Publications

2019
Stanford FC, Fitch AK. Editorial: Pediatric Obesity: A Focus on Treatment Options. Front Pediatr. 2019;7 :177.
Rickard FA, Torre Flores LP, Malhotra S, Toth AT, Bader A, Stanford FC, Lee H, Bredella MA, Misra M, Singhal V. Comparison of Measured and Estimated Resting Energy Expenditure in Adolescents and Young Adults With Severe Obesity Before and 1 Year After Sleeve Gastrectomy. Front Pediatr. 2019;7 :37.Abstract
Resting energy expenditure (REE) is often evaluated in adults and adolescents with obesity to estimate caloric requirements when advising dietary changes. However, data are lacking regarding the accuracy of methods used to clinically assess REE in adolescents with severe obesity. Moreover, there are no data regarding the effects of sleeve gastrectomy (SG) on REE in adolescents. We evaluated the accuracy and error rate between estimated and measured REE in adolescents with severe obesity and changes in REE following (SG). (CSS): 64 adolescents and young adults, 14-22 years old, with moderate to severe obesity were enrolled. We measured REE (mREE) by indirect calorimetry and estimated REE (eREE) using Derumeaux (Deru), Mifflin-St Jeor (MS), Harris Benedict (HB), and World Health Organization (WHO) equations. DXA was used to determine body composition. Bland Altman analysis evaluated agreement between eREE and mREE. : 12 subjects had repeat indirect calorimetry and DXA 1 year after SG. Longitudinal analysis was used to assess changes in REE and body composition. : Median BMI was 45.2 kg/m and median age was 18.0 (16.3-19.9) years. mREE correlated strongly with eREE . Bland Altman analysis demonstrated that only a few points were beyond the 1.96 SD limit of disagreement. However, there was considerable overestimation of mREE by most equations. : In the subset that underwent SG, after 12-months, absolute REE decreased from 1709 (1567.7-2234) to 1580.5 (1326-1862.5) Calories ( = 0.002); however, the ratio of REE/Total Body Weight (TBW) increased from 13.5 ± 2.3 at baseline to 15.5 ± 2.2 at 1 year ( = 0.043). When evaluating parameters affecting % total weight loss, we found that it correlated positively with REE/TBW at 12 months ( = 0.625; = 0.03) and negatively with % fat mass at 12 months ( = -0.669; = 0.024). In adolescents with moderate-severe obesity, despite a correlation between mREE using indirect calorimetry and eREE using the Deru, MS, HB, and WHO equations, there is significant over-estimation of REE at the individual level, challenging their clinical utility. One year after SG, REE/TBW increased and strongly correlated with % total weight loss in adolescents.
Mushannen T, Cortez P, Stanford FC, Singhal V. Obesity and Hypogonadism-A Narrative Review Highlighting the Need for High-Quality Data in Adolescents. Children (Basel). 2019;6 (5).Abstract
The prevalence of obesity continues to rise in adult and pediatric populations throughout the world. Obesity has a direct impact on all organ systems, including the reproductive system. This review summarizes current knowledge about the effects of obesity on the male reproductive system across age, highlighting the need for more data in children and adolescents. Male hypogonadism is commonly seen in patients with obesity and affects the onset, duration, and progression of puberty. Different pathophysiologic mechanisms include increased peripheral conversion of testosterone to estrone and increased inflammation due to increased fat, both of which lead to suppression of the hypothalamic-pituitary-gonadotropin (HPG) axis and delayed development of secondary sexual characteristics in adolescent males. Evaluation of the HPG axis in obesity includes a thorough history to exclude other causes of hypogonadism and syndromic associations. Evaluation should also include investigating the complications of low testosterone, including increased visceral fat, decreased bone density, cardiovascular disease risk, and impaired mood and cognition, among others. The mainstay of treatment is weight reduction, but medications such as testosterone and clomiphene citrate used in adults, remain scarcely used in adolescents. Male hypogonadism associated with obesity is common and providers who care for adolescents and young adults with obesity should be aware of its impact and management.
Yuan W, Yu K-H, Palmer N, Stanford FC, Kohane I. Evaluation of the association of bariatric surgery with subsequent depression. Int J Obes (Lond). 2019.Abstract
BACKGROUND/OBJECTIVES: Bariatric surgery is helpful in enabling sustained weight loss, but effects on depression are unclear. Reductions in depression-related symptoms and increases in suicide rate have both been observed after bariatric surgery, but these observations are confounded by the presence of pre-existing depression. The goal of this study is to evaluate the effect of bariatric surgery on subsequent depression diagnosis. SUBJECTS/METHODS: In this observational study, a prospective cohort study was simulated by evaluating depression risk based on diagnostic codes. An administrative database was utilized for this study, containing records and observations between 1 January 2008 through 29 February 2016 of enrolled patients in the United States. Individuals considered in this analysis were enrolled in a commercial health insurance program, observed for at least 6 months prior to surgery, and met the eligibility criteria for bariatric surgery. In all, 777,140 individuals were considered in total. RESULTS: Bariatric surgery was found to be significantly associated with subsequent depression relative to both non-surgery controls (HR = 1.31, 95% CI, 1.27-1.34, P < 2e-32) and non-bariatric abdominal surgery controls (HR = 2.15, 95% CI, 2.09-2.22, P < 2e-32). Patients with pre-surgical psychiatric screening had a reduced depression hazard ratio with respect to patients without (HR = 0.85, 95% CI, 0.81-0.89, P = 3.208e-12). Men were found to be more susceptible to post-bariatric surgery depression compared with women. Pre-surgical psychiatric evaluations reduced the magnitude of this effect. Relative to bariatric surgeries as a whole, vertical sleeve gastrectomy had a lower incidence of depression, while Roux-en Y Gastric Bypass and revision/removal surgeries had higher rates. CONCLUSIONS: In individuals without a history of depression, bariatric surgery is associated with subsequent diagnosis of depression. This study provides guidance for patients considering bariatric surgery and their clinicians in terms of evaluating potential risks and benefits of surgery.
Singhal V, Sanchita S, Malhotra S, Bose A, Flores LPT, Valera R, Stanford FC, Slattery M, Rosenblum J, Goldstein MA, et al. Suboptimal bone microarchitecure in adolescent girls with obesity compared to normal-weight controls and girls with anorexia nervosa. Bone. 2019;122 :246-253.Abstract
BACKGROUND: Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normal-weight controls. Whereas bone parameters that increase fracture risk are well characterized in anorexia nervosa (AN), the other end of nutritional spectrum, these data are lacking in adolescents with obesity. OBJECTIVE: Our objective was to compare bone parameters in adolescent girls across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB. METHODS: We assessed bone endpoints in 153 adolescent girls 14-21 years old: 50 OB, 48 controls and 55 AN. We used (i) DXA to assess aBMD at the lumbar spine, proximal femur and whole body, and body composition, (ii) high resolution peripheral quantitative CT (HRpQCT) to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and (iii) finite element analysis to assess failure load (a strength estimate) at the distal radius and tibia. All aBMD, microarchitecture and FEA analyses were controlled for age and race. RESULTS: Groups did not differ for age or height. Areal BMD Z-scores at all sites were highest in OB, intermediate in controls and lowest in AN (p < 0.0001). At the radius, cortical area and thickness were higher in OB compared to AN and control groups (p = 0.001) while trabecular area did not differ across groups. Compared to controls, OB had higher cortical porosity (p = 0.003), higher trabecular thickness (p = 0.024), and higher total, cortical and trabecular vBMD and rod BV/TV (p < 0.04). Plate BV/TV did not differ in OB vs. controls, but was higher than in AN (p = 0.001). At the tibia, total, cortical, and trabecular area and cortical thickness were higher in OB vs. controls and AN (p < 0.005). OB also had higher cortical porosity (p < 0.007) and lower trabecular thickness (p < 0.02) than the other two groups. Trabecular number, total and trabecular vBMD, and rod BV/TV were higher in OB vs. controls and AN (p < 0.02), while cortical vBMD and plate BV/TV did not differ in OB vs. the other two groups. Finally, failure load (a strength estimate) was higher in OB at the radius and tibia compared to controls and AN (p < 0.004 for all). However, after adjusting for body weight, failure load was lower in OB vs. controls at both sites (p < 0.05), and lower than in AN at the distal tibia. CONCLUSION: Not all bone parameters demonstrate appropriate adaptation to higher body weight. Cortical porosity and plate BV/TV at the radius and tibia, and cortical vBMD and trabecular thickness at the tibia are particularly at risk. These effects may contribute to the higher risk for fracture reported in OB vs. controls.
Rickard FA, Flores LPT, Malhotra S, Toth AT, Bader A, Stanford FC, Lee H, Bredella MA, Misra M, Singhal V. Comparison of Measured and Estimated Resting Energy Expenditure in Adolescents and Young Adults With Severe Obesity Before and 1 Year After Sleeve Gastrectomy. Frontiers in Pediatrics [Internet]. 2019;7 :37. Publisher's VersionAbstract

Abstract

Introduction: Resting energy expenditure (REE) is often evaluated in adults and adolescents with obesity to estimate caloric requirements when advising dietary changes. However, data are lacking regarding the accuracy of methods used to clinically assess REE in adolescents with severe obesity. Moreover, there are no data regarding the effects of sleeve gastrectomy (SG) on REE in adolescents. We evaluated the accuracy and error rate between estimated and measured REE in adolescents with severe obesity and changes in REE following (SG). Materials and Methods: Cross-sectional study (CSS): 64 adolescents and young adults, 14-22 years old, with moderate to severe obesity were enrolled. We measured REE (mREE) by indirect calorimetry and estimated REE (eREE) using Derumeaux (Deru), Mifflin-St Jeor (MS), Harris Benedict (HB), and World Health Organization (WHO) equations. DXA was used to determine body composition. Bland Altman analysis evaluated agreement between eREE and mREE. Longitudinal study: 12 subjects had repeat indirect calorimetry and DXA 1 year after SG. Longitudinal analysis was used to assess changes in REE and body composition. Results: CSS: Median BMI was 45.2 kg/m2 and median age was 18.0 (16.3-19.9) years. mREE correlated strongly with eREE . Bland Altman analysis demonstrated that only a few points were beyond the 1.96 SD limit of disagreement. However, there was considerable overestimation of mREE by most equations. Longitudinal Study: In the subset that underwent SG, after 12-months, absolute REE decreased from 1709 (1567.7-2234) to 1580.5 (1326-1862.5) Calories (p = 0.002); however, the ratio of REE/Total Body Weight (TBW) increased from 13.5 ± 2.3 at baseline to 15.5 ± 2.2 at 1 year (p = 0.043). When evaluating parameters affecting % total weight loss, we found that it correlated positively with REE/TBW at 12 months (R = 0.625; p = 0.03) and negatively with % fat mass at 12 months (R = -0.669; p = 0.024). Discussion: In adolescents with moderate-severe obesity, despite a correlation between mREE using indirect calorimetry and eREE using the Deru, MS, HB, and WHO equations, there is significant over-estimation of REE at the individual level, challenging their clinical utility. One year after SG, REE/TBW increased and strongly correlated with % total weight loss in adolescents.

Stanford FC, Stevens JR, Stern TA ed. Facing Overweight and Obesity. Boston: MGH Psychiatry Academy; 2019. Publisher's VersionAbstract
Facing Overweight and Obesity is for anyone whose life is affected by this problem. Written by leading physicians in their fields, Facing Overweight and Obesity combines top-tier medical information and compassionate counsel on being overweight, with a caring approach to the emotional aspects of living with weight-related conditions. This book provides easily readable and trustworthy information; it is divided into chapters that ask and answer pertinent questions about being overweight and its medical, surgical, and psychiatric care. A glossary of terms and tables is provided to educate the reader (e.g., about nutrition, diet, exercise and risk-reduction); on-line resources and references are also provided.
Stanford FC, Lee M, Hur C. Race, Ethnicity, Sex, and Obesity: Is It Time to Personalize the Scale?. Mayo Clin Proc. 2019;94 (2) :362-363.
Stanford FC. Controversial issues: A practical guide to the use of weight loss medications after bariatric surgery for weight regain or inadequate weight loss. Surg Obes Relat Dis. 2019;15 (1) :128-132.
Palad CJ, Yarlagadda S, Stanford FC. Weight stigma and its impact on paediatric care. Curr Opin Endocrinol Diabetes Obes. 2019;26 (1) :19-24.Abstract
PURPOSE OF REVIEW: This review aims to evaluate current research findings relevant to weight stigmatization, to acknowledge the deleterious impact it has on the health of the paediatric population and to provide insight to optimize future guidelines for the treatment of individuals with overweight and obesity. RECENT FINDINGS: Obesity prevalence continues to rise in the USA with estimates in children from ages 2-19 years of 18.5%, an all-time high. With the increase in obesity, there has been a concomitant increase in weight stigma, which affects both youth and general population across varied levels of socioeconomic status and body sizes. SUMMARY: Weight stigma is a contributing phenomenon to the current obesity epidemic, as individuals with stigmatized experiences (weight-based teasing, bullying, victimization) have increased risks for acquiring adverse health outcomes that encompass the physical, behavioural and psychological. Weight stigma can also lead affected individuals to internalize such experiences which decrease their overall quality of life. Sources of stigma may come from peers, family, educators, media, as well as healthcare professionals, as highlighted in this review. Efforts to establish prevention and treatment strategies for weight stigma may generate further traction to help improve global obesity rates. VIDEO ABSTRACT.
Voss JD, Pavela G, Stanford FC. Obesity as a threat to national security: the need for precision engagement. Int J Obes (Lond). 2019;43 (3) :437-439.
2018
Stanford FC, Toth AT, Shukla AP, Pratt JS, Cena H, Biino G, Aronne LJ. Weight Loss Medications in Older Adults After Bariatric Surgery for Weight Regain or Inadequate Weight Loss: A Multicenter Study. Bariatr Surg Pract Patient Care. 2018;13 (4) :171-178.Abstract
Weight loss medications are effective to confer additional weight loss after bariatric surgery in the general population, but they have not been evaluated in adults 60 years of age and older. We performed a retrospective study identifying 35 patients who were ≥60 years old and had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) from 2000 to 2014, and were subsequently prescribed weight loss medications. Linear regression analyses were performed to determine beta coefficients of certain predictor variables being associated with weight loss. Patients lost weight on medications with an average body mass index (BMI) change of -2.74 kg/m, standard deviation = 2.6 kg/m. RYGB patients lost a greater percentage of BMI on medication than SG (SG; -1.38 ± 1.49 kg/m and RYGB; -3.37 ± 2.83 kg/m,  = 0.0372). Patients with hypertension were less likely to lose weight on medications (β = 16.76,  = 0.004, and 95% confidence interval = 5.85-27.67). Weight loss medications are a useful treatment to confer additional weight loss in adults 60 years of age and older after RYGB and SG.
Griggs CL, Perez NP, Goldstone RN, Kelleher CM, Chang DC, Stanford FC, Pratt JS. National Trends in the Use of Metabolic and Bariatric Surgery Among Pediatric Patients With Severe Obesity. JAMA Pediatr. 2018;172 (12) :1191-1192.
Campoverde Reyes KJ, Misra M, Lee H, Stanford FC. Weight Loss Surgery Utilization in Patients Aged 14-25 With Severe Obesity Among Several Healthcare Institutions in the United States. Front Pediatr. 2018;6 :251.Abstract
Obesity is associated with early co-morbidities and higher mortality. Even though weight loss surgery (WLS) in adolescents with severe obesity reliably achieves safe and lasting improvement in BMI and superior resolution of comorbid diseases, its utilization among young patients in the clinical practice stands unclear. To show the prevalence of weight loss surgery utilization rates in adolescents and young adults among several healthcare institutions in the United States. WLS in 14-25 years old between 2000 and 2017 was obtained from Washington University, Morehouse Medical, University of Texas, Wake Forest Baptist Medical Center, Beth Israel Deaconess Medical Center, Boston Children's Hospital, Boston Medical Center, and Partners Healthcare using the Shared Health Research Information Network (SHRINE) and Research Patient Data Registry (RPDR) web-based query tools. ICD-9 codes were used for bariatric surgery. Among 2500635 individuals, 18008 (0.7%) had severe obesity. At Partners, 1879 patients had severe obesity, of which 404 (21.5%) underwent WLS, whereas at Washington University, 44 (2.5%) of 1788 the underwent WLS. 13 (2.3%) of the 575 at BIDMC, 43 (1.5%) of the 2969 at BMC, and 37 (0.4%) of 8908 at BCH underwent WLS ( < 0.0001 for all). Even though WLS has shown to be the most effective treatment to create sustainable changes in metabolic derangements for moderate to severe obesity and its comorbidities, it has been underutilized. Further studies need to be conducted to ensure WLS is utilized for those patients who would achieve the most benefit.
Stanford FC, Kyle TK. Respectful Language and Care in Childhood Obesity. JAMA Pediatr. 2018;172 (11) :1001-1002.
Toth AT, Gomez G, Shukla AP, Pratt JS, Cena H, Biino G, Aronne LJ, Stanford FC. Weight Loss Medications in Young Adults after Bariatric Surgery for Weight Regain or Inadequate Weight Loss: A Multi-Center Study. Children (Basel). 2018;5 (9).Abstract
This paper presents a retrospective cohort study of weight loss medications in young adults aged 21 to 30 following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between November 2000 and June 2014. Data were collected from patients who used topiramate, phentermine, and/or metformin postoperatively. Percentage of patients achieving ≥5%, ≥10%, or ≥15% weight loss on medications was determined and percent weight change on each medication was compared to percent weight change of the rest of the cohort. Our results showed that 54.1% of study patients lost ≥5% of their postsurgical weight; 34.3% and 22.9% lost ≥10% and ≥15%, respectively. RYGB had higher median percent weight loss (-8.1%) than SG (-3.3%) ( = 0.0515). No difference was found in median percent weight loss with medications started at weight plateau (-6.0%) versus after weight regain (-5.4%) ( = 0.5304). Patients taking medications at weight loss plateau lost 41.2% of total body weight from before surgery versus 27.1% after weight regain ( = 0.076). Median percent weight change on metformin was -2.9% compared to the rest of the cohort at -7.7% ( = 0.0241). No difference from the rest of the cohort was found for phentermine ( = 0.2018) or topiramate ( = 0.3187). Topiramate, phentermine, and metformin are promising weight loss medications for 21 to 30 year olds. RYGB patients achieve more weight loss on medications but both RYGB and SG benefit. Median total body weight loss from pre-surgical weight may be higher in patients that start medication at postsurgical nadir weight. Participants on metformin lost significantly smaller percentages of weight on medications, which could be the result of underlying medical conditions.
Singhal V, Torre Flores LP, Stanford FC, Toth AT, Carmine B, Misra M, Bredella MA. Differential associations between appendicular and axial marrow adipose tissue with bone microarchitecture in adolescents and young adults with obesity. Bone. 2018;116 :203-206.Abstract
Marrow adipose tissue (MAT) in humans is distributed differentially across age and skeletal site. We have shown impaired microarchitecture and reduced bone strength at appendicular sites in conditions associated with high MAT of the axial skeleton in adults (including conditions of over- and undernutrition). Data are lacking regarding differences in MAT content of the appendicular versus the axial skeleton, and its relationship with bone microarchitecture and strength. Furthermore, data are conspicuously lacking in adolescents, a time when hematopoietic marrow is progressively converted to fatty marrow. The purpose of our study was to examine differential associations between appendicular (distal tibia) and axial (lumbar spine) MAT and bone microarchitecture and strength estimates of the distal tibia in adolescents with obesity. We hypothesized that compared to MAT of the axial skeleton (lumbar spine), MAT of the appendicular skeleton (distal tibia) would show stronger associations with bone microarchitecture and strength estimates of the appendicular skeleton (distal tibia). We evaluated 32 adolescents and young adults (27 females) with obesity; with a mean age of 17.8 ± 2.1 years and median body mass index (BMI) of 41.34 kg/m, who underwent dual energy X-ray absorptiometry (DXA) for total fat mass, proton MR spectroscopy (1H-MRS) of the distal tibia and 4th lumbar vertebra for MAT, high resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia for volumetric bone mineral density (vBMD) and microarchitecture, and micro finite element analysis (FEA) for distal tibial strength estimates. Linear correlations between bone parameters and MAT were determined using the Spearman or Pearson methods, depending on data distribution. Lumbar spine MAT was inversely associated with age (r = -0.36; p = 0.037). Total and trabecular vBMD and trabecular number at the distal tibia were inversely associated with MAT at the distal tibia (r = -0.39, p = 0.025; r = -0.51, p = 0.003; r = -0.42, p = 0.015 respectively) but not with lumbar spine MAT (r = -0.19, p = 0.27; r = -0.18, p = 0.3; r = 0.005, p = 0.97 respectively). In adolescents and young adults with obesity, the associations between MAT and appendicular bone parameters differ depending on the site of MAT assessment i.e. axial vs. appendicular. Studies evaluating these endpoints in adolescents and young adults with obesity should take the site of MAT assessment into consideration.
De Giuseppe R, Braschi V, Bosoni D, Biino G, Stanford FC, Nappi RE, Cena H. Dietary underreporting in women affected by polycystic ovary syndrome: A pilot study. Nutr Diet. 2018.Abstract
AIM: The first-line therapy for polycystic ovary syndrome (PCOS) is weight loss focussing on diet and regular exercise; measurement of diet and energy intake (EI) is important to determine associations between nutrients and health in women with PCOS. The EI underreporting (UR) is a condition characterised by reports of habitual EI that is implausibly low, compared with estimated requirements. This case-control study aims to evaluate UR in women with PCOS. METHODS: Thirty-six women with PCOS were enrolled according to the Rotterdam criteria; 37 healthy women were enrolled as controls. INCLUSION CRITERIA: age range 18-45 and body mass index ≥18.5 kg/m in subjects without eating disorders and/or diabetes mellitus. Nutritional assessment included: anthropometry, basal metabolic rate (BMR), weight history and physical activity assessment. Subjects completed a non-consecutive three-day dietary diary to identify energy and macronutrient intake. UR was calculated (Goldberg Index: EI/BMR). RESULTS: Although women with PCOS reported a significantly higher mean BMR than controls (P < 0.0001), their EI was lower (P < 0.001), suggesting an UR in 47.2% of women with PCOS versus 2.7% of controls (P < 0.0001). The EI from simple sugars was lower in women with PCOS than controls (P < 0.01). The protein intake was increased in controls than women with PCOS (P < 0.0001). Weight cycling was more frequent in women with PCOS (P < 0.001). Logistic regression analysis identified UR associated with PCOS (P = 0.001). CONCLUSIONS: Women with PCOS underreport foods rich in simple sugars rather than underreport their total dietary intake. These results may have implications for the interpretation of diet and health correlations in this patient population.
Pratt JSA, Browne A, Browne NT, Bruzoni M, Cohen M, Desai A, Inge T, Linden BC, Mattar SG, Michalsky M, et al. ASMBS pediatric metabolic and bariatric surgery guidelines, 2018. Surg Obes Relat Dis. 2018;14 (7) :882-901.Abstract
The American Society for Metabolic and Bariatric Surgery Pediatric Committee updated their evidence-based guidelines published in 2012, performing a comprehensive literature search (2009-2017) with 1387 articles and other supporting evidence through February 2018. The significant increase in data supporting the use of metabolic and bariatric surgery (MBS) in adolescents since 2012 strengthens these guidelines from prior reports. Obesity is recognized as a disease; treatment of severe obesity requires a life-long multidisciplinary approach with combinations of lifestyle changes, nutrition, medications, and MBS. We recommend using modern definitions of severe obesity in children with the Centers for Disease Control and Prevention age- and sex-matched growth charts defining class II obesity as 120% of the 95th percentile and class III obesity as 140% of the 95th percentile. Adolescents with class II obesity and a co-morbidity (listed in the guidelines), or with class III obesity should be considered for MBS. Adolescents with cognitive disabilities, a history of mental illness or eating disorders that are treated, immature bone growth, or low Tanner stage should not be denied treatment. MBS is safe and effective in adolescents; given the higher risk of adult obesity that develops in childhood, MBS should not be withheld from adolescents when severe co-morbidities, such as depressed health-related quality of life score, type 2 diabetes, obstructive sleep apnea, and nonalcoholic steatohepatitis exist. Early intervention can reduce the risk of persistent obesity as well as end organ damage from long standing co-morbidities.
Bennett SE, Schmitt WP, Stanford FC, Baron JM. Case 22-2018: A 64-Year-Old Man with Progressive Leg Weakness, Recurrent Falls, and Anemia. N Engl J Med. 2018;379 (3) :282-289.

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