Amphia Ziekenhuis

In multiple sclerosis (MS), depression and anxiety are common, yet their relation to disease progression is unclear. We investigated whether Hospital Anxiety and Depression Scale (HADS) symptoms predict neurological disability progression. In our prospective cohort of people with primary progressive MS (PPMS), depressive and anxiety symptoms were assessed using HADS. Disability progression at 1 and 2years was assessed using three predefined endpoints: (1) Expanded Disability Status Scale (EDSS), (2) a three-variable composite endpoint (EDSS, Timed 25-Foot Walk (T25FW), or Arm Function in Multiple Sclerosis Questionnaire (AMSQ)), and (3) a five-variable composite endpoint (EDSS, T25FW, AMSQ, Symbol Digit Modalities Test (SDMT), or Patient-Determined Disease Steps (PDDS)). Logistic regression modelled whether HADS scores predicted disability progression. Boruta feature selection identified the most informative HADS items. One hundred eleven adults with PPMS completed the HADS (all ≥ 1-year follow-up; 62 ≥ 2years). Progression occurred predominantly on individual domains. At 1year, higher total HADS scores predicted progression on the five-variable composite endpoint (OR 3.10, [95% CI 0.99-9.75], p = 0.05; AUC 0.59, [95% CI 0.47-0.70]). At 2years, the depression sub-score consistently predicted progression on EDSS (OR 8.88, [95% CI 1.12-70.66], p = 0.04), and the five-variable composite endpoint (OR 9.46,[95% CI 1.50-59.52], p = 0.02). Boruta feature selection identified HADS depression-associated items 6 and 8 as best predictors; together achieving similar predictive accuracy compared to the full HADS questionnaire. Higher HADS scores, particularly depressive symptoms, predicted disability progression. These findings indicate prognostic value of patient-reported outcomes in predicting disease worsening and their potential use in guiding personalised treatment in progressive MS.

Reducing AF-related symptoms and improving health-related quality of life (HRQoL) are important drivers in the decision for pulmonary vein isolation (PVI) in treating symptomatic atrial fibrillation (AF). We assessed the association between various patient characteristics, intervention, and outcome variables, and HRQoL both prior to and one year after PVI, with specific attention to groups that did not improve or were still impaired in HRQoL post PVI. Observational, retrospective multicenter cohort study within 8hospitals participating in the Netherlands Heart Registration (NHR). Patients who underwent PVI between 2016 and 2019 and completed the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire both prior to and one year after were included. Accepted cut-off values for impaired HRQoL and clinically important difference (CID) were used. Mean AFEQT score (n = 2,534) was 55.6 ± 19.7 prior to intervention and 79.8 ± 20.2 after. Post-PVI, 39.5% of the population was still impaired in HRQoL (< 80points), and 19.2% failed to achieve CID (delta ≥ 5points). Lower baseline AFEQT-score (odds ratio [OR], 0.96 [per 1‑point increase]; 95% CI, 0.96-0.97; p < 0.001) and female sex (odds ratio [OR], 1.42; 95% CI, 1.16-1.75; p < 0.001) were the most prominent related factors with impaired HRQoL post-PVI. Higher baseline AFEQT-score (odds ratio [OR], 1.04 [per 1‑point increase]; 95% CI, 1.04-1.05; p < 0.001) was strongly associated with failure to achieve CID. Despite amajor increase in HRQoL across the population, over one-third of patients were still impaired in HRQoL post-PVI. Multiple factors were identified that may guide counselling of AF patients about treatment choice.

Abstract Background Endoscopy is the gold standard for assessing treatment effectiveness in ulcerative colitis (UC) patients, but it is an invasive procedure and therefore frequent repeated procedures are not feasible routine practice. Biochemical measures are used as proxy endpoints alongside clinical parameters. However, discrepancies between clinical and biochemical remission are commonly seen in clinical trials and daily practice. We conducted a large real-world cohort study to assess divergence between clinical and biochemical parameters over time in UC patients starting advanced agents. Methods Data were obtained from the Dutch Initiative on Crohn and Colitis (ICC) Registry. UC patients initiating anti-TNFα agents, vedolizumab, IL-(12/)23 inhibitors, or JAK inhibitors before 1 November 2024 were included; those with colectomy were excluded. Clinical remission was defined as Simple Clinical Colitis Activity Index ≤2, and biochemical remission as faecal calprotectin ≤250µg/g. Divergence was defined as the proportion of patients in either clinical or biochemical remission, divided by those with both measures available at treatment start (week 0), week 12 (±6 weeks), week 24 (±6 weeks), and week 52 (±8 weeks). Differences between the different treatment classes were analysed using Pearson’s χ2 or Fisher’s exact tests. Results A total of 777 patients were included. Availability of data varied over time; both clinical and biochemical data were available for 394 patients (45.7%) and 171 patients (22.0%) at baseline and week 52, respectively. Divergence fluctuated across the different treatment classes and in general (Figure 1), from 20.7% (95%CI 16.7-25.3) at baseline to 29.8% (95%CI 23.2-37.4) at week 52. When divergence occurred, clinical remission was more frequently observed than biochemical remission. Patients on anti-TNF agents were, on average, more likely to exhibit divergent remission outcomes, although differences between medication classes were not statistically significant. Among patients with divergence at baseline, 22/77 (28.6%) showed divergence up to week 12, and one patient showed persistent divergence up to week 52, being in biochemical remission at week 0, 24, and 52, but in clinical remission only at week 12. Conclusion Divergence between clinical and biochemical remission in ulcerative colitis is common, dynamic, and varies across advanced treatment classes. This persistent disconnect highlights that clinical remission alone is an insufficient primary endpoint in therapeutic trials. Robust research into the mechanisms and determinants of this divergence is essential to inform evidence-based, multidimensional endpoints and to refine treatment targets in clinical practice. Conflict of interest: Verleye, Loriane: No conflict of interest Bloemen, Hannah: No conflict of interest Pierik, Marieke: Grant: TKI, MLDS, Galapagos, Janssen-Cilag, Takeda, Pfizer Other: Financial support to institution for consultancy or lectures: Takeda, Janssen-Cilag, BMS, MSD, Abbvie, Galapagos, Ferring Winkens, Bjorn: No conflict of interest Visschedijk, Marijn: Speakers fees from Jansen-Cilag, Abbvie, Ferring, Alfasigma, Takeda. Van der Meulen - de Jong, Andrea Elisabeth: Speaking fees from Alfasigma, Ferring and Abbvie. Advisory board fees from Abbvie, Alfasigma, Ferring, Janssen, Takeda, Vedanta and grant/research support from Alfasigma, Cablon and Norgine. van Schaik, Fiona: FDM van Schaik has received consultancy fees from Takeda, Galapagos and AbbVie, speaker’s honoraria from Galapagos, Lilly, AbbVie and Janssen-Cilag B.V., hospitality fees from Ferring and dr. Falk Farma and an unrestricted research grant from Takeda. Naber, Myrthe: No conflict of interest Löwenberg, Mark: Consultancy/lecture fees from Abbvie, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, Johnson &amp; Johnson, Medtronic, Pfizer, Takeda, Tillotts. Grants received from Alfasigma, NFU transformation deal, ZonMW and TKI. De Vries, Annemarie C.: Grant: Grants, advisory boards: Pfizer, Galapagos, Takeda, Janssen Bodelier, Alexander: Participation in advisory boards of: Johnson &amp; Johnson, Eli Lilly, Sanofi. Received unrestricted grant from Amphia research fund. Smid, Jael: No conflict of interest Duijvestein, Marjolijn: Grant: Speaking fees from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, Dr. Falk, Advisory board fees from Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos/Alfasigma, Janssen, Takeda Grant/Research support: Pfizer, Bristol Meyers Squibb, Galapagos, Alfasigma, Janssen, Lilly Mujagić, Zlatan: Grants from ZonMw, Niels Stensen Fellowship, Maag Lever Darm Stichting (MLDS), Academische Alliantie Fonds (AAF), Top consortium for Knowledge and Innovation (TKI) and Galapagos, advisory board fees from Johnson &amp; Johnson, Eli Lilly, Pfizer (paid to host institution) and speaker’s fees from Friso – Friesland Campina, Galapagos / Alfasigma, Eli Lilly, Takeda (paid to host institution).

Increased application of neoadjuvant therapy (NAT) and adjuvant therapy (AT) could limit treatment options for pancreatic ductal adenocarcinoma (PDAC) recurrence. This study aimed to identify patterns of recurrence-focused treatment and survival following different primary treatment strategies. All patients who underwent PDAC resection in the Netherlands (2014-2019) were included. Patients were divided into five groups according to their primary treatment strategy: (1) resection only, (2) gemcitabine-based NAT + resection, (3) FOLFIRINOX-based NAT + resection, (4) resection + gemcitabine-based AT, and (5) resection + FOLFIRINOX-based AT. Differences in recurrence-focused treatment and post-recurrence survival (PRS) were assessed using multivariable logistic and Cox-proportional hazards analyses and were presented as odds ratios (ORs) and hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs), respectively. In total, 1739 patients (median follow-up of 51 [interquartile range 34-64] months) were included, of whom 1272 (73%) had disease recurrence.In these patients, recurrence-focused treatmentwas administered in 64/124 (52%) after FOLFIRINOX-based NAT compared with 74/410 (18%) with resection only (OR 4.13 [95% CI 3.34-5.12]; P<0.001), 29/70 (41%) with gemcitabine-based NAT (OR 1.61 [95% CI 1.21-2.15]; P<0.001), 239/604 (39%) with gemcitabine-based AT (OR 1.73 [95% CI 1.43-2.09]; P<0.001), and 24/64 (38%) with FOLFIRINOX-based AT (OR 1.44 [95% CI 1.06-1.95]; P=0.02). Recurrence-focused treatment was associated with a median PRS of 11 (95% CI 10-13) months compared with 3 (95% CI 2-3) months in patients with best supportive care (HR 0.31 [95% CI 0.26-0.37]; P<0.001). Recurrence-focused treatment differs between patients with PDAC who received different primary treatment strategies and is associated with improved PRS.

BackgroundThe preferred timing of treatment of nonculprit lesions in patients with ST-segment elevation myocardial infarction (STEMI) remains uncertain. A comparison of immediate percutaneous coronary intervention (PCI) guided by instantaneous wave-free ratio (iFR) and deferred PCI guided by cardiac stress magnetic resonance imaging (MRI) in patients with STEMI and multivessel disease is warranted.MethodsIn this international, investigator-initiated, open-label, randomized, controlled trial, patients with STEMI and at least one nonculprit lesion who had undergone successful primary PCI were randomly assigned in a 1:1 ratio to immediate iFR-guided PCI (in lesions with >50% stenosis and an iFR of ≤0.89 [normal value, >0.89]) or deferred cardiac stress MRI–guided PCI within 6 weeks after randomization. The primary end point was a composite of death from any cause, recurrent myocardial infarction, or hospitalization for heart failure at 3-year follow-up.ResultsThe trial included 1146 patients (558 in the iFR group and 588 in the MRI group) with a mean (±SD) age of 63±11 years; 78% were men. A total of 237 of 556 patients (42.6%) in the iFR group and 110 of 587 patients (18.7%) in the MRI group underwent nonculprit-lesion coronary-artery PCI. A primary-end-point event occurred in 50 patients (9.3%) in the iFR group and in 55 patients (9.8%) in the MRI group (hazard ratio, 0.95; 95% confidence interval, 0.65 to 1.40; P=0.81). Serious adverse events occurred in 145 patients in the iFR group and in 181 in the MRI group.ConclusionsAmong patients with STEMI who have undergone successful primary PCI, immediate iFR-guided PCI was not superior to deferred cardiac stress MRI–guided PCI of nonculprit coronary-artery lesions with respect to death from any cause, recurrent myocardial infarction, or hospitalization for heart failure at 3 years. (Funded by Philips Volcano and others; iMODERN ClinicalTrials.gov number, NCT03298659.)