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  1. Article ; Online: Adapting vector surveillance using Bayesian experimental design: An application to an ongoing tick monitoring program in the southeastern United States.

    Case, B K M / Dye-Braumuller, Kyndall C / Evans, Chris / Li, Huixuan / Rustin, Lauren / Nolan, Melissa S

    Ticks and tick-borne diseases

    2024  Volume 15, Issue 3, Page(s) 102329

    Abstract: Maps of the distribution of medically-important ticks throughout the US remain lacking in spatial and temporal resolution in many areas, leading to holes in our understanding of where and when people are at risk of tick encounters, an important baseline ... ...

    Abstract Maps of the distribution of medically-important ticks throughout the US remain lacking in spatial and temporal resolution in many areas, leading to holes in our understanding of where and when people are at risk of tick encounters, an important baseline for informing public health response. In this work, we demonstrate the use of Bayesian Experimental Design (BED) in planning spatiotemporal surveillance of disease vectors. We frame survey planning as an optimization problem with the objective of identifying a calendar of sampling locations that maximizes the expected information regarding some goal. Here we consider the goals of understanding associations between environmental factors and tick presence and minimizing uncertainty in high risk areas. We illustrate our proposed BED workflow using an ongoing tick surveillance study in South Carolina parks. Following a model comparison study based on two years of initial data, several techniques for finding optimal surveys were compared to random sampling. Two optimization algorithms found surveys better than all replications of random sampling, while a space-filling heuristic performed favorably as well. Further, optimal surveys of just 20 visits were more effective than repeating the schedule of 111 visits used in 2021. We conclude that BED shows promise as a flexible and rigorous means of survey design for vector control, and could help alleviate pressure on local agencies by limiting the resources necessary for accurate information on arthropod distributions. We have made the code for our BED workflow publicly available on Zenodo to help promote the application of these methods to future surveillance efforts.
    MeSH term(s) Animals ; Humans ; United States ; Ticks ; Bayes Theorem ; Southeastern United States/epidemiology
    Language English
    Publishing date 2024-03-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2541872-5
    ISSN 1877-9603 ; 1877-959X
    ISSN (online) 1877-9603
    ISSN 1877-959X
    DOI 10.1016/j.ttbdis.2024.102329
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effects of maternal nutrient restriction during the periconceptional period on placental development in the mouse.

    Van Gronigen Case, Gerialisa / Storey, Kathryn M / Parmeley, Lauren E / Schulz, Laura C

    PloS one

    2021  Volume 16, Issue 1, Page(s) e0244971

    Abstract: Maternal undernutrition has detrimental effects on fetal development and adult health. Total caloric restriction during early pregnancy followed by adequate nutrition for the remainder of gestation, is particularly linked to cardiovascular and metabolic ... ...

    Abstract Maternal undernutrition has detrimental effects on fetal development and adult health. Total caloric restriction during early pregnancy followed by adequate nutrition for the remainder of gestation, is particularly linked to cardiovascular and metabolic disease risks during adulthood. The placenta is responsible for transport of nutrients from the maternal to fetal circulation, and the efficiency with which it does so can be adjusted to the maternal nutrient supply. There is evidence that placental adaptations to nutrient restriction in early pregnancy may be retained even when adequate nutrition is restored later in pregnancy, leading to a potential mismatch between placental efficiency and maternal nutrient supplies. However, in the mouse, 50% caloric restriction from days 1.5-11.5 of gestation, while temporarily altering placental structure and gene expression, had no significant effect on day 18.5. The periconceptional period, during which oocyte maturation, fertilization, and preimplantation development occur may be especially critical in creating lasting impact on the placenta. Here, mice were subjected to 50% caloric restriction from 3 weeks prior to pregnancy through d11.5, and then placental structure, the expression of key nutrient transporters, and global DNA methylation levels were examined at gestation d18.5. Prior exposure to caloric restriction increased maternal blood space area, but decreased expression of the key System A amino acid transporter Slc38a4 at d18.5. Neither placental and fetal weights, nor placental DNA methylation levels were affected. Thus, total caloric restriction beginning in the periconceptional period does have a lasting impact on placental development in the mouse, but without changing placental efficiency.
    MeSH term(s) Animals ; Caloric Restriction/adverse effects ; DNA Methylation ; Female ; Fertilization ; Fetal Development ; Male ; Mice ; Nutrients/deficiency ; Placenta/anatomy & histology ; Placentation/physiology ; Pregnancy ; Prenatal Nutritional Physiological Phenomena ; Real-Time Polymerase Chain Reaction ; Trophoblasts
    Language English
    Publishing date 2021-01-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0244971
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The link between post-traumatic stress disorder and systemic lupus erythematosus.

    Goldschen, Lauren / Ellrodt, Jack / Amonoo, Hermioni L / Feldman, Candace H / Case, Siobhan M / Koenen, Karestan C / Kubzansky, Laura D / Costenbader, Karen H

    Brain, behavior, and immunity

    2022  Volume 108, Page(s) 292–301

    Abstract: Systemic lupus erythematosus (SLE) is a heterogeneous, multisystem autoimmune disorder characterized by unpredictable disease flares. Although the pathogenesis of SLE is complex, an epidemiologic link between posttraumatic stress disorder (PTSD) and the ... ...

    Abstract Systemic lupus erythematosus (SLE) is a heterogeneous, multisystem autoimmune disorder characterized by unpredictable disease flares. Although the pathogenesis of SLE is complex, an epidemiologic link between posttraumatic stress disorder (PTSD) and the development of SLE has been identified, suggesting that stress-related disorders alter the susceptibility to SLE. Despite the strong epidemiologic evidence connecting PTSD and SLE, gaps remain in our understanding of how the two may be connected. Perturbations in the autonomic nervous system, neuroendocrine system, and at the genomic level may cause and sustain immune dysregulation that could lower the threshold for the development and propagation of SLE. We first describe shared risk factors for SLE and PTSD. We then describe potential biological pathways which may facilitate excessive inflammation in the context of PTSD. Among those genetically predisposed to SLE, systemic inflammation that accompanies chronic stress may fan the flames of smoldering SLE by priming immune pathways. Further studies on the connection between trauma and inflammation will provide important data on pathogenesis, risk factors, and novel treatments for SLE.
    MeSH term(s) Humans ; Stress Disorders, Post-Traumatic ; Lupus Erythematosus, Systemic/complications ; Risk Factors ; Genetic Predisposition to Disease ; Inflammation
    Language English
    Publishing date 2022-12-17
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2022.12.012
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  4. Article ; Online: Effects of maternal nutrient restriction during the periconceptional period on placental development in the mouse.

    Gerialisa Van Gronigen Case / Kathryn M Storey / Lauren E Parmeley / Laura C Schulz

    PLoS ONE, Vol 16, Iss 1, p e

    2021  Volume 0244971

    Abstract: Maternal undernutrition has detrimental effects on fetal development and adult health. Total caloric restriction during early pregnancy followed by adequate nutrition for the remainder of gestation, is particularly linked to cardiovascular and metabolic ... ...

    Abstract Maternal undernutrition has detrimental effects on fetal development and adult health. Total caloric restriction during early pregnancy followed by adequate nutrition for the remainder of gestation, is particularly linked to cardiovascular and metabolic disease risks during adulthood. The placenta is responsible for transport of nutrients from the maternal to fetal circulation, and the efficiency with which it does so can be adjusted to the maternal nutrient supply. There is evidence that placental adaptations to nutrient restriction in early pregnancy may be retained even when adequate nutrition is restored later in pregnancy, leading to a potential mismatch between placental efficiency and maternal nutrient supplies. However, in the mouse, 50% caloric restriction from days 1.5-11.5 of gestation, while temporarily altering placental structure and gene expression, had no significant effect on day 18.5. The periconceptional period, during which oocyte maturation, fertilization, and preimplantation development occur may be especially critical in creating lasting impact on the placenta. Here, mice were subjected to 50% caloric restriction from 3 weeks prior to pregnancy through d11.5, and then placental structure, the expression of key nutrient transporters, and global DNA methylation levels were examined at gestation d18.5. Prior exposure to caloric restriction increased maternal blood space area, but decreased expression of the key System A amino acid transporter Slc38a4 at d18.5. Neither placental and fetal weights, nor placental DNA methylation levels were affected. Thus, total caloric restriction beginning in the periconceptional period does have a lasting impact on placental development in the mouse, but without changing placental efficiency.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Cross-scale analysis reveals interacting predictors of annual and perennial cover in Northern Great Basin rangelands.

    Case, Madelon F / Davies, Kirk W / Boyd, Chad S / Aoyama, Lina / Merson, Joanna / Penkauskas, Calvin / Hallett, Lauren M

    Ecological applications : a publication of the Ecological Society of America

    2024  , Page(s) e2953

    Abstract: Exotic annual grass invasion is a widespread threat to the integrity of sagebrush ecosystems in Western North America. Although many predictors of annual grass prevalence and native perennial vegetation have been identified, there remains substantial ... ...

    Abstract Exotic annual grass invasion is a widespread threat to the integrity of sagebrush ecosystems in Western North America. Although many predictors of annual grass prevalence and native perennial vegetation have been identified, there remains substantial uncertainty about how regional-scale and local-scale predictors interact to determine vegetation heterogeneity, and how associations between vegetation and cattle grazing vary with environmental context. Here, we conducted a regionally extensive, one-season field survey across burned and unburned, grazed, public lands in Oregon and Idaho, with plots stratified by aspect and distance to water within pastures to capture variation in environmental context and grazing intensity. We analyzed regional-scale and local-scale patterns of annual grass, perennial grass, and shrub cover, and examined to what extent plot-level variation was contingent on pasture-level predictions of site favorability. Annual grasses were widespread at burned and unburned sites alike, contrary to assumptions of annual grasses depending on fire, and more common at lower elevations and higher temperatures regionally, as well as on warmer slopes locally. Pasture-level grazing pressure interacted with temperature such that annual grass cover was associated positively with grazing pressure at higher temperatures but associated negatively with grazing pressure at lower temperatures. This suggests that pasture-level temperature and grazing relationships with annual grass abundance are complex and context dependent, although the causality of this relationship deserves further examination. At the plot-level within pastures, annual grass cover did not vary with grazing metrics, but perennial cover did; perennial grasses, for example, had lower cover closer to water sources, but higher cover at higher dung counts within a pasture, suggesting contrasting interpretations of these two grazing proxies. Importantly for predictions of ecosystem response to temperature change, we found that pasture-level and plot-level favorability interacted: perennial grasses had a higher plot-level cover on cooler slopes, and this difference across topography was starkest in pastures that were less favorable for perennial grasses regionally. Understanding the mechanisms behind cross-scale interactions and contingent responses of vegetation to grazing in these increasingly invaded ecosystems will be critical to land management in a changing world.
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1074505-1
    ISSN 1939-5582 ; 1051-0761
    ISSN (online) 1939-5582
    ISSN 1051-0761
    DOI 10.1002/eap.2953
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Trajectories of depressive symptoms through adolescence as predictors of cortical thickness in the orbitofrontal cortex: An examination of sex differences.

    Nielsen, Johanna D / Case, Julia A C / Divers, Ross M / Kautz, Marin M / Alloy, Lauren B / Olino, Thomas M

    Psychiatry research. Neuroimaging

    2020  Volume 303, Page(s) 111132

    Abstract: Previous research has found associations between orbitofrontal cortex (OFC) structure and symptoms of major depression, though specific aspects of this complex relationship remain unclear. The current study examined sex differences in the influence of ... ...

    Abstract Previous research has found associations between orbitofrontal cortex (OFC) structure and symptoms of major depression, though specific aspects of this complex relationship remain unclear. The current study examined sex differences in the influence of individual trajectories of depressive symptoms on cortical thickness (CT) in the OFC during late adolescence. Fifty-four participants enrolled in an ongoing longitudinal study completed assessments of depression symptoms at baseline (M
    MeSH term(s) Adolescent ; Adolescent Behavior/psychology ; Cross-Sectional Studies ; Depressive Disorder, Major/diagnostic imaging ; Depressive Disorder, Major/psychology ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging/trends ; Male ; Middle Aged ; Predictive Value of Tests ; Prefrontal Cortex/diagnostic imaging ; Prospective Studies ; Sex Characteristics
    Language English
    Publishing date 2020-06-20
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 445361-x
    ISSN 1872-7506 ; 1872-7123 ; 0925-4927 ; 0165-1781
    ISSN (online) 1872-7506 ; 1872-7123
    ISSN 0925-4927 ; 0165-1781
    DOI 10.1016/j.pscychresns.2020.111132
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Functions of Non-Suicidal Self-Injury in Late Adolescence: A Latent Class Analysis.

    Case, Julia A C / Burke, Taylor A / Siegel, David M / Piccirillo, Marilyn L / Alloy, Lauren B / Olino, Thomas M

    Archives of suicide research : official journal of the International Academy for Suicide Research

    2019  Volume 24, Issue sup2, Page(s) S165–S186

    Abstract: This study employed latent class analysis utilizing an array of features of non-suicidal self-injury (NSSI) in order to identify distinct subgroups of self-injurers. Participants were 359 undergraduates with NSSI history. Indicator variables were ... ...

    Abstract This study employed latent class analysis utilizing an array of features of non-suicidal self-injury (NSSI) in order to identify distinct subgroups of self-injurers. Participants were 359 undergraduates with NSSI history. Indicator variables were lifetime and last year frequency rates, number of methods, scarring, pain during self-injury, and functions of NSSI. Analyses yielded mild/experimental NSSI, moderate NSSI, moderate multiple functions NSSI, and severe NSSI groups, endorsing low, moderate, moderate multiple functions, and high frequencies of self-injury and presence of functions, respectively. Following class assignment, groups differed on self-esteem, social support and belongingness, internalizing symptoms, suicidal ideation and behaviors, and additional NSSI constructs. These subtype analyses emphasize matching phenotypes of NSSI to specific interventions considering dimensions of clinical functioning.
    MeSH term(s) Adolescent ; Humans ; Latent Class Analysis ; Self-Injurious Behavior/epidemiology ; Students ; Suicidal Ideation ; Suicide, Attempted
    Language English
    Publishing date 2019-05-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 1283671-0
    ISSN 1543-6136 ; 1381-1118
    ISSN (online) 1543-6136
    ISSN 1381-1118
    DOI 10.1080/13811118.2019.1586607
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: De novo design of picomolar SARS-CoV-2 miniprotein inhibitors.

    Cao, Longxing / Goreshnik, Inna / Coventry, Brian / Case, James Brett / Miller, Lauren / Kozodoy, Lisa / Chen, Rita E / Carter, Lauren / Walls, Alexandra C / Park, Young-Jun / Strauch, Eva-Maria / Stewart, Lance / Diamond, Michael S / Veesler, David / Baker, David

    Science (New York, N.Y.)

    2020  Volume 370, Issue 6515, Page(s) 426–431

    Abstract: Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. We designed inhibitors using two de novo ... ...

    Abstract Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. We designed inhibitors using two de novo design approaches. Computer-generated scaffolds were either built around an ACE2 helix that interacts with the spike receptor binding domain (RBD) or docked against the RBD to identify new binding modes, and their amino acid sequences were designed to optimize target binding, folding, and stability. Ten designs bound the RBD, with affinities ranging from 100 picomolar to 10 nanomolar, and blocked SARS-CoV-2 infection of Vero E6 cells with median inhibitory concentration (IC
    MeSH term(s) Amino Acid Sequence ; Angiotensin-Converting Enzyme 2 ; Animals ; Antiviral Agents/chemistry ; Betacoronavirus/drug effects ; Binding Sites ; COVID-19 ; Chlorocebus aethiops ; Coronavirus Infections ; Cryoelectron Microscopy ; Drug Design ; Molecular Docking Simulation ; Pandemics ; Peptidyl-Dipeptidase A/chemistry ; Pneumonia, Viral ; Protein Binding/drug effects ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/antagonists & inhibitors ; Spike Glycoprotein, Coronavirus/chemistry ; Vero Cells
    Chemical Substances Antiviral Agents ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-09-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abd9909
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: An Evidence-Based Guideline Improves Outcomes for Patients With Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome.

    Taylor, Maria L / Hoyt, Kacie J / Han, Joseph / Benson, Leslie / Case, Siobhan / Chandler, Mia T / Chang, Margaret H / Platt, Craig / Cohen, Ezra M / Day-Lewis, Megan / Dedeoglu, Fatma / Gorman, Mark / Hausmann, Jonathan S / Janssen, Erin / Lee, Pui Y / Lo, Jeffrey / Priebe, Gregory P / Lo, Mindy S / Meidan, Esra /
    Nigrovic, Peter A / Roberts, Jordan E / Son, Mary Beth F / Sundel, Robert P / Alfieri, Maria / Yeun, Jenny Chan / Shobiye, Damilola M / Degar, Barbara / Chang, Joyce C / Halyabar, Olha / Hazen, Melissa M / Henderson, Lauren A

    The Journal of rheumatology

    2022  Volume 49, Issue 9, Page(s) 1042–1051

    Abstract: Objective: To compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG).: Methods: A management ... ...

    Abstract Objective: To compare clinical outcomes in children with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) who were managed before and after implementation of an evidence-based guideline (EBG).
    Methods: A management algorithm for MAS-HLH was developed at our institution based on literature review, expert opinion, and consensus building across multiple pediatric subspecialties. An electronic medical record search retrospectively identified hospitalized patients with MAS-HLH in the pre-EBG (October 15, 2015, to December 4, 2017) and post-EBG (January 1, 2018, to January 21, 2020) time periods. Predetermined outcome metrics were evaluated in the 2 cohorts.
    Results: After the EBG launch, 57 children were identified by house staff as potential patients with MAS-HLH, and rheumatology was consulted for management. Ultimately, 17 patients were diagnosed with MAS-HLH by the treating team. Of these, 59% met HLH 2004 criteria, and 94% met 2016 classification criteria for MAS complicating systemic juvenile idiopathic arthritis. There was a statistically significant reduction in mortality from 50% before implementation of the EBG to 6% in the post-EBG cohort (
    Conclusion: While the observed improvements may be partially attributed to advances in treatment of MAS-HLH that have accumulated over time, this analysis also suggests that a multidisciplinary treatment pathway for MAS-HLH contributed meaningfully to favorable patient outcomes.
    MeSH term(s) Humans ; Child ; Macrophage Activation Syndrome/drug therapy ; Macrophage Activation Syndrome/diagnosis ; Lymphohistiocytosis, Hemophagocytic/therapy ; Retrospective Studies ; C-Reactive Protein ; Biomarkers
    Chemical Substances C-Reactive Protein (9007-41-4) ; Biomarkers
    Language English
    Publishing date 2022-07-15
    Publishing country Canada
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 194928-7
    ISSN 1499-2752 ; 0315-162X
    ISSN (online) 1499-2752
    ISSN 0315-162X
    DOI 10.3899/jrheum.211219
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  10. Article ; Online: Immune-Related Adverse Events as Clinical Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors.

    Martini, Dylan J / Goyal, Subir / Liu, Yuan / Evans, Sean T / Olsen, T Anders / Case, Katherine / Magod, Benjamin L / Brown, Jacqueline T / Yantorni, Lauren / Russler, Greta Anne / Caulfield, Sarah / Goldman, Jamie M / Nazha, Bassel / Harris, Wayne B / Kissick, Haydn T / Master, Viraj A / Kucuk, Omer / Carthon, Bradley C / Bilen, Mehmet Asim

    The oncologist

    2021  Volume 26, Issue 10, Page(s) e1742–e1750

    Abstract: Background: Immune checkpoint inhibitors (ICIs) are an important treatment for metastatic renal cell carcinoma (mRCC). These agents may cause immune-related adverse events (irAEs), and the relationship between irAEs and outcomes is poorly understood. We ...

    Abstract Background: Immune checkpoint inhibitors (ICIs) are an important treatment for metastatic renal cell carcinoma (mRCC). These agents may cause immune-related adverse events (irAEs), and the relationship between irAEs and outcomes is poorly understood. We investigated the association between irAEs and clinical outcomes in patients with mRCC treated with ICIs.
    Methods: We performed a retrospective study of 200 patients with mRCC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on irAEs were collected from clinic notes and laboratory values and grades were determined using Common Terminology Criteria in Adverse Events version 5.0. The association with overall survival (OS) and progression-free survival (PFS) was modeled by Cox proportional hazards model. Logistic regression models were used to define odds ratios (ORs) for clinical benefit (CB). Landmark analysis and extended Cox models were used to mitigate lead-time bias by treating irAEs as a time-varying covariate.
    Results: Most patients (71.0%) were male, and one-third of patients (33.0%) experienced at least one irAE, most commonly involving the endocrine glands (13.0%), gastrointestinal tract (10.5%), or skin (10.0%). Patients who experienced irAEs had significantly longer OS (hazard ratio [HR], 0.52; p = .013), higher chance of CB (OR, 2.10; p = .023) and showed a trend toward longer PFS (HR, 0.71; p = .065) in multivariate analysis. Patients who had endocrine irAEs, particularly thyroid irAEs, had significantly longer OS and PFS and higher chance of CB. In a 14-week landmark analysis, irAEs were significantly associated with prolonged OS (p = .045). Patients who experienced irAEs had significantly longer median OS (44.5 vs. 18.2 months, p = .005) and PFS (7.5 vs. 3.6 months, p = .003) without landmark compared with patients who did not.
    Conclusion: We found that patients with mRCC treated with ICIs who experienced irAEs, particularly thyroid irAEs, had significantly improved clinical outcomes compared with patients who did not have irAEs. This suggests that irAEs may be effective clinical biomarkers in patients with mRCC treated with ICIs. Future prospective studies are warranted to validate these findings.
    Implications for practice: This study found that early onset immune-related adverse events (irAEs) are associated with significantly improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). In this site-specific irAE analysis, endocrine irAEs, particularly thyroid irAEs, were significantly associated with improved clinical outcomes. These results have implications for practicing medical oncologists given the increasing use of ICIs for the treatment of mRCC. Importantly, these results suggest that early irAEs and thyroid irAEs at any time on treatment with ICIs may be clinical biomarkers of clinical outcomes in patients with mRCC treated with ICIs.
    MeSH term(s) Biomarkers ; Carcinoma, Renal Cell/drug therapy ; Humans ; Immune Checkpoint Inhibitors ; Kidney Neoplasms/drug therapy ; Male ; Retrospective Studies
    Chemical Substances Biomarkers ; Immune Checkpoint Inhibitors
    Language English
    Publishing date 2021-07-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1002/onco.13868
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