Glucocorticoid receptor expression in 20 solid tumor types using immunohistochemistry assay.

BackgroundGlucocorticoid receptor (GR) activity plays a role in many aspects of human physiology and may play a crucial role in chemotherapy resistance in a wide variety of solid tumors. A novel immunohistochemistry (IHC) based assay has been previously developed and validated in order to assess GR immunoreactivity in triple-negative breast cancer. The current study investigates the standardized use of this validated assay to assess GR expression in a broad range of solid tumor malignancies.MethodsArchived formalin-fixed paraffin-embedded tumor bank samples (n=236) from 20 different solid tumor types were analyzed immunohistochemically. Nuclear staining was reported based on the H-score method using differential intensity scores (0, 1+, 2+, or 3+) with the percent stained (out of at least 100 carcinoma cells) recorded at each intensity.ResultsGR was expressed in all tumor types that had been evaluated. Renal cell carcinoma, sarcoma, cervical cancer, and melanoma were those with the highest mean H-scores, indicating high levels of GR expression. Colon, endometrial, and gastric cancers had lower GR staining percentages and intensities, resulting in the lowest mean H-scores.ConclusionA validated IHC assay revealed GR immunoreactivity in all solid tumor types studied and allowed for standardized comparison of reactivity among the different malignancies.ImpactBaseline expression levels of GR may be a useful biomarker when pharmaceutically targeting GR in research or clinical setting

Phase I clinical trial of the Src inhibitor dasatinib with dacarbazine in metastatic melanoma.

BackgroundSrc inhibitors sensitise melanoma cells to chemotherapy in preclinical models. The combination of dasatinib and dacarbazine was tested in a phase I trial in melanoma.MethodsPatients had ECOG performance status 0-2 and normal organ function. Dacarbazine was administered on day 1 and dasatinib on day 2 through 19 of each 21-day cycle. Both were escalated from 50 mg b.i.d. of dasatinib and 800 mg m(-2) of dacarbazine. Available pre-treatment biopsies were sequenced for BRAF, NRAS, and C-Kit mutations.ResultsDose-limiting toxicity was reached at dasatinib 70 mg b.i.d./dacarbazine 1000 mg m(-2), and was predominantly haematological. In 29 patients receiving dasatinib 70 mg b.i.d., the objective response rate (ORR) was 13.8%, the clinical benefit rate (ORR+SD) was 72.4%, the 6-month progression-free survival (PFS) was 20.7%, and the 12-month overall survival (OS) was 34.5%. Two out of three patients who were wild type for BRAF, NRAS, and c-KIT mutations had confirmed partial responses, and one had a minor response.ConclusionThe recommended phase II dose is dasatinib 70 mg b.i.d with dacarbazine 800 mg m(-2). PFS and OS data for dasatinib at 70 mg b.i.d. with dacarbazine compared favourably with historical controls. Preliminary data support evaluating tumour mutation status further as a biomarker of response

Recognition of cognitive impairment and depressive symptoms in older patients with heart failure

INTRODUCTION: Cognitive impairment and depression in patients with heart failure (HF) are common comorbidities and are associated with increased morbidity, readmissions and mortality. Timely recognition of cognitive impairment and depression is important for providing optimal care. The aim of our study was to determine if these disorders were recognised by clinicians and, secondly, if they were associated with hospital admissions and mortality within 6 months’ follow-up. METHODS: Patients (aged ≥65 years) diagnosed with HF were included from the cardiology outpatient clinic of Gelre Hospitals. Cognitive status was evaluated with the Montreal Cognitive Assessment test (score ≤22). Depressive symptoms were assessed with the Geriatric Depression Scale (score >5). Patient characteristics were collected from electronic patient files. The clinician was blinded to the tests and asked to assess cognitive status and mood. RESULTS: We included 157 patients. Their median age was 79 years (65–92); 98 (62%) were male. The majority had New York Heart Association functional class II. Cognitive impairment was present in 56 (36%) patients. Depressive symptoms were present in 21 (13%) patients. In 27 of 56 patients (48%) cognitive impairment was not recognised by clinicians. Depressive symptoms were not recognised in 11 of 21 patients (52%). During 6 months’ follow-up 24 (15%) patients were readmitted for HF-related reasons and 18 (11%) patients died. There was no difference in readmission and mortality rate between patients with or without cognitive impairment and patients with or without depressive symptoms. CONCLUSION: Cognitive impairment and depressive symptoms were infrequently recognised during outpatient clinic visits

Particle decay in false vacuum

We revisit the problem of decay of a metastable vacuum induced by the presence of a particle. For the bosons of the `master field' the problem is solved in any number of dimensions in terms of the spontaneous decay rate of the false vacuum, while for a fermion we find a closed expression for the decay rate in (1+1) dimensions. It is shown that in the (1+1) dimensional case an infrared problem of one-loop correction to the decay rate of a boson is resolved due to a cancellation between soft modes of the field. We also find the boson decay rate in the `sine-Gordon staircase' model in the limits of strong and weak coupling.Comment: 19 pages, 2 figure

Multidisciplinary decision-making in older patients with cancer, does it differ from younger patients?

Background: In order to tailor treatment to the individual patient, it is important to take the patients context and preferences into account, especially for older patients. We assessed the quality of information used in the decision-making process in different oncological MDTs and compared this for older (>70 years) and younger patients. Patients and methods: Cross-sectional observations of oncological MDTs were performed, using an observation tool in a University Hospital. Primary outcome measures were quality of input of information into the discussion for older and younger patients. Secondary outcomes were the contribution of different team members, discussion time for each case and whether or not a treatment decision was formulated. Results: Five-hundred and three cases were observed. The median patient age was 63 year, 32% were >70. In both age groups quality of patient-centered information (psychosocial information and patient's view) was poor. There was no difference in quality of information between older and younger patients, only for comorbidities the quality of information for older patients was better. There was no significant difference in the contributions by team members, discussion time (median 3.54 min) or number of decision reached (87.5%). Conclusion: For both age groups, we observed a lack of patient-centered information. The only difference between the age groups was for information on comorbidities. There were also no differences in contributions by different team members, case discussion time or number of decisions. Decision-making in the observed oncological MDTs was mostly based on medical technical information. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Search filters to identify geriatric medicine in Medline

Objectives To create user-friendly search filters with high sensitivity, specificity, and precision to identify articles on geriatric medicine in Medline. Design A diagnostic test assessment framework was used. A reference set of 2255 articles was created by hand-searching 22 biomedical journals in Medline, and each article was labeled as 'relevant', 'not relevant', or 'possibly relevant' for geriatric medicine. From the relevant articles, search terms were identified to compile different search strategies. The articles retrieved by the various search strategies were compared with articles from the reference set as the index test to create the search filters. Measures Sensitivity, specificity, precision, accuracy, and number-needed-to-read (NNR) were calculated by comparing the results retrieved by the different search strategies with the reference set. Results The most sensitive search filter had a sensitivity of 94.8%, a specificity of 88.7%, a precision of 73.0%, and an accuracy of 90.2%. It had an NNR of 1.37. The most specific search filter had a specificity of 96.6%, a sensitivity of 69.1%, a precision of 86.6%, and an accuracy of 89.9%. It had an NNR of 1.15. Conclusion These geriatric search filters simplify searching for relevant literature and therefore contribute to better evidence-based practice. The filters are useful to both the clinician who wants to find a quick answer to a clinical question and the researcher who wants to find as many relevant articles as possible without retrieving too many irrelevant article

Preoperative physical performance as predictor of postoperative outcomes in patients aged 65 and older scheduled for major abdominal cancer surgery:A systematic review

Background: Abdominal cancer surgery is associated with considerable morbidity in older patients. Assessment of preoperative physical status is therefore essential. The aim of this review was to describe and compare the objective physical tests that are currently used in abdominal cancer surgery in the older patient population with regard to postoperative outcomes. Methods: Medline, Embase, CINAHL and Web of Science were searched until 31 December 2020. Non-interventional cohort studies were eligible if they included patients ≥65 years undergoing abdominal cancer surgery, reported results on objective preoperative physical assessment such as Cardiopulmonary Exercise Testing (CPET), field walk tests or muscle strength, and on postoperative outcomes. Results: 23 publications were included (10 CPET, 13 non-CPET including Timed Up & Go, grip strength, 6-minute walking test (6MWT) and incremental shuttle walk test (ISWT)). Meta-analysis was precluded due to heterogeneity between study cohorts, different cut-off points, and inconsistent reporting of outcomes. In CPET studies, ventilatory anaerobic threshold and minute ventilation/carbon dioxide production gradient were associated with adverse outcomes. ISWT and 6MWT predicted outcomes in two studies. Tests addressing muscle strength and function were of limited value. No study compared different physical tests. Discussion: CPET has the ability to predict adverse postoperative outcomes, but it is time-consuming and requires expert assessment. ISWT or 6MWT might be a feasible alternative to estimate aerobic capacity. Muscle strength and function tests currently have limited value in risk prediction. Future research should compare the predictive value of different physical instruments with regard to postoperative outcomes in older surgical patients