No abstract

Complex rearrangement patterns and mitotic errors are hallmarks of most pancreatic ductal adenocarcinomas (PDAC), a disease with dismal prognosis despite some therapeutic advances in recent years. DNA double-strand breaks (DSB) bear the greatest risk of provoking genomic instability, and DNA damage repair (DDR) pathways are crucial in preserving genomic integrity following a plethora of damage types. Two major repair pathways dominate DSB repair for safeguarding the genome integrity: non-homologous end joining and homologous recombination (HR). Defective HR, but also alterations in other DDR pathways, such as BRCA1, BRCA2, ATM and PALB2, occur frequently in both inherited and sporadic PDAC. Personalised treatment of pancreatic cancer is still in its infancy and predictive biomarkers are lacking. DDR deficiency might render a PDAC vulnerable to a potential new therapeutic intervention that increases the DNA damage load beyond a tolerable threshold, as for example, induced by poly (ADP-ribose) polymerase inhibitors. The Pancreas Cancer Olaparib Ongoing (POLO) trial, in which olaparib as a maintenance treatment improved progression-free survival compared with placebo after platinum-based induction chemotherapy in patients with PDAC and germline BRCA1/2 mutations, raised great hopes of a substantially improved outcome for this patient subgroup. This review summarises the relationship between DDR and PDAC, the prevalence and characteristics of DNA repair mutations and options for the clinical management of patients with PDAC and DNA repair deficiency.

In patients with inflammatory bowel disease, proactive therapeutic drug monitoring of infliximab over a 2-year period was associated with higher rates of mucosal healing and lower surgical requirements compared with a conventional cohort treated without therapeutic drug monitoring.

Background and study aims Previous studies have suggested a high prevalence of musculoskeletal injuries (MI) in endoscopists. Little evidence has come from European countries. Our main aim was to evaluate the prevalence, type, and impact of MI among Portuguese endoscopists. We also sought to identify risk factors for the development, severity and number of endoscopy-related MI. Material and methods A 48-question electronic survey was developed by a multidisciplinary group. The electronic survey was sent to all members of Portuguese Society of Gastroenterology (n = 705) during May 2019. Study data were collected and managed using REDCap electronic data capture tools hosted at SPG – CEREGA. Results The survey was completed by 171 endoscopists (response rate of 24.3 %), 55.0 % female with a median age of 36 years (range 26–78). The prevalence of at least one MI related to endoscopy was 69.6 % (n = 119), the most frequent being neck pain (30.4 %) and thumb pain (29.2 %). The median time for MI development was 6 years (range 2 months-30 years). Severe pain was reported by 19.3 %. Change in endoscopic technique was undertaken by 61.3 % and reduction in endoscopic caseload was undertaken by 22.7 %. Missing work was reported by 10.1 %, with the median time off from work being 30 days (range 1–90). Female gender and ≥ 15 years in practice were independently associated with MI and severe pain. Years in practice, weekly-time performing endoscopy, and gender were significant predictors of the number of MI. Conclusions Prevalence of MI was significant among Portuguese endoscopists and had a relevant impact on regular and professional activities.

Background The impact of inflammatory bowel disease (IBD) on sexual health is a leading concern among patients. Most studies focus on sexual dysfunction rather than patient-perceived sexual quality of life (SQoL). We aimed to assess SQoL in IBD patients compared with healthy controls. Methods This is a multicenter, cross-sectional study of IBD patients (n = 575 with Crohn’s disease and n = 294 with ulcerative colitis), compared with healthy controls (n = 398), that used an anonymous self-administered questionnaire. This multimodal questionnaire included sociodemographic data and 4 validated instruments: Short IBD Questionnaire, Social Desirability Scale, Sexual QoL Questionnaire–Male/Female, Nine-item Patient Health Questionnaire. Results Inflammatory bowel disease patients reported lower SQoL (men: 77.29 vs 83.83; P < 0.001; women: 70.40 vs 81.63; P < 0.001) compared with controls. Among IBD patients, SQoL was positively correlated with health-related quality of life (HRQoL) and negatively correlated with depression symptoms. Perianal disease was associated with lower HRQoL and higher incidence of depression, but only impacted SQoL in men. In linear regression analysis for men, SQoL was associated with age, marital status, and depression (β, –2.101; 95% confidence interval [CI], –2.505 to –1.696; P < 0.001). In women, SQoL was associated with depression (β, –1.973; 95% CI, –2.313 to –1.632; P < 0.001) only. Conclusions Patients with IBD had impaired SQoL compared with healthy controls. Age, widow status, and depression were independent predictors of SQoL in men with IBD, whereas in women depression was the only independent predictor. Emotional and self-esteem issues were the main concerns reported by IBD patients regarding sexual health.