Flevoziekenhuis

Objective To compare the association of the severity categories of the 2001-National Institutes of Health (NIH), the 2018-NIH and the 2019-Jensen bronchopulmonary dysplasia (BPD) definitions with neurodevelopmental and respiratory outcomes at 2 and 5 years’ corrected age (CA), and several BPD risk factors. Design Single-centre historical cohort study with retrospective data collection. Setting Infants born between 2009 and 2015 at the Amsterdam University Medical Centers, location Amsterdam Medical Center. Patients Preterm infants born at gestational age (GA) <30 weeks and surviving up to 36 weeks’ postmenstrual age. Interventions Perinatal characteristics, (social) demographics and comorbidities were collected from the electronic patient records. Main outcome measures The primary outcomes were neurodevelopmental impairment (NDI) or late death, and respiratory morbidity at 2 and 5 years’ CA. Using logistic regression and Brier scores, we investigated if the ordinal grade severity is associated with incremental increase of adverse long-term outcomes. Results 584 preterm infants (median GA: 28.1 weeks) were included and classified according to the three BPD definitions. None of the definitions showed a clear ordinal incremental increase of risk for any of the outcomes with increasing severity classification. No significant differences were found between the three BPD definitions (Brier scores 0.169–0.230). Respiratory interventions, but not GA, birth weight or small for GA, showed an ordinal relationship with BPD severity in all three BPD definitions. Conclusion The severity classification of three BPD definitions showed low accuracy of the probability forecast on NDI or late death and respiratory morbidity at 2 and 5 years’ CA, with no differences between the definitions.

Introduction: During the first COVID-19 outbreak in 2020 in the Netherlands, the incidence of pulmonary embolism (PE) appeared to be high in COVID-19 patients admitted to the intensive care unit (ICU). This study was performed to evaluate the incidence of PE during hospital stay in COVID-19 patients not admitted to the ICU. Methods: Data were retrospectively collected from 8 hospitals in the Netherlands. Patients admitted between February 27, 2020, and July 31, 2020, were included. Data extracted comprised clinical characteristics, medication use, first onset of COVID-19-related symptoms, admission date due to COVID-19, and date of PE diagnosis. Only polymerase chain reaction (PCR)-positive patients were included. All PEs were diagnosed with computed tomography pulmonary angiography (CTPA). Results: Data from 1,852 patients who were admitted to the hospital ward were collected. Forty patients (2.2%) were diagnosed with PE within 28 days following hospital admission. The median time to PE since admission was 4.5 days (IQR 0.0-9.0). In all 40 patients, PE was diagnosed within the first 2 weeks after hospital admission and for 22 (55%) patients within 2 weeks after onset of symptoms. Patient characteristics, pre-existing comorbidities, anticoagulant use, and laboratory parameters at admission were not related to the development of PE. Conclusion: In this retrospective multicenter cohort study of 1,852 COVID-19 patients only admitted to the non-ICU wards, the incidence of CTPA-confirmed PE was 2.2% during the first 4 weeks after onset of symptoms and occurred exclusively within 2 weeks after hospital admission.

Evaluation of guidelines in actual practice is a crucial step in guideline improvement. A retrospective evaluation of the Dutch guideline for children with fever without an apparent source (FWS) showed 50% adherence in young infants. We prospectively evaluated adherence to the Dutch guideline and its impact on management in current practice. Prospective observational multicenter cross-sectional study, including children 3 days to 16 years old presented for FWS at one of seven emergency departments in participating secondary and tertiary care hospitals in the Netherlands. Adherence to the Dutch FWS guideline, adapted from the National Institute for Health and Care Excellence (NICE) guideline, was evaluated, and patterns in non-adherence and the impact of non-adherence on clinical outcomes and resource use were explored. Adherence to the guideline was 192/370 (52%). Adherence was lowest in patients categorized as high risk for severe infection (72/187, 39%), compared to the low-risk group (64/73, 88%). Differences in adherence were significant between risk categories (P < 0.001) but not between age categories. In case of non-adherence, less urinalysis, fewer bacterial cultures (blood, urine, and cerebral spinal fluid), and less empirical antibiotic treatment were performed (P < 0.050). Clinical outcomes were not significantly different between the non-adherence and the adherence group, particularly regarding missed severe infections. Conclusions: We found a high non-adherence rate of 48%, which did not lead to unfavorable clinical outcomes. This substantiates the need for a critical reevaluation of the FWS guideline and its indications for bacterial cultures, viral testing, and antibiotic treatment. What is Known: • Despite the development of national guidelines, variation in practice is still substantial in the assessment of febrile children to distinguish severe infection from mild self-limiting disease. • Previous retrospective research suggests low adherence to national guidelines for febrile children in practice. What is New: • In case of non-adherence to the Dutch national guideline, similar to the National Institute for Health and Care Excellence (NICE) guideline from the United Kingdom, physicians have used fewer resources than the guideline recommended without increasing missed severe infections.

STUDY QUESTION What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference −1.2%, 95% CI: −3.4% to 1.5%; P = 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS We studied 1160 infertile women (18–41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies—management based on HyfoSy results versus HSG results—the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference −1.2%; 95% CI: −3.4% to 1.5%). For the procedures itself, HyFoSy cost €136 and HSG €280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were €3307 for the HyFoSy strategy and €3427 for the HSG strategy (mean difference €−119; 95% CI: €−125 to €−114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was €10 042, meaning that by using HyFoSy instead of HSG we would save €10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S) FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting—and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER International Clinical Trials Registry Platform No. NTR4746.

Objectives The main objective was to generate a GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis and to test its reliability. To this end, we assessed the validity, feasibility and applicability of ultrasound assessment of finger entheses to incorporate them into the scoring system. Methods The study consisted of a stepwise process. First, in cadaveric specimens, we identified enthesis sites of the fingers by ultrasound and gross anatomy, and then verified presence of entheseal tissue in histological samples. We then selected the entheses to be incorporated into a dactylitis scoring system through a Delphi consensus process among international experts. Next, we established and defined the ultrasound components of dactylitis and their scoring systems using Delphi methodology. Finally, we tested the interobserver and intraobserver reliability of the consensus- based scoring systemin patients with psoriatic dactylitis. Results 32 entheses were identified in cadaveric fingers. The presence of entheseal tissues was confirmed in all cadaveric samples. Of these, following the consensus process, 12 entheses were selected for inclusion in GLOUDAS. Ultrasound components of GLOUDAS agreed on through the Delphi process were synovitis, tenosynovitis, enthesitis, subcutaneous tissue inflammation and periextensor tendon inflammation. The scoring system for each component was also agreed on. Interobserver reliability was fair to good (κ 0.39–0.71) and intraobserver reliability good to excellent (κ 0.80–0.88) for dactylitis components. Interobserver and intraobserver agreement for the total B-mode and Doppler mode scores (sum of the scores of the individual abnormalities) were excellent (interobserver intraclass correlation coefficient (ICC) 0.98 for B-mode and 0.99 for Doppler mode; intraobserver ICC 0.98 for both modes). Conclusions We have produced a consensus-driven ultrasound dactylitis scoring system that has shown acceptable interobserver reliability and excellent intraobserver reliability. Through anatomical knowledge, small entheses of the fingers were identified and histologically validated.

Objective(s): Unmet needs of relatives of patients with advanced cancer not only reduce their own health-related quality of life, but may also negatively affect patients’ health outcomes. The aim of this study was to assess changes in relatives’ unmet needs of patients with advanced cancer in the last year of life and to identify differences in unmet needs by gender and type of relationship. Methods: Relatives of patients with advanced cancer in the Netherlands were included in a prospective, longitudinal, observational study. Relatives’ unmet needs were measured every 3 months with an adapted version of the Problems and Needs in Palliative Care (PNPC) questionnaire Caregiver form (44 items, 12 domains). Questionnaires completed in the patients’ last year of life were analyzed. Change of unmet needs in the last year, and differences in unmet needs by gender and type of relationship were analyzed. Results: A total of 409 relatives were included with a median of 4 unmet needs in the patient's last year. Unmet needs were most prevalent at all time points during the last year in the domains “caring for the patient” (highest need = 35%) and “psychological issues” (highest need = 40%). The number of unmet needs of relatives did not change significantly during the last year of life ( P=.807). There were no significant differences in the number of unmet needs between male and female partners and between partners and other relatives. Conclusion: The most unmet needs for relatives were in the domains “caring for the patient” and “psychological issues.” Professional support should focus on these items. Within these domains, it seems especially important that relatives get more knowledge and support about what scenarios to expect and how to deal with them.

Background The most common intestinal operation in Crohn’s disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption. Methods This is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs. Discussion The research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines. Trial registration NCT05246917 for HAND2END and NCT05578235 for End2End (http://www.clinicaltrials.gov/).

Background The multitude of medical and surgical treatment options for perianal fistulizing Crohn’s disease (pCD) impels differences in management. This study aimed to assess management of pCD in current clinical practice in the Netherlands. Methods Patients with active pCD (i.e. visible external fistula opening or patent fistula tract on imaging) were included in a prospective multicenter cohort study in 41 Dutch academic and non-academic hospitals from September 2022 to March 2023. pCD-related clinical, radiological and surgical data were prospectively collected during a follow-up period of 6 months and retrospectively collected from pCD diagnosis until inclusion. Primary outcome of the study was adherence to the international guidelines on pCD management during the disease course (from pCD diagnosis until end of follow-up). Adequate adherence was defined as (I) imaging for pCD diagnosis using magnetic resonance imaging (MRI) and/or endo-anal ultrasound (EUS), (II) endoscopic evaluation of concomitant proctitis, (III) use of antibiotics for symptomatic response, (IV) initiation of an anti-tumour necrosis factor (TNF) agent for maintenance therapy, (V) fistula surgery aiming at fistula closure in case of surgically amendable disease and (VI) decision making by a multidisciplinary team (gastroenterologist and surgeon)(Figure 1). Results 449 patients with active pCD (52% female) were included(Table 1). At inclusion, median age and median pCD duration were 37.2 years (IQR 28.8–49.4) and 3.1 years (IQR 1.1–7.1). 54% of patients were treated in a non-academic hospital. 89% of patients were treated with CD medication, which concerned anti-TNF agents in 82% of these patients. As recommended by guidelines, a MRI (99%) and/or EUS (9%) were performed in the vast majority of patients (97%) for pCD diagnosis. Following diagnosis, endoscopy was performed in 81% of patients. During the disease course, antibiotics were initiated in 55% of patients and at least one anti-TNF agent(s) was started in 84% of patients for maintenance therapy (73% infliximab, 53% adalimumab, 26% both agents). Surgery aiming for fistula closure was performed in 38% of patients during the disease course. 60% of patients were discussed in a multidisciplinary team (MDT). Conclusion This study demonstrated a high adherence to international guidelines on pCD management concerning imaging at diagnosis, endoscopic evaluation for concomitant proctitis and treatment with anti-TNF agents. Adherence to use of antibiotics for symptoms, performance of fistula surgery aiming at fistula closure and decision making in a MDT is moderate and standardization may optimize pCD management.

Background Further refinement of clinical risk stratification for postoperative endoscopic recurrence in patients with Crohn’s disease is required to identify patients who will benefit from prophylactic therapy. Therefore, we aimed to assess risk factors for endoscopic recurrence in a large prospective, multicenter cohort study. Methods CD patients (≥16 years) scheduled for ileocolic (re-)resection (ICR) and those who underwent an ileocolonoscopy at 6 months following ICR were included. Primary outcome of the study was endoscopic recurrence (modified Rutgeerts’ score ≥ i2b at 6 months). Multivariable logistic regression was performed to identify clinical risk factors. The model included a random effect for the study center to correct for potential correlation between treating center and the outcome. Results In total, 298 patients underwent ICR (79.2% primary ICR, 20.8% re-resection) after a median disease duration of 5.3 years (IQR 1.0 – 12.4). 60.4% of patients were female with a median age at surgery of 34.1 years (IQR 25.7 – 50.5). 67.8% of the patients were exposed to ≥1 biological prior to surgery. Postoperative prophylactic medication (<12 weeks to ICR) was initiated in 85/298 (28.5%) patients; 24.7% immunomodulator, 29.4% anti-TNF, 27.1% combination therapy [immunomodulator with anti-TNF agent], 4.7% vedolizumab, 14.1% ustekinumab. Mean time to postoperative ileocolonoscopy was 6.2 months (SD 1.3). Endoscopic recurrence was diagnosed in 37.9% of the patients. Multivariable logistic regression identified active smoking (adjusted OR [aOR] 3.12; 95% CI 1.63 – 5.98) and penetrating disease behaviour (aOR 1.92; 95% CI 1.04 – 3.57) as risk factors for endoscopic recurrence, whilst ileocolic disease (versus ileal disease; aOR 0.27; 95% CI 0.15 – 0.49) and postoperative prophylactic medication (aOR 0.24; 95% CI 0.12 – 0.47) were identified as protective factors for endoscopic recurrence (Table 1). Conclusion Active smoking and penetrating disease behaviour at time of surgery were identified as risk factors for early postoperative recurrence in Crohn’s disease. Reversely, ileocolic disease at time of surgery and initiation of postoperative prophylactic medication were identified as protective factors for early endoscopic recurrence. Young age at surgery, perianal disease and a prior intestinal resection, included as risk factors in the current international guidelines, were not associated with early endoscopic postoperative recurrence in this large prospective cohort study.

Introduction As maternal age during pregnancy is rising all over the world, there is a growing need for prognostic factors that determine maternal and perinatal outcomes in older women. Material and methods This study is a retrospective cohort study of women aged 40 years or older at the time of delivery in four Santeon hospitals across the Netherlands between January 2016 and December 2019. Outcomes were compared between women of 40–44 years (advanced maternal age) and 45 years and older (very advanced maternal age). Primary outcome was unplanned cesarean section, secondary outcomes included postpartum hemorrhage and neonatal outcomes. Multivariate regression analysis was performed to analyze predictive factors for unplanned cesarean sections in women who attempted vaginal delivery. Subsequently, a predictive model and risk scores were constructed to predict unplanned cesarean section. Results A cohort of 1660 women was analyzed; mean maternal age was 41.4 years, 4.8% of the women were 45 years and older. In both groups, more than half of the women had not delivered vaginally before. Unplanned cesarean sections were performed in 21.1% of the deliveries in advanced maternal age and in 29.1% in very advanced maternal age. Four predictive factors were significantly correlated with unplanned cesarean sections: higher body mass index (BMI), no previous vaginal delivery, spontaneous start of delivery and number of days needed for cervical priming. A predictive model was constructed from these factors with an area under the curve of 0.75 (95% confidence interval 0.72–0.78). A sensitivity analysis in nulliparous women proved that BMI, days of cervical priming, age, and gestational age were risk factors, whereas spontaneous start of delivery and induction were protective factors. There was one occurrence of neonatal death. Conclusions Women of advanced maternal age and those of very advanced maternal age have a higher chance of having an unplanned cesarean section compared to the general obstetric population in the Netherlands. Unplanned cesarean sections can be predicted through use of our predictive model. Risk increases with higher BMI, no previous vaginal delivery, and increasing number of days needed for cervical priming, whereas spontaneous start of labor lowers the risk. In nulliparous women, age and gestational age also increase risk, but induction lowers the risk of having an unplanned cesarean section.

High-grade B-cell lymphoma patients with MYC and BCL2 rearrangements (HGBL-MYC/BCL2) respond poorly to immuno-chemotherapy compared to diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) patients without a MYC rearrangement. This suggests a negative impact of lymphoma-intrinsic MYC on the immune system. To investigate this, we compared circulating T-cells and NK-cells of HGBL-MYC/BCL2 patients (n=66), DLBCL NOS patients (n=53) and age-matched healthy donors (HDs, n=16) by flow cytometry and performed proliferation, cytokine production and cytotoxicity assays. As compared to HDs, both lymphoma subtypes displayed similar frequencies of CD8+ T-cells, but decreased CD4+ T-cells. Regulatory T-cell (Treg) frequencies were reduced only in DLBCL NOS patients. Activated (HLA-DR+/CD38+) T-cells, PD-1+CD4+ T-cells and PD-1+Tregs were increased in both lymphoma subtypes, but PD-1+CD8+ T-cells were increased only in HGBL-MYC/BCL2. DLBCL NOS patients, but not HGBL-MYC/BCL2 patients, exhibited higher frequencies of senescent T-cells compared to HDs. Functional assays showed no overt differences between both lymphoma groups and HDs. Deeper analyses revealed that PD-1+ T-cells of HGBL-MYC/BCL2 patients were exhausted with impaired cytokine production and degranulation. DLBCL NOS patients, but not HGBL-MYC/BCL2 patients, exhibited higher frequencies of NK-cells expressing inhibiting receptor NKG2A. Both lymphoma subtypes exhibited lower TIM-3+ and DNAM-1+ expressing NK-cells. Although NK-cells of HGBL-MYC/BCL2 patients showed less degranulation, they were not defective in cytotoxicity. In conclusion, our results demonstrate an increased exhaustion in circulating T-cells of HGBL-MYC/BCL2 patients. Nonetheless, the overall intact peripheral T-cell and NK-cell functions in these patients emphasize the importance to investigate potential immune evasion in the microenvironment of MYC-rearranged lymphomas.

Purpose Evaluation of guidelines in actual practice is a crucial step in guideline improvement. Retrospective evaluation of the Dutch guideline for children with fever without an apparent source (FWS) showed 50% adherence in young infants. We prospectively evaluated adherence to the Dutch guideline and its impact on management in current practice. Methods Prospective observational multicenter study, including children three days to sixteen years old presented for FWS at one of seven Emergency Departments in participating secondary and tertiary care hospitals in the Netherlands. Adherence to the Dutch FWS guideline, adapted from the National Institute for Health and Care Excellence (NICE) guideline, was evaluated and patterns in non-adherence and the impact of non-adherence on clinical outcomes and resource use were explored. Results Adherence to the guideline was 192/370 (52%). Adherence was lowest in patients categorized as high risk for severe infection (72/187, 39%), compared to the low risk group (64/73, 88%). Differences in adherence were significant between risk categories (P < 0.001) but not between age categories. In case of non-adherence, less urinalysis, less bacterial cultures (blood, urine and cerebral spinal fluid) and less empirical antibiotic treatment were performed (P < 0.050). Clinical outcomes were not significantly different between the non-adherence and the adherence group, particularly regarding missed severe infections. Conclusions We found a high non-adherence rate of 48%, which did not lead to unfavorable clinical outcomes. This substantiates the need for a critical reevaluation of the FWS guideline and its indications for bacterial cultures, viral testing and antibiotic treatment.

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Aims The primary aim of this study was to present the mid-term follow-up of a multicentre randomized controlled trial (RCT) which compared the functional outcome following routine removal (RR) to the outcome following on-demand removal (ODR) of the syndesmotic screw (SS). Methods All patients included in the ‘ROutine vs on DEmand removal Of the syndesmotic screw’ (RODEO) trial received the Olerud-Molander Ankle Score (OMAS), American Orthopaedic Foot and Ankle Hindfoot Score (AOFAS), Foot and Ankle Outcome Score (FAOS), and EuroQol five-dimension questionnaire (EQ-5D). Out of the 152 patients, 109 (71.7%) completed the mid-term follow-up questionnaire and were included in this study (53 treated with RR and 56 with ODR). Median follow-up was 50 months (interquartile range 43.0 to 56.0) since the initial surgical treatment of the acute syndesmotic injury. The primary outcome of this study consisted of the OMAS scores of the two groups. Results The median OMAS score was 85.0 for patients treated with RR, and 90.0 for patients treated with ODR (p = 0.384), indicating no significant difference between ODR and RR. The secondary outcome measures included the AOFAS (88.0 in the RR group and 90.0 for ODR; p = 0.722), FAOS (87.5 in the RR group and 92.9 for ODR; p = 0.399), and EQ-5D (0.87 in the RR group and 0.96 for ODR; p = 0.092). Conclusion This study demonstrated no functional difference comparing ODR to RR in syndesmotic injuries at a four year follow-up period, which supports the results of the primary RODEO trial. ODR should be the standard practice after syndesmotic screw fixation. Cite this article: Bone Jt Open 2023;4(12):957–963.