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STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Mullerian € hormone (AMH)? SUMMARY ANSWER: Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. WHAT IS KNOWN ALREADY: Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. STUDY DESIGN, SIZE, DURATION: This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatme

Purpose: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. Methods: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. Results: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. Conclusion:HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.

Background: Gait adaptability is of utmost importance for keeping balance during gait in patients with knee osteoarthritis, also after total knee arthroplasty (TKA). The aims of this explorative study are: (1) assess the effect of age, knee osteoarthritis and TKA on gait adaptability; (2) assess changes in gait adaptability pre-to post-TKA and (3) their relation to functional outcomes. Methods: Gait adaptability was measured using a Target Stepping Test (TST) in knee osteoarthritis patients before (preTKA) and 12 months after TKA (postTKA) and compared to asymptomatic old (AsOld) and young adults (AsYng). TST imposed an asymmetrical gait pattern with projected stepping targets at high walking speed. Gait adaptability was determined through stepping accuracy on the targets. The Oxford Knee Score (OKS) and Timed-Up-and-Go test (TUG) measured patients’ physical function. Results: 12 preTKA, 8 postTKA, 18 AsYng, 21 AsOld were tested. Age showed no effect on TST-stepping accuracy. PreTKA showed worse TST-stepping accuracy compared to AsYng and AsOld (7.7; 6.2 cm difference). PostTKA showed an improvement of 52% in TST-stepping accuracy compared to preTKA (3.2 cm). Higher stepping accuracy preTKA predicted higher stepping accuracy post-TKA. In addition, low preTKA stepping accuracy predicted more improvement postTKA. Pre-to post-TKA improvement of stepping accuracy was related to improvement on the TUG (Beta = 0.17, p = 0.024), but not to OKS. Conclusions: Gait adaptability is improved following TKA in knee osteoarthritis patients and no longer significantly worse than asymptomatic adults. The relation of gait adaptability to function is shown by its relation to the TUG and shows to have predictive value pre-to post-TKA.

Background: Gait adaptability is of utmost importance for keeping balance during gait in patients with knee osteoarthritis, also after total knee arthroplasty (TKA). The aims of this explorative study are: (1) assess the effect of age, knee osteoarthritis and TKA on gait adaptability; (2) assess changes in gait adaptability pre-to post-TKA and (3) their relation to functional outcomes. Methods: Gait adaptability was measured using a Target Stepping Test (TST) in knee osteoarthritis patients before (preTKA) and 12 months after TKA (postTKA) and compared to asymptomatic old (AsOld) and young adults (AsYng). TST imposed an asymmetrical gait pattern with projected stepping targets at high walking speed. Gait adaptability was determined through stepping accuracy on the targets. The Oxford Knee Score (OKS) and Timed-Up-and-Go test (TUG) measured patients’ physical function. Results: 12 preTKA, 8 postTKA, 18 AsYng, 21 AsOld were tested. Age showed no effect on TST-stepping accuracy. PreTKA showed worse TST-stepping accuracy compared to AsYng and AsOld (7.7; 6.2 cm difference). PostTKA showed an improvement of 52% in TST-stepping accuracy compared to preTKA (3.2 cm). Higher stepping accuracy preTKA predicted higher stepping accuracy post-TKA. In addition, low preTKA stepping accuracy predicted more improvement postTKA. Pre-to post-TKA improvement of stepping accuracy was related to improvement on the TUG (Beta = 0.17, p = 0.024), but not to OKS. Conclusions: Gait adaptability is improved following TKA in knee osteoarthritis patients and no longer significantly worse than asymptomatic adults. The relation of gait adaptability to function is shown by its relation to the TUG and shows to have predictive value pre-to post-TKA., Biomechatronics & Human-Machine Control