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Contains fulltext : 291552.pdf (Publisher’s version ) (Open Access) BACKGROUND: Childhood cancer survivors appear to be at increased risk of frailty and sarcopenia, but evidence on the occurrence of and high-risk groups for these aging phenotypes is scarce, especially in European survivors. The aim of this cross-sectional study was to assess the prevalence of and explore risk factors for pre-frailty, frailty, and sarcopenia in a national cohort of Dutch childhood cancer survivors diagnosed between 1963 and 2001. METHODS: Eligible individuals (alive at the time of study, living in the Netherlands, age 18-45 years, and had not previously declined to participate in a late-effects study) from the Dutch Childhood Cancer Survivor Study (DCCSS-LATER) cohort were invited to take part in this cross-sectional study. We defined pre-frailty and frailty according to modified Fried criteria, and sarcopenia according to the European Working Group on Sarcopenia in Older People 2 definition. Associations between these conditions and demographic and treatment-related as well as endocrine and lifestyle-related factors were estimated with two separate multivariable logistic regression models in survivors with any frailty measurement or complete sarcopenia measurements. FINDINGS: 3996 adult survivors of the DCCSS-LATER cohort were invited to participate in this cross-sectional study. 1993 non-participants were excluded due to lack of response or a decline to participate and 2003 (50·1%) childhood cancer survivors aged 18-45 years were included. 1114 (55·6%) participants had complete frailty measurements and 1472 (73·5%) participants had complete sarcopenia measurements. Mean age at participation was 33·1 years (SD 7·2). 1037 (51·8%) participants were male, 966 (48·2%) were female, and none were transgender. In survivors with complete frailty measurements or complete sarcopenia measurements, the percentage of pre-frailty was 20·3% (95% CI 18·0-22·7), frailty was 7·4% (6·0-9·0), and sarcopenia was 4·4% (3·5-5·6). In the models for pre-frailty, underweight (odds ratio [OR] 3·38 [95% CI 1·92-5·95]) and obesity (OR 1·67 [1·14-2·43]), cranial irradiation (OR 2·07 [1·47-2·93]), total body irradiation (OR 3·17 [1·77-5·70]), cisplatin dose of at least 600 mg/m(2) (OR 3·75 [1·82-7·74]), growth hormone deficiency (OR 2·25 [1·23-4·09]), hyperthyroidism (OR 3·72 [1·63-8·47]), bone mineral density (Z score ≤-1 and >-2, OR 1·80 [95% CI 1·31-2·47]; Z score ≤-2, OR 3·37 [2·20-5·15]), and folic acid deficiency (OR 1·87 [1·31-2·68]) were considered significant. For frailty, associated factors included age at diagnosis between 10-18 years (OR 1·94 [95% CI 1·19-3·16]), underweight (OR 3·09 [1·42-6·69]), cranial irradiation (OR 2·65 [1·59-4·34]), total body irradiation (OR 3·28 [1·48-7·28]), cisplatin dose of at least 600 mg/m(2) (OR 3·93 [1·45-10·67]), higher carboplatin doses (per g/m(2); OR 1·15 [1·02-1·31]), cyclophosphamide equivalent dose of at least 20 g/m(2) (OR 3·90 [1·65-9·24]), hyperthyroidism (OR 2·87 [1·06-7·76]), bone mineral density Z score ≤-2 (OR 2·85 [1·54-5·29]), and folic acid deficiency (OR 2·04 [1·20-3·46]). Male sex (OR 4·56 [95%CI 2·26-9·17]), lower BMI (continuous, OR 0·52 [0·45-0·60]), cranial irradiation (OR 3·87 [1·80-8·31]), total body irradiation (OR 4·52 [1·67-12·20]), hypogonadism (OR 3·96 [1·40-11·18]), growth hormone deficiency (OR 4·66 [1·44-15·15]), and vitamin B12 deficiency (OR 6·26 [2·17-1·81]) were significantly associated with sarcopenia. INTERPRETATION: Our findings show that frailty and sarcopenia occur already at a mean age of 33 years in childhood cancer survivors. Early recognition and interventions for endocrine disorders and dietary deficiencies could be important in minimising the risk of pre-frailty, frailty, and sarcopenia in this population. FUNDING: Children Cancer-free Foundation, KiKaRoW, Dutch Cancer Society, ODAS Foundation. 01 april 2023

Purpose: To assess the presence of upper extremity pain after stroke over time and the course of its intensity in patients with persistent pain. Materials and methods: Patients with stroke completed a question on the presence of upper extremity pain (yes/no) and rated its intensity with a visual analogue scale (0-10) at 3, 18, and 30 months after starting multidisciplinary rehabilitation. The presence of upper extremity pain and its intensity over time were analysed with Generalized Estimating Equations models and Linear Mixed Models, respectively. Results: 678 patients were included. The proportions of patients reporting upper extremity pain were 41.8, 36.0, and 32.7% at 3, 18, and 30 months, respectively, with the decline in proportions reaching statistical significance (odds ratio 0.82, 95% confidence interval 0.74-0.92, p < 0.001). At all time points, in those reporting pain the median intensity was 5.0 (interquartile ranges (IQR) 4.0-7.0 at 3 and 3.0-6.0 at 18 and 30 months). In the 73 patients with persistent pain, there was no significant change in intensity over time. Conclusions: The proportion of patients reporting upper extremity pain after stroke was considerable, despite a significant decrease in 2.5 years. In patients reporting persistent pain, the intensity did not change over time.

Objective: To examine patient activation from the start of stroke rehabilitation and its course up until the 6-month follow-up. Design: Inception cohort study with a follow-up of 6 months. Setting: Multidisciplinary rehabilitation facility. Participants: A total of 478 patients (N=478) with stroke who received inpatient or outpatient rehabilitation, with a median age of 63.0 years (interquartile range, 56.0-70.0 years) with 308 (64.2%) being men. The study was completed by 439 patients (91.8%). Interventions: Not applicable. Main Outcome Measures: Patient activation was measured with the Patient Activation Measure (PAM) (score 0-100, 4 levels, where a higher score and level denotes more patient activation). The PAM was measured at the start of the rehabilitation (baseline) and 3 and 6 months thereafter and was analyzed using the multivariate mixed model analysis. Results: At baseline, the mean PAM score was 60.2 +/- 14.3, with the number of patients in PAM levels 1, 2, 3, and 4 being 76 (17.8%), 85 (19.9%), 177 (41.4%), and 90 (21.0%), respectively. The multivariate mixed-model analysis demonstrated that the PAM score increased over time (baseline 60.2 +/- 14.3 vs 3 months 60.7 +/- 14.8 vs 6 months 61.9 +/- 18.0; P.007). Between baseline and 6 months, 122 patients (41.4%) remained at the same PAM level, 105 patients (35.6%) increased, and 68 patients (23.1%) decreased. At all time points, > 35% of patients were in level 1 or 2. Conclusions: PAM scores increased slightly over time from the start of rehabilitation up to the 6-month follow-up. However, more than one-third of patients remained at low levels (ie, level 1 and 2) of patient activation, which indicates that specific interventions during rehabilitation to increase patient activation might be of value. Archives of Physical Medicine and Rehabilitation 2022;103:1360-7 (c) 2022 by the American Congress of Rehabilitation Medicine. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Background Childhood cancer survivors appear to be at increased risk of frailty and sarcopenia, but evidence on the occurrence of and high-risk groups for these aging phenotypes is scarce, especially in European survivors. The aim of this cross-sectional study was to assess the prevalence of and explore risk factors for pre-frailty, frailty, and sarcopenia in a national cohort of Dutch childhood cancer survivors diagnosed between 1963 and 2001.Methods Eligible individuals (alive at the time of study, living in the Netherlands, age 18-45 years, and had not previously declined to participate in a late-effects study) from the Dutch Childhood Cancer Survivor Study (DCCSS-LATER) cohort were invited to take part in this cross-sectional study. We defined pre-frailty and frailty according to modified Fried criteria, and sarcopenia according to the European Working Group on Sarcopenia in Older People 2 definition. Associations between these conditions and demographic and treatment-related as well as endocrine and lifestyle-related factors were estimated with two separate multivariable logistic regression models in survivors with any frailty measurement or complete sarcopenia measurements.Findings 3996 adult survivors of the DCCSS-LATER cohort were invited to participate in this cross-sectional study. 1993 non-participants were excluded due to lack of response or a decline to participate and 2003 (50.1%) childhood cancer survivors aged 18-45 years were included. 1114 (55.6%) participants had complete frailty measurements and 1472 (73.5%) participants had complete sarcopenia measurements. Mean age at participation was 33.1 years (SD 7.2). 1037 (51.8%) participants were male, 966 (48.2%) were female, and none were transgender. In survivors with complete frailty measurements or complete sarcopenia measurements, the percentage of pre-frailty was 20.3% (95% CI 18.0-22.7), frailty was 7.4% (6.0-9.0), and sarcopenia was 4.4% (3.5-5.6). In the models for pre-frailty, underweight (odds ratio [OR] 3.38 [95% CI 1.92-5.95]) and obesity (OR 1.67 [1.14-2.43]), cranial irradiation (OR 2.07 [1.47-2.93]), total body irradiation (OR 3.17 [1.77-5.70]), cisplatin dose of at least 600 mg/m2 (OR 3.75 [1.82-7.74]), growth hormone deficiency (OR 2.25 [1.23-4.09]), hyperthyroidism (OR 3.72 [1.63-8.47]), bone mineral density (Z score -2, OR 1.80 [95% CI 1.31-2.47]; Z score

Purpose Study objectives were to estimate the cumulative incidence of death due to different causes of death (CODs) and investigate the effect of invasive aspergillosis (IA) on each separate COD in a cohort of older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) included in the Haemato-Oncology Foundation for Adults in the Netherlands (HOVON) 43 randomized controlled trial. Methods Pre-collected data from the trial was obtained from the HOVON data center and relevant clinical information was extracted. The cumulative incidence of death due to different CODs was estimated with a competing risk model and the association between each COD and prognostic factors, including IA, were investigated with a cause-specific hazard Cox regression model. Results In total 806 patients were included, mean age of 70 years and 55% were male. The cumulative incidences of death due to leukaemia or infection at 3, 6, 12 and 36 months were 0.06, 0.11, 0.23, 0.42 and 0.17, 0.19, 0.22, 0.25 respectively. Incidence of IA was 21% and diagnosis of IA up until the final chemotherapy cycle was associated with an increased risk of dying from leukaemia (cause-specific hazard ratio (CSHR): 1.75, 95% CI 1.34–2.28) and a trend was seen for infection (CSHR: 1.36, 95% CI 0.96–1.91). Conclusion Leukaemia was the most likely cause of death over time, however in the first year after diagnosis of AML or high-risk MDS infection was the most likely cause of death. Patients with IA had a relatively increased risk of dying from leukaemia or infection.

Background:Aneurysmal bone cysts (ABC) are rare benign cystic bone tumors, generally diagnosed in children and adolescents. Proximal femoral ABCs may require specific treatment strategies because of an increased pathologic fracture risk. As few reports are published on ABCs, specifically for this localization, consensus regarding optimal treatment is lacking. We present a large retrospective study on the treatment of pediatric proximal femoral ABCs. Methods:All eligible pediatric patients with proximal femoral ABC were included, from 11 tertiary referral centers for musculo-skeletal oncology (2000-2021). Patient demographics, diagnostics, treatments, and complications were evaluated. Index procedures were categorized as percutaneous/open procedures and osteosynthesis alone. Primary outcomes were: time until full weight-bearing and failure-free survival. Failure was defined as open procedure after primary surgery, >3 percutaneous procedures, recurrence, and/or fracture. Risk factors for failure were evaluated. Results:Seventy-nine patients with ABC were included [mean age, 10.2 (+/- SD4.0) y, n=56 male]. The median follow-up was 5.1 years (interquartile ranges=2.5 to 8.8).Index procedure was percutaneous procedure (n=22), open procedure (n=35), or osteosynthesis alone (n=22). The median time until full weight-bearing was 13 weeks [95% confidence interval (CI)=7.9-18.1] for open procedures, 9 weeks (95% CI=1.4-16.6) for percutaneous, and 6 weeks (95% CI=4.3-7.7) for osteosynthesis alone (P=0.1). Failure rates were 41%, 43%, and 36%, respectively. Overall, 2 and 5-year failure-free survival was 69.6% (95% CI=59.2-80.0) and 54.5% (95% CI=41.6-67.4), respectively. Risk factors associated with failure were age younger than 10 years [hazard ratios (HR)=2.9, 95% CI=1.4-5.8], cyst volume >55 cm(3) (HR=1.7, 95% CI=0.8-2.5), and fracture at diagnosis (HR=1.4, 95% CI=0.7-3.3). Conclusions:As both open and percutaneous procedures along with osteosynthesis alone seem viable treatment options in this weight-bearing location, optimal treatment for proximal femoral ABCs remains unclear. The aim of the treatment was to achieve local cyst control while minimizing complications and ensuring that children can continue their normal activities as soon as possible. A personalized balance should be maintained between undertreatment, with potentially higher risks of pathologic fractures, prolonged periods of partial weight-bearing, or recurrences, versus overtreatment with large surgical procedures, and associated risks.

Background: Childhood cancer survivors are at risk of developing skeletal comorbidities later in life. We aimed to assess risk factors for low and very low bone mineral density (BMD), and the risk of and risk factors for any fractures and vertebral fractures in a national cohort of Dutch adult childhood cancer survivors.Methods: In this cross-sectional study, we used data from the DCCSS LATER cohort, which comprised individuals who were alive for at least 5 years after diagnosis of childhood cancer (ie, histologically confirmed malignancies or Langerhans cell histiocytosis), were diagnosed before the age of 19 years, and who had been treated at one of seven Dutch paediatric oncology centres between 1963 and 2002 (hereafter referred to as survivors). For this study, we invited survivors aged 18-45 years, who were alive as of Oct 10, 2016, living in the Netherlands, and who were deemed eligible by their treating physician to participate. We assessed BMD using dual-energy x-ray absorptiometry (DXA). Self-reported fractures that occurred at least 5 years after cancer diagnosis were assessed using available medical history and compared with population-level data from the Swedish national registry. We assessed vertebral fractures in a subset of participants using a vertebral fracture assessment. We assessed associations between the occurrence of low (Z-score of