Actualisation 2023 des lignes directrices de pratique clinique pour la prise en charge de l'ostéoporose et la prévention des fractures au Canada.

CONTEXTE: Au Canada, plus de 2 millions de personnes vivent avec l'ostéoporose, une maladie qui accroît le risque de fracture, ce qui fait augmenter la morbidité et la mortalité, et entraîne une perte de qualité de vie et d'autonomie. La présente actualisation des lignes directrices vise à accompagner les professionnelles et professionnels de la santé au Canada dans la prestation de soins visant à optimiser la santé osseuse et à prévenir les fractures chez les femmes ménopausées et les hommes de 50 ans et plus. MÉTHODES: Le présent document fournit une actualisation des lignes directrices de pratique clinique de 2010 d'Ostéoporose Canada sur le diagnostic et la prise en charge de l'ostéoporose au pays. Nous avons utilisé l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) et effectué l'assurance de la qualité conformément aux normes de qualité et de présentation des rapports de la grille AGREE II (Appraisal of Guidelines for Research & Evaluation). Les médecins de premier recours et les patientes et patients partenaires ont été représentés à tous les niveaux des comités et des groupes ayant participé à l'élaboration des lignes directrices, et ont participé à toutes les étapes du processus pour garantir la pertinence des informations pour les futurs utilisateurs et utilisatrices. Le processus de gestion des intérêts concurrents a été entamé avant l'élaboration des lignes directrices et s'est poursuivi sur toute sa durée, selon les principes du Réseau international en matière de lignes directrices. Dans la formulation des recommandations, nous avons tenu compte des avantages et des risques, des valeurs et préférences de la patientèle, des ressources, de l'équité, de l'acceptabilité et de la faisabilité; la force de chacune des recommandations a été déterminée en fonction du cadre GRADE. RECOMMANDATIONS: Les 25 recommandations et les 10 énoncés de bonne pratique sont répartis en sections : activité physique, alimentation, évaluation du risque de fracture, instauration du traitement, interventions pharmacologiques, durée et séquence du traitement, et monitorage. La prise en charge de l'ostéoporose devrait se fonder sur le risque de fracture, établi au moyen d'une évaluation clinique réalisée avec un outil d'évaluation du risque de fracture validé. L'activité physique, l'alimentation et la pharmacothérapie sont des éléments essentiels à la stratégie de prévention des fractures, qui devraient être personnalisés. INTERPRÉTATION: Les présentes lignes directrices ont pour but d'outiller les professionnelles et professionnels de la santé et la patientèle afin qu'ensemble ils puissent parler de l'importance de la santé osseuse et du risque de fracture tout au long de la vie adulte avancée. La détection et la prise en charge efficace de la fragilité osseuse peuvent contribuer à réduire les fractures et à préserver la mobilité, l'autonomie et la qualité de vie.

Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update.

BACKGROUND: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. METHODS: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. RECOMMENDATIONS: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. INTERPRETATION: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

No difference in cerebral perfusion between the wild-type and the 5XFAD mouse model of Alzheimer's disease.

Neuroimaging with [2,2-dimethyl-3-[(2R,3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(2R,3E)-3-hydroxyiminobutan-2-yl]azanide;oxo(99Tc)technetium-99(3+) ([99mTc]HMPAO) single photon emission computed tomography (SPECT) is used in Alzheimer's disease (AD) to evaluate regional cerebral blood flow (rCBF). Hypoperfusion in select temporoparietal regions has been observed in human AD. However, it is unknown whether AD hypoperfusion signatures are also present in the 5XFAD mouse model. The current study was undertaken to compare baseline brain perfusion between 5XFAD and wild-type (WT) mice using [99mTc]HMPAO SPECT and determine whether hypoperfusion is recapitulated in 5XFAD mice. 5XFAD and WT mice underwent a 45 min SPECT scan, 20 min after [99mTc]HMPAO administration. Whole brain and regional standardized uptake values (SUV) and regional relative standardized uptake values (SUVR) with whole brain reference were compared between groups. Brain perfusion was similar between WT and 5XFAD brains. Whole brain [99mTc]HMPAO retention revealed no significant difference in SUV (5XFAD, 0.372 ± 0.762; WT, 0.640 ± 0.955; p = 0.536). Similarly, regional analysis revealed no significant differences in [99mTc]HMPAO metrics between groups (SUV: 0.357 ≤ p ≤ 0.640; SUVR: 0.595 ≤ p ≤ 0.936). These results suggest apparent discrepancies in rCBF between human AD and the 5XFAD model. Establishing baseline perfusion patterns in 5XFAD mice is essential to inform pre-clinical diagnostic and therapeutic drug discovery programs.

Intra-individual comparison of 18F-sodium fluoride PET-CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial.

BACKGROUND: Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) and 18F-sodium fluoride (18F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer. METHODS: MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada. Patients aged 18 years or older with breast or prostate cancer with a WHO performance status of 0-2 and with high risk or clinical suspicion for bone metastasis, but without previously documented bone involvement, were eligible. 18F-NaF PET-CT and 99mTc-MDP SPECT were done within 14 days of each other for each participant. Two independent reviewers interpreted each modality without knowledge of other imaging findings. The primary endpoint was the overall accuracy of 99mTc-MDP SPECT and 18F-NaF PET-CT scans for the detection of bone metastases in the per-protocol population. A combination of histopathological, clinical, and imaging follow-up for up to 24 months was used as the reference standard to assess the imaging results. Safety was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT01930812, and is complete. FINDINGS: Between July 11, 2014, and March 3, 2017, 290 patients were screened, 288 of whom were enrolled (64 participants with breast cancer and 224 with prostate cancer). 261 participants underwent both 18F-NaF PET-CT and 99mTc-MDP SPECT and completed the required follow-up for statistical analysis. Median follow-up was 735 days (IQR 727-750). Based on the reference methods used, 109 (42%) of 261 patients had bone metastases. In the patient-based analysis, 18F-NaF PET-CT was more accurate than 99mTc-MDP SPECT (84·3% [95% CI 79·9-88·7] vs 77·4% [72·3-82·5], difference 6·9% [95% CI 1·3-12·5]; p=0·016). No adverse events were reported for the 288 patients recruited. INTERPRETATION: 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice in patients with high-risk prostate or breast cancer. FUNDING: Canadian Institutes of Health Research.

The Pathogenesis and Clinical Management of Cutaneous Melanoma: An Evidence-Based Review.

Cutaneous malignant melanoma (CM) is the leading cause of skin cancer-related mortality and accounts for approximately 1,250 deaths in Canada each year. It is also one of few cancers continuing to display rates of increasing incidence throughout the world. The past decade has brought significant growth in our understanding of the pathogenesis and clinical management of CM. This evidence-based review synthesizes that knowledge, beginning with a review of the epidemiology and etiology of the disease followed by a broad review of the roles of diagnostic imaging in its management. Special attention is given to the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) in supporting assessment at primary presentation of disease, follow-up to surgical and nonsurgical treatment, and for the surveillance of high-risk asymptomatic patients. After a brief review of current treatment options, this article concludes with a demonstration of how and when uncertainty exists at the point of care systematic review processes may be used to resolve clinical questions. Learning Objectives: By the end of this Continuing Medical Education article, participants will be able to 1. Describe the epidemiology and etiology of cutaneous melanoma, 2. Describe broadly the role of diagnostic imaging in the clinical management of cutaneous melanoma, 3. Describe the specific roles and limitations of 18F-FDG PET/CT in the clinical management of cutaneous melanoma, 4. Describe broadly the best practice in the treatment of cutaneous melanoma, 5. Define the value of systematic review for synthesizing knowledge pertaining to a specific clinical question, and 6. Discuss the utility of 18F FDG PET/CT in the management of early-stage (AJCC 0-IIc) cutaneous melanoma. This is a CME article and provides the equivalent of 2 hours of continuing education that may be applied to your professional development credit system. A 12-question multiple choice quiz follows this reading. Please note that no formalized credit (Category A) is available from CAMRT.

Use of radioiodine-131 scan to measure influence of surgical discipline, practice, and volume on residual thyroid tissue after total thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND: Our study's purpose is to determine the influence of surgical discipline, surgeon site, and volume on remnant thyroid tissue visualized on radioactive iodine-131 (I-131) scans after total thyroidectomy and I-131 ablation in patients with well-differentiated thyroid carcinomas. METHODS: We retrospectively reviewed all cases of patients who received I-131 therapeutic ablation and postablation radioactive I-131 scans at our center after thyroidectomy to calculate the fraction of administered dose multiplied by 1000 (UDR1000). RESULTS: The remnant thyroid tissue (ie, the UDR1000), between academic and community surgeons was 0.471 (±0.705) and 1.190 (±2.487), respectively (P = .001). The UDR1000 between otolaryngology-head and neck surgery and general surgery was 0.654 (±1.575) and 1.043 (±1.625), respectively (P = .159). The UDR1000 partitioned by patient frequencies of <10, 10 to 19, and ≥20 patients yielded 1.255 (±2.554), 0.926 (±2.084), and 0.467 (±0.721), respectively (P = .003). CONCLUSION: Our study found statistically significant differences in residual thyroid tissue visualized on radioactive I-131 scans based on surgeon parameters.

Thyrotoxicosis Associated with a Hypopharyngeal Toxic Nodular Thyroid.

Ectopic thyroid is a rare developmental anomaly which may be either asymptomatic or present with thyroid dysfunction as well as pressure symptoms. Here we present a novel case of thyrotoxicosis associated with a hypopharyngeal multinodular thyroid in a female. Removal of the ectopic thyroid led to normalization of the thyroid status.

Positron Emission Tomography/Computerized Tomography in Newly Diagnosed Patients with Giant Cell Arteritis Who Are Taking Glucocorticoids.

OBJECTIVE: Large vessel uptake on positron emission tomography/computerized tomography (PET/CT) supports the diagnosis of giant cell arteritis (GCA). Its value, however, in patients without arteritis on temporal artery biopsy and in those receiving glucocorticoids remains unknown. We compared PET/CT results in GCA patients with positive (TAB+) and negative temporal artery biopsies (TAB-), and controls. METHODS: Patients with new clinically diagnosed GCA starting treatment with glucocorticoids underwent temporal artery biopsy and PET/CT. Using a visual semiquantitative approach, 18F-fluorodeoxyglucose (FDG) uptake was scored in 8 vascular territories and summed overall to give a total score in patients and matched controls. RESULTS: Twenty-eight patients with GCA and 28 controls were enrolled. Eighteen patients with GCA were TAB+. Mean PET/CT scores after an average of 11.9 days of prednisone were higher in patients with GCA compared to controls, for both total uptake (10.34 ± 2.72 vs 7.73 ± 2.56; p = 0.001), and in 6 of 8 specific vascular territories. PET/CT scores were similar between TAB+ and TAB- patients with GCA. The optimal cutoff for distinguishing GCA cases from controls was a total PET/CT score of ≥ 9, with an area under the receiver-operating characteristic curve of 0.75, sensitivity 71.4%, and specificity 64.3%. Among patients with GCA, these measures correlated with greater total PET/CT scores: systemic symptoms (p = 0.015), lower hemoglobin (p = 0.009), and higher platelet count (p = 0.008). CONCLUSION: Vascular FDG uptake scores were increased in most patients with GCA despite exposure to prednisone; however, the sensitivity and specificity of PET/CT in this setting were lower than those previously reported.

Spectrum of CT Findings in Thoracic Extranodal Non-Hodgkin Lymphoma.

Non-Hodgkin lymphoma (NHL) frequently manifests in extranodal structures in the chest, often in the form of secondary involvement but occasionally as primary disease. Because staging and treatment are affected by the presence of extranodal disease at imaging, radiologists' interpretation and management of suspicious findings are critical to patient care. Unfortunately, owing to considerable imaging overlap with other diseases, primary extranodal lymphoma is difficult to diagnose with imaging alone. Radiologists should have a heightened degree of suspicion in patients at risk (including patients with immune compromise, autoimmune diseases, or a history of stem cell or solid organ transplant) or with particular imaging appearances (including the vertebral wraparound sign, nonresolving consolidation, an infiltrative soft-tissue mass, and lesions demonstrating vascular encasement without invasion). For patients with known NHL, positron emission tomography/computed tomography (PET/CT) using fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) is now preferred for routine staging in most cases. CT remains heavily used, and identification of subtle extranodal involvement with CT can be improved with use of intravenous contrast material and careful review of multiplanar images. Pericardial effusion, pleural soft tissue (even when mild), mass-like consolidation, perilymphatic nodularity, and new lytic bone lesions are particularly suggestive of secondary involvement in a patient with known NHL. Magnetic resonance imaging is a helpful problem-solving tool when equivocal findings would change staging and treatment. This comprehensive review illustrates the spectrum of CT manifestations of extranodal NHL in the chest, including the pleura, lung, airways, heart, pericardium, esophagus, chest wall, and breast. ©RSNA, 2017.

Investigating the Impact of Positron Emission Tomography-Computed Tomography Versus Computed Tomography Alone for High-risk Volume Selection in Head and Neck and Lung Patients Undergoing Radiotherapy: Interim Findings.

INTRODUCTION: The aim of this study was to quantify the impact of positron emission tomography-computed tomography (PET-CT) on clinical target volume (CTV) selection in non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC) cancer patients. METHODS: Eight radiation oncologists with expertise in either NSCLC or HNSCC prospectively contoured target volumes with and without PET-CT findings. All volumes were contoured manually, and computed tomography (CT)-alone contours were identified as gross tumour volume CT and clinical target volume (CTV) CT, whereas those contoured with the aid of PET-CT were GTV PET and CTV PET. PET-CT contours were used for actual treatment delivery. Test treatment plans were generated based on the CT-alone volumes and applied to the final PET-CT contours. PET-CT had an impact if the test plans failed department quality assurance guidelines. For each patient, the dose to critical structures and any changes in the treatment plan were recorded. RESULTS: Eighty patients (49 HNSCC and 31 NSCLC) were analyzed. PET-CT impacted 42.9% of HNSCC cases and 45.2% of NSCLC cases. On average, PET-CT volumes were significantly larger than CT-alone volumes for HNSCC cases (P < .01) but not for NSCLC cases (P = .29). For organs at risk, no statistically significant differences were noted, with the exception of mean parotid dose for the right and left parotids (P = .0137and P = .0330, respectively). CONCLUSIONS: Interim analysis of data found that the use of PET-CT in the radiation therapy planning process impacted CTV selection, resulting in a major change in radiation therapy plans in 43.7% (HNSCC 42.9% and NSCLC 45.2%) of patients.

Atypical Femoral Fractures: A Teaching Perspective.

This article provides an overview of atypical femoral fractures with a highlight on their radiographic findings. Potent antiresorptive agents such as bisphosphonates or denosumab have been associated with the development of such fractures. However, at this time, a causal association has not been conclusively established. Atypical femoral fractures are insufficiency fractures, which frequently present with bone pain. Early identification of characteristic radiographic features and withdrawal of antiresorptive therapy may prevent the development of completed atypical femoral fractures.

Peripheral dysgraphia: dissociations of lowercase from uppercase letters and of print from cursive writing.

Clinical analyses of patients with acquired dysgraphia provide unique opportunities to understand the cognitive and neural organization of written language production. We report J.B., a 50-year-old woman with peripheral dysgraphia who had prominent dissociations in her ability to write in lowercase versus uppercase and print versus cursive. We gave J.B. a series of tasks that evaluated her skills at writing uppercase and lowercase print and cursive, spelling aloud and in writing, writing numbers and symbols, and visual letter recognition and imagery. She was impaired in printing letters, with lowercase more affected than uppercase, but her cursive writing was relatively intact. This pattern was consistent across letter, word, and nonword writing tasks. She was unimpaired on tasks assessing her visual recognition and imagery of lowercase and uppercase letters. Her writing of numbers was preserved. J.B.'s handwriting disorder was accompanied by a central phonological dysgraphia. Our findings indicate functional independence of graphomotor programs for print and cursive letter styles and for letters and numbers. We discuss the relationship between peripheral and central writing disorders.

Is lower socioeconomic status associated with more advanced thyroid cancer stage at presentation? A study in two Canadian centers.

BACKGROUND: Some studies have shown a higher incidence of thyroid cancer in patients with insurance coverage and higher socioeconomic status (SES), and a higher thyroid cancer stage in patients with lower SES, suggesting SES-related health disparity in thyroid cancer. However, it is not known if the same is evident under a universal healthcare system such as that in Canada. METHODS: We used data from the Canadian Thyroid Cancer Consortium, a large thyroid cancer registry that collects data from two major thyroid cancer referral centers (London, Ontario, and Halifax, Nova Scotia). We included patients who presented with thyroid cancer between 1998 and 2011. We determined age at presentation, sex, and thyroid cancer status using the American Joint Committee on Cancer (AJCC) staging criteria. Individuals' postal codes were used to retrieve data from the Canadian census for the years 1996, 2001, and 2006 to approximate household income. Ordered logistic regression was used to determine odds ratios of presenting with more advanced stage thyroid cancer as they relate to income, age, and sex. RESULTS: We included 1701 patients: 1334 cases from London and 367 from Halifax. Thyroid cancer was diagnosed more frequently in the higher SES groups (p<0.001). Compared to patients in the top income quintile, patients in the lowest and second-lowest income quintiles had significantly higher odds of having more advanced stage thyroid cancer at presentation (OR 1.58, p=0.002; 1.37, p=0.024 respectively). CONCLUSIONS: Our study suggests that, similar to countries that lack a universal healthcare system, health disparity in thyroid cancer also exists in Canada. It appears that while thyroid cancers were diagnosed more frequently in Canadian patients of higher SES, Canadian patients in the lower SES groups had more advanced stage thyroid cancer at presentation.

Synthesis and preliminary evaluation of piperidinyl and pyrrolidinyl iodobenzoates as imaging agents for butyrylcholinesterase.

PURPOSE: The purpose of this study is to synthesize and evaluate specific agents for molecular imaging of butyrylcholinesterase (BuChE), known to be associated with neuritic plaques and neurofibrillary tangles in Alzheimer's disease (AD). In this study, these agents were tested in a normal rat model. The distribution of radiolabel was compared with known BuChE histochemical distribution in the rat brain. PROCEDURES: Iodobenzoate esters were synthesized and tested, through spectrophotometric analysis, as specific substrates for BuChE. These compounds were converted to the corresponding (123)I esters from tributyltin intermediates and purified for studies in the rat model. Whole body dynamic scintigraphic images were obtained for biodistribution studies. Autoradiograms of brain sections were obtained and compared to histochemical distribution of the enzyme in this model system. RESULTS: The three iodobenzoate esters studied were specific substrates for BuChE. Whole body biodistribution studies with (123)I-labeled compounds showed rapid disappearance from the body while radioactivity was retained in the head region. Brain section autoradiography of animals injected with these labeled compounds indicated that most areas known to contain BuChE corresponded to areas of radioactivity accumulation. CONCLUSION: BuChE-specific radiolabeled iodobenzoates enter the brain and, in general, label areas known to exhibit BuChE activity in histochemical studies. Such molecules may represent a new direction for the development of agents for the molecular imaging of BuChE in the living brain, especially in regions where BuChE-containing neuropathological structures appear in AD.