Citations

Radiation segmentectomy is a versatile, safe, and effective ablative therapy for early-stage hepatocellular carcinoma. Advances in radiation segmentectomy patient selection, procedural technique, and dosimetry have positioned this modality as a curative-intent and guideline-supported treatment for patients with solitary HCC. This review describes key radiation segmentectomy concepts and summarizes the existing literary knowledgebase.

Staphylococcus aureus skin colonization and eosinophil infiltration are associated with many inflammatory skin disorders, including atopic dermatitis, bullous pemphigoid, Netherton’s syndrome, and prurigo nodularis. However, whether there is a relationship between S. aureus and eosinophils and how this interaction influences skin inflammation is largely undefined. We show in a preclinical mouse model that S. aureus epicutaneous exposure induced eosinophil-recruiting chemokines and eosinophil infiltration into the skin. Remarkably, we found that eosinophils had a comparable contribution to the skin inflammation as T cells, in a manner dependent on eosinophil-derived IL-17A and IL-17F production. Importantly, IL-36R signaling induced CCL7-mediated eosinophil recruitment to the inflamed skin. Last, S. aureus proteases induced IL-36α expression in keratinocytes, which promoted infiltration of IL-17-producing eosinophils. Collectively, we uncovered a mechanism for S. aureus proteases to trigger eosinophil-mediated skin inflammation, which has implications in the pathogenesis of inflammatory skin diseases.

111 Background: Comparative evidence of quality of life (QoL) outcomes regarding life-prolonging treatments for the management of first-line treatment of metastatic castration sensitive prostate cancer (mCSPC) is not known. Methods: This systematic review uses the living interactive evidence synthesis framework (PMID: 36862387). Phase III randomized controlled trials assessing contemporary systemic treatments in mCSPC were included. Small sample size adjusted standardized mean differences (SMD; Hedges’ g) with 95% confidence intervals (CI) were computed for global QoL at 3, 6, 12, and 24 mo. Positive SMD indicated better health-related QoL, with zero indicating a null effect. Mixed treatment comparisons were made using a network meta-analysis. P-scores were computed; a higher score indicated better QoL. Results: Of 10 clinical trials initially included, eight trials (15 references) reported QoL. At 3mo global QoL was improved with abiraterone (AAP)+ADT compared to D+ADT (SMD: 0.26; 95% CI: 0.13-0.39), enzalutamide (E)+ADT (0.18; 0.03-0.33), and ADT (0.14; 0.02-0.27). At 6mo, AAP+ADT significantly improved global QoL compared to D+ADT (0.74; 0.62-0.87), E+ADT (1.74; 1.56-1.92), and ADT (1.79; 1.65-1.93). D+ADT also improved global QoL at 6mo compared to ADT (1.05; 0.93-1.16) but not when compared to E+ADT. At 12mo, AAP+ADT improved global QoL compared to E+ADT (0.20; 0.05-0.34) and ADT (0.19; 0.07-0.31) but not compared to D+ADT (0.05; -0.07-0.17). D+ADT also improved global QoL at 12mo compared to ADT (0.14; 0.03-0.24) (Table). Global QoL has not been reported for ARASENS trial at this time. These results are available on the Living interactive website. Conclusions: The totality of evidence suggests improved global QoL with androgen-pathway inhibitors (API) doublet therapy. D+ADT may offer better QoL at longer 6 and 12 months of follow-up. QoL data for triplet therapy is still emerging and will be incorporated in the living review as soon as it becomes available. [Table: see text]

ImportanceYoung women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers.ObjectiveTo investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers.Design, Setting, and ParticipantsInternational, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023.ExposurePregnancy after breast cancer.Main Outcomes and MeasuresPrimary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer–specific survival, overall survival, pregnancy, and fetal and obstetric outcomes.ResultsOf 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer–specific survival and overall survival.Conclusions and RelevanceIn this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival.Trial RegistrationClinicalTrials.gov Identifier: NCT03673306