Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer.

PURPOSE: To examine patterns of radiotherapy (RT) and endocrine therapy (ET) use, associations between RT omission and ET adherence, and associations among ET and RT use and disease recurrence in older women with early-stage, estrogen receptor-positive breast cancer. METHODS: Women age 65 and older diagnosed with hormone receptor-positive, clinically node-negative breast cancer between 2005 and 2018 and who did not undergo mastectomy were included. Multinomial logistic regression was used to examine the trends in practice patterns over time and by age. Kaplan-Meier estimates were used to estimate the probability of ET discontinuation. Cox proportional hazards models were constructed to assess associations between recurrence and ET/RT. RESULTS: Of the 484 enrolled patients, 47.9% patients underwent RT and initiated ET, 27.4% received ET alone, 10.2% received RT alone, and 13.8% patients received neither. Older patients had a higher probability of receiving ET alone or neither ET nor RT (both p < 0.001). The probability of initiating ET was greater among patients who underwent RT than those who omitted RT (p < 0.001). Regardless of RT status (RT or no RT), initiation and continuation of ET may be associated with reduced risk of recurrence. CONCLUSION: Patients who opt for no adjuvant therapy, or who do not tolerate ET, are at increased risk of disease recurrence if they omit RT. Clinicians should consider the likelihood a patient will adhere to ET prior to recommending omission of RT.

The effect of angiotensin-(1-7) in mouse unilateral ureteral obstruction.

Angiotensin-(1-7) is a ligand for the Mas receptor and may protect against tissue injury associated with renin-angiotensin system activation. We determined the effects of endogenous or exogenous angiotensin-(1-7) in mice with unilateral ureteral obstruction (UUO). Mice with UUO were treated with or without the angiotensin-(1-7) antagonist A779 or with 6, 24, or 62 µg/kg per hour exogenous angiotensin-(1-7). After 10 days, kidneys were harvested for histology, immunoblots, and measurement of NADPH oxidase. Compared with controls, A779 treatment significantly increased fibronectin, transforming growth factor-ß, and α-smooth muscle actin expression in obstructed kidneys and enhanced tubulointerstitial injury, apoptosis, and NADPH oxidase. Unexpectedly, administration of angiotensin-(1-7) to mice with UUO caused injury in obstructed kidneys compared with controls and increased macrophage infiltration. In obstructed kidneys from mice with gene deletion of Mas (Mas(-/-)), apoptosis and macrophage infiltration were increased compared with wild-type mice. Angiotensin-(1-7) (but not A779) further increased apoptosis and macrophage influx in obstructed kidneys from Mas(-/-) mice, compared with untreated Mas(-/-) mice. These data indicate that endogenous angiotensin-(1-7) protects against kidney injury in UUO. In mice with or without the Mas receptor, however, delivery of exogenous angiotensin-(1-7) worsens kidney damage. The results suggest dose-dependent effects of angiotensin-(1-7) in the kidney in UUO, with endogenous angiotensin-(1-7) promoting repair pathways via interaction with Mas and higher amounts exacerbating injury.

Anticoagulant and antiplatelet therapy in patients with chronic kidney disease: risks versus benefits review.

PURPOSE OF REVIEW: Atrial fibrillation and cardiovascular death are increased in end-stage renal disease (ESRD) patients compared to the general population. The effect of anticoagulant and antiplatelet medications for these indications in ESRD is unclear. However, both classes of medications have been used for the preservation of vascular access. This review explores the risks and benefits of anticoagulant and antiplatelet medications in ESRD. RECENT FINDINGS: ESRD patients with atrial fibrillation have a two and three-fold greater risk of death and stroke, respectively, than ESRD patients without atrial fibrillation. Warfarin does not appear to decrease this risk, and increases the risk of bleeding and vascular calcification. Warfarin also does not appear to be effective for vascular access preservation. In a few large observational studies, antiplatelet agents did not decrease the risk of cardiovascular death, but confounding by indication is likely. Antiplatelet agents do appear to prolong unassisted arteriovenous graft patency, but the effect is modest. SUMMARY: The role of anticoagulant and antiplatelet agents for atrial fibrillation and cardiovascular disease in ESRD remains unclear. Well designed randomized controlled trials to determine the role of anticoagulation in ESRD patients with atrial fibrillation, and anticoagulant and antiplatelet medications in the preservation of central venous catheter function are required.

Angiotensin-(1-7) in kidney disease: a review of the controversies.

Ang-(1-7) [angiotensin-(1-7)] is a biologically active heptapeptide component of the RAS (renin-angiotensin system), and is generated in the kidney at relatively high levels, via enzymatic pathways that include ACE2 (angiotensin-converting enzyme 2). The biological effects of Ang-(1-7) in the kidney are primarily mediated by interaction with the G-protein-coupled receptor Mas. However, other complex effects have been described that may involve receptor-receptor interactions with AT(1) (angiotensin II type 1) or AT(2) (angiotensin II type 2) receptors, as well as nuclear receptor binding. In the renal vasculature, Ang-(1-7) has vasodilatory properties and it opposes growth-stimulatory signalling in tubular epithelial cells. In several kidney diseases, including hypertensive and diabetic nephropathy, glomerulonephritis, tubulointerstitial fibrosis, pre-eclampsia and acute kidney injury, a growing body of evidence supports a role for endogenous or exogenous Ang-(1-7) as an antagonist of signalling mediated by AT(1) receptors and thereby as a protector against nephron injury. In certain experimental conditions, Ang-(1-7) appears to paradoxically exacerbate renal injury, suggesting that dose or route of administration, state of activation of the local RAS, cell-specific signalling or non-Mas receptor-mediated pathways may contribute to the deleterious responses. Although Ang-(1-7) has promise as a potential therapeutic agent in humans with kidney disease, further studies are required to delineate its signalling mechanisms in the kidney under physiological and pathophysiological conditions.

Comparing Boston naming test short forms in a rehabilitation sample.

The Boston Naming Test (BNT) has multiple short forms that do not include the noose item that have been primarily examined in dementia populations. This study compared BNT short forms with standard administration (BNT-S) in physical medicine and rehabilitation patients who underwent outpatient evaluation. The sample (N = 480) was 34% female and 91% white with average age of 46 years (SD = 15) and average education of 14 years (SD = 3). Five 15-item short forms were calculated: Consortium to Establish a Registry for Alzheimer's disease (CERAD-15); Lansing; and Mack 1, 2, and 4 (Mack-15.1, -15.2). Three 30-item short forms were calculated: Mack A, Saxon A, and BNT odd items. BNT-S and short forms were compared with Spearman correlations. Cronbach's alpha was calculated for all BNT forms. Impaired BNT scores were determined with norm-referenced scores (T < 36 and T < 40). Area under the curve (AUC) values were compared across short forms with impaired BNT as criterion. BNT-S showed strong correlations with 30-item (rho = 0.92-0.93) and 15-item short forms (rho = 0.80-0.87) except for CERAD-15 (rho = 0.69). Internal consistency was acceptable for all short forms (alpha = 0.72-0.86). BNT-S was impaired in 17% and 33% of participants at 35 T and 39 T cutoffs, respectively. BNT short forms showed excellent to outstanding classification accuracy predicting impairment using both cutoffs. BNT short forms warrant further study in rehabilitation settings.

Psychometric Equivalence of Standard and Prorated Boston Naming Test Scores.

This study compared prorated Boston Naming Test (BNT-P; omitting the noose item) and standard administration (BNT-S) scores in physical medicine and rehabilitation patients (N = 480). The sample was 34% female and 91% White with average age and education of 46 (SD = 15) and 14 (SD = 3) years, respectively. BNT-P was calculated by summing correct responses excluding item 48 and estimating the 60-item score with cross multiplication and division. BNT-P and BNT-S scores were compared via concordance correlation (CC) coefficients; reflected and log transformed data were examined with equivalence tests. BNT-P and BNT-S scores showed almost perfect agreement (CC = .99). Transformed scores demonstrated equivalence (±1.1 points). Raw and scaled score differences were 0 in 88% and 96% of cases, respectively. Race and ethnicity accounted for item 48 outcomes while controlling for age and education. Findings support the utility of prorated BNT scores in rehabilitation patients.

Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial.

PURPOSE: Neoadjuvant gemcitabine and cisplatin (GC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). On the basis of the activity of atezolizumab (A) in metastatic BC, we tested neoadjuvant GC plus A for MIBC. METHODS: Eligible patients with MIBC (cT2-T4aN0M0) received a dose of A, followed 2 weeks later by GC plus A every 21 days for four cycles followed 3 weeks later by a dose of A before RC. The primary end point was non-muscle-invasive downstaging to < pT2N0. RESULTS: Of 44 enrolled patients, 39 were evaluable. The primary end point was met, with 27 of 39 patients (69%) < pT2N0, including 16 (41%) pT0N0. No patient with < pT2N0 relapsed and four (11%) with ≥ pT2N0 relapsed with a median follow-up of 16.5 months (range: 7.0-33.7 months). One patient refused RC and two developed metastatic disease before RC; all were considered nonresponders. The most common grade 3-4 adverse event (AE) was neutropenia (n = 16; 36%). Grade 3 immune-related AEs occurred in five (11%) patients with two (5%) requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range: 5.1-17 weeks), and no patient failed to undergo RC because of AEs. Four of 39 (10%) patients had programmed death-ligand 1 (PD-L1)-positive tumors and were all < pT2N0. Of the patients with PD-L1 low or negative tumors, 23 of 34 (68%) achieved < pT2N0 and 11 of 34 (32%) were ≥ pT2N0 (P = .3 for association between PD-L1 and < pT2N0). CONCLUSION: Neoadjuvant GC plus A is a promising regimen for MIBC and warrants further study. Patients with < pT2N0 experienced improved relapse-free survival. The PD-L1 positivity rate was low compared with published data, which limits conclusions regarding PD-L1 as a predictive biomarker.