Malnutrition, poor food intake, and adverse healthcare outcomes in non-critically ill obese acute care hospital patients

Obesity, defined as a BMI\ua0≥\ua030\ua0kg/m, has demonstrated protective associations with mortality in some diseases. However, recent evidence demonstrates that poor nutritional status in critically ill obese patients confounds this relationship. The purpose of this paper is to evaluate if poor nutritional status, poor food intake and adverse health-related outcomes have a demonstrated association in non-critically ill obese acute care hospital patients.This is a secondary analysis of the Australasian Nutrition Care Day Survey dataset (N\ua0=\ua03122), a prospective cohort study conducted in hospitals from Australia and New Zealand in 2010. At baseline, hospital dietitians recorded participants' BMI, evaluated nutritional status using Subjective Global Assessment (SGA), and recorded 24-h\ua0food intake (as 0%, 25%, 50%, 75%, and 100% of the offered food). Post-three months, participants' length of stay (LOS), readmissions, and in-hospital mortality data were collected. Bivariate and regression analyses were conducted to investigate if there were an association between BMI, nutritional status, poor food intake, and health-related outcomes.Of the 3122 participants, 2889 (93%) had eligible data. Obesity was prevalent in 26% of the cohort (n\ua0=\ua0750; 75% females; 61\ua0±\ua015 years; 37\ua0±\ua07\ua0kg/m). Fourteen percent (n\ua0=\ua0105) of the obese patients were malnourished. Over a quarter of the malnourished obese patients (N\ua0=\ua030/105, 28%) consumed ≤25% of the offered meals. Most malnourished obese patients (74/105, 70%) received standard diets without additional nutritional support. After controlling for confounders (age, disease type and severity), malnutrition and intake ≤25% of the offered meals independently trebled the odds of in-hospital mortality within 90 days of hospital admission in obese patients.Although malnourished obese experienced significantly adverse health-related outcomes they were least likely to receive additional nutritional support. This study demonstrates that BMI alone cannot be used as a surrogate measure for nutritional status and warrants routine nutritional screening for all hospital patients, and subsequent nutritional assessment and support for malnourished patients

Phosphorylation of pRb: mechanism for RB pathway inactivation in MYCN-amplified retinoblastoma.

A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1(-/-) , 83%), 29 with one (RB1(+/-) , 12%) and 13 with no detectable mutations (RB1(+/+) , 5%). Eighteen tumors carried MYCN amplification between 29 and 110 copies: 12 had two (RB1(-/-) ) or one RB1 (RB1(+/-) ) mutations, while six had no mutations (RB1(+/+) ). Immunohistochemical staining of tumor sections with antibodies against pRb and phosphorylated Rb (ppRb) displayed high levels of pRb and ppRb in both RB1(+/+) and RB1(+/-) tumors with MYCN amplification compared to no expression of these proteins in a classic RB1(-/-) , MYCN-low tumor. These results establish that high MYCN amplification can be present in retinoblastoma with or without coding sequence mutations in the RB1 gene. The functional state of pRb is inferred to be inactive due to phosphorylation of pRb in the MYCN-amplified retinoblastoma without coding sequence mutations. This makes inactivation of RB1 by gene mutation or its protein product, pRb, by protein phosphorylation, a necessary condition for initiating retinoblastoma tumorigenesis, independent of MYCN amplification

Dietary modification for women after breast cancer treatment: a narrative review

Diet is thought to account for about 25% of cancers in developed countries. It is well documented that the risks associated with both the breast cancer itself and its treatments are important for women previously treated for breast cancer. Women are at risk of recurrence of the primary disease and prone to develop treatment-induced co-morbidities, some of which are thought to be modified by diet. With a view to making dietary recommendations for the breast cancer patients we encounter in our clinical nursing research, we mined the literature to scope the most current robust evidence concerning the role of the diet in protecting women against the recurrence of breast cancer and its potential to ameliorate some of the longer-term morbidities associated with the disease. We found that the evidence about the role of the diet in breast cancer recurrence is largely inconclusive. However, drawing on international guidelines enabled us to make three definitive recommendations. Women at risk of breast cancer recurrence, or who experience co-morbidities as a result of treatment, should limit their exposure to alcohol, moderate their nutritional intake so it does not contribute to postmenopausal weight gain, and should adhere to a balanced diet. Nursing education planned for breast cancer patients about dietary issues should ideally be individually tailored, based on a good understanding of the international recommendations and the evidence underpinning the

Assessing the discordance rate between local and central HER2 testing in women with locally determined HER2-negative breast cancer.

BackgroundThe importance of human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive marker in invasive breast cancer is well established. Accurate assessment of HER2 status is essential to determine optimal treatment options.MethodsBreast cancer tumor tissue samples from the VIRGO observational cohort tissue substudy that were locally HER2-negative were retested centrally with both US Food and Drug Administration (FDA)-approved immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, using FDA-approved assay cutoffs; results were compared.ResultsOf the 552 unique patient samples centrally retested with local HER2-negative results recorded, tumor samples from 22 (4.0%) patients were determined to be HER2-positive (95% confidence interval [CI] = 2.5%-5.7%). Of these, 18 had been tested locally by only one testing methodology; 15 of 18 were HER2-positive after the central retesting, based on the testing methodology not performed locally. Compared with the 530 patients with centrally confirmed HER2-negative tumors, the 22 patients with centrally determined HER2-positive tumors were younger (median age 56.5 versus 60.0 years) and more likely to have ER/PR-negative tumors (27.3% versus 22.3%). These patients also had shorter median progression-free survival (6.4 months [95% CI = 3.8-15.9 months] versus 9.1 months [95% CI = 8.3-10.3 months]) and overall survival (25.9 months [95% CI = 13.8-not estimable] versus 27.9 months [95% CI = 25.0-32.9 months]).ConclusionsThis study highlights the limitations of employing just one HER2 testing methodology in current clinical practice. It identifies a cohort of patients who did not receive potentially efficacious therapy because their tumor HER2-positivity was not determined by the test initially used. Because of inherent limitations in testing methodologies, it is inadvisable to rely on a single test to rule out potential benefit from HER2-targeted therapy

Morbidity burden and community-based palliative care are associated with rates of hospital use by people with schizophrenia in the last year of life: A population-based matched cohort study

Objective: People with schizophrenia face an increased risk of premature death from chronic diseases and injury. This study describes the trajectory of acute care health service use in the last year of life for people with schizophrenia and how this varied with receipt of community based specialist palliative care and morbidity burden. Method: A population-based retrospective matched cohort study of people who died from 01/01/ 2009 to 31/12/2013 with and without schizophrenia in Western Australia. Hospital inpatient, emergency department, death and community-based care data collections were linked at the person level. Rates of emergency department presentations and hospital admissions over the last year of life were estimated. Results: Of the 63508 decedents, 1196 (1.9%) had a lifetime history of schizophrenia. After adjusting for confounders and averaging over the last year of life there was no difference in the overall rate of ED presentation between decedents with schizophrenia and the matched cohort (HR 1.09; 95%CI 0.99–1.19). However, amongst the subset of decedents with cancer, choking or intentional self-harm recorded on their death certificate, those with schizophrenia presented to ED more often. Males with schizophrenia had the highest rates of emergency department use in the last year of life. Rates of hospital admission for decedents with schizophrenia were on average half (HR 0.53, 95%CI 0.44–0.65) that of the matched cohort although this varied by cause of death. Of all decedents with cancer, 27.5% of people with schizophrenia accessed community-based specialist palliative care compared to 40.4% of the matched cohort (p\u3c0.001). Rates of hospital admissions for decedents with schizophrenia increased 50% (95% CI: 10%-110%) when enrolled in specialist palliative care. Conclusion: In the last year of life, people with schizophrenia were less likely to be admitted to hospital and access community-based speciality palliative care, but more likely to attend emergency departments if male. Community-based specialist palliative care was associated with increased rates of hospital admissions

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Survivin a radiogenetic promoter for glioblastoma viral gene therapy independently from CArG motifs

BACKGROUND: Radiogenetic therapy is a novel approach in the treatment of cancer, which employs genetic modification to alter the sensitivity of tumor cells to the effect of applied radiation. AIM: To select a potent radiation inducible promoter in the context of brain tumors and to investigate if CArG radio responsive motifs or other elements in the promoter nucleotide sequences can correlate to its response to radiation. METHODS: To select initial candidates for promoter inducible elements, the levels of mRNA expression of six different promoters were assessed using Quantitative RTPCR in D54 MG cells before and after radiation exposure. Recombinant Ad/reporter genes driven by five different promoters; CMV, VEGF, FLT-1, DR5 and survivin were constructed. Glioma cell lines were infected with different multiplicity of infection of the (promoter) Ad or CMV Ad. Cells were then exposed to a range of radiation (0–12 Gy) at single fraction. Fluorescent microscopy, Luc assay and X-gal staining was used to detect the level of expression of related genes. Different glioma cell lines and normal astrocytes were infected with Ad survivin and exposed to radiation. The promoters were analyzed for presence of CArG radio-responsive motifs and CCAAT box consensus using NCBI blast bioinformatics software. RESULTS: Radiotherapy increases the expression of gene expression by 1.25–2.5 fold in different promoters other than survivin after 2 h of radiation. RNA analysis was done and has shown an increase in copy number of tenfold for survivin. Most importantly cells treated with RT and Ad Luc driven by survivin promoter showed a fivefold increase in expression after 2 Gy of radiation in comparison to non-irradiated cells. Presence or absence of CArG motifs did not correlate with promoter response to radiation. Survivin with the best response to radiation had the lowest number of CCAAT box. CONCLUSION: Survivin is a selective potent radiation inducible promoter for glioblastoma viral gene therapy and this response to radiation could be independent of CArG motifs

Evidence Inference 2.0: More Data, Better Models

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.Comment: Accepted as workshop paper into BioNLP Updated results from SciBERT to Biomed RoBERT

"True Believers" or Numerical Terrorism at the Nuclear Power Plant

For decades, there has been a heated debate about whether or not nuclear power plants contribute to childhood cancer in their respective neighbourhoods, with statisticians testifying on both sides. The present paper points to some flaws in the pro-arguments, taking a recent study prepared for the political party "Bündnis 90 / Grüne" as a specimen. Typical mistakes include an understatement of the size of tests of significance, disregard of important covariates and extreme reliance on very few selected data points.