Macula Vision Research Foundation

Real-world data on tolerability of concurrent radiation therapy (RT) and abemaciclib are limited. This study described real-world utilization and safety of concurrent RT and abemaciclib in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). This retrospective study accessed data from the Flatiron Health United States nationwide deidentified electronic health records-derived longitudinal database. Abemaciclib initiation date was the index date (September 2017-September 2021). Concurrent RT was defined as receipt of any RT with ≥1 day of overlap with abemaciclib therapy. The minimum follow-up time was 90 days. Patient characteristics, treatment patterns, and real-world adverse events (rwAEs) were presented descriptively; Kaplan-Meier methods were used to assess time to treatment discontinuation. This study included 174 female patients with a median follow-up time of 17.5 (IQR, 10.1-26.5) months. The median age was 63.0 (IQR, 54.0-71.0) years, 8.0% had Eastern Cooperative Oncology Group Performance Status ≥ 2 at index and 31.0% had MBC. Prior to abemaciclib use, 20.1% and 28.2% of patients had chemotherapy or other CDK4/6 inhibitors, respectively. About half of the patients (47.7%) received abemaciclib in combination with fulvestrant, and 76.4% initiated abemaciclib at 150 mg twice daily. Overall, 151 patients (86.8%) initiated RT at or after initiation of abemaciclib. During concurrent RT and abemaciclib use, 76.4% of patients had no dose change in abemaciclib; 16.7% and 2.3% had a dose hold or dose reduction, respectively; 4.0% discontinued abemaciclib. The incidence of rwAEs during concurrent abemaciclib + RT were diarrhea (73.0%), fatigue (62.6%), rash (27.6%), and neutropenia (23.0%). The median (95% CI) time to treatment discontinuation was 368 (290-516) days. Most patients did not require a dose modification or interruption with concurrent RT and abemaciclib. These findings suggest that the addition of RT to abemaciclib therapy is well tolerated in patients with HR+, HER2- MBC.

Background:Cirrhosis and cirrhosis-related deaths have risen in the United States in recent years. Ascites is a common complication, often requiring large-volume paracentesis (LVP). The American Association for the Study of Liver Diseases (AASLD) recommends the administration of albumin in conjunction with LVP to prevent further complications of cirrhosis. Emerging research in cirrhosis care reveals significant variations in outcomes among different demographics. Therefore, we assessed the use of guideline-adherent albumin and outcomes in U.S. patients undergoing LVPs, particularly at the intersection of race, ethnicity, socioeconomic disparities, and cirrhosis.Methods:This retrospective study utilized Cerner Real World Data to identify adults with cirrhosis and ascites undergoing LVP between January 2016 and June 2022. We assessed albumin utilization patterns across racial and ethnic groups and payor types, and their overall impact on acute kidney injury (AKI)-related hospitalization using an adjusted generalized linear model (aGLM).Results:We identified 736 patients: 301 in the LVP + albumin group and 435 in the LVP-only group. Despite clinical recommendations, only 41% undergoing LVPs received albumin. White patients and commercially insured patients received albumin at higher rates (p=0.042 and p=0.009, respectively). The overall rate of AKI-related admissions within the 30-day post-procedure period was 26%. However, patients who received albumin during LVP had a 36% lower risk of short-term AKI-related hospitalization (OR: 0.64; p=0.03).Conclusions:These findings indicate a potential for broader albumin utilization in U.S. patients with refractory ascites undergoing repeated LVPs to reduce AKI-related admissions.

The Ames test is required by regulatory agencies worldwide for assessing the mutagenic and carcinogenic potential of chemical compounds. This test uses several strains of bacteria to evaluate mutation induction: positive results in the assay are predictive of rodent carcinogenicity. As an initial step to understanding how well the assay may detect mutagens present as constituents of complex mixtures such as botanical extracts, a cross-sector working group examined the within-laboratory reproducibility of the Ames test using the extensive, publicly available National Toxicology Program (NTP) Ames test database comprising more than 3000 distinct test articles, most of which are individual chemicals. This study focused primarily on NTP tests conducted using the standard Organization for Economic Co-operation and Development Test Guideline 471 preincubation test protocol with 10% rat liver S9 for metabolic activation, although 30% rat S9 and 10 and 30% hamster liver S9 were also evaluated. The reproducibility of initial negative responses in all strains with and without 10% S9, was quite high, ranging from 95% to 99% with few exceptions. The within-laboratory reproducibility of initial positive responses for strains TA98 and TA100 with and without 10% rat liver S9 was ≥90%. Similar results were seen with hamster S9. As expected, the reproducibility of initial equivocal responses was lower, <50%. These results will provide context for determining the optimal design of recommended test protocols for use in screening both individual chemicals and complex mixtures, including botanicals.

Patient-reported outcomes (PROs), including treatment satisfaction, patient well-being, and quality of life, are becoming increasingly important contributors to treatment decisions in clinical practice and the evaluation of health care services. PROs have been included in a number of clinical trials in patients with type 2 diabetes (T2D), including those investigating glucagon-like peptide-1 receptor agonists (GLP-1RAs). The first oral GLP-1RA, oral semaglutide, was approved in the United States in 2019. Four PROs were included in the PIONEER clinical study program that evaluated oral semaglutide in patients with T2D across the full diabetes disease spectrum. PRO findings in the PIONEER studies were generally similar for oral semaglutide and comparators, with some exceptions. Improvements in a number of the 36-item Short Form Survey domains were observed for oral semaglutide versus placebo, including general health, bodily pain, physical component summary, social functioning, and mental health. For general health and social functioning, differences significantly favored oral semaglutide versus empagliflozin, whereas role-physical and the physical component summary significantly favored empagliflozin compared with oral semaglutide. The Diabetes Treatment Satisfaction Questionnaire findings indicated that oral semaglutide improved feelings of unacceptably high blood sugars versus placebo (in PIONEER 4, 5, and 8) and sitagliptin (in PIONEER 7). Significant improvements in craving control and craving for savory were observed with oral semaglutide versus empagliflozin in the Control of Eating Questionnaire (in PIONEER 2). These data provide valuable information that can facilitate a patient-centered approach and guide decision-making in managed care to optimize each patient's treatment experience.

While guidelines support metformin as a therapeutic option for diabetic patients with mild-to-moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2015). Associations (adjusted hazard ratio, 95% LCL aHR95% UCL ) of diabetes regimens (with and excluding metformin) in the first year post-transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post-transplant; most also received diabetes comedications. Compared to those who received insulin-based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin-based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.

From the *Institute for Dermatopathology, Conshohocken, Pennsylvania; and †Dermatopathologishe Gemeinschaftspraxis, Friedrichshafen, Germany. Reprints: not available.