Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study.

BACKGROUND: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. PATIENTS AND METHODS: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. RESULTS: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). CONCLUSIONS: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CLINICAL TRIALS NUMBER: CFEM345DDE19.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

A Rare Case of Diffuse Hemangiomatosis of the Spleen with Splenic Rupture following Aortic Valve Replacement.

In this paper we present a rare case of splenic rupture that occurred after an open aortic valve replacement in a male patient with hemangiomatosis of the spleen and the liver. The patient was treated with an emergency splenectomy. He showed no other sings of associated systemic disorder, such as Klippel-trénaunay syndrome or Proteus syndrome.

Comparison of the Radiation Dose from Cone Beam Computed Tomography and Multidetector Computed Tomography in Examinations of the Hand.

PURPOSE: Comparison of radiation dose of cone beam computed tomography (CBCT) and multidetector computed tomography (MDCT) in examinations of the hand. MATERIALS AND METHODS: Dose calculations were carried out by means of Monte Carlo simulations in MDCT and CBCT. A corpse hand was examined in a 320-row MDCT scanner and a dedicated extremities CBCT scanner with standard protocols and multiple low-dose protocols. The image quality of the examinations was evaluated by 5 investigators using a Likert scale from 1 (very good) to 5 (very poor) regarding depiction of cortical bone, cancellous bone, joint surfaces, soft tissues and artifacts. For a sum of ratings of all structures < 50 a good overall image quality was expected. The studies with at least good overall image quality were compared with respect to the dose. RESULTS: The dose of the standard examination was 13.21 (12.96 to 13.46 CI) mGy in MDCT and 7.15 (6.99 to 7.30 CI) mGy in CBCT. The lowest dose in a study with good overall image quality was 4.54 (4.43 to 4.64 CI) mGy in MDCT and 5.72 (5.59 to 5.85 CI) mGy in CBCT. CONCLUSION: Although the dose of the standard protocols in the CBCT is lower than in the MDCT, the MDCT can realize a good overall image quality at a lower dose than the CBCT. Dose optimization of CT examination protocols for the hand is useful in both modalities, the MDCT has an even greater potential for optimization. KEY POINTS: • Low dose examinations of the hand are feasible in CBCT and MDCT.• In default settings CBCT has a lower dose than MDCT.• MDCT enables a good image quality at a lower dose than CBCT. Citation Format: • Neubauer J, Neubauer C, Gerstmair A et al. Comparison of the Radiation Dose from Cone Beam Computed Tomography and Multidetector Computed Tomography in Examinations of the Hand. Fortschr Röntgenstr 2016; 188: 488 - 493.

Optical Sensing of Microbial Life on Surfaces.

The label-free detection of microbial cells attached to a surface is an active field of research. The field is driven by the need to understand and control the growth of biofilms in a number of applications, including basic research in natural environments, industrial facilities, and clinical devices, to name a few. Despite significant progress in the ability to monitor the growth of biofilms and related living cells, the sensitivity and selectivity of such sensors are still a challenge. We believe that among the many different technologies available for monitoring biofilm growth, optical techniques are the most promising, as they afford direct imaging and offer high sensitivity and specificity. Furthermore, as each technique offers different insights into the biofilm growth mechanism, our analysis allows us to provide an overview of the biological processes at play. In addition, we use a set of key parameters to compare state-of-the-art techniques in the field, including a critical assessment of each method, to identify the most promising types of sensors. We highlight the challenges that need to be overcome to improve the characteristics of current biofilm sensor technologies and indicate where further developments are required. In addition, we provide guidelines for selecting a suitable sensor for detecting microbial cells on a surface.

Spatial Resolution and Refractive Index Contrast of Resonant Photonic Crystal Surfaces for Biosensing.

By depositing a resolution test pattern on top of a Si3N4 photonic crystal resonant surface, we have measured the dependence of spatial resolution on refractive index contrast Δn. Our experimental results and finite-difference time-domain (FDTD) simulations at different refractive index contrasts show that the spatial resolution of our device reduces with reduced contrast, which is an important consideration in biosensing, where the contrast may be of order 10-2. We also compare 1-D and 2-D gratings, taking into account different incidence polarizations, leading to a better understanding of the excitation and propagation of the resonant modes in these structures, as well as how this contributes to the spatial resolution. At Δn = 0.077, we observe resolutions of 2 and 6 µm parallel to and perpendicular to the grooves of a 1-D grating, respectively, and show that for polarized illumination of a 2-D grating, resolution remains asymmetrical. Illumination of a 2-D grating at 45° results in symmetric resolution. At very low index contrast, the resolution worsens dramatically, particularly for Δn < 0.01, where we observe a resolution exceeding 10 µm for our device. In addition, we measure a reduction in the resonance linewidth as the index contrast becomes lower, corresponding to a longer resonant mode propagation length in the structure and contributing to the change in spatial resolution.

Hydrogen induced optically-active defects in silicon photonic nanocavities.

We demonstrate intense room temperature photoluminescence (PL) from optically active hydrogen- related defects incorporated into crystalline silicon. Hydrogen was incorporated into the device layer of a silicon on insulator (SOI) wafer by two methods: hydrogen plasma treatment and ion implantation. The room temperature PL spectra show two broad PL bands centered at 1300 and 1500 nm wavelengths: the first one relates to implanted defects while the other band mainly relates to the plasma treatment. Structural characterization reveals the presence of nanometric platelets and bubbles and we attribute different features of the emission spectrum to the presence of these different kind of defects. The emission is further enhanced by introducing defects into photonic crystal (PhC) nanocavities. Transmission electron microscopy analyses revealed that the isotropicity of plasma treatment causes the formation of a higher defects density around the whole cavity compared to the ion implantation technique, while ion implantation creates a lower density of defects embedded in the Si layer, resulting in a higher PL enhancement. These results further increase the understanding of the nature of optically active hydrogen defects and their relation with the observed photoluminescence, which will ultimately lead to the development of intense and tunable crystalline silicon light sources at room temperature.

Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up.

The Enchondroma is a common, benign, cartilage forming tumour. They usually occur as a single, asymptomatic lesion. Occasionally patients present with multiple enchondromas which is generally defined as enchondromatosis. This entity encompasses several different subtypes including Ollier disease and Maffucci syndrome (enchondromatosis associated with soft tissue haemangiomas) as the most commons. Some of them have a complicated clinical course when malignant transformation occurs. This malignant progression is a well known fact especially in enchondromatosis, but up to now there is still a lack of recommendations concerning the follow up. The aim of this article is to review the clinical and imaging features of patients with solitary enchondroma and enchondromatosis focusing on the development of secondary chondrosarcoma and the follow up.

Observation of soliton compression in silicon photonic crystals.

Solitons are nonlinear waves present in diverse physical systems including plasmas, water surfaces and optics. In silicon, the presence of two photon absorption and accompanying free carriers strongly perturb the canonical dynamics of optical solitons. Here we report the first experimental demonstration of soliton-effect pulse compression of picosecond pulses in silicon, despite two photon absorption and free carriers. Here we achieve compression of 3.7 ps pulses to 1.6 ps with <10 pJ energy. We demonstrate a ~1-ps free-carrier-induced pulse acceleration and show that picosecond input pulses are critical to these observations. These experiments are enabled by a dispersion-engineered slow-light photonic crystal waveguide and an ultra-sensitive frequency-resolved electrical gating technique to detect the ultralow energies in the nanostructured device. Strong agreement with a nonlinear Schrödinger model confirms the measurements. These results further our understanding of nonlinear waves in silicon and open the way to soliton-based functionalities in complementary metal-oxide-semiconductor-compatible platforms.

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study.

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1-5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5-10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information.

Bidirectional multiplexing of heralded single photons from a silicon chip.

We demonstrate integrated spatial multiplexing of heralded single photons generated from a single 96 µm long silicon photonic crystal waveguide in a bidirectional pump configuration. By using a low-loss fiber-coupled opto-ceramic switch, the multiplexing technique enhances the brightness of the single photon source by 51.2±4.0% while maintaining the coincidence-to-accidental ratio. Compared with the demonstration of multiplexing two individual sources, the bidirectional pump scheme represents a twofold reduction in the footprint of nonlinear devices for future large-scale integration of on-chip single photon sources. The 51.2±4.0% gain will make any quantum operation requiring n photons 1.5(n) times faster.

Integrated spatial multiplexing of heralded single-photon sources.

The non-deterministic nature of photon sources is a key limitation for single-photon quantum processors. Spatial multiplexing overcomes this by enhancing the heralded single-photon yield without enhancing the output noise. Here the intrinsic statistical limit of an individual source is surpassed by spatially multiplexing two monolithic silicon-based correlated photon pair sources in the telecommunications band, demonstrating a 62.4% increase in the heralded single-photon output without an increase in unwanted multipair generation. We further demonstrate the scalability of this scheme by multiplexing photons generated in two waveguides pumped via an integrated coupler with a 63.1% increase in the heralded photon rate. This demonstration paves the way for a scalable architecture for multiplexing many photon sources in a compact integrated platform and achieving efficient two-photon interference, required at the core of optical quantum computing and quantum communication protocols.

Enhanced 1.54 µm emission in Y-Er disilicate thin films on silicon photonic crystal cavities.

We introduce an Y-Er disilicate thin film deposited on top of a silicon photonic crystal cavity as a gain medium for active silicon photonic devices. Using photoluminescence analysis, we demonstrate that Er luminescence at 1.54 µm is enhanced by coupling with the cavity modes, and that the directionality of the Er optical emission can be controlled through far-field optimization of the cavity. We determine the maximum excitation power that can be coupled into the cavity to be 12 mW, which is limited by free carrier absorption and thermal heating. At maximum excitation, we observe that nearly 30% of the Er population is in the excited state, as estimated from the direct measurement of the emitted power. Finally, using time-resolved photoluminescence measurements, we determine a value of 2.3 for the Purcell factor of the system at room temperature. These results indicate that overcoating a silicon photonic nanostructure with an Er-rich dielectric layer is a promising method for achieving light emission at 1.54 µm wavelength on a silicon platform.

Unenhanced versus multiphase MDCT in patients with hematuria, flank pain, and a negative ultrasound.

OBJECTIVES: To compare the impact of unenhanced and contrast-enhanced multi-detector computed tomography (MDCT) for the detection of urinary stones and urinary obstruction in patients with suspected renal colic. METHODS: 95 patients with suspected renal colic underwent a three-phase MDCT for evaluation of the urinary tract. The unenhanced scan and the multiphase examination were reviewed retrospectively by two radiologists for the characterization of urinary stones and signs of obstruction. Results of unenhanced MDCT were compared with those obtained during the second review of the entire multiphase examination. RESULTS: Overall diagnosis of urinary stones revealed an accuracy of 97.0% for unenhanced, and 98.9% for multiphase MDCT with a significant difference between both protocols (mixed-effects logistic regression: odds ratio 3.3; p=0.019). With 3 versus 15 false positive ratings, multiphase MDCT was superior to unenhanced MDCT for the diagnosis of urinary stones. There was no significant difference in detecting signs of obstruction. Inter-reader agreement for overall stone detection was excellent on both unenhanced (kappa 0.84) and multiphase (kappa 0.88) MDCT. CONCLUSION: Contrast-enhanced multiphase MDCT offers distinct advantages compared to an unenhanced approach for the assessment of urinary stone disease, and therefore should be considered as a complementary examination for patients with inconclusive findings.

Ultracompact all-optical XOR logic gate in a slow-light silicon photonic crystal waveguide.

We demonstrate an ultracompact, chip-based, all-optical exclusive-OR (XOR) logic gate via slow-light enhanced four-wave mixing (FWM) in a silicon photonic crystal waveguide (PhCWG). We achieve error-free operation (<10⁻9) for 40 Gbit/s differential phase-shift keying (DPSK) signals with a 2.8 dB power penalty. Slowing the light to vg = c/32 enables a FWM conversion efficiency, η, of -30 dB for a 396 µm device. The nonlinear FWM process is enhanced by 20 dB compared to a relatively fast mode of vg = c/5. The XOR operation requires ≈ 41 mW, corresponding to a switching energy of 1 pJ/bit. We compare the slow-light PhCWG device performance with experimentally demonstrated XOR DPSK logic gates in other platforms and discuss scaling the device operation to higher bit-rates. The ultracompact structure suggests the potential for device integration.

Slotted photonic crystal cavities with integrated microfluidics for biosensing applications.

We demonstrate the detection of dissolved avidin concentrations as low as 15 nM or 1 µg/ml using functionalized slotted photonic crystal cavities with integrated microfluidics. With a cavity sensing surface area of approximately 2.2 µm(2), we are able to detect surface mass densities of order 60 pg/mm(2) corresponding to a bound mass of approximately 100 ag. The ultra-compact size of the sensors makes them attractive for lab-on-a-chip applications where high densities of independent sensing elements are desired within a small area. The high sensitivity over an extremely small area is due to the strong modal overlap with the analyte enabled by the slotted waveguide cavity geometry that we employ. This strong overlap results in larger shifts in the cavity peak wavelength when compared to competing approaches.

Propofol, remifentanil and mivacurium: fast track surgery with poor intubating conditions.

BACKGROUND: Mivacurium is widespread used because it is the non-depolarizing muscle relaxant with the shortest duration time. Therefore, it seems to be ideal for fast track or ambulatory surgery. However, especially in combination with propofol and remifentanil onset time remains unclear and incidence of poor intubating conditions seems to be higher than in other regimes of anesthesia. METHODS: We included 35 ear, nose and throat (ENT) patients in this study. Muscle relaxation was measured by acceleromyograhpy at the adductor pollicis muscle (a.p.m.) and intubating conditions were evaluated. Anesthesia was induced with 2.5 mg kg-1 propofol and 1 µg kg-1 remifentanil and intubation was performed three minutes after the administration of 0.2 mg kg-1 mivacurium. Open vocal cords conjoined with full relaxation of the a.p.m., easy mouth opening and prevention of coughing and bucking represented the primary endpoint in this study. RESULTS: Only 20% of patients (N.=7) had optimal intubating conditions and achieved the primary endpoint. In 21 patients (60%) a complete block of the a.p.m. could not be achieved and in six patients (17%) the vocal cords were closed. In seven patients (20%) we observed difficult mouth opening and in 11 patients (31%) coughing and bucking. In addition, we found a prolonged onset time of 228±95 seconds (mean±SD). CONCLUSION: In combination with propofol and remifentanil the muscle relaxant agent mivacurium led to uncertain muscle relaxation and to poor intubating conditions. Therefore the study was aborted after 35 patients. Probably mivacurium is not a useful muscle relaxant agent if fast and deep muscle relaxation is needed. The advantage of a short duration time is foiled by intubation complications due to insufficient muscle relaxation.

Mode structure of coupled L3 photonic crystal cavities.

We investigate the energy splitting, quality factor and polarization of the fundamental modes of coupled L3 photonic crystal cavities. Four different geometries are evaluated theoretically, before experimentally investigating coupling in a direction at 30◦ to the line of the cavities. In this geometry, a smooth variation of the energy splitting with the cavity separation is predicted and observed, together with significant differences between the polarizations of the bonding and anti-bonding states. The controlled splitting of the coupled states is potentially useful for applications that require simultaneous resonant enhancement of two transitions.

Four-wave mixing in slow light engineered silicon photonic crystal waveguides.

We experimentally investigate four-wave mixing (FWM) in short (80 µm) dispersion-engineered slow light silicon photonic crystal waveguides. The pump, probe and idler signals all lie in a 14 nm wide low dispersion region with a near-constant group velocity of c/30. We measure an instantaneous conversion efficiency of up to -9dB between the idler and the continuous-wave probe, with 1W peak pump power and 6 nm pump-probe detuning. This conversion efficiency is found to be considerably higher (>10 × ) than that of a Si nanowire with a group velocity ten times larger. In addition, we estimate the FWM bandwidth to be at least that of the flat band slow light window. These results, supported by numerical simulations, emphasize the importance of engineering the dispersion of PhC waveguides to exploit the slow light enhancement of FWM efficiency, even for short device lengths.

Copper-phthalocyanine based metal-organic interfaces: the effect of fluorination, the substrate, and its symmetry.

Metal-organic interfaces based on copper-phthalocyanine monolayers are studied in dependence of the metal substrate (Au versus Cu), of its symmetry [hexagonal (111) surfaces versus fourfold (100) surfaces], as well as of the donor or acceptor semiconducting character associated with the nonfluorinated or perfluorinated molecules, respectively. Comparison of the properties of these systematically varied metal-organic interfaces provides new insight into the effect of each of the previously mentioned parameters on the molecule-substrate interactions.