SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in breast cancer patients with distant metastases at initial presentation

<p>Abstract</p> <p>Background</p> <p>Five percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.</p> <p>Design</p> <p>Randomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.</p> <p>Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.</p> <p>Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.</p> <p>Discussion</p> <p>The SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01392586">NCT01392586</a>.</p

Blood pressure measurements for diagnosing hypertension in primary care:room for improvement

Background: In the adult population, about 50% have hypertension, a risk factor for cardiovascular disease and subsequent premature death. Little is known about the quality of the methods used to diagnose hypertension in primary care. Objectives: The objective was to assess the frequency of use of recognized methods to establish a diagnosis of hypertension, and specifically for OBPM, whether three distinct measurements were taken, and how correctly the blood pressure levels were interpreted. Methods: A retrospective population-based cohort study using electronic medical records of patients aged between 40 and 70 years, who visited their general practitioner (GP) with a new-onset of hypertension in the years 2012, 2016, 2019, and 2020. A visual chart review of the electronic medical records was used to assess the methods employed to diagnose hypertension in a random sample of 500 patients. The blood pressure measurement method was considered complete if three or more valid office blood pressure measurements (OBPM) were performed, or home-based blood pressure measurements (HBPM), the office- based 30-minute method (OBP30), or 24-hour ambulatory blood pressure measurements (24 H-ABPM) were used. Results: In all study years, OBPM was the most frequently used method to diagnose new-onset hypertension in patients. The OBP-30 method was used in 0.4% (2012), 4.2% (2016), 10.6% (2019), and 9.8% (2020) of patients respectively, 24 H-ABPM in 16.0%, 22.2%, 17.2%, and 19.0% of patients and HBPM measurements in 5.4%, 8.4%, 7.6%, and 7.8% of patients, respectively. A diagnosis of hypertension based on only one or two office measurements occurred in 85.2% (2012), 87.9% (2016), 94.4% (2019), and 96.8% (2020) of all patients with OBPM. In cases of incomplete measurement and incorrect interpretation, medication was still started in 64% of cases in 2012, 56% (2016), 60% (2019), and 73% (2020). Conclusion: OBPM is still the most often used method to diagnose hypertension in primary care. The diagnosis was often incomplete or misinterpreted using incorrect cut-off levels. A small improvement occurred between 2012 and 2016 but no further progress was seen in 2019 or 2020. If hypertension is inappropriately diagnosed, it may result in under treatment or in prolonged, unnecessary treatment of patients. There is room for improvement in the general practice setting.</p

UV photodestruction of CH bonds and the evolution of the 3.4 mu m feature carrier. I. The case of aliphatic and aromatic molecular species

Wetensch. publicatieFaculteit der Wiskunde en Natuurwetenschappe

Dissociation of the benzene molecule by UV and soft X-rays in circumstellar environment

Benzene molecules, present in the proto-planetary nebula CRL 618, are ionized and dissociated by UV and X-ray photons originated from the hot central star and by its fast wind. Ionic species and free radicals produced by these processes can lead to the formation of new organic molecules. The aim of this work is to study the photoionization and photodissociation processes of the benzene molecule, using synchrotron radiation and time of flight mass spectrometry. Mass spectra were recorded at different energies corresponding to the vacuum ultraviolet (21.21 eV) and soft X-ray (282-310 eV) spectral regions. The production of ions from the benzene dissociative photoionization is here quantified, indicating that C6H6 is more efficiently fragmented by soft X-ray than UV radiation, where 50% of the ionized benzene molecules survive to UV dissociation while only about 4% resist to X-rays. Partial ion yields of H+ and small hydrocarbons such as C2H2+, C3H3+ and C4H2+ are determined as a function of photon energy. Absolute photoionization and dissociative photoionization cross sections have also been determined. From these values, half-life of benzene molecule due to UV and X-ray photon fluxes in CRL 618 were obtained.Comment: The paper contains 8 pages, 9 figures and 4 tables. Accepted to be published on MNRAS on 2008 November 2

A search for interstellar anthracene toward the Perseus anomalous microwave emission region

We report the discovery of a new broad interstellar (or circumstellar) band at 7088.8 +- 2.0 \AA coincident to within the measurement uncertainties with the strongest band of the anthracene cation (C$_{14}$H$_{10}$$^+$) as measured in gas-phase laboratory spectroscopy at low temperatures (Sukhorukov et al.2004). The band is detected in the line of sight of star Cernis 52, a likely member of the very young star cluster IC 348, and is probably associated with cold absorbing material in a intervening molecular cloud of the Perseus star forming region where various experiments have recently detected anomalous microwave emission. From the measured intensity and available oscillator strength we find a column density of N$_{an^+}$= 1.1(+-0.4) x 10$^{13}$ cm$^{-2}$ implying that ~0.008% of the carbon in the cloud could be in the form of C$_{14}$H$_{10}$$^+$. A similar abundance has been recently claimed for the naphthalene cation (Iglesias-Groth et al. 2008) in this cloud. This is the first location outside the Solar System where specific PAHs are identified. We report observations of interstellar lines of CH and CH$^+$ that support a rather high column density for these species and for molecular hydrogen. The strength ratio of the two prominent diffuse interstellar bands at 5780 and 5797 \AA suggests the presence of a ``zeta'' type cloud in the line of sight (consistent with steep far-UV extinction and high molecular content). The presence of PAH cations and other related hydrogenated carbon molecules which are likely to occur in this type of clouds reinforce the suggestion that electric dipole radiation from fast spinning PAHs is responsible of the anomalous microwave emission detected toward Perseus.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Societ

A search for diffuse bands in the circumstellar envelopes of post-AGB stars

In this work we present the results of a systematic search for diffuse bands (DBs, hereafter) in the circumstellar envelopes of a carefully selected sample of post-AGB stars. We concentrated on the analysis of 9 of the DBs most commonly found in the interstellar medium. The strength of these features is determined using high resolution optical spectroscopy and the results obtained are compared with literature data on field stars affected only by interstellar reddening. Based on the weak features observed in the subsample of post-AGB stars dominated by circumstellar reddening we conclude that the carrier(s) of these DBs must not be present in the circumstellar environment of these sources, or at least not under the excitation conditions in which DBs are formed. The conclusion is applicable to all the post-AGB stars studied, irrespective of the dominant chemistry or the spectral type of the star considered. A detailed radial velocity analysis of the features observed in individual sources confirms this result, as the Doppler shifts measured are found to be consistent with an interstellar origin.Comment: Accepted for A&

Laboratory investigations of the interaction between benzene and bare silicate grain surfaces

Experimental results on the thermal desorption of benzene (C6H6) from amorphous silica (SiO2) are presented. The amorphous SiO2 substrate was imaged using atomic force microscopy (AFM), revealing a surface morphology reminiscent of that of interplanetary dust particles (IDPs). Temperature programmed desorption (TPD) experiments were conducted for a wide range of C6H6 exposures, yielding information on both C6H6-SiO2 interactions and the C6H6-C6H6 interactions present in the bulk C6H6 ice. The low coverage experiments reveal complicated desorption behaviour that results both from porosity and roughness in the SiO2 substrate, and repulsive interactions between C6H6 molecules. Kinetic parameters were obtained through a combination of direct analysis of the TPD traces and kinetic modelling, demonstrating the coverage dependence of both desorption energy and pre-exponential factor. Experiments were also performed whereby the pores were blocked by pre-exposure of the SiO2 to water vapour. C6H6 was observed to be adsorbed preferentially on the SiO2 film not covered by H2O at the temperature at which these experiments were performed. This observation means that intermolecular repulsion likely becomes important at smaller C6H6 exposures on grains with a H2O mantle. Kinetic modelling of C6H6 multilayer desorption yields kinetic parameters in good agreement with previous studies, with the SiO2 having little impact on the desorption beyond the first few layers.Comment: 23 pages, including 6 figures and 1 table ; Submitted to MNRA