All Publications


  • Cutaneous Neurofibromas and Quality of Life in Adults With Neurofibromatosis Type 1. JAMA dermatology Lin, M. J., Yao, H., Vera, K., Patel, E., Johnson, M., Caroline, P., Ramos, J., Mehta, J., Hu, X., Blakeley, J. O., Romo, C. G., Sarin, K. Y. 2024

    Abstract

    There is a burgeoning interest in therapeutic development for cutaneous neurofibromas (cNFs), a major cause of morbidity in persons with neurofibromatosis type 1 (NF1). To determine meaningful clinical trial outcomes, deeper understanding is needed regarding how cNFs are associated with quality of life (QoL). However, this understanding has been hampered by challenges in recruiting participants with this rare genetic disease.To develop a large, crowdsourced validated registry of persons with NF1 and determine the association of specific cNF features with QoL, pain, and itch.From May 2021 to December 2023, a decentralized platform was developed and recruited persons 40 years or older with NF1 and at least 1 cNF from 49 states and 12 countries, who provided clinical survey data, detailed photographs, and genetic sequencing data. Photographs from 583 participants were scored on 12 features of cNFs, including general severity, number, size, facial severity, color, and subtypes.cNF features derived from participant-supplied photographs.Total Skindex scores and subdomain scores (symptoms, emotion, function, pain, and itch).Of 583 participants, 384 (65.9%) were female, and the mean (range) age was 51.7 (40.0-83.0) years. Female sex, general severity, number, size, and facial severity of cNFs were negatively associated with QoL, as demonstrated by increased total Skindex scores. QoL had the largest association with the number of cNFs and presence of facial cNFs. Increasing number of cNFs was associated with worse QoL, and even individuals with a low cNF burden (<10 total cNFs) experienced a decrease in QoL.The results of this study suggest that reducing cNF number, particularly on the face, may be associated with improved QoL in individuals with NF1. In addition, early intervention before the development of numerous tumors may lead to the highest benefit in QoL. These data potentially provide insight into which individuals and cNF tumors may benefit most from therapy and highlights the utility of a completely decentralized, photograph-validated and age-controlled study for rare genetic disease. This cohort will allow analysis of disease and tumor heterogeneity after full phenotypic expression is achieved in NF1 and potentially serves as an example in its design for other rare diseases that struggle from poor recruitment.

    View details for DOI 10.1001/jamadermatol.2024.2912

    View details for PubMedID 39196570

  • Single-Lesion Skin Cancer Risk Stratification Triage Pathway. JAMA dermatology Chen, Y., Gui, H., Yao, H., Adu-Brimpong, J., Javitz, S., Golovko, V., Ko, J., Daneshjou, R., Chiou, A. S. 2024

    Abstract

    Importance: Access to timely dermatologic care remains a challenge, especially for patients with new skin lesions. Assessing the efficiency of new triage pathways may assist in better resource allocation and shorter time to care.Objective: To evaluate whether a rule-based triage system was associated with better skin cancer risk stratification of patients and reduced wait times.Design, Setting, and Participants: This retrospective quality improvement cohort study of patients referred to Stanford University dermatology clinics was conducted between November 2017 and January 2023. A rules-based triage system based on a priori-determined high-risk lesion characteristics was implemented.Exposures: Referral reasons and risk factors of patients provided by their primary care physicians.Main Outcomes and Measures: Biopsy results of patients (diagnosis of any skin cancer and melanoma) at their visit or within 6 months after the visit. Regression models were used to assess the association between risk factors at referral and (1) biopsy outcomes and (2) time to first visit, adjusting for sociodemographic factors.Results: Among 37 478 patients (mean [SD] age, 54 (18) years; 21 292 women [57%]), the rates of aggregate biopsy, malignant biopsy specimens, and melanoma were comparable across patients seen after (n=12 302) and before (n=25 176) the implementation of the new triage pathway. Patients seen through the lesion pathway had a higher risk of having malignant biopsy results (adjusted risk ratio [aRR], 1.6; 95% CI, 1.4-1.9) and melanoma (aRR, 2.0; 95% CI, 1.2-3.2) than those not seen through the pathway. Lesions that were concerning to referring clinicians for skin cancer were associated with an increased risk of skin cancer (all skin cancer: aRR, 2.8; 95% CI, 2.2-3.5; melanoma: aRR, 2.02; 95% CI, 1.1-3.7). Patients in the 3 high-risk lesion groups were seen faster in the new triage pathway (mean reduction, 26 days; 95% CI, 18-34 days).Conclusions and Relevance: In this study, a new automated, rules-based referral pathway was implemented that expedited care for patients with high-risk skin cancer. This reform may have contributed to improving patient stratification, reducing the time from referral to first encounter, and maintaining accuracy in identifying malignant lesions. The findings highlight the potential to optimize clinical resource allocation by better risk stratification of referred patients.

    View details for DOI 10.1001/jamadermatol.2024.1832

    View details for PubMedID 38922597

  • A torpor-like state (TLS) in mice slows blood epigenetic aging and prolongs healthspan. bioRxiv : the preprint server for biology Jayne, L., Lavin-Peter, A., Roessler, J., Tyshkovskiy, A., Antoszewski, M., Ren, E., Markovski, A., Sun, S., Yao, H., Sankaran, V. G., Gladyshev, V. N., Brooke, R. T., Horvath, S., Griffith, E. C., Hrvatin, S. 2024

    Abstract

    Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase health span, remain unknown. We demonstrate that the activity of a spatially defined neuronal population in the avMLPA, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor like state (TLS) in mice. Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves health span. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the pro-longevity effect of torpor-like states is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the pro-longevity effects of torpor and hibernation and support the growing body of evidence that Tb is an important mediator of aging processes.

    View details for DOI 10.1101/2024.03.20.585828

    View details for PubMedID 38585858

    View details for PubMedCentralID PMC10996477

  • Healthcare-Associated Clostridioides difficile Infection: Learning the Perspectives of Healthcare Workers to Build Successful Strategies. American journal of infection control Lev, V., Anbarchian, T., Yao, H., Bhat, A., Britt, P., Shieh, L. 2023

    Abstract

    BACKGROUND: Clostridioides difficile (C. difficile) is one of the most common healthcare-associated infections that negatively impacts patient care and healthcare costs. This study takes a unique approach to C. difficile infection (CDI) control by investigating key prevention obstacles through the perspectives of Stanford Health Care (SHC) frontline healthcare personnel.METHODS: An anonymous qualitative survey was distributed at SHC, focusing on knowledge and practice of CDI prevention guidelines, as well as education, communication, and perspectives regarding CDI at SHC.RESULTS: 112 survey responses were analyzed. Our findings unveiled gaps in personnel's knowledge of C. difficile diagnostic guidelines, and revealed a need for targeted communication and guideline-focused education. Healthcare staff shared preferences and recommendations, with the majority recommending enhanced communication of guidelines and information as a strategy for reducing CDI rates. The findings were then used to design and propose internal recommendations for SHC to mitigate the gaps found.DISCUSSION: Many guidelines and improvement strategies are based on strong scientific and medical foundations; however, it is important to ask whether these guidelines are effectively translated into practice. Frontline healthcare workers hold empirical perspectives that could be key in infection control.CONCLUSIONS: Our findings emphasize the importance of including frontline healthcare personnel in infection prevention decision-making processes and the strategies presented here can be applied to mitigating infections in different healthcare settings.

    View details for DOI 10.1016/j.ajic.2023.08.008

    View details for PubMedID 37579972

  • Neurons that regulate mouse torpor NATURE Hrvatin, S., Sun, S., Wilcox, O. F., Yao, H., Lavin-Peter, A. J., Cicconet, M., Assad, E. G., Palmer, M. E., Aronson, S., Banks, A. S., Griffith, E. C., Greenberg, M. E. 2020; 583 (7814): 115-+

    Abstract

    The advent of endothermy, which is achieved through the continuous homeostatic regulation of body temperature and metabolism1,2, is a defining feature of mammalian and avian evolution. However, when challenged by food deprivation or harsh environmental conditions, many mammalian species initiate adaptive energy-conserving survival strategies-including torpor and hibernation-during which their body temperature decreases far below its homeostatic set-point3-5. How homeothermic mammals initiate and regulate these hypothermic states remains largely unknown. Here we show that entry into mouse torpor, a fasting-induced state with a greatly decreased metabolic rate and a body temperature as low as 20 °C6, is regulated by neurons in the medial and lateral preoptic area of the hypothalamus. We show that restimulation of neurons that were activated during a previous bout of torpor is sufficient to initiate the key features of torpor, even in mice that are not calorically restricted. Among these neurons we identify a population of glutamatergic Adcyap1-positive cells, the activity of which accurately determines when mice naturally initiate and exit torpor, and the inhibition of which disrupts the natural process of torpor entry, maintenance and arousal. Taken together, our results reveal a specific neuronal population in the mouse hypothalamus that serves as a core regulator of torpor. This work forms a basis for the future exploration of mechanisms and circuitry that regulate extreme hypothermic and hypometabolic states, and enables genetic access to monitor, initiate, manipulate and study these ancient adaptations of homeotherm biology.

    View details for DOI 10.1038/s41586-020-2387-5

    View details for Web of Science ID 000623830500002

    View details for PubMedID 32528180

    View details for PubMedCentralID PMC7449701