Review of bone health in women with estrogen receptor-positive breast cancer receiving endocrine therapy.

In estrogen-receptor-positive tumors, adjuvant endocrine therapy has been shown to be highly beneficial for both overall and disease-free survival. Estradiol is key in regulating bone and mineral physiology, and several studies found a strong correlation between these therapies and the risk of fractures. Since these therapies are often given for 5 through 10 years, the timing for bisphosphonates or denosumab initiation seems essential to managing bone metabolism. However, gray zones and discrepancies between guidelines remain as to the best threshold when to start antiresorptive treatment, or whether antiresorptive treatment should be administered to every woman undergoing adjuvant endocrine therapy, independent of their risk factors for fractures. Treatment options and strategies should be discussed at the start of hormone adjuvant therapy to come to a shared decision with the patient, with the final aim of reducing the risk of future fractures as much as possible. This review will cover present guidelines and literature on antiresorptive treatment in this setting, to provide clinicians with useful clues for managing these patients.

Mild autonomous cortisol secretion in adrenal incidentalomas and risk of fragility fractures: a large cross-sectional study.

OBJECTIVE: Mild autonomous cortisol secretion (MACS) has been associated with a higher prevalence of osteoporosis, although most data rely on single-center studies with limited sample size. We aimed to assess the prevalence of fragility fractures and contributing factors in a large cohort of patients with adrenal incidentalomas. DESIGN AND METHODS: Medical records of 1023 patients with adrenal incidentalomas from 1990 to 2019 were reviewed, and 735 patients were selected. Clinically obtained electronic radiological images closest to first endocrine evaluation, such as lateral views of spine X-rays or CT thoraco-abdominal scans, were reviewed to screen for asymptomatic morphometric vertebral fractures. Clinical fragility fractures, hormonal, and dual-energy x-ray absorptiometry (DXA) indices were also recorded. RESULTS: Four hundred seventy-four patients had nonfunctioning (NF) adrenal incidentalomas, 238 had MACS and 23 adrenal Cushing's syndrome (AC). Prevalence of fragility fractures was different (P = .018) between groups, respectively, 24.1% (NF), 34.0% (MACS), and 30.4% (AC), with significant difference between NF and MACS (P = .012). When analyzed separately by sex and menopausal status, this difference remained significant in postmenopausal women (P = .011), with a fracture prevalence of 22.2% (NF) and 34.6% (MACS). Fracture prevalence was similar in males. Women with MACS aged ≥65 years reported a 48.8% prevalence of fractures, as compared with 29.5% in NF (P < .01). In postmenopausal women, fragility fractures were associated with age (odds ratio [OR] 1.1, P < .001), smoking (OR 1.8, P = .048), and 1 mg-dexamethasone suppression test (DST) cortisol (OR 3.1, P = .029), while in men, only age was associated with fragility fractures. CONCLUSIONS: A considerable fracture burden was shown in postmenopausal women with adrenal incidentalomas and MACS, with clinical implications for the evaluation and management of bone metabolism.

Prognostic Utility of the New Definition of Difficult-to-Treat Resistance Among Patients With Gram-Negative Bloodstream Infections.

BACKGROUND: To compare the prognostic utility of the new definition of difficult-to-treat resistance (DTR) vs established definitions in a cohort of patients with Gram-negative bloodstream infections (GNBSIs). METHODS: This was a retrospective single-center study of adult patients with monomicrobial GNBSI, hospitalized from 2013 to 2016. DTR was defined as isolate demonstrating intermediate or resistant phenotype to all reported agents in the carbapenem, beta-lactam, and fluoroquinolone classes. Carbapenem resistance (CR) was defined according to 2015 Centers for Disease Control and Prevention criteria. Each isolate was further classified according to the Magiorakos et al. criteria as non-multidrug-resistant (non-MDR), MDR, extensively drug-resistant (XDR), or pan-drug-resistant (PDR). The primary outcome was all-cause 30-day mortality. RESULTS: Overall, 1576 patients were analyzed. Enterobacteriaceae accounted for 88.7% of BSIs, with Escherichia coli (n = 941) and Klebsiella pneumoniae (n = 326) being the most common pathogens. Pseudomonas aeruginosa was the most common nonfermentative bacteria (n = 130, 8.2%). Overall, 11% of strains were defined as DTR and 13% as CR. Episodes were further classified as non-MDR (68.8%), MDR (21.9%), XDR (8.8%), and PDR (0.4%). The prevalence rates of DTR, CR, and XDR were similar among Enterobacteriaceae and Acinetobacter baumannii, whereas they differed in P. aeruginosa. All the analyzed resistance definitions significantly improved prediction of 30-day mortality when introduced into a baseline multivariate model, to a similar degree: 9%, 10%, and 11% for DTR, Magiorakos, and CR definitions, respectively. CONCLUSIONS: DTR seems a promising tool to identify challenging GNBSIs, mainly those due to P. aeruginosa. With the availability of new agents for CR infections, further multicenter assessments of DTR are needed.