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Background For patients undergoing surgery at an Ambulatory Surgical Center, recent changes to Centers for Medicare and Medicaid Services policy allow for the omission of a 30-day preoperative History and Physical (H&P). Preoperative H&Ps for low-risk surgery may contribute to health care waste and lead to unnecessary preoperative testing and treatment cascades. Methods In this qualitative study, we conducted 30 semi-structured interviews with surgeons who frequently perform low-risk surgeries. We aimed to evaluate surgeon perspectives on the continued use of the 30-day preoperative H&P and specifically the potential risks and benefits associated with the elimination of a preoperative H&P requirement from institutional practice. We used an interpretive description approach to generate a thematic description. Results Most participants felt that the 30-day preoperative H&P was low value and frequently described it as “unnecessary,” “redundant,” or “just checking a box.” Many viewed the 30-day requirement as arbitrary and felt that new H&P findings were rare and unlikely to influence surgical care. The participants who favored the preoperative H&P felt it was a safeguard to ensure “nothing was missed” and were less likely to be burdened by the requirement than participants who felt it was low value. Conclusions Surgeons performing low-risk procedures question the utility and value of conducting a preoperative H&P within 30 days of surgery. De-implementation of the 30-day preoperative H&P for low-risk patients may increase convenience for patients and providers. Furthermore, it may improve value in surgery by increasing access to services for patients with greater need for preoperative assessment.

In most women ≥ 70 years old with hormone-receptor-positive breast cancer, axillary staging and adjuvant radiotherapy provide no survival advantage over surgery and hormone therapy alone. Despite recommendations for their omission, sentinel lymph node biopsy (SLNB) and adjuvant radiotherapy rates remain high. While treatment side effects are well documented, less is known about the incremental spending associated with SLNB and adjuvant radiotherapy. Using a statewide multipayer claims registry, we examined spending associated with breast cancer treatment in a retrospective cohort of women ≥ 70 years old undergoing surgery. 9074 women ≥70 years old underwent breast cancer resection between 2012 and 2019, with 78% (n = 7122) receiving SLNB and/or adjuvant radiotherapy within 90 days of surgery. Women undergoing SLNB were more likely to receive radiation (51% vs. 28%; p < 0.001 and OR = 2.68). Average 90-day spending varied substantially based upon treatment received, ranging from US$10,367 (breast-conserving surgery alone) to US$27,370 (mastectomy with SLNB and adjuvant radiotherapy). The relative increases in 90-day treatment spending in the breast-conserving surgery cohort was 65% for SLNB, 82% for adjuvant radiotherapy, and 120% for both treatments. SLNB and adjuvant radiotherapy have significant spending implications in older women with breast cancer, even though they are unlikely to improve survival.

Background Recognizing the need to raise awareness of core diversity, equity, and inclusion (DEI) issues in the healthcare system, our previously developed Cultural Complications Curriculum aims to support institutions in reducing cultural error. As we continue program deployment, we discuss the opportunity to apply the Cultural Complications Curriculum to multidisciplinary audiences, such as in cancer programs. Methods We discuss applicability of the Cultural Complications Curriculum to cancer programs and practices, including how to tailor case discussions to oncology audiences. By emphasizing the unique characteristics of the multidisciplinary care environment and anticipating potential barriers to curriculum implementation, we demonstrate how the Cultural Complications Curriculum may support culture improvement across broad audiences. Results The successful application of the Cultural Complication Curriculum to multidisciplinary care programs will depend on appreciating differences in background knowledge, tailoring discussions to audience needs, and adapting material by incorporating new data and addressing emerging DEI issues. Multidisciplinary environments may require innovative approaches to education including virtual platforms, increased collaboration across centers and systems, and support from professional societies. In integrated care environments, like oncology, effective DEI discussions call for the engagement of a variety of medical specialties and departments. Conclusions To meet the needs of an increasingly diverse patient population and workforce, our approach to DEI education must embrace the interdependent nature of care delivery. In oncology and other multidisciplinary care environments, application of the Cultural Complications Curriculum may be the first step to combating cultural error by engaging a broader demographic within our healthcare system.

Sleep is necessary for recovery from physiological insults such as surgery. Although previous research has focused on sleep in the intensive care unit and medical setting, little is known about sleep quality among inpatients recovering from elective surgery. Therefore, we examined sleep quality and barriers to sleep among postsurgical inpatients.We conducted an explanatory sequential mixed-method study among adult general-care surgical inpatients who underwent elective surgery. We used a quantitative survey to examine sleep quality and interruptions followed by a qualitative phone interview with a subsample of participants to examine barriers and aids to sleep in the hospital. Results were analyzed using descriptive statistics of survey data and descriptive coding of interview transcripts.Of 113, 102 (90%) eligible patients completed the survey. Less than half (n = 48, 47%) of patients reported sleeping well the previous night and 93% reported less sleep in the hospital compared with at home. Patients reported a median of 5 (4-7) interruptions each night. Patients with3 sleep interruptions were more likely to report poor sleep than those with ≤3 interruptions (P 0.001). Phone interview responses cited barriers to sleep including staff interruptions and roommate noise when sharing a room but not pain. Patients suggested that improved timing and knowledge of interruptions or noise-reduction aids would facilitate sleep.Most patients do not sleep well while recovering from elective surgery in the hospital, and most sleep disruptions are modifiable. Minimizing interruptions at night by clustering care, informing patients of scheduled interruptions, and increasing access to noise-reduction aids may improve sleep quality. Optimal efforts to improve sleep quantity and quality will ultimately require a multilevel, multicomponent strategy.

BACKGROUND: Mirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity. METHODS: We treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m(2)) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [(18)F]-2-fluoro-d-2-deoxy-d-glucose ((18)F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test. RESULTS: Chronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion. CONCLUSION: These findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT03049462. FUNDING: This work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).

In most women ≥ 70 years old with hormone-receptor-positive breast cancer, axillary staging and adjuvant radiotherapy provide no survival advantage over surgery and hormone therapy alone. Despite recommendations for their omission, sentinel lymph node biopsy (SLNB) and adjuvant radiotherapy rates remain high. While treatment side effects are well documented, less is known about the incremental spending associated with SLNB and adjuvant radiotherapy.Using a statewide multipayer claims registry, we examined spending associated with breast cancer treatment in a retrospective cohort of women ≥ 70 years old undergoing surgery.9074 women ≥70 years old underwent breast cancer resection between 2012 and 2019, with 78% (n = 7122) receiving SLNB and/or adjuvant radiotherapy within 90 days of surgery. Women undergoing SLNB were more likely to receive radiation (51% vs. 28%; p0.001 and OR = 2.68). Average 90-day spending varied substantially based upon treatment received, ranging from US$10,367 (breast-conserving surgery alone) to US$27,370 (mastectomy with SLNB and adjuvant radiotherapy). The relative increases in 90-day treatment spending in the breast-conserving surgery cohort was 65% for SLNB, 82% for adjuvant radiotherapy, and 120% for both treatments.SLNB and adjuvant radiotherapy have significant spending implications in older women with breast cancer, even though they are unlikely to improve survival.

Introduction Unnecessary health care not only drive up costs, but also contribute to avoidable patient harms, underscoring an ethical obligation to eliminate practices which are harmful, lack evidence, and prevent spending on more beneficial services. To date, de-implementation ethics discussions have been limited and focused on clinical ethics principles. An analysis of de-implementation ethics in the broader context of the health care system is lacking. Methods To better understand the ethical considerations of de-implementation, recognizing it as a health care systems issue, we applied Krubiner and Hyder's bioethical framework for health systems activity. We examine ethics principles relevant to de-implementation, which either call for or facilitate the reduction of low value surgery. Results and Discussion From 11 health systems principles proposed by Krubiner and Hyder, we identified the 5 principles most pertinent to the topic of de-implementation: evidence and effectiveness, transparency and public engagement, efficiency, responsiveness, and collaboration. An analysis of de-implementation through the lens of these principles not only supports de-implementation but proves an obligation at the health system level to eliminate low value care. Recognizing the challenge of defining “value,” the proposed framework may increase the legitimacy and objectivity of de-implementation. Conclusions While there is no single ideal ethical framework from which to approach de-implementation, a health systems framework allows for consideration of the systems-level factors impacting de-implementation. Framing de-implementation as a health systems issue with systems-wide ethical implications empowers providers to think about new ways to approach potential roadblocks to reducing low-value care.

Importance Through the Choosing Wisely campaign, surgical specialties identified 4 low-value breast cancer operations. Preliminary data suggest varying rates of deimplementation and have identified patient-level and clinician-level determinants of continued overuse. However, little information exists about facility-level variation or determinants of differential deimplementation. Objective To identify variation and determinants of persistent use of low-value breast cancer surgical care. Design, Setting, and Participants Retrospective cohort study in which reliability-adjusted facility rates of each procedure were calculated using random-intercept hierarchical logistic regression before and after evidence demonstrated that each procedure was unnecessary. The National Cancer Database is a prospective cancer registry of patients encompassing approximately 70% of all new cancer diagnoses from more than 1500 facilities in the United States. Data were analyzed from November 2019 to August 2020. The registry included women 18 years and older diagnosed as having breast cancer between 2004 and 2016 and meeting inclusion criteria for each Choosing Wisely recommendation. Main Outcomes and Measures Rate of each low-value breast cancer procedure based on facility type and breast cancer volume categories before and after the release of data supporting each procedure’s omission. Results The total cohort included 920 256 women with a median age of 63 years. Overall, 86% self-identified as White, 10% as Black, 3% as Asian, and 4.5% as Hispanic. Most women in this cohort were insured (51% private and 47% public), were living in a metropolitan or urban area (88% and 11%, respectively), and originated from the top half of income-earning households (65.5%). While there was significant deimplementation of axillary lymph node dissection and lumpectomy reoperation in response to guidelines supporting omission of these procedures, rates of contralateral prophylactic mastectomy and sentinel lymph node biopsy in older women increased during the study period. Academic research programs and high-volume facilities overall demonstrated the greatest reduction in use of these low-value procedures. There was significant interfacility variation for each low-value procedure. Facility-level axillary lymph node dissection rates ranged from 7% to 47%, lumpectomy reoperation rates ranged from 3% to 62%, contralateral prophylactic mastectomy rates ranged from 9% to 67%, and sentinel lymph node biopsy rates ranged from 25% to 97%. Pearson correlation coefficient for each combination of 2 of the 4 procedures was less than 0.11, suggesting that hospitals were not consistent in their deimplementation performance across all 4 procedures. Many were high outliers in one procedure but low outliers in another. Conclusions and Relevance Interfacility variation demonstrates a performance gap and an opportunity for formal deimplementation efforts targeting each procedure. Several facility-level characteristics were associated with differential deimplementation and performance.

This quality improvement study describes the cancer types, treatments, and services often targeted in the recommendations generated by oncology societies for the Choosing Wisely campaign.

Background For average-risk women with unilateral breast cancer, contralateral prophylactic mastectomy (CPM) offers no survival benefit and contributes to increased costs and patient harm. Despite recommendations from professional societies against CPM, utilization of this service is increasing, partly due to patients’ desire for breast symmetry when undergoing mastectomy. Most women with small tumors are candidates for breast-conserving surgery (BCS) and could avoid CPM. We describe CPM utilization in women with small, unilateral tumors, and identify determinants of possible overuse. Methods Using the National Cancer Database, we identified women with unilateral, T1 breast cancer. We evaluated utilization of BCS, unilateral mastectomy, and CPM and assessed patient, tumor, and facility factors associated with CPM. Results Of 765,487 women with small, unilateral breast cancer, 69% underwent BCS and 31% chose mastectomy. Of 176,673 women ≥70 y, 75% underwent BCS and 25% chose mastectomy. CPM rates in both cohorts have increased since 2006. Decreased adjuvant radiotherapy in older women was associated with increased BCS rates. Patient factors (younger age, white race, private insurance, and breast reconstruction), tumor factors (lobular histology, higher grade, and human epidermal growth factor receptor 2 positive/estrogen receptor negative status), and facility factors (type and geographic location) were associated with increased CPM rates compared with unilateral mastectomy in multivariable models. Conclusions Most women with small unilateral breast cancer are candidates for BCS, yet one-third elects to undergo a mastectomy, of which a rising percentage opts for CPM. Tailoring deimplementation strategies to factors influencing treatment may help reduce CPM utilization and associated financial toxicity, pain, and disability.

INTRODUCTION: or women over 70 years with early-stage breast cancer, the routine use of sentinel lymph node biopsy (SLNB) and adjuvant radiotherapy offers no overall survival benefit and may be perceived as undesirable by many women. National guidelines allow for possible omission of these practices in older women. Our objective was to assess the availability of web-based educational materials targeting older women and their age-specific treatment recommendations. METHODS: We systematically assessed the websites of the top 25 “Best Hospitals for Cancer” ranked by the U.S. News & World Report, as well as the websites of four prominent national cancer organizations. RESULTS: Websites for the leading cancer hospitals and national cancer organizations contain extremely limited information directed towards older patients with breast cancer. Both SLNB and adjuvant radiotherapy were described as treatments “typically,” “most often,” or “usually” used in combination with breast-conserving surgery, without noting circumstances for possible omission. Specifically, no hospital website and only one national organization included information on the recommendation to avoid routine SLNB. Only two hospitals and two national organizations included information suggesting possible omission of adjuvant radiotherapy in patients over 70 years. DISCUSSION: The absence of online material for older patients with breast cancer represents a gap potentially contributing to overtreatment by framing SLNB and adjuvant radiotherapy as necessary. Informational resources available to women ≥ 70 years may aid in informed physician-patient communication and decision-making, which may reduce SLNB and adjuvant radiotherapy in patients who might opt out of these procedures if fully informed about them.

IMPORTANCE: Overtreatment of early-stage breast cancer results in increased morbidity and cost without improving survival. Major surgical organizations participating in the Choosing Wisely campaign identified 4 breast cancer operations as low value: (1) axillary lymph node dissection for limited nodal disease in patients receiving lumpectomy and radiation, (2) re-excision for close but negative lumpectomy margins for invasive cancer, (3) contralateral prophylactic mastectomy in patients at average risk with unilateral cancer, and (4) sentinel lymph node biopsy in women 70 years or older with hormone receptor–positive cancer. OBJECTIVE: To evaluate the extent to which these procedures have been deimplemented, determine the implications of decreased use, and recognize possible barriers and facilitators to deimplementation. EVIDENCE REVIEW: A systematic review of published literature on use trends in breast surgery was performed in accordance with PRISMA guidelines. The Ovid, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases were searched for original research with relevance to the Choosing Wisely recommendations of interest. Eligible studies were examined for data about use, and any patient-level, clinician-level, or system-level factors associated with use. FINDINGS: Concordant with recommendations, national rates of axillary lymph node dissection for patients with limited nodal disease have decreased by approximately 50% (from 44% in 2011 to 30% to 34% in 2012 and 25% to 28% in 2013), and national rates of lumpectomy margin re-excision have decreased by nearly 40% (from 16% to 34% before to 14% to 18% after publication of a consensus statement). Conversely, national rates of contralateral prophylactic mastectomy continue to rise each year, accounting for up to 30% of all mastectomies for breast cancer (range in all mastectomy cases: 2010–2012, 28%−30%; 1998

INTRODUCTION: Guidelines allow for the omission of sentinel lymph node biopsy (SLNB) and post-lumpectomy radiotherapy in women ≥70 years old with hormone receptor positive (HR+) breast cancer. Despite this, national data suggest these procedures have not been widely de-implemented. Our objectives were to evaluate trends in SLNB and post-lumpectomy radiotherapy utilization in patients who are eligible for omission and evaluate patient preferences as a target for de-implementation of low-value care. METHODS: We performed a sequential explanatory mixed-methods study by first analyzing an institutional database of patients ≥70 years old with HR+ breast cancer who received surgical treatment from 2014-2018. Based on the quantitative data, we conducted semi-structured interviews with women identified as high or low utilizers of breast cancer treatments to elicit patient perspectives on de-implementation. RESULTS: SLNB and post-lumpectomy radiotherapy were performed in 68% and 43% of patients who met criteria for omission, respectively. There was a significant decrease in SLNB rates from 2014-2018. Forty-nine percent of patients were classified as high utilizers and 26% were classified as low utilizers. Qualitative analysis found that the most important factors influencing decision-making regarding SLNB and post-lumpectomy radiotherapy omission for both high and low utilizers were trust in their provider and desire for peace of mind. CONCLUSIONS: Despite efforts to de-implement low-value care, older women with HR+ breast cancer remain at risk of overtreatment. Patient perspectives suggest that multi-level de-implementation strategies will need to target provider practice patterns and patient-provider communication to promote high quality decision-making and reduction in breast cancer overtreatment.

Summary Introduction Utilizing a qualitative phenomenological design, the Defining Successful Outcomes and Trade-offs study examined stakeholder perspectives regarding optimal healthcare delivery and outcomes for individuals with a difference/disorder of sex development (DSD). Objective We describe study methods and provide an overview of themes and subthemes. Study design Interviews were conducted with individuals with a DSD (n=24), parents of those with a DSD (n=19), healthcare providers (n=37), and others (n=30). Primary questions regarding clinical management of patients with DSD were: “What is a successful outcome?” and “How do you achieve it?” Results Themes included: understanding of DSD diagnosis and self-efficacy in management is necessary but complex; patient and family psychological well-being; support from others versus being stigmatized; affected person experiences physical health and accepts the implications of their condition; complexities in DSD decision making, roles and expectations; and knowledgeable providers and multidisciplinary teams are essential, notwithstanding persisting barriers (See Summary Figure). Participants recognized competing values potentially forcing trade-offs in decision making. Discussion. Recognition of diverse and sometimes conflicting perspectives regarding optimal pathways of care and outcomes – both within and among those with DSD and their providers –promises to enhance shared decision making. Conclusion Diverse perspectives and perceptions of trade-offs associated with DSD healthcare emphasize the need to tailor care for patients and families.

Obesity results from the accumulation of excess white adipose tissue, and its increasing rates worldwide pose a significant risk to overall health due to its multiple comorbidities, like type 2 diabetes. A novel treatment strategy is to increase energy expenditure through activation of brown and beige adipocytes, which can use uncoupling protein 1 (UCP1) for thermogenesis. In addition to having different developmental lineages, brown and beige adipocytes differ functionally regarding the additional mechanisms by which they generate heat. Most human fat depots are not easily accessible, so little is known about their developmental and functional characteristics. In this study, we collected adipose tissue from 11 patients (age 16-84, 4 female/7 male) who had undergone autopsy. We sampled from 7 anatomically distinct fat depots: subcutaneous (sc), omental (om), retroperitoneal (rp), pericardial (pc), periadrenal (pa), paraspinal (ps), and supraclavicular (sv). We measured mRNA levels of lineage and functional genes associated with brown, beige, and white adipocytes. Energy storing white adipocytes were defined by high leptin expression, while energy expending brown and beige cells were defined by high UCP1; these were further distinguished as having a brown lineage using Zic1 and beige via Tbx1. Principal component analysis showed three different clusters of genes consistent with the brown, beige, and white lineages. Functionally, based on expression of leptin and UCP1 for white and brown fat, respectively, the sc and om were white (P In summary, human adipose tissue is not merely white or brown but instead is composed of many depots with distinct developmental lineages and functional capacities. These differences will be important when trying to use brown and beige adipocyte thermogenesis to treat obesity and diabetes. Disclosure J.W. Johnson: None. C. Cero: None. A. O'Mara: None. J.D. Linderman: None. A.S. Baskin: None. A. Cypess: None.

In rodent models, the β3-adrenergic receptor (AR) is responsible for thermogenesis in brown adipose tissue (BAT) and lipolysis in white adipose tissue (WAT). In contrast, the contribution of β3-AR in human adipocytes is controversial due to the low expression of the β3-AR in WAT and access only to partial β3-AR agonists. Mirabegron, an FDA-approved drug for overreactive bladder, is a selective human β3-AR agonist. In a recent clinical trial, mirabegron activated human BAT thermogenesis and WAT lipolysis. Therefore, we investigated the distribution and relative contribution of β1/2/3-AR in (i) whole white (hWAT) and brown (hBAT) adipose tissue from human autopsies and (ii) immortalized human white (hWA) and brown (hBA) adipocytes. Among the three β-ARs, β1-AR and β2-AR are similarly expressed in brown and white adipose tissue, whereas β3-AR has the highest expression in hBAT. In immortalized differentiated cells, hBA have a significantly higher expression of β3-AR compared to hWA. To assess the functionally of these receptors in adipocytes, dose-response curves of agonist-stimulated lipolysis were investigated in differentiated human and mouse adipocytes. We observed that stimulation of any one of the three β-ARs in human adipocytes induces a significant increase in glycerol release, a lipolytic byproduct. However, the effective dose of mirabegron to activate β3-AR-mediated lipolysis in white and brown adipocytes via mirabegron was significantly lower (hWA: EC50 2.55E-09; hBA: EC50 6.31E-09) compared to specific activators of β1-AR or β2-AR. In summary, we identify a major role played by the β3-AR in the regulation of human BAT thermogenesis and WAT lipolysis, both in vivo and in vitro. Due to the comparatively minimal effects of mirabegron treatment on the cardiovascular system, selective β3-AR agonists may be the optimal choice for targeted stimulation of human WAT and BAT. Disclosure C. Cero: None. A. O'Mara: None. J.W. Johnson: None. A.S. Baskin: None. J.D. Linderman: None. A. Cypess: None.

Introduction: Medicare beneficiaries often report that the process of choosing a prescription drug plan is frustrating and confusing and many do not enroll in the plan that covers their drugs at the lowest cost. Methods: We conducted 4 focus groups to understand beneficiaries’ experiences in selecting a drug plan to identify what resources and factors were most important to them. Participants were patients served by a multispecialty delivery system and were primarily affluent and Caucasian. Results: While low cost was essential to many, other characteristics like having the same plan as a partner, company reputation, convenience, and anticipation of possible future health problems were sometimes more important. Although some used resources including insurance brokers, counselors, and websites beyond Medicare.gov , many expressed a desire for greater assistance with and greater simplicity in the choice process. Conclusion: Although older adults would likely benefit from greater assistance in choosing Medicare Part D prescription drug plans, more research is necessary to understand how to help with decision-making in this context.

β3-adrenergic receptor (AR) agonists are approved to treat only overactive bladder. However, rodent studies suggest that these drugs could have other beneficial effects on human metabolism. We performed tissue receptor profiling and showed that the human β3-AR mRNA is also highly expressed in gallbladder and brown adipose tissue (BAT). We next studied the clinical implications of this distribution in 12 healthy men given one-time randomized doses of placebo, the approved dose of 50 mg, and 200 mg of the β3-AR agonist mirabegron. There was a more-than-dose-proportional increase in BAT metabolic activity as measured by [18F]-2-fluoro-D-2-deoxy-d-glucose positron emission tomography/computed tomography (medians 0.0 vs. 18.2 vs. 305.6 mL ⋅ mean standardized uptake value [SUVmean] ⋅ g/mL). Only the 200-mg dose elevated both nonesterified fatty acids (68%) and resting energy expenditure (5.8%). Previously undescribed increases in gallbladder size (35%) and reductions in conjugated bile acids were also discovered. Therefore, besides urinary bladder relaxation, the human β3-AR contributes to white adipose tissue lipolysis, BAT thermogenesis, gallbladder relaxation, and bile acid metabolism. This physiology should be considered in the development of more selective β3-AR agonists to treat obesity-related complications.

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m2; 8 obese, BMI 34.8 ± 3.3 kg/m2] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1–71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT—cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal—with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.