Metastasectomy for colorectal pulmonary metastases: a survey among members of the European Society of Thoracic Surgeons.

Surgical management of pulmonary metastases in colorectal cancer patients is a debated topic. There is currently no consensus on this matter, which sparks considerable risk for international practice variation. The European Society of Thoracic Surgeons (ESTS) ran a survey to assess current clinical practices and to determine criteria for resection among ESTS members. All ESTS members were invited to complete an online questionnaire of 38 questions on current practice and management of pulmonary metastases in colorectal cancer patients. In total, 308 complete responses were received (response rate: 22%) from 62 countries. Most respondents consider that pulmonary metastasectomy for colorectal pulmonary metastases improves disease control (97%) and improves patients' survival (92%). Invasive mediastinal staging in case of suspicious hilar or mediastinal lymph nodes is indicated (82%). Wedge resection is the preferred type of resection for a peripheral metastasis (87%). Minimally invasive approach is the preferred approach (72%). For a centrally located colorectal pulmonary metastasis, the preferred form of treatment is a minimally invasive anatomical resection (56%). During metastasectomy, 67% of respondents perform mediastinal lymph node sampling or dissection. Routine chemotherapy is rarely or never given following metastasectomy (57% of respondents). This survey among the ESTS members underlines the change in practice of pulmonary metastasectomy with an increasing tendency in favour of minimally invasive metastasectomy and surgical resection is preferred over other types of local treatment. Criteria for resectability vary and controversy remains regarding lymph node assessment and the role of adjuvant treatment

Effect of Three Legumes Containing Different Condensed Tannin Concentrations on the in Vitro Formation of the Pastoral Flavour Compound; Skatole

Feeding legumes, such as white clover (Trifolium repens), results in higher intakes and increased animal production compared to grasses (Ulyatt, 1981). Skatole is produced in the rumen from plant protein fermentation and is associated with undesirable pastoral flavours in meat (Young et al. 2002). Feeding white clover causes a greater skatole concentration in the rumen compared to perennial ryegrass (Lolium perenne) or Lotus corniculatus, as the protein in white clover is highly soluble and rapidly degraded (Schreurs et al., 2004). The condensed tannins (CT) in Lotus species slow protein degradation in the rumen (Aerts et al., 1999). The aim of this study was to determine the effect of legumes with different concentrations of CT on skatole formation

Selection into medicine : the predictive validity of an outcome-based procedure

Acknowledgements: The authors would like to thank Dr. Kelly Dore for valuable advice and sharing Computer-based Assessment for Sampling Personal characteristics (CASPer) assignments in order to develop our Situational Judgement Test and Angela Verheyen and Guus Smeets for their essential support in gathering data.Peer reviewedPublisher PD

Two European Cornus L. feeding leafmining moths, Antispila petryi Martini, 1899, sp. rev. and A. treitschkiella (Fischer von Röslerstamm, 1843) (Lepidoptera, Heliozelidae): an unjustified synonymy and overlooked range expansion

Antispila treitschkiella (Fischer von Röslerstamm, 1843) and A. petryi Martini, 1899, sp. rev. were regarded as synonymous since 1978, but are shown to be two clearly separated species with different hostplants, life histories, DNA barcodes and morphology. Antispila treitschkiella feeds on Cornus mas L., is bivoltine, and has, by following its ornamentally planted host, greatly expanded its range in north-western Europe. In contrast A. petryi feeds on the widespread native C. sanguinea L., is univoltine, and is one of only two Antispila species previously resident in the British Isles, the Netherlands and northern Europe. Consequently, the increase in abundance of A. treitschkiella in the Netherlands since the early 1990s and in Great Britain in recent years must be regarded as part of a recent expansion into north-western Europe, whereas the native A. petryi is hardly expanding and less abundant. In Britain, detailed surveys of parks and living collections confirmed the monophagy of these two species. A search of British herbarium samples provided no evidence for an earlier date of establishment. Information on recognition of all stages, including DNA barcodes, and distribution is provided, and these two species are compared with the third European Cornus L. leafminer, A. metallella (Denis & Schiffermüller, 1775)

Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment

Cut-Off Points for Mild, Moderate, and Severe Pain on the Numeric Rating Scale for Pain in Patients with Chronic Musculoskeletal Pain: Variability and Influence of Sex and Catastrophizing

Objectives. The 0 – 10 Numeric Rating Scale (NRS) is often used in pain management. The aims of our study were to determine the cut-off points for mild, moderate and severe pain in terms of pain-related interference with functioning in patients with chronic musculoskeletal pain, to measure the variability of the optimal cut-off points, and to determine the influence of patients’ catastrophizing and their sex on these cut-off points. Methods. 2854 patients were included. Pain was assessed by the NRS, functioning by the Pain Disability Index (PDI) and catastrophizing by the Pain Catastrophizing Scale (PCS). Cut-off point schemes were tested using ANOVAs with and without using the PSC scores or sex as co-variates and with the interaction between CP scheme and PCS score and sex, respectively. The variability of the optimal cut-off point schemes was quantified using bootstrapping procedure. Results and conclusion. The study showed that NRS scores ≤5 correspond to mild, scores of 6-7 to moderate and scores ≥8 to severe pain in terms of pain-related interference with functioning. Bootstrapping analysis identified this optimal NRS cut-off point scheme in 90 % of the bootstrapping samples. The interpretation of the NRS is independent of sex, but seems to depend on catastrophizing. In patients with high catastrophizing tendency, the optimal cut-off point scheme equals that for the total study sample, but in patients with a low catastrophizing tendency, NRS scores ≤3 correspond to mild, scores of 4-6 to moderate and scores ≥7 to severe pain in terms of interference with functioning. In these optimal cut-off schemes, NRS scores of 4 and 5 correspond to moderate interference with functioning for patients with low catastrophizing tendency and to mild interference for patients with high catastrophizing tendency. Theoretically one would therefore expect that among the patients with NRS scores 4 and 5 there would be a higher average PDI score for those with low catastrophizing than for those with high catastrophizing. However, we found the opposite. The fact that we did not find the same optimal CP scheme in the subgroups with lower and higher catastrophizing tendency may be due to chance variability

Ionizing Radiation Stimulates Expression of Pro-Osteoclastogenic Genes in Marrow and Skeletal Tissue

Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically-active, cancellous-bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total-body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16wk), male C57BL/6J mice were exposed to either 2Gy gamma rays (137Cs, 0.8Gy/min) or heavy ions (56Fe, 600MeV, 0.50-1.1Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is 10Gy) or accumulates over long-duration, interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4hrs-7d later. Gamma irradiation caused a prompt (2.6-fold within 4hrs) and persistent (peaking at 4.1-fold within 1d) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappaB-ligand (Rankl) within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3d of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (e.g., monocyte chemotactic protein-1 increased 11.9-fold, tumor necrosis factor-alpha increased 1.7- fold over controls). Marrow expression of the RANKL decoy receptor, osteoprotegerin (Opg), also rose after irradiation (11.3-fold). The ratio Rankl/Opg in marrow was increased 1.8-fold, a net pro-resorption balance. As expected, radiation increased a serum marker of resorption (tartrate resistant acid phosphatase) and led to cancellous bone loss (16% decrease in bone volume/total volume) through reduced trabecular struts. We conclude that total-body irradiation (gamma or heavy-ion) caused temporal, concerted regulation of gene expression within marrow and mineralized tissue for select cytokines which are responsible for osteoclastogenesis and elevated resorption; this is likely to account for rapid and progressive 52 deterioration of cancellous microarchitecture following exposure to ionizing radiation

Identification of the PS1 Thr147Ile Variant in a Family with Very Early Onset Dementia and Expressive Aphasia

Background: Early onset dementias have variable clinical presentations and are often difficult to diagnose. We established a family pedigree that demonstrated consistent recurrence of very early onset dementia in successive generations. Objective and Method: In order to refine the diagnosis in this family, we sequenced the exomes of two affected family members and relied on discrete filtering to identify disease genes and the corresponding causal variants. Results: Among the 720 nonsynonymous single nucleotide polymorphisms (SNPs) shared by two affected members, we found a C to T transition that gives rise to a Thr147Ile missense substitution in the presenilin 1 (PS1) protein. The presence of this same mutation in a French early-onset Alzheimer’s disease family, other affected members of the family, and the predicted high pathogenicity of the substitution strongly suggest that it is the causal variant. In addition to exceptionally young age of onset, we also observed significant limb spasticity and early loss of speech, concurrent with progression of dementia in affected family members. These findings extend the clinical presentation associated with the Thr147Ile variant. Lastly, one member with the Thr147Ile variant was treated with the PKC epsilon activator, bryostatin, in a compassionate use trial after successful FDA review. Initial improvements with this treatment were unexpectedly clear, including return of some speech, increased attentional focus, ability to swallow, and some apparent decrease in limb spasticity. Conclusions: Our findings confirm the role of the PS1 Thr147Ile substitution in Alzheimer’s disease and expand the clinical phenotype to include expressive aphasia and very early onset of dementia

Continuous oral contraceptives versus long-term pituitary desensitization prior to IVF/ICSI in moderate to severe endometriosis:study protocol of a non-inferiority randomized controlled trial

STUDY QUESTIONS: The primary objective is to investigate if continuous use of oral contraceptives is non-inferior compared to long-term pituitary desensitization with a GnRH agonist prior to IVF/ICSI in patients with moderate to severe endometriosis with regard to treatment efficacy. Secondary objectives concern treatment safety and cost-effectiveness. WHAT IS KNOWN ALREADY: Long-term pituitary desensitization with a GnRH agonist for 3-6 months prior to IVF/ICSI improves clinical pregnancy rates in women suffering from endometriosis. However, discussion about this treatment strategy exists because of its uncomfortable side effects. Alternatively, IVF/ICSI pre-treatment with continuously administered oral contraceptives may offer fewer side-effects and lower (in)direct costs, as well as encouraging IVF outcomes in women with endometriosis. To date, these two different IVF/ICSI pre-treatment strategies in women with endometriosis have not been directly compared. STUDY DESIGN SIZE DURATION: An open-label, parallel two-arm randomized controlled multicenter trial is planned, including patients with moderate to severe endometriosis. To demonstrate an absolute difference of 13% (delta of 10% with non-inferiority margin of 3%) with a power of 80% 137 patients per group are sufficient. Taking into account a withdrawal of patients of 10% and a cancelation rate of embryo transfer after ovarian pick up of 10% (for instance due to fertilization failure), the sample size calculation is rounded off to 165 patients per group; 330 patients in total will be included. After informed consent, eligible patients will be randomly allocated to the intervention or reference group by using web based block randomization stratified per centre. Study inclusion is expected to be complete in 3-5 years. PARTICIPANTS/MATERIALS SETTING METHODS: The research population consists of patients with moderate to severe endometriosis (ASRM III/IV) who are scheduled for their first, second or third IVF/ICSI treatment attempt. Women aged over 41 years, younger than 18 years, with a known contraindication for the use of oral contraceptives and/or GnRH agonists or with severe male factor infertility will be excluded from participation. After informed consent patients are allocated to the intervention group (one-phase oral contraceptive continuously during three subsequent months) or the reference group (three Leuprorelin 3.75 mg i.m./s.c. depot injections during three subsequent months). Tibolon 2.5 mg can be given daily as add-back therapy in the reference group. After 3 months of pre-treatment the IVF/ICSI stimulation phase will be started. The primary outcome is live birth rate after fresh embryo transfer. Secondary outcomes are cumulative live birth rate after one IVF/ICSI treatment cycle (including fresh and frozen embryo transfers up to 15 months after randomization), ongoing pregnancy rate and time to pregnancy. In addition, treatment outcome parameters, adverse events, side-effects during the first 3 months, complications, recurrence of endometriosis (complaints), quality of life, patient preferences, safety and costs effectiveness will be reported. Measurements will be performed at baseline and at 3, 6, 9, 12 and 15 months after randomization. STUDY FUNDING/COMPETING INTERESTs: All authors have no conflict of interest related to this manuscript. The department of reproductive medicine of the Amsterdam UMC location VUmc has received several research and educational grants from Guerbet, Merck and Ferring not related to the submitted work. TRIAL REGISTRATION NUMBER: The trial is registered as the COPIE trial (Continuous use of Oral contraceptives as an alternative for long-term Pituitary desensitization with a GnRH agonist prior to IVF/ICSI in Endometriosis patients) in the Dutch Trial Register (Ref. No. NTR6357, http://www.trialregister.nl). TRIAL REGISTRATION DATE: 16 March 2017. DATE OF FIRST PATIENT’S ENROLMENT: Enrollment is planned for November 2018