Intrapatient Changes in CT-Based Body Composition After Initiation of Semaglutide (Glucagon-Like Peptide-1 Agonist) Therapy.

Background: The long-acting glucagon-like peptide-1 receptor agonist semaglutide is used to treat type 2 diabetes or obesity in adults. Clinical trials have observed associations of semaglutide with weight loss, improved diabetic control, and cardiovascular risk reduction. Objective: To evaluate intrapatient changes in body composition after initiation of semaglutide therapy by applying an automated suite of CT-based artificial intelligence (AI) body composition tools. Methods: This retrospective study included adult patients with semaglutide treatment who underwent abdominopelvic CT both within 5 years before and within 5 years after semaglutide initiation, between January 2016 and November 2023. An automated suite of previously validated CT-based AI body composition tools was applied to pre-semaglutide and post-semaglutide scans to quantify visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area, skeletal muscle area and attenuation, intermuscular adipose tissue (IMAT) area, liver volume and attenuation, and trabecular bone mineral density (BMD). Patients with ≥5-kg weight loss and ≥5-kg weight gain between scans were compared. Results: The study included 241 patients (mean age, 60.4±12.4 years; 151 women, 90 men). In the weight-loss group (n=67), the post-semaglutide scan, versus pre-semaglutide scan, showed decrease in VAT area (341.1 vs 309.4 cm2, p<.001), SAT area (371.4 vs 410.7 cm2, p<.001), muscle area (179.2 vs 193.0, p<.001), and liver volume (2379.0 vs 2578 HU, p=.009), and increase in liver attenuation (74.5 vs 67.6 HU, p=.03). In the weight-gain group (n=48), the post-semaglutide scan, versus pre-semaglutide scan, showed increase in VAT area (334.0 vs 312.8, p=.002), SAT area (485.8 vs 488.8 cm2, p=.01), and IMAT area (48.4 vs 37.6, p=.009), and decrease in muscle attenuation (5.9 vs 13.1, p<.001). Other comparisons were not significant (p>.05). Conclusion: Patients using semaglutide who lost versus gained weight demonstrated distinct patterns of changes in CT-based body composition measures. Those with weight loss exhibited overall favorable shifts in measures related to cardiometabolic risk. Muscle attenuation decrease in those with weight gain is consistent with decreased muscle quality. Clinical Impact: Automated CT-based AI tools provide biomarkers of body composition changes in patients using semaglutide beyond that which is evident by standard clinical measures.

Spectrum of Heterotopic and Ectopic Splenic Conditions.

A spectrum of heterotopic and ectopic splenic conditions may be encountered in clinical practice as incidental asymptomatic detection or symptomatic diagnosis. The radiologist needs to be aware of these conditions and their imaging characteristics to provide a prompt correct diagnosis and avoid misdiagnosis as neoplasm or lymphadenopathy. Having a strong knowledge base of the embryologic development of the spleen improves understanding of the pathophysiologic basis of these conditions. Spleen-specific imaging techniques-such as technetium 99m (99mTc)-labeled denatured erythrocyte scintigraphy, 99mTc-sulfur colloid liver-spleen scintigraphy, and MRI with ferumoxytol intravenous contrast material-can also be used to confirm the presence or absence of splenic tissue. Heterotopic splenic conditions include splenules and splenogonadal fusion (discontinuous or continuous forms). These heterotopic conditions are caused by incomplete fusion of the splenic primordia (splenule) and abnormal fusion of the gonadal and splenic tissue (splenogonadal fusion). Ectopic splenic conditions arise in patients with a prior splenic injury (splenosis), laxity or maldevelopment of the splenic ligaments (wandering spleen), or heterotaxy syndromes (polysplenia and asplenia). Importantly, these heterotopic and ectopic splenic conditions can also manifest with complications, including vascular torsion and rupture. ©RSNA, 2024.

Twice-weekly glucocorticosteroids in infants and young boys with Duchenne muscular dystrophy.

INTRODUCTION: Glucocorticosteroids (GC) are effective in slowing weakness in boys with Duchenne muscular dystrophy (DMD). METHODS: This is a multisite, 1-year, open-label trial of twice-weekly prednisolone (5 mg/kg/dose) in infants/young boys (0.4-2.4 years) with DMD. We compared changes in Bayley III Scales of Infant Development (Bayley-III) with untreated boys followed for 1 year (historical control cohort [HCC]). Twenty-three of 25 participants completed the study. RESULTS: Treated boys gained an average of 0.5 points on the Bayley-III gross motor scaled score (GMSS) compared with the HCC who, on average, declined 1.3 points (P = 0.03). All boys maintained linear growth, and none developed Cushingoid features. Excessive weight gain occurred in 13 of 23 (56%) boys. DISCUSSION: This study provides evidence that twice-weekly GC is well tolerated in infants and young boys with DMD and improves GMSS. Excessive weight gain is a potential risk. Longer follow-up is required to determine whether early GC initiation is feasible in most infants/boys with DMD. Muscle Nerve 59:650-657, 2019.

Electrical impedance myography in individuals with collagen 6 and laminin α-2 congenital muscular dystrophy: a cross-sectional and 2-year analysis.

INTRODUCTION: Electrical impedance myography (EIM) is a noninvasive electrophysiological technique that characterizes muscle properties through bioimpedance. We compared EIM measurements to function, strength, and disease severity in a population with congenital muscular dystrophy (CMD). METHODS: Forty-one patients with CMD, either collagen 6 related disorders (COL6-RD; n = 21) or laminin α-2-related disorders (LAMA2-RD; n = 20), and 21 healthy pediatric controls underwent 2 yearly EIM exams. In the CMD cohorts, EIM was compared with functional and strength measurements. RESULTS: Both CMD cohorts exhibited change over time and had correlation with disease severity. The 50-kHZ phase correlated well with function and strength in the COL6-RD cohort but not in the LAMA2-RD cohort. DISCUSSION: EIM is a potentially useful measure in clinical studies with CMD because of its sensitivity to change over a 1-year period and correlation with disease severity. For COL6-RD, there were also functional and strength correlations. Muscle Nerve 57: 54-60, 2018.

Rasch analysis of clinical outcome measures in spinal muscular atrophy.

INTRODUCTION: Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). METHODS: Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. RESULTS: Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. CONCLUSIONS: The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges.

MR imaging of penile pathology and prostheses.

Penile MRI is a vital yet underutilized diagnostic tool that provides detailed information crucial for managing various penile pathologies. Due to its infrequent use, many radiology trainees lack confidence in interpreting these exams. This article reviews the anatomy, key technical considerations, and interpretive pearls for penile trauma, Peyronie's disease, priapism, penile neoplasms, prosthesis evaluation, and a few miscellaneous conditions. Through illustrative case examples, this review aims to enhance the understanding and proficiency of radiologists in performing and interpreting penile MRI in these clinical scenarios.

Contrast-enhanced ultrasound of renal masses in the pre-transplant setting: literature review with case highlights.

With the rising incidence of chronic kidney disease worldwide, an increasing number of patients are expected to require renal transplantation, which remains the definitive treatment of end stage renal disease. Medical imaging, primarily ultrasonography and contrast-enhanced CT and/or MRI, plays a large role in pre-transplantation assessment, especially in the characterization of lesions within the native kidneys. However, patients with CKD/ESRD often have relative contraindications to CT- and MR-contrast agents, limiting their utilization within this patient population. Contrast-enhanced ultrasound (CEUS), which combines the high temporal and spatial resolution of ultrasonography with intravascular microbubble contrast agents, provides a promising alternative. This review aims to familiarize the reader with the literature regarding the use of CEUS in the evaluation of cystic and solid renal lesions and provide case examples of its use at our institution in the pre-transplant setting.

Correlation of HbA1c levels with CT-based body composition biomarkers in diabetes mellitus and metabolic syndrome.

Diabetes mellitus and metabolic syndrome are closely linked with visceral body composition, but clinical assessment is limited to external measurements and laboratory values including hemoglobin A1c (HbA1c). Modern deep learning and AI algorithms allow automated extraction of biomarkers for organ size, density, and body composition from routine computed tomography (CT) exams. Comparing visceral CT biomarkers across groups with differing glycemic control revealed significant, progressive CT biomarker changes with increasing HbA1c. For example, in the unenhanced female cohort, mean changes between normal and poorly-controlled diabetes showed: 53% increase in visceral adipose tissue area, 22% increase in kidney volume, 24% increase in liver volume, 6% decrease in liver density (hepatic steatosis), 16% increase in skeletal muscle area, and 21% decrease in skeletal muscle density (myosteatosis) (all p < 0.001). The multisystem changes of metabolic syndrome can be objectively and retrospectively measured using automated CT biomarkers, with implications for diabetes, metabolic syndrome, and GLP-1 agonists.

Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3: The Phase 2 TOPAZ Study.

BACKGROUND AND OBJECTIVES: Currently approved therapies for spinal muscular atrophy (SMA) reverse the degenerative course, leading to better functional outcome, but they do not address the impairment arising from preexisting neurodegeneration. Apitegromab, an investigational, fully human monoclonal antibody, inhibits activation of myostatin (a negative regulator of skeletal muscle growth), thereby preserving muscle mass. The phase 2 TOPAZ trial assessed the safety and efficacy of apitegromab in individuals with later-onset type 2 and type 3 SMA. METHODS: In this study, designed to investigate potential meaningful combinations of eligibility and treatment regimen for future studies, participants aged 2-21 years received IV apitegromab infusions every 4 weeks for 12 months in 1 of 3 cohorts. Cohort 1 stratified ambulatory participants aged 5-21 years into 2 arms (apitegromab 20 mg/kg alone or in combination with nusinersen); cohort 2 evaluated apitegromab 20 mg/kg combined with nusinersen in nonambulatory participants aged 5-21 years; and cohort 3 blindly evaluated 2 randomized apitegromab doses (2 and 20 mg/kg) combined with nusinersen in younger participants ≥2 years of age. The primary efficacy measure was mean change from baseline using the Hammersmith Functional Motor Scale version appropriate for each cohort. Data were analyzed using a paired t test with 2-sided 5% type 1 error for the mean change from baseline for predefined cohort-specific primary efficacy end points. RESULTS: Fifty-eight participants (mean age 9.4 years) were enrolled at 16 trial sites in the United States and Europe. Participants had been treated with nusinersen for a mean of 25.9 months before enrollment in any of the 3 trial cohorts. At month 12, the mean change from baseline in Hammersmith scale score was -0.3 points (95% CI -2.1 to 1.4) in cohort 1 (n = 23), 0.6 points (-1.4 to 2.7) in cohort 2 (n = 15), and in cohort 3 (n = 20), the mean scores were 5.3 (-1.5 to 12.2) and 7.1 (1.8 to 12.5) for the 2-mg/kg (n = 8) and 20-mg/kg (n = 9) arms, respectively. The 5 most frequently reported treatment-emergent adverse events were headache (24.1%), pyrexia (22.4%), upper respiratory tract infection (22.4%), cough (22.4%), and nasopharyngitis (20.7%). No deaths or serious adverse reactions were reported. DISCUSSION: Apitegromab led to improved motor function in participants with later-onset types 2 and 3 SMA. These results support a randomized, placebo-controlled phase 3 trial of apitegromab in participants with SMA. TRIAL REGISTRATION INFORMATION: This trial is registered with ClinicalTrials.gov (NCT03921528). CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that apitegromab improves motor function in later-onset types 2 and 3 spinal muscular atrophy.

Interobserver Agreement Between Primary Sonographers and Secondary Overreaders for Screening and Surveillance Liver Ultrasounds Using Ultrasound Liver Imaging Reporting and Data System.

ABSTRACT: The authors aim to identify if primary sonographers and secondary reviewers, both radiologists and sonographers, are likely to assign the same Ultrasound Liver Imaging Reporting and Data System (US LI-RADS) scores for liver surveillance ultrasounds. Institutional review board approval was obtained. Sonographers were familiarized with US LI-RADS via radiologist-led lectures. Three sonographers prospectively scored 170 screening examinations using US LI-RADS recommendations. Scans were retrospectively rescored by a fourth sonographer and a radiologist, both of whom were blinded to the original scores. Results were analyzed with weighted and nonweighted Cohen kappa statistical analysis methods. There was near-perfect agreement between primary and secondary sonographers and primary sonographer and radiologist (kappa of 0.87 and 0.92, respectively) for US LI-RADS category (cat) scores. However, only substantial and moderate agreements were noted for visualization (vis) scores between primary and secondary sonographers and primary sonographer and radiologist (weighted kappa of 0.73 and 0.48, respectively). There was vis score disagreement between the primary sonographer and radiologist in 60 (35.3%) cases. In 35 (20%) cases, the radiologist assigned a lower/more conservative vis score. There was vis score disagreement between the primary and secondary reviewing sonographers in 30 (17.6%) cases. In 12 (7%) cases, the secondary sonographer assigned a more conservative vis score. Although a good degree of concordance was noted between the groups, radiologists will need to generate their own US LI-RADS scoring to accurately reflect their impression and appropriately steer management.

Development of Duchenne Video Assessment scorecards to evaluate ease of movement among those with Duchenne muscular dystrophy.

BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) adopt compensatory movement patterns as muscles weaken. The Duchenne Video Assessment (DVA) measures patient ease of movement through identification of compensatory movement patterns. The DVA directs caregivers to video record patients performing specific movement tasks at home using a secure mobile application, and DVA-certified physical therapists (PTs) score the videos using scorecards with prespecified compensatory movement criteria. The goal of this study was to develop and refine the DVA scorecards. METHODS: To develop the initial scorecards, 4 PTs collaboratively created compensatory movement lists for each task, and researchers structured the lists into scorecards. A 2-round modified Delphi process was used to gather expert opinion on the understandability, comprehensiveness, and clinical meaningfulness of the compensatory movements on the scorecards. Eight PTs who had evaluated ≥50 patients with DMD and participated in ≥10 DMD clinical trials were recruited for the panel. In Round 1, panelists evaluated compensatory movement criteria understandability via questionnaire and tested the scorecards. In Round 2, panelists participated in an in-person meeting to discuss areas of disagreement from Round 1 and reach consensus (≥75% agreement) on all revisions to the scorecards. RESULTS: During the Round 1 revisions to the scorecards, there were 67 changes (44%) to the wording of 153 original compensatory movement criteria and 3 criteria were removed. During the Round 2 revisions to the scorecards, there were 47 changes (31%) to the wording of 150 compensatory movement criteria, 20 criteria were added, and 30 criteria were removed. The panel reached 100% agreement on all changes made to scorecards during Round 2. CONCLUSION: PTs with extensive experience evaluating patients with DMD confirmed that the compensatory movement criteria included in the DVA scorecards were understandable, comprehensive, and clinically meaningful.

Social Media and Clinical Trials in Pediatric Disease: Musings From the Bench.

The use of social media in clinical trials, for recruiting and retention as well as for collecting data, has become increasingly common. However, little has been documented in respect to the guidelines for its use and the possible effects it may have on clinical trials. In this review, we provide an overview of the guidance that has been published and muse the pros and cons of the use of social media in trials for rare disease.

Clinical outcome assessments in Duchenne muscular dystrophy and spinal muscular atrophy: past, present and future.

Scores and scales used in pediatric motor development for neuromuscular disorders have evolved greatly since the beginning of their development. In this review we provide a brief history of scales used in pediatric patients with neuromuscular disorders and an update regarding the advancement of the scales commonly used in patients with spinal muscular atrophy and Duchenne muscular dystrophy. We focus on the collaborative effort that has led to the development of outcomes and speak to the possible future of Clinical Outcome Assessments.

Role of Ultrasound for Chronic Liver Disease and Hepatocellular Carcinoma Surveillance.

Ultrasound plays a vital role in the evaluation of patients with chronic liver disease and in hepatocellular carcinoma (HCC) surveillance in populations at risk for developing HCC. Semiannual ultrasound for HCC surveillance is universally recommended by all liver societies around the world. Advanced ultrasound techniques, such as elastography and contrast-enhanced ultrasound, offer additional benefits in imaging evaluation of chronic liver disease. Major benefits of ultrasound include its high safety profile and relatively low cost.

The Minimal Clinical Important Difference (MCID) in Annual Rate of Change of Timed Function Tests in Boys with DMD.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare x-linked recessive genetic disorder affecting 1 in every 5000-10000 [1, 2]. This disease leads to a variable but progressive sequential pattern of muscle weakness that eventually causes loss of important functional milestones such as the ability to walk. With promising drugs in development to ameliorate the effects of muscle weakness, these treatments must be associated with a clinically meaningful functional change. OBJECTIVE: The objective of this analysis is to determine both distribution, minimal detectable change (MDC), and anchor-based, minimal clinically important difference, (MCID) of 12 month change values in standardized time function tests (TFT) used to monitor disease progression in DMD. METHOD: This is a retrospective analysis of prospectively collected data from a multi-center prospective natural history study with the Cooperative International Neuromuscular Research Group (CINRG). This study calculated MDC and MCID values for 3 commonly used timed function tests typically used to monitor disease progression; supine to stand (STS), 10 meter walk/run (10MWT), and 4 stair climb (4SC). MDC used standard error of measurement (SEM) while MCID measurements used the Vignos scale as an anchor to determine clinical change in functional status. RESULTS: All 3 TFT were significantly important clinical endpoints to detect MDC and MCID changes. MDC and MCID 12 month changes were significant in 10MWT (-0.138, -0.212), Supine to Stand (-0.026, -0.023) and 4 stair climb (-0.034, -0.035) with an effect size greater or close to 0.2. CONCLUSION: The 3 TFT are clinically meaningful endpoints used to establish change in DMD. MCID values were higher than MDC values indicating that an anchor-based approach using Vignos as a clinically meaningful loss of lower extremity abilities is appropriate to assess change in boys with DMD.

Correlation of placental MR imaging signs and pathologic diagnosis of placenta accreta spectrum: Retrospective single center case series.

INTRODUCTION: Alongside initial screening obstetric US, use of placental MRI has been increasing in the last few decades to aid with antenatal diagnosis and delivery planning in Placenta Accreta Spectrum (PAS). The aim of this study was to determine if the MRI pathophysiological sign subcategories described in the current literature can predict the severity of pathologic diagnosis. METHODS: Institutional imaging records were reviewed for placental MRIs performed for suspicion of PAS in the last decade. Electronic health records were searched for patient history and pathology. The 59 MRI studies were reviewed using the 11 MRI signs described by the SAR and ESUR joint consensus statement. Further breakdown of the signs was divided by underlying pathophysiologic subcategories including gross morphologic, interface and tissue architecture signs. RESULTS: Pathologic diagnosis yielded 34 cases: accreta 4/34, incerta 14/34, percreta 10/34 and normal 6/34. Of the accreta cases all of them demonstrated at least two interface and half of the cases had tissue architecture signs, 13/14 increta cases demonstrated interface signs and 12/14 demonstrated tissue architecture signs, 9/10 percreta cases had two interface and at least six demonstrated three tissue architecture signs. Statistical analysis showed significant difference between pathologic diagnosis and the number of positive interface signs with p = 0.02. DISCUSSION: Interface signs were the most objective and sensitive MRI subcategory. Statistical analysis determined there was a significant difference between PAS diagnosis and number of interface signs present. This subcategory has the most overlap with classic US signs which are traditionally used before MRI referral.

Consensus Guidelines for Improving Quality of Assessment and Training for Neuromuscular Diseases.

Critical components of successful evaluation of clinical outcome assessments (COAs) in multisite clinical trials and clinical practice are standardized training, administration, and documented reliability of scoring. Experiences of evaluators, alongside patient differences from regional standards of care, may contribute to heterogeneity in clinical center's expertise. Achieving low variability and high reliability of COA is fundamental to clinical research and to give confidence in our ability to draw rational, interpretable conclusions from the data collected. The objective of this manuscript is to provide a framework to guide the learning process for COAs for use in clinics and clinical trials to maximize reliability and validity of COAs in neuromuscular disease (NMD). This is a consensus-based guideline with contributions from fourteen leading experts in clinical outcomes and the field of clinical outcome training in NMD. This framework should guide reliable and valid assessments in NMD specialty clinics and clinical trials. This consensus aims to expedite study start up with a progressive training pathway ranging from research naïve to highly experienced clinical evaluators. This document includes recommendations for education guidelines and roles and responsibilities of key stakeholders in COA assessment and implementation to ensure quality and consistency of outcome administration across different settings.

A Cross-Sectional Study of Nemaline Myopathy.

OBJECTIVE: Nemaline myopathy (NM) is a rare neuromuscular condition with clinical and genetic heterogeneity. To establish disease natural history, we performed a cross-sectional study of NM, complemented by longitudinal assessment and exploration of pilot outcome measures. METHODS: Fifty-seven individuals with NM were recruited at 2 family workshops, including 16 examined at both time points. Participants were evaluated by clinical history and physical examination. Functional outcome measures included the Motor Function Measure (MFM), pulmonary function tests (PFTs), myometry, goniometry, and bulbar assessments. RESULTS: The most common clinical classification was typical congenital (54%), whereas 42% had more severe presentations. Fifty-eight percent of individuals needed mechanical support, with 26% requiring wheelchair, tracheostomy, and feeding tube. The MFM scale was performed in 44 of 57 participants and showed reduced scores in most with little floor/ceiling effect. Of the 27 individuals completing PFTs, abnormal values were observed in 65%. Last, bulbar function was abnormal in all patients examined, as determined with a novel outcome measure. Genotypes included mutations in ACTA1 (18), NEB (20), and TPM2 (2). Seventeen individuals were genetically unresolved. Patients with pathogenic ACTA1 and NEB variants were largely similar in clinical phenotype. Patients without genetic resolution had more severe disease. CONCLUSION: We present a comprehensive cross-sectional study of NM. Our data identify significant disabilities and support a relatively stable disease course. We identify a need for further diagnostic investigation for the genetically unresolved group. MFM, PFTs, and the slurp test were identified as promising outcome measures for future clinical trials.

Meeting Code Blue Requirements Using a Team-Based Simulation.

Immediate high-quality cardiopulmonary resuscitation (CPR) and early defibrillation are essential to survival, yet CPR skills deteriorate without frequent repetition. Basic Life Support-focused Code Blue team-based simulation is needed in continuing education to bridge this gap. This article outlines a teaching plan for hospital orientation and subsequent scenarios to improve the resuscitation response. [J Contin Educ Nurs. 2020;51(5):205-208.].