BACKGROUND. CT muscle metrics hold promise for opportunistic sarcopenia screening and individualized clinical risk stratification, but reference values applicable across broad populations are lacking. OBJECTIVE. The purpose of this study was to estimate reference cutoff values for CT skeletal muscle metrics using data from populations of healthy young adults. EVIDENCE ACQUISITION. The PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases were searched through January 1, 2025, for studies reporting skeletal muscle index (SMI) and/or skeletal muscle density (SMD) on CT at the L3 vertebral level in healthy young adults (age range, 18-45 years). For SMI and SMD in both men and women, a random-effects meta-analysis was used to estimate interstudy SD (as a measure of variance among studies) and mean values for a theoretic global population of healthy young adults. The presence of significant heterogeneity among individual study means was assessed using the Q statistic. Cutoff values for the theoretic global population corresponding with a T-score of -2 (i.e., values ≥ 2 SDs below the theoretic global population's mean value) were calculated, incorporating the meta-analysis results and pooled intrastudy variance. EVIDENCE SYNTHESIS. The meta-analysis included 14 studies (16,958 individuals; 11,819 men, 5139 women) reporting SMI, of which seven studies (11,175 individuals; 8372 men, 2803 women) also reported SMD. The estimated global mean value for SMI was 54.6 in men and 42.4 in women and for SMD was 47.4 HU in men and 43.6 HU in women. The interstudy SD for SMI was 5.4 in men and 4.3 in women and for SMD was 1.9 in men versus 3.2 in women; significant heterogeneity was present among individual study means for both SMI and SMD in both men and women (all p < .001). The cutoff value corresponding with a T-score of -2 for SMI was 36.3 in men and 27.5 in women and for SMD was 36.4 HU in men and 28.1 HU in women. CONCLUSION. This meta-analysis of studies performed in healthy young adults provides reference mean values and standardized cutoffs analogous to a T-score of -2 for SMI and SMD at the L3 level on abdominal CT. CLINICAL IMPACT. These results can aid opportunistic screening for sarcopenia.

Objective Patients with rheumatoid arthritis (RA) in sustained remission/low disease activity with tumor necrosis factor inhibitor (TNFi) treatment may be candidates for treatment de-escalation. We compared the frequency of relapses and flares of RA after TNFi discontinuation with TNFi continuation among such patients. We also investigated predictors of relapse. Methods This randomized, double-blind, placebo controlled noninferiority trial enrolled adults with RA who were treated with either adalimumab, etanercept, or infliximab, and who had a Disease Activity Score 28-C-reactive protein (DAS-CRP) < 2.6 for at least six months. Patients were randomly assigned 2:1 to either placebo injections/infusions (i.e. discontinuation) or active TNFi. Patients, investigators, and study staff were masked to treatment assignment. The primary endpoint was relapse over 48 weeks, defined as either DAS29-CRP ≥ 2.6 or treatment escalation. Secondary endpoints included flare, defined as an increase in DAS28-CRP ≥ 1.2 from baseline. Results The study was stopped early based on an interim analysis that rejected noninferiority. At study interruption, 102 patients (69 placebo; 33 active TNFi) were randomized. Relapses occurred in 59.4 % of the placebo group and 18.1 % of the active TNFi group (hazard ratio 4.88; 95 % confidence interval 2.05, 11.61). Flares occurred in 43.5 % and 15.1 % of these groups, respectively. Over 48 weeks, successful discontinuation was achieved in 55 % of patients who discontinued adalimumab and 26 % of patients who discontinued etanercept. Conclusion Discontinuation of maintenance TNFi resulted in higher rates of relapse of RA than continuation. Trial Registration Clinicaltrials.gov NCT01793519

Myositis is defined as inflammation within skeletal muscle and is a subcategory of myopathy, which is more broadly defined as any disorder affecting skeletal muscle. Myositis may be encountered as a component of autoimmune and connective tissue diseases, where it is described as idiopathic inflammatory myopathy (IIM). Myositis can also be caused by infections as well as toxins and drugs, including newer classes of medications. MRI plays an important role in the diagnosis and evaluation of patients with suspected myositis, but many entities may have imaging features similar to those of myositis and can be considered myositis mimics. These include muscular dystrophies, denervation, deep venous thrombosis, diabetic myonecrosis, muscle injury, heterotopic ossification, and even neoplasms. In patients with suspected myositis, definitive diagnosis may require integrated analysis of imaging findings with clinical, laboratory, and pathology data. The objectives of this article are to review the fundamental features of myositis, including recent updates in terminology and consensus guidelines for IIMs; the most important MRI differential diagnostic considerations for myositis (i.e., myositis mimics); and new horizons, including the potential importance of artificial intelligence and multimodal integrated diagnostics in the evaluation of patients with muscle disorders.

BACKGROUND. Sarcopenia is commonly assessed on CT by use of the skeletal muscle index (SMI), which is calculated as the skeletal muscle area (SMA) at L3 divided by patient height squared (i.e., a height scaling power of 2). OBJECTIVE. The purpose of this study was to determine the optimal height scaling power for SMA measurements on CT and to test the influence of the derived optimal scaling power on the utility of SMI in predicting all-cause mortality. METHODS. This retrospective study included 16,575 patients (6985 men, 9590 women; mean age, 56.4 years) who underwent abdominal CT from December 2012 through October 2018. The SMA at L3 was determined using automated software. The sample was stratified into two groups: 5459 patients without major medical conditions (based on ICD-9 and ICD-10 codes) who were included in the analysis for determining the optimal height scaling power and 11,116 patients with major medical conditions who were included for the purpose of testing this power. The optimal scaling power was determined by allometric analysis (whereby regression coefficients were fitted to log-linear sex-specific models relating height to SMA) and by analysis of statistical independence of SMI from height across scaling powers. Cox proportional hazards models were used to test the influence of the derived optimal scaling power on the utility of SMI in predicting all-cause mortality. RESULTS. In allometric analysis, the regression coefficient of log(height) in patients 40 years old and younger was 1.02 in men and 1.08 in women, and in patients older than 40 years old, it was 1.07 in men and 1.10 in women (all p <.05 vs regression coefficient of 2). In analyses for statistical independence of SMI from height, the optimal height scaling power (i.e., those yielding correlations closest to 0) was, in patients 40 years old and younger, 0.97 in men and 1.08 in women, whereas in patients older than 40 years old, it was 1.03 in men and 1.09 in women. In the Cox model used for testing, SMI predicted all-cause mortality with a higher concordance index using of a height scaling power of 1 rather than 2 in men (0.675 vs 0.663, p <.001) and in women (0.664 vs 0.653, p <.001). CONCLUSION. The findings support a height scaling power of 1, rather than a conventional power of 2, for SMI computation. CLINICAL IMPACT. A revised height scaling power for SMI could impact the utility of CT-based sarcopenia diagnoses in risk assessment.

Supplementary Table 2 from Glomus Tumors in Neurofibromatosis Type 1: Genetic, Functional, and Clinical Evidence of a Novel Association

During continuous peristaltic reflex activity of the isolated guinea-pig ileum a model stress stimulus, elevated intraluminal pressure (120 mm H2O) plus increased longitudinal tension (3 g) was applied for 2 min. The resulting inhibition of peristalsis outlasted the initial stimulus by several min. The inhibitory interval was shortened or abolished in the presence of naloxone (0.5 μM), an opiate receptor antagonist, or in the preparations made acutely tolerant to morphine. This seems to suggest an involvement of endorphins. An inhibition of endogenous prostaglandin synthesis by indomethacin (5 μM) decreased the amplitude of peristaltic longitudinal muscle contractions, and these contractions were increased in response to the stress stimulus in the presence of naloxone. Thus the response of the guinea-pig ileum to stress stimulation could be profoundly modified by an interference with endorphin and prostaglandin systems.

Sarcopenia is defined as the loss of muscle mass, strength, and function. Increasing evidence shows that sarcopenia is common in patients with rheumatic disorders. Although sarcopenia can be diagnosed using bioelectrical impedance analysis or DXA, increasingly it is diagnosed using CT, MRI, and ultrasound. In rheumatic patients, CT and MRI allow "opportunistic" measurement of body composition, including surrogate markers of sarcopenia, from studies obtained during routine patient care. Recognition of sarcopenia is important in rheumatic patients because sarcopenia can be associated with disease progression and poor outcomes. This article reviews how opportunistic evaluation of sarcopenia in rheumatic patients can be accomplished and potentially contribute to improved patient care.

To examine the relationship between vertebral trabecular bone mineral density (tBMD), vertebral strength, and syndesmophytes in patients with ankylosing spondylitis (AS) using quantitative computed tomography (QCT). We performed QCT of the spine to measure syndesmophytes and tBMD in 5 vertebrae (T11–L3) in 61 patients with AS. Finite element analysis was performed to measure vertebral strength in compressive overload, including in trabecular and cortical compartments. In cross-sectional analyses, we examined associations of syndesmophyte height with tBMD and vertebral strength in each vertebra. In 33 patients followed up for 2 years, we investigated whether baseline tBMD and vertebral strength predicted syndesmophyte growth in the same vertebra, and vice versa. In the cross-sectional analyses, 126 vertebrae had bridging, 77 vertebrae had nonbridging syndesmophytes, and 83 vertebrae had no syndesmophytes. There were strong inverse associations between syndesmophyte height and tBMD, total strength, and trabecular strength only among bridged vertebrae. In the longitudinal analysis, nonbridged vertebrae with low tBMD (adjusted β = –0.01 [95% confidence interval (95% CI) –0.019, –0.0012]) and low strength (adjusted β = –0.0003 [95% CI –0.0004, –0.0002]) had more syndesmophyte growth over time. Similar associations were absent among bridged vertebrae. Conversely, vertebrae with bridging at baseline had a significant loss in percent tBMD over time (adjusted β = –0.001 [95% CI –0.0017, –0.0004]). Associations between syndesmophytes and vertebral density and strength in AS differ between bridged and nonbridged vertebrae. Among nonbridged vertebrae, low tBMD and strength are associated with syndesmophyte growth. Bridging is associated with large subsequent losses in tBMD, possibly due to mechanical offloading.

YY Objective To compare muscle ultrasound (MUS) parameters in patients with juvenile JDM and healthy controls, and examine their association with JDM disease activity measures and MRI. Methods MUS of the right mid-rectus femoris was performed in 21 patients with JDM meeting probable or definite Bohan and Peter criteria and 28 demographically matched healthy control subjects. MUS parameters were quantitated by digital image processing and correlated with JDM disease activity measures and semi-quantitative thigh MRI short tau inversion recovery (STIR) and T1 scores. Results Rectus femoris MUS echogenicity was increased (median 47.8 vs 38.5, P = 0.002) in patients with JDM compared with controls. Rectus femoris MUS echogenicity correlated with Physician Global Activity (PGA), Manual Muscle Testing (MMT), and Childhood Myositis Assessment Scale (CMAS) (r(s) 0.4-0.54). Some MUS parameters correlated with functional quantitative measures of muscle strength: resting RF area on MUS strongly correlated with knee extension quantitative muscle testing (r(s) 0.76), and contracted area correlated with proximal MMT, knee extension quantitative muscle testing, and CMAS (r(s) 0.71-0.80). MUS echogenicity correlated with both STIR and T1 MRI (r(s) 0.43), and T1 MRI correlated inversely with RF contracted area (r(s) -0.49) on MUS. There were differences in pre- and post-exercise vascular power and colour Doppler on MUS in patients with JDM vs controls, with the percentage change of post-exercise vascular power Doppler lower in JDM compared with controls (7.1% vs 100.0%). Conclusions These data suggest MUS may be a valuable imaging modality to assess JDM disease activity and damage.

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Objective Rapidly progressive idiopathic arthritis of the hip (RPIA) is defined by progressive joint space narrowing of > 2 mm or > 50% within 1 year. Our aims were to assess (a) the occurrence of RPIA after intra-articular steroid injection, and (b) possible risk factors for RPIA including: patient age, BMI, joint space narrowing, anesthetic and steroid selections, bone mineral density, and pain reduction after injection. Materials and methods A retrospective search of our imaging database identified 1471 patients who had undergone fluoroscopically guided hip injection of triamcinolone acetonide (Kenalog) and anesthetic within a 10-year period. Patient data, including hip DXA results and patient-reported pain scores, were recorded. Pre-injection and follow-up radiographs were assessed for joint space narrowing, femoral head deformity, and markers of osteoarthritis. Osteoarthritis was graded by Croft score. Associations between patient characteristics and outcome variables were analyzed. Results One hundred six of 1471 injected subjects (7.2%) met the criteria for RPIA. A control group of 161 subjects was randomly selected from subjects who underwent hip injections without developing RPIA. Compared to controls, patients with RPIA were older, had narrower hip joint spaces, and higher Croft scores before injection (p < 0.05). Patients who developed RPIA did not differ from controls in sex, BMI, hip DXA T-score, anesthetic and steroid injectates, or pain improvement after injection. Conclusion We found that approximately 7% of patients undergoing steroid hip injection developed RPIA. More advanced patient age, greater joint space narrowing, and more severe osteoarthritis are risk factors for the development of RPIA after intra-articular steroid injection.

Juvenile dermatomyositis (JDM) is a systemic vasculopathy with weakness and rash, frequently exhibiting a chronic/polycyclic course, and treated with broad immunosuppression. An interferon (IFN) signature correlates with disease activity.1 Interferonopathies have been successfully targeted by janus kinase (JAK) inhibitors.2 3 We report the first comprehensive prospective evaluation of JAK inhibition (baricitinib) in JDM. Four patients (5.8–20.7 years old), with chronically active JDM (≥3/6 core set measures)4 who had failed three to six immunomodulatory medications, were enroled on compassionate use study NCT01724580 (online supplementary methods, online supplementary table 1). Biologics other than intravenous immunoglobulin were washed out and other medications continued.### Supplementary data [annrheumdis-2020-218690supp001.pdf] Subjects were assessed before and 4, 8, 12 and 24 weeks after starting baricitinib (4–8 mg/day divided two times per day) dosed by weight and renal function.3 Significant improvement was noted by week 4 in Physician Global Activity, Patient/Parent Global Activity, and Extramuscular Global Activity, and Cutaneous Dermatomyositis Disease Area and Severity Index (figure 1, online supplementary table 2). Two patients with baseline weakness improved by week 4 (ACR/EULAR Myositis Response Criteria) and showed clinically relevant improvement in Manual Muscle Testing-8 by week 8, confirmed by blinded MRI assessment (online supplementary figures 1 and 2). There was no significant change in muscle enzymes (online supplementary table 3), though some had variable elevations with stable/improved strength. Daily corticosteroids were decreased (0.28 to 0.18 mg/kg/day); other immunosuppressive medications were decreased/discontinued (online supplementary table 1). There were no flares/worsening requiring increased immunosuppression. There was no notable change in calcinosis (n=2). Figure 1 Change in disease activity and pharmacodynamic markers on baricitinib treatment. (A–D) Multiple clinical assessments are shown at …

Question Can magnetic resonance imaging assist with diagnosis and management of immune checkpoint inhibitor (ICI)-associated arthritis? Findings In this case series of 8 patients with ICI-induced inflammatory arthritis, magnetic resonance imaging was used to identify synovitis and tenosynovitis as common features of ICI-induced inflammatory arthritis; erosive joint disease was less common but was also detected. Meaning These findings suggest that magnetic resonance imaging may provide utility in distinguishing inflammatory arthritis from other causes of joint pain in patients receiving ICI therapy and identifying patients at increased risk of joint damage. Importance Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for an ever-increasing number of cancers. However, their use has also led to the emergence of immune-related adverse events, such as ICI-induced inflammatory arthritis. A reproducible, reliable, and accessible modality is needed to assess and distinguish early ICI-induced inflammatory arthritis and help in management. Magnetic resonance imaging (MRI) of joints may be helpful for early diagnosis, guiding therapeutic decision-making, and identifying patients at high risk for erosive disease. Objective To assess the role of MRI of joints in patients with ICI-induced inflammatory arthritis. Design, Setting, and Participants This retrospective case series included patients enrolled at the National Institutes of Health Clinical Center in Bethesda, Maryland. Patients were evaluated by the rheumatology consultation service between December 27, 2016, and May 28, 2019. A retrospective health record review was performed to determine demographic characteristics, clinical characteristics of inflammatory arthritis and malignant tumors, and imaging findings. Inclusion criteria were patients who were enrolled on various institutional review board-approved protocols of ICIs, developed joint-related symptoms, and had MRI data for at least 1 joint. Data were analyzed from June 1, 2019, to September 1, 2019. Exposures Undergoing MRI of at least 1 joint. Main Outcomes and Measures All MRIs were reviewed for synovitis, tenosynovitis, bone marrow edema, and soft tissue conditions. Results A total of 8 patients (mean [SD] age, 58.8 [5.2] years; 6 women and 2 men) between the ages of 50 and 65 years who were undergoing ICI therapy for a variety of malignant tumors were included in this study. Only 1 patient was receiving combined ICI therapy. The results of 13 separate MRI examinations were reviewed. The most commonly performed MRIs were of the hands and wrists (9 MRIs), followed by knee examinations (3 MRIs). Tenosynovitis and synovitis were frequently seen in the hands and wrists. Bone marrow edema and erosions were also found in 3 patients, suggesting early damage. In larger joints (ie, knees and ankles), joint effusions and synovial thickening were characteristic. Most patients (5 patients) were treated with corticosteroids and had good responses. In patients with high-risk features on MRI imaging (eg, bone marrow edema, erosions), disease-modifying antirheumatic drug therapy was also discussed as a treatment option. Conclusions and Relevance These findings suggest that advanced imaging may help to distinguish ICI-induced inflammatory arthritis from other causes of joint pain, aid in identifying patients at increased risk of joint damage, and provide utility in monitoring inflammatory arthritis treatment response in patients receiving ICI therapy. This case series examines the use of magnetic resonance imaging to identify arthritis associated with use of immune checkpoint inhibitors in patients with cancer.

To determine the relationship between CT-derived muscle metrics and standardized metrics of sarcopenia in patients undergoing routine CT imaging. Data collected in 443 consecutive patients included body CT, grip strength, usual gait speed, and responses to SARC-F and FRAIL scale questionnaires. Functional and clinical metrics of sarcopenia were acquired at the time of CT. Metrics were analyzed using the diagnostic framework of the European Working Group on Sarcopenia in Older People (EWGSOP2). The skeletal muscle index (SMI) and skeletal muscle density (SMD) were measured at the T12 and L3 levels. Statistical methods include linear prediction models and ROC analysis. T12-SMD and L3-SMD in women and T12-SMD and L3-SMI in men show weak but significant (p < 0.05) predictive value for gait speed, after adjusting for subject age and body mass index. The prevalence of abnormal CT SMI at T12 and L3 was 29% and 71%, respectively, corresponding to prevalences of confirmed sarcopenia by EWGSOP2 of 10% and 15%, respectively. The agreement of abnormal SARC-F and FRAIL scale screening and EWGSOP2 confirmed sarcopenia was slight to fair (kappa: 0.20–0.28). CT cutpoints, based on EWGSOP2 criteria for abnormal grip strength or gait speed, are generally lower than cutpoints based on normative population data. Collection of clinical and functional sarcopenia information at the point of imaging care can be accomplished quickly and safely. CT-derived muscle metrics show convergent validity with gait speed. Only a minority of subjects with low CT metrics have confirmed sarcopenia by EWGSOP2 definition.

OBJECTIVE:To analyze the MRI characteristics of distal superficial medial collateral ligament (sMCL) tears and to identify features of tears displaced superficial to the pes anserinus (Stener-like lesion (SLL)).MATERIALS AND METHODS:Knee MRI examinations at four institutions were selected which showed tears of the sMCL located distal to the joint line. MRIs were evaluated for a SLL, a wavy contour to the sMCL, and the location of the proximal sMCL stump. Additional coexistent knee injuries were recorded.RESULTS:The study included 51 patients (mean age, 28 years [sd, 12]). A SLL was identified in 20 of 51 cases. The proximal stump margin was located significantly (p < 0.01) more distal and more medial with a SLL (mean = 33 mm [sd = 11 mm] and mean = 6.5 mm [sd = 2.5 mm], respectively), than without a SLL (mean = 19 mm [sd = 16 mm] and mean = 4.8 mm [sd = 2.4 mm], respectively). Medial compartment osseous injury was significantly (p < 0.05) more common with a SLL (75%) than without a SLL (42%). The frequency of concomitant injuries in the group (ACL tear, 82%; PCL tear, 22%; deep MCL tear, 61%; lateral compartment osseous injury, 94%) did not differ significantly between patients with and without a SLL.CONCLUSION:A distal sMCL tear should be considered when MRI depicts a wavy appearance of the sMCL. Distal sMCL tears have a frequent association with concomitant knee injuries, especially ACL tears and lateral femorotibial osseous injuries. A SLL is particularly important to recognize because of implications for treatment.

Objective:To describe the imaging findings of patients treated with subchondroplasty (SCP) of the ankle and hindfoot. Materials and Methods: Eighteen patients (10 men, 8 women; age mean 43.1 years [range 20.1-67.7 years]) underwent ankle and hindfoot SCP at a single center over a 14-month period. Imaging data were reviewed retrospectively by 2 radiologists by consensus interpretation, including preoperative radiography (18), computed tomography (CT) (11), and magnetic resonance imaging (MRI) (13) and postoperative radiography (10), CT (4), and MRI (6). Follow-up imaging was acquired 1 month to 1.6 years following SCP. Results: Indications for SCP included symptomatic bone marrow lesions (BMLs) secondary to an osteochondral lesion (OCL) (16/18) or stress fracture (2/18). While focal radiodensity related to the SCP procedure was retrospectively identifiable on postoperative radiography in all except 1 case (10/11), postprocedural findings were not described by the interpreting radiologist in 6/11 cases. On CT, the average injected synthetic calcium phosphate (CaP) volume was 1.15 cm3 (SD = 0.33 cm3); mean CT attenuation of the injectate was 1220 HU (range 1058-1465 HU). In all patients who had pre- and postoperative MRI (5/18), BML size decreased on follow-up MRI. Extra-osseous extrusion of CaP was not seen on postoperative radiography, CT, or MRI. Conclusion: Physicians should be aware of the expanding preoperative indications and postoperative imaging findings of SCP, which is being performed with increasing frequency in the ankle and hindfoot. Levels of Evidence: Diagnostic, Level III: Retrospective cohort study