Single-cell RNA-seq reveals intratumoral heterogeneity in osteosarcoma patients: A review.

While primary bone malignancies make up just 0.2% of all cancers, osteosarcoma (OS) is the third most common cancer in adolescents. Due to its highly complex and heterogeneous tumor microenvironment (TME), OS has proven difficult to treat. There has been little to no improvement in therapy for this disease over the last 40 years. Even the recent success of immunotherapies in other blood-borne and solid malignancies has not translated to OS. With frequent recurrence and lung metastases continuing to pose a challenge in the clinic, recent advancements in molecular profiling, such as single-cell RNA sequencing (scRNA-seq), have proven useful in identifying novel biomarkers of OS tumors while providing new insight into this TME that could potentially lead to new therapeutic options. This review combines the analyses of over 150,000 cells from 18 lesions ranging from primary, recurrent, and metastatic OS lesions, revealing distinct cellular populations and gene signatures that exist between them. Here, we detail these previous findings and ultimately convey the intratumoral heterogeneity that exists within OS tumor specimens.

Electronic consultations (E-consults) and their outcomes: a systematic review.

OBJECTIVE: Electronic consultations (e-consults) are clinician-to-clinician communications that may obviate face-to-face specialist visits. E-consult programs have spread within the US and internationally despite limited data on outcomes. We conducted a systematic review of the recent peer-reviewed literature on the effect of e-consults on access, cost, quality, and patient and clinician experience and identified the gaps in existing research on these outcomes. MATERIALS AND METHODS: We searched 4 databases for empirical studies published between 1/1/2015 and 2/28/2019 that reported on one or more outcomes of interest. Two investigators reviewed titles and abstracts. One investigator abstracted information from each relevant article, and another confirmed the abstraction. We applied the GRADE criteria for the strength of evidence for each outcome. RESULTS: We found only modest empirical evidence for effectiveness of e-consults on important outcomes. Most studies are observational and within a single health care system, and comprehensive assessments are lacking. For those outcomes that have been reported, findings are generally positive, with mixed results for clinician experience. These findings reassure but also raise concern for publication bias. CONCLUSION: Despite stakeholder enthusiasm and encouraging results in the literature to date, more rigorous study designs applied across all outcomes are needed. Policy makers need to know what benefits may be expected in what contexts, so they can define appropriate measures of success and determine how to achieve them.

Effects of medium chain triglycerides supplementation on insulin sensitivity and beta cell function: A feasibility study.

OBJECTIVE: Medium chain triglycerides (MCT) have unique metabolic properties which may improve insulin sensitivity (Si) and beta cell function but data in humans are limited. We conducted a 6-week clinical trial of MCT oil supplementation. METHODS: 22 subjects without diabetes (8 males, 14 females, mean ± standard error age 39±2.9 years, baseline BMI 27.0±1.4 kg/m2) were counseled to maintain their body weight and physical activity (PA) during the trial. Dietary intake, PA data, body composition, and resting energy expenditure (REE) were obtained through dietary recall, international PA questionnaire, dual x-ray absorptiometry, and indirect calorimetry, respectively. MCT prescriptions were given based on REE and PA to replace part of dietary fat with 30 grams of MCT per 2000 kcal daily. Insulin-modified frequently sampled intravenous glucose tolerance tests were performed before and after MCT to measure changes in Si, acute insulin response (AIR), disposition index (DI), and glucose effectiveness (Sg). RESULTS: MCT were well tolerated and weight remained stable (mean change 0.3 kg, p = 0.39). Fasting REE, respiratory quotient, and body composition were stable during the intervention. There were no significant changes in mean fasting glucose, insulin, insulin resistance, fasting total ketones, Si, AIR, DI, Sg, leptin, fructosamine, and proinsulin. The mean change in Si was 0.5 10-4 min-1 per mU/L (95% CI: -1.4, 2.4), corresponding to a 12% increase from baseline, and the range was -4.7 to 12.9 10-4 min-1 per mU/L. Mean total adiponectin decreased significantly from 22925 ng/mL at baseline to 17598 ng/mL at final visit (p = 0.02). The baseline clinical and laboratory parameters were not significantly associated with the change in Si. DISCUSSION: There were a wide range of changes in the minimal model parameters of glucose and insulin metabolism in subjects following 6 weeks of MCT as an isocaloric substitution for part of usual dietary fat intake. Since this was a single-arm non-randomized study without a control group, it cannot be certain whether these changes were due to MCT so further randomized controlled trials are warranted.

Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction.

Hyperinsulinemia is strongly associated with type 2 diabetes. Racial and ethnic minority populations are disproportionately affected by diabetes and obesity-related complications. This mini-review provides an overview of the genetic and environmental factors associated with hyperinsulinemia with a focus on racial and ethnic differences and its metabolic consequences. The data used in this narrative review were collected through research in PubMed and reference review of relevant retrieved articles. Insulin secretion and clearance are regulated processes that influence the development and progression of hyperinsulinemia. Environmental, genetic, and dietary factors are associated with hyperinsulinemia. Certain pharmacotherapies for obesity and bariatric surgery are effective at mitigating hyperinsulinemia and are associated with improved metabolic health. Hyperinsulinemia is associated with many environmental and genetic factors that interact with a wide network of hormones. Recent studies have advanced our understanding of the factors affecting insulin secretion and clearance. Further basic and translational work on hyperinsulinemia may allow for earlier and more personalized treatments for obesity and metabolic diseases.

Patient Characteristics Associated with Receipt of Prescription Weight-Management Medications Among Veterans Participating in MOVE!

OBJECTIVE: Weight-management medications (WMM) are recommended for the treatment of obesity. This study examined characteristics associated with initial receipt of WMM among eligible veterans in the first year following enrollment in the Veterans Health Administration (VHA) MOVE! behavioral weight-management program. METHODS: We conducted a retrospective cohort study of VHA patients with obesity or overweight and obesity-related comorbidities who enrolled in MOVE! from October 2013 to September 2016 (N = 153,939). Multivariable logistic regression models estimated predictors of having a filled prescription for WMM and for orlistat. RESULTS: A total of 1.1% of these veterans received WMM. The most common WMM included orlistat (70.4%), phentermine/topiramate (11.2%), and bupropion/naltrexone (9.7%). Female sex, higher BMI, obstructive sleep apnea, osteoarthritis, depression, lower back pain, and alcohol abuse were associated with greater odds of use of WMM, whereas age over 65 years, Hispanic ethnicity, and required co-payments were associated with lower odds. Among patients receiving WMM, older age, black race, female sex, higher BMI, cardiovascular disease, lower back pain, and congestive heart failure were associated with use of orlistat versus any other WMM. CONCLUSIONS: Of patients engaged in MOVE! in the VHA, 1.1% received WMM. WMM are underutilized among veterans. Additional research is needed to understand barriers to incorporating WMM into comprehensive obesity treatment plans.

Sustained Improvement in Type 2 Diabetes Mellitus is Common After Treatment of Hepatitis C Virus With Direct-acting Antiviral Therapy.

GOALS: To determine whether diabetic patients with hepatitis C virus (HCV) treated with direct-acting antiviral agents have improved diabetes, accounting for change in both hemoglobin A1c (HbA1c) and diabetes medications, and whether any improvement was sustained. BACKGROUND: HCV infection is associated with an increased risk of diabetes, with improvement in glycemic control after eradication. There remains uncertainty about the durability and magnitude of this effect. STUDY: HbA1c and diabetes medications were recorded at 6-month intervals for 1.5 years pretreatment and posttreatment for 122 patients. Subjects were classified as having improved diabetes if there was a decrease in HbA1c≥0.5% with no increase in diabetes medications or a decrease in diabetes medications with a stable HbA1c. RESULTS: HbA1c at the nearest time point before treatment was 8.4%±1.9%, compared with 7.8%±1.7% after treatment, a mean difference of 0.6% [95% CI (0.2, 0.9), P<0.01]. A linear mixed effects model incorporating each subject's repeated measurements over time also demonstrated a reduction after treatment of 0.5% [95% CI, (0.3, 0.8), P<0.001]. Accounting for both HbA1c and diabetes medications, 42 of 122 (34%) had an improvement in diabetes after HCV treatment, and 20 of 28 (71%) of these subjects sustained improvement at 1.5 years follow-up. Prescription of insulin was associated with improved diabetes. CONCLUSIONS: Treatment of HCV with direct-acting antiviral agents was associated with improved diabetes in a significant portion of patients with an average reduction in HbA1c of clinically significant magnitude. Among responders, this effect was sustained over 1.5 years of follow-up.

Weight Recidivism After Roux-en-Y Gastric Bypass Surgery: An 11-Year Experience in a Multiethnic Medical Center.

OBJECTIVE: Weight recidivism following Roux-en-Y gastric bypass (RYGB) is common and is associated with recurrence of comorbidities. Studies with long-term follow-up of recidivism quantified by weight regain (WR) are lacking. A retrospective review of all RYGB at our center from 2004 to 2015 was performed to examine the effects of race and type 2 diabetes on WR following RYGB. METHODS: Multivariable linear mixed models were used for the effects of time and race on weight, WR relative to nadir weight (WR/nadir), and WR relative to maximal weight loss, and Cox regressions were used for low, moderate, and high WR/nadir. RESULTS: A total of 1,395 participants were identified. The sample was limited to African American (AA), Caucasian American (CA), and Hispanic American (HA) participants. The effects of time (P < 0.0001), race (P < 0.0001), and race × time interaction (P = 0.0008) on weight trajectory were significant. AA had significantly more WR than CA (P < 0.01). AA and HA had a higher hazard ratio for having low, moderate, and rapid WR/nadir. CONCLUSIONS: Racial disparities after RYGB include WR and particularly affect AA. Understanding the etiologic factors that contribute to these disparities is important to optimize the long-term clinical outcomes of bariatric surgery.

Protein sparing therapies in acute illness and obesity: a review of George Blackburn's contributions to nutrition science.

Protein sparing therapies were developed to mitigate the harms associated with protein-calorie malnutrition and nitrogen losses induced by either acute illness or hypocaloric diets in patients with obesity. We review the development of protein sparing therapies in illness and obesity with a focus on the pioneering contributions of George Blackburn, MD, PhD. He recognized that protein-calorie malnutrition is a common and serious clinical condition and developed new approaches to its treatment in hospitalized patients. His work with stable isotopes and with animal models provided answers about the physiological nutritional requirements and metabolic changes across a spectrum of conditions with varying degrees of stress and catabolism. This led to improvements in enteral and parenteral nutrition for patients with acute illness. Blackburn also demonstrated that lean body mass can be preserved during weight loss with carefully designed very low calorie treatments which became known as the protein sparing modified fast (PSMF). We review the role of the PSMF as part of the comprehensive management of obesity.

A SIMPLE INTERVENTION RAISED RESIDENT-PHYSICIAN WILLINGNESS TO ASSIST TRANSGENDER PATIENTS SEEKING HORMONE THERAPY.

OBJECTIVE: Lack of physician knowledge about transgender medicine is a barrier to care. An intervention with medical students changed attitudes about providing transgender medical care, but it is unknown whether at the level of postgraduate education an intervention could have a similar effect. We conducted such an intervention with resident-physicians. METHODS: An intervention on transgender medicine covering the durability of gender identity and hormonal treatment regimens was added to the curriculum for residents. An anonymous survey assessed the residents' knowledge and willingness to assist with hormonal therapy before and after the lecture. RESULTS: The percent of residents who agreed that they felt sufficiently knowledgeable to assist with hormonal therapy for a female-to-male patient increased significantly, from 5% before to 76% following the lecture (χ(2), 24.7; degrees of freedom, 1; P<.001). The percent of residents who reported that they felt sufficiently knowledgeable to assist with hormonal therapy for a male-to-female patient increased significantly, from 5% before to 71% following the lecture (χ(2), 24.0; degrees of freedom, 1; P<.001). The intervention increased resident knowledge about hormonal therapy for hypogonadal men (χ(2), 11.4; degrees of freedom, 1; P<.001) and women (χ(2), 9.4; degrees of freedom, 1; P = .002). The intervention made more residents agree that gender identity has a biologic basis that remains constant (P<.001) and that hormonal and surgical therapies should be offered (P = .047). CONCLUSION: The lecture significantly increased residents' knowledge and willingness to assist with hormonal therapy for transgender patients.