Kathryn 'Katie' Czepiel

All Publications

• Hymecromone Promotes Longevity and Insulin Sensitivity in Mice. Cells Nagy, N., Czepiel, K. S., Kaber, G., Stefanovski, D., Hargil, A., Pennetzdorfer, N., Targ, R., Reghupaty, S. C., Wight, T. N., Vernon, R. B., Hull-Meichle, R. L., Marshall, P., Medina, C. O., Martinez, H., Kalinowski, A., Paladini, R. D., Garantziotis, S., Knowles, J. W., Bollyky, P. L. 2024; 13 (20)

  Abstract

  Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find that 4-MU extends median survival from 122 weeks (control) to 154 weeks (4-MU), an increase of 32 weeks (p < 0.0001 by Log-rank Mantel Cox test). The maximum lifespan of 4-MU treated mice increased from 159 to 194 weeks. In tandem with these effects, 4-MU enhances insulin sensitivity, a metabolic parameter known to regulate lifespan, as measured by insulin tolerance testing (ITT) as well as frequent sampling intra venous glucose tolerance tests (FSIVGTTs). We further observed that 4-MU treated mice weigh less while consuming the same amount of food, indicating that 4-MU treatment alters energy expenditure. However, we do not observe changes in tissue HA content in this model. We conclude that 4-MU promotes insulin sensitivity and longevity but that the underlying mechanism, and the contribution of HA is unclear. 4-MU, already approved in various countries for hepatobiliary conditions, is currently under investigation and clinical development as a therapy for several chronic inflammatory conditions. These data suggest that the beneficial effects of 4-MU on tissue metabolism may include effects on longevity.

  View details for DOI 10.3390/cells13201727

  View details for PubMedID 39451245

• The Many Names of Fatty Liver Disease: Strengths and Limitations of Metabolic (Dysfunction)-Associated Fatty Liver Disease. Childhood obesity (Print) Czepiel, K. S., Stanford, F. C. 2022

  View details for DOI 10.1089/chi.2022.0104

  View details for PubMedID 35649197

• Food as Medicine for Obesity Treatment and Management. Clinical therapeutics Johnson, V. R., Washington, T. B., Chhabria, S., Wang, E. H., Czepiel, K., Reyes, K. J., Stanford, F. C. 2022

  Abstract

  PURPOSE: Nutrition is an important lifestyle modification used in the treatment of obesity. The purpose of this review is to highlight different dietary interventions used to promote weight loss in both adults and children.METHODS: A search using PubMed was performed for articles on topics related to nutrition and management and/or treatment of obesity in adults adolescents and children. The literature was reviewed and pertinent sources were used for this narrative review.DISCUSSION: There are many effective nutrition interventions used to treat obesity, including altering macronutrient composition, implementing different dietary patterns, and changing meal timing. Although these interventions can induce weight loss in adults, management of obesity in children is more difficult given their varied nutrition needs in growth and development. The use of food as medicine in obesity treatment is individualized based on patient's age, food preference, and concurrent medical conditions.IMPLICATIONS: Given the multifactorial etiology of obesity, treatment requires multidisciplinary care beyond nutrition intervention.

  View details for DOI 10.1016/j.clinthera.2022.05.001

  View details for PubMedID 35618570

• Association Between Weight Promoting Medication Use and Weight Status Among Children and Adolescents in the United States ACADEMIC PEDIATRICS Claridy, M. D., Perez, N. P., Czepiel, K. S., Acholonu, N. O., Stanford, F. 2022; 23 (1): 102-108

  View details for Web of Science ID 000921372700001

• Bariatric surgery in the treatment of adolescent obesity: current perspectives in the United States. Expert review of endocrinology & metabolism Malhotra, S., Czepiel, K. S., Akam, E. Y., Shaw, A. Y., Sivasubramanian, R., Seetharaman, S., Stanford, F. C. 2021; 16 (3): 123-134

  Abstract

  Introduction: Rates of severe obesity in adolescents have increased at an alarming rate. Unfortunately, there are limited successful treatments for severe obesity in adolescents. Metabolic and bariatric surgery (MBS) is the most effective treatment available for adolescents with Class 2 and above severe obesity and has demonstrated variable degrees of sustained long-term weight loss which leads to resolution of multiple associated conditions and an improved quality of life.Areas covered: We discuss the current landscape of MBS in adolescents and evidence to support its long-term safety and efficacy. A literature search through PubMed, ResearchGate and HOLLIS Harvard Library Online Catalog was performed from the date of inception until 3/15/2021. A combination of the following keywords was used: Pediatric metabolic/bariatric surgery; long term outcomes of Pediatric metabolic/bariatric surgery, perioperative assessment, pediatric metabolic/bariatric surgery barriers; attitudes toward metabolic/bariatric surgery.Expert opinion: MBS is emerging as a safe and effective treatment strategy for adolescents with severe obesity, with recent studies demonstrating durable and sustainable weight loss. There remains an urgent need for longitudinal studies to assess durability of weight loss. Obesity stigma and bias, limited access to tertiary care centers, and skepticism around the treatment of obesity poses a major challenge.

  View details for DOI 10.1080/17446651.2021.1914585

  View details for PubMedID 33879013

• Exploring Pediatric Obesity Training, Perspectives, and Management Patterns Among Pediatric Primary Care Physicians. Obesity (Silver Spring, Md.) Campoverde Reyes, K. J., Perez, N. P., Czepiel, K. S., Shaw, A. Y., Stanford, F. C. 2021; 29 (1): 159-170

  Abstract

  Significant variability exists in the amount of formal obesity training obtained by physicians caring for pediatric patients. The study objective was to assess the relationship between formal obesity training and pediatrics physicians' perceptions, practice patterns, overall knowledge, and confidence during management of pediatric obesity.An anonymous survey was distributed via email from February 2020 through March 2020 at a large academic system. Internal medicine/pediatrics (46 total) and pediatrics (104 total) primary care providers were selected. Data were collected on the total number of obesity-related training hours by quartiles, demographics, physicians' clinical practice patterns, and physicians' knowledge of pediatric obesity management, along with their perceptions, attitudes, and beliefs.A total of 73 survey participants completed the survey: 69% were female, 77% were older than 40 years, and 74% were White. Physicians with the highest training were most likely to feel confident when managing pediatric obesity. However, only 20% of all physicians felt confident providing pre- and post-bariatric surgery care, and just 6% of physicians self-reported achieving management success.Increased obesity training improves physicians' confidence and leads to familiarity with management guidelines. Formal obesity training should be prioritized during residency and beyond so that physicians who care for pediatric patients are better equipped to offer unbiased and effective care.

  View details for DOI 10.1002/oby.22990

  View details for PubMedID 33184987

  View details for PubMedCentralID PMC7902290

• Treatment of Obesity: Pharmacotherapy Trends of Office-Based Visits in the United States From 2011 to 2016. Mayo Clinic proceedings Claridy, M. D., Czepiel, K. S., Bajaj, S. S., Stanford, F. C. 2021

  Abstract

  To examine pharmacotherapy for obesity in the United States from 2011 to 2016 using a large, nationally representative sample.Data were obtained during 6 years, 2011 to 2016, from the National Ambulatory Medical Care Survey. There were 3 types of visits identified: patients with obesity and an antiobesity drug mention; patients with obesity and no antiobesity drug mention; and patients without obesity and with antiobesity drug mention. The χ2 test was used to compare characteristics across each type of visit. To predict the odds of an antiobesity medication mention for patients with obesity, a logistic regression analysis was conducted.Of the overall weighted 196,872,870 office-based physician visits made by patients with obesity from 2011 to 2016, 1% mentioned an antiobesity drug. In addition, there were 760,470 office-based physician visits by patients without obesity but with an antiobesity medication mention. An antiobesity drug mention was more likely for those aged 51 years or older and those residing in the South (adjusted odds ratio, 5.31 95% CI, 1.19 to 23.59).There was a slight increase in antiobesity medication mentions, from 0.26% in 2011 to 0.28% in 2016, but only 1% of office-based visits for patients with obesity received a prescription for an antiobesity medication. Physicians tended to prescribe antiobesity medications to those with obesity aged 51 years or older and residing in the South. Antiobesity medication for treatment of obesity is significantly underused.

  View details for DOI 10.1016/j.mayocp.2021.07.021

  View details for PubMedID 34728060

• Dexmedetomidine-Associated Hyperpyrexia in Three Critically Ill Patients With Coronavirus Disease 2019. Critical care explorations Czepiel, K. S., Lucas, A. T., Whalen, M. J., Mojica, J. E. 2020; 2 (9): e0213

  Abstract

  To present three patients with severe coronavirus disease 2019 infection who developed life-threatening hyperpyrexia while being treated with dexmedetomidine for sedation.Clinical records.Case report.Relevant clinical information.We describe three patients, a 60-year-old female, 43-year-old female, and 46-year-old male, who were hospitalized in surge ICUs during the coronavirus disease 2019 pandemic in the early spring of 2020. All developed hyperpyrexia, defined as a temperature above 41.1°C, following an increase in dexmedetomidine dosing to above 1.5 µg/kg/hr. Fevers resolved following discontinuation of dexmedetomidine.While the exact mechanism of hyperpyrexia remains unclear, findings in this study suggest that high doses of dexmedetomidine infusion are associated with hyperpyrexia in a seemingly dose-dependent fashion in critically ill patients with coronavirus disease 2019. Coronavirus disease 2019 infection causes a hyperinflammatory state characterized by pro-inflammatory cytokine dysregulation. Dexmedetomidine, a centrally acting alpha-2 agonist, may alter hypothalamic temperature regulation through disturbances in neurotransmitter expression and metabolism. We postulate that the use of high-dose dexmedetomidine in a hyperinflammatory state may increase the risk of developing hyperpyrexia in this severe disease state.

  View details for DOI 10.1097/CCE.0000000000000213

  View details for PubMedID 32984835

  View details for PubMedCentralID PMC7498133

• Pharmacotherapy for the Treatment of Overweight and Obesity in Children, Adolescents, and Young Adults in a Large Health System in the US. Frontiers in endocrinology Czepiel, K. S., Perez, N. P., Campoverde Reyes, K. J., Sabharwal, S., Stanford, F. C. 2020; 11: 290

  Abstract

  Lifestyle modifications focused on diet, physical activity, and behavior have a modest impact on weight reduction in children, adolescents, and young adults (YA) with overweight and obesity. Several anti-obesity medications (AOMs) have been approved by the Food and Drug Administration (FDA) for use among adult patients with a body mass index (BMI) ≥27 kg/m2 and at least one obesity-related illness. However, only two FDA-approved AOMs are available for use in children and adolescents, which leads to the frequent off-label use of adult AOMs among this population. We sought to investigate current prescribing patterns of AOMs from school age through to young adulthood in a large unified health system. Using a centralized clinical data registry containing the health data of ~6.5 million patients, individuals aged 5-25 years old with overweight and obesity who were taking one of eight commonly prescribed AOMs from 2009 to 2018 were extracted. A total of 1,720 patients were identified, representing 2,210 medication prescribing instances. The cohort was further stratified as children (5-12 years old), adolescents (13-18 years old), and YA (19-25 years old). The mean BMI at the time of medication initiation was 34.0, 39.1, and 39.6 kg/m2, respectively, which corresponded to a BMI z-score (BMIz) of 2.4 and 2.3 for children and adolescents, respectively. Metformin was the most commonly prescribed medication across all ages, including off-label use for weight-loss among children and adolescents. The most commonly off-label prescribed AOM among YA was topiramate. Multivariable analyses demonstrated phentermine was the most effective AOM, with a 1.54% total body weight among YA (p = 0.05) and a 0.12 decrease in BMIz among adolescents (p = 0.003) greater final weight loss when compared to the respective overall frequency-weighted means. Our study demonstrates a statistically significant weight loss among adolescents and young adults on select pharmacotherapy. The small magnitude of this effect should be interpreted carefully, as it is likely an underestimate in the absence of a true control group. Pharmacotherapy should therefore be considered in conjunction with other multimodal therapies such as lifestyle modification and metabolic and bariatric surgery when treating overweight and obesity.

  View details for DOI 10.3389/fendo.2020.00290

  View details for PubMedID 32477270

  View details for PubMedCentralID PMC7237714

• Preoperative considerations for the pediatric patient undergoing metabolic and bariatric surgery. Seminars in pediatric surgery Pratt, J. S., Roque, S. S., Valera, R., Czepiel, K. S., Tsao, D. D., Stanford, F. C. 2020; 29 (1): 150890

  Abstract

  To ensure successful outcomes in pediatric patients with severe obesity who undergo metabolic and bariatric surgery (MBS), a number of pre-operative patient management options should be considered. This manuscript will review the indications and contraindications of MBS and special considerations for youth who might benefit from MBS. The treatment team conducts a thorough pre-operative evaluation, assessing risks and benefits of surgical intervention, and prepares patients and families to be successful with MBS by providing education about the surgical intervention and lifestyle changes that will be necessary. This article reviews the pre-operative considerations for adolescents with severe obesity who are being considered for MBS, based upon recent clinical practice guidelines.

  View details for DOI 10.1016/j.sempedsurg.2020.150890

  View details for PubMedID 32238283

• Strategies in the Management of Adolescent Obesity. Current pediatrics reports Johnson, V. R., Cao, M., Czepiel, K. S., Mushannen, T., Nolen, L., Stanford, F. C. 2020; 8 (2): 56-65

  Abstract

  We review the current options to manage adolescent obesity which include nutrition, physical activity, behavior modification, sleep management, pharmacotherapy and surgery. Since lifestyle interventions alone are often not effective in adolescents, a multi-disciplinary treatment approach is necessary in management.Medications (often used off-label) and metabolic/bariatric surgery are effective treatment strategies to treat adolescents with severe obesity.The use of pharmacotherapy and surgery is limited due to lack of pediatric obesity tertiary care centers. With more centers, the treatment of adolescent obesity will improve and aid to decrease the prevalence of adult obesity.

  View details for DOI 10.1007/s40124-020-00214-9

  View details for PubMedID 32632353

  View details for PubMedCentralID PMC7337011

• They didn't cover this in lecture: The formation and dissolution of the patient-provider relationship. Perspectives on medical education Czepiel, K. S. 2018; 7 (Suppl 1): 16-17

  View details for DOI 10.1007/s40037-018-0426-9

  View details for PubMedID 29691727

  View details for PubMedCentralID PMC6002276