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Novel biomarkers are needed to improve current imperfect risk prediction models for cancer-associated thrombosis (CAT). We recently identified an RNA-sequencing profile that associates with CAT in colorectal cancer (CRC) patients, with REG4, SPINK4, and SERPINA1 as the top-3 upregulated genes at mRNA level. In the current study, we investigated whether protein expression of REG4, SPINK4 and alpha-1 antitrypsin (A1AT, encoded by SERPINA1) in the tumor associated with CAT in an independent cohort of CRC patients. From 418 patients with resected CRC, 18 patients who developed CAT were age, sex, and tumor stage-matched to 18 CRC patients without CAT. Protein expression was detected by immunohistochemical staining and scored blindly by assessing the H-score (percentage positive cells*scoring intensity). The association with CAT was assessed by means of logistic regression, using patients with an H-score below 33 as reference group. The odds ratios (ORs) for developing CAT for patients with A1AT high , REG4 high , SPINK4 high tumors were 3.5 (95%CI 0.8-14.5), 2.0 (95%CI 0.5-7.6) and 2.0 (95%CI 0.5-7.4) when compared to A1AT low , REG4 low , SPINK4 low , respectively. The OR was increased to 24.0 (95%CI 1.1-505.1) when two proteins were combined (A1AT high /REG4 high ). This nested case-control study shows that combined protein expression of A1AT and REG4 associate with CAT in patients with colorectal cancer. Therefore, REG4/A1AT are potential biomarkers to improve the identification of patients with CRC who may benefit from thromboprophylaxis., (© 2023. The Author(s).)

Objective: Our study aimed to describe the prevalence and characteristics of gastrointestinal and eating problems in Dravet syndrome (DS) and other SCN1A-related seizure disorders and to determine the association between the occurrence of gastrointestinal and eating problems and core features of DS., Methods: Gastrointestinal and eating problems were assessed with a questionnaire in a Dutch cohort of participants with an SCN1A-related seizure disorder. Associations between the number of gastrointestinal and eating problems and core features of DS, seizure severity, level of intellectual disability, impaired mobility, behavioral problems, and use of anti-seizure medication, were explored by multivariate ordinal regression analyses. Symptoms were divided into the categories dysphagia-related, behavioral, and gastrointestinal, and were assessed separately., Results: One hundred sixty-nine participants with an SCN1A-related seizure disorder, of whom 118 (69.8%) with DS and 51 (30.2%) with Generalized Epilepsy with Febrile Seizures Plus / Febrile Seizures (GEFS+/FS), the non-DS phenotype, were evaluated. Gastrointestinal and eating problems were highly prevalent in DS participants, 50.8% had more than three symptoms compared to 3.9% of non-DS participants. Of participants with DS, 17.8% were fully or partly fed by a gastric tube. Within the three different symptom categories, the most prevalent dysphagia-related symptom was drooling (60.7%), distraction during mealtimes (61.4%) the most prevalent behavioral symptom, and constipation and loss of appetite (both 50.4%) the most prevalent gastrointestinal symptoms. DS participants who use a wheelchair (odds ratio (OR) 4.9 95%CI (1.9-12.8) compared to walking without aid), who use ≥3 anti-seizure medications (ASM) (OR 5.9 95%CI (1.9-18.2) compared to <3 ASM) and who have behavioral problems (OR 3.0 95%CI (1.1-8.1) compared to no behavioral problems) had more gastrointestinal and eating problems., Conclusion: Gastrointestinal and eating problems are frequently reported symptoms in DS. Distinguishing between symptom categories will lead to tailored management of patients at risk, will improve early detection, and enable a timely referral to a dietitian, behavioral expert, and/or speech therapist, ultimately aiming to improve the quality of life of both patients and caregivers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Clopidogrel is used as secondary prevention after cerebral ischaemia. Previous, mainly Asian, studies have shown that genetic variations in CYP2C19 are associated with an increased risk of recurrent stroke in clopidogrel-treated patients. Evidence on the impact of this drug-gene interaction in European neurology patients is currently limited. The aim of this study is to compare the prevalence of CYP2C19 loss-of-function (LoF) alleles in a population with recurrent cerebral ischaemia to two reference groups from the same region., Methods: CYP2C19-genotyping (*2 and *3) was performed in clopidogrel-treated patients who presented with a recurrent ischaemic stroke/transient ischaemic attack (TIA). Genotype distributions were compared with two reference groups; a cohort of consecutive patients who underwent elective coronary stent implantation and a cohort of healthy Dutch volunteers., Results: In total, 188 cases with a recurrent ischaemic event were identified, of whom 38 (20.2%) experienced an early recurrent event (24 hours to 90 days after the previous event). Among the total case group, 43.6% of the patients carried at least one CYP2C19 LoF allele, compared with 27.6% and 24.7% in respectively the cardiology and the healthy volunteers reference groups (P < .001 for both comparisons). Among the cases with an early recurrent event, 55.3% of patients were carriers of at least one CYP2C19 LoF allele (P < .0001)., Conclusion: In this clopidogrel-treated population with recurrent cerebral ischaemia, the frequency of CYP2C19 LoF alleles was significantly higher than in reference groups, especially in early recurrent events. This study adds to the growing body of evidence that genotype-guided antiplatelet therapy could improve patient outcomes., (© 2022 British Pharmacological Society.)

Background: Checklists are increasingly used to measure quality of care. Recently we implemented an antibiotic checklist in nine Dutch hospitals and showed that use of the checklist resulted in more appropriate antibiotic use. While more appropriate antibiotic use was associated with a reduction in length of stay, use of the checklist in itself was not. In the current study we explored discrepancies between reported and actually performed checklist items at the patient level to test the validity of checklist answers, to evaluate whether discrepancies between reported and actually performed checklist items could explain the lack of effect of checklist use on length of stay, and to identify missed opportunities for performance per checklist item., Methods: Checklist answers represented reported performance. Actual performance was assessed by data from the patients' medical files. Reported and actually performed checklist items could be 'both YES'; 'both NO'; 'YES reported, NOT actually performed'; or 'NO reported, YES actually performed'. We determined an overall 'both YES' score per checklist, and used mixed models to evaluate whether an association existed between this overall score and patient's length of hospital stay. Finally, we analysed whether the items that were not actually performed, could have been performed., Results: Between January and October 2015 physicians filled in 1207 checklists. In total 7881 items were checked. Most items were 'both YES' (3392/7881, 43.0%) or 'both NO' (2601/7881, 33.0%). The number of 'YES reported, NOT actually performed' items was 1628/7881 (20.7%) compared to 260/7881 (3.3%) 'NO reported, YES actually performed' items. The level of discrepancy between reported and actually performed items differed per checklist item. The item 'prescribe antibiotic treatment according to the local guideline' had the highest percentage of 'YES reported, NOT actually performed' items, namely 45.1%. A higher overall 'both YES' score of the checklist was significantly associated with a shorter length of hospital stay. Of all checklist items 21.8% were not performed while they could have been performed., Conclusions: Checklist answers do not accurately assess actual provided care. As actual performance of the antibiotic checklist items is associated with length of stay, efforts to increase actual performance appear to be justified.