Supramolecularly engineered bacteria mediated calcium overload and immunotherapy of tumors.

Intracellular Ca2+ nanogenerators, such as calcium carbonate, calcium peroxide, and calcium phosphate nanoparticles, have shown promise in calcium overload-mediated tumor therapy. However, their effectiveness is often hampered by poor targeting, low accumulation, and limited penetration into tumor cells, leading to suboptimal therapeutic outcomes. This strategy aims to achieve synergistic Ca2+ overload and immunotherapy of tumors. Methods: A supramolecular conjugate of engineered living bacteria (facultative anaerobic Salmonella typhimurium VNP20009, VNP) with CaCO3 nanoparticles was developed for targeted delivery of curcumin-loaded CaCO3 into tumors. Results: Both CaCO3 nanoparticles and the loaded Ca2+ efflux inhibiting agent, curcumin (CUR), demonstrated significant enhancement of intracellular Ca2+ overload, resulting in apoptosis of tumor cells via mitochondrial dysfunction. Moreover, VNP exhibited excellent tumor-targeting ability, colonization in tumor tissues, and anticancer activity with minimal side effects. Conclusion: The conjugate of VNP and CaCO3 not only enhances the efficiency of common cancer treatments but also synergizes Ca2+ overload with cancer immunotherapy, thereby offering a promising approach for improving therapeutic outcomes in cancer treatment.

First site-specific conjugation method for native goat IgG antibodies via glycan remodeling at the conserved Fc region.

Despite their triumph in treating human diseases, antibody therapies for animals have gained momentum more slowly. However, the first approvals of animal antibodies for osteoarthritic pain in cats and dogs may herald the dawn of a new era. For example, goats are vital to economies around the world for their milk, meat, and hide products. It is therefore imperative to develop therapies to safeguard goats-with antibodies at the forefront. Goat antibodies will be crucial in the development of therapeutic antibodies, for example, as tracers to study antibody distribution in vivo, reagents to develop other therapeutic antibodies, and therapeutic agents themselves (e.g., antibody-drug conjugates). Hamstringing this effort is a still-burgeoning understanding of goat antibodies and their derivatization. Historically, goat antibody conjugates were generated through stochastic chemical modifications, producing numerous attachment sites and modification ratios, thereby deleteriously impacting antigen binding. Site-specific methods exist but often require substantial engineering and have not been demonstrated with goat antibodies. Nevertheless, we present herein a novel method to site-specifically conjugate native goat antibodies: chemo-enzymatic remodeling of the native Fc N-glycan introduces a reactive azide handle, after which click chemistry with strained alkyne partners affords homogeneous conjugates labeled only on the Fc domain. This process is robust, and resulting conjugates retain their antigen binding and specificity. To our knowledge, our report is the first for site-specific conjugation of native goat antibodies. Furthermore, our approach should be applicable to other animal antibodies-even with limited structural information-with similar success.

APIR: Aggregating Universal Proteomics Database Search Algorithms for Peptide Identification with FDR Control.

Advances in mass spectrometry (MS) have enabled high-throughput analysis of proteomes in biological systems. The state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide-spectrum matches (PSMs), which convert mass spectra to peptide sequences. Different database search algorithms use distinct search strategies and thus may identify unique PSMs. However, no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and a control on the false discovery rate (FDR). To fill in this gap, we proposed a statistical framework, Aggregation of Peptide Identification Results (APIR), that is universally compatible with all database search algorithms. Notably, under an FDR threshold, APIR is guaranteed to identify at least as many, if not more, peptides as individual database search algorithms do. Evaluation of APIR on a complex proteomics standard dataset showed that APIR outpowers individual database search algorithms and empirically controls the FDR. Real data studies showed that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search algorithms. The APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis, e.g., differential gene expression analysis on RNA sequencing data. The APIR R package is available at https://github.com/yiling0210/APIR.

Engineered Skin Substitutes in Dermatologic Surgery: A Systematic Review.

BACKGROUND: Artificial skin substitutes are a flexible alternative to autografting in Mohs micrographic surgery (MMS), but the characteristics and clinical outcomes of skin substitutes are not well defined. OBJECTIVE: Summarize clinical data of skin substitutes in MMS for cutaneous malignancy. METHODS: A MEDLINE/Embase/Web of Science search was conducted. Articles with original data on outcomes after skin substitute use in MMS for cutaneous malignancy were included. Articles not in English or without original data were excluded. Bias was assessed using the Oxford CEBM Levels of Evidence Table. Outcomes were synthesized using weighted averages. This study was prospectively registered in PROSPERO. RESULTS: Of 1,007 articles, 40 met eligibility for inclusion. In total, 898 patients who underwent MMS and received a skin substitute were included. Xenografts were most commonly used ( n = 613). Semi-synthetic grafts (∼$<1/cm 2 ) and xenografts (∼$10/cm 2 ) are most affordable. Overall, outcomes were excellent for all skin substitutes, with a small proportion of patients experiencing correctable complications. CONCLUSION: Skin substitutes are highly effective in MMS, with enormous potential. While the data demonstrate positive outcomes, they predominately draw from small, retrospective studies or case reports. There is also a scarcity of data comparing skin substitutes with each other or controls. Prospective studies are recommended.

AI driven analysis of MRI to measure health and disease progression in FSHD.

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.

Reconstructing Nasal Defects With Acellular Dermal Matrix After Mohs Micrographic Surgery: A 12-year Experience.

BACKGROUND AND OBJECTIVE: Large defects of the nose after Mohs surgery pose a significant reconstructive challenge to both dermatologic and reconstructive surgeons. The authors present their 12-year experience utilizing acellular dermal matrices for nasal reconstruction. METHODS: A retrospective review of patients undergoing Mohs surgery and alloplastic nasal reconstruction with acellular dermal matrices between 2010 and 2022 was performed. Patients who underwent single-stage reconstruction and dual-stage reconstruction with skin graft with at least 90 days of follow-up were included. RESULTS: Fifty-one patients met criteria with a median age of 77 years. Fifty-three lesions were reconstructed with acellular dermal matrices. The most common lesion location was nasal sidewall (50%) with a mean defect size of 10.8 cm 2 . 30.8% underwent same-day acellular dermal matrix reconstruction, with 69.2% undergoing two-stage reconstruction. Acellular dermal matrices successfully reconstructed acquired defects in 94.2% of lesions. Average time to re-epithelialization was 27.6 + 6.2 days. Average time to repigmentation was 145.35 + 86 days. No recurrences were recorded. Total complication rate was 9.62%. Average size for successful healing was 10.8 cm 2 . Average defect size for complication or failure was 14.7 cm 2 . Seven sites (13.46%) underwent aesthetic improvement procedures. CONCLUSION: Acellular bilayer wound matrix is an adequate reconstructive option for single or dual-stage reconstruction of the nose with low complication and revision rates.

Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.

BACKGROUND: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38ß MAPK) for the treatment of facioscapulohumeral muscular dystrophy. METHODS: We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4-driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. FINDINGS: Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45·7 (SD 12·5) years. Least squares mean changes from baseline in DUX4-driven gene expression did not differ significantly between the losmapimod (0·83 [SE 0·61]) and placebo (0·40 [0·65]) groups (difference 0·43 [SE 0·56; 95% CI -1·04 to 1·89]; p=0·56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drug-related) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. INTERPRETATION: Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy. FUNDING: Fulcrum Therapeutics.

Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial.

Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly to current therapies. Here we report a completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose and a recommended phase 2 dose plan. Secondary objectives included overall survival, disease response, cytokine dynamics and tumor immune contexture biomarkers. This trial evolved to evaluate three routes of locoregional T cell administration (intratumoral (ICT), intraventricular (ICV) and dual ICT/ICV) and two manufacturing platforms, culminating in arm 5, which utilized dual ICT/ICV delivery and an optimized manufacturing process. Locoregional CAR-T cell administration was feasible and well tolerated, and as there were no dose-limiting toxicities across all arms, a maximum tolerated dose was not determined. Probable treatment-related grade 3+ toxicities were one grade 3 encephalopathy and one grade 3 ataxia. A clinical maximum feasible dose of 200 × 106 CAR-T cells per infusion cycle was achieved for arm 5; however, other arms either did not test or achieve this dose due to manufacturing feasibility. A recommended phase 2 dose will be refined in future studies based on data from this trial. Stable disease or better was achieved in 50% (29/58) of patients, with two partial responses, one complete response and a second complete response after additional CAR-T cycles off protocol. For rGBM, median overall survival for all patients was 7.7 months and for arm 5 was 10.2 months. Central nervous system increases in inflammatory cytokines, including IFNγ, CXCL9 and CXCL10, were associated with CAR-T cell administration and bioactivity. Pretreatment intratumoral CD3 T cell levels were positively associated with survival. These findings demonstrate that locoregional IL-13Rα2-targeted CAR-T therapy is safe with promising clinical activity in a subset of patients. ClinicalTrials.gov Identifier: NCT02208362 .

Relationship Between Hand Function and Handheld Ultrasound Imaging in Inclusion Body Myositis.

OBJECTIVE: Ultrasound studies in inclusion body myositis (IBM) have reported a characteristic pattern of increased echointensity in the flexor digitorum profundus (FDP) with relative sparing of the flexor carpi ulnaris (FCU). We examined the relationship between echointensity of the FDP and FCU muscles and hand strength or patient-reported outcomes (PROs). METHODS: A total of 15 patients with IBM were recruited. Ultrasound images of the FDP and FCU muscles were obtained by a point-of-care ultrasound and graded using the modified Heckmatt score. Hand grip and neutral pinch strength were measured by dynamometry. PROs were assessed by the IBM Upper Extremity Function Scale. RESULTS: FDP and/or FCU modified Heckmatt score showed a significant relationship with grip, neutral pinch strength, and PROs. CONCLUSIONS: Point-of-care ultrasound examination of the forearm may serve as an extension of the neuromuscular examination. The semi-qualitative echointensity rating based on modified Heckmatt score seems to correlate well with the objective strength measurement and PROs.

Metastatic gastric adenocarcinoma to the cutaneous neck and chest wall.

This case describes an atypical cutaneous presentation of metastatic gastric carcinoma in a patient initially presenting with dysphagia and a sclerotic red plaque overlying the anterior neck and chest. Skin biopsy revealed metastatic adenocarcinoma from the upper gastrointestinal tract. Esophagogastroduodenoscopy revealed stage IV metastatic gastric adenocarcinoma. Treatment with chemotherapy was initiated.

Regional and bilateral MRI and gene signatures in facioscapulohumeral dystrophy: implications for clinical trial design and mechanisms of disease progression.

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.

Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts.

Janus kinase (JAK) inhibitors are approved for many dermatologic disorders, but their use is limited by systemic toxicities including serious cardiovascular events and malignancy. To overcome these limitations, injectable hydrogels are engineered for the local and sustained delivery of baricitinib, a representative JAK inhibitor. Hydrogels are formed via disulfide crosslinking of thiolated hyaluronic acid macromers. Dynamic thioimidate bonds are introduced between the thiolated hyaluronic acid and nitrile-containing baricitinib for drug tethering, which is confirmed with 1H and 13C nuclear magnetic resonance (NMR). Release of baricitinib is tunable over six weeks in vitro and active in inhibiting JAK signaling in a cell line containing a luciferase reporter reflecting interferon signaling. For in vivo activity, baricitinib hydrogels or controls are injected intradermally into an imiquimod-induced mouse model of psoriasis. Imiquimod increases epidermal thickness in mice, which is unaffected when treated with baricitinib or hydrogel alone. Treatment with baricitinib hydrogels suppresses the increased epidermal thickness in mice treated with imiquimod, suggesting that the sustained and local release of baricitinib is important for a therapeutic outcome. This study is the first to utilize a thioimidate chemistry to deliver JAK inhibitors to the skin through injectable hydrogels, which has translational potential for treating inflammatory disorders.

Using Integra for Reconstruction of Facial Defects after Mohs Micrographic Surgery.

Background: We aimed to identify how Integra bilayer wound matrix has expanded facial reconstruction options after Mohs surgery due to its reliability in both single- and dual-stage reconstruction. Methods: A retrospective review of patients undergoing Mohs surgery and alloplastic facial reconstruction with Integra between 2012 and 2022 was performed. Patients who underwent single-stage reconstruction and dual-stage reconstruction with skin graft with at least 90 days of follow-up were included. Results: One hundred thirty patients with a median age of 76 years were included. Basal cell carcinoma was the most common malignancy (39%). One hundred forty-two lesions were treated and reconstructed same-day with Integra. Lesions most commonly involved the nose (34%) and forehead (22%). The mean postoperative defect size was 26.9 cm2. An estimated 45.5% (n = 60) of defect sites underwent single-stage reconstruction with healing by secondary intention, whereas 54.5% (n = 72) underwent dual-stage reconstruction with skin graft. Integra success rate was 90.2%. Average time to re-epithelialization was 32.2 + 7.3 days. Average time to repigmentation was 169.5 + 14.6 days. The complication rate was 12.8% (n = 17), with 12 undergoing debridement, three needing new Integra graft, and seven needing new skin grafts. Average size for successful healing without complication was 26.6 cm2. Nineteen sites (13.2%) underwent aesthetic improvement procedures, with the majority occurring after dual-stage reconstruction (n = 13). Conclusions: Integra is a reliable outpatient reconstructive option for facial Mohs defects that can increase the threshold for autologous tissue harvesting and successfully reconstruct large defects of 26.6 cm2 on average with low complication and reoperation rates.

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival.

Introduction: Avelumab is a programmed cell death-ligand 1 (PD-L1) inhibitor approved by the Food and Drug Administration for advanced Merkel cell carcinoma (MCC). Studies conducted in real-world settings have shed light on its effectiveness and safety in clinical settings. Areas Covered: Real-world studies on avelumab for MCC from North and South America, Europe, and Asia have been presented in this review. Most studies are on patients over age 70 and have a male-predominant sex ratio. Overall response rates range from 29.1% to 72.1%, (disease control rate: 60.0-72.7%; complete response rate: 15.8%-37.2%; partial rate: 18.2-42.1%; stable disease: 7.1-30.9%; progressive disease: 7.1-40.0%) and median progression free survival ranges from 8.1 to 24.1 months depending on the population studied. Immunosuppressed patients appear to benefit from avelumab as well, with response rates equivalent to the general population. Patients receiving avelumab as a first-line agent tend to have better outcomes than those using it as a second-line therapy. Fatigue, infusion-related reactions, and dyspnea were some of the most common adverse events identified in real-world studies. Autoimmune hepatitis and thyroiditis were also observed. Conclusion: The use of avelumab as a safe and effective treatment option for advanced MCC is supported by real-world data, although additional study is required to assess long-term efficacy and safety outcomes.

Cutaneous mantle cell lymphoma presenting as a diffuse morbilliform rash: A case report.

This case describes a patient with known mantle cell lymphoma without cutaneous involvement presenting with a diffuse morbilliform rash during an inpatient admission for bacterial pneumonia. The patient was thought to have a hypersensitivity to antibiotics but failed to improve after the offending agents were stopped. A skin biopsy revealed metastatic cutaneous mantle cell lymphoma. Treatment with high-dose corticosteroids and chemotherapy was initiated resulting in the resolution of the rash.

Expansion of endogenous T cells in CSF of pediatric CNS tumor patients undergoing locoregional delivery of IL13R〿2-targeting CAR T cells: an interim analysis.

Outcomes for pediatric brain tumor patients remain poor, and there is optimism that chimeric antigen receptor (CAR) T cell therapy can improve prognosis. Here, we present interim results from the first six pediatric patients treated on an ongoing phase I clinical trial (NCT04510051) of IL13BBζ-CAR T cells delivered weekly into the lateral cerebral ventricles, identifying clonal expansion of endogenous CAR-negative CD8+ T cells in the cerebrospinal fluid (CSF) over time. Additionally, of the five patients evaluable for disease response, three experienced transient radiographic and/or clinical benefit not meeting protocol criteria for response. The first three patients received CAR T cells alone; later patients received lymphodepletion before the first infusion. There were no dose limiting toxicities (DLTs). Aside from expected cytopenias in patients receiving lymphodepletion, serious adverse events possibly attributed to CAR T cell infusion were limited to one episode of headache and one of liver enzyme elevation. One patient withdrew from treatment during the DLT period due to a Grade 3 catheter-related infection and was not evaluable for disease response, although this was not attributed to CAR T cell infusion. Importantly, scRNA- and scTCR-sequence analyses provided insights into CAR T cell interaction with the endogenous immune system. In particular, clonally expanded endogenous CAR- T cells were recovered from the CSF, but not the peripheral blood, of patients who received intraventricular IL13BBζ-CAR T cell therapy. Additionally, although immune infiltrates in CSF and post-therapy tumor did not generally correlate, a fraction of expanded T cell receptors (TCRs) was seen to overlap between CSF and tumor. This has important implications for what samples are collected on these trials and how they are analyzed. These initial findings provide support for continued investigation into locoregionally-delivered IL13BBζ-CAR T cells for children with brain tumors.

Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting.

Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumors. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies. Here, we describe CAR T cells targeting tumor-associated glycoprotein-72 (TAG72), utilizing the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. CAR T cell-mediated IFNγ production facilitated by IL-12 signaling is required for tumor cell killing, which is recapitulated by engineering an optimized membrane-bound IL-12 (mbIL12) molecule in CAR T cells. These T cells show improved antigen-dependent T cell proliferation and recursive tumor cell killing in vitro, with robust in vivo efficacy in human ovarian cancer xenograft models. Locoregional administration of mbIL12-engineered CAR T cells promotes durable anti-tumor responses against both regional and systemic disease in mice. Safety and efficacy of mbIL12-engineered CAR T cells is demonstrated using an immunocompetent mouse model, with beneficial effects on the immunosuppressive tumor microenvironment. Collectively, our study features a clinically-applicable strategy to improve the efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting regional and systemic disease.

Lean tissue mass measurements by dual-energy X-ray absorptiometry and associations with strength and functional outcome measures in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive disease of skeletal muscle. Dual energy X-ray absorptiometry (DEXA) is a widely available, cost-effective and sensitive technique for measuring whole body and regional lean tissue mass and has been used in prior clinical trials in neuromuscular diseases. The Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD (ReSolve) study is a prospective, longitudinal, observational multisite study. We obtained concurrent DEXA scans and functional outcome measurements in 185 patients with FSHD at the baseline visit. We determined the associations between lean tissue mass in the upper and lower extremities and corresponding clinical outcome measures. There were moderate correlations between upper and lower extremity lean tissue mass and their corresponding strengths and function. Lean tissue mass obtained by DEXA scan may be useful as a biomarker in future clinical trials in FSHD.