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Context Whilst radioactive iodine (RAI) is often administered in the treatment for differentiated thyroid carcinoma (DTC), long-term data on male fertility after RAI are scarce. Objective To evaluate long-term male fertility after RAI for DTC, and to compare semen quality before and after RAI. Design, setting, and patients Multicenter study including males with DTC ≥2 years after their final RAI treatment with a cumulative activity of ≥3.7 GBq. Main outcome measure(s) Semen analysis, hormonal evaluation, and a fertility-focused questionnaire. Cut-off scores for ‘low semen quality’ were based on reference values of the general population as defined by the World Health Organization (WHO). Results Fifty-one participants had a median age of 40.5 (interquartile range (IQR): 34.0–49.6) years upon evaluation and a median follow-up of 5.8 (IQR: 3.0–9.5) years after their last RAI administration. The median cumulative administered activity of RAI was 7.4 (range: 3.7–23.3) GBq. The proportion of males with a low semen volume, concentration, progressive motility, or total motile sperm count did not differ from the 10th percentile cut-off of a general population (P = 0.500, P = 0.131, P = 0.094, and P = 0.500, respectively). Cryopreserved semen was used by 1 participant of the 20 who had preserved semen. Conclusions Participants had a normal long-term semen quality. The proportion of participants with low semen quality parameters scoring below the 10th percentile did not differ from the general population. Cryopreservation of semen of males with DTC is not crucial for conceiving a child after RAI administration but may be considered in individual cases.

Background: Azithromycin maintenance therapy is widely used in cystic fibrosis (CF), but little is known about its long-term safety. We investigated whether chronic azithromycin use is safe regarding renal function, hepatic cell toxicity and QTc-interval prolongation. Methods: Adult CF patients (72 patients using azithromycin for a cumulative period of 364.8 years and 19 controls, 108.8 years) from two CF-centers in the Netherlands with azithromycin (non)-use for at least three uninterrupted years were studied retrospectively. Results: There was no difference in mean decline of estimated glomerular filtration rate (eGFR), nor in occurrence of eGFR-events. No drug-induced liver injury could be attributed to azithromycin. Of the 39 azithromycin users of whom an ECG was available, 4/39 (10.3%) had borderline and 4/39 (10.3%) prolonged QTc-intervals, with 7/8 patients using other QTc-prolonging medication. Of the control patients 1/6 (16.7%) had a borderline QTc-interval, without using other QTc-prolonging medication. No cardiac arrhythmias were observed. Conclusion: We observed no renal or hepatic toxicity, nor cardiac arrythmias during azithromycin use in CF patients for a mean study duration of more than 5 years. One should be aware of possible QTc-interval prolongation, in particular in patients using other QTc-interval prolonging medication.

Background Pediatric differentiated thyroid cancer (DTC) has an excellent prognosis but unknown late effects of treatment. The initial cardiac evaluation showed subclinical diastolic dysfunction in 20% of adult survivors. The objective of this follow-up study was to determine the clinical course of this finding. Methods This multicenter study, conducted between 2018 and 2020, re-evaluated survivors after 5 years. The primary endpoint was echocardiographic diastolic cardiac function (depicted by the mean of the early diastolic septal and early diastolic lateral tissue velocity (e’ mean)). Secondary endpoints were other echocardiographic parameters and plasma biomarkers. Results Follow-up evaluation was completed in 47 (71.2%) of 66 survivors who had completed their initial evaluation. Of these 47 survivors, 87.2% were women. The median age was 39.8 years (range: 18.8–60.3), and the median follow-up after the initial diagnosis was 23.4 years (range: 10.2–48.8). Between the first and second evaluation, the e’ mean significantly decreased by 2.1 cm/s (s.d. 2.3 cm/s, P < 0.001). The median left ventricular ejection fraction did not significantly change (58.0% vs 59.0%, P= NS). In the best explanatory model of e’ mean, multivariate linear regression analysis showed that BMI and age were significantly associated with e’ mean (β coefficient: −0.169, 95% CI: −0.292; −0.047, P = 0.008 and β coefficient: −0.177, 95% CI: −0.240; −0.113, P < 0.001, respectively). Conclusions and relevance In these relatively young survivors of pediatric DTC, diastolic function decreased significantly during 5-year follow-up and is possibly more pronounced than in normal aging. This finding requires further follow-up to assess clinical consequences.

BackgroundRecurrent delivery of tidal mechanical energy (ME) inflicts ventilator-induced lung injury (VILI) when stress and strain exceed the limits of tissue tolerance. Mechanical power (MP) is the mathematical description of the ME delivered to the respiratory system over time. It is unknown how ME relates to underlying lung pathology and outcome in mechanically ventilated children. We therefore tested the hypothesis that ME per breath with tidal volume (Vt) normalized to bodyweight correlates with underlying lung pathology and to study the effect of resistance on the ME dissipated to the lung.MethodsWe analyzed routinely collected demographic, physiological, and laboratory data from deeply sedated and/or paralyzed children ResultsData of 312 patients with a median age of 7.8 (1.7–44.2) months was analyzed. Age (p p p ConclusionsME better related to underlying lung pathology and patient outcome than MP. The delivery of generated energy to the lung was not dependent on ETT size during PC ventilation. Further studies are needed to identify injurious MErs thresholds in ventilated children.

BackgroundImprovement in depression within the first 2 weeks of antidepressant treatment predicts good outcomes, but non-improvers can still respond or remit, whereas improvers often do not.AimsWe aimed to investigate whether early improvement of individual depressive symptoms better predicts response or remission.MethodWe obtained individual patient data of 30 trials comprising 2184 placebo-treated and 6058 antidepressant-treated participants. Primary outcome was week 6 response; secondary outcomes were week 6 remission and week 12 response and remission. We compared models that only included improvement in total score by week 2 (total improvement model) with models that also included improvement in individual symptoms.ResultsFor week 6 response, the area under the receiver operating characteristic curve and negative and positive predictive values of the total improvement model were 0.73, 0.67 and 0.74 compared with 0.77, 0.70 and 0.71 for the item improvement model. Model performance decreased for week 12 outcomes. Of predicted non-responders, 29% actually did respond by week 6 and 43% by week 12, which was decreased from the baseline (overall) probabilities of 51% by week 6 and 69% by week 12. In post hoc analyses with continuous rather than dichotomous early improvement, including individual items did not enhance model performance.ConclusionsExamining individual symptoms adds little to the predictive ability of early improvement. Additionally, early non-improvement does not rule out response or remission, particularly after 12 rather than 6 weeks. Therefore, our findings suggest that routinely adapting pharmacological treatment because of limited early improvement would often be premature.Declaration of interestNone.

Background: Allergic contact dermatitis caused by p-phenylenediamine (PPD) is a health concern for hair dye users. Because of its lower sensitization potency, the PPD derivative 2-methoxymethyl-p-phenylenediamine (ME-PPD) has been developed as an alternative hair dye for primary prevention. However, cross-elicitation responses can occur in PPD-allergic subjects.Objectives: To compare cross-elicitation responses to ME-PPD in open use and diagnostic patch testing of PPD-allergic subjects with hair dye-related allergic contact dermatitis.Methods: Reactions to ME-PPD were investigated in 25 PPD-allergic subjects by performing (1) 45-minute open use testing with a hair dye containing 2.0% of either ME-PPD or PPD, and (2) patch testing with increasing ME-PPD concentrations (0.1%-2.0% pet.).Results: Of the 25 PPD-allergic subjects, 21 (84%) reacted to open use testing with a hair dye containing 2.0% PPD, and testing with 2.0% ME-PPD led to cross-elicitation in 12 (48%). When patch tested with increasing ME-PPD concentrations, 13 (52%) cross-reacted at 0.1% (lowest dose) and 21 (84%) at 2.0% (highest dose), indicating decreased reactivity as compared with published PPD dose-response data.Conclusion: In line with the decreased cross-reactivity of ME-PPD in hair dye open use testing, PPD-allergic subjects show an attenuated cross-elicitation dose response to ME-PPD in patch testing.

Contains fulltext : 245660.pdf (Publisher’s version ) (Closed access) Background: Survivors of pediatric differentiated thyroid carcinoma (DTC) receive thyrotropin-suppressive therapy to minimize disease recurrence. However, knowledge about long-term effects of subclinical hyperthyroidism on bone mineral density (BMD) in pediatric DTC survivors is scarce, as is the information regarding long-term consequences of permanent hypoparathyroidism on BMD. We evaluated BMD in pediatric DTC survivors and investigated if BMD was affected by subclinical hyperthyroidism and/or permanent hypoparathyroidism during long-term follow-up. Methods: In this nationwide longitudinal study, we determined BMD in the lumbar spine and femur by dual energy X-ray absorptiometry in 65 pediatric DTC survivors. Measurements were repeated after minimal 5 years of follow-up in 46 pediatric DTC survivors. BMD results were evaluated according to the recommendations of the International Society for Clinical Densitometry (ISCD) and WHO. At both visits, we determined biochemical parameters and markers of bone resorption (C-terminal telopeptide of type I collagen [β-CTX]) and formation (N-propeptide of type I collagen [PINP] and osteocalcin). Results: First and second BMD measurements were done after a median follow-up of 17.0 (interquartile range [IQR] 8.0-25.0) and 23.5 (IQR 14.0-30.0) years after diagnosis, respectively. Median age at diagnosis was 15 years (IQR 13.0-17.0). Twenty-nine percent of the survivors had subclinical hyperthyroidism. In most survivors, BMD T- and Z-scores were within the reference range during both BMD evaluations. However, after 23.5 years of follow-up, a low BMD was found in 13.0%. In the 13 survivors with permanent hypoparathyroidism, BMD values did not differ after 5 years of follow-up compared with baseline values or in comparison with the 33 survivors without permanent hypoparathyroidism. During follow-up, turnover markers β-CTX and PINP remained stable. Conclusions: This longitudinal study of pediatric DTC survivors demonstrated normal and stable median lumbar spine and femur BMD values after a median time of 17 and 23.5 years after diagnosis. However, compared with controls, a lower BMD was still found in 13.0% after prolonged follow-up despite intensive follow-up. Based on the studied follow-up period, these data do not provide convincing evidence in support of standard monitoring of bone mass among DTC survivors, but may be restricted to individual cases at low frequency. Trial Registration: This follow-up study was registered in The Netherlands Trial Register under no. NL3280 (www.trialregister.nl/trial/3280).

Donor brain death (BD) is initiated by an increase in intracranial pressure (ICP), which subsequently damages the donor lung. In this study, we investigated whether the speed of ICP increase affects quality of donor lungs, in a rat model for fastversusslow BD induction. Rats were assigned to 3 groups: 1) control, 2) fast BD induction (ICP increase over 1 min) or 3) slow BD induction (ICP increase over 30 min). BD was induced by epidural inflation of a balloon catheter. Brain-dead rats were sacrificed after 0.5 hours, 1 hour, 2 hours and 4 hours to study time-dependent changes. Hemodynamic stability, histological lung injury and inflammatory status were investigated. We found that fast BD induction compromised hemodynamic stability of rats more than slow BD induction, reflected by higher mean arterial pressures during the BD induction period and an increased need for hemodynamic support during the BD stabilization phase. Furthermore, fast BD induction increased histological lung injury scores and gene expression levels of TNF-α and MCP-1 at 0.5 hours after induction. Yet after donor stabilization, inflammatory status was comparable between the two BD models. This study demonstrates fast BD induction deteriorates quality of donor lungs more on a histological level than slow BD induction.

Background For years, paediatric critical care practitioners used the adult American European Consensus Conference (AECC) and revised Berlin Definition (BD) for acute respiratory distress syndrome (ARDS) to study the epidemiology of paediatric ARDS (PARDS). In 2015, the paediatric specific definition, Paediatric Acute Lung Injury Consensus Conference (PALICC) was developed. The use of non-invasive metrics of oxygenation to stratify disease severity were introduced in this definition, although this potentially may lead to a confounding effect of disease severity since it is more common to place indwelling arterial lines in sicker patients. We tested the hypothesis that PALICC outperforms AECC/BD in our high acuity PICU, which employs a liberal use of indwelling arterial lines and high-frequency oscillatory ventilation (HFOV). Methods We retrospectively collected data from children Results Data from 909 out of 2433 patients was eligible for analysis. AECC/BD identified 35 (1.4%) patients (mortality 25.7%), whereas PALICC identified 135 (5.5%) patients (mortality 14.1%). All but two patients meeting AECC/Berlin criteria were also identified by PALICC. Almost half of the cohort (45.2%) had mild, 33.3% moderate and 21.5% severe PALICC PARDS at onset. Highest mortality rates were seen in patients with AECC acute lung injury (ALI)/mild Berlin and severe PALICC PARDS. The AUC-ROC for Berlin was the highest 24 h (0.392 [0.124–0.659]) after onset. PALICC showed the highest AUC-ROC at the same moment however higher than Berlin (0.531 [0.345–0.716]). Mortality rates were significantly increased in patients with bilateral consolidations (9.3% unilateral vs 26.3% bilateral, p = 0.025). Conclusions PALICC identified more new cases PARDS than the AECC/Berlin definition. However, both PALICC and Berlin performed poorly in terms of mortality risk stratification. The presence of bilateral consolidations was associated with a higher mortality rate. Our findings may be considered in future modifications of the PALICC criteria.

Background: Pseudomonas aeruginosa (Pa) is the predominant pulmonary pathogen in patients with cystic fibrosis (CF). Tobramycin nebulization is used for the eradication of Pa infection. Nowadays, tobramycin dry powder inhalation (DPI) is available as well. This study reports the results of eradicating Pa with tobramycin DPI versus nebulization. Methods: Adult CF patients with a Pa isolation between September 2010 and September 2017 from the University Medical Centre Groningen (UMCG), the Netherlands, were included in this retrospective study. Results: In total 27 Pa isolations were recorded. In 13 of these, eradication was attempted with tobramycin, 7 with DPI and 6 with nebulization. DPI eradicated Pa successfully in six isolations (85.7%). Of these, one patient received additional oral ciprofloxacin and one received intravenous ceftazidime. Nebulization eradicated three Pa isolations (50.0%), in two of these, additional oral ciprofloxacin was given. Conclusion: Eradication rates of DPI tobramycin are comparable with those for nebulized tobramycin reported in the literature. This study suggests that DPI tobramycin is an alternative to nebulized tobramycin for eradication of Pa. Trial registration: The Medical Ethics Committee of the UMCG granted a waiver (METC2017-349), as they concluded that this study was not subject to the Medical Research Involving Human Subjects Act. The reviews of this paper are available via the supplemental material section.

Tyrosinemia type 1 (TT1) treatment with 2-(2-nitro-4-trifluormethyl-benzyl)-1,3-cyclohexanedione (NTBC) and a phenylalanine-tyrosine restricted diet is associated with low phenylalanine concentrations. Phenylalanine supplementation is prescribed without comprehensive consideration about its effect on metabolic control. We investigated the effect of phenylalanine supplementation on bloodspot phenylalanine, tyrosine, NTBC and succinylacetone. Eleven TT1 patients received 0, 20 and 40 mg/kg/day phenylalanine supplementation with the phenylalanine-tyrosine free L-amino acid supplements. Bloodspots were collected before breakfast, midday and evening meal. Differences between study periods, sample times and days within a study period were studied using (generalized) linear mixed model analyses. Twenty and 40 mg/kg/day phenylalanine supplementation prevented daytime phenylalanine decreases (p = 0.05) and most low phenylalanine concentrations, while tyrosine concentrations increased (p &lt, 0.001). Furthermore, NTBC and succinylacetone concentrations did not differ between study periods. To conclude, 20 mg/kg/day phenylalanine supplementation can prevent most low phenylalanine concentrations without increasing tyrosine to concentrations above the target range or influencing NTBC and succinylacetone concentrations, while 40 mg/kg/day increased tyrosine concentrations to values above the targeted range. Additionally, this study showed that the effect of phenylalanine supplementation, and a possible phenylalanine deficiency, should be assessed using pre-midday meal blood samples that could be combined with an overnight fasted sample when in doubt.

Background: It has been suggested that antidepressant benefits are smaller for mild than severe depression. Because antidepressants are also used for anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), we examined the influence of severity for these disorders.Methods: We used individual patient data of eight trials (3,430 participants) for generalized anxiety disorder (GAD); four trials (1,195 participants) for social anxiety disorder (SAD); four trials (1,132 participants) for OCD; three trials (1,071 participants) for PTSD; and 10 trials (2,151 participants) for panic disorder (PD). Mixed-effects models were used to investigate an interaction between severity and treatment group.Results: For GAD and PD, severity moderated antidepressant efficacy. The antidepressant-placebo difference was 1.4 (95% CI: 0.4-2.5; SMD: 0.21) Hamilton Anxiety Rating Scale (HAM-A) points for participants with mild GAD (baseline HAM-A=10), increasing to 4.0 (3.4-4.6; SMD: 0.45) or greater for severely ill participants (HAM-A >= 30). For PD, the difference was 0.4 (0.3-0.6) panic attacks/2weeks for participants with 10 panic attacks/2weeks at baseline, increasing to 4.7 (3.0-6.4) for participants with 40. For SAD, OCD, and PTSD, no interaction was found. Across severity levels, the differences were 16.1 (12.9-19.3; SMD: 0.59) Liebowitz Social Anxiety Scale points, 3.4 (2.5-4.4, SMD: 0.39) Yale-Brown Obsessive-Compulsive Scale points, and 10.3 (6.9-13.6; SMD: 0.41) Clinician-Administered PTSD Scale points.Conclusions: Antidepressants are equally effective across severity levels for SAD, OCD, and PTSD. For GAD and PD, however, benefits are small at low severity, and the benefit-risk ratio may be unfavorable for these patients.

Introduction In hereditary tyrosinemia type 1 (HT1) patients, the dose of NTBC that leads to the absence of toxic metabolites such as succinylacetone (SA) is still unknown. Therefore, the aims of this study were to investigate the variation and concentrations of 2-(2-nitro-4-trifluormethyl-benzyl)-1,3-cyclohexanedione (NTBC) during the day in relation to the detection of SA, while comparing different dosing regimens. Methods All patients were treated with NTBC (mean 1.08 ± 0.34 mg/kg/day) and a low phenylalanine-tyrosine diet. Thirteen patients received a single dose of NTBC and five patients twice daily. Home bloodspots were collected four times daily for three consecutive days measuring NTBC and SA concentrations. Statistical analyses were performed by using mixed model analyses and generalized linear mixed model analyses to study variation and differences in NTBC concentrations and the correlation with SA, respectively. Results NTBC concentrations varied significantly during the day especially if NTBC was taken at breakfast only (p = 0.026), although no significant difference in NTBC concentrations between different dosing regimens could be found (p = 0.289). Momentary NTBC concentrations were negatively correlated with SA (p

Purpose: To identify a surrogate marker for late xerostomia 12 months after radiation therapy(Xer12m), according to information obtained shortly after treatment.Methods and Materials: Differences in parotid gland (PG) were quantified in image biomarkers (ΔIBMs) before and 6 weeks after radiation therapy in 107 patients. By performing stepwise forward selection, ΔIBMs that were associated with Xer12m were selected. Subsequently other variables, such as PG dose and acute xerostomia scores, were added to improve the prediction performance. All models were internally validated.Results: Prediction of Xer12m based on PG surface reduction (ΔPG-surface) was good (area under the receiver operating characteristic curve, 0.82). Parotid gland dose was related to ΔPG-surface (PR2 = 0.27). The addition of acute xerostomia scores to the ΔPG-surface improved the prediction of Xer12m significantly, and vice versa. The final model including ΔPG-surface and acute xerostomia had outstanding performance in predicting Xer12m early after radiation therapy (area under the receiver operating characteristic curve, 0.90).Conclusions: Parotid gland surface reduction was associated with late xerostomia. The early posttreatment model with ΔPG-surface and acute xerostomia scores can be considered as a surrogate marker for late xerostomia.

Background Patients with curable esophageal cancer (EC) who proceed beyond the original Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect that extending the CROSS eligibility criteria for nCRT has on treatment-related toxicity and overall survival (OS) in EC. Methods The study enrolled 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0) treated with the CROSS schedule followed by esophagectomy. Group 1 consisted of 89 patients who met the CROSS criteria, and group 2 consisted of 72 patients who met the extended eligibility criteria, i.e. a tumor length greater than 8 cm (n = 24), more than 10% weight loss (n = 35), more than 2–4 cm extension in the stomach (n = 21), celiac lymph node metastasis (n = 13), and/or age over 75 years (n = 2). The study assessed the differences in nCRT-associated toxicity [National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3] and 90-day postoperative mortality. Moreover, the prognostic value for OS was assessed with multivariate Cox regression analysis. Results No difference was found in nCRT-associated toxicity (P = 0.117), postoperative complications (P = 0.783), and 90-day mortality (P = 0.492). The OS differed significantly (P = 0.004), with a median of 37.3 months [95% confidence interval (CI), 10.4–64.2 months] for group 1 and 17.2 months (95% CI 13.8–20.7 months) for group 2. Pathologic N stage (P = 0.023), pathologic T stage (P = 0.043), and group 2 (P = 0.008) were independent prognostic factors for OS. Conclusions Extension of the CROSS study eligibility criteria for nCRT did not affect nCRT-associated toxicity, postoperative complications, and postoperative mortality, but was prognostic for OS. Electronic supplementary material The online version of this article (doi:10.1245/s10434-017-5797-3) contains supplementary material, which is available to authorized users.

Background Kidney transplantation is associated with harmful processes affecting the viability of the graft. One of these processes is associated with the phenomenon of ischaemia–reperfusion injury. Anaesthetic conditioning is a widely described strategy to attenuate ischaemia–reperfusion injury. We therefore conducted the Volatile Anaesthetic Protection of Renal Transplants-1 trial, a pilot project evaluating the influence of two anaesthetic regimens, propofol- vs sevoflurane-based anaesthesia, on biochemical and clinical outcomes in living donor kidney transplantation. Methods Sixty couples were randomly assigned to the following three groups: PROP (donor and recipient propofol), SEVO (donor and recipient sevoflurane), and PROSE (donor propofol and recipient sevoflurane). The primary outcome was renal injury reflected by urinary biomarkers. The follow-up period was 2 yr. Results Three couples were excluded, leaving 57 couples for analysis. Concentrations of kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and heart-type fatty acid binding protein (H-FABP) in the first urine upon reperfusion showed no differences. On day 2, KIM-1 concentrations were higher in SEVO [952.8 (interquartile range 311.8–1893.0) pg mmol−1] compared with PROP [301.2 (202.0–504.7) pg mmol−1]. This was the same for NAG: SEVO, 1.835 (1.162–2.457) IU mmol−1vs PROP, 1.078 (0.819–1.713) IU mmol−1. Concentrations of H-FABP showed no differences. Measured glomerular filtration rate at 3, 6, and 12 months showed no difference. After 2 yr, there was a difference in the acute rejection rate (P=0.039). Post hoc testing revealed a difference between PROP (35%) and PROSE (5%; P=0.020). The difference between PROP and SEVO (11%) was not significant (P=0.110). Conclusions The SEVO group showed higher urinary KIM-1 and NAG concentrations in living donor kidney transplantation on the second day after transplantation. This was not reflected in inferior graft outcome. Clinical trial registration NCT01248871.

Background and purpose: Current models for the prediction of late patient-rated moderate-to-severe xerostomia (XER12m) and sticky saliva (STIC12m) after radiotherapy are based on dose-volume parameters and baseline xerostomia (XERbase) or sticky saliva (STICbase) scores. The purpose is to improve prediction of XER12m, and STIC12m with patient-specific characteristics, based on CT image biomarkers (IBMs).Methods: Planning CT-scans and patient-rated outcome measures were prospectively collected for 249 head and neck cancer patients treated with definitive radiotherapy with or without systemic treatment. The potential IBMs represent geometric. CT intensity and textural characteristics of the parotid and sub mandibular glands. Lasso regularisation was used to create multivariable logistic regression models, which were internally validated by bootstrapping.Results: The prediction of XER12m could be improved significantly by adding the IBM "Short Run Emphasis" (SRE), which quantifies heterogeneity of parotid tissue, to a model with mean contra-lateral parotid gland dose and XERbase. For STIC12m, the IBM maximum CT intensity of the submandibular gland was selected in addition to STICbase and mean dose to submandibular glands.Conclusion: Prediction of XER12m and STIC12m was improved by including IBMs representing heterogeneity and density of the salivary glands, respectively. These IBMs could guide additional research to the patient-specific response of healthy tissue to radiation dose. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

Study Design: Cross-sectional.Introduction: Southampton Hand Assessment Procedure (SHAP) provides function scores for hand grips (prehensile patterns) and an overall score, the index of function (IOF). The underlying equations of SHAP are not publicly available, which induces opacity. Furthermore, SHAP has been scarcely tested in prosthetic users.Methods: Issues with SHAP-IOF are discussed: an alternative scoring system, that is, linear index of function (LW) and a weighted version (W-LIF) are presented. In LIF, task times are transformed linearly, relative to SHAP norms, and are computed into LIF-prehensile patterns (LIFpp). LIF and IOF were compared using data of 27 experienced prosthetic users.Results: High correlation and agreement between LIF and IOF was found: LIFpp vs IOFpp ranged from r = 0.880 to r = 0.988, and W-LIF vs 10F had a correlation coefficient of r = 0.984.Discussion: SHAP data of prosthetic users are valuable benchmarks for health care professionals. LIF calculations are a good and cost free alternative for 10F scores.Conclusion(s): Measurements with LIF and 10F may be considered similar, but LIF is transparent and easier to use than 10F. Level of Evidence: Clinical measurement and cross-sectional. (C) 2016 Hanley & Belfus, an imprint of Elsevier Inc. All rights reserved.

Background. Beyond the acute illness phase, chikungunya constitutes a public health problem given its chronic disease phase, which may include long-term arthralgia, arthritis, fatigue, and depression. Currently, there is no consensus on how to define chikungunya chronicity.Methods. A comprehensive cross-sectional survey was performed in Curacao in June and July 2015 to evaluate 304 adult laboratory-confirmed chikungunya patients 3-16 months after diagnosis. We developed a novel tool, the Curacao Long-Term Chikungunya Sequelae (CLTCS) score, to classify chronic chikungunya disease and estimate its burden regarding disease duration, clinical presentation, and impact on quality of life.Results. Disease persistence was estimated to be 79% one month after symptom onset and 64% after 400 days. Chikungunya persistence was characterized by higher proportions of arthralgia, weakness, myalgia, and age 41-60 years. Individuals were classified as "highly affected," "mildly affected," and "recovered." "Highly affected" disease status was associated with clinical complaints (arthralgia, weakness, loss of vitality, and being diabetic) and major decreases in quality-of-life scores.Conclusions. In the Caribbean, a high proportion of chikungunya patients remains chronically affected. We propose the CLTCS as a suitable score to easily and rapidly classify the severity of chikungunya chronic disease and to assess the need for symptom-alleviating treatment.

Background & aims: During treatment for cancer, children experience many side effects such as lack of appetite, nausea, and vomiting. As a result, ensuring adequate intake puts pressure on both the child and the parent. This study aims to determine the prevalence, causes and consequences of eating and feeding problems in children treated for cancer. Methods: Parents of 85 children with cancer completed the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) and symptoms, BMI, energy intake, feeding style, and parental distress were measured at 0, 3, 6 and 12 months after diagnosis. Results: Parent-reports revealed that almost a quarter of the children experienced eating disorder: 15.7% experienced problems related to diminished intake and 8.6% related to excessive intake. Prevalence of feeding disorders related to parents’ behavior was 21.1%. In children

Background: Clinical nodal (cN) staging is a key element in treatment decisions in patients with esophageal cancer (EC). The reliability of cN status regarding the effect on response and survival after neoadjuvant chemoradiotherapy (nCRT) with esophagectomy was evaluated in determining the up- and downstaged pathological nodal (pN) status after surgery alone. Material and methods: From a prospective database, we included all 395 EC patients who had surgery with curative intent with or without nCRT between 2000 and 2015. All patients were staged by a standard pretreatment protocol: 16-64 mdCT, 18 F-FDG-PET or 18 F-FDG-PET/CT and EUS ± FNA. After propensity score matching on baseline clinical tumor and nodal (cT/N) stage and histopathology, a surgery-alone and nCRT group (each N = 135) were formed. Clinical and pathological N stage was scored as equal (cN = pN), downstaged (cN > pN) or upstaged (cN p value Results: The surgery-alone and nCRT group did not differ in cT/N status. Pathologic examination revealed equal staging (32 vs. 27%), nodal up (43 vs. 16%) and downstaging (25 vs. 56%), respectively (p p = .002) and lymph-angioinvasion (p = .016) in surgery-alone, and upper abdominal cN metastases (p = .012) and lymph node ratio (p = .034) in the nCRT group. Conclusions: Despite modern staging methods, correct cN staging remains difficult in EC. Nodal overstaging (cN > pN) occurred more often than understaging impeding an adequate assessment of pathologic complete response and prognosis after nCRT. Preoperative assessment of true nodal response after nCRT in EC remains difficult with clinical nodal upstaging (16% vs. 43%) and downstaging (56% vs. 25%) after nCRT and surgery alone, respectively.

PURPOSE: The purpose of this study was to evaluate the influence of immersion in a virtual reality environment on knee biomechanics in patients after ACL reconstruction (ACLR). It was hypothesized that virtual reality techniques aimed to change attentional focus would influence altered knee flexion angle, knee extension moment and peak vertical ground reaction force (vGRF) in patients following ACLR.METHODS: Twenty athletes following ACLR and 20 healthy controls (CTRL) performed a step-down task in both a non-virtual reality environment and a virtual reality environment displaying a pedestrian traffic scene. A motion analysis system and force plates were used to measure kinematics and kinetics during a step-down task to analyse each single-leg landing.RESULTS: A significant main effect was found for environment for knee flexion excursion (P = n.s.). Significant interaction differences were found between environment and groups for vGRF (P = 0.004), knee moment (P < 0.001), knee angle at peak vGRF (P = 0.01) and knee flexion excursion (P = 0.03). There was larger effect of virtual reality environment on knee biomechanics in patients after ACLR compared with controls.CONCLUSION: Patients after ACLR immersed in virtual reality environment demonstrated knee joint biomechanics that approximate those of CTRL. The results of this study indicate that a realistic virtual reality scenario may distract patients after ACLR from conscious motor control. Application of clinically available technology may aid in current rehabilitation programmes to target altered movement patterns after ACLR.LEVEL OF EVIDENCE: Diagnostic study, Level III.

BACKGROUND: The purpose of this study was to provide more insight in the course of cytokine concentrations related to pathologic response (pR) and complications after neoadjuvant chemoradiotherapy (NCRT) and esophagectomy in esophageal cancer patients.METHODS: Patients treated with NCRT followed by transthoracic esophagectomy (n = 35) or transthoracic esophagectomy alone (n = 8) were included. Eight different cytokine concentrations were determined during NCRT, esophagectomy, and the first postoperative week.RESULTS: Platelet-activating factor before NCRT was associated with pR (P = .011) and remained elevated in patients with a better response. Concentrations of intestinal fatty acid-binding protein and angiopoietin 1 (Ang-1) were different between patients with and without NCRT. Decreased concentrations of Ang-1 on the third postoperative day were associated with postoperative complications (P = .046).CONCLUSIONS: In this observational study, elevated platelet-activating factor concentrations before NCRT were associated with pR. NCRT is associated with decreased Ang-1 concentrations, whereas reduced Ang-1 concentrations were associated with postoperative complications. (C) 2016 Elsevier Inc. All rights reserved.

Item does not contain fulltext INTRODUCTION: Treatment for differentiated thyroid carcinoma (DTC) in pediatric patients is based mainly on evidence from adult series due to lack of data from pediatric cohorts. Our objective was to evaluate presentation, treatment-related complications, and long-term outcome in patients with pediatric DTC in The Netherlands. PATIENTS AND METHODS: In this nationwide study, presentation, complications, and outcome of patients with pediatric DTC (age at diagnosis

Item does not contain fulltext This study focused on comparing muscle activities predicted by the Musculoskeletal Modeling System with EMG from ten healthy subjects who performed normal walking, one-legged forward hopping and side jumping. Eight EMG electrodes measured the activity of eight right leg muscles. Specific thresholds per muscle were applied on the EMG prior comparison. These thresholds were determined by equalizing the duration of EMG to AMS muscle activity. Three graph variables, number of onsets, offsets and hills were used to quantify the level of agreement by using Cohens kappa analysis. The Pearson correlation coefficient was also calculated as a result comparison. Overall, visual inspection showed comparable activity patterns. However, when quantifying them some differences became apparent. The mean level of agreement of all tests was

Background. Circumferential resection margins (CRM) for esophageal cancer (EC), defined by the College of American Pathologists (CAP; >0 mm) or the Royal College of Pathologists (RCP; >1 mm) as tumor-free (R0), are based on a surgery-alone approach. We evaluated the usefulness of both definitions in current practice with neoadjuvant chemoradiotherapy (nCRT).Methods. CRMs were measured in 209 patients (104 with nCRT) with locally advanced EC after transthoracic esophagectomy. Local recurrence and cancer related death were scored as events. Patients were followed for at least 2 years or until death. Prognostic factors (P Results. Independent prognostic factors (P Conclusions. nCRT affected the CRM cutoff values. After nCRT, the CRM R0 according to the CAP was only prognostic for 2-year LRFS. However, in the surgery-alone group, it was prognostic for both the 2-year DFS and LRFS.

Background: Patients with differentiated thyroid carcinoma (DTC) have a favorable prognosis after treatment with thyroidectomy, radioiodine, and TSH suppression. However, treatment is associated with long-term cardiovascular toxicity. The aim of this study was to evaluate whether there is an increased risk of atrial fibrillation (AF) in DTC patients and whether AF occurrence is related to DTC treatment.Patients and Methods: Incident AF was compared between 518 DTC patients and 1563 matched controls. A cumulative incidence curve was plotted, and competing risk regression analyses with adjustment for all-cause mortality were performed. Within the DTC cohort, associations between time-varying DTC treatment variables and incident AF were analyzed.Results: For both cohorts, the mean age was 48.6 years (75% of subjects were women). The AF incidence rate was 6.2/1000 person-years for DTC patients and 2.7/1000 person-years for controls. DTC patients had a 2.25-fold (95% confidence interval [CI], 1.40-3.63) and 2.47-fold (95% CI, 1.55-3.95) increased AF risk in crude and fully adjusted analyses, respectively. Within the DTC cohort, the TSH level (which was suppressed in 85.7% of patients) was not associated with AF, whereas a higher cumulative radioiodine dose slightly increased AF risk: subdistribution hazard ratio, 1.04 (95% CI, 1.01-1.08) per 50 mCi (1.85 GBq) increase, after adjustment.Conclusion: Patients with DTC have an increased AF risk, independent from established AF risk factors. We could not demonstrate a relation between TSH and AF, whereas a higher cumulative radioiodine dose was associated with a slightly increased AF risk. Electrocardiogram screening for AF may be warranted during follow-up of DTC patients to allow early diagnosis and treatment of AF and to prevent its complications.

Objectives: Measures of frailty (Groningen Frailty Indicator, GFI) and case complexity (INTERMED for the Elderly, IM-E-SA) may assist healthcare professionals to allocate healthcare resources. Both instruments have been evaluated with good psychometric properties. Limited evidence has been published about their predictive validity. Thus, our aim is to evaluate the predictive validity of both instruments on healthcare costs.Methods: Multivariate linear regression models were developed to estimate associations between the predictors frailty (GFI) and/or case complexity (IM-E-SA) and the healthcare costs (in log transformed) in the following year. All models were adjusted for demographics and the presence of morbidity.Results: In the multivariate regression analyses the continuous scores of the GFI and IM-E-SA remained significant predictors for total healthcare costs. Adjusted beta s for GFI and IM-E-SA were respectively 0.14 (95% CI 0.10-0.18) and 0.06 (95% CI 0.04-0.07). The corresponding explained variance (R-2) for both models was 0.40. Frailty remained a significant predictor of long-term care costs (adjusted beta 0.13 [95% CI 0.09-0.16]), while case complexity was a significant predictor of curative care costs (adjusted beta 0.03 195% CI 0.02-0.05]).Conclusions: The GFI and IM-E-SA both accurately predict total healthcare costs in the following year. (C) 2015 Elsevier Inc. All rights reserved.

Dengue, a viral mosquito-borne disease currently affects more than 2.5 billion people living in endemic areas worldwide. In vector control, social mobilization and community behavioral changes are of crucial importance. Here, we identified the factors influencing community dengue preventive practices in a high-transmission urban area in Venezuela. Between September 2013 and February 2014, a cross-sectional study at the household level was carried out in Maracay city, Venezuela. A precoded questionnaire was used to obtain information on people's knowledge, attitudes, and use of preventive practices in relation to dengue. Concomitantly, entomological data was collected from households. In 80% of the 105 included households, 1-5 preventive practices (e.g., repellents, insecticides) against mosquito bites were used. However, 57% of the examined houses had potential Aedes breeding sites indoors and/or outdoors, most of which positive for Aedes spp. larvae/pupae. Preventive practices were associated with a previous dengue infection (P = 0.030) and a better knowledge on dengue symptoms and transmission route (P = 0.020). In turn, knowledge was associated with feeling at risk (P

Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted). After 4 hrs, tissue was collected, mitochondria isolated and assessed with high-resolution respirometry. Quantitative proteomics, qPCR, and biochemistry was performed on stored tissue/plasma. Following BD, the liver increased glycolytic gene expression (Pfk-1) with decreased glycogen stores, while the kidneys increased anaerobic- (Ldha) and decreased gluconeogenic-related gene expression (Pck-1). Hepatic oxygen consumption increased, while renal perfusion decreased. ATP levels dropped in both organs while mitochondrial respiration and complex I/ATP synthase activity were unaffected. In conclusion, the liver responds to increased metabolic demands during BD, enhancing aerobic metabolism with functional mitochondria. The kidneys shift towards anaerobic energy production while renal perfusion decreases. Our findings highlight the need for an organ-specific approach to assess and optimise graft quality prior to transplantation, to optimise hepatic metabolic conditions and improve renal perfusion while supporting cellular detoxification.

Objective The impact of childhood differentiated thyroid carcinoma (DTC) on psychosocial development has not yet been studied. The aim of this study was to evaluate the achievement of psychosocial developmental milestones in long-term survivors of childhood DTC. Design and methods Survivors of childhood DTC diagnosed between 1970 and 2013 were included. Reasons for exclusion were age 35 years at follow-up, a follow-up period n = 30). A comparison group non-affected with cancer (n = 508) and other childhood cancer survivors (CCS) were also used to compare psychosocial development. To assess the achievement of psychosocial milestones (social, autonomy and psychosexual development), the course of life questionnaire (CoLQ) was used. Results We included 39 survivors of childhood DTC (response rate 83.0%, mean age at diagnosis 15.6 years, and mean age at evaluation 26.1 years). CoLQ scores did not significantly differ between survivors of childhood DTC and the two non-affected groups. CoLQ scores of childhood DTC survivors were compared to scores of other CCS diagnosed at similar ages (n = 76). DTC survivors scored significantly higher on social development than other CCS, but scores were similar on autonomy and psychosexual developmental scales. Conclusions Survivors of childhood DTC showed similar development on social, autonomy, and psychosexual domains compared to non-affected individuals. Social development was slightly more favorable in DTC survivors than in other CCS, but was similar on autonomy and psychosexual domains.

Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis 18 years and follow-up 5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4% women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction P = 0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed.Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac aging.

Background and purpose: Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance to CRT, possibly through an association with a cancer stem cell phenotype.Material and methods: 101 EC patients treated with nCRT and surgery were included. Sufficient pretreatment biopsy material was present in 71 patients, of which 53 patients were non-complete responders on nCRT (nCR). Protein expression was examined using immunohistochemistry (IHC). Prognostic factors were determined using Cox regression analysis for disease free survival (DFS) and cause specific survival (CSS) in the complete cohort, the pre-treatment biopsies group and post-treatment nCR group.Results: Low CD44 expression in the nCR group was an independent prognostic factor for both DFS and CSS (DFS HR 2.81, p = 0.002 and CSS HR 3.48, p = 0.002). Absent SOX2 expression in pretreatment biopsies was related to systemic recurrence (p = 0.029) while low,SHH in pretreatment biopsies was an independent prognostic factor for a poor DES (HR 2.27, p = 0.036). No relation between marker expression and response to nCRT was observed.Conclusions: Low expression of CD44 and SHH are associated with a poor survival outcome in EC patients treated with nCRT. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Background & aims: Despite a widespread belief that adequate dietary intake is needed to maintain weight during childhood cancer treatment, conclusive data about adequacy of intake are lacking. Therefore, we aimed to assess the adequacy of energy and protein intake in a heterogeneous childhood cancer population against 3 different norms.Methods: We conducted a prospective cohort study of 115 children diagnosed with cancer and assessed dietary intake after diagnosis and at 3, 6, and 12 months. Intake was assessed against recommended daily allowances (RDA), intake in healthy controls, and calculated individual requirements; and subsequently related to changes in nutritional status:Results: Energy intake was lower than RDA and lower than in healthy controls at all measurement points; whereas energy intake matched individual requirements at 2 of the 4 measurement points. Protein intake in childhood cancer patients was lower than in healthy children. However, protein intake was almost twice the RDA and one and a half times the individual requirements. During the study period, weight and fat mass (FM) increased significantly while fat free mass (FFM) remained low. Energy intake was negatively associated with weight and FM, and protein intake was not associated with FFM.Conclusions: The patients' weight increased; whereas their energy intake was lower than RDA and lower than in,healthy controls. This indicates that the average intake was more than adequate. Percentage intake of individual requirements matched with increased weight. Therefore, the use of this norm is preferable to RDA or intake in healthy controls when determining the adequacy of dietary intake in both clinical practice and futures studies. (C) 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Purpose: Malnutrition in childhood cancer patients has been associated with lower health-related quality of life (HRQOL). However, this association has never actually been tested. Therefore, we aimed to determine the association between nutritional status and HRQOL in children with cancer. Methods: In 104 children, aged 2–18 years and diagnosed with hematological, solid, or brain malignancies, nutritional status and HRQOL were assessed at diagnosis and at 3, 6, and 12 months using the child- and parent-report versions of the PedsQL 4.0 Generic scale and the PedsQL 3.0 Cancer Module. Scores on both scales range from 0 to 100. Results: Undernourished children (body mass index (BMI) or fat-free mass 2 SDS) reported lower scores on emotional (−8.0) and cognitive functioning (−9.2) and on the cancer summary scale (−6.6), whereas parent-report scores were lower on social functioning (−7.5). Weight loss (>0.5 SDS) was associated with lower scores on physical functioning (−13.9 child-report and −10.7 parent-report), emotional (−7.4) and social functioning (−6.0) (child-report), pain (−11.6), and nausea (−7.8) (parent-report). Parents reported worse social functioning and more pain in children with weight gain (>0.5 SDS) compared with children with stable weight status. Conclusions: Undernutrition and weight loss were associated with worse physical and social functioning, whereas overnutrition and weight gain affected the emotional and social domains of HRQL. Interventions that improve nutritional status may contribute to enhanced health outcomes in children with cancer.

Background. It has been suggested that markers associated with cancer stem cells (CSC) may play a role in esophageal cancer. Our aim was to investigate the expression pattern of proposed CSC markers ALDH1, Axin2, BMI1, CD44, and SOX2 in esophageal adenocarcinoma (EAC) and to relate their expression to survival.Methods. In this study we included 94 EAC patients and examined the expression of the above-mentioned markers by using immunohistochemistry on tissue microarrays. Expression was scored as positive or negative or categorized as low or high in terms of an immunoreactivity score (IRS). Expression rates were related to clinicopathologic characteristics and overall and disease-free survival (DFS).Results. In a multivariate analysis, negative expression of CD44 and of SOX2 were both significant prognostic factors for DFS [hazard ratio (HR), 1.73; 95 % confidence interval (CI), 1.00-2.96; P = 0.046 and HR, 2.06; 95 % CI 1.14-3.70 P = 0.016). When CD44 and SOX2 expression were analyzed together, negative SOX2 expression was an independent prognostic factor for DFS (HR, 1.91; 95 % CI 1.05-3.46; P = 0.034). Low IRS scores for ALDH1 or Axin2 were associated with a reduced median survival (12.8 vs. 28.7 and 12.1 vs. 25.5 months, respectively). However, these markers and BMI1 were not prognostic factors for survival.Conclusions. Loss of CD44 expression and loss of SOX2 expression are prognostic factors of poor survival in EAC patients. This suggests a role of these proteins in EAC that requires further investigation.

Background: The assessment of the early motor repertoire is a widely used method for assessing the infant's neurological status.Aim: To determine the association between the early motor repertoire and language development.Study design: Prospective cohort study.Subjects: 22 term children born after normal pregnancy; video recorded for the assessment of the early motor repertoire including their motor optimality score (MOS), according to Prechtl, at 3 and 5 months post term.Outcome measures: At 4 years 7 months and 10 years 5 months, we tested the children's language performance by administering three tests for expressive language and two for receptive language.Results: Smooth and fluent movements at 3 months of age was associated with better expressive language outcome at both 4 years 7 months and 10 years 5 months (betas 0.363 and 0.628). A higher MOS at 5 months was associated with better expressive language at both ages (betas 0.486 and 0.628). The item postural patterns at 5 months was the only aspect associated with poorer expressive language outcome (beta - 0.677).Conclusion: Predominantly, qualitative aspects of the early motor repertoire at the age of 3 and 5 months are associated with language development.

Aim For reliable assessment of ataxia severity in children, the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society aimed to validate the Scale for Assessment and Rating of Ataxia (SARA) according to age. Method Twenty-two pediatric ataxia experts from 15 international institutions scored videotaped SARA performances in 156 typically developing children (4–16y: m/f=1; 12 children per year of age; including nine different nationalities). We determined age-dependency and reliability of pediatric SARA scores by a mixed model. Results In typically developing children, age was the only variable that revealed a relationship with SARA scores (p

Context:Little is known about long-term quality of life (QoL) of survivors of pediatric differentiated thyroid carcinoma. Therefore, this study aimed to evaluate generic health-related QoL (HRQoL), fatigue, anxiety, and depression in these survivors compared with matched controls, and to evaluate thyroid cancer–specific HRQoL in survivors only.Design:Survivors diagnosed between 1970 and 2013 at age ≤18 years, were included. Exclusion criteria were a follow-up Results:Sixty-seven survivors and 56 controls. Median age of survivors at evaluation was 34.2 years (range, 18.8 to 61.7). Median follow-up was 17.8 years (range, 5.0 to 44.7). On most QoL subscales, scores of survivors and controls did not differ significantly. However, survivors had more physical problems (P = 0.031), role limitations due to physical problems (P = 0.021), and mental fatigue (P = 0.016) than controls. Some thyroid cancer–specific complaints (e.g., sensory complaints and chilliness) were present in survivors. Unemployment and more extensive disease or treatment characteristics were most frequently associated with worse QoL.Conclusions:Overall, long-term QoL in survivors of pediatric DTC was normal. Survivors experienced mild impairment of QoL in some domains (physical problems, mental fatigue, and various thyroid cancer–specific complaints). Factors possibly affecting QoL need further exploration.

Background: In vitro studies have shown the feasibility of coronary lesion grading with computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) as compared to histology, whereas OCT had the highest discriminatory capacity.Objective: We investigated the ability of CTA and IVUS to differentiate between early and advanced coronary lesions in vivo, OCT serving as standard of reference.Methods: Multimodality imaging was prospectively performed in 30 NSTEMI patients. Plaque characteristics were assessed in 1083 cross-sections of 30 culprit lesions, co-registered among modalities. Absence of plaque, fibrous and fibrocalcific plaque on OCT were defined as early plaque, whereas lipid rich-plaque on OCT was defined as advanced plaque. Odds ratios adjusted for clustering were calculated to assess associations between plaque types on CTA and IVUS with early or advanced plaque.Results: Normal findings on CTA as well as on IVUS were associated with early plaque. Non-calcified, calcified plaques and the napkin ring sign on cm were associated with advanced plaque. On IVUS, fatty and calcified plaques were associated with advanced plaque.Conclusions: In vivo coronary plaque characteristics on CTA and IVUS are associated with plaque characteristics on OCT. Of note, normal findings on CTA and IVUS relate to early lesions on OCT. Nevertheless, multiple plaque features on CTA and IVUS are related to advanced plaques on OCT, which may make it difficult to use qualitative plaque assessment in clinical practice. (C) 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Introduction: Gaining regular insight into the nature and severity of distress by a psychosocial nurse coupled with referral to psychosocial and/or paramedical healthcare provider(s) is an experimental supportive care approach. We sought to examine the effects of this approach on quality of life (QoL), patient's mood and satisfaction, end-of-life care and survival in patients with lung cancer.Methods: Patients with newly diagnosed or recurrent lung cancer starting systemic therapy were randomly assigned to receive usual care or the experimental approach. Patients were followed up at 1, 7, 13 and 25 weeks after randomisation with the EORTC-QLQ-C30, the European Quality of Life-5D, the Hospital Anxiety and Depression Scale and the Patient Satisfaction Questionnaire-III. Primary outcome was the mean change in the EORTC-QLQ-C30 global QoL-score between 1 and 25 weeks.Results: A total of 223 patients were randomised of whom 111 (50%) completed all four assessments (44% in the usual care group versus 55% in the experimental group). No significant difference was found in the mean change global QoL-score (-2.4, 95% CI: 12.1-7.2; P = 0.61), nor in the other patient-reported outcomes., Fewer patients in the experimental group received chemotherapy shortly before the end-of-life, and median survival was comparable (10.3 versus 10.1 months, P = 0.62). Of the 112 dropouts, 33 died and 79 discontinued participation for other reasons.Conclusions: This supportive care approach neither improved QoL nor other patient-reported outcomes in patients with lung cancer. However, it reduced the use of chemotherapy shortly before the end of life. Possibly, (late) side effects of systemic therapy may have obscured effects of our intervention on QoL. (C) 2016 Elsevier Ltd. All rights reserved.

The Southampton Hand Assessment Procedure (SHAP) evaluates the functionality of normal, injured or prosthetic hands. The aim was to evaluate the learning effects of SHAP tasks and the appropriateness of the time limits applied per task in novice prosthetic users.Right-handed unimpaired volunteers (n = 24, mean age 21.8 years) completed 8 SHAP sessions over 5 consecutive days using a prosthetic simulator. The execution times of SHAP tasks were transformed into 6 prehensile patterns, the functionality profile, and the index of function, a general functionality score. Learning effects in task times were analysed using multilevel analysis.Learning effects occurred in all SHAP tasks. Tasks, sex, sessions, tasks-sessions interaction, and the first session of the day contributed (p 0.01) to the execution times. Tasks were performed more slowly by females and more slowly on the first session of the day. In several tasks time limits were exceeded by 25% of participants in at least the first 3 sessions, which affected the calculation of the functionality profile and index of function scores.The learning effects of SHAP in novice prosthetic users require consideration when conducting a reliability study. SHAP scores in novice prosthetic-hand users are confounded by learning effects and exceeded time limits.

AIM: Nasal continuous positive airway pressure (NCPAP) has been proposed as an early first-line support for infants with severe respiratory syncytial virus (RSV) infection. We hypothesised that infants METHODS: Retrospective cohort analysis of infants admitted to two paediatric intensive care units, one primarily using NCPAP and one exclusively using IMV, between January 2008 and February 2010.RESULTS: We studied 133 (NCPAP n = 89, IMV n = 46) consecutively admitted infants. On admission, disease severity [i.e. Paediatric RISk of Mortality (PRISM) II score (NCPAP 5.1 ± 2.8 vs. IMV 12.2 ± 6.0, p < 0.001) and SpO2 /Fi O2 ratio (NCPAP 309 ± 81 vs. IMV 135 ± 98, p < 0.001)] was higher in the IMV group. NCPAP remained independently associated with shorter ventilatory support (hazard ratio 2.3, 95% CI 1.1-4.7, p = 0.022) after adjusting for PRISM II score, PCO2 , SpO2 /Fi O2 ratio, bronchopulmonary dysplasia and occurrence of clinically suspected secondary bacterial pneumonia.CONCLUSION: Nasal continuous positive airway pressure was independently associated with a shorter duration of ventilatory support. Differences in baseline disease severity mandate a randomised trial before the routine use of NCPAP can be recommended.

Rocker profiles are commonly used in the prevention of diabetic foot ulcers. Rockers are mostly stiffened to restrict toe plantarflexion to ensure proper offloading. It is also described that toe dorsiflexion should be restricted. However, the difference in effect on plantar pressure between rigid rockers that restrict this motion and flexible rockers that do not is unknown. In-shoe plantar pressure data were collected for a control shoe and the same shoe with rigid and flexible rockers with the apex positioned at 50% and 60%. For 29 healthy female adults peak plantar pressure (PP), maximum mean pressure (MMP) and force-time integral (FTI) were determined for seven regions of the foot. Generalized estimate equation was used to analyse the effect of the different shoes on the outcome measures for these regions. Compared to the control shoe a significant increase of PP and FTI was found at the first toe for both rigid rockers and the flexible rocker with the apex positioned at 60%, while MMP was significantly increased in rockers with an apex position of 60% (p

Previous studies in rodents have indicated that only a minor fraction of the immunoglobulin heavy chain variable region (IGHV-Cμ) transcripts carry somatic mutations and are considered memory B cells. This is in marked contrast to humans where nearly all marginal zone B (MZ-B) cells are mutated. Here we show in rats that the proportion of mutated IgM+ MZ-B cells varies significantly between the various IGHV genes analyzed, ranging from 27% mutated IGHV5 transcripts to 65% mutated IGHV4 transcripts. The observed data on mutated sequences in clonally-related B cells with a MZ-B cell or follicular B (FO-B) cell phenotype indicates that mutated IgM+ MZ-B and FO-B cells have a common origin. To further investigate the origin of mutated IgM+ MZ-B cells we determined whether mutations occurred in rearranged IGHV-Cμ transcripts using IGHV4 and IGHV5 genes from neonatal rat MZ-B cells and FO-B cells. We were not able to detect mutations in any of the IGHV4 and IGHV5 genes expressed by MZ-B cells or FO-B cells obtained from neonatal rat spleens. Germinal centres (GCs) are absent from neonatal rat spleen in the first few weeks of their life, and no mutations were found in any of the neonatal sequences, not even in the IGHV4 gene family which accumulates the highest number of mutated sequences (66%) in the adult rat. Therefore, these data do not support the notion that MZ-B cells in rats mutate their IGHV genes as part of their developmental program, but are consistent with the notion that mutated rat MZ-B cells require GCs for their generation. Our findings support that the splenic MZ of rats harbors a significant number of memory type IgM+ MZ-B cells with mutated IGHV genes and propose that these memory MZ-B cells are probably generated as a result of an antigen driven immune response in GCs, which still remains to be proven.

Objective: To test the hypothesis that transfusion of leukocyte-depleted RBC preparations within the first 48 hours of PICU stay was independently associated with prolonged duration of mechanical ventilation, irrespective of surgery type and disease severity.Design: Retrospective, observational study.Setting: Single-center PICU in The Netherlands.Patients: Children less than 18 years consecutively admitted after pediatric cardiac surgery between February 2007 and February 2010.Interventions: None.Measurements and Main Results: Data from 335 patients were used for analysis of whom 86 (25.7%) were transfused during the first 48 hours of PICU stay. Duration of mechanical ventilation (115 +/- 19 hours vs. 25 +/- 4 hours, p Conclusions: Transfusion of leukocyte-depleted RBCs within the first 48 hours of PICU stay after cardiac surgery is independently associated with prolonged duration of mechanical ventilation. (Pediatr Crit Care Med 2013; 14:298-305)

Definitive (chemo)radiotherapy is employed in esophageal cancer patients as an alternative for patients considered medically unfit for surgery or having unresectable tumors. We evaluated a population-based cohort to improve the selection for intensified nonsurgical strategies and to identify prognostic factors.Patients who had squamous cell carcinoma (SCC) or adenocarcinoma (AC) were treated in four referral centers in the north-east Netherlands with definitive chemoradiotherapy (dCRT) or radiotherapy (dRT) between 1996 and 2008.Of the 287 included patients, 110 were treated with dCRT and 177 with dRT. Median overall survival (OS) was 11 months (95 % confidence interval: 10-12 months), with OS of 22 and 8 % and disease-free survival (DFS) of 16 and 5 % at 2 and 5 years, respectively. DFS at 2 and 5 years was 24 and 9 % for SCC versus 10 and 2 % for AC patients (P = 0.006). OS after 2 and 5 years was 29 and 14 % for SCC patients versus 17 and 3 % for AC patients (P = 0.044). On multivariate Cox regression, SCC was an independent prognostic factor for DFS [P = 0.020, hazard ratio (HR) = 0.71] and OS (P = 0.047, HR = 0.76). On matched cohort analysis, DFS was higher in the dCRT group compared with dRT patients (P = 0.016). The locoregional failure rate was lower in the dCRT group and in SCC patients (P = 0.001 and 0.046).Long-term results and the local control rate in SCC patients were better after definitive (chemo)radiotherapy compared with in AC patients. SCC was an independent prognostic factor for survival. Definitive chemoradiotherapy leads to improved local control rate and DFS.

Background and purpose: The aim of this study was to develop and validate a method to select head and neck cancer patients for adaptive radiotherapy (ART) pre-treatment. Potential pre-treatment selection criteria presented in recent literature were included in the analysis.Materials and methods: Deviations from the planned parotid gland mean dose (PG Delta Dmean) were estimated for 113 head and neck cancer patients by re-calculating plans on repeat CT scans. Uni- and multivariable linear regression analyses were performed to select pre-treatment parameters, and ROC curve analysis was used to determine cut off values, for selecting patients with a PG dose deviation larger than 3 Gy. The patient selection method was validated in a second patient cohort of 43 patients.Results: After multivariable analysis, the planned PG Dmean remained the only significant parameter for PG Delta Dmean. A sensitivity of 91% and 80% could be obtained using a threshold of PG Dmean of 22.2 Gy, for the development and validation cohorts, respectively. This would spare 38% (development cohort) and 24% (validation cohort) of patients from the labour-intensive ART procedure.Conclusions: The presented method to select patients for ART pre-treatment reduces the labour of ART, contributing to a more effective allocation of the department resources. (C) 2016 The Author(s). Published by Elsevier Ireland Ltd.

This article summarises the results of a newly developed technique that utilises Meniscus Arrows(A (R)) for the arthroscopic fixation of displaced tibial spine fractures in children and adolescents.Twelve tibial spine fractures in the knees of eleven children between 6 and 15 years old, with an average age of 12 years, were arthroscopically fixed with Meniscus Arrows(A (R)), after a reduction of their fractures. This was followed by 5 weeks immobilisation in a plaster of Paris. Postoperative follow-up included radiographs, Lachmann tests on all of the children's knees and KT-1000 tests of eight out of twelve of the children's knees. The postoperative follow-up time ranged from 3 to 10 years, with patients being seen for an average of 4 years.All of the fractures consolidated uneventfully, and all of the patients returned unrestricted to their previous activity level. The Lachmann tests revealed no, or a non-functional, laxity in any of the patients' knees. The KT-1000 tests showed a difference between the operated side, and non-operated side, of between 3 mm in the first knee operated on and an average of 1 mm in the remaining knees.The arthroscopic fixation of tibial spine fractures using Meniscus Arrows(A (R)) showed that this minimally invasive procedure resulted in the uneventful consolidation of all twelve of the fractures, with excellent results, and without the need for a second, hardware removal, operation. Level of Evidence: Level IV.