Transcriptome-Wide Association Study for Inflammatory Bowel Disease Reveals Novel Candidate Susceptibility Genes in Specific Colon Subsites and Tissue Categories.

Background And Aims: Genome-wide association studies [GWAS] for inflammatory bowel disease [IBD] have identified 240 risk variants. However, the benefit of understanding the genetic architecture of IBD remains to be exploited. Transcriptome-wide association studies [TWAS] associate gene expression with genetic susceptibility to disease, providing functional insight into risk loci.

Solving the enigma of POLD1 p.V295M as a potential cause of increased cancer risk.

Germline variants that affect the proofreading activity of polymerases epsilon (POLE) and delta (POLD1) predispose to colorectal adenomas and carcinomas, among other cancers. All cancer-associated pathogenic variants reported to date consist of non-disruptive genetic changes affecting the sequence that codifies the exonuclease domain (ED). Generally, disruptive (frameshift, stop-gain) POLE and POLD1 variants and missense variants outside the ED do not predispose to cancer.

First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma.

Background: Budigalimab is a humanized, recombinant immunoglobulin G1 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We present the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic data from patients enrolled in the head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) expansion cohorts of the phase 1 first-in-human study of budigalimab monotherapy (NCT03000257; registered 15 December 2016).

Patients And Methods: Patients with recurrent/metastatic HNSCC or locally advanced/metastatic NSCLC naive to PD-1/PD-1-ligand inhibitors were enrolled; patients were not selected on the basis of oncogene driver mutations or PD-L1 status.

Positive impact of a faecal-based screening programme on colorectal cancer mortality risk.

Introduction: The effectiveness of colorectal cancer (CRC) screening programs is directly related to participation and the number of interval CRCs. The objective was to analyse specific-mortality in a cohort of individuals invited to a CRC screening program according to type of CRC diagnosis (screen-detected cancers, interval cancers, and cancers among the non-uptake group).

Material And Methods: Retrospective cohort that included invitees aged 50-69 years of a CRC screening program (target population of 85,000 people) in Catalonia (Spain) from 2000-2015 with mortality follow-up until 2020.

Adoptive cell therapy for solid tumors: Chimeric antigen receptor T cells and beyond.

Adoptive cell therapy with chimeric antigen receptor T cells has caused a significant revolution in the treatment of hematological malignancies. Unfortunately, for solid tumors, this treatment modality has been proven insufficient to achieve significant antitumor activity. The use of modified T cell receptors towards tumor-associated antigens (NY-ESO, MAGE-A4) has recently shown antitumor activity in synovial sarcoma.

Sleep duration and napping in relation to colorectal and gastric cancer in the MCC-Spain study.

Sleep duration is a novel and potentially modifiable risk factor for cancer. We evaluated the association of self-reported sleep duration and daytime napping with odds of colorectal and gastric cancer. We included 2008 incident colorectal cancer cases, 542 gastric cancer cases and 3622 frequency-matched population controls, recruited in the MCC-Spain case-control study (2008-2013).

First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors.

Purpose: We investigated safety, tolerability, pharmacokinetics, and antitumor activity of the protein tyrosine kinase 7 (PTK7)-targeted, auristatin-based antibody-drug conjugate (ADC) PF-06647020/cofetuzumab pelidotin (NCT02222922).

Patients And Methods: Patients received PF-06647020 intravenously every 3 weeks at 0.2-3.

Pharmacokinetics and safety of capmatinib with food in patients with MET-dysregulated advanced solid tumors.

Purpose: In the Phase II GEOMETRY mono-1 study, the potent and selective mesenchymal-epithelial transition (MET) inhibitor capmatinib exhibited considerable efficacy in MET exon 14 skipping (METex14)-mutated metastatic non-small cell lung cancer at a dose of 400 mg BID. The current recommended dose is 400 mg BID in tablet formulation, with or without food. This article reports the pharmacokinetic (PK) profile, safety, and tolerability of capmatinib 300 and 400 mg BID given with food in MET-dysregulated advanced solid tumors.

Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer.

Background: Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite.

Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Lessons Learned: Cemiplimab in combination with radiation therapy, cyclophosphamide, and granulocyte macrophage colony-stimulating factor did not demonstrate efficacy above what can be achieved with other PD-1 inhibitor monotherapies in patients with refractory and metastatic head and neck squamous cell carcinoma. The safety profile of cemiplimab combination therapy was consistent with previously reported safety profiles of cemiplimab monotherapy. No new safety signal was observed.

Evaluation of the Effects of Repeat-Dose Dabrafenib on the Single-Dose Pharmacokinetics of Rosuvastatin (OATP1B1/1B3 Substrate) and Midazolam (CYP3A4 Substrate).

Dabrafenib is an oral BRAF kinase inhibitor approved for the treatment of various BRAF V600 mutation-positive solid tumors. In vitro observations suggesting cytochrome P450 (CYP) 3A induction and organic anion transporting polypeptide (OATP) inhibition prompted us to evaluate the effect of dabrafenib 150 mg twice daily on the pharmacokinetics of midazolam 3 mg (CYP3A substrate) and rosuvastatin 10 mg (OATP1B1/1B3 substrate) in a clinical phase 1, open-label, fixed-sequence study in patients with BRAF V600 mutation-positive tumors. Repeat dabrafenib dosing resulted in a 2.

UVA-Degradable Collagenase Nanocapsules as a Potential Treatment for Fibrotic Diseases.

Peyronie and Dupuytren are pathologies characterized by the appearance of localized fibrotic lesions in an organ. These disorders originate from an excessive production of collagen in the tissue provoking dysfunction and functional limitations to the patients. Local administration of collagenase is the most used treatment for these fibrotic-type diseases, but a high lability of the enzyme limits its therapeutic efficacy.

Genetically determined telomere length and multiple myeloma risk and outcome.

Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs.

Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, as monotherapy in patients with pretreated non-small cell lung cancer (NSCLC): Data from the Phase 1 NSCLC expansion cohort.

Objectives: Blockade of programmed cell death-1 (PD-1) and its ligand (PD-L1) has transformed the treatment of NSCLC. In a first-in-human, Phase 1, dose escalation and cohort expansion study, cemiplimab, a monoclonal antibody directed against PD-1, was evaluated for the treatment of patients with advanced solid tumors (NCT02383212). Here, we report results in patients with advanced NSCLC from the dose expansion cohort.

Effect of the combination of automated peripheral mechanical stimulation and physical exercise on aerobic functional capacity and cardiac autonomic control in patients with Parkinson's disease: a randomized clinical trial protocol.

Background: Automated peripheral mechanical stimulation (AMPS) has been proposed as a new complementary therapy with potential for improving motor and cardiovascular abnormalities in Parkinson's disease (PD). However, AMPS long-term effects and its combination with physical exercise are unknown. Thus, this study aims to compare the effects of a program of 12 weeks of physical exercise with a 12-week intervention program combining physical exercise and AMPS on the aerobic capacity, cardiac autonomic control, and gait parameters in patients with PD.

Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts.

The role of genetic variation in autophagy-related genes in modulating autophagy and cancer is poorly understood. Here, we comprehensively investigated the association of autophagy-related variants with colorectal cancer (CRC) risk and provide new insights about the molecular mechanisms underlying the associations. After meta-analysis of the genome-wide association study (GWAS) data from four independent European cohorts (8006 CRC cases and 7070 controls), two loci, ( = 2.

Cemented Dual Mobility Cup for Primary Total Hip Arthroplasty in Elder Patients with High-Risk Instability.

Several studies have shown that double mobility (DM) cups reduce postoperative dislocations. Does the cemented dual mobility cup reduce dislocations in a specific cohort of elder patients with a high dislocation risk? Our hypothesis is that this implant is optimal for elder patients because it reduces early dislocation. We have retrospectively reviewed elder patients who underwent total hip arthroplasty (THA) with cemented double mobility cup between March 2009 and January 2018.

Choice of CTO scores to predict procedural success in clinical practice. A comparison of 4 different CTO PCI scores in a comprehensive national registry including expert and learning CTO operators.

Background: We aimed to compare the performance of the recent CASTLE score to J-CTO, CL and PROGRESS CTO scores in a comprehensive database of percutaneous coronary intervention of chronic total occlusion procedures.

Methods: Scores were calculated using raw data from 1,342 chronic total occlusion procedures included in REBECO Registry that includes learning and expert operators. Calibration, discrimination and reclassification were evaluated and compared.

Coffee consumption and colorectal cancer risk: a multicentre case-control study from Italy and Spain.

Background: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent.

Aim: To provide further information on the risk of colorectal cancer in relation to coffee consumption.

Cortical activity and gait parameter characteristics in people with multiple sclerosis during unobstructed gait and obstacle avoidance.

Background: People with Multiple Sclerosis (PwMS) present higher cortical activity during walking. However, the cortical activity during gait while avoiding an obstacle is still not clear.

Objective: To investigate cortical activity and gait spatial-temporal parameters in PwMS during two different gait tasks (i.

Tumor immune infiltration estimated from gene expression profiles predicts colorectal cancer relapse.

A substantial fraction of patients with stage I-III colorectal adenocarcinoma (CRC) experience disease relapse after surgery with curative intent. However, biomarkers for predicting the likelihood of CRC relapse have not been fully explored. Therefore, we assessed the association between tumor infiltration by a broad array of innate and adaptive immune cell types and CRC relapse risk.

Consumption of ultra-processed foods and drinks and colorectal, breast, and prostate cancer.

Aims: To study whether the consumption of ultra-processed foods and drinks is associated with breast, colorectal, and prostate cancers.

Methods: Multicentric population-based case-control study (MCC-Spain) conducted in 12 Spanish provinces. Participants were men and women between 20 and 85 years of age with diagnoses of colorectal (n = 1852), breast (n = 1486), or prostate cancer (n = 953), and population-based controls (n = 3543) frequency-matched by age, sex, and region.

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.

Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).