The value of axillary, facial, occipital, subclavian and common carotid arteries ultrasound in the diagnosis of giant cell arteritis.

OBJECTIVE: To assess the diagnostic value for GCA in adding the axillary arteries (AX) to the temporal artery (TA) ultrasound, particularly in patients with a cranial phenotype of the disease; and to investigate the utility of facial (FA), occipital (OC), subclavian (SC), and common carotid (CC) ultrasound in patients with suspected GCA. METHODS: Patients with new-onset GCA and a positive ultrasound of the TA, AX, FA, OC, SC or CC, followed at the rheumatology departments of two academic centres, were retrospectively included. RESULTS: 230 patients were assessed. TA halo sign was identified in 206/230 (89.6%) cases, FA in 40/82 (48.8%), OC in 17/69 (24.6%), AX in 56/230 (24.3%), SC in 31/57 (54.4%), and CC in 14/68 (20.6%). Negative TA ultrasound was found in 24/230 (10.4%) patients: 22 had AX involvement, 1 exclusive OC involvement and 1 exclusive SC involvement. Adding AX evaluation to the TA ultrasound increased the diagnostic yield for GCA in 9.6%, whereas adding OC or SCs to the TA and AX ultrasound increased it in 1.4% and 1.8%, respectively. No value was found in adding the FA or CCs. Notably, 13 patients with cranial symptoms and 4 with exclusively cranial symptoms showed negative TA ultrasound but positive AX ultrasound. CONCLUSION: Adding the evaluation of AXs to the TA ultrasound increased the number of patients diagnosed with GCA, even in cases of predominantly cranial symptoms. In the subset of patients where these arteries were assessed, no substantial benefit was found in adding the FA, OC, SC or CC arteries to the TA and AX ultrasonographic assessment.

Lifestyle Modifications and Nonpharmacologic Interventions to Improve Outcomes in Psoriatic Arthritis: A Systematic Review.

PURPOSE: Psoriatic arthritis (PsA) is a multisystem inflammatory disorder associated with significant mortality and morbidity, including functional impairment and psychological disability. Although evidence-based treatment recommendations are available for the use of drug treatments in PsA, there is little guidance for health professionals on nonpharmacologic and psychological interventions that may be useful in PsA. The objective of this systematic review (SR) was to identify how lifestyle modifications and the use of nonpharmacologic and psychological interventions may improve the outcomes of patients with PsA. METHODS: Studies were included if they evaluated adults diagnosed with PsA and included exposure to nonpharmacologic interventions, psychological interventions, and lifestyle modifications. The outcomes used needed to have been validated in PsA. A systematic literature search was run on May 28, 2021, in the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), EMBASE, Global Health, MEDLINE, and PsycINFO databases to identify articles related to lifestyle modifications and nonpharmacologic or psychological interventions for adults with PsA published between 2010 and 2021. Two review authors independently screened and selected full-text studies for inclusion in the SR. Risk of bias was assessed with either the Risk of Bias 2 (ie, RoB 2) tool or Critical Appraisal Skills Program checklist depending on the study type. FINDINGS: The search strategy identified 26,132 references. Eight studies examining lifestyle modifications and the effect on PsA were eligible to be included in the SR. Three of the 8 studies were randomized controlled trials, and 5 were nonrandomized studies. Three studies assessed physical activity, 3 assessed diet, 1 study assessed smoking, and another study assessed mud bath therapy. There was large heterogeneity between studies, and the measures of disease activity, and psychological and functional outcomes varied widely between studies. IMPLICATIONS: Although this SR identified 8 relevant studies, these studies did not provide high-quality evidence to guide patients for non-drug treatments of PsA. The effectiveness of these interventions has therefore not been established. We found that physical activity seems to have a positive impact on disease activity and psychological well-being. Further well-designed research studies are needed to develop treatment recommendations. PROSPERO identifier: CRD42021257404.

ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance.

Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype. Differentiating myofibroblasts in vitro and myoCAFs cultured ex vivo display activated ATM signaling, and targeting ATM genetically or pharmacologically could suppress and reverse differentiation. ATM activation was regulated by the reactive oxygen species-producing enzyme NOX4, both through DNA damage and increased oxidative stress. Targeting fibroblast ATM in vivo suppressed myoCAF-rich tumor growth, promoted intratumoral CD8 T-cell infiltration, and potentiated the response to anti-PD-1 blockade and antitumor vaccination. This work identifies a novel pathway regulating myoCAF differentiation and provides a rationale for using ATM inhibitors to overcome CAF-mediated immunotherapy resistance. SIGNIFICANCE: ATM signaling supports the differentiation of myoCAFs to suppress T-cell infiltration and antitumor immunity, supporting the potential clinical use of ATM inhibitors in combination with checkpoint inhibition in myoCAF-rich, immune-cold tumors.