180 research outputs found
123I-Methyljodbenzylguanidin- (MIBG-) Szintigraphie: Paradoxe Nuklidspeicherung eines onkozytären Nebennierenrindenkarzinoms
Zusammenfassung: Das mit Radiojod markierte Katecholaminanalogon Methyljodbenzylguanidin (MIBG) eignet sich aufgrund seiner selektiven Aufnahme in chromaffine Gewebe in hervorragender Weise für die bildgebende Diagnostik des Phäochromozytoms und besitzt hier nach Literaturangaben eine Sensitivität von etwa 90% und eine Spezifität von annähernd 100%. Die falsch-positive oder paradoxe MIBG-Speicherung einer adrenokortikalen Neoplasie stellt demgegenüber eine Rarität dar. Wir berichten über diese Situation am Beispiel eines metastasierten onkozytären Nebennierenrindenkarzinoms mit teilweise therapeutisch genutzter MIBG-Speicherung in verschiedenen Tumormanifestatione
Ultra-High Energy Cosmic Ray Nuclei from Individual Magnetized Sources
We investigate the dependence of composition, spectrum and angular
distributions of ultra-high energy cosmic rays above 10^19 eV from individual
sources on their magnetization. We find that, especially for sources within a
few megaparsecs from the observer, observable spectra and composition are
severely modified if the source is surrounded by fields of ~ 10^-7 Gauss on
scales of a few megaparsecs. Low energy particles diffuse over larger distances
during their energy loss time. This leads to considerable hardening of the
spectrum up to the energy where the loss distance becomes comparable to the
source distance. Magnetized sources thus have very important consequences for
observations, even if cosmic rays arrive within a few degrees from the source
direction. At the same time, details in spectra and chemical composition may be
intrinsically unpredictable because they depend on the unknown magnetic field
structure. If primaries are predominantly nuclei of atomic mass A accelerated
up to a maximum energy E_max with spectra not much softer than E^-2, secondary
protons from photo-disintegration can produce a conspicuous peak in the
spectrum at energy ~ E_max/A. A related feature appears in the average mass
dependence on energy.Comment: 15 pages, 16 ps figures, published version with minor changes, see
http://stacks.iop.org/1475-7516/2004/i=08/a=01
Constrained Simulations of the Magnetic Field in the Local Universe and the Propagation of UHECRs
We use simulations of LSS formation to study the build-up of magnetic fields
(MFs) in the ICM. Our basic assumption is that cosmological MFs grow in a MHD
amplification process driven by structure formation out of a seed MF present at
high z. Our LCDM initial conditions for the density fluctuations have been
statistically constrained by the observed galaxies, based on the IRAS 1.2-Jy
all-sky redshift survey. As a result, prominent galaxy clusters in our
simulation coincide closely with their real counterparts. We find excellent
agreement between RMs of our simulated clusters and observational data. The
improved resolution compared to previous work also allows us to study the MF in
large-scale filaments, sheets and voids. By tracing the propagation of UHE
protons in the simulated MF we construct full-sky maps of expected deflection
angles of protons with arrival energies E=1e20eV and 4e19eV, respectively.
Strong deflections are only produced if UHE protons cross clusters, however
covering only a small area on the sky. Multiple crossings of sheets and
filaments over larger distances may give rise to noticeable deflections,
depending on the model adopted for the magnetic seed field. Based on our
results we argue that over a large fraction of the sky the deflections are
likely to remain smaller than the present experimental angular sensitivity.
Therefore, we conclude that forthcoming air shower experiments should be able
to locate sources of UHE protons and shed more light on the nature of
cosmological MFs.Comment: 3revised version, JCAP, accepte
Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score.
PURPOSE: The phase III KEYNOTE-048 (ClinicalTrials.gov identifier: NCT02358031) trial of pembrolizumab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) included planned efficacy analyses in the total population and in participants with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1 and CPS ≥ 20. To further characterize the predictive value of PD-L1 expression on outcome, we conducted efficacy analyses in the PD-L1 CPS < 1 and CPS 1-19 subgroups in KEYNOTE-048. METHODS: Participants with R/M HNSCC and no prior systemic therapy for R/M disease were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Post hoc efficacy analyses of the PD-L1 CPS < 1 and CPS 1-19 subgroups were performed. RESULTS: Of 882 participants enrolled, 128 had PD-L1 CPS < 1 and 373 had CPS 1-19. For pembrolizumab versus cetuximab-chemotherapy, the median overall survival was 7.9 versus 11.3 months in the PD-L1 CPS < 1 subgroup (hazard ratio [HR], 1.51 [95% CI, 0.96 to 2.37]) and 10.8 versus 10.1 months in the CPS 1-19 subgroup (HR, 0.86 [95% CI, 0.66 to 1.12]). For pembrolizumab-chemotherapy versus cetuximab-chemotherapy, the median overall survival was 11.3 versus 10.7 months in the PD-L1 CPS < 1 subgroup (HR, 1.21 [95% CI, 0.76 to 1.94]) and 12.7 versus 9.9 months in the CPS 1-19 subgroup (HR, 0.71 [95% CI, 0.54 to 0.94]). CONCLUSION: Increased efficacy of pembrolizumab or pembrolizumab-chemotherapy was observed with increasing PD-L1 expression. PD-L1 CPS < 1 subgroup analysis was limited by small participant numbers. Results from the PD-L1 CPS 1-19 subgroup support previous findings of treatment benefit with pembrolizumab monotherapy and pembrolizumab-chemotherapy in patients with PD-L1 CPS ≥ 1 tumors. Although PD-L1 expression is informative, exploration of additional predictive biomarkers is needed for low PD-L1-expressing HNSCC
Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study.
PURPOSE: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented. METHODS: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment. RESULTS: The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio [HR], 0.61; 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes. CONCLUSION: With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy
Late term tolerance in head neck cancer patients irradiated in the IMRT era
BACKGROUND: The aim was to quantify severe transient and persisting late term effects in our single institution head neck cancer (HNC) cohort treated with curatively intended intensity modulated radiation therapy (IMRT). Hypothesis was if a 2-year follow up (FU) is sufficient to estimate the long term tolerance in HNC irradiated in the IMRT era. METHODS: Between 01/2002-8/2012, 707/1211 (58%) consecutively treated IMRT patients met the inclusion criteria of a FU time >12 months and loco-regional disease control (LRC). 45% presented with loco-regionally advanced disease; 55% were referred for curative definitive IMRT (66Gy-72Gy in 30--35 fractions), 45% underwent postoperative IMRT (60-66Gy in 30--33 fractions). Systemic concomitant therapy was administered in 85%. Highly consistent treatment procedures were performed with respect to contouring processes, dose constraints, radiation schedules, and the use of systemic therapy. Grade 3/4 late term effects were prospectively assessed and analyzed with respect to subgroups at particular risk for specific late effects. RESULTS: Mean/median FU of the cohort was 41/35 months (15--124). 13% of the patients (92/707) experienced any grade 3/4 late effects (101 events in 92/707 patients), 81% in the first 12 months after radiation. 4% of all developed persisting late grade 3/4 effects (25 events in 25/707 patients). CONCLUSIONS: IMRT led to a high late term tolerance in loco-regionally disease free HNC patients. The onset of any G3/4 effects showed a plateau at 2 years. The question of the cervical vessel tolerance in disease free long time survivors is still open and currently under evaluation at our institution
Non-thermal processes in cosmological simulations
Non-thermal components are key ingredients for understanding clusters of
galaxies. In the hierarchical model of structure formation, shocks and
large-scale turbulence are unavoidable in the cluster formation processes.
Understanding the amplification and evolution of the magnetic field in galaxy
clusters is necessary for modelling both the heat transport and the dissipative
processes in the hot intra-cluster plasma. The acceleration, transport and
interactions of non-thermal energetic particles are essential for modelling the
observed emissions. Therefore, the inclusion of the non-thermal components will
be mandatory for simulating accurately the global dynamical processes in
clusters. In this review, we summarise the results obtained with the
simulations of the formation of galaxy clusters which address the issues of
shocks, magnetic field, cosmic ray particles and turbulence.Comment: 27 pages, 16 figures, accepted for publication in Space Science
Reviews, special issue "Clusters of galaxies: beyond the thermal view",
Editor J.S. Kaastra, Chapter 15; work done by an international team at the
International Space Science Institute (ISSI), Bern, organised by J.S.
Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke
Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry
AimsTo analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients.Methods and resultsPatients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6-12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.ConclusionIn 'real world' clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available
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