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1.
Clin Genet ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856159

ABSTRACT

Arthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.

2.
Orthop Traumatol Surg Res ; 109(8): 103718, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37865232

ABSTRACT

BACKGROUND: The Pedi-IKDC is an English-language, knee-specific, paediatric questionnaire used by orthopaedic surgeons around the world as a valuable patient-reported outcome measure (PROM). The objective of this study was thus to extend the applicability of the Pedi-IKDC to French-speaking Canadian patients, for both clinical practice and research, by developing a French-language cross-cultural adaptation of the original version. HYPOTHESIS: The French adaptation of the Pedi-IKDC is valid and reliable for evaluating French-speaking children with knee conditions. PATIENTS AND METHODS: The Pedi-IKDC was translated to French by a panel of orthopaedic surgeons then back-translated by a professional translator. The original English version and the back-translation were compared to assess their similarity and confirm the faithfulness of the French translation. The validity of the French version was then tested at a major paediatric hospital in French-speaking Canada, in 203 children, including 163 with knee pain and 40 without knee symptoms. Internal consistency, construct validity, and discriminant capacity of the French version were assessed. RESULTS: Internal consistency of the Pedi-IKDC adaptation was excellent (Cronbach's alpha, 0.934 in the knee-pain group). Construct validity was robust, with all nine hypotheses adapted from the original Pedi-IKDC article demonstrating strong (n=7) or moderate (n=2) correlations (p<0.001). The evaluation of discriminant capacity identified no statistically significant score differences according to most of the respondent characteristics (body mass index, age group, type of diagnosis, and type of treatment). However, scores differed significantly between females and males. DISCUSSION: The French-language cross-cultural adaptation of the Pedi-IKDC obtained using a universally recognized method for translating PROMs demonstrated good performance, with psychometric properties similar to those of the original Pedi-IKDC and of its Danish, Italian, and Russian adaptations. LEVEL OF EVIDENCE: II.


Subject(s)
Cross-Cultural Comparison , Language , Male , Female , Humans , Child , Canada , Surveys and Questionnaires , Pain , Psychometrics , Reproducibility of Results
3.
Vascular ; : 17085381231155669, 2023 Feb 04.
Article in English | MEDLINE | ID: mdl-36738272

ABSTRACT

INTRODUCTION: An infected popliteal pseudoaneurysm has never been described in the pediatric population. Physicians need to be aware of its presentation and management, in order to diagnose and treat this medical condition adequately. METHODS: We describe the case of a 14-year-old boy who developed myositis and cellulitis centered at the popliteal fossa after playing basketball. A treatment of intravenous cefazolin was started. 5 days later, he experienced a knee pain flare-up, which turned out to be a popliteal pyomyositis with a pseudoaneurysm of the popliteal artery. A saphenous vein graft bypass of the popliteal artery and an excision of the popliteal pseudoaneurysm were performed. Intravenous cefazolin was continued for 6 weeks and prophylactic acetylsalicylic acid for 6 months. RESULTS AND CONCLUSION: This case highlighted the importance of repeating radiologic investigations if a patient suffering from soft tissue infection has persistent pain after several days of appropriate antibiotics. A popliteal pseudoaneurysm can be diagnosed with ultrasound imaging and treated with a popliteal-popliteal bypass. Our patient needed a catheter-guided dilation of the anastomosis at the vein graft 6 months post-surgery, and then evolved favorably and went back to playing basketball 6 months post-dilation.

4.
J Child Orthop ; 16(1): 46-54, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35615390

ABSTRACT

Background: Recurrence remains the main challenge in the treatment of clubfoot. The primary goal of this study is to determine if ultrasound measurements are associated with recurrence after successful management with the Ponseti method. Furthermore, other factors are identified which can be associated with recurrence of the deformity. Methods: Seventy-six infants (114 idiopathic clubfeet), all treated with the Ponseti technique were reviewed. All patients had an ultrasound evaluation by the same radiologist at the beginning of the treatment. Recurrence, defined as the need to return to Ponseti casting, was recorded at a mean follow-up of 5 years. Measurements of association with recurrence were obtained for the following ultrasound measures: the medial talonavicular displacement (MTa-N), the medial malleolus to navicular distance (MM-N), the talocalcaneal angle (Ta-C), and the distal tibial physis to proximal calcaneal apophysis distance (Ti-C). Subsequently, a multivariate logistic regression analysis modeling recurrence examined patients' characteristics, compliance, Achilles tenotomy, and ultrasound measurements. Results: Recurrence rate was 22% noted in 17 patients. On univariate analysis, relapse was associated with increased MTa-N (p = 0.038), decreased MM-N (p = 0.008), and decreased Ti-C (p = 0.023). On multivariate analysis, we identified the Ti-C as the only ultrasound measurement significantly associated with recurrence (p = 0.026). Other significant predictors for relapse in this study were noncompliance with orthosis (OR = 139.0 (95% CI: 8.7-2224.0), p < 10-3), and omitting percutaneous Achilles tenotomy in clubfoot treatment (OR = 23.9 (95% CI: 1.2-493.6), p = 0.041). Conclusion: The Ti-C sonographic measurement at the start of treatment can be a useful adjunct to help identify high-risk patients for recurrence of deformity. Non-compliance with bracing and omitting percutaneous Achilles tenotomy are also predictive factors. Level of evidence: Prognostic study, Level III.

5.
Medicine (Baltimore) ; 100(47): e27959, 2021 Nov 24.
Article in English | MEDLINE | ID: mdl-34964784

ABSTRACT

ABSTRACT: The aim was to evaluate the safety of a physeal-sparing anterior cruciate ligament reconstruction technique (ACLR), performed with Orthopediatrics (Warsaw, IN) equipment, by assessing complications.Skeletally immature patients who underwent all-epiphyseal ACLR between 2015 and 2017 with postoperative follow-up were included in this retrospective study. Complications, demographic, clinical, surgical, and imaging data was retrieved from an urban tertiary pediatric hospital database. Physeal status, limb-length discrepancies (LLD), and angular deformities were assessed on preoperative and postoperative radiographs, growth disturbances were reported, and initial and follow-up diameters of tunnels were compared.Nineteen ACLRs were included from 18 patients, 4 females and 14 males, with bone age at surgery of 13.3 ± 1.0 years. At a mean follow-up of 19.2 ±â€Š10.1 months, there were no symptomatic growth disorders requiring intervention. There were: 2 (11.1%) unilateral early physeal closures, 2 (10.5%) new angular deformities (5°-10°), 4 (22.2%) LLD (1-2 cm), 1 (5.6%) contralateral ACLR, 1 (5.6%) femoral screw removal, 2 (10.5%) graft ruptures, and 1 meniscal tear (5.3%). Mean tunnel widening was 1.7 mm and 1.5 mm on the femoral and tibial side, respectively, and no massive osteolysis was recorded at the polyetheretherketone implant site.The complication rates were comparable to those in similar studies, with no growth-related complications at 19.2 months.


Subject(s)
Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction , Anterior Cruciate Ligament/surgery , Epiphyses/surgery , Knee Injuries , Anterior Cruciate Ligament Injuries/diagnostic imaging , Child , Female , Humans , Knee Injuries/surgery , Male , Pediatrics , Postoperative Complications , Retrospective Studies , Treatment Outcome
6.
Comput Biol Med ; 136: 104681, 2021 09.
Article in English | MEDLINE | ID: mdl-34332349

ABSTRACT

Adolescent Idiopathic Scoliosis (AIS) is a deformation of the spine and it is routinely diagnosed using posteroanterior and lateral radiographs. The Risser sign used in skeletal maturity assessment is commonly accepted in AIS patient's management. However, the Risser sign is subject to inter-observer variability and it relies mainly on the observation of ossification on the iliac crests. This study proposes a new machine-learning-based approach for Risser sign skeletal maturity assessment using EOS radiographs. Regions of interest including right and left humeral heads; left and right femoral heads; and pelvis are extracted from the radiographs. First, a total of 24 image features is extracted from EOS radiographs using a ResNet101-type convolutional neural network (CNN), pre-trained from the ImageNet database. Then, a support vector machine (SVM) algorithm is used for the final Risser sign classification. The experimental results demonstrate an overall accuracy of 84%, 78%, and 80% respectively for iliac crests, humeral heads, and femoral heads. Class activation maps using Grad-CAM were also investigated to understand the features of our model. In conclusion, our machine learning approach is promising to incorporate a large number of image features for different regions of interest to improve Risser grading for skeletal maturity. Automatic classification could contribute to the management of AIS patients.


Subject(s)
Scoliosis , Adolescent , Humans , Scoliosis/diagnostic imaging
7.
Mediators Inflamm ; 2020: 6401969, 2020.
Article in English | MEDLINE | ID: mdl-32148442

ABSTRACT

We investigated activation status, cytotoxic potential, and gut homing ability of the peripheral blood Natural Killer (NK) cells in Crohn disease (CD) patients. For this purpose, we compared the expression of different activating and inhibitory receptors (KIR and non-KIR) and integrins on NK cells as well as their recent degranulation history between the patients and age-matched healthy controls. The study was conducted using freshly obtained peripheral blood samples from the study participants. Multiple color flow cytometry was used for these determinations. Our results show that NK cells from treatment-naïve CD patients expressed higher levels of activating KIR as well as other non-KIR activating receptors vis-à-vis healthy controls. They also showed increased frequencies of the cells expressing these receptors. The expression of several KIR and non-KIR inhibitory receptors tended to decrease compared with the cells from healthy donors. NK cells from the patients also expressed increased levels of different gut-homing integrin molecules and showed a history of increased recent degranulation events both constitutively and in response to their in vitro stimulation. Furthermore, treatment of the patients tended to reverse these NK cell changes. Our results demonstrate unequivocally, for the first time, that peripheral blood NK cells in treatment-naïve CD patients are more activated and are more poised to migrate to the gut compared to their counterpart cells from healthy individuals. Moreover, they show that treatment of the patients tends to normalize their NK cells. The results suggest that NK cells are very likely to play a role in the immunopathogenesis of Crohn disease.


Subject(s)
Crohn Disease/metabolism , Killer Cells, Natural/metabolism , Adalimumab/therapeutic use , Adolescent , Azathioprine/therapeutic use , Child , Crohn Disease/immunology , Female , Flow Cytometry , Humans , Infliximab/therapeutic use , Killer Cells, Natural/immunology , Male , Prednisone/therapeutic use , Receptors, KIR/genetics , Receptors, KIR/metabolism , Tumor Necrosis Factor-alpha/metabolism
8.
Radiol Artif Intell ; 2(3): e180063, 2020 May.
Article in English | MEDLINE | ID: mdl-33937822

ABSTRACT

PURPOSE: To develop an automatic method for the assessment of the Risser stage using deep learning that could be used in the management panel of adolescent idiopathic scoliosis (AIS). MATERIALS AND METHODS: In this institutional review board approved-study, a total of 1830 posteroanterior radiographs of patients with AIS (age range, 10-18 years, 70% female) were collected retrospectively and graded manually by six trained readers using the United States Risser staging system. Each radiograph was preprocessed and cropped to include the entire pelvic region. A convolutional neural network was trained to automatically grade conventional radiographs according to the Risser classification. The network was then validated by comparing its accuracy against the interobserver variability of six trained graders from the authors' institution using the Fleiss κ statistical measure. RESULTS: Overall agreement between the six observers was fair, with a κ coefficient of 0.65 for the experienced graders and agreement of 74.5%. The automatic grading method obtained a κ coefficient of 0.72, which is a substantial agreement with the ground truth, and an overall accuracy of 78.0%. CONCLUSION: The high accuracy of the model presented here compared with human readers suggests that this work may provide a new method for standardization of Risser grading. The model could assist physicians with the task, as well as provide additional insights in the assessment of bone maturity based on radiographs.© RSNA, 2020.

9.
J Pediatr Hematol Oncol ; 42(3): 222-227, 2020 04.
Article in English | MEDLINE | ID: mdl-30855315

ABSTRACT

We report 11 children with vertebral lesion of Langerhans cell histiocytosis (LCH) diagnosed and treated between 2000 and 2015. Vertebral lesions were usually present at LCH diagnosis. No child developed neurologic symptoms. Among 29 vertebral lesions, only 2 were unstable. Chemotherapy was used in all children but 3. A LCH recurrence was observed in 6 patients, involving vertebrae in 4 cases. All children were disease-free at their last follow-up. Sequelae were more often radiologic than clinical. Since potential recurrences and incomplete bone regeneration exist, discussion about optimal treatment and long-term follow-up of vertebral lesions are essential.


Subject(s)
Histiocytosis, Langerhans-Cell/complications , Histiocytosis, Langerhans-Cell/pathology , Spinal Diseases/etiology , Spinal Diseases/pathology , Adolescent , Canada , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies
10.
Sci Rep ; 9(1): 10074, 2019 07 11.
Article in English | MEDLINE | ID: mdl-31296888

ABSTRACT

Adolescent idiopathic scoliosis is the most prevalent spine deformity and the molecular mechanisms underlying its pathophysiology remain poorly understood. We have previously found a differential impairment of melatonin receptor signaling in AIS osteoblasts allowing the classification of patients into three biological endophenotypes or functional groups (FG1, FG2 and FG3). Here, we provide evidence that the defect characterizing each endophenotype lies at the level of Gαi proteins leading to a systemic and generalized differential impairment of Gi-coupled receptor signaling. The three Gαi isoforms exhibited a selective serine phosphorylation patterns for each AIS endophenotype resulting in a differential reduction in Gαi protein activity as determined by cellular dielectric spectroscopy and small interfering RNA methods. We found that one endophenotype (FG2) with phosphorylated Gαi1 and Gαi2 was consistently associated with a significantly high risk of spinal deformity progression when compared to the other two endophenotypes (FG1 and FG3). We further demonstrated that each endophenotype is conserved among affected family members. This study expands our understanding of the mechanism underlying the Gi-coupled receptor signaling dysfunction occurring in AIS and provides the first evidence for its hereditary nature. Collectively, our findings offers a new perspective on Gαi hypofunctionality in a human disease by revealing specific serine phosphorylation signatures of Gαi isoforms that may facilitate the identification of AIS patients at risk of spinal deformity progression.


Subject(s)
GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Osteoblasts/metabolism , Receptors, Melatonin/metabolism , Scoliosis/metabolism , Adolescent , Cells, Cultured , Child , Cohort Studies , Disease Progression , Female , GTP-Binding Protein alpha Subunits, Gi-Go/genetics , Humans , Male , Phenotype , Prognosis , Protein Isoforms/genetics , RNA, Small Interfering/genetics , Risk , Scoliosis/genetics , Signal Transduction
11.
Eur Spine J ; 28(6): 1342-1348, 2019 06.
Article in English | MEDLINE | ID: mdl-30848365

ABSTRACT

PURPOSE: The aim of this study was to evaluate the factors associated with timing of lowest hemoglobin (Hb) level and the need for postoperative blood transfusion in posterior spinal fusion for adolescent idiopathic scoliosis. METHODS: We conducted a retrospective review of all adolescent scoliosis patients undergoing posterior spinal fusion at our institution, 2002-2014. Surgery consisted of segmental pedicle screw fixation using multi-level pedicle screws. Blood-saving techniques were used in all patients. Data included Cobb angle, pre- and postoperative Hb levels, preoperative autologous blood donation (PABD), surgery duration, and allogeneic or autologous transfusion. We used linear and logistic regressions for statistical analysis. RESULTS: There were 456 patients (402 female, 54 male), mean age 16 ± 5 years. Lowest Hb was observed on postoperative Days 2 (32.2%) and 3 (33.3%); 45.1% of postoperative transfusions occurred on Day 2. One hundred and eighty-eight (41%) patients who provided PABD had significantly lower preoperative Hb and received more transfusions intraoperatively (22.6% vs. 5.2%) and postoperatively (20% vs. 6.3%) than others. Probability of transfusion increased 49.6 (95% CI 17.40-141.37) times with preoperative Hb < 11 g/dL as compared to preoperative Hb > 14 g/dL. Probability of transfusion increased 4.3- and 9.8-fold when surgery duration exceeded 5 and 6 h, respectively. Probability of transfusion increased 3.3- and 5.3-fold with Cobb angle > 70° and 80°, respectively. CONCLUSIONS: We identified clear patient-specific perioperative parameters that affect risk of perioperative blood transfusion, including Cobb angle, PABD and preoperative Hb. Hb measurement beyond postoperative Day 3 is considered unnecessary unless clinically indicated. These slides can be retrieved under Electronic Supplementary Material.


Subject(s)
Blood Loss, Surgical , Blood Transfusion/statistics & numerical data , Hemoglobins/metabolism , Scoliosis/surgery , Spinal Fusion/adverse effects , Adolescent , Adult , Child , Female , Humans , Kyphosis/surgery , Logistic Models , Male , Pedicle Screws , Perioperative Care/methods , Postoperative Period , Retrospective Studies , Spinal Fusion/instrumentation , Spinal Fusion/methods , Young Adult
12.
Sci Rep ; 9(1): 4268, 2019 03 12.
Article in English | MEDLINE | ID: mdl-30862935

ABSTRACT

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in children. With the use of more modern, efficient treatments, 5-year survival has reached more than 90% in this population. However, this achievement comes with many secondary and long-term effects since more than 65% of the survivors experience at least one severe complication, including the metabolic syndrome and cardiovascular diseases. The main objective of the present work was to characterize the composition of HDL particles isolated from pediatric ALL survivors. HDLs from 8 metabolically healthy ALL survivors, 8 metabolically unhealthy ALL survivors and 8 age- and gender-matched controls were analyzed. The HDL fraction from the survivors contained less cholesterol than the controls. In addition, proteomic analyses revealed an enrichment of pro-thrombotic (e.g., fibrinogen) and pro-inflammatory (e.g., amyloid A) proteins in the HDLs deriving from metabolically unhealthy survivors. These results indicate an alteration in the composition of lipid and protein content of HDL from childhood ALL survivors with metabolic disorders. Although more work is needed to validate the functionality of these HDLs, the data seem relevant for survivor health given the detection of potential biomarkers related to HDL metabolism and functionality in cancer.


Subject(s)
Cancer Survivors , Cardiovascular Diseases/metabolism , Lipoproteins, HDL/metabolism , Metabolic Syndrome/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Adult , Biomarkers , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Female , Humans , Lipid Metabolism , Lipoproteins, HDL/blood , Male , Metabolic Syndrome/blood , Metabolic Syndrome/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Proteomics , Young Adult
13.
J Orthop Res ; 37(3): 727-736, 2019 03.
Article in English | MEDLINE | ID: mdl-30756421

ABSTRACT

In absence of school scoliosis screening programs (SSSP) in Canada, this study examined the relationships between the lay person's perception of morbidity and the appropriateness of referral in orthopedics. A cross-sectional study was conducted with all children consecutively referred in orthopedics for suspected scoliosis. The 831 participants were classified as Appropriate, Late, or Inappropriate referrals for the orthopedic setting. Perceived morbidity was operationalized by: the scoliosis detection originator, the perceptions of the seriousness of the condition and urgency to consult a physician, the perception of the general health, as well as Visible Back Deformity, Self-image, and Pain. Direct associations between the perceived morbidity and the appropriateness of referral were found in all scoliosis-specific measures; the most discriminant variable was Visible Back Deformity. Lay perceived morbidity is a good indicator of the objective morbidity, and thus reflects in the appropriateness of referral status. The important role of the lay persons in symptoms appraisal does not however insure appropriate referral. Searching for alternatives to SSSP would wisely include a health promotion and medical management program. Statement of Clinical Significance: Perceived morbidity by the lay persons is strongly associated with the objectively evaluated severity of scoliosis deformity. Therefore, in absence of SSSP, lay person awareness plays an important role in symptom recognition and search for care. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.


Subject(s)
Referral and Consultation/statistics & numerical data , Scoliosis/psychology , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male , Referral and Consultation/standards
14.
Knee Surg Sports Traumatol Arthrosc ; 27(7): 2361-2367, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30465095

ABSTRACT

PURPOSE: The Knee Injury Osteoarthritis Outcome Score (KOOS) questionnaire is one of the frequently used outcome scores in pediatric studies. However, a recent study demonstrated that the pediatric population had a limited understanding of some of its questions. Therefore, the KOOS-Child questionnaire was developed specifically for this population. Our team produced a French adaptation based on the English version. The objective of the current study was to validate the French adaptation of the KOOS-Child questionnaire. METHODS: After ethic board approval, the questionnaire was translated from English to French by two French speaking orthopedic surgeons. Following consensus, the translated version was retranslated to English by a professional translator. A group of experts compared the original and back translated version and decided on a final adapted questionnaire version. Ninety-nine 8-16 year-old patients were prospectively recruited from our pediatric orthopedic surgery clinic. Twenty-one control participants and 78 patients suffering from knee pain were recruited. The participants were asked to answer the translated French version of the KOOS-Child questionnaire and two validated French pediatric quality of life surveys. RESULTS: Statistical analysis demonstrated no statistically significant demographic difference between the control population and the patients suffering from a knee pathology. The mean for the five different domains of the KOOS-Child questionnaire showed statistical differences (p < 0.001) between the two groups. Construct validity was demonstrated through testing of previously validated hypothesis of correlation. Internal consistency was also confirmed in injured patients. CONCLUSIONS: In conclusion, the current study results demonstrate good to excellent internal consistency, good construct validity and inconclusive discriminant capacity of the French adaptation of the KOOS-Child questionnaire. LEVEL OF EVIDENCE: II.


Subject(s)
Knee Injuries/psychology , Pain/diagnosis , Patient Reported Outcome Measures , Surveys and Questionnaires , Adolescent , Child , Female , Humans , Male , Orthopedics , Pain/etiology , Pain/psychology , Quality of Life , Reproducibility of Results , Translations
15.
Metabolism ; 85: 151-160, 2018 08.
Article in English | MEDLINE | ID: mdl-29563052

ABSTRACT

BACKGROUND: Childhood acute lymphoblastic leukemia (cALL) is the most prevalent form of cancer in children. Due to advances in treatment and therapy, young cALL subjects now achieve a 90% survival rate. However, this tremendous advance does not come without consequence since ~2/3 of cALL survivors are affected by long-term and late, severe complications. Although the metabolic syndrome is a very serious sequel of cALL, the mechanisms remain undefined. It is also surprising to note that the mitochondrion, a central organelle in metabolic functions and the main cellular energy generator, have not yet been explored. OBJECTIVES: To determine whether cALL survivors exhibit impairments in their mitochondrial functions and proteomic profiling in relationship with metabolic disorders in cALL survivors compared to healthy controls. METHODS AND RESULTS: Anthropometric measures, metabolic characteristics and lipid profiles were assessed, mitochondria isolated from peripheral blood mononuclear cells, and proteomic analyzed. Our data demonstrated that metabolically. Unhealthy survivors exhibited several metabolic syndrome components (e.g. overweight, insulin resistance, dyslipidemia, inflammation) whereas Healthy cALL survivors resemble the Controls. In line with these abnormalities, functional experiments in these subjects revealed a significant decrease in the protein expression of mitochondrial antioxidant superoxide dismutase, PGC1-α transcription factor (a key modulator of mitochondrion biogenesis), and an increase in pro-apoptotic cytochrome c. Proteomic analysis of mitochondria by mass spectrometry revealed changes in the regulation of proteins related to inflammation, apoptosis, energy production, redox and antioxidant activity, fatty acid ß-oxidation, protein transport and metabolism, and signalling pathways between groups. CONCLUSIONS: Through the use of proteomic analysis, our work demonstrated a number of significant alterations in protein expression in mitochondria of cALL survivors, especially the metabolically Unhealthy survivor group. Further investigation of these proteins may help delineate the mechanisms by which mitochondrial dysfunctions exert cardiometabolic derangements in cALL survivors.


Subject(s)
Cancer Survivors , Cardiovascular Diseases/metabolism , Metabolic Diseases/metabolism , Metabolic Syndrome/metabolism , Mitochondria/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Adult , Female , Humans , Leukocytes, Mononuclear/metabolism , Male , Proteomics , Young Adult
16.
CMAJ ; 189(35): E1107-E1111, 2017 Sep 05.
Article in English | MEDLINE | ID: mdl-28874431

ABSTRACT

BACKGROUND: Kingella kingae has been increasingly identified in patients with osteoarticular infections. Our main objective was to evaluate the association between carriage of K. kingae in the oropharynx of preschool children and osteoarticular infections. METHODS: We conducted this prospective case-control study in 2 tertiary care pediatric hospitals (Canada and Switzerland) between 2014 and 2016. Potential cases were children aged 6 to 48 months with a presumptive diagnosis of osteoarticular infection according to the treating emergency physician. Confirmed cases were those with diagnosis of osteomyelitis or septic arthritis proven by positive findings on technetium-labelled bone scan or magnetic resonance imaging or identification of a microorganism in joint aspirate or blood. For each case, we recruited 4 age-matched controls from among children presenting to the same emergency department for trauma. The independent variable was presence of oropharyngeal K. kingae DNA identified by a specific polymerase chain reaction assay. We determined the association between oropharyngeal carriage of K. kingae and definitive osteoarticular infection. RESULTS: The parents of 77 children admitted for suspected osteoarticular infection and 286 controls were invited to participate and provided informed consent. We identified K. kingae in the oropharynx of 46 (71%) of 65 confirmed cases and 17 (6%) of 286 controls; these results yielded an odds ratio of 38.3 (95% confidence interval 18.5-79.1). INTERPRETATION: Detection of oropharyngeal K. kingae was strongly associated with osteoarticular infection among children presenting with symptoms suggestive of such infection.


Subject(s)
Arthritis, Infectious/microbiology , Carrier State/microbiology , Kingella kingae/isolation & purification , Neisseriaceae Infections/diagnosis , Neisseriaceae Infections/epidemiology , Osteomyelitis/microbiology , Arthritis, Infectious/diagnostic imaging , Canada , Case-Control Studies , Child, Preschool , Female , Hospitals, Pediatric , Humans , Infant , Magnetic Resonance Imaging , Male , Odds Ratio , Oropharynx/microbiology , Osteomyelitis/diagnostic imaging , Polymerase Chain Reaction , Prospective Studies , Switzerland
17.
J Lipid Res ; 58(5): 982-993, 2017 05.
Article in English | MEDLINE | ID: mdl-28274961

ABSTRACT

Survivors of acute lymphoblastic leukemia (ALL), the most common cancer in children, are at increased risk of developing late cardiometabolic conditions. However, the mechanisms are not fully understood. This study aimed to characterize the plasma lipid profile, Apo distribution, and lipoprotein composition of 80 childhood ALL survivors compared with 22 healthy controls. Our results show that, despite their young age, 50% of the ALL survivors displayed dyslipidemia, characterized by increased plasma triglyceride (TG) and LDL-cholesterol, as well as decreased HDL-cholesterol. ALL survivors exhibited lower plasma Apo A-I and higher Apo B-100 and C-II levels, along with elevated Apo C-II/C-III and B-100/A-I ratios. VLDL fractions of dyslipidemic ALL survivors contained more TG, free cholesterol, and phospholipid moieties, but less protein. Differences in Apo content were found between ALL survivors and controls for all lipoprotein fractions except HDL3 HDL2, especially, showed reduced Apo A-I and raised Apo A-II, leading to a depressed Apo A-I/A-II ratio. Analysis of VLDL-Apo Cs disclosed a trend for higher Apo C-III1 content in dyslipidemic ALL survivors. In conclusion, this thorough investigation demonstrates a high prevalence of dyslipidemia in ALL survivors, while highlighting significant abnormalities in their plasma lipid profile and lipoprotein composition. Special attention must, therefore, be paid to these subjects given the atherosclerotic potency of lipid and lipoprotein disorders.


Subject(s)
Cancer Survivors , Lipoproteins/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Apolipoproteins E/blood , Apolipoproteins E/genetics , Dyslipidemias/complications , Female , Humans , Lipoprotein Lipase/genetics , Lipoproteins/blood , Lipoproteins/genetics , Male , Polymorphism, Genetic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Receptors, LDL/genetics , Young Adult
18.
Pediatr Radiol ; 46(2): 193-209; quiz 190-2, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26459012

ABSTRACT

Foot deformity in infants is the most common congenital musculoskeletal condition. A precise diagnosis can sometimes be impossible to establish clinically. Radiologic imaging plays a major role in the evaluation of musculoskeletal abnormalities. However conventional imaging techniques, such as plain radiographs of the foot, are of very little help in this age group because of the lack of ossification of the tarsal bones. US presents a significant advantage because it permits the visualization of cartilaginous structures. This leads to the detailed assessment of foot deformities in infants. Furthermore, US can also be used as a dynamic imaging modality. Different scanning views are beneficial to evaluate the complete anatomy of the foot; depending on the suspected clinical diagnosis, some planes are more informative to display the pathological features of a specific deformity. We describe the US findings of five of the most common foot deformities referred to our pediatric orthopedic clinic (clubfoot, simple metatarsus adductus, skewfoot, and oblique and vertical talus). For each deformity we propose a specific imaging protocol based on US to provide an accurate diagnosis. US is a complementary tool to the clinical examination for determining the diagnosis and the severity of the deformity and also for monitoring the efficacy of treatment. Radiologists investigating foot deformities in infants should consider using US for the detailed assessment of the foot in this age group.


Subject(s)
Foot Deformities, Congenital/diagnostic imaging , Foot/diagnostic imaging , Image Enhancement/methods , Patient Positioning/methods , Ultrasonography/methods , Diagnosis, Differential , Female , Humans , Infant , Infant, Newborn , Male
19.
J Orthop Res ; 34(2): 290-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26213189

ABSTRACT

Fusionless implants are used to correct pediatric progressive spinal deformities, most of them spanning the intervertebral disc. This study aimed at investigating the effects of in vivo static versus dynamic compression application and removal on discs of growing rats. A microloading device applied compression. 48 immature rats (28 d.o.) were divided into two groups (43d, 53d). Each group included four subgroups: control (no surgery), sham (device installed without loading), static (0.2 MPa) and dynamic compressions (0.2 MPa ± 30% with 0.1 Hz). In 43d subgroups, compression was applied for 15 days. In 53d subgroups, compression was followed by 10 days without loading. Disc heights, nucleus/annulus volumetric proportions and nucleus proteoglycan contents were analyzed using one-way ANOVA and post-hoc Tukey comparisons (p < 0.05). Disc heights of 43d and 53d static and dynamic loading rats were lower than shams (p < 0.05). Volumetric proportions remained similar. At 43d, nucleus proteoglycan contents increased in both static and dynamic loading rats. However, at 53d, static loading rats had lower proteoglycan content than dynamic loading rats (p < 0.05). Disc structure is altered following static compression removal, but nucleus proteoglycan content remaining elevated in dynamic group. Dynamic fusionless implants would better preserve disc integrity.


Subject(s)
Intervertebral Disc/physiology , Spinal Diseases/surgery , Animals , Male , Prostheses and Implants , Proteoglycans/metabolism , Rats, Sprague-Dawley , Stress, Mechanical , Weight-Bearing
20.
Bone ; 81: 662-668, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26416149

ABSTRACT

Mechanical loadings influence bone growth and are used in pediatric treatments of musculoskeletal deformities. This in vivo study aimed at evaluating the effects of static and dynamic compression application and subsequent removal on bone growth, mineralization and neuropathic pain markers in growing rats. Forty-eight immature rats (28 days old) were assigned in two groups (2- and 4 weeks experiment duration) and four subgroups: control, sham, static, and dynamic. Controls had no surgery. A micro-loading device was implanted on the 6th and 8th caudal vertebrae of shams without loading, static loading at 0.2 MPa or dynamic loading at 0.2 MPa ± 30% and 0.1 Hz. In 2-week subgroups, compression was maintained for 15 days prior to euthanasia, while in 4- week subgroups, compression was removed for 10 additional days. Growth rates, histomorphometric parameters and mineralization intensity were quantified and compared. At 2 weeks, growth rates and growth plate heights of loaded groups (static/dynamic)were significantly lower than shams (p b 0.01).However, at 4 weeks, both growth rates and growth plate heights of loaded groups were similar to shams. At 4 weeks, alizarin red intensity was significantly higher in dynamics compared to shams (p b 0.05) and controls (p b 0.01). Both static and dynamic compressions enable growth resumption after loading removal, while preserving growth plate histomorphometric integrity. However, mineralization was enhanced after dynamic loading removal only. Dynamic loading showed promising results for fusionless treatment approaches for musculoskeletal deformities.


Subject(s)
Bone Development/physiology , Weight-Bearing/physiology , Animals , Biomechanical Phenomena , Bone Density/physiology , Male , Rats , Rats, Sprague-Dawley , Stress, Mechanical
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