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Background: The Goutallier classification (GC) is used to assess fatty atrophy in rotator cuff (RC) tears, yet limitations exist. A battery of 3-dimensional (3D) magnetic resonance imaging (MRI) volumetric scores (VSs) was developed to provide comprehensive characterization of RC pathology. The purposes of this study were to (1) describe the correlation between GC and VSs for supraspinatus changes in RC tears, (2) characterize the chronicity of RC tears using a battery of 12 VS measurements, and (3) compare GC and VSs to determine which method most closely corresponds with preoperative patient-reported outcome measures (PROMs)., Methods: Preoperative shoulder MRIs were reviewed after arthroscopic RC repair. Preoperative GC stage and Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) scores were collected. The battery of VSs included fat infiltration (FIS), muscle size (MSS), and relative volume contribution (RCS) for each RC muscle. Backward linear regression was performed to compare GC stage with preoperative PROMIS PF and PI to determine which VS measurement most closely correlated with preoperative PROMs., Results: Eighty-two patients underwent RC repair (mean age 55 ± 8.2 years, 63% male, 68% GC stage ≤1). In evaluation of the supraspinatus, there was a moderate positive correlation between GC and FIS (r = 0.459, P < .001); strong negative correlations were observed between MSS (r = -0.800, P < .001) and RCS (r = -0.745, P < .001) when compared to GC. A negligible linear correlation was observed between GC and preoperative PROMIS PF (r = -0.106, P = .343) and PI (r = -0.071, P = .528). On multivariate analysis, subscapularis MSS (β >0, P = .064) was a positive predictor and subscapularis FIS (β <0, P = .137), teres minor MSS (β <0, P = .141), and FIS (β <0, P = .070) were negative predictors of preoperative PF (r = 0.343, P = .044); in contrast, supraspinatus MSS (β >0, P = .009) and FIS (β >0, P = .073), teres minor FIS (β >0, P = .072), and subscapularis FIS (β >0, P = .065) were positive predictors of preoperative PI (r = 0.410, P = .006)., Conclusion: Although the criterion standard in evaluation of RC pathology, GC demonstrated negligible correlation with preoperative functional disability. Alternatively, a battery of 3D VSs showed strong correlation with GC through a quantitative, comprehensive evaluation of the RC unit including several moderate predictors of preoperative functional disability., (Published by Elsevier Inc.)

Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers., (© 2024. The Author(s).)

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA, indicating that regional biopsies can accurately measure progression in the whole muscle and providing a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design. An unanticipated finding was the strong correlations of molecular signatures in the bilateral comparisons, including markers of B-cells and other immune cell populations, suggesting that a systemic immune cell infiltration of skeletal muscle might have a role in disease progression., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in white-skinned populations. There is little information on the epidemiology of cSCC, and even less on advanced cases (acSCC). Therefore, we analyzed acSCC patients to describe their characteristics, management, and outcomes over time., Methods: A single-center retrospective study was conducted over a period of 5 years, including all patients who started systemic therapy for acSCC. The patient characteristics, cSCC management, response to therapy, and survival were recorded. Patients were stratified into equal chronological periods (periods 1 and 2). A subgroup analysis was performed to compare patients who received immunotherapy (group 1) with those who did not (group 2)., Results: The study included 127 patients, and patient numbers increased by an average of 19.7% per year. Most patients were male (88/127), elderly (mean 81.6 years), with comorbidities, and 27.6% were immunocompromised. The median overall survival (OS) was higher in period 2 (20 months) than in period 1 (10 months) (hazard ratio [95% confidence interval] = 0.62 [0.39; 0.98], p = 0.04). The risk of progression increased with age and immunosuppression. Of the 64 patients who received second-line therapy, 38 had immunotherapy (group 1) and 26 received other therapies (group 2). Immunotherapy reduced mortality and progression by 71% (p = 0.004) and 67% (p = 0.002), respectively., Conclusions: Patients with acSCC are usually very frail and elderly. OS increased over time, with a twofold improvement between periods 1 and 2, whereas progression-free survival (PFS) did not increase. Access to immunotherapy reduced mortality in a majority of patients in period 2. Immunosuppression and advanced age were associated with lower PFS., (© 2024. The Author(s).)

Objective analysis of rotator cuff (RC) atrophy and fatty infiltration (FI) from clinical MRI is limited by qualitative measures and variation in scapular coverage. The goals of this study were to: develop/evaluate a method to quantify RC muscle size, atrophy, and FI from clinical MRIs (with typical lateral only coverage) and then quantify the effects of age and sex on RC muscle. To develop the method, 47 full scapula coverage CTs with matching clinical MRIs were used to: correct for variation in scan capture, and ensure impactful information of the RC is measured. Utilizing this methodology and automated artificial intelligence, 170 healthy clinical shoulder MRIs of varying age and sex were segmented, and each RC muscle's size, relative contribution, and FI as a function of scapula location were quantified. A two-way ANOVA was used to examine the effect of age and sex on RC musculature. The analysis revealed significant (p < 0.05): decreases in size of the supraspinatus, teres minor, and subscapularis with age; decreased supraspinatus and increased infraspinatus relative contribution with age; and increased FI in the infraspinatus with age and in females. This study demonstrated that clinically obtained MRIs can be utilized for automatic 3D analysis of the RC. This method is not susceptible to coverage variation or patient size. Application of methodology in a healthy population revealed differences in RC musculature across ages and FI level between sexes. This large database can be used to reference expected muscle characteristics as a function of scapula location and could eventually be used in conjunction with the proposed methodology for analysis in patient populations., (© 2023. Springer Nature Limited.)

BRAF V600 wild-type advanced melanomas quickly reach a therapeutic dead-end, after immunotherapy failure. Even if preclinical studies have suggested sensitivity to MEK inhibitors such as trametinib in NRAS, NF1 or GNA mutated melanoma, therapeutic options are limited for these patients. We present a retrospective monocentric study of 22 patients with advanced melanoma treated by trametinib after immunotherapy resistance. Melanomas harboured NRAS (20), NF1 (1) or GNA 11 (1) mutations. For most of them (18), anti-PD1 was associated with trametinib. A disease-control was reported in 36% of patients (8/22), with six stable diseases and two partial responses according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Median progression-free survival was 2 months (1-14) and median overall survival was 6.5 months (2-24). In patients with progressive disease (14/22), dissociated radiologic responses and clinical benefits such as pain reduction were seen in five patients. High blood level of lactate dehydrogenase (LDH) seemed associated with trametinib failure, without significance ( P  = 0.06). Adverse events (grade 1-3) occurred in 91% of patients during the first weeks of treatment, mainly papulo-pustular rashes (77%), leg oedemas (36%), asthenia (18%) and diarrhoea (14%). This real-life study showed that trametinib may benefit some metastatic melanoma that progressed after chemotherapy and immune checkpoint inhibitors. Objective disease control (partial response or stable disease) using RECIST criteria was observed in 36% of patients. Because of frequent side-effects which can alter the quality of life and the short response duration, this off-label option has to be discussed with the patient. Studies with combination therapy with trametinib to improve relapse-free survival and lower side-effects are ongoing., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The authors aimed to develop and validate an automated artificial intelligence (AI) algorithm for three-dimensional (3D) segmentation of all four rotator cuff (RC) muscles to quantify intramuscular fat infiltration (FI) and individual muscle volume. The dataset included retrospectively collected RC MRI scans in 232 patients (63 with normal RCs, 169 with RC tears). A two-stage AI model was developed to segment all RC muscles and their FI in each stage. For comparison, single-stage and Otsu filtering models were created. Using the two-stage model, segmentation performance demonstrated high Dice scores (mean, 0.92 ± 0.14 [SD]), low volume errors (mean, 5.72% ± 9.23), and low FI errors (mean, 1.54% ± 2.79) when validated in 30 scans. There was a significant correlation between the 3D FI in the RC tear scans with a Goutallier grade (ρ = 0.53, P < .001) and FI found from a single two-dimensional (2D) section (all muscles, ρ > 0.70; P < .001). However, Bland-Altman analysis of the 3D compared with the 2D analyses of FI demonstrated a proportional bias (all muscles, P < .001). Compared with Goutallier classification or single-image quantification, the AI method allowed for more variability in images and led to objective separate quantifications of muscle volume and FI in all RC muscles. Keywords: Rotator Cuff, Artificial Intelligence, Segmentation, Fat Infiltration, Muscle Volume, MRI, Shoulder Supplemental material is available for this article. © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: L.R. National Institutes of Health (NIH) Small Business Innovation Research (SBIR) grant; Springbok Analytics also provided financial support; patent pending for U.S. application no. 17/664,893: Systems and Methods for Extremity Analysis and Modeling using Medical Imaging, filed May 25, 2022 (175340.00002); Springbok Analytics stock options. X.F. Springbok support paid to author; consulting fees from Springbok; stock/stock options in Springbok. M.C. NIH SBIR grant; Springbok Analytics employee; patent pending for U.S. application no. 17/664,893: Systems and Methods for Extremity Analysis and Modeling using Medical Imaging, filed May 25, 2022 (175340.00002). O.D. NIH SBIR grant; Springbok Analytics; patent pending for U.S. application no. 17/664,893: Systems and Methods for Extremity Analysis and Modeling using Medical Imaging, filed May 25, 2022 (175340.00002); stock options in Springbok. E.B.L. Employment at University of Virginia (UVA) (payments made to UVA for author’s work on this study). B.C.W. No relevant relationships. A.J.S. Board of directors, The Society of Military Orthopaedic Surgeons; committee member, The American Orthopaedic Society for Sports Medicine; personal fees from Arthroscopy journal. J.H. Equity as a consultant for Springbok; stock/stock options in Springbok. I.J.A. No relevant relationships. S.S.B. Springbok Analytics; NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases grant (R41 AR078720); patent pending for U.S. application no. 17/664,893: Systems and Methods for Extremity Analysis and Modeling using Medical Imaging, filed May 25, 2022 (175340.00002); stock options in Springbok Analytics., (© 2023 by the Radiological Society of North America, Inc.)

Primary cutaneous large B-cell lymphomas (PCLBCL) represent a diagnostic challenge because they are classified as PCLBCL, leg type (PCLBCL, LT) or primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC), which differ by prognosis and therapeutic requirement. Unclassified cases with discordant clinical presentations, morphologies, and immunophenotypes may be classified into the not otherwise specified (PCLBCL, NOS) category based on ancillary molecular analyses. Cell-of-origin profiling as germinal centre (GC) type or non-GC type by immunohistochemistry is not considered reproducible because of variable CD10 expression. In a series of 55 PCLBCL cases with > 80% large cells, we reported 21 PCFCL, LC cases as GC-type and 27 PCLBCL, LT as non-GC-type; 7 cases were considered PCLBCL, NOS. Here, we demonstrate the accuracy of molecular profiling of PCLBCL as GC or non-GC type using a reverse transcriptase multiplex ligation assay (RT-MLPA). RT-MLPA classified the seven PCLBCL, NOS cases in accordance with their mutational profile. An integrative principal component analysis confirmed the main criteria and the relevance of genomic profiling of PCFCL, LC as GC-derived, and PCLBCL, LT as non-GC-derived. Both the cell-of-origin classification of PCLBCL and the integrative analysis identified two clinically relevant subgroups according to overall survival, which may help to standardize PCLBCL diagnosis and patient management., Competing Interests: The authors have declared that no competing interests exist.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. Combination of ICI with ipilimumab cytotoxic T-lymphocyte antigen-4 and nivolumab [anti-programmed cell death-1 (PD-1)] improves tumoral response compared to anti-PD1 monotherapy in melanoma patients, but is associated with more severe and multiple immune-related adverse events. We report the first case of aseptic cystitis induced by ipilimumab and nivolumab combination in a 61-year-old melanoma patient. She described after two infusions, diarrhea, pollakiuria, intense bladder pain, urinary urgency, and nocturia. Repeated negative urine culture tests led to perform cystoscopy. Mucosal bladder biopsies showed lymphocytic T-cells infiltration in intraepithelial and in subepithelial connective tissue, which were consistent with the diagnosis of immune-related aseptic cystitis. Aseptic cystitis is a rare and poorly known side-effect related to ICI. Only four other cases with anti-PD1 monotherapy were found in literature, only in Japanese patients. It simulates bacterial cystitis with negative urinary tests, and is often associated with atypical symptoms like diarrhea, which may delay the diagnosis. Oral steroids appear to be the most efficient therapeutic options., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

In French Guiana, five species are associated with Cutaneous Leishmaniasis (CL). Though infections with Leishmania guyanensis, L. (V.) braziliensis and L. (L.) amazonensis have been extensively described, there are few available clinical and genetic data on L. (V.) lainsoni and L. (V.) naiffi. We determined the clinical and epidemiological features of all cases of CL due to L. (V.) naiffi and L. (V.) lainsoni diagnosed in French Guiana between 2003 and 2019. Phylogenetic analysis was performed by sequencing a portion of HSP70 and cyt b genes. Five cases of L. naiffi and 25 cases of L. lainsoni were reported. Patients infected by L. (V.) lainsoni were usually infected on gold camps, mostly along the Maroni river (60%), while L. naiffi was observed in French patients infected on the coast (100%). A high number of pediatric cases (n = 5; 20%) was observed for L. (V.) lainsoni. A mild clinical course was observed for all cases of L. (V.) naiffi. HSP70 and cyt b partial nucleotide sequence analysis revealed different geographical clusters within L. (V.) naiffi and L. (V.) lainsoni but no association were found between phylogenetic and clinical features. Our data suggest distinct socio-epidemiological features for these two Leishmania species. Patients seem to get infected with L. (V.) naiffi during leisure activities in anthropized coastal areas, while L. (V.) lainsoni shares common features with L. (V.) guyanensis and braziliensis and seems to be acquired during professional activities in primary forest regions. Phylogenetic analysis has provided information on the intraspecific genetic variability of L. (V.) naiffi and L. (V.) lainsoni and how these genotypes are distributed at the geographic level., Competing Interests: The authors have declared that no competing interests exist.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) preferentially involves the lower limb in elderly subjects. A combination of polychemotherapy and rituximab has improved prognosis. However, about 50% of patients will experience progression or relapse without any predictive biologic marker of therapeutic response. The mutational profile of PCLBCL-LT has highlighted mutations contributing to constitutive NF-κB and B-cell receptor (BCR) signaling pathways but has not demonstrated clinical utility. Therefore, the mutational status of 32 patients with PCLBCL-LT (14 patients with complete durable response and 18 patients with relapsing or refractory disease) was determined with a dedicated lymphopanel. Tumor pairs at diagnosis and relapse or progression were analyzed in 14 relapsing or refractory patients. Patients with PCLBCL-LT harboring one mutation that targets one of the BCR signaling genes, CD79A/B or CARD11, displayed a reduced progression-free survival and specific survival (median 18 months, P = 0.002 and 51 months, P = 0.03, respectively, whereas median duration in the wild-type group was not reached) and were associated with therapeutic resistance (P = 0.0006). Longitudinal analyses revealed that MYD88 and CD79B were the earliest and among the most mutated genes. Our data suggest that evaluating BCR mutations in patients with PCLBCL-LT may help to predict first-line therapeutic response and to select targeted therapies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)