Groene Hart Ziekenhuis

ObjectivesThe TREAT EARLIER trial showed in clinically suspect arthralgia (CSA) that methotrexate induced reductions in subclinical inflammation and related disease burden during the year of treatment, which was sustained thereafter. We studied whether the treatment response defined at the level of subclinical joint inflammation was present in all treated CSA patients and, if not, what characterises the subgroup of responders.MethodsCSA patients with subclinical inflammation were randomised to receive an intramuscular glucocorticoid injection and a 1-year course of methotrexate. Treatment response was defined as a reduction of MRI-detected synovitis, tenosynovitis or osteitis levels beyond the smallest detectable change at 12 months. Baseline clinical and imaging characteristics were studied in relation to treatment response. Predictive values were determined.Results44 of 115 (38%) treated patients had an MRI-defined treatment response. These patients also significantly improved in pain and physical functioning (−22 Visual Analogue Scale pain, −0.29 Health Assessment Questionnaire). Baseline clinical variables were not independently associated with this response, in contrast to the severity of subclinical joint inflammation. Tenosynovitis and osteitis levels in particular were predictive. Patients with ≥2 sites with tenosynovitis or a combination of osteitis and tenosynovitis (with ≥1 of these features at ≥2 sites) had high positive predictive values (PPV 77%, 79%). PPVs were similar in ACPA-positive and ACPA-negative patients at increased risk for rheumatoid arthritis (RA).ConclusionsCSA patients with subclinical inflammation who responded best to methotrexate during the first year were identified by increased levels of subclinical inflammation at diagnosis, primarily due to multiple sites of tenosynovitis with/without osteitis. These data may contribute to personalised medicine for arthralgia at risk for RA.

BackgroundPhysical activity (PA) is associated with improved overall survival (OS) among colorectal cancer (CRC) patients, but research on PA changes after diagnosis remains limited. This study examines associations between OS and changes in PA from CRC diagnosis onward, across stage- and treatment-related subgroups.MethodsData were analyzed from patients in two large CRC cohorts (PLCRC and COLON) enrolled between August 2010 and December 2022 (follow-up until February 1st, 2024). This included 3395 stage I–IIA patients who underwent surgery only, 2406 stage IIB/C–III patients who received (neo-)adjuvant therapy, and 669 metastatic CRC (mCRC) patients. PA was assessed via the validated SQUASH questionnaire at diagnosis (T0), and at 6, 12, and 24 months post-diagnosis (T6 to T24). Moderate-to-vigorous-intensity recreational activity was quantified by calculating Metabolic Equivalent of Task (MET) hours per week. Associations with OS were examined for change (active [tertile 2 and 3] vs inactive [tertile 1]) between timepoints using multivariable Cox proportional hazards models.ResultsAmong surgery-only patients, change from inactivity to activity between T0 and T6 was significantly associated with OS (HR = 0.58, 95% CI = 0.35 to 0.96). For (neo-)adjuvantly treated patients, significant associations were observed between T6 and T12 (HR = 0.53, 95% CI = 0.31 to 0.90). Among mCRC patients, a significant association was observed between T6 and T12 (HR = 0.53, 95% CI = 0.29 to 0.99).ConclusionChanging from inactivity to activity is significantly associated with prolonged survival during the early months post-diagnosis for surgery-only CRC patients, and later for those undergoing (neo-)adjuvant therapy or with metastatic disease. Validation is warranted in interventional studies.

Restrictive red blood cell transfusion strategies are widely recommended for acute anemia but may not adequately address the needs of chronically anemic patients with transfusion-dependent myelodysplastic syndromes or myeloproliferative neoplasms. For these patients with chronic anemia, alleviating symptoms and improving quality of life are key objectives. This study evaluates the impact of additional red blood cell (RBC) transfusions administered alongside standard-of-care transfusions on heart rate, physical activity, quality of life, and cognitive function. This interim analysis of a randomized, multicenter, within-subject, cross-over trial evaluated 12 transfusion-dependent patients receiving three transfusion regimens: standard-of-care, standard-of-care + 1 additional unit, and standard-of-care + 2 additional units. The primary outcome was heart rate, and secondary outcomes were physical activity, quality of life, and cognitive performance. Heart rate and activity were continuously monitored, while questionnaires and cognitive tasks assessed outcomes at predefined visits. Greater hemoglobin augmentation was associated with significant reductions in heart rate, with the largest decrease in patients receiving the standard-of-care + 2 regimen. Quality of life and fatigue measures showed transient improvements with more red blood cells transfused, though these changes were not statistically significant. Cognitive performance trends suggested possible benefits, but findings were inconsistent. Physical activity, as measured by daily step count, was unaffected by transfusions. This interim analysis suggests that higher post-transfusion hemoglobin is associated with lower heart rate, reflecting enhanced oxygen delivery. Wearable monitoring was sensitive to these changes. Nonsignificant, hypothesis-generating trends toward improved QoL, fatigue, and cognition were observed.

BackgroundTimely integration of palliative care has numerous benefits for patients with incurable cancer. Based on a recent national Delphi study on the timely integration of palliative care in oncology, three recommendations were formulated regarding 1) advance care planning (ACP), 2) routine symptom monitoring during the last year of life, and 3) involving the Specialist Palliative Care Team (SPCT) during the last three months of life. This pilot study aimed to assess the feasibility of these recommendations in the Dutch context.MethodsFour Dutch hospitals implemented these recommendations for three months. Feasibility was assessed in three ways. First, the extent to which the recommendations were applied was assessed by analysis of electronic medical records (EMRs) of 542 patients with incurable cancer. Second, the extent to which clinicians (n = 27) found the recommendations applicable was assessed using a questionnaire including the Measurement Instrument for Determinants of Innovations (MIDI) and self-administrated questions. Last, patients’ experiences (n = 70) were assessed using the EORTC IN-PATSAT and self-administrated questions regarding using the recommendations.ResultsThe recommendation on ACP was applied in 49% of eligible patients and the recommendation on symptom monitoring and SPCT in 58%. Most clinicians agreed that all three recommendations were important to achieve timely integration of palliative care (85%). The majority reported being able to conduct ACP discussions (78%), to consider involving the SCPT in case of complexity (73%), and to offer SPCT consultation in case of a life expectancy of ≤ 3 months (68%). A minority reported being able to pay attention to symptom monitoring across the four dimensions (42%) and to record outcomes in the EMR (19%). Patients who received care according to the recommendations were equally satisfied with care compared to those who received standard care, except when symptoms of social problems were monitored; these patients were more satisfied with care, respectively 83.1(SD 18.7) vs 71.2(SD 20.1).ConclusionsImplementing the recommendations for timely integration of palliative care in daily clinical oncology practice seems feasible. The key is to address practical issues, including information exchange about ACP and symptom management among all involved clinicians.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12913-025-13199-2.

Optimal treatment duration is unknown in metastatic renal cell carcinoma (mRCC) responding to immune checkpoint inhibitors (ICPIs). Prolonged treatment can lead to late toxicity, burden for day clinics and financial impact. This multicenter retrospective study included mRCC patients responding to ipilimumab/nivolumab in first-line or nivolumab in later lines, who were treated for at least 21 months and did not stop for toxicity. Progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were modeled non- and semi-parametrically. The effect of elective ICPI discontinuation (i.e. treatment interruption at the clinician's discretion) between 21 and 25 months on PFS was assessed by a causal inference approach using artificial censoring along with inverse probability of censoring weighting. Ninety-five patients were included with a median follow-up of 62.1 (95% confidence interval [CI]: 57.3-67.5) months. Fifty-four received ipilimumab/nivolumab, whereas 41 patients received nivolumab, for a median treatment duration of 33.8 (95% CI: 28.5-39.6) months. Fifty-seven patients discontinued ICPIs electively. Three-year PFS after discontinuation was 57.1% (95% CI: 34.3-95.1), 3-year OS 67.5% (95% CI: 37.0-100.0), and 3-year CSS 90.0% (95% CI: 73.2-100.0). Fifteen (15.8%) patients discontinued ICPIs between 21 and 25 months. Compared to 80 patients who were treated longer, they had more often a metachronous metastatic pattern (p=0.048) and a complete response (p=0.045). Elective ICPI stop between 21 and 25 months did not significantly impact the hazard for progression/death (adjusted HR 1.08, 95% CI: 0.64-1.84, p=0.766). Among mRCC patients responding to ICPI, elective therapy discontinuation approximately 24 months after initiation does not appear to compromise outcomes compared to continuing therapy.

Early prediction of disability progression in multiple sclerosis (MS) remains challenging despite its critical importance for therapeutic decision-making. We present the first systematic evaluation of personalized federated learning (PFL) for 2-year MS disability progression prediction, leveraging multi-center real-world data from over 26,000 patients. While conventional federated learning (FL) enables privacy-aware collaborative modeling, it remains vulnerable to institutional data heterogeneity. PFL overcomes this challenge by adapting shared models to local data distributions without compromising privacy. We evaluated two personalization strategies: a novel AdaptiveDualBranchNet architecture with selective parameter sharing, and personalized fine-tuning of global models, benchmarked against centralized and client-specific approaches. Baseline FL underperformed relative to personalized methods, whereas personalization significantly improved performance, with personalized FedProx and FedAVG achieving ROC-AUC scores of 0.8398 ± 0.0019 and 0.8384 ± 0.0014, respectively. These findings establish personalization as critical for scalable, privacy-aware clinical prediction models and highlight its potential to inform earlier intervention strategies in MS and beyond.

Background/Objectives: The co-existence of multiple compression sites on the same nerve can pose a clinical and diagnostic challenge, warranting a different treatment strategy. This so-called double crush syndrome (DCS) has mainly been investigated in the upper limb. Only a few studies have investigated DCS for the lower limb. In this article, a single-center illustrative clinical case series is presented, and current literature on L5 nerve root (NR) and concomitant common peroneal nerve (CPN) is reviewed. Methods: All patients presenting between 2019 and 2022 with L5 nerve root (NR) compression and, along their clinical courses, concomitant compression of the common peroneal nerve (CPN) at the fibular head were included. Information on clinical features, diagnostics and surgeries was obtained. The outcome was assessed at the last outpatient follow-up appointment. In addition, an extensive literature review has been conducted. Results: Fourteen patients were included with a mean follow-up of 6.8 months. The majority had pain (71%) or motor deficits (71%). Seven patients were referred for clinical and radiological L5 NR compression but were also found to have CPN compression; the other seven patients had persisting or recurrent symptoms after surgically or conservatively treated L5 NR compression, suggestive of additional peroneal neuropathy. All patients had CPN decompression at the fibular head, with successful results obtained in 93% of the patients. Pain of the lower leg improved in all patients, and dorsiflexion function improved in 78%. Conclusions: Concomitant L5 NR and CPN appear to occur more frequently than expected. Peroneal neuropathy can present simultaneously with L5 nerve radiculopathy or after surgically or conservatively treated L5 NR compression. Overlapping symptoms and variation in clinical presentations make it difficult to diagnose and, therefore, underrecognized. More awareness among treating physicians of this specific double crush syndrome is important to prevent any delay in treatment, in this case, a less invasive common peroneal nerve release at the fibular head, and to avoid unnecessary (additional) spinal surgery.

With tumor genomic and gene-expression profiling (GEP), this study investigated the immune-molecular signatures of a unique cohort of diffuse large B-cell lymphoma of the bone (bone-DLBCL), including primary bone (PB-DLBCL, n = 52) and polyostotic-DLBCL (n = 20), in comparison to nodal DLBCLs with germinal center B-cell (GCB) phenotype (nodal-DLBCL-GCB, n = 34). PB-DLBCL and polyostotic-DLBCL shared similar genomic profiles and transcriptomic signatures, justifying their collective analysis as bone-DLBCL. Differential incidences of EZH2, HIST1H1E, and MYC aberrations (p < 0.05) confirmed the distinct oncogenic evolution between bone-DLBCL and nodal-DLBCL-GCB. Differentially expressed genes were identified between bone-DLBCL and nodal-DLBCL-GCB (p < 0.001), substantiated by distinct gene-set enrichment analysis (GSEA). In contrast to a more ‘depleted’ phenotype for nodal-DLBCL-GCB, bone-DLBCL primarily exhibited an ‘intermediate/rich’ tumor microenvironment (TME) signature (p = 0.001), as determined by a previously published gene set. Unsupervised clustering defined two distinct groups that aligned with previously reported immune-enriched TME clusters: an ‘immune-rich’ cluster largely consisting of bone-DLBCLs (75%, p = 0.002) with superior survival (p = 0.030), and a poor-prognostic ‘immune-low’ cluster, including mostly nodal-DLBCL-GCB (61%). Single-sample (ss)GSEA showed higher scores for regulatory T cells, immunosuppressive/prolymphoma cytokines, and vascular endothelial cells in immune-rich samples (p < 0.001). Additionally, CIBERSORTx revealed a higher abundance of regulatory T cells and activated mast cells in the immune-rich cluster (p < 0.001). These findings were confirmed at protein level, where CD3 and FOXP3 immunochemistry showed significant overlap with the gene-expression data (p < 0.001). Conclusively, PB-DLBCL and polyostotic-DLBCL share immune-molecular TME characteristics, supporting their classification as a unified bone-DLBCL entity. The distinct immune-rich TME profile of bone-DLBCL associated with superior survival potentially shapes emerging immunomodulatory strategies

According to the nationally imposed standard of care in the Netherlands, severely injured patients should be brought to a Level-1 trauma center for primary treatment. If not, they are considered to be undertriaged. This study aimed to determine the incidence of undertriage among severely injured geriatric patients and to evaluate the relation between hospital-undertriage and patient outcomes in elderly. This retrospective cohort study used anonymized data from the regional trauma registry of 1,431 patients aged ≥70 years with an Injury Severity Score ≥16 that were admitted to hospitals within the Trauma Region West-Netherlands between 2015 and 2022. Poor patient outcome was defined as in-hospital mortality or as a Glasgow Outcome Scale (GOS) score ≤3 at hospital discharge. The association between hospital level and poor outcomes was analyzed using multivariable logistic regression analysis with adjustment for confounders after multiple imputation of missing values. Seventeen percent of the severely injured geriatric patients were primarily transported to a Level-2/3 hospital. Female patients, older patients, and patients that had suffered a low-energy fall were most likely to be undertriaged. The adjusted odds ratio's for in-hospital mortality and GOS score ≤3 in Level-1 versus Level-2/3 hospitals were 1.26 (95 % confidence interval, 0.83-1.93; p = 0.28) and 0.81 (95 % confidence interval, 0.57-1.15; p = 0.24), respectively. Undertriaged severely injured geriatric patients did not have a higher risk for poor outcomes. Level-2/3 hospitals seem to present a safe alternative for the treatment of these patients.