Physical impairments, activity limitations, and participation restrictions of childhood acute lymphoblastic leukemia survivors with and without hip osteonecrosis: a PETALE cohort study.

PURPOSE: Long-term musculoskeletal complications represent a growing burden for survivors of childhood acute lymphoblastic leukemia (cALL). This study aimed to describe physical impairments, activity limitations, and participation restrictions in a high-risk subgroup of cALL survivors of the PETALE cohort. METHODS: This cross-sectional study, using observational data from the PETALE cohort, included a subgroup of survivors who presented high-risk criteria for late effects. Outcomes measures consisted of hip magnetic resonance imaging, maximal isometric muscle strength (MIMS) or torque (MIMT), range of motion (ROM), Near Tandem Balance (NTB), 6-Minute Walk Test (6MWT), Five Time Sit-to-Stand Test (FTSST), and health-related quality of life. Descriptive statistics and regression analyses were performed. RESULTS: Survivors (n = 97, 24.2 ± 6.7 years old) showed limited grip strength, FTSST, and NTB performance compared to reference values (p < 0.001). Thirteen participants (14.6%, 18 hips) had hip osteonecrosis (ON) (53.8% male). Higher severity hip ON was found in female survivors (66.7% vs. 22.2%). Survivors with hip ON had reduced hip external rotation ROM compared to those without (p < 0.05). Relationships were found between MIMS and ROM outcomes (r = 0.32, p < 0.01) and with 6MWT (r = 0.39-0.41, p < 0.001). Our multiple linear regression model explained 27.6% of the variance of the 6MWT. CONCLUSIONS: Survivors in our subgroup had clinically significant physical impairments and activity limitations, and those with hip ON showed worst hip impairment outcomes. IMPLICATIONS FOR CANCER SURVIVORS: These findings emphasize the importance of long-term follow-up including physical therapy assessment to help early identification and management of physical impairments and activity limitations in survivors of cALL.

Effects of polyphenol supplementation on hepatic steatosis, intima-media thickness and non-invasive vascular elastography in obese adolescents: a pilot study protocol.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible. METHODS AND ANALYSIS: This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12-18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study's feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome. ETHICS AND DISSEMINATION: This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. CLINICALTRIALS: gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023. TRIAL REGISTRATION NUMBER: NCT03994029.

Development of a semi-automatic segmentation technique based on mean magnetic resonance imaging intensity thresholding for volumetric quantification of plexiform neurofibromas.

Rationale and objectives: Plexiform neurofibromas (PNs) are peripheral nerve tumors that occur in 25-50 % of patients with neurofibromatosis type 1. PNs may have complex, diffused, and irregular shapes. The objective of this work was to develop a volumetric quantification method for PNs as clinical assessment is currently based on unidimensional measurement. Materials and methods: A semi-automatic segmentation technique based on mean magnetic resonance imaging (MRI) intensity thresholding (SSTMean) was developed and compared to a similar and previously published technique based on minimum image intensity thresholding (SSTMini). The performance (volume and computation time) of the two techniques was compared to manual tracings of 15 tumors of different locations, shapes, and sizes. Performance was also assessed using different MRI sequences. Reproducibility was assessed by inter-observer analysis. Results: When compared to manual tracing, quantification performed with SSTMean was not significantly different (mean difference: 1.2 %), while volumes computed by SSTMini were significantly different (p < .0001, mean difference: 13.4 %). Volumes quantified by SSTMean were also significantly different than the ones assessed by SSTMini (p < .0001). Using SSTMean, volumes quantified with short TI inversion recovery, T1-, and T2-weighted imaging were not significantly different. Computation times used by SSTMean and SSTMini were significantly lower than for manual segmentation (p < .0001). The highest difference measured by two users was 8 cm3. Conclusion: Our method showed accuracy compared to a current gold standard (manual tracing) and reproducibility between users. The refined segmentation threshold and the possibility to define multiple regions-of-interest to initiate segmentation may have contributed to its performance. The versatility and speed of our method may prove useful to better monitor volumetric changes in lesions of patients enrolled in clinical trials to assessing response to therapy.

Case report: Success of allogeneic hematopoietic stem cell transplantation for refractory systemic-onset juvenile idiopathic arthritis.

Objectives: This study reports cases of systemic-onset juvenile idiopathic arthritis (sJIA) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center and reviews published outcomes of allo-HSCT in sJIA. Methods: We present a case report of two patients with sJIA who underwent allo-HSCT at a tertiary pediatric hospital. Each patient's disease course and allo-HSCT protocol/outcome are described. Outcomes of published cases of allo-HSCT in sJIA were compared to our experience. Results: Two patients with sJIA had allo-HSCT. Both failed multiple lines of disease-modifying anti-rheumatic drugs and experienced severe disease/treatment-related complications. Despite post-HSCT complications, both recovered without sequelae. Five years post-HSCT, patient 1 is in complete remission (CR) and is off medications. Patient 2 was in CR until 11 months post-HSCT after which he developed three disease flares. At 4 years post-HSCT he is currently in CR on Adalimumab monotherapy. Engraftment was excellent with a donor chimerism of 100% for patient 1 and 93% for patient 2. In the literature, the outcome of allo-HSCT is reported in 13 sJIA patients. When merging those with our 2 patients, 1/15 patients died and 13/14 achieved CR, of which 12 are off medications (median [range] follow-up: 2.2 [0.2-7.0] years). Extended follow-up data on 11 of the 13 reported sJIA patients showed that an additional 3 patients flared at 3, 4, and 10 years post-HSCT. Conclusion: We report two patients with severe/refractory sJIA who underwent successful allo-HSCT and achieved CR. Allo-HSCT is a potential curative option for severe/refractory sJIA. It should be considered only after failure of conventional sJIA treatments and when an HLA-matched donor is available in order to lower transplant-related mortality. The outcomes of reported sJIA patients who received allo-HSCT are encouraging but long-term follow-up data are needed to better characterized the risk-benefit ratio of this procedure.

Plasma copeptin is increased and associated with smaller kidney volume in young adults born very preterm.

Background: Plasma copeptin, a surrogate marker for vasopressin levels, is increased in neonates born preterm, particularly in those with a more severe neonatal course, as reflected by bronchopulmonary dysplasia. Copeptin levels in adulthood are unknown. Methods: In this case-control study of 101 adults born very preterm (<30 weeks of gestation) and 105 control adults born full-term, a comprehensive clinical and biological assessment was performed, including blood pressure measurements, kidney ultrasound and determination of plasma copeptin, renin activity, angiotensin II, aldosterone, apelin, sodium and potassium, serum and morning urine osmolality. Results: The median age in the study was 23.1 years [interquartile range (IQR) 21.2-24.8] and 57% were females. In males, the median copeptin levels were 8.2 pmol/L (IQR 6.3-12.4) and 6.1 pmol/L (IQR 4.3-9.0) in the preterm and term groups, respectively (P = 0.022). In females, the median copeptin levels were 5.2 pmol/L (IQR 3.9-7.6) and 4.0 pmol/L (IQR 2.8-5.7) in the preterm and term groups, respectively (P = 0.005). Adults born preterm with a history of bronchopulmonary dysplasia had further increased copeptin levels. The kidney volume, adjusted for height, was smaller and albuminuria was higher in the preterm group, and both were associated with higher plasma copeptin levels. Conclusions: Plasma copeptin is higher in young adults born preterm and is related to a more severe neonatal course and smaller kidney volume.

Current applications for measuring pediatric intima-media thickness.

Intima-media thickness is a known subclinical radiologic marker of the early manifestations of atherosclerotic disease. It is the thickness of the vessel wall, most often the carotid artery. Intima-media thickness is measured on conventional US manually or automatically. Other measurement techniques include radiofrequency US. Because there is variation in its measurement, especially in children, several recommendations have been set to increase the measurement's validity and comparability among studies. Despite these recommendations, several pitfalls should be avoided, and quality control should be performed to avoid erroneous interpretation. This article summarizes current literature in relation to the clinical applications for intima-media thickness measurement in children with known risk factors such as obesity, liver steatosis, hypercholesterolemia, diabetes, hypertension, systemic inflammatory diseases, cancer survival, kidney and liver transplant, and sickle cell disease or beta thalassemia major. Most potential indications for intima-media thickness measurement remain in the research domain and should be interpreted combined with other markers. The objective of diagnosing an increased intima-media thickness is to start a multidisciplinary treatment approach to prevent disease progression and its sequelae in adulthood.

Velopharyngeal Space Assessment in Patients Undergoing Le Fort 1 Maxillary Advancement.

The effects of maxillary advancement on velopharyngeal anatomy have primarily been studied using lateral cephalometric radiographs. However, with recent advances in orthognathic surgery, there is an increased need for more detailed and precise imaging such as computerized tomographic (CT) scan reconstructions, to help in surgical planning and to measure outcomes. The purpose of this study was to compare the pre- and post-operative velopharyngeal anatomic configuration modifications as measured on CT scans. METHODS: This is a retrospective cohort study of 44 patients with and without cleft palate who were treated with maxillary advancement. The pre- and post-operative CT scans were compared with respect to pre-established landmarks. Linear distances, cross-sectional areas, and volumes were measured using 3-dimensional CT scan reconstructions. RESULTS: For the linear distances measured, a statistically significant difference was found when comparing the pre- and post-operative measures of the narrowest part of the nasopharynx and the narrowest part of the retropalatal airway space (P = 0.001 and 0.026, respectively). Retropalatal cross-sectional areas, nasopharyngeal cross-sectional areas, and the volumetric assessment of the nasopharyngeal space showed no statistically significant differences when comparing pre- and post-operative scans (P < 0.05). Mean changes in the measures did not differ over time (pre- and post-operative) depending on whether there was a prior history of cleft palate repair. CONCLUSIONS: Although structural modifications of the pharyngeal space are inherent to maxillary advancement, its surface area and volume do not significantly change. The use of 3-dimensional reconstruction using CT scans should be the first choice for evaluation of the upper airway.

Arterial Structure and Stiffness Are Altered in Young Adults Born Preterm.

OBJECTIVE: Preterm birth has been associated with changes in arterial structure and function. Association with complications occurring during the neonatal period, including bronchopulmonary dysplasia, on vascular outcomes in adulthood is unknown. Approach and Results: We evaluated a cohort of 86 adults born preterm (below 30 weeks of gestation), compared to 85 adults born term, at a mean age of 23 years. We performed ultrasonographic assessment of the dimensions of the ascending aorta, carotid and brachial arteries, and estimated flow-mediated dilation, carotid-femoral pulse wave velocity, augmentation index corrected for heart rate, and carotid intima-media thickness. All analyses were performed with and without adjustment for potential confounding variables, including height, sex, and body mass index. Ascending aorta diameter in diastole was smaller in the preterm group, but carotid and brachial arteries were similar. Carotid and brachial strain, a marker of arterial distensibility, was smaller in the preterm group, while carotid-femoral pulse wave velocity, was similar between groups, indicating similar aortic stiffness. Carotid intima-media thickness, endothelial function flow-mediated dilation, blood nitrite, and nitrate levels were similar between groups. Individuals with bronchopulmonary dysplasia had lower brachial artery strain suggesting long-term association of this neonatal complication with vascular structure. Diastolic blood pressure was higher in the preterm group and was associated with decreased brachial and carotid distensibility. CONCLUSIONS: Young adults born preterm display alterations in arterial distensibility that are associated with a history of bronchopulmonary dysplasia.