THE BENEFIT OF SHORT-TERM WEIGHT LOSS WITH ANTI-OBESITY MEDICATIONS IN REAL-WORLD CLINICAL PRACTICE.

Objective: The effectiveness of anti-obesity medications (AOMs) outside of clinical trials is unclear. The objective of this study was to compare the short-term effectiveness of AOMs in real-world practice. Methods: This retrospective study included adults aged ≥18 years, with body mass index ≥30 kg/m2 or ≥27 kg/m2 with at least one obesity-related comorbidity who were prescribed phentermine hydrochloride, phenterminetopiramate, bupropion-naltrexone, or lorcaserin for 12 consecutive weeks between 2006 and 2016 at a large tertiary healthcare system. Propensity score-matched cohorts were created for each pair of AOMs. The primary outcomes were percent and absolute weight loss from baseline after 12 weeks. A prediction model was constructed to estimate weight loss with different AOMs based on demographic and clinical data. Results: Of the 3,411 patients included in this study, patients lost an average of 3.45% of body weight from baseline. All AOMs were associated with a significant weight loss from baseline (P<.0001). Patients lost the highest percentage of body weight on phentermine hydrochloride (3.75 ± 5.66%), followed by phentermine-topiramate (3.63 ± 5.7%), bupropion-naltrexone (2.66 ± 5.03%), and lorcaserin (1.84 ± 6.69%). In propensity-matched cohorts, patients taking phentermine hydrochloride lost more weight than those taking lorcaserin or bupropion-naltrexone, and patients taking phentermine topiramate lost more weight than patients taking lorcaserin. Conclusion: In real-world practice, AOMs are associated with clinically meaningful weight loss of 2 to 4% after 12 weeks. In this study, phentermine hydrochloride and phentermine topiramate produced the most weight loss. AOMs should be seriously considered as part of the armamentarium to treat patients with obesity. Abbreviations: AOM = anti-obesity medication; BMI = body mass index; EMR = electronic medical record; FDA = Food and Drug Administration; T2D = type 2 diabetes.

Patient Perceptions of Landscape and Abstract Art in Inpatient Cardiac Units: A Cross-Sectional Survey.

PURPOSE: The purpose of this exploratory study was to capture the influence of artwork in the hospital corridors within cardiothoracic inpatients. BACKGROUND: This study builds on previous research to determine the preferred types of artwork (landscape vs. abstract) in the hospital setting as well as the influence of the art itself. METHODS: Participants engaged in surveys with predefined single-choice responses and semistructured one-on-one interviews. RESULTS: Data were obtained from 45 participants, 15 from each of the units (Landscape, Abstract, or Mixed). A higher percentage of participants reported a positive impact on the Landscape Unit; however, the positive responses on the Abstract and Mixed Units were also notable. Eighty-two percent of responses from patients on the Abstract Unit were positive, as were 82% from the Landscape Unit and the Mixed Unit. CONCLUSIONS: Although landscape was preferred, abstract and mixed art also had positive responses and abstract did not have a negative effect. All genres of art have a place in a hospital; however, strategies should be developed that include more education, engagement, and interpretation of the artwork.

Identifying conserved molecular targets required for cell migration of glioblastoma cancer stem cells.

Glioblastoma (GBM) is the most prevalent primary malignant brain tumor and is associated with extensive tumor cell infiltration into the adjacent brain parenchyma. However, there are limited targeted therapies that address this disease hallmark. While the invasive capacity of self-renewing cancer stem cells (CSCs) and their non-CSC progeny has been investigated, the mode(s) of migration used by CSCs during invasion is currently unknown. Here we used time-lapse microscopy to evaluate the migratory behavior of CSCs, with a focus on identifying key regulators of migration. A head-to-head migration assay demonstrated that CSCs are more invasive than non-CSCs. Time-lapse live cell imaging further revealed that GBM patient-derived CSC models either migrate in a collective manner or in a single cell fashion. To uncover conserved molecular regulators responsible for collective cell invasion, we utilized the genetically tractable Drosophila border cell collective migration model. Candidates for functional studies were generated using results from a targeted Drosophila genetic screen followed by gene expression analysis of the human homologs in GBM tumors and associated GBM patient prognosis. This strategy identified the highly conserved small GTPase, Rap1a, as a potential regulator of cell invasion. Alteration of Rap1a activity impaired the forward progress of Drosophila border cells during development. Rap1a expression was elevated in GBM and associated with higher tumor grade. Functionally, the levels of activated Rap1a impacted CSC migration speed out of spheres onto extracellular matrix. The data presented here demonstrate that CSCs are more invasive than non-CSCs, are capable of both collective and single cell migration, and express conserved genes that are required for migration and invasion. Using this integrated approach, we identified a new role for Rap1a in the migration of GBM CSCs.

Association between shared medical appointments and weight loss outcomes and anti-obesity medication use in patients with obesity.

OBJECTIVE: In shared medical appointments (SMAs), multiple patients with a similar clinical diagnosis are seen by a multidisciplinary team for interactive group sessions. Very few studies have specifically studied SMAs and weight loss in patients with obesity. This study compared weight loss outcomes and anti-obesity medication (AOM) access between patients with obesity managed through (SMAs) versus individual appointments. METHODS: Retrospective study of adults seen for obesity between September 2014 and February 2017 at Cleveland Clinic Institute of Endocrinology and Metabolism. Percent weight loss from baseline was compared between two propensity score-matched populations: patients who attended ≥1 SMA and patients managed with individual medical appointments. RESULTS: From all eligible patients identified (n=310 SMA, n=1,993 non-SMA), 301 matched pairs were evaluated for weight loss. The SMA group (n=301) lost a mean of 4.2%, 5.2% and 3.8% of baseline weight over 6, 12 and 24 months; the non-SMA group (n=301) lost significantly less weight (1.5%, 1.8% and 1.6%, respectively) (paired t-test, P<.05). All patients were eligible for US Food and Drug Administration-approved AOMs based on obesity diagnosis; however, 49.8% (150/301) of matched SMA patients were prescribed an AOM versus 12.3% (37/301) of matched non-SMA patients. CONCLUSION: This study suggests that SMAs may offer a promising alterative for obesity management and one that may facilitate greater utilization of AOMs. In propensity score-matched cohorts, SMAs were associated with greater weight loss outcomes when compared to usual care facilitated through individual medical appointments alone.

Obesity: Are shared medical appointments part of the answer?

Shared medical appointments, in which a multidisciplinary team of healthcare providers meets with multiple patients in a group setting, may be an option for treating patients with obesity. To be effective, shared medical appointments need to address patients' nutrition, physical activity, appetite suppression, stress management, and sleep.

MET signaling in keratinocytes activates EGFR and initiates squamous carcinogenesis.

The receptor tyrosine kinase MET is abundant in many human squamous cell carcinomas (SCCs), but its functional significance in tumorigenesis is not clear. We found that the incidence of carcinogen-induced skin squamous tumors was substantially increased in transgenic MT-HGF (mouse metallothionein-hepatocyte growth factor) mice, which have increased abundance of the MET ligand HGF. Squamous tumors also erupted spontaneously on the skin of MT-HGF mice that were promoted by wounding or the application of 12-O-tetradecanoylphorbol 13-acetate, an activator of protein kinase C. Carcinogen-initiated tumors had Ras mutations, but spontaneous tumors did not. Cultured keratinocytes from MT-HGF mice and oncogenic RAS-transduced keratinocytes shared phenotypic and biochemical features of initiation that were dependent on autocrine activation of epidermal growth factor receptor (EGFR) through increased synthesis and release of EGFR ligands, which was mediated by the kinase SRC, the pseudoproteases iRhom1 and iRhom2, and the metallopeptidase ADAM17. Pharmacological inhibition of EGFR caused the regression of MT-HGF squamous tumors that developed spontaneously in orthografts of MT-HGF keratinocytes combined with dermal fibroblasts and implanted onto syngeneic mice. The global gene expression profile in MET-transformed keratinocytes was highly concordant with that in RAS-transformed keratinocytes, and a core RAS/MET coexpression network was activated in precancerous and cancerous human skin lesions. Tissue arrays revealed that many human skin SCCs have abundant HGF at both the transcript and protein levels. Thus, through the activation of EGFR, MET activation parallels a RAS pathway to contribute to human and mouse cutaneous cancers.