBL-2H3 mast cells. The therapeutic efficacy of P. santalinus extract in 2,4-dinitrochlorobenzene-induced atopic dermatitis was evaluated through morphological, physiological, and immunological analysis. P. santalinus extract inhibited β-hexosaminidase and histamine release and reduced tumor necrosis factor-α, interleukin-4, and prostaglandin E2 secretion. Furthermore, P. santalinus extract suppressed atopic dermatitis-like skin lesions by regulating the serum levels of immunoglobulin E and immunoglobulin G2a, and messenger ribonucleic acid expression of T helper cell 1- and T helper cell 2-related mediators in the skin lesions. Histopathological analyses showed a decrease in epidermal thickness and intradermal inflammatory cell infiltration. These results suggested that P. santalinus extract might have beneficial effects in treating allergic and atopic dermatitis-like skin disorders.
Antiprotozoal Germacranolide Sesquiterpene Lactones from Tanacetum sonbolii
Authors: Mofidi Tabatabaei Sahar , Nejad Ebrahimi Samad , Salehi Peyman , Sonboli Ali , Tabefam Marzieh , Kaiser Marcel , Hamburger Matthias , Moridi Farimani Mahdi
Published: January 2019

A phytochemical investigation of extracts from flowers and aerial parts of Tanacetum sonbolii afforded 7 new germacranolide sesquiterpene lactones. The structures were established by a combination of 1- and 2-dimensional nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry, and electronic circular dichroism. The in vitro antiprotozoal activity of the compounds against Trypanosoma brucei rhodesiense and cytotoxicity against rat myoblast (L6) cells were determined. Compounds 4 and 5 showed IC50 values of 5.1 and 10.2 µM and selectivity indices of 3.9 and 4.0, respectively.
Triterpenoids from Hibiscus sabdariffa L. with PPARδ/γ Dual Agonist Action: In Vivo, In Vitro and In Silico Studies
Authors: Giacoman-Martínez Abraham , Alarcón-Aguilar Francisco , Zamilpa Alejandro , Hidalgo-Figueroa Sergio , Navarrete-Vázquez Gabriel , García-Macedo Rebeca , Román-Ramos Rubén , Almanza-Pérez Julio
Published: January 2019

Hibiscus sabdariffa is a medicinal plant consumed as a diuretic and anti-obesity remedy. Several pharmacological studies have shown its beneficial effects in metabolism. Peroxisome proliferator-activated receptors δ and γ may play a role in the actions of H. sabdariffa. These nuclear receptors regulate lipid and glucose metabolism and are therapeutic targets for type 2 diabetes. This research aimed to perform a phytochemical study guided by a bioassay from H. sabdariffa to identify compounds with peroxisome proliferator-activated receptor δ and peroxisome proliferator-activated receptor γ agonist activity, supported by messenger ribonucleic acid expression, molecular docking, lipid accumulation, and an antihyperglycemic effect. An oral glucose tolerance test in mice with the aqueous extract of H. sabdariffa and the dichloromethane extract of H. sabdariffa was performed. The dichloromethane extract of H. sabdariffa exhibited an antihyperglycemic effect. The dichloromethane extract of H. sabdariffa was fractioned, and four fractions were evaluated in 3T3-L1 adipocytes on peroxisome proliferator-activated receptor δ, peroxisome proliferator-activated receptor γ, fatty acid transporter protein, and glucose transporter type 4 messenger ribonucleic acid expression. Fraction F3 exhibited peroxisome proliferator-activated receptor δ/γ dual agonist activity, and a further fractionation yielded two subfractions, F3-1 and F3-2, which also increased peroxisome proliferator-activated receptor δ and peroxisome proliferator-activated receptor γ expression. Subfractions were analyzed by GC/MS. The main compounds identified in F3-1 were linoleic acid, oleic acid, and palmitic acid, while in F3-2, the main compounds identified were α-amyrin and lupeol. These molecules were subjected to molecular docking analysis. α-Amyrin and lupeol showed the highest affinity. Moreover, both produced an increase in peroxisome proliferator-activated receptor δ, peroxisome proliferator-activated receptor γ, fatty acid transporter protein, and glucose transporter type 4 expression. Additionally, α-amyrin and lupeol decreased lipid accumulation in 3T3-L1 adipocytes and blood glucose in mice. Until now, α-amyrin and lupeol have not been reported with activity on peroxisome proliferator-activated receptors. This study provides evidence that α-amyrin and lupeol possess antidiabetic effects through a peroxisome proliferator-activated receptor δ/γ dual agonist action.
Towards curative therapy of chronic viral hepatitis
Authors: Bartenschlager Ralf , Urban Stephan , Protzer Ulrike
Published: January 2019

Persistent infection with hepatitis viruses is a major medical burden that unfortunately is often ignored in the general public. This results in a massive under-diagnosis of these infections. According to the world health organization, the number of people dying every year from the consequence of hepatitis virus infection has surpassed the death rate caused by malaria and HIV and is equivalent to the one of tuberculosis. These numbers call for more intense efforts to devise more effective, ideally curative therapies that must become as widely accessible as they are e. g. for HIV infected individuals. A major step forward has been the development of curative antiviral therapy for chronic hepatitis C. In the case of hepatitis D virus, new drug candidates have been developed that should receive conditional approval very soon. For chronic hepatitis B, development is lagging behind but thanks to a re-emerging interest of pharmaceutical industry that was triggered by the success of hepatitis C therapy and the availability of novel infection systems, new attempts towards curative approaches for this highly prevalent infection are undertaken. Here we summarize the current status of therapy development for chronic viral hepatitis that ultimately aims at cure.
Interleukin-10 Protects Schwann Cells against Advanced Glycation End Products-Induced Apoptosis via NF-κB Suppression
Authors: Xu Shiqing , Bao Weijie , Men Xiuli , Liu Ying , Sun Jie , Li Jing , Liu Honglin , Cai Hanqing , Zhang Wenjian , Lou Jinning , Peng Liang
Published: January 2019

Demyelination resulting from Schwann cell injury is a main pathological feature of diabetic neuropathy, and a key contributor to this process may be inflammation due to advanced glycation end products (AGEs). Therefore, protection by anti-inflammation agents is anticipated. In this study, we showed that interleukin-10 (IL-10), an anti-inflammatory cytokine, inhibits apoptosis of Schwann cells induced by AGEs in vitro. We isolated and cultured Schwann cells from rat sciatic nerves. As detected by flow cytometry, apoptosis of Schwann cells markedly increased following incubation with AGEs for 48 h. However, pretreatment with IL-10 inhibited AGE-induced apoptosis. The effect of IL-10 on NF-κB, which is a very important regulator of inflammation, was also evaluated, and results showed high levels of phospho-NF-κB and nuclear localization of NF-κB in cells incubated with AGEs but low levels of phospho-NF-κB and cytoplasmic localization in the cells incubated with IL-10, indicating the activation of NF-κB by AGEs and inhibition of NF-κB by IL-10. Moreover, incubating Schwann cells with an NF-κB inhibitor (caffeic acid phenethyl ester) for 30 min before adding AGEs mimicked IL-10, lowering the amount of reactive oxygen species and activity of caspase-3 and also decreasing apoptosis in Schwann cells. These results indicate that IL-10 may protect Schwann cells against AGE-induced apoptosis by attenuating oxidative stress via the inhibition of activation of NF-κB.
Cytotoxic Prenylated Xanthones from the Leaves of Garcinia bracteata
Authors: Zhang Bao-Jun , Fu Wen-Wei , Wu Rong , Yang Jin-Ling , Yao Cai-Yun , Yan Bing-Xiong , Tan Hong-Sheng , Zheng Chang-Wu , Song Zhi-Jun , Xu Hong-Xi
Published: January 2019

Six new prenylated xanthones (1–6) and seventeen known xanthones were isolated from extracts of Garcinia bracteata leaves. Their structures were determined by extensive NMR and MS spectroscopic data analysis. The inhibitory activities of the isolates were assayed on HeLa, A549, PC-3, HT-29, and WPMY-1 cell lines. Compounds 1 and 15–17 showed moderate inhibitory effects on tumor cell growth, with IC50s ranging from 3.7 to 14.7 µM.
Selenosilane-Promoted Selective Mild Transformation of N-Thiophthalimides into Symmetric Disulfides
Authors: Viglianisi Caterina , Bonardi Chiara , Ermini Elena , Capperucci Antonella , Menichetti Stefano , Tanini Damiano
Published: January 2019

The reactivity of N-thiophthalimides with silyl chalcogenides is described. Treatment of N-thiophthalimides with bis(trimethylsilyl) sulfide [(Me3Si)2S] leads to the formation of a mixture of the corresponding disulfides and trisulfides. On the other hand, N-thiophthalimides react with bis(trimethylsilyl) selenide [(Me3Si)2Se] under TBAF catalysis to smoothly give variously substituted diaryl, divinyl, and dialkyl disulfides; formation of a selenotrisulfide (dithiaselane, RSSeSR) is rationalized as an intermediate. Exploiting the different chemical behavior of silyl chalcogenides, we have disclosed a novel, selective, and operationally simple method to access disulfides in good yields under mild conditions.
Lewis Acid Catalyzed Regio- and Diastereoselective Synthesis of Spiroisoxazolines via One-Pot Sequential Knoevenagel
Condensation/1,3-Dipolar Cycloaddition Reaction
Authors: Bazgir Ayoob , Yazdani Hossein
Published: January 2019

A ZnCl2-catalyzed regio- and diastereoselective one-pot sequential Knoevenagel condensation/1,3-dipolar cycloaddition reaction of CH acids (oxindole, 1,3-indandione, and 3H-pyrazol-3-one), aldehydes, and dibromoformaldoxime has been established. The method allows the synthesis of diversely functionalized spiroisoxazolines in good isolated yields under mild reaction conditions. Moreover, the preparation of spiroindene-isoxazole-1,3-diones containing benzoimidazole or benzothiazole moieties as new ligands for the metal-catalyzed coupling reactions and C–H activation is demonstrated.
One-Pot Synthesis of N-Arylated Amines by Hydroaminomethyl­ation of 2,5-Dihydrofuran with Aromatic Amines
Authors: Wang Lailai , Zheng Zhiwen
Published: January 2019

A new efficient catalytic system for one-step synthesis of N-arylated amines, for example, an important intermediate, 4-ethyl-N-[(tetrahydrofuran-3-yl)methyl]aniline, is achieved by using different rhodium precursor and phosphorus ligands catalyzed hydroaminomethylation of aniline and its derivatives with heterocyclic and/or cyclic olefins. By screening the reaction parameters, the optimal reaction conditions are found as follows: methanol as a solvent, PPh3 as a ligand, [Rh(cod)2]BF4 as a catalyst precursor, a P/Rh ratio of 5:1, syngas pressure 4 MPa (H2/CO = 3:1), 100 °C, 20 hours, and no additives. The conversion of aniline reaches >99% and the yield of N-[(tetrahydrofuran-3-yl)methyl]aniline is up to 99% using this catalytic system. Moreover, the reaction of aniline and various cyclic olefins is investigated under the optimal conditions, and excellent conversion and good yields are obtained.
Cyclopropenium-Activated DMSO for Swern-Type Oxidation
Authors: Guo Tianfo , Gao Yu , Li Zhenjiang , Liu Jingjing , Guo Kai
Published: January 2019

Swern oxidation is widely used to convert alcohols into their corresponding carbonyl compounds. However, the conventional method with use of the volatile oxalyl chloride as an activator requires the reaction to be conducted below −60 °C. We discovered that 3,3-dichloro-1,2-diphenylcyclopropene (DDC) can be used as a new activator for Swern-type oxidations of alcohols, which can be conducted at −20 °C. This new protocol features mild and fast reactions with easy operation. Furthermore, the activator DDC is easy to handle, and diphenylcyclopropenone can be recovered quantitively. This new type of Swern oxidation shows a broad scope of substrates including benzylic, allylic, aliphatic, and biobased alcohols, and gives high yields of up to 93%.
Highly Selective Reductive Cross-Amination between Aniline or Nitroarene Derivatives and Alkylamines Catalyzed by Polysilane-Immobilized Rh/Pt Bimetallic Nanoparticles
Authors: Suzuki Aya , Miyamura Hiroyuki , Kobayashi Shū
Published: January 2019

Reductive cross-amination between imine intermediates generated through partial hydrogenation of aniline or nitroarene derivatives and alkylamines is an ideal method for obtaining N-alkylated cyclohexylamine derivatives; however, no such transformations have hitherto been established. Here, we report a highly selective reductive cross-amination using aniline derivatives and alkylamines catalyzed by heterogeneous Rh/Pt bimetallic nanoparticles under mild conditions. The catalyst was recovered and reused for five runs, keeping high activity. In this reaction, imine intermediates generated during the course of partial hydrogenation of aniline derivatives were trapped immediately by strongly interacting primary alkylamines with the catalyst, which caused a highly selective transformation to give the desired products, while suppressing dicyclohexylamine formation.
2-[18F]Fluorophenylalanine: Synthesis by Nucleophilic 18F-Fluorination and Preliminary Biological Evaluation
Authors: Neumaier Bernd , Modemann Daniel , Zlatopolskiy Boris , Urusova Elizaveta , Zischler Johannes , Craig Austin , Ermert Johannes , Guliyev Mehrab , Endepols Heike
Published: January 2019

2-[18F]Fluorophenylalanine (2-[18F]FPhe), a promising PET tracer for imaging of cerebral infarction and tumors, was efficiently prepared from an easily accessible iodonium salt precursor using Cu-mediated radiofluorination under ‘low base’ or ‘minimalist’ conditions. Whereas significant racemization was initially observed if the ‘minimalist’ protocol was applied for radiolabeling, it was completely suppressed by the careful adjustment of 18F– preprocessing. The initial biological study revealed a higher uptake of 2-[18F]FPhe in different tumor cells in comparison to that of [18F]FET. In contrast to 4-[18F]FPhe, which suffered from rapid defluorination in vivo, 2-[18F]FPhe demonstrated a sufficient in vivo stability. Conclusively, 2-[18F]FPhe is a promising PET probe that is now readily available using Cu-mediated radiofluorination under ‘minimalist’ or ‘low base’ conditions. The simplicity of the translation of the proposed procedures to automated synthesis modules allows a broad biological evaluation of 2-[18F]FPhe. Notably, a novel protocol for the preparation of N-Boc protected amino acids from the respective Ni-Schiff base complexes was developed that avoided application of strongly acidic conditions.
Carbon Dioxide-Driven Palladium-Catalyzed C–H Activation of Amines: A Unified Approach for the Arylation of Aliphatic and Aromatic Primary and Secondary Amines
Authors: Young Michael , Kapoor Mohit , Chand-Thakuri Pratibha , Maxwell Justin , Liu Daniel , Zhou Hanyang
Published: January 2019

Amines are an important class of compounds in organic chemistry and serve as an important motif in various industries, including pharmaceuticals, agrochemicals, and biotechnology. Several methods have been developed for the C–H functionalization of amines using various directing groups, but functionalization of free amines remains a challenge. Here, we discuss our recently developed carbon dioxide driven highly site-selective γ-arylation of alkyl- and benzylic amines via a palladium-catalyzed C–H bond-activation process. By using carbon dioxide as an inexpensive, sustainable, and transient directing group, a wide variety of amines were arylated at either γ-sp3 or sp2 carbon–hydrogen bonds with high selectivity based on substrate and conditions. This newly developed strategy provides straightforward access to important scaffolds in organic and medicinal chemistry without the need for any expensive directing groups.

1 Introduction

2 C(sp3)–H Arylation of Aliphatic Amines

3 C(sp2)–H Arylation of Benzylamines

4 Mechanistic Questions

5 Future Outlook
An Investigation of the Reactions between Azido Alcohols and Phosphoramidites
Authors: Wu Jian , Bishop Lee , Guo Jiatong , Guo Zhongwu
Published: January 2019

The reactions of several β-, γ-, and δ-azido alcohols with dibenzyl and dimethyl N,N-diisopropylphosphoramidites were examined. Detailed analysis of the intermediates and products formed from the reactions under different conditions provided useful information to gain insights into their mechanisms involving intramolecular Staudinger reaction, as well as the structure–reactivity relationships of both substrates. The reactions of γ- and δ-azido alcohols with dibenzyl N,N-diisopropylphosphoramidite could produce 6- and 7-membered cyclic phosphoramidates, thereby providing a new synthetic method for these biologically important molecules.