A SARS-CoV-2 Cluster in an Acute Care Hospital.

BACKGROUND: Little is known about clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in acute care hospitals. OBJECTIVE: To describe the detection, mitigation, and analysis of a large cluster of SARS-CoV-2 infections in an acute care hospital with mature infection control policies. DESIGN: Descriptive study. SETTING: Brigham and Women's Hospital, Boston, Massachusetts. PARTICIPANTS: Patients and staff with cluster-related SARS-CoV-2 infections. INTERVENTION: Close contacts of infected patients and staff were identified and tested every 3 days, patients on affected units were preemptively isolated and repeatedly tested, affected units were cleaned, room ventilation was measured, and specimens were sent for whole-genome sequencing. A case-control study was done to compare clinical interactions, personal protective equipment use, and breakroom and workroom practices in SARS-CoV-2-positive versus negative staff. MEASUREMENTS: Description of the cluster, mitigation activities, and risk factor analysis. RESULTS: Fourteen patients and 38 staff members were included in the cluster per whole-genome sequencing and epidemiologic associations. The index case was a symptomatic patient in whom isolation was discontinued after 2 negative results on nasopharyngeal polymerase chain reaction testing. The patient subsequently infected multiple roommates and staff, who then infected others. Seven of 52 (13%) secondary infections were detected only on second or subsequent tests. Eight of 9 (89%) patients who shared rooms with potentially contagious patients became infected. Potential contributing factors included high viral loads, nebulization, and positive pressure in the index patient's room. Risk factors for transmission to staff included presence during nebulization, caring for patients with dyspnea or cough, lack of eye protection, at least 15 minutes of exposure to case patients, and interactions with SARS-CoV-2-positive staff in clinical areas. Whole-genome sequencing confirmed that 2 staff members were infected despite wearing surgical masks and eye protection. LIMITATION: Findings may not be generalizable. CONCLUSION: SARS-CoV-2 clusters can occur in hospitals despite robust infection control policies. Insights from this cluster may inform additional measures to protect patients and staff. PRIMARY FUNDING SOURCE: None.

Clinical predictors of hypoxic pneumonia in children from the Eastern Highlands Province, Papua New Guinea: secondary analysis of two prospective observational studies.

Background: Pneumonia is the leading cause of death in young children globally and is prevalent in the Papua New Guinea highlands. We investigated clinical predictors of hypoxic pneumonia to inform local treatment guidelines in this resource-limited setting. Methods: Between 2013 and 2020, two consecutive prospective observational studies were undertaken enrolling children 0-4 years presenting with pneumonia to health-care facilities in Goroka Town, Eastern Highlands Province. Logistic regression models were developed to identify clinical predictors of hypoxic pneumonia (oxygen saturation <90% on presentation). Model performance was compared against established criteria to identify severe pneumonia. Findings: There were 2067 cases of pneumonia; hypoxaemia was detected in 36.1%. The strongest independent predictors of hypoxic pneumonia were central cyanosis on examination (adjusted odds ratio [aOR] 5.14; 95% CI 3.47-7.60), reduced breath sounds (aOR 2.92; 95% CI 2.30-3.71), and nasal flaring or grunting (aOR 2.34; 95% CI 1.62-3.38). While the model developed to predict hypoxic pneumonia outperformed established pneumonia severity criteria, it was not sensitive enough to be clinically useful at this time. Interpretation: Given signs and symptoms are unable to accurately detect hypoxia, all health care facilities should be equipped with pulse oximeters. However, for the health care worker without access to pulse oximetry, consideration of central cyanosis, reduced breath sounds, nasal flaring or grunting, age-specific tachycardia, wheezing, parent-reported drowsiness, or bronchial breathing as suggestive of hypoxaemic pneumonia, and thus severe disease, may prove useful in guiding management, hospital referral and use of oxygen therapy. Funding: Funded by Pfizer Global and the Bill & Melinda Gates Foundation.

Pneumococcal carriage, serotype distribution, and antimicrobial susceptibility in Papua New Guinean children vaccinated with PCV10 or PCV13 in a head-to-head trial.

BACKGROUND: Children in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13). METHODS: Infants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC). RESULTS: S. pneumoniae was isolated from 883/1063 NPS collected at 1-23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6-97.6%) of PCV10 recipients and 88.6% (95%CI 80.1-94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2-29.5) than PCV13 recipients (9.3%, 95%CI 4.1-17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC ≥ 0.12 µg/mL), but resistance was rare (1.1%) using the non-meningitis cut-off (MIC ≥ 8 µg/mL). Non-susceptibility to trimethoprim-sulfamethoxazole (SXT) was common: 23.2% of isolates showed intermediate resistance (MIC 1/19-2/38 µg/mL) and 16.9% full resistance (MIC ≥ 4/76 µg/mL). PCV serotypes 14 and 19A were commonly non-susceptible to both penicillin (14, 97%; 19A, 70%) and SXT (14, 97%; 19A, 87%). CONCLUSION: Even after PCV10 or PCV13 vaccination, children living in a high-risk setting such as PNG continue to experience high levels of pneumococcal colonization, including carriage of highly antimicrobial-resistant PCV serotypes. The study is registered with ClinicalTrials.gov (CTN NCT01619462).

High-molecular-weight and total adiponectin levels and incident symptomatic peripheral artery disease in women: a prospective investigation.

BACKGROUND: Adiponectin is linked to reduced diabetes risk and may be antiatherogenic, yet clinical data show no consistent relationship with incident cardiovascular events, especially among women. To our knowledge, no prior prospective studies have evaluated adiponectin, including high-molecular-weight (HMW) adiponectin, and incident peripheral artery disease (PAD). METHODS AND RESULTS: We evaluated the relationship of total adiponectin, HMW adiponectin, and the HMW-to-total adiponectin ratio with incident symptomatic PAD in a prospective, nested case-control study conducted within the Women's Health Study (n=110 cases, n=230 controls, frequency matched in strata defined by 5-year age categories, smoking, fasting status, and follow-up time; median cohort follow-up=13.2 years). Baseline median levels of HMW and total adiponectin were significantly lower in women developing PAD than in those remaining event free (HMW: 3.3 versus 3.8 µg/mL, P=0.0005; total: 5.6 versus 7.4 µg/mL, P<0.0001). The ratio did not differ significantly between groups. Age-adjusted PAD odds ratios (95% confidence intervals) across tertiles were 1.0, 0.66 (0.39-1.13), and 0.40 (0.22-0.74) for HMW and 1.0, 0.74 (0.43-1.25), and 0.35 (0.18-0.65) for total adiponectin (P(trend)=0.004 and 0.001, respectively). Results were similar after adjustment for traditional cardiovascular risk factors, use of postmenopausal hormone therapy, high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, leptin, hemoglobin A(1c), and fasting insulin (adjusted odds ratio and 95% confidence interval for HMW: 1.0, 0.62 [0.29-1.34], 0.30 [0.12-0.74]; total: 1.0, 0.46 [0.22-1.00], 0.30 [0.12-0.76]; P(trend)=0.01 for both). CONCLUSIONS: Total and HMW adiponectin are inversely associated with incident PAD among initially healthy women. These prospective data support a protective role for this adipokine in peripheral atherosclerosis development.

Insulin resistance and incident peripheral artery disease in the Cardiovascular Health Study.

Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by two methods. PAD was first defined as the development of an abnormal ankle-brachial index (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively defined as the development of clinical PAD (time-to-event analysis). The study samples included adults over the age of 65 years who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, body mass index (BMI), smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n = 2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95% confidence interval [CI] 1.20-2.71). In the clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio = 2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95% CI 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults.

Effectiveness of 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia and hospitalisation in Eastern Highlands Province, Papua New Guinea: An observational cohort study.

Background: Pneumonia is a leading cause of childhood mortality with Streptococcus pneumoniae a major contributor. Pneumococcal conjugate vaccines (PCVs) have been introduced into immunisation programs in many low- to middle-income countries (LMICs) yet there is a paucity of data evaluating the effectiveness in these settings. We assess the effectiveness of 13-valent PCV (13vPCV) against hypoxic pneumonia, hospitalisation and other clinical endpoints in children <5 years living in Eastern Highlands Province, Papua New Guinea (PNG). Methods: Data from two consecutive prospective observational studies (2013-2019) enrolling children <60 months presenting with pneumonia were included. Hypoxic pneumonia was defined as oxygen saturations <90%. Outcomes included hospitalisation, severe clinical pneumonia and death. 13vPCV status was determined using written records. Logistic regression models were used to estimate the odds ratios of key outcomes by 13vPCV vaccination status adjusted for confounders using inverse probability of treatment weighting. Findings: Data from 2067 children (median age; 9 months [IQR: 5-11]) were included. 739 children (36.1%) were hypoxic and 623 (30.4%) hospitalised. Twelve children (0.6% of total cohort) died in hospital. 670 children (32.7%) were fully 13vPCV-vaccinated. 13vPCV vaccination was associated with a 28.7% reduction (95% confidence interval [CI]: 9.9; 43.6%) in hypoxic pneumonia and a 57.4% reduction (38.0; 70.7%) in pneumonia hospitalisation. Interpretation: 13vPCV vaccination is effective against hypoxic pneumonia and pneumonia hospitalisation in PNG children. Strategies to improve access to and coverage of 13vPCV in PNG and other similar LMICs are urgently required. Funding: Funded by Pfizer Global and the Bill & Melinda Gates Foundation.

Remote vs In-home Physician Visits for Hospital-Level Care at Home: A Randomized Clinical Trial.

Importance: Home hospital care is the substitutive provision of home-based acute care services usually associated with a traditional inpatient hospital. Many home hospital models require a physician to see patients at home daily, which may hinder scalability. Whether remote physician visits can safely substitute for most in-home visits is unknown. Objective: To compare remote and in-home physician care. Design, Setting, and Participants: This randomized clinical trial assessed 172 adult patients at an academic medical center and community hospital who required hospital-level care for select acute conditions, including infection, heart failure, chronic obstructive pulmonary disease, and asthma, between August 3, 2019, and March 26, 2020; follow-up ended April 26, 2020. Interventions: All patients received acute care at home, including in-home nurse or paramedic visits, intravenous medications, remote monitoring, and point-of-care testing. Patients were randomized to receive physician care remotely (initial in-home visit followed by daily video visit facilitated by the home hospital nurse) vs in-home care (daily in-home physician visit). In the remote care group, the physician could choose to see the patient at home beyond the first visit if it was felt to be medically necessary. Main Outcomes and Measures: The primary outcome was the number of adverse events, compared using multivariable Poisson regression at a noninferiority threshold of 10 events per 100 patients. Adverse events included a fall, pressure injury, and delirium. Secondary outcomes included the Picker Patient Experience Questionnaire 15 score (scale of 0-15, with 0 indicating worst patient experience and 15 indicating best patient experience) and 30-day readmission rates. Results: A total of 172 patients (84 receiving remote care and 88 receiving in-home physician care [control group]) were randomized; enrollment was terminated early because of COVID-19. The mean (SD) age was 69.3 (18.0) years, 97 patients (56.4%) were female, 77 (45.0%) were White, and 42 (24.4%) lived alone. Mean adjusted adverse event count was 6.8 per 100 patients for remote care patients vs 3.9 per 100 patients for control patients, for a difference of 2.8 (95% CI, -3.3 to 8.9), supporting noninferiority. For remote care vs control patients, the mean adjusted Picker Patient Experience Questionnaire 15 score difference was -0.22 (95% CI, -1.00 to 0.56), supporting noninferiority. The mean adjusted 30-day readmission absolute rate difference was 2.28% (95% CI, -3.23% to 7.79%), which was inconclusive. Of patients in the remote group, 16 (19.0%) required in-home visits beyond the first visit. Conclusions and Relevance: In this study, remote physician visits were noninferior to in-home physician visits during home hospital care for adverse events and patient experience, although in-home physician care was necessary to support many patients receiving remote care. Our findings may allow for a more efficient, scalable home hospital approach but require further research. Trial Registration: ClinicalTrials.gov Identifier: NCT04080570.

No association between hemoglobin A1c and in-hospital mortality in patients with diabetes and acute myocardial infarction.

BACKGROUND: Patients with diabetes have increased in-hospital mortality following acute myocardial infarction (AMI), with studies suggesting higher risk with both hypoglycemia and hyperglycemia. We assessed whether a J-shaped relation exists between hemoglobin A1c (A1C) in patients with diabetes and AMI. METHODS: We assessed the associations between A1C and in-hospital mortality using data from a nationwide sample of AMI patients who had both prior diabetes and measurement of A1C (N = 15,337). RESULTS: When evaluated continuously, we observed no evidence of a J-shaped relation between A1C and in-hospital mortality in multivariable analysis (test for linearity P = .89). Patients with lowest (<5.5%) and highest A1C (≥9.5%) had a crude mortality rate of 4.6% and 2.8%, respectively, compared with 3.8% among those in the referent A1C category (6.5% to <7%). In multivariable regression, we observed no association between low A1C (<5.5%, odds ratio 0.81, 95% CI 0.47-1.39) or high A1C (A1C ≥9.5, odds ratio 1.31, 95% CI 0.94-1.83) and mortality as compared with the referent group. These findings can only be generalized to the subset of patients with diabetes who had A1C assessed during their hospitalization; these patients tended to be healthier than those in whom A1C was not assessed. CONCLUSION: In this large contemporary cohort of patients with diabetes presenting with AMI, we did not observe a J-shaped association between A1C and mortality.

National Hospital Initiatives to Improve Performance on Heart Failure Readmission Metrics.

BACKGROUND: The passage of the Hospital Readmissions Reduction Program (HRRP) has been associated with been associated with decreased risk-standardized readmission rates for heart failure (HF) patients. However, some quantitative analyses have shown association between HRRP and increased mortality for hospitalized HF patients. Qualitative information on what hospital programs were actually implemented can help us understand if this trend is a causal effect of the law or an unrelated trend. PURPOSE: To perform a systematic literature review to synthesize evidence on what clinical programs American hospitals implemented in response to HRRP. METHODS: Following PRISMA guidelines, we conducted a systematic review in April 2020 that included a search of PubMed, the Cochrane Library and Cumulative Index to Nursing and Allied Literature (CINAHL) for studies related to hospital strategies to reduce HF readmissions. RESULTS: Of 20 included articles, 8 were qualitative (survey and interviews), 3 were systematic reviews, 5 were single site quality improvement (QI) initiatives, 2 were plans for ongoing randomized control trials (RCTs), one was a plan for a future RCT and one was an observational analysis. We found that interventions hospitals undertook in response to HRRP to reduce HF readmissions fell into four categories: inpatient care, discharge, transitional care and data collection/administration. The majority of interventions were related to transitional care, most commonly scheduling follow up appointments within 7-14 days of discharge, performing post-discharge phone calls and partnering with community physicians. CONCLUSIONS: We did not find any published evidence of practices that could mechanistically be linked to harm to HF patients enacted by hospitals in response to HRRP. For example, no programs encouraged emergency department providers to discharge patients from emergency departments. We found QI initiatives, improved discharge planning and increased post-discharge follow up.

Virtual Team Rounding: A Cross-Specialty Inpatient Care Staffing Program to Manage COVID-19 Surges.

PROBLEM: The SARS-CoV-2 (COVID-19) pandemic presented numerous challenges to inpatient care, including overtaxed inpatient medicine services, surges in patient censuses, disrupted patient care and educational activities for trainees, underused providers in certain specialties, and personal protective equipment shortages and new requirements for physical distancing. In March 2020, as the COVID-19 surge began, an interdisciplinary group of administrators, providers, and trainees at Brigham and Women's Hospital created an inpatient virtual staffing model called the Virtual Team Rounding Program (VTRP). APPROACH: The conceptual framework guiding VTRP development was rapid-cycle innovation. The VTRP was designed iteratively using feedback from residents, physician assistants, attendings, and administrators from March to June 2020. The VTRP trained and deployed a diverse set of providers across specialties as "virtual rounders" to support inpatient teams by joining and participating in rounds via videoconference and completing documentation tasks during and after rounds. The program was rapidly scaled up from March to June 2020. OUTCOMES: In a survey of inpatient providers at the end of the pilot phase, 10/10 (100%) respondents reported they were getting either "a lot" or "a little" benefit from the VTRP and did not find the addition of the virtual rounder burdensome. During the scaling phase, the program grew to support 24 teams. In a survey at the end of the contraction phase, 117/187 (62.6%) inpatient providers who worked with a virtual rounder felt the rounder saved them time. VTRP leadership collaboratively and iteratively developed best practices for challenges encountered during implementation. NEXT STEPS: Virtual rounding provides a valuable extension of inpatient teams to manage COVID-19 surges. Future work will quantitatively and qualitatively assess the impact of the VTRP on inpatient provider satisfaction and well-being, virtual rounders' experiences, and patient care outcomes.

Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants.

BACKGROUND: Papua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world. METHODS: Nasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray. RESULTS: Pneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log10genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes. CONCLUSION: PNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered.

Implementation of a skilled nursing facility readmission review process.

30-day readmissions for patients at skilled nursing facilities (SNF) are common and preventable. We implemented a readmission review process for patients readmitted from two SNFs, involving an electronic review tool and monthly conferences. The electronic review tool captures information related to preventability and factors contributing to readmission. The study included 128 patients, readmitted within 30 days from 1 October 2015 through 1 May 2017, at a tertiary care academic medical centre in Boston, MA, and two partnering SNFs. There was a discrepancy in preventability rating between SNF and hospital reviewers, with 79.7% of cases rated not preventable by the SNF, and 58.6% by the hospital. There was moderate positive correlation between the hospital's and SNFs' preventability ratings (rs=0.652, p<0.001). In most cases, the SNF reviewers felt that no factors contributed (57.8%), and hospital reviewers felt that issues with end-of-life planning (14.1%) and medical complexity (12.5%) were major factors. Despite the lack of strong correlation between SNF and hospital responses, several cross-continuum quality improvement projects were developed. We found that implementation of a SNF readmission review process employing bidirectional review by SNF and hospital was feasible, and facilitated systems-based improvement in the transition from hospital to postacute care.

Relation of Iliac Artery Calcium With Adiposity Measures and Peripheral Artery Disease.

Arterial calcification is associated with cardiovascular morbidity and mortality. To improve the understanding of the pathogenesis involved with iliac artery calcium (IAC), we sought to examine the associations between the burden of IAC with adiposity measures and peripheral artery disease (PAD). Participants (n = 1,236, 52% women, mean age 60 years) were drawn from the Framingham Heart Study Offspring cohort who underwent multidetector computed tomography. The extent of IAC was quantified based on calcified atherosclerotic plaques detected in the iliac arteries. High IAC was defined based on gender-specific 90th percentile cut-off points from a healthy referent subsample. PAD is defined as an ankle-brachial index < 0.9, intermittent claudication, and/or history of lower extremity revascularization. The association between PAD and IAC was assessed using multivariable-adjusted logistic regression models. The burden of high IAC was 20.5% in women and 25.5% in men. High IAC was not associated with generalized (body mass index) or area-specific (waist circumference, and volumes of thoracic periaortic, abdominal subcutaneous, and visceral adipose tissue) adiposity measures (all p ≥0.22). High IAC was associated with increased odds of PAD (odds ratio 10.36, 95% confidence interval 4.28 to 25.09). This association persisted even after additionally adjusting for coronary artery calcium (odds ratio 11.25, 95% confidence interval 4.29 to 29.53). Burden of IAC was associated with an increased risk of PAD.

Adipose Tissue Depots and Their Cross-Sectional Associations With Circulating Biomarkers of Metabolic Regulation.

BACKGROUND: Visceral adipose tissue (VAT) and fatty liver differ in their associations with cardiovascular risk compared with subcutaneous adipose tissue (SAT). Several biomarkers have been linked to metabolic derangements and may contribute to the pathogenicity of fat depots. We examined the association between fat depots on multidetector computed tomography and metabolic regulatory biomarkers. METHODS AND RESULTS: Participants from the Framingham Heart Study (n=1583, 47% women) underwent assessment of SAT, VAT, and liver attenuation. We measured circulating biomarkers secreted by adipose tissue or liver (adiponectin, leptin, leptin receptor, fatty acid binding protein 4, fetuin-A, and retinol binding protein 4). Using multivariable linear regression models, we examined relations of fat depots with biomarkers. Higher levels of fat depots were positively associated with leptin and fatty acid binding protein 4 but negatively associated with adiponectin (all P<0.001). Associations with leptin receptor, fetuin-A, and retinol binding protein 4 varied according to fat depot type or sex. When comparing the associations of SAT and VAT with biomarkers, VAT was the stronger correlate of adiponectin (ß=-0.28 [women]; ß=-0.30 [men]; both P<0.001), whereas SAT was the stronger correlate of leptin (ß=0.62 [women]; ß=0.49 [men]; both P<0.001; P<0.001 for comparing VAT versus SAT). Although fetuin-A and retinol binding protein 4 are secreted by the liver in addition to adipose tissue, associations of liver attenuation with these biomarkers was not stronger than that of SAT or VAT. CONCLUSIONS: SAT, VAT, and liver attenuation are associated with metabolic regulatory biomarkers with differences in the associations by fat depot type and sex. These findings support the possibility of biological differences between fat depots.