Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer.

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype.

Redefining synchronous colorectal cancers based on tumor clonality.

To analyze the possible clonal origin of a part of Synchronous colorectal cancer (SCRC), we studied 104 paired-SCRCs from 52 consecutive patients without hereditary forms of CRC. We used a Single-Nucleotide Polymorphism array to characterize the genomic profiles, and subsequently used a statistical application to define them according to clonality within the same individual. We categorized the ensuing groups according to colonic location to identify differential phenotypes.

Adherence to the International Committee of Medical Journal Editors' (ICMJE) prospective registration policy and implications for outcome integrity: a cross-sectional analysis of trials published in high-impact specialty society journals.

Background: Registration of clinical trials is critical for promoting transparency and integrity in medical research; however, trials must be registered in a prospective fashion to deter unaccounted protocol modifications or selection of alternate outcomes that may enhance favorability of reported findings. We assessed adherence to the International Committee of Medical Journal Editors' (ICMJE) prospective registration policy and identified the frequency of registrations occurring after potential observation of primary outcome data among trials published in the highest-impact journals associated with US professional medical societies. Additionally, we examined whether trials that are unregistered or registered after potential observation of primary outcome data were more likely to report favorable findings.

Assessment of Pragmatism in Recently Published Randomized Clinical Trials.

This database study evaluates the labeling, justifications, and limitations of pragmatic randomized clinical trials published in 2016.

The Secretion of miR-200s by a PKCζ/ADAR2 Signaling Axis Promotes Liver Metastasis in Colorectal Cancer.

Most colorectal cancer (CRC)-related deaths are due to liver metastases. PKCζ is a tumor suppressor in CRC with reduced expression in metastasis. Given the importance of microRNAs (miRNAs) in regulating cellular plasticity, we performed an unbiased screening and identified the miR-200 family as the most relevant miRNAs downregulated by PKCζ deficiency.

Real-world evidence: How pragmatic are randomized controlled trials labeled as pragmatic?

Introduction: Pragmatic randomized controlled trials (RCTs) mimic usual clinical practice and they are critical to inform decision-making by patients, clinicians and policy-makers in real-world settings. Pragmatic RCTs assess effectiveness of available medicines, while explanatory RCTs assess efficacy of investigational medicines. Explanatory and pragmatic are the extremes of a continuum.

TWEAK and RIPK1 mediate a second wave of cell death during AKI.

Acute kidney injury (AKI) is characterized by necrotic tubular cell death and inflammation. The TWEAK/Fn14 axis is a mediator of renal injury. Diverse pathways of regulated necrosis have recently been reported to contribute to AKI, but there are ongoing discussions on the timing or molecular regulators involved.

Clinical Trials Transparency: Where Are We Today?

To prevent reporting bias, policies and regulations mandating trial prospective registration and disclosure of results have been implemented since 2005. To achieve full trial transparency, open access to participants' deidentified data policies have been issued. Funders and journals have made critical decisions on these requirements in 2017 that will impact the current scenario.

Cell death-based approaches in treatment of the urinary tract-associated diseases: a fight for survival in the killing fields.

Urinary tract-associated diseases comprise a complex set of disorders with a variety of etiologic agents and therapeutic approaches and a huge global burden of disease, estimated at around 1 million deaths per year. These diseases include cancer (mainly prostate, renal, and bladder), urinary tract infections, and urolithiasis. Cell death plays a key role in the pathogenesis and therapy of these conditions.

Detection of G12D in colorectal cancer stool by droplet digital PCR.

Aim: To assess G12D mutation detection by droplet digital PCR (ddPCR) in stool-derived DNA from colorectal cancer (CRC) patients.

Methods: In this study, tumor tissue and stool samples were collected from 70 patients with stage I-IV CRC diagnosed by preoperative biopsy. mutational status was determined by pyrosequencing analysis of DNA obtained from formalin-fixed paraffin-embedded (FFPE) tumor tissues.

Patients' beliefs regarding informed consent for low-risk pragmatic trials.

Background: The requirement to obtain written informed consent may undermine the potential of pragmatic randomized clinical trials (pRCTs) to improve evidence-based care. This requirement could compromise trials statistical power or even force it to close them down prematurely. However, recent data from the U.

Who is willing to participate in low-risk pragmatic clinical trials without consent?

Purpose: General notification offers a possible alternative to written informed consent for pragmatic randomized controlled trials (pRCTs). It involves patients being informed through brochures, posters, and letters that research is being conducted simultaneously to providing clinical care and that patients will be enrolled in pRCTs without study-specific consent. A previous survey found that a substantial minority of respondents endorsed general notification.

Mutations in cause autosomal recessive retinitis pigmentosa with intellectual disability.

Background: Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy, with a worldwide prevalence of 1 in 4000 persons. While in most cases of RP, the disease is limited to the eye (non-syndromic), over 40 forms of syndromic RP have been described.

Objectives: To identify the genetic basis for syndromic RP in three unrelated families from Israel and Spain.

Could phase 3 medicine trials be tagged as pragmatic? A case study: The Salford COPD trial.

Randomized clinical trials (RCTs) can be classified as explanatory or pragmatic. Currently, explanatory and pragmatic are considered to be the extremes of a continuum: Many trials have some features of both explanatory and pragmatic RCTs. The Salford Chronic Obstructive Respiratory Disease (COPD) trial was an open-label phase 3 RCT assessing an experimental product (fluticasone furoate-vilanterol) vs usual care.

Targeting of regulated necrosis in kidney disease.

The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response.

Current and Emerging Applications of Droplet Digital PCR in Oncology.

The clinical management of cancer has evolved in recent years towards more personalized strategies that require a comprehensive knowledge of the complex molecular features involved in tumor growth and evolution, and the development of drug resistance mechanisms leading to disease progression. Droplet digital PCR (ddPCR) has become one of the most accurate and reliable tools for the examination of genetic alterations in a wide variety of cancers because of its high sensitivity and specificity. ddPCR is currently being applied for absolute allele quantification, rare mutation detection, analysis of copy number variations, DNA methylation, and gene rearrangements in different kinds of clinical samples.