Citations

505 Background: SWOG S1007 was a phase 3 randomized trial to evaluate the benefit of endocrine therapy alone (ET) or with chemotherapy (CET) in pts with HR+/HER2- invasive breast cancer with recurrence score (RS) ≤ 25. There was no invasive disease-free survival (IDFS) benefit for CET compared to ET in postmenopausal women However, in premenopausal women CET had an IDFS improvement compared to ET (HR=0.60; 95% 0.43-0.83). The objective was to further refine patient subgroups who benefit from CET, we measured baseline hormone levels in S1007 pts to quantify their menstrual status by serum hormone levels and associated clinical outcomes. Methods: Serum estradiol (E), progesterone (P), follicular stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and inhibin B (IB) were assessed on baseline serum samples from 1,015 pts who self-reported being premenopausal and age < 55. Magnetic fluorescent bead-based immunoassays ( i.e., Luminex assays) or colorimetric ELISAs were performed at the Biomarker Discovery Laboratory at the University of Kansas Medical Center to measure hormone levels. Associations of the markers (both continuous and dichotomized) with IDFS and distant relapse-free survival (DRFS) were tested for prognosis and prediction of CET benefit using Cox regression. Results: Single baseline measurement of IB, P, E, LH, FSH, or combination of E/LH/FSH, was not prognostic for IDFS or predictive for chemotherapy benefit. However, AMH levels (≥10 pg/mL) showed significant interaction with chemotherapy benefit (p=0.019), and risk increased with continuous AMH with ET alone, but not CET (p=0.03). Compared to ET alone, CET was beneficial in the 79% of premenopausal patients with AMH levels ≥10 pg/mL, a standard cutoff to define normal ovarian reserve (HR=0.48; 95% 0.33-0.69, adjusting for RS). CET was not beneficial in the 21% with AMH < 10 (HR=1.21; 95% 0.60-2.43). Absolute 5-year IDFS benefit of CET for RS ≤ 25 was 7.8% (95.2%-87.4%) for AMH ≥ 10 vs. -1.7% (89.1%-90.8%) for AMH < 10. DRFS showed a similar pattern with CET benefit in AMH ≥10 pg/mL (5-year DRFS benefit: 4.4%; HR=0.41; 95% 0.25-0.68, adjusting for RS) and no benefit in AMH < 10 (5-year DRFS benefit: -0.9%, HR=1.50; 95% 0.62-3.63). Conclusions: Among self-reported premenopausal patients < age 55, pts with baseline serum AMH levels ≥10 pg/mL showed significant benefit from CET compared to patients with AMH levels <10 pg/mL. AMH levels were a better indicator of CET benefit than self-reported menopause status, age, or E/LH/FSH levels. Use of AMH-based selection of patients may inform who most benefits from the addition of adjuvant chemotherapy to ET. Clinical trial information: NCT01272037 .

Abstract Background The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI. Methods Records of NAFLD patients from 2000–2022 were reviewed. Patients were categorized as lean (18.5–22.9 kg/m2), overweight (23–24.9 kg/m2), and obese (&gt;25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group. Results Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6–22.5], 24.2 [23.7–24.6], and 28.3 [26.6–30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9–9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related). Conclusions Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients. Key messages What is already known on this topic What this study adds How this study might affect research, practice, or policy

AbstractCardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing‐induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre‐procedure evaluation and preparation, implant procedure management, follow‐up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.