Los Angeles Medical Center

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.)

Background: Ovarian cystectomy is standard treatment for endometrioma but is associated with decreased ovarian reserve. Catheter-directed sclerotherapy (CDS) is an ovary-sparing image-guided alternative; however, supporting evidence comprises retrospective comparative and prospective single-arm studies. Objective: To compare CDS and ovarian cystectomy in terms of therapeutic efficacy and effect on ovarian function in women with ovarian endometrioma through a randomized controlled trial. Methods: This prospective pilot study enrolled women evaluated for unilateral unilocular endometrioma measuring >3 cm from March 20221 to July 2024. Participants were randomized to treatment by fluoroscopic and ultrasound-guided CDS or laparoscopic cystectomy. The primary endpoint was percentage decline from baseline to 12 months in serum anti-Müllerian hormone (AMH) (an ovarian functional reserve marker). Additional procedural and 12-month outcomes were assessed including the Endometriosis Health Profile-30 (EHP-30) questionnaire addressing endometriosis-related symptoms and quality of life (lower score: better status). Results: The analysis included 40 participants: 20 randomized to CDS (mean age, 32.8 years), and 20 (mean age, 35.1.1 years) to cystectomy. Mean 12-month percentage decline in AMH (primary outcome) was smaller for CDS than cystectomy (14.9% vs 39.8%, P=.02). No complications occurred after CDS; one complication occurred after cystectomy. Hospital length of study was significantly shorter after CDS (2.3±0.5 days) than cystectomy (4.2±0.7 days) (P<.001). From baseline to 12 months, ultrasound-based cyst size significantly decreased for CDS (5.8±1.5 to 0.6±0.7 cm; P<.001) and cystectomy (5.3±1.4 to 0.0±0.0 cm; P<.001); mean AMH was not significantly different for CDS (3.1±2.2 to 2.7±1.7 ng/mL; P=.08) but decreased significantly for cystectomy (3.3±3.0 to 2.0±1.8 ng/mL; P<.001); mean CA-125 decreased significantly for CDS (69.2±61.7 to 17.3±14.2 U/mL; P<.001) and cystectomy (54.6±35.8 to 14.8±8.2 U/mL; P<.001); and mean EHP-30 score decreased significantly for CDS (31.3±12.8 to 6.3±6.9; P<.001) and cystectomy (34.5±18.0 to 8.1±4.3; P<.001). CA-125 and EHP-30 score were not significantly different between groups at 12 months (P>.05). No 12-month recurrence occurred in either group. Conclusion: CDS was associated with better preservation of ovarian reserve versus cystectomy, without significant difference for therapeutic efficacy measures. Clinical Impact: These results advance the level of evidence supporting CDS as an ovary-sparing cystectomy alternative for appropriately selected patients.

Targeted therapies, including pembrolizumab and CDK4/6 inhibitors, have expanded treatment options for breast cancer subtypes such as triple-negative (TNBC) and hormone receptor-positive/HER2-negative cancers. However, their impact on surgical outcomes in two-stage prepectoral breast reconstruction remains unclear. This study evaluates surgical outcomes in patients receiving pembrolizumab or CDK4/6 inhibitors. A retrospective review was conducted of all patients at a single institution who underwent immediate two-stage prepectoral reconstruction at a single center between January 2018 and October 2024 with ≥3 months of follow-up. Exclusion criteria included autologous, delayed, or direct-to-implant reconstructions, and chemotherapy after implant exchange. Variables analyzed included cancer characteristics, treatments, and postoperative complications. Major complications were defined as those requiring readmission or reoperation. Statistical analyses were performed using Fisher's Exact and Wilcoxon Rank Sum tests. Of 472 patients, 27 received pembrolizumab and 30 received CDK4/6 inhibitors. Pembrolizumab had significantly higher seroma rates during expansion (44.4% vs. 27%, p=0.05). After implant exchange, major complications (26.3% vs. 8%, p=0.02) and reoperation rates (19.1% vs. 3.7%, p=0.01) were significantly higher. Patients receiving CDK4/6 inhibitors did not experience an increased risk of infection; in fact, the observed rate of minor infections was lower (0.0% vs. 12.4%, p=0.04), although no significant differences were seen in other outcomes. Pembrolizumab is a promising therapy for TNBC, but its association with increased seromas, major complications, and reoperations warrants further investigation. Use of CDK4/6 inhibitors was not associated with an increased risk of infection following tissue expander placement.

Role of labor induction requiring cervical preparation for full-term, low-risk pregnant patients is under active investigation. The objective of this study was to describe nationwide temporal trends, characteristics, and outcomes associated with labor induction requiring cervical preparation at full-term gestation for low-risk pregnant patients in the United States. This cross-sectional study queried the Agency for Healthcare Research and Quality mechanism's Healthcare Cost and Utilization Project National Inpatient Sample. Study population included 5,003,348 hospital deliveries at 39-406/7weeks' gestation for singleton, cephalic low-risk pregnancy from 2018 to 2022, excluding historically known presumed pre-labor pregnancy risk factors. Exposure was labor induction status, defined as the performance of cervical preparation (ripening or mechanical dilation), with or without adjunctive intervention (artificial rupture of membranes or oxytocin administration). Main outcome measures were set as cesarean delivery as the primary outcome; induction failure, chorioamnionitis, umbilical cord prolapse, in-labor uterine rupture, postpartum hemorrhage, severe maternal morbidity and mortality as the secondary outcomes, assessed with multivariable generalized linear model. A total of 618,785 (12.4%) deliveries had labor induction requiring cervical preparation. The rate increased from 8.8 to 14.4% between QT1/2018-QT2/2020 (P-trend < .001), at which the rate started gradually decreasing when the COVID-19 pandemic occurred (14.4% at QT2/2020 to 13.4% at QT4/2022, P-trend = .04). The majority of cervical preparation was ripening alone (69.9%), followed by mechanical dilation alone (20.7%) and both ripening and mechanical dilation (9.4%). During the 5-year study period, cervical preparation with mechanical dilation alone (14.4% to 26.9%) and both ripening and mechanical dilation (4.6% to 11.4%) increased (both, P-trend < .001); adjunctive use of both oxytocin and artificial rupture of membranes (18.7% to 27.0%) and oxytocin alone (15.0% to 18.8%) increased while artificial rupture of membranes alone decreased (29.5% to 23.0%) (all, P-trend < .001). When compared to 4,384,563 deliveries without labor induction cervical preparation, induction was associated with cesarean delivery (17.1% vs 9.2%, adjusted-incidence rate ratio [aIR] 1.75, 95% confidence interval [CI] 1.74-1.76), chorioamnionitis (3.2% vs 1.9%, aIR 1.67, 95%CI 1.64-1.69), umbilical cord prolapse (0.2% vs 0.1%, aIR 1.67, 95%CI 1.58-1.77), in-labor uterine rupture (21.8 vs 7.8 per 100,000, aIR 2.66, 95%CI 2.17-3.25), postpartum hemorrhage (5.7% vs 3.9%, aIR 1.42, 95%CI 1.40-1.44), severe maternal morbidity (0.4% vs 0.2%, aIR 1.61, 95%CI 1.54-1.68), and maternal mortality (4.8 vs 0.7 per 100,000, aIR 7.34, 95%CI 4.37-12.33). In conclusion, this nationwide cross-sectional assessment suggests the increasing trend of full-term labor induction for study-defined low-risk pregnancy may have stopped during the COVID-19 pandemic in the United States. The observed association with cesarean delivery and adverse outcomes related to labor induction requiring cervical preparation warrant further investigation.

Background: Implant-based reconstruction (IBR) is the most common method of breast reconstruction after mastectomy. Prior studies have demonstrated that complications rates vary with incision type. We evaluated whether incision type affected culture positivity in IBR complications. Methods: A retrospective cohort study was performed of all patients undergoing mastectomy for cancer or cancer prophylaxis with IBR from 2012 to 2023. Abstracted data included patient characteristics, oncologic treatment history, mastectomy and reconstruction characteristics, culture positivity, infectious organism, and antibiotic treatment history. Results: A total of 6901 patients underwent post-mastectomy implant-based reconstruction, 183 (2.7%) patients had unplanned operative intervention for IBR complications, and 80/183 (43.7%) had culture-positive IBR infections. Culture-negative and culture-positive groups were similar in patient characteristics and oncologic treatment history. There was no difference in mastectomy incision types. The most common organisms were methicillin-sensitive Staphylococcus aureus, Pseudomonas aeruginosa, and coagulase-negative Staphylococcus. More patients in the culture-positive group were treated with antibiotics (81.2% vs. 51.5%, p = 0.0005). Antibiotic therapy duration was longer in the culture-negative group (8.52 vs. 5.78 days, p = 0.039). Among different incision types, there was no significant difference in duration of antibiotic therapy. Conclusions: No association between mastectomy incision type and culture-positive infections was observed among IBR complications in this study. Antibiotics may sterilize cultures, but operative intervention is still often required for IBR infections.

In an era of heightened global competition in science and technology and geopolitical tensions, United States leadership in science has been diminishing. The 2025 Nature Index found that in elite science journals, China accounted for 56% of the publications in 2024, whereas the US contributed only 10%. This is in stark contrast to 5 years earlier when the US still topped the ranking-but China's surge was becoming apparent. The rapid change indicates that a remodeling of the US science ecosystem is warranted, including the creation of new paths to earning PhDs in science, technology, engineering, and mathematics (STEM) fields, if the United States is to cultivate a much needed, highly skilled scientific workforce.