Exposure to weak opioids and risk of gastrointestinal tract cancers:A series of nested case-control studies

Aims: There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract. Methods: A series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use. Results: There was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively). Conclusions: In this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.</p

An integrated behavioral health to non-communicable disease in Cambodia

Noncommunicable diseases (NCD’s) such as type 2 diabetes and hypertension are increasing in Cambodia. Clinicians in Cambodia do not routinely offer behavioral interventions to address the lifestyle behaviors such as poor nutrition, lack of physical activity and tobacco smoking that contribute to poor outcomes for NCD’s. Behavioral conditions such as depression and substance use disorder that are frequently comorbid with NCD’s also contribute to poor clinical outcomes are also not routinely addressed in medical settings in Cambodia. Integrated healthcare is the systematic, team-based approach to delivering behavioral interventions to address lifestyle and behavioral conditions that underlie poor outcomes for NCD’s delivered by a Behavioral Health Consultant (BHC). Research on type 2 diabetes and hypertension risk factors such as nutrition, physical activity, tobacco smoking and alcohol misuse demonstrates the need for a new workforce of BHC’s to improve quality and outcomes. A model of integrated behavioral health designed by this research team uses a Health Risk Assessment, a social worker or community health worker in the BHC role, and smartphone app platform for patient health self-management is recommended

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pseudomonas aeruginosa Phenotypes Associated With Eradication Failure in Children With Cystic Fibrosis

Background. Pseudomonas aeruginosa is a key respiratory pathogen in people with cystic fibrosis (CF). Due to its association with lung disease progression, initial detection of P. aeruginosa in CF respiratory cultures usually results in antibiotic treatment with the goal of eradication. Pseudomonas aeruginosa exhibits many different phenotypes in vitro that could serve as useful prognostic markers, but the relative relationships between these phenotypes and failure to eradicate P. aeruginosa have not been well characterized

Pseudomonas aeruginosa in vitro Phenotypes Distinguish Cystic Fibrosis Infection Stages and Outcomes

Rationale: Pseudomonas aeruginosa undergoes phenotypic changes during cystic fibrosis (CF) lung infection. Although mucoidy is traditionally associated with transition to chronic infection, we hypothesized that additional in vitro phenotypes correlate with this transition and contribute to disease

AHA/ACC Guidelines for Preventing Heart Attack and Death in Patients With Atherosclerotic Cardiovascular Disease: 2001 Update: A Statement for Healthcare Professionals From the American Heart Association and the American College of Cardiology

"Since the original publication (in 1995) of the American Heart Association (AHA) consensus statement on secondary prevention, which was endorsed by the American College of Cardiology (ACC), important evidence from clinical trials has emerged that further supports the merits of aggressive risk reduction therapies for patients with atherosclerotic cardiovascular disease. As noted in that statement, aggressive risk factor management clearly improves patient survival, reduces recurrent events and the need for interventional procedures, and improves the quality of life for these patients. The compelling evidence from recent clinical trials was the impetus to revise the 1995 guidelines (Table). As examples, the many lipid reduction trials have generated significant changes in the National Heart, Lung, and Blood Institute’s Adult Treatment Panel III report. This report further defined target cholesterol levels, expanded indications for drug treatment, and initiated therapy earlier. Accumulating β-blocker data have resulted in broader indications for a larger patient group. The Heart Outcomes Prevention Evaluation (HOPE) trial has demonstrated the benefit of ACE inhibitor therapy in high-risk patients with cardiovascular disease without a history of an acute event. Further data from ongoing trials should provide insight into the potential benefits of treating lower risk patients with combined therapies. The Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial has provided evidence for clopidogrel benefit in certain patients. Diabetes management recommendations have been updated to include recent guidelines from the American Diabetes Association for risk factor management of diabetics and the growing body of evidence showing diabetics at high risk for cardiovascular events. The Heart and Estrogen/progestin Replacement Study (HERS) documented that hormone replacement therapy is ineffective for secondary prevention. The writing group revising this document also considered other important trials and reports, and they are included in the selected reading list.