Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

Background: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date.

Objective: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence.

Clinical decision support for severe trauma patients: Machine learning based definition of a bundle of care for hemorrhagic shock and traumatic brain injury.

Background: Deviation from guidelines is frequent in emergency situations, and this may lead to increased mortality. Probably because of time constraints, 55% is the greatest reported guidelines compliance rate in severe trauma patients. This study aimed to identify among all available recommendations a reasonable bundle of items that should be followed to optimize the outcome of hemorrhagic shocks (HSs) and severe traumatic brain injuries (TBIs).

Prehospital triage of acute aortic syndrome using a machine learning algorithm.

Background: Acute aortic syndrome (AAS) comprises a complex and potentially fatal group of conditions requiring emergency specialist management. The aim of this study was to build a prediction algorithm to assist prehospital triage of AAS.

Methods: Details of consecutive patients enrolled in a regional specialist aortic network were collected prospectively.

Association of Early, High Plasma-to-Red Blood Cell Transfusion Ratio With Mortality in Adults With Severe Bleeding After Trauma.

Importance: Optimal transfusion management is crucial when treating patients with trauma. However, the association of an early, high transfusion ratio of fresh frozen plasma (FFP) to packed red blood cells (PRBC) with survival remains uncertain.

Objective: To study the association of an early, high FFP-to-PRBC ratio with all-cause 30-day mortality in patients with severe bleeding after trauma.

Intraoperative management of brain-dead organ donors by anesthesiologists during an organ procurement procedure: results from a French survey.

Background: This study aimed at describing usual anesthetic practices for brain-dead donors (BDD) during an organ procurement (OP) procedure and to assess the knowledge and self-confidence of French anesthesiologists with this practice.

Methods: An electronic and anonymous survey with closed-questions about anesthetic management of BDD was distributed to French anesthesiologists via the mailing list of the French Society of Anesthesiology and Intensive Care Medicine.

Results: Four hundred fifty-eight responses were analyzed.

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres.

Morphological Factors Related to Nodal Metastases in Neuroendocrine Tumors of the Appendix: A Multicentric Retrospective Study.

Objective: The aim of this study was to evaluate clinical and morphological features related to nodal involvement in appendiceal neuroendocrine tumors (NETs), to identify patients who should be referred for oncological radicalization with hemicolectomy.

Background: Appendiceal NETs are usually diagnosed accidentally after appendectomy; the indications for right hemicolectomy are currently based on several parameters (ie, tumor size, grading, proliferative index, localization, mesoappendiceal invasion, lymphovascular infiltration). Available guidelines are based on scarce evidence inferred by small, retrospective, single-institution studies, resulting in discordant recommendations.

Alternative polyadenylation of ZEB1 promotes its translation during genotoxic stress in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis. The standard chemotherapeutic drug, gemcitabine, does not offer significant improvements for PDAC management due to the rapid acquisition of drug resistance by patients. Recent evidence indicates that epithelial-to-mesenchymal transition (EMT) of PDAC cells is strictly associated to early metastasization and resistance to chemotherapy.

Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Background: In the phase 3 RADIANT-4 trial, everolimus increased progression-free survival compared with placebo in patients with advanced, progressive, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (NETs). We now report the health-related quality of life (HRQOL) secondary endpoint.

Methods: RADIANT-4 is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 97 centres in 25 countries worldwide.

The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients.

Different inflammation-based scores such as the neutrophil/lymphocyte ratio (NLR), the Odonera Prognostic Nutritional Index (PNI), the Glasgow Prognostic Score, the platelet/lymphocyte ratio, and the C-reactive protein/albumin ratio have been found to be significantly associated with pancreatic cancer (PDAC) prognosis. However, most studies have investigated patients undergoing surgery, and few of them have compared these scores. We aimed at evaluating the association between inflammatory-based scores and PDAC prognosis.

Active Surveillance Beyond 5 Years Is Required for Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms Undergoing Non-Operative Management.

Objectives: To evaluate the results of active surveillance beyond 5 years in patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WF) and high-risk stigmata (HRS) undergoing non-operative management.

Methods: Patients with a minimum follow-up of 5 years who underwent surveillance with at least yearly magnetic resonance imaging were included. New onset of and predictors of WF/HRS during follow-up as well as long-term survival were analyzed.

Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.

Unlabelled:  Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis.

Aim: To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center.

Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples.

Introduction: Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake.

Objectives: In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L; duration: 9 months, n = 10).

Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome.

Natural uranium (NU), a component of the earth's crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.

Risk of pancreatic malignancy and mortality in branch-duct IPMNs undergoing surveillance: A systematic review and meta-analysis.

Background: Safety of non-operative management for low-risk branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated.

Aim: To perform a systematic review/meta-analysis to determine their risk of developing pancreatic malignancy and of pancreatic malignancy-related deaths.

Methods: A MEDLINE search was performed and methodology was based on PRISMA statement.

Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study.

Background: Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population.

Methods: In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide.

Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable disease. Poor prognosis is due to multiple reasons, including acquisition of resistance to gemcitabine, the first-line chemotherapeutic approach. Thus, there is a strong need for novel therapies, targeting more directly the molecular aberrations of this disease.

Can we trust untargeted metabolomics? Results of the metabo-ring initiative, a large-scale, multi-instrument inter-laboratory study.

The metabo-ring initiative brought together five nuclear magnetic resonance instruments (NMR) and 11 different mass spectrometers with the objective of assessing the reliability of untargeted metabolomics approaches in obtaining comparable metabolomics profiles. This was estimated by measuring the proportion of common spectral information extracted from the different LCMS and NMR platforms. Biological samples obtained from 2 different conditions were analysed by the partners using their own in-house protocols.

Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples.

Because uranium is a natural element present in the earth's crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions.

Dietary exposure biomarker-lead discovery based on metabolomics analysis of urine samples.

Although robust associations between dietary intake and population health are evident from conventional observational epidemiology, the outcomes of large-scale intervention studies testing the causality of those links have often proved inconclusive or have failed to demonstrate causality. This apparent conflict may be due to the well-recognised difficulty in measuring habitual food intake which may lead to confounding in observational epidemiology. Urine biomarkers indicative of exposure to specific foods offer information supplementary to the reliance on dietary intake self-assessment tools, such as FFQ, which are subject to individual bias.

The metabolomic approach identifies a biological signature of low-dose chronic exposure to cesium 137.

Reports have described apparent biological effects of (137)Cs (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to (137)Cs through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states.

Development and validation of a standardized protocol to monitor human dietary exposure by metabolite fingerprinting of urine samples.

Conventional tools for measuring dietary exposure have well recognized limitations. Measurement of food-derived metabolites in biofluids provides an alternative approach and our aim was to develop an experimental protocol which ensures that extraneous variability does not obscure metabolic signals from ingested foods. Healthy adults consumed a standardized meal in the evening before each test day and collected pooled overnight urine.

Diagnosis and management of pernicious anemia.

Pernicious anemia is a macrocytic anemia due to cobalamin deficiency, which is the result of intrinsic factor deficiency. Pernicious anemia is associated with atrophic body gastritis, whose diagnostic criteria are based on the histologic evidence of gastric body atrophy associated with hypochlorhydria. Serological markers suggesting the presence of oxyntic mucosa damage are increased levels of fasting gastrin and decreased levels of Pepsinogen I.

Polyphenols and human health: a prospectus.

The lay press often heralds polyphenols as panacea for all sorts of diseases. The rationale is that their antioxidant activity would prevent free radical damage to macromolecules. However, basic and clinical science is showing that the reality is much more complex than this and that several issues, notably content in foodstuff, bioavailability, or in vivo antioxidant activity are yet to be resolved.