Metabolic syndrome parameters, determinants, and biomarkers in adult survivors of childhood cancer: Protocol for the Dutch childhood cancer survivor study on metabolic syndrome (Dutch LATER METS)

Background: Potential late effects of treatment for childhood cancer include adiposity, insulin resistance, dyslipidemia, and hypertension. These risk factors cluster together as metabolic syndrome and increase the risk for development of diabetes mellitus and cardio- and cerebrovascular disease. Knowledge on risk factors, timely diagnosis, and preventive strategies is of importance to prevent cardio- and cerebrovascular complications and improve quality of life. Currently, no national cohort studies on the prevalence and determinants of metabolic syndrome in childhood cancer survivors, including biomarkers and genetic predisposition, are available. Objective: The objectives of the Dutch LATER METS study are to assess 1) the prevalence and risk factors of metabolic syndrome and its separate components, and 2) the potential diagnostic and predictive value of additional biomarkers for surveillance of metabolic syndrome in the national cohort of adult long-term survivors of childhood cancer. Methods

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart

Glaucoma screening during regular optician visits: The feasibility and specificity of screening in real life

Purpose: To determine the feasibility and specificity of glaucoma screening during regular optician visits. Methods: In four optician shops, glaucoma screening was offered to 400 consecutive visitors aged 45 years or above. If the visitor agreed to participate, an intraocular pressure measurement and - in those with a pressure below 25 mmHg - a frequency-doubling perimeter (FDT) C20-1 visual field screening test were performed. Those with an elevated pressure or at least one reproducibly abnormal test location on FDT were referred to our hospital. Results: Three-hundred and fifty-two of 400 consecutive visitors (88%) were screened. Fifteen of the unscreened visitors were not screened because they were already regularly checked by an ophthalmologist related to glaucoma. Forty-two of 352 screened participants (12%) were referred. Of these 42 referrals, seven were diagnosed with glaucoma, 10 were diagnosed with ocular hypertension (OHT), 12 did not have any eye disease, seven had an eye disease other than glaucoma or OHT that was diagnosed previously and six were newly diagnosed with an eye disease other than glaucoma or OHT. The specificity of the screening protocol was 91% (95% confidence interval 88-94%). Conclusions: Glaucoma screening at the optician shop was feasible, but the specificity of the screening protocol was rather low. With more stringent cut-off points (30 mmHg; at least two reproducibly abnormal test locations), the specificity could be improved to 96% (94-98%), apparently without a significant loss of sensitivity. This suggests that screening during regular optician visits might be a viable approach

ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis

Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49–0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90–1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72–4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, www.trialregister.nl]

Overweight in the Dutch National Cohort of Long-Term Survivors of Childhood Cancer

BACKGROUND Overweight is a common problem in the general population, but occurs more frequently among childhood cancer survivors (CCS) and is regarded as a late adverse effect. However, risk factors are not fully elucidated and it is often disguised in CCS because they can have normal weight but high fat percentage (fat%) on dual-energy X-ray absorptiometry (DXA, gold standard). We aimed to assess overweight prevalence in a nationwide survivor cohort, to clarify risk factors and to identify which measurement method captures overweight best. METHODS The prevalence of overweight and obesity (body mass index (BMI) ≥25 and ≥30 kg/m 2) was assessed in the Dutch nationwide cohort of adult CCS treated between 1963 and 2002. Risk factors for overweight were analyzed using multivariable logistic regression models. In addition, overweight prevalence was calculated according to fat%, waist circumference (WC), waist/hip ratio (WHR) and waist/height ratio (WHtR). The validity of BMI, WC, WHR and WHtR for characterizing obesity, compared to fat% (expressed as false-negative percentage and in logistic regression models to identify treatment-related risk factors for disguised overweight) was studied. RESULTS A total of 2,338 (51.2% male) survivors (54.7% hematologic malignancies) participated, with mean age 35.5 (±9.3) years and 28.3 (±8.4) years follow-up. In men and women respectively, overweight prevalence was 45.9% and 43.8%, for obesity this was 11.2% and 15.5%. Risk factors for overweight included overweight at cancer diagnosis (adjusted odds ratio (aOR) 3.43, p<0.001), cranial radiotherapy (CRT, aOR 3.27, p<0.001) and growth hormone deficiency (GHD) (unadjusted OR 2.28, p<0.001, after adjustment the effect partially disappeared, aOR 1.60, p=0.072). Previous treatment with corticosteroids was not associated with overweight. Using BMI, WC, WHR and WHtR, similar overweight prevalence was observed. However, this was 58.4% in men and even 83.7% in women when measured with DXA. Disguised overweight was more frequent after treatment with abdominal radiotherapy, high dose anthracyclines and stem cell transplantation (SCT) (aOR up to 3.37). CONCLUSIONS Overweight occurs in almost half of all long-term CCS, and risk factors include overweight at cancer diagnosis, CRT and potentially GHD. DXA identified overweight in an additional 25% of survivors. In CCS treated with abdominal irradiation, anthracyclines and SCT, overweight is more often missed with conventional methods. Hence, in these risk groups DXA needs serious consideration in surveillance, to enable early intervention and prevent complications of overweight including diabetes and atherosclerotic disease