Inzidenz und Differentialdiagnose unterschiedlicher synchroner Leberraumforderungen bei Erstdiagnose einer malignen Grunderkrankung : Stellenwert von Klinik, Ultraschall, CT, MRT, PET-CT und Histologie

Hintergrund: Ziel der Studie ist es, die Inzidenz synchroner fokaler Leberläsionen bei Erstdiagnose einer malignen Grunderkrankung zu bestimmen. Außerdem soll der Stellenwert der Bildgebungen CEUS, CT, MRT und PET-CT in der Abklärung der Leberraumforderungen untersucht werden. Patienten und Methoden: N = 446 Patienten mit synchroner Leberraumforderung bei Erstdiagnose einer malignen Grunderkrankung, welche am Universitätsklinikum Marburg sonographisch abgeklärt wurden, wurden in die Studie aufgenommen. Es wurde die endgültige Diagnose der Leberraumforderung verwendet. Der Einsatz und die Ergebnisse von CEUS, CT, MRT und PET-CT wurden miteinander verglichen. Ergebnisse: Von den n = 446 Leberläsionen waren n = 182 (40,8%) benigne und n = 264 (59,2%) maligne. Bei den benignen Leberraumforderungen handelte es sich um n = 94 Zysten (21,1%), n = 55 Hämangiome (12,3%), n = 21 fokale Fettverteilungsstörungen (4,7%), n = 4 fokal noduläre Hyperplasien (0,9%), n = 3 nicht weiter spezifizierte gutartige Läsionen (0,7%), n = 2 Regeneratknoten (0,4%) und n = 1 Adenom (0,2%). Bei den malignen Läsionen handelte es sich um n = 250 Metastasen (56,1%) und n = 14 Primärtumoren der Leber (3,1%). Es zeigte sich kein signifikanter Unterschied in der Sensitivität auf Malignität einer Leberraumforderung zwischen den unterschiedlichen Bildgebenden Verfahren Sonographie mit CEUS, CT, MRT und PET-CT. In der Spezifität für Malignität liegt die CT signifikant niedriger als die CEUS, alle anderen Verfahren unterscheiden sich nicht signifikant in der Spezifität. Fazit: Synchrone Leberraumforderungen bei Erstdiagnose einer malignen Grunderkrankung sind in 59,2% der Fälle maligne und sollten aufgrund der hohen therapeutischen Relevanz bei Lebermetastasen immer abschließend geklärt werden. Sonographie mit CEUS, CT, MRT und PET-CT sind für die Differenzierung und Spezifizierung synchroner Leberraumforderungen bei Erstdiagnose eine malignen Grunderkrankung in der klinischen Praxis von annähernd gleichem Stellenwert. Da bei Erstdiagnose einer malignen Grunderkrankung die Feststellung von Lebermetastasen oft schon für ein palliatives Behandlungssetting ausreicht, wären in diesem Fall weitere Erkenntnisse aus CT, MRT und PET-CT für die Therapieentscheidung nicht mehr relevan

Registrierung von Aufnahmen des Augenhintergrundes zur Erstellung großflächiger Kompositionsaufnahmen: Registration of fundus images for generating wide field composite images of the retina

Die Zusammensetzung von Aufnahmen des menschlichen Augenhintergrundes zu Kompositionsbildern stellt hohe Anforderungen an die verwendeten Verfahren. Erhebliche Beleuchtungsunterschiede innerhalb und zwischen den Bildern, strukturlose Bereiche und nichtlineare Verzerrungen stellen hierbei die größten Probleme dar. Die vorliegende Arbeit präsentiert einen automatischen Algorithmus zur Registrierung von Fundusaufnahmen sowie deren Transformation und Überlagerung zu großflächigen Kompositionsaufnahmen. Das Verfahren nutzt dabei sowohl den flächenbasierten als auch den punktbasierten Ansatz. Als Ähnlichkeitsmaß dient jeweils der normierte Korrelationskoeffizient, der sich im Vergleich zu ebenfalls untersuchten unterschiedlichen Definitionen der Transinformation als am besten geeignet erwies. Den Transformationen der Bilder liegt ein vollständig quadratisches Modell zugrunde, das die annähernd sphärische Oberfläche der Retina berücksichtigt und anhand visueller und quantitativer Bewertung aus insgesamt 5 untersuchten Modellen ausgewählt wurde. Der entwickelte Algorithmus erwies sich bei der Validierung an realen klinischen Daten als robust und zuverlässig. Die visuelle und quantitative Analyse der berechneten Bildmontagen ergab eine hohe Genauigkeit. Probleme können auftreten, wenn die zu registrierenden Bilder sehr unscharf sind oder sehr wenige relevante Strukturen enthalten

Transmitted drug resistance and subtype patterns of viruses from reported new HIV diagnoses in Germany, 2017–2020

Background The transmission of resistant HIV variants jeopardizes the effective use of antiretrovirals for therapy and prophylaxis. Molecular surveillance of new HIV diagnoses with a focus on prevalence and type of resistance associated mutations and the subtype of circulating viruses is mandatory. Method From 2017 to 2020, 11,527 new HIV diagnoses were reported in Germany to the Robert Koch Institute (RKI). Protease (PR) and reverse-transcriptase (RT) sequences were obtained from 4559 (39.6%) cases, and PR, RT and integrase (IN) sequences were obtained from 3097 (26.9%) cases. The sequences were analyzed with data from the national HIV reports. Results Among all cases in the analysis, the proportion of primary resistance was 4.3% for nucleoside reverse- transcriptase inhibitors (NRTIs), 9.2% for non-NRTI (NNRTIs), 3.3% for protease inhibitors (PIs) and 1.4% for integrase inhibitors (INIs). Dual-class resistance was highest for NRTIs/NNRTIs with 1.2%. There was no trend in the proportion of viruses resistant to drug classes. Most individual key mutations associated with relevant resistance had a prevalence below 1% including K65R (0.1%) and M184V (0.6%). A notable exception was K103NS, with a prevalence of 2.9% and a significant increase (pTrend=0.024) during 2017–2020. In this period, diagnoses of infections with HIV-1 subtype B were the most common at 58.7%, but its prevalence was declining (pTrend=0.049) while the frequency of minority subtypes (each < 1%) increased (pTrend=0.007). Subtype B was highest (75.6%) in men who have sex with men (MSM) and lowest in reported heterosexual transmissions (HETs, 22.6%). Conclusion The percentage of primary resistance was high but at a stable level. A genotypic determination of resistance is therefore still required before the start of therapy. The subtype diversity of circulating HIV-1 is increasing.Peer Reviewe

The clustering of the SDSS-IV extended Baryon Oscillation Spectroscopic Survey DR14 quasar sample : anisotropic Baryon Acoustic Oscillations measurements in Fourier-space with optimal redshift weights

We present a measurement of the anisotropic and isotropic Baryon Acoustic Oscillations (BAO) from the extended Baryon Oscillation Spectroscopic Survey Data Release 14 quasar sample with optimal redshift weights. Applying the redshift weights improves the constraint on the BAO dilation parameter α(zeff) by 17%. We reconstruct the evolution history of the BAO distance indicators in the redshift rangeof 0.8 < z < 2.2. This paper is part of a set that analyses the eBOSS DR14 quasar sample.PostprintPeer reviewe

The clustering of the SDSS-IV extended Baryon Oscillation Spectroscopic Survey DR14 quasar sample: Anisotropic Baryon Acoustic Oscillations measurements in Fourier-space with optimal redshift weights

We present a measurement of the anisotropic and isotropic Baryon Acoustic Oscillations (BAO) from the extended Baryon Oscillation Spectroscopic Survey Data Release 14 quasar sample with optimal redshift weights. Applying the redshift weights improves the constraint on the BAO dilation parameter $\alpha(z_{\rm eff})$ by 17\%. We reconstruct the evolution history of the BAO distance indicators in the redshift range of $0.8<z<2.2$. This paper is part of a set that analyses the eBOSS DR14 quasar sample.Comment: 8 pages, 6 figures, 3 tables; This paper is part of a set that analyses the eBOSS DR14 quasar sample; MNRAS submitte

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Long-acting injectable Cabotegravir + Rilpivirine for HIV maintenance therapy: Week 48 pooled analysis of phase 3 ATLAS and FLAIR trials

BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA &lt;50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA &lt;50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association

The clustering of the SDSS-IV extended Baryon Oscillation Spectroscopic Survey DR14 quasar sample: first measurement of baryon acoustic oscillations between redshift 0.8 and 2.2

We present measurements of the Baryon Acoustic Oscillation (BAO) scale in redshift-space using the clustering of quasars. We consider a sample of 147,000 quasars from the extended Baryon Oscillation Spectroscopic Survey (eBOSS) distributed over 2044 square degrees with redshifts $0.8 < z < 2.2$ and measure their spherically-averaged clustering in both configuration and Fourier space. Our observational dataset and the 1400 simulated realizations of the dataset allow us to detect a preference for BAO that is greater than 2.8$\sigma$. We determine the spherically averaged BAO distance to $z = 1.52$ to 3.8 per cent precision: $D_V(z=1.52)=3843\pm147 \left(r_{\rm d}/r_{\rm d, fid}\right)\$Mpc. This is the first time the location of the BAO feature has been measured between redshifts 1 and 2. Our result is fully consistent with the prediction obtained by extrapolating the Planck flat $\Lambda$CDM best-fit cosmology. All of our results are consistent with basic large-scale structure (LSS) theory, confirming quasars to be a reliable tracer of LSS, and provide a starting point for numerous cosmological tests to be performed with eBOSS quasar samples. We combine our result with previous, independent, BAO distance measurements to construct an updated BAO distance-ladder. Using these BAO data alone and marginalizing over the length of the standard ruler, we find $\Omega_{\Lambda} > 0$ at 6.6$\sigma$ significance when testing a $\Lambda$CDM model with free curvature.Comment: Accepted by MNRAS; BAO distance likelihood available in source files 'QSOv1.9fEZmock_BAOchi2.dat'; full set of data to be public eventually from SDSS websit

The 13th Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-IV Survey Mapping Nearby Galaxies at Apache Point Observatory

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in July 2014. It pursues three core programs: APOGEE-2,MaNGA, and eBOSS. In addition, eBOSS contains two major subprograms: TDSS and SPIDERS. This paper describes the first data release from SDSS-IV, Data Release 13 (DR13), which contains new data, reanalysis of existing data sets and, like all SDSS data releases, is inclusive of previously released data. DR13 makes publicly available 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA,the first data released from this survey. It includes new observations from eBOSS, completing SEQUELS. In addition to targeting galaxies and quasars, SEQUELS also targeted variability-selected objects from TDSS and X-ray selected objects from SPIDERS. DR13 includes new reductions ofthe SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification. DR13 releases new reductions of the APOGEE-1data from SDSS-III, with abundances of elements not previously included and improved stellar parameters for dwarf stars and cooler stars. For the SDSS imaging data, DR13 provides new, more robust and precise photometric calibrations. Several value-added catalogs are being released in tandem with DR13, in particular target catalogs relevant for eBOSS, TDSS, and SPIDERS, and an updated red-clump catalog for APOGEE.This paper describes the location and format of the data now publicly available, as well as providing references to the important technical papers that describe the targeting, observing, and data reduction. The SDSS website, http://www.sdss.org, provides links to the data, tutorials and examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ~6-year operations of SDSS-IV.PostprintPeer reviewe