Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line therapy for advanced, EGFR-mutated nonsmall cell lung cancer (NSCLC). However, their benefit is limited in patients who have co-existing tumor suppressor gene (TSG) mutations, highlighting a need for intensified strategies to improve outcomes. ACROSS2 (ClinicalTrials.gov identifier NCT04500717) is the first prospective, multicenter, randomized phase 3 study to compare the third-generation EGFR-TKI aumolertinib in combination with carboplatin-pemetrexed versus aumolertinib monotherapy in patients who had NSCLC with EGFR mutations and concomitant TSG mutations. In total, 126 patients were enrolled and randomly assigned to either combination therapy (n = 62) or monotherapy (n = 64). The primary end point was median progression-free survival (PFS). At a median follow-up of 25.3 months, combination therapy significantly prolonged median PFS compared with monotherapy (19.78 vs 16.53 months; hazard ratio, 0.58; 95% confidence interval, 0.34-0.97). Landmark PFS rates at 12, 18, and 24 months were 78.7% versus 65.3%, 67.2% versus 40.8%, and 41.0% versus 29.9%, respectively. Subgroup analyses demonstrated a clear PFS benefit in patients who had co-existing tumor protein p53 (TP53) mutations. Grade 3 or greater adverse events occurred in 25.9% of patients who received combination therapy versus 17.2% of those who received monotherapy; no drug-related deaths were observed. Overall survival data were immature (data maturity, 4%). The ACROSS2 trial provides the first prospective evidence supporting a genotype-directed, chemotherapy-targeted intensification approach favoring aumolertinib plus carboplatin-pemetrexed for this molecularly defined population.
BACKGROUND:Vulvar lichen simplex chronicus (VLSC) is a chronic inflammatory dermatosis that remains difficult to manage long term. Fractional CO2 laser (FxCO2) combined with topical corticosteroids (TCs) has emerged as a potential therapeutic strategy; however, high-quality long-term evidence remains limited. OBJECTIVE:To evaluate the long-term efficacy and safety of FxCO2 combined with TC in patients with VLSC. STUDY DESIGN:This retrospective single-center study included 172 patients with biopsy-confirmed VLSC treated between 2016 and 2024. All patients received at least one FxCO2 + TC treatment session. Primary outcomes included pruritus improvement, recurrence, and subjective symptom relief. Secondary outcomes assessed patient satisfaction, treatment adherence, and adverse events. RESULTS:FxCO2 combined with TC treatment was effective, achieving an initial pruritus improvement rate of 90.12% (155/172). Subjective symptom improvement was reported by 91.86% (158/172) of patients, and patient satisfaction was 88.95% (153/172). Among those who improved, 50.58% (80/155) achieved improvement after 3 treatments, and the median duration of improvement was 18.0 months (range, 12-54 months). The recurrence rate was 14.84% (23/155), with a median time to recurrence of 36.0 months (range, 12-60 months). Adverse events occurred in 15.70% (27/172) of patients, with dryness being the most common (6.40%, 11/172). No clinical signs of deterioration or atypical progression were noted throughout the follow-up. CONCLUSION:FxCO2 combined with TC treatment is effective and well tolerated in women with VLSC, providing long-term symptom relief with low recurrence and acceptable safety. This combined approach may represent a promising therapeutic option for managing intense pruritus associated with VLSC.
This study aimed to evaluate the efficacy and safety of combining transarterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs), with or without programmed death-1 (PD-1) inhibitors (ICI), as first-line therapy for intermediate-advanced hepatocellular carcinoma (HCC) in a real-world setting. This multicentre retrospective cohort study enrolled patients with intermediate-advanced HCC who received either TACE combined with TKIs and PD-1 inhibitors (TACE-TKI-ICI) or TACE plus TKIs (TACE-TKI) from January 2019 to December 2023. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Propensity score matching (PSM) was used to reduce bias. A total of 514 patients with intermediate-advanced HCC were analyzed, 263 patients in the TACE-TKI-ICI group and 251 patients in the TACE-TKI group. After PSM (1:1), 241 patients were included in each group. The TACE-TKI-ICI group had significantly longer median PFS (13.8 vs. 10.8 months; hazard ratio [HR] = 0.73; 95
The Minisci-type reaction is arguably one of the most straightforward methods for constructing C–C bonds through functionalization of heteroarenes. This radical-based strategy has been particularly valuable for preparing polysubstituted N-heterocycles and has garnered significant attention due to the predictability of the reaction outcomes based on the properties of the carbon-centered radicals and heteroarenes involved. In recent years, a novel approach has emerged: light-induced Minisci-type transformations, where C-H functionalization reactions can be promoted under mild conditions. Notably, direct decarboxylative reactions via photocatalysis have been developed without the need for pretreatment of the reaction partners, resulting in highly economical and efficient procedures. This review summarizes recent advancements in photoinduced decarboxylative Minisci-type reactions, including mechanistic explorations of the formation of diverse radicals. Moreover, these transformations are categorized by the types of radical precursors used. The potential applications and existing limitations of each protocol are also discussed in detail, aiming to provide a comprehensive toolbox and guidance for drug discovery.
Background:Remimazolam is increasingly used for procedural sedation because of its rapid onset, rapid recovery and favourable haemodynamic profile. However, hiccups remain a clinically relevant adverse event that may interfere with endoscopic manipulation. The independent and combined effects of remimazolam dose and injection rate on hiccup occurrence have not been well characterized. Methods:In this prospective, randomized, double-blind, 2×2 factorial trial, adult patients undergoing painless colonoscopy were randomized to receive remimazolam at 0.3 or 0.4 mg kg-1, administered over 10s or 20s. The primary endpoint was hiccup incidence. Secondary endpoints included body movement, supplemental bolus requirements, time to loss of eyelash reflex, recovery time, haemodynamic changes, Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores and postoperative Numeric Rating Scale (NRS) scores. Multivariable logistic regression evaluated the independent effects of dose and injection rate on hiccup incidence and tested for interaction. Results:Both the higher remimazolam dose (0.4 mg kg-1) and the slower bolus injection rate (20s) were independently associated with a lower incidence of hiccups. After adjustment for age, sex, body mass index, smoking status, hypertension and diabetes, the 0.4 mg kg-1 regimen showed lower odds of hiccups than the 0.3 mg kg-1 regimen, and 20s administration showed lower odds than 10s. No significant dose × rate interaction was detected. The higher-dose regimen was additionally associated with fewer body movements and supplemental boluses, without increased haemodynamic compromise. Conclusion:Both a higher remimazolam dose and a slower bolus injection rate were independently associated with a lower incidence of hiccups during painless colonoscopy. Remimazolam 0.4 mg kg-1 administered over 20s may offer the most favourable balance between hiccup prevention, procedural conditions and haemodynamic stability.
