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Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re‐transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15‐year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re‐DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re‐DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re‐DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.
Die Applikation von Medikamenten zur konservativen Behandlung von Patientinnen mit ektopen Schwangerschaften ist weltweit seit vielen Jahren im klinischen Alltag erfolgreich eingesetzt worden. Am erfolgreichsten zeigte sich über die Jahre, die medikamentöse Methotrexatgabe. Dies wurde eindrucksvoll in in-vivo und in in-vitro Studien bewiesen. Ausgangsbedingungen für die vorliegende Untersuchung sind die zahlreichen experimentellen Untersuchungen zur Wirkung von Prostaglandinen auf den mütterlichen Organismus (speziell glatte Muskelzellen der Blutgefäße, des Uterus und Tubenmuskulatur sowie das Corpus luteum) und die zahlreichen klinischen Fallberichte und Studien zur Anwendung von Prostaglandinen zur Behandlung der EUG. In vitro Studien zu der Wirkweise von Prostaglandinen auf ektopes Schwangerschaftsgewebe gibt es nur in geringer Zahl. Da Prostaglandin E2 in der Geburtshilfe einen festen Platz in der Geburtsinduktion und Zervixreifung hat, haben wir Prostaglandin E2 in vitro auf seine Wirkung auf ektopes Trophoblastengewebe untersucht. In der hier vorgelegten Arbeit sollte die Fragestellung überprüft werden, inwieweit eine medikamentöse Wirkung von Prostaglandin E2 Dinoproston auf Trophoblastengewebe aus extrauterinen Schwangerschaften in einem standardisierten Gewebekultursystem besteht. Aus operativ gewonnenen Extrauteringraviditäten des ersten Trimenons wurde Choriongewebe extrahiert, und in unterschiedlichen Konzentrationen der Wirkstoff Prostaglandin E2 Dinoproston 12 Stunden nach Kulturansatz den Gewebekulturen zugesetzt. Eine weitere Choriongewebekulturzellreihe wurde erst am 6. Tag mit Prostaglandin E2 behandelt. Das durch die Throphoblastenzellen sezernierte Humane Chorion Gonadotropin (HCG) wurde den Kulturen alle zwei Tage entnommen und gemessen. Alle Kulturen zeigten Sekretion von HCG innerhalb der ersten 16 Tage. Das Ergebnis dieser Versuchsreihen zeigte, dass weder die unterschiedlichen Prostaglandin E2-Konzentrationen, noch der Zeitpunkt der Zugabe, eine signifikante Auswirkung auf die HCG Sekretion von ektopen Schwangerschaften hat. Die Kontrollgruppe mit intrauterinem Trophoblastenmaterial bestätigt die fehlende Wirkung auf Throphoblastengewebe in der Zellkultur.
A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at sNN−−−√=2.76 TeV is reported. Jets are reconstructed from charged particles using the anti-kT jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η|<0.5. The transverse momentum pT of charged particles is measured down to 0.15 GeV/c which gives access to the low pT fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high pT leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R=0.2 and R=0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R<0.3.
Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 < pT,assoc < pT,trig < 5.0 GeV/c is examined, to include correlations induced by jets originating from low momentum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |η| < 0.9. The near-side long-range pseudorapidity correlations observed in high-multiplicity p–Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton–parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p–Pb collisions. Further, the number scales only in the intermediate multiplicity region with the number of binary nucleon–nucleon collisions estimated with a Glauber Monte-Carlo simulation.
Simple Summary: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Clinical phenotypes of frequent mutations and their impact on patient outcome are well established. However, the role of rare mutations often remains elusive. We retrospectively analyzed 1529 newly diagnosed and intensively treated AML patients for mutations of BCOR and BCORL1. We report a distinct co-mutational pattern that suggests a role in disease progression rather than initiation, especially affecting mechanisms of DNA-methylation. Further, we found loss-of-function mutations of BCOR to be independent markers of poor outcomes in multivariable analysis. Therefore, loss-of-function mutations of BCOR need to be considered for AML management, as they may influence risk stratification and subsequent treatment allocation.
Abstract: Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
Ziel: Die Evaluation der DEGUM-Mammasonografiekurse nach objektivierbaren Kriterien war Ziel dieser Arbeit. Damit sollte die Qualität der Kurse überprüft werden, um eine flächendeckende Fort- und Weiterbildung auf hohem Niveau anzubieten.
Material und Methoden: 10 Qualitätskriterien, orientierend an den Vorgaben der KBV-Ultraschallvereinbarungen wurden als Qualitätsparameter definiert. Alle Kursleiter des Arbeitskreises Mammasonografie der DEGUM wurden angeschrieben. Dabei wurden die 10 definierten Qualitätskriterien überprüft.
Ergebnisse: Alle Kurse erfüllten die Voraussetzungen bezüglich der Qualität des Kursleiters, der Kursdauer und Unterrichtseinheiten sowie der Anzahl an Kursteilnehmern pro Ultraschallgerät. In 1 von 9 Kursen wurde die Zeit der praktischen Übungen, gefordert sind 50 %, unterschritten. Die Voraussetzungen für den Abschlusskurs (200 selbst durchgeführte und dokumentierte Fälle) sind in den Kursankündigungen zum Teil nicht klar definiert. Ein strukturierter Lehrkatalog fehlt.
Schlussfolgerung: Die DEGUM-Mammasonografiekurse werden auf hohem Niveau angeboten und erfüllen zum größten Teil die Anforderungen der KBV. Trotz der hohen Qualität der DEGUM-Kurse sind Optimierungsoptionen im Bereich Kursankündigung und strukturierter Lehrkatalog möglich.
We present results on transverse momentum (pT) and rapidity (y) differential production cross sections, mean transverse momentum and mean transverse momentum square of inclusive J/ψ and ψ(2S) at forward rapidity (2.5 < y < 4) as well as ψ(2S)-to-J/ψ cross section ratios. These quantities are measured in pp collisions at center of mass energies s√=5.02 and 13 TeV with the ALICE detector. Both charmonium states are reconstructed in the dimuon decay channel, using the muon spectrometer. A comprehensive comparison to inclusive charmonium cross sections measured at s√=2.76, 7 and 8 TeV is performed. A comparison to non-relativistic quantum chromodynamics and fixed-order next-to-leading logarithm calculations, which describe prompt and non-prompt charmonium production respectively, is also presented. A good description of the data is obtained over the full pT range, provided that both contributions are summed. In particular, it is found that for pT > 15 GeV/c the non-prompt contribution reaches up to 50% of the total charmonium yield.
The first measurements of anisotropic flow coefficients vn for mid-rapidity charged particles in Xe–Xe collisions at √sNN = 5.44 TeV are presented. Comparing these measurements to those from Pb–Pb collisions at √sNN = 5.02 TeV, v2 is found to be suppressed for mid-central collisions at the same centrality, and enhanced for central collisions. The values of v3 are generally larger in Xe–Xe than in Pb–Pb at a given centrality. These observations are consistent with expectations from hydrodynamic predictions. When both v2 and v3 are divided by their corresponding eccentricities for a variety of initial state models, they generally scale with transverse density when comparing Xe–Xe and Pb–Pb, with some deviations observed in central Xe–Xe and Pb–Pb collisions. These results assist in placing strong constraints on both the initial state geometry and medium response for relativistic heavy-ion collisions.