Spaarne Ziekenhuis

Malignant and non-malignant cells within the tumor microenvironment (TME) actively secrete extracellular vesicles (EVs) that may mediate intercellular communication or enter the blood stream. Circulating EVs in Diffuse Large B-Cell Lymphoma (DLBCL) patients are a promising source of liquid biopsy biomarkers; however, whether different cellular components of the TME preferentially secrete small (S-) and/or large (L-) EVs is still unknown. With an established density-gradient separation protocol and tunable resistive pulse sensing analysis, we demonstrate that DLBCL cells in culture produce 100-1000-fold higher numbers of S-EVs (50-200nm) compared with L-EVs (200-1000nm) and very large EVs (>1000nm). In contrast, the plasma from DLBCL patients contains comparable concentrations of S- and L-EVs, consistent with various cellular origins. Small RNA sequencing showed minor differences in miRNA content between plasma S- and L-EVs; however, messenger RNA sequencing revealed stark differences in cargo between EV-size subtypes and between healthy donors and patients. Deconvolution analysis with single-cell sequencing data from 17 DLBCL tumor tissues as reference using the Statescope algorithm indicated that circulating S-EVs from malignant cells outnumber the L-EVs. In contrast, TME macrophage-, T cell-, and natural killer-derived L-EVs outnumber S-EVs. Together, these findings suggest that circulating S- and L-EVs can originate from distinct cellular compartments within the DLBCL TME, representing complementary biological information. These observations have important implications for the development of EV-based liquid biopsy strategies.

A broad arm sling is traditionally applied following shoulder surgery for protection of repair and 'for comfort'. It has never been proved however that the use of a sling actually leads to reduced pain. The aim of our prospective study was to quantify a patient's immediate post-surgical pain with and without a sling, with the hypothesis being that it is in fact more comfortable not to have it on. Following surgery, a sling was applied as usual, and a pain score obtained within the first 4 hours. The sling was then removed and the score immediately repeated. The sling was left off until discharge, then used again as dictated by the nature of the surgery performed. The mean pain score prior to sling removal was 4.59. The mean score following sling removal was 3.24, a mean reduction in 10-point Numerical Pain Scale of 1.35 points (p < 0.001). Sixty-two out of 85 patients experienced some reduction in pain after removal of the sling. No patient reported an increase in pain. Our study shows that the simple action of allowing the operated arm to rest free of a sling reduces pain in the immediate post-surgical period.

Patients with an osteochondral lesion of the talus (OLT) often present with deep ankle pain, but the direct relationship between structural damage and the perceived pain remains unclear. The aim of this study was therefore to determine whether pain is associated with demographic and radiologic (computed tomography [CT]-only) lesion characteristics. This cross-sectional study was conducted in patients with symptomatic OLTs at a tertiary referral academic hospital. The primary outcome was the Pain subscale of the Foot and Ankle Outcome Score (FAOS). Secondary outcomes included the Numeric Rating Scale (NRS) for pain at rest and during walking, as well as the other FAOS subscales. Associations with patient demographics, lesion size, morphology, and location were assessed using univariate linear regression, followed by multivariate linear regression with backward selection. A total of 310 patients were included. In the final multivariate model for the FAOS Pain subscale, higher age (β = -0.18, P = .04) and smoking (β = -8.70, P < .001) were significantly associated with worse pain scores. Lesion morphology characterized by the presence of an osteochondral fragment was associated with lower NRS pain scores during walking. For NRS pain at rest, worse scores were significantly associated with female sex, higher body mass index, smoking, non-primary lesion nature, and greater lesion depth. No association was found between CT-based radiologic lesion characteristics and patient-reported pain as measured by the FAOS Pain subscale. In secondary analyses, some lesion characteristics showed associations, but these were limited and directionally inconsistent. These findings suggest structural damage alone does not seem to fully explain the patient's pain. Given the CT‑only approach and other design constraints, further research is warranted.

IntroductionThe Latarjet procedure is the mainstay treatment in high-demand patients with substantial glenoid bone loss or after failed capsulolabral repairs. Patients typically return to sport (RTS) within 6 months postoperatively, requiring intensive rehabilitation. Current rehabilitation protocols focus on mobility, strength and stability. Yet, psychological factors, such as fear of reinjury, are the main reason not to RTS. Therefore, this study aims to determine whether integrating psychological interventions into postoperative rehabilitation improves patient-reported shoulder function compared with physical therapy alone.Methods and analysisThis monocentric randomised controlled trial will enrol 52 patients undergoing a Latarjet procedure for anterior shoulder instability. Participants will be equally and randomly assigned to either postoperative physical therapy combined with cognitive behavioural therapy or physical therapy alone. Eligibility criteria include patients aged 18–67 years undergoing an open or arthroscopic Latarjet procedure at our institution. Exclusion criteria include posterior or multidirectional instability, rotator cuff tear, prior shoulder surgery, anxiety disorder, using anxiolytics, neurological disorder, systemic disease, previous hospitalisation for shoulder pain and proximal humerus fractures.The primary outcome is the Western Ontario Shoulder Index at 6 months postoperatively. Secondary outcomes include incidence of recurrent dislocations, RTS and return-to-work rates, Tampa Scale of Kinesiophobia for Shoulder Instability, subjective shoulder value and visual analogue score for pain at 6 months postoperatively as well as the Shoulder Instability Return to Sport after Injury scale at 4.5 months postoperatively.Ethics and disseminationThis study was approved by the French Committee of Person Protection West I. The national registration number is 2023-A02057-38. The study has been registered at Clinicaltrials.gov with trial registration number NCT06154889. Patients are not financially compensated for participation and are allowed to withdraw from the study at any time without any preconditions. The final results of the study will be submitted for publication in a peer-reviewed journal and an abstract of the study will be submitted to international scientific meetings by the end of 2026. Data will be made available by the corresponding author on reasonable request.Registration detailsThe study has been registered at Clinicaltrials.gov with trial registration number NCT06154889. The trial sponsor is Vivalto Santé.Trial registration numberNCT06154889.

AimRobotic assisted Trans Abdominal Retromuscular Umbilical Prosthesis (rTARUP) is being increasingly performed to treat Ventral Hernia. Prospective (long-term) studies are scarce. In this study we investigated 125 patients with short and long-term follow-up, regarding surgical and hernia-related quality-of-life outcomes.Material and MethodsPatients undergoing rTARUP were selected from consecutive prospectively collected databases from two teaching hospitals from the Netherlands. The patients were operated by experienced surgeons in a standardized manner. Patient characteristics and short-term outcomes after surgery were retrospectively reviewed and follow up data about hernia recurrence and quality of life was prospectively collected.Results125 rTARUP patients were included for analysis. The most common hernia type was primary (n = 61), followed by recurrent (n = 37) and incisional (n = 27). The median surgical time was 90 min. 44/61 (72%) patients with a primary ventral hernia were treated as daycase. The 30-day complication rate was 7.2%. Median follow up was 24 months after which a large majority of patients (84%) reported to feel better or much better. There were 3 reoperations for recurrences (2.4%).ConclusionrTARUP is a safe and effective procedure that can be performed in a timely manner, with short hospital stay and a low complication rate. Further research is needed into economical costs and benefits to fully justify the use of robotic surgery for these indications.

IntroductionFusion achievement is considered a crucial factor in recovery following anterior discectomy. Nevertheless, the direct correlation between fusion and clinical outcomes, such as pain and disability, remains ambiguous due to inconsistent fusion measurement methods. Recent advancements in diagnostic fusion criteria now enable a more accurate fusion assessment. This study aimed to assess the association between fusion and clinical outcomes in patients undergoing anterior cervical discectomy.MethodsThis post-hoc analysis was conducted using data from the NEtherlands Cervical Kinematics (NECK) trial (NTR1289). Patients with a single level herniated disc that underwent anterior cervical discectomy between 2010 and 2014 were evaluated at 52, 104, and 260 weeks. Fusion was assessed using dynamic radiographs, applying the de Vries-Vleggeert criterion (≤3.0° Cobb angle and ≤2.0 mm interspinous distance). Clinical outcomes included the Neck Disability Index (NDI) and Visual Analog Scale (VAS) for arm and neck pain. Linear and logistic regressions were performed to evaluate correlations.ResultsFusion was present in 57% (52 weeks), 75% (104 weeks), and 83% (260 weeks) of patients. Linear regression analyses revealed a clear trend suggesting favorable long-term VAS arm and neck pain scores in the patient’s demonstrating fusion with statistically significant lower VAS arm pain (mean difference: –18.9, 95% CI –36.9 to –0.9, p = 0.040) in the fusion group at 260 weeks follow-up. At earlier follow-up points, the differences in VAS arm pain did show a trend, but did not reach statistical significance (W52: 6.0, 95% CI –6.6 to 18.6, p = 0.346; W104: –11.5, 95% CI –24.2 to 1.3, p = 0.076). VAS neck pain scores showed a trend, but no statistically significant differences between groups across follow-up (W52: 3.2, 95% CI –8.1 to 14.5, p = 0.572; W104: –1.5, 95% CI –13.8 to 10.8, p = 0.808; W260: –12.7, 95% CI –30.9 to 5.6, p = 0.170). No significant differences were observed in NDI outcomes at any time point (W52: 3.2, 95% CI –4.8 to 11.2, p = 0.431; W104: –3.7, 95% CI –11.6 to 4.2, p = 0.358; W260: 2.5, 95% CI –7.2 to 12.1, p = 0.608). Logistic regression analysis using success rates based on established cut-off values showed a trend towards patients with fusion having markedly higher odds of success long term, with a significant higher odd of success in VAS arm pain at 260 weeks FU (OR 9.88, 95% CI 1.55–62.80, p = 0.015).ConclusionA comparative analysis indicated reduced arm and neck pain in the fusion group at the 260-week follow-up. This finding becomes apparent only in the long-term post-intervention period, suggesting that muscle tension may function as a natural brace during the initial years following surgery. This tension effectively limits excessive flexion-extension movements, thereby mitigating discomfort. These results have potential implications for routine clinical surgical practice. Future studies with larger sample sizes are needed to validate these findings, including short-term follow-up.

Berendsen, Remco R., Dirk C.A.A. de Vries, Alea Steger, Nadine Herold, Feico J.J. Halbertsma, Adriaan F. Norbart, Hannes Gatterer, and Bengt Kayser. Lack of altitude medicine knowledge among mountaineers in the Italian Alps. High Alt Med Biol. 26:361-373, 2025. Introduction: In 2022, expert consensus defined a set of minimum altitude medicine knowledge statements for laypersons traveling to high altitudes (STAK: strengthening altitude knowledge). We used these statements to assess knowledge among mountaineers in the Italian Alps. Methods: Mountaineers in a hut (3,647 m) completed an online STAK-based questionnaire, also indicating their confidence after each answer. A score of ≥19/28 was used as a statistical threshold, exceeding chance alone. Logistic regression assessed the link between confidence and correctness; multivariate regression explored demographic, educational, and behavioral predictors of achieving an above-threshold score. Results: Of 576 participants, 412 (72%) were included in the final analysis and 115 (28%) scored ≥19. Among them, 59% of medical professionals, 36% of mountain guides, and 23% of general participants reached the threshold; the medical professionals scored significantly higher than the general participants (p < 0.001). Both being a mountain guide (odds ratios [OR]: 2.3, 95% confidence intervals [CI]: 1.0-5.0, p < 0.05) and being a medical professional (OR: 4.5, 95% CI: 2.1-10.0, p < 0.001) were associated with higher scores. Conclusion: Using STAK as a benchmark, we found a substantial lack of altitude medicine knowledge in mountaineers, even among guides and medical professionals. These findings suggest a potential for targeted educational interventions.

ABSTRACTThis prospective study assessed the prevalence, type, and consequences of persistent symptoms following a nonhospitalized SARS‐CoV‐2 infection by comparing infected and noninfected children and adults of Dutch households. Two comparable prospective household studies were conducted during two pandemic phases. At baseline, all household members were tested for SARS‐CoV‐2 with 10 consecutive saliva samples during a 6‐week period using RT‐PCR. Questionnaires assessing persistent symptoms, health‐related quality of life (HRQoL), anxiety, and depressive symptoms were collected at 6 and 12 months. Of the 297 included participants (median age 34 years, IQR 12–48), 201 (67.7%) tested positive for SARS‐CoV‐2. At 6 months, only one child reported persistent symptoms. SARS‐CoV‐2‐infected adults (> 18 years) reported more pulmonary symptoms (15.2% vs. 3.4%, p = 0.023), and tended to report more fatigue (12.8% vs. 3.4%, p = 0.061) and exertion‐related symptoms (8.8% vs. 1.7%, p = 0.107) compared to the negative adults. Adult participants with persistent symptoms reported decreased HRQoL and increased anxiety and depressive symptoms. This study found that SARS‐CoV‐2‐positive adults tended to have higher prevalence of respiratory symptoms, fatigue, and exertion‐related symptoms 6 months after SARS‐CoV‐2 infection, whereas children rarely reported persistent symptoms. Persistent symptoms were associated with a reduced HRQoL and increased anxiety and depression.