Prognostic impact of CD4-positive T cell subsets in early breast cancer : a study based on the FinHer trial patient population

Background: The clinical importance of tumor-infiltrating cluster of differentiation 4 (CD4) T cells is incompletely understood in early breast cancer. We investigated the clinical significance of CD4, forkhead box P3 (FOXP3), and B cell attracting chemokine leukocyte chemoattractant-ligand (C-X-C motif) 13 (CXCL13) in early breast cancer. Methods: The study is based on the patient population of the randomized FinHer trial, where 1010 patients with early breast cancer were randomly allocated to adjuvant chemotherapy containing either docetaxel or vinorelbine, and human epidermal growth factor receptor 2 (HER2)-positive patients were also allocated to trastuzumab or no trastuzumab. Breast cancer CD4, FOXP3, and CXCL13 contents were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), and their influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates in the entire cohort and in selected molecular subgroups. Interactions between variables were analyzed using Cox regression. The triple-negative breast cancer (TNBC) subset of the HE10/97 randomized trial was used for confirmation. Results: High CXCL13 was associated with favorable DDFS in univariable analysis, and independently in multivariable analysis (HR 0.44, 95% CI 0.29-0.67, P Conclusions: The results provide a high level of evidence that humoral immunity influences the survival outcomes of patients with early breast cancer, in particular of those with TNBC.Peer reviewe

ARGOS: the laser guide star system for the LBT

ARGOS is the Laser Guide Star adaptive optics system for the Large Binocular Telescope. Aiming for a wide field adaptive optics correction, ARGOS will equip both sides of LBT with a multi laser beacon system and corresponding wavefront sensors, driving LBT's adaptive secondary mirrors. Utilizing high power pulsed green lasers the artificial beacons are generated via Rayleigh scattering in earth's atmosphere. ARGOS will project a set of three guide stars above each of LBT's mirrors in a wide constellation. The returning scattered light, sensitive particular to the turbulence close to ground, is detected in a gated wavefront sensor system. Measuring and correcting the ground layers of the optical distortions enables ARGOS to achieve a correction over a very wide field of view. Taking advantage of this wide field correction, the science that can be done with the multi object spectrographs LUCIFER will be boosted by higher spatial resolution and strongly enhanced flux for spectroscopy. Apart from the wide field correction ARGOS delivers in its ground layer mode, we foresee a diffraction limited operation with a hybrid Sodium laser Rayleigh beacon combination.12 page(s

Long-term survival with modern therapeutic agents against metastatic melanoma-vemurafenib and ipilimumab in a daily life setting

Despite new therapeutic options, metastatic melanoma remains to be one of the most fatal tumors. With the development of BRAF inhibitors and immune checkpoint inhibitors, overall survival could be prolonged significantly for the first time. Clinical studies implied that even long-term survival is possible with both types of drugs, but predictive markers are so far missing. In this study, we analyzed survival data from patients that received the first-in-class substances vemurafenib and ipilimumab, respectively, during the time period from registration of the drugs until availability of combination treatments. We aimed to evaluate the possibility of long-term survival in a daily life setting and to characterize patients that benefit from these drugs in order to gain insight into predictive attributes. Eighty patients were evaluated who were treated with either vemurafenib (n = 40) or ipilimumab (n = 40), and overall survival was analyzed. Subgroup analysis was performed for patients who were still alive 24 months after induction of therapy (long-term survival). Median overall survival (OS) was 8.0 months for patients treated with vemurafenib and 10.0 months for patients treated with ipilimumab (log-rank P value = 0.689). Long-term survival was achieved in 32.5% of patients (42.3% vemurafenib, 57.7% ipilimumab). Negative predictors of long-term survival in the vemurafenib group were brain and liver metastases, as well as elevated LDH, S100ß and liver enzymes. For ipilimumab, an increase in lymphocytes and eosinophils during course of treatment correlated with long-term survival. Our real-life experience shows that long-term survival is possible with using both therapeutic agents, vemurafenib and ipilimumab. Pattern of metastases and laboratory values might be of interest in decision making for a specific therapeutic approach. Combination of drugs and observational studies in larger patient cohorts are necessary to further validate our findings

Recruiting former melanoma patients via hospitals in comparison to office-based dermatologists in a register-based cohort study that required indirect contact

Abstract Background There are detailed reviews about different recruitment strategies, but not with regard to differences between recruitment of hospital-based versus office-based physicians. Within this study, the two different recruitment schemes are compared. Advantages and disadvantages of different ways of recruitment in registry-based studies are discussed. Methods In a cross-sectional cancer-registry-based study, long-term melanoma patients were contacted by dermatologists rather than directly by the registry on the basis of the legal situation. Logistic regression models and generalized estimating equations were used to assess effects of various patient and physician characteristics on participation and data quality. Especially differences between hospital-based versus office-based dermatologists are evaluated. Results Seventy two out of 112 contacted dermatologists took part in the study (64.3%). The cooperation proportion was 52.2% (689 participants/1320 contacted patients). Participants and non-participants differed regarding age and sex, but not regarding other social demographic factors and cancer stage. We did not observe a difference in patient participation between hospital-based versus office-based dermatologists (OR 1.08 [CI 0.84–1.39]; p = 0.57). However, medical data provided by the cancer registry were better for participants registered and recruited by hospitals. Conclusions In cohort studies with epidemiological cancer registries, recruitment via physicians has potential disadvantages and is more complex. If this indirect way of contact is mandatory, we recommend recruitment procedures including hospital-based rather than office-based physicians. However, physician characteristics were not associated with outcome

Course of the intraocular pressure (IOP) fluctuations at all timepoints during the first (”pre-op”, blue line) and second diurnal-nocturnal IOP profile (”post-op”, green line) [mmHg].

<p>Course of the intraocular pressure (IOP) fluctuations at all timepoints during the first (”pre-op”, blue line) and second diurnal-nocturnal IOP profile (”post-op”, green line) [mmHg].</p

Status report on the Large Binocular Telescope's ARGOS ground-layer AO system

ARGOS, the laser-guided adaptive optics system for the Large Binocular Telescope (LBT), is now under construction at the telescope. By correcting atmospheric turbulence close to the telescope, the system is designed to deliver high resolution near infrared images over a field of 4 arc minute diameter. Each side of the LBT is being equipped with three Rayleigh laser guide stars derived from six 18 W pulsed green lasers and projected into two triangular constellations matching the size of the corrected field. The returning light is to be detected by wavefront sensors that are range gated within the seeing-limited depth of focus of the telescope. Wavefront correction will be introduced by the telescope's deformable secondary mirrors driven on the basis of the average wavefront errors computed from the respective guide star constellation. Measured atmospheric turbulence profiles from the site lead us to expect that by compensating the ground-layer turbulence, ARGOS will deliver median image quality of about 0.2 arc sec across the JHK bands. This will be exploited by a pair of multi-object near-IR spectrographs, LUCIFER1 and LUCIFER2, with 4 arc minute field already operating on the telescope. In future, ARGOS will also feed two interferometric imaging instruments, the LBT Interferometer operating in the thermal infrared, and LINC-NIRVANA, operating at visible and near infrared wavelengths. Together, these instruments will offer very broad spectral coverage at the diffraction limit of the LBT's combined aperture, 23 m in size

Course of the intraocular pressure values (IOP) at all timepoints in the first (”pre-op”) and second diurnal-nocturnal IOP profile (”post-op”).

<p>Course of the intraocular pressure values (IOP) at all timepoints in the first (”pre-op”) and second diurnal-nocturnal IOP profile (”post-op”).</p

Mean intraocular pressure values (IOP) on the first and second day of the first diurnal-nocturnal IOP profile.

<p>Outliers—values beyond 1.5 x interquartile range—are marked as circles (“out” values) and stars (“far out” values).</p

Mean intraocular pressure (IOP) measured during daytime, at night and during the whole first (“pre-op”) and second diurnal-nocturnal IOP (“post-op”) profile [mmHg].

<p>Outliers—values beyond 1.5 x interquartile range—are marked as circles (“out” values) and stars (“far out” values).</p