Massachusetts General Hospital

Fibroepithelial lesions (FELs) diagnosed on core needle biopsy frequently prompt surgical excision because of the diagnostic uncertainty between fibroadenomas (FAs) and phyllodes tumors (PTs). We sought to identify clinical and ultrasound features associated with FEL subtypes to inform individualized surgical decision-making. We performed a retrospective review of women diagnosed with FELs on core biopsy between 2003 and 2024 who underwent diagnostic ultrasound and surgical excision. Clinical and sonographic features were compared between (1) FAs and PTs and (2) benign versus borderline/malignant PTs. Predictors were assessed using univariate and multivariable logistic regression. Among 694 FELs in 673 women, 405 (58.4%) were FAs and 289 (41.6%) were PTs. PTs occurred in older patients (median 40 vs. 32 years), with larger tumors (2.4 vs. 1.9 cm) and higher body mass index (BMI; 25.8 vs. 23.5 kg/m2; all p < 0.001). On multivariable analysis, increasing age (odds ratio [OR] 1.045; 95% confidence interval [CI] 1.027-1.064), increasing BMI (OR 1.036; 95% CI 1.006-1.067), larger tumor size (OR 1.460; 95% CI 1.290-1.672), and non-circumscribed margins (OR 0.688; 95% CI 0.492-0.961) independently predicted PTs. On multivariable analysis of 289 PTs, tumor size (OR 1.363; 95% CI 1.179-1.616) and postmenopausal status (OR 3.052; 95% CI 1.141-8.258) were independently associated with borderline/malignant subtypes (n = 78). Younger, premenopausal patients with normal-range BMI and small, circumscribed tumors demonstrate features strongly associated with fibroadenomas, whereas increasing size, BMI, and postmenopausal status identify higher-risk PTs. These findings support integrating clinical risk stratification into shared decision-making for the management of indeterminate FELs.

To evaluate the use of the Model Predictive Filtering (MPF) method to improve temporal resolution of magnetic resonance temperature imaging (MRTI) for monitoring laser interstitial thermal therapy (LITT) ablations. Using a Green's function method for solving differential equations, a treatment-specific power matrix Q was derived from a LITT heating and used in the Pennes bioheat equation (PBHE) to model a subsequent higher power heating and supplement subsampled k-space data. This MPF method was evaluated using both 3D segmented EPI data and a tissue mimicking phantom and clinical LITT treatment data after retrospective subsampling. Reconstruction accuracy was assessed via thermal dose and analysis of the hottest voxel and region-of-voxels over time. In the phantom data, temporal resolution equivalent to a 12-slice acquisition was produced with larger fields-of-view (24 and 36 slices, R = 2 and 3) with good hottest voxel-over-time accuracy and 240 CEM43 volume agreement (Dice similarity coefficient, DSC 0.7). In the in vivo data, MPF reconstruction showed excellent 240 CEM43 volume agreement for both orthogonal slices (DSC 0.9 for R = 2 and 3). The sagittal and coronal slices showed excellent hottest voxel accuracy for subsampling of R 3, with an RMSE ≤ 1°C. Hottest voxel RMSE remained within 1°C-3°C up to a subsampling factor of 5. The MPF algorithm allowed for large field-of-view (FOV) volumetric temperature imaging without decreasing temporal resolution in phantom heatings. Bi-planar clinical treatment data reconstruction showed good accuracy for the application of MPF to in vivo data.

BackgroundBrepocitinib is a first-in-class, oral, selective TYK2–JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis.MethodsIn this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence.ResultsA total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, −2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial.ConclusionsIn adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.)

Cytokines dimerize two receptor chains to activate Janus kinases and STAT transcription factors that regulate immune cells but have therapeutic liabilities. We engineered “Trikines” to compel cis formation of three-chain cytokine receptor complexes at the cell surface that induce bespoke STAT transcriptional signaling programs optimized for therapeutic efficacy. Designed Trikines co-activated pSTAT5 and pSTAT3 signatures distinct from any natural cytokines, by assembling trimeric combinations of Interleukin-2 (IL-2), Interleukin-10 (IL-10), and Interleukin-21 (IL-21) receptors. An IL-2-based-Trikine restrained terminal differentiation of T cells, promoted stemness, and enhanced durability of tumor control without toxicity. Unexpectedly, an IL-10-based Trikine induced immune infiltration into poorly immunogenic tumors, showing striking efficacy in small cell lung cancer and pancreatic cancer models. Trikines obviate the need for cell engineering to customize STAT signatures for immunotherapy.

Large long-term assessments of opioid effectiveness and dose stability for those with dopamine agonist augmentation of restless legs syndrome (RLS) are lacking. We present 5-year longitudinal findings from the National RLS Opioid Registry. Five-hundred participants taking opioids for RLS were interviewed at baseline about RLS symptoms, opioid medications and doses, sleep, and mental health. Participants subsequently completed online surveys every 6months. Changes from baseline to 5-year follow-up in morphine milligram equivalents (MMEs), excluding those taking buprenorphine, were evaluated by group-based trajectory modeling. Independent associations with opioid dose changes were determined using multiple logistic regression. At 5 years of follow-up, 410 (364 excluding any taking buprenorphine) participants remained for this analysis. Most participants are female (57.1 per cent) and white (98.3 per cent), with an average age of 64.7 (±10.6) and 88.8 per cent had a history of dopamine agonist augmentation. The median daily MME at 5 years was 37.5 (equivalent to methadone 8.0mg or oxycodone 25.0mg), an increase of 7.5 MME from baseline. Opioid doses increased from baseline to 5 years in 49.5 per cent of participants and decreased in 20.0 per cent of participants. Group-based trajectory analysis identified four distinct groups: decrease (3.4 per cent of participants; average MME change = -15.7 ± 12.4), no/little change (66.1 per cent of participants; average MME change = 1.5 ± 8.0), small increase (23.9 per cent of participants; average MME change = 22.0 ± 11.6), and large increase (3.4 per cent of participants; average MME change = 49.2 ± 18.7). RLS severity was stable from baseline (13.3 ± 9.6) to 5 years (13.1 ± 9.0) according to the International Restless Legs Syndrome Study Group Severity Scale. Opioid doses in augmented RLS remain largely stable over 5 years of follow-up. Low-dose opioids provide an effective long-term option for augmented RLS.

Practicing CBT skills outside of therapy sessions is a core component of effective treatment, yet meaningful engagement can be difficult during periods of elevated psychological distress. Smartphone-based ecological momentary interventions (EMIs) offer a promising approach to support real-time skill use, but most research has focused on frequency rather than quality of engagement. This study examined the quality of CBT skills practice in a 28-day smartphone-based EMI following inpatient discharge and explored its associations with internal context and intervention effectiveness. Twenty-three adults hospitalized for suicidal thoughts and behaviors participated, selecting and practicing one of three guided CBT skills exercises (Mindful Emotional Awareness, Countering Emotional Behavior, or Cognitive Flexibility) up to three times daily. A structured coding system was used to rate the completeness and relevance of 945 total exercises (0-2 scale). Quality varied primarily within individuals and was lower during moments of high suicidal intent and urge. When combining across all skills, quality was not associated with proximal change. However, higher-quality Countering Emotional Behavior practice predicted greater reductions in suicidal intent, and higher-quality Countering Emotional Behavior and Cognitive Flexibility practice predicted greater reductions in anger. These findings suggest that momentary distress can impact engagement quality, and that the short-term impact of skills practice may depend on both the specific CBT strategy and type of distress targeted. Understanding and enhancing engagement quality is a key step toward optimizing mobile interventions for individuals in the midst of psychological distress.