Lessons Learned From TranslateCovid, a Multilingual Online Resource Hub for Asian American and Pacific Islander Communities and Beyond.

The COVID-19 pandemic exacerbated health disparities among immigrant communities. Delivering accurate information and addressing misinformation on protective measures and vaccination to linguistically disadvantaged groups was critical for mitigating the effects of the pandemic. One group that was especially vulnerable to miscommunication about COVID-19 was non-native English-speaking immigrants. To address these disparities, the Asian American Studies Center and the Fielding School of Public Health at the University of California, Los Angeles, partnered to create a multilingual resource hub, TranslateCovid.org, to disseminate credible and reliable information about COVID-19 safety measures, the science behind the vaccines, and vaccine safety. We identified >1300 verified resources in 60 languages from government, academic, and nonprofit organizations and reposted them on the TranslateCovid website. We also developed public service announcement videos on handwashing, use of face masks, and social distancing in 10 languages and a fact sheet for frequently asked questions in 20 languages. We used a participatory approach to develop strategies for disseminating these resources. We discuss lessons learned, including strategies for forming government, community, and academic partnerships to support the timely development and dissemination of information. We conclude with a discussion on the unique role of universities in promoting equitable access to public health resources among immigrant communities in times of crisis.

Safety and Effectiveness of Track Cauterization for Lung Cryoablation.

PURPOSE: To evaluate the safety and efficacy of track cauterization for lung cryoablation through comparison of post-procedural adverse event (AE) rates. MATERIAL AND METHODS: Fifty-nine patients who underwent 164 percutaneous lung cryoablation between 2013 to 2018 were included in this retrospective study. The study cohort was subdivided into whether track cauterization was conducted at the end of the procedure. Also, the study cohort was subdivided into procedures conducted with 1 - 2 probes and 3 - 4 probes. Post-ablation AE rates were assessed by immediate and delayed (equal or more than one month), pneumothorax, hemothorax, pleural effusion, and whether intervention was required. Univariate and multivariate logistic regression analyses were used to compare differences in AE rates. RESULTS: Procedures with track cautery were 2.6 times less likely to exhibit pleural effusion (p=0.017). Procedures conducted with a higher number of probes were 3.8 times more likely to receive interventions (p<0.001), 1.6 times more likely to experience pneumothorax (p=0.037), and 2.1 times more likely to experience pleural effusion (p=0.003). History of lung surgery, increased number of probes, size of the probe, and absence of track cautery showed to be a significant predictor of AEs and need for interventions (p<0.05). CONCLUSIONS: Track cauterization in lung cryoablation proves to reduce pleural effusion, but no difference in pneumothorax or delayed AEs. Decreasing the number of probes leads to a lower rate of AEs.

Redefining the molecular rejection states in 3230 heart transplant biopsies: Relationships to parenchymal injury and graft survival.

The first-generation Molecular Microscope (MMDx) system for heart transplant endomyocardial biopsies used expression of rejection-associated transcripts (RATs) to diagnose not only T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) but also acute injury. However, the ideal system should detect rejection without being influenced by injury, to permit analysis of the relationship between rejection and parenchymal injury. To achieve this, we developed a new rejection classification in an expanded cohort of 3230 biopsies: 1641 from INTERHEART (ClinicalTrials.gov NCT02670408), plus 1589 service biopsies added to improve the power of the machine learning algorithms. The new system used 6 rejection classifiers instead of RATs and generated 7 rejection archetypes: No rejection, 48%; Minor, 24%; TCMR1, 2.3%; TCMR2, 2.7%; TCMR/mixed, 2.7%; early-stage ABMR, 3.9%; and fully developed ABMR, 16%. Using rejection classifiers eliminated cross-reactions with acute injury, permitting separate assessment of rejection and injury. TCMR was associated with severe-recent injury and late atrophy-fibrosis and rarely had normal parenchyma. ABMR was better tolerated, seldom producing severe injury, but in later biopsies was often associated with atrophy-fibrosis, indicating long-term risk. Graft survival and left ventricular ejection fraction were reduced not only in hearts with TCMR but also in hearts with severe-recent injury and atrophy-fibrosis, even without rejection.

Multiparametric Radiogenomic Model to Predict Survival in Patients with Glioblastoma.

BACKGROUND: Clinical, histopathological, and imaging variables have been associated with prognosis in patients with glioblastoma (GBM). We aimed to develop a multiparametric radiogenomic model incorporating MRI texture features, demographic data, and histopathological tumor biomarkers to predict prognosis in patients with GBM. METHODS: In this retrospective study, patients were included if they had confirmed diagnosis of GBM with histopathological biomarkers and pre-operative MRI. Tumor segmentation was performed, and texture features were extracted to develop a predictive radiomic model of survival (<18 months vs. ≥18 months) using multivariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regularization to reduce the risk of overfitting. This radiomic model in combination with clinical and histopathological data was inserted into a backward stepwise logistic regression model to assess survival. The diagnostic performance of this model was reported for the training and external validation sets. RESULTS: A total of 116 patients were included for model development and 40 patients for external testing validation. The diagnostic performance (AUC/sensitivity/specificity) of the radiomic model generated from seven texture features in determination of ≥18 months survival was 0.71/69.0/70.3. Three variables remained as independent predictors of survival, including radiomics (p = 0.004), age (p = 0.039), and MGMT status (p = 0.025). This model yielded diagnostic performance (AUC/sensitivity/specificity) of 0.77/81.0/66.0 (training) and 0.89/100/78.6 (testing) in determination of survival ≥ 18 months. CONCLUSIONS: Results show that our radiogenomic model generated from radiomic features at baseline MRI, age, and MGMT status can predict survival ≥ 18 months in patients with GBM.

Molecular states associated with dysfunction and graft loss in heart transplants.

BACKGROUND: We explored the changes in gene expression correlating with dysfunction and graft failure in endomyocardial biopsies. METHODS: Genome-wide microarrays (19,462 genes) were used to define mRNA changes correlating with dysfunction (left ventricular ejection fraction [LVEF] ≤ 55) and risk of graft loss within 3 years postbiopsy. LVEF data was available for 1,013 biopsies and survival data for 779 patients (74 losses). Molecular classifiers were built for predicting dysfunction (LVEF ≤ 55) and postbiopsy 3-year survival. RESULTS: Dysfunction is correlated with dedifferentiation-decreased expression of normal heart transcripts, for example, solute carriers, along with increased expression of inflammation genes. Many genes with reduced expression in dysfunction were matrix genes such as fibulin 1 and decorin. Gene ontology (GO) categories suggested matrix remodeling and inflammation, not rejection. Genes associated with the risk of failure postbiopsy overlapped dysfunction genes but also included genes affecting microcirculation, for example, arginase 2, which reduces NO production, and endothelin 1. GO terms also reflected increased glycolysis and response to hypoxia, but decreased VEGF and angiogenesis pathways. T cell-mediated rejection was associated with reduced survival and antibody-mediated rejection with relatively good survival, but the main determinants of survival were features of parenchymal injury. Both dysfunction and graft loss were correlated with increased biopsy expression of BNP (gene NPPB). Survival probability classifiers divided hearts into risk quintiles, with actuarial 3-year postbiopsy survival >95% for the highest versus 50% for the lowest. CONCLUSIONS: Dysfunction in transplanted hearts reflects dedifferentiation, decreased matrix genes, injury, and inflammation. The risk of short-term loss includes these changes but is also associated with microcirculation abnormalities, glycolysis, and response to hypoxia.

Special Considerations and Techniques of Interventions in Lung Transplant Recipients.

Lung transplant remains an important treatment option for patients with end-stage lung diseases providing improvement in survival rates and quality of life. Specialized considerations should be applied with interventions of lung transplant recipients as they host specific anatomic variations and high risk towards certain complications. In this article, we highlight the role of interventional radiology for lung transplant recipients along with discussion of interventional techniques. Specific emphasis is placed on describing and explaining the techniques pertained to the points of anastomosis, diagnosis and treatment of malignancies, and management of complications in lung transplant recipients.

Genetic Contribution to End-Stage Cardiomyopathy Requiring Heart Transplantation.

BACKGROUND: Many cardiovascular disorders propel the development of advanced heart failure that necessitates cardiac transplantation. When treatable causes are excluded, studies to define causes are often abandoned, resulting in a diagnosis of end-stage idiopathic cardiomyopathy. We studied whether DNA sequence analyses could identify unrecognized causes of end-stage nonischemic cardiomyopathy requiring heart transplantation and whether the prevalence of genetic causes differed from ambulatory cardiomyopathy cases. METHODS: We performed whole exome and genome sequencing of 122 explanted hearts from 101 adult and 21 pediatric patients with idiopathic cardiomyopathy from a single center. Data were analyzed for pathogenic/likely pathogenic variants in nuclear and mitochondrial genomes and assessed for nonhuman microbial sequences. The frequency of damaging genetic variants was compared among cardiomyopathy cohorts with different clinical severity. RESULTS: Fifty-four samples (44.3%) had pathogenic/likely pathogenic cardiomyopathy gene variants. The frequency of pathogenic variants was similar in pediatric (42.9%) and adult (43.6%) samples, but the distribution of mutated genes differed (P=8.30×10-4). The prevalence of causal genetic variants was significantly higher in end-stage than in previously reported ambulatory adult dilated cardiomyopathy cases (P<0.001). Among remaining samples with unexplained causes, no damaging mitochondrial variants were identified, but 28 samples contained parvovirus genome sequences, including 2 samples with 6- to 9-fold higher levels than the overall mean levels in other samples. CONCLUSIONS: Pathogenic variants and viral myocarditis were identified in 45.9% of patients with unexplained end-stage cardiomyopathy. Damaging gene variants are significantly more frequent among transplant compared with patients with ambulatory cardiomyopathy. Genetic analyses can help define cause of end-stage cardiomyopathy to guide management and risk stratification of patients and family members.

Profiling of repetitive RNA sequences in the blood plasma of patients with cancer.

Liquid biopsies provide a means for the profiling of cell-free RNAs secreted by cells throughout the body. Although well-annotated coding and non-coding transcripts in blood are readily detectable and can serve as biomarkers of disease, the overall diagnostic utility of the cell-free transcriptome remains unclear. Here we show that RNAs derived from transposable elements and other repeat elements are enriched in the cell-free transcriptome of patients with cancer, and that they serve as signatures for the accurate classification of the disease. We used repeat-element-aware liquid-biopsy technology and single-molecule nanopore sequencing to profile the cell-free transcriptome in plasma from patients with cancer and to examine millions of genomic features comprising all annotated genes and repeat elements throughout the genome. By aggregating individual repeat elements to the subfamily level, we found that samples with pancreatic cancer are enriched with specific Alu subfamilies, whereas other cancers have their own characteristic cell-free RNA profile. Our findings show that repetitive RNA sequences are abundant in blood and can be used as disease-specific diagnostic biomarkers.

Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids.

Mutant KRAS regulates transposable element (TE) RNA and interferon-stimulated gene (ISG) expression, but it remains unclear whether diverse mutations in KRAS affect different TE RNAs throughout the genome. We analyzed the transcriptomes of 3D human lung cancer spheroids that harbor KRAS(G12C) mutations to determine the landscape of TE RNAs regulated by mutant KRAS(G12C). We found that KRAS(G12C) signaling is required for the expression of LINE- and LTR-derived TE RNAs that are distinct from TE RNAs previously shown to be regulated by mutant KRAS(G12D) or KRAS(G12V). Moreover, KRAS(G12C) inhibition specifically upregulates SINE-derived TE RNAs from the youngest Alu subfamily AluY. Our results reveal that TE RNA dysregulation in KRAS-driven lung cancer cells is mutation-dependent, while also highlighting a subset of young, Alu-derived TE RNAs that are coordinately activated with innate immunity genes upon KRAS(G12C) inhibition.

The COVID-19 Pandemic and Adult Cardiac Transplantation: Impact, Interventions, and Implications.

In this review, we provide a comprehensive overview of the impact of the COVID-19 pandemic on adult heart transplantation. We highlight the decline in the number of adult transplantations performed throughout the pandemic as a consequence of restrictions imposed on individual programs and hospitals. There were challenges to maintaining cardiac transplant activity at multiple levels, including organ donation in intensive care units, logistical difficulties with organ procurement, and rapidly changing resource considerations at health system and jurisdictional levels. We also review the impact of COVID-19 on cardiac transplant recipients. Despite the high rates of morbidity and mortality observed during the initial phases of the pandemic among heart transplant patients infected with COVID-19, the availability of effective vaccines, pre-exposure prophylaxis, and specific antiviral therapies have drastically improved outcomes over time. Vaccines have proven to be safe and effective in reducing infections and illness severity, but specific considerations in the immunocompromised solid organ transplant population apply, including the need for additional booster doses to achieve sufficient immunisation. We further outline the strong rationale for vaccination before transplantation wherever possible. Finally, the COVID-19 response created a number of barriers to safe and efficient post-transplantation care. Given the need for frequent evaluation and monitoring, especially in the first several months after cardiac transplantation, the pandemic provided the impetus to improve virtual care delivery and explore noninvasive rejection surveillance through gene expression profiling. We hope that lessons learned will allow us to prepare and pivot effectively during future pandemics and health care emergencies.

Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny.

Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Mapping the chromatin dynamics of functionally defined cell populations will shed mechanistic insight into 2 major, unanswered questions in stem cell biology: how does epigenetic identity contribute to a cell type's lineage potential, and how do cascades of chromatin remodeling dictate ensuing fate decisions? Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. Oligopotent progenitor populations operating between the HSCs and unipotent cells play essential roles in effecting hematopoietic homeostasis. To test the hypothesis that selective HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during progenitor differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points. Additionally, quantification of genome-wide peak count and size revealed overall greater chromatin accessibility in HSCs, allowing us to identify HSC-unique peaks as putative regulators of self-renewal and multilineage potential. Finally, CRISPRi-mediated targeting of ATACseq-identified putative CREs in HSCs allowed us to demonstrate the functional role of selective CREs in lineage-specific gene expression. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.

Parental Refusals of Blood Transfusions from COVID-19 Vaccinated Donors for Children Needing Cardiac Surgery.

There is a growing trend of refusal of blood transfusions from COVID-19 vaccinated donors. We highlight three cases where parents have refused blood transfusions from COVID-19 vaccinated donors on behalf of their children in the setting of congenital cardiac surgery. These families have also requested accommodations such as explicit identification of blood from COVID-19 vaccinated donors, directed donation from a COVID-19 unvaccinated family member, or use of a non-standard blood supplier. We address the ethical challenges posed by these issues. We describe the current screening and safety processes for standard blood donation and explore the importance of donor anonymity and challenges with directed donation and non-standard blood suppliers. We present an ethical framework using the Best Interest Standard, the Zone of Parental Discretion, and the Harm Principle when considering these refusals. Finally, we provide recommendations for how to approach these requests as they potentially become more commonplace in pediatrics.

Assessing the Relationship Between Molecular Rejection and Parenchymal Injury in Heart Transplant Biopsies.

BACKGROUND: The INTERHEART study (ClinicalTrials.gov #NCT02670408) used genome-wide microarrays to detect rejection in endomyocardial biopsies; however, many heart transplants with no rejection have late dysfunction and impaired survival. We used the microarray measurements to develop a molecular classification of parenchymal injury. METHODS: In 1320 endomyocardial biopsies from 645 patients previously studied for rejection-associated transcripts, we measured the expression of 10 injury-induced transcript sets: 5 induced by recent injury; 2 reflecting macrophage infiltration; 2 normal heart transcript sets; and immunoglobulin transcripts, which correlate with time. We used archetypal clustering to assign injury groups. RESULTS: Injury transcript sets correlated with impaired function. Archetypal clustering based on the expression of injury transcript sets assigned each biopsy to 1 of 5 injury groups: 87 Severe-injury, 221 Late-injury, and 3 with lesser degrees of injury, 376 No-injury, 526 Mild-injury, and 110 Moderate-injury. Severe-injury had extensive loss of normal transcripts (dedifferentiation) and increase in macrophage and injury-induced transcripts. Late-injury was characterized by high immunoglobulin transcript expression. In Severe- and Late-injury, function was depressed, and short-term graft failure was increased, even in hearts with no rejection. T cell-mediated rejection almost always had parenchymal injury, and 85% had Severe- or Late-injury. In contrast, early antibody-mediated rejection (AMR) had little injury, but late AMR often had the Late-injury state. CONCLUSIONS: Characterizing heart transplants for their injury state provides new understanding of dysfunction and outcomes and demonstrates the differential impact of T cell-mediated rejection versus AMR on the parenchyma. Slow deterioration from AMR emerges as a major contributor to late dysfunction.

A Practical Approach to Invasive Testing in Ischemia With No Obstructive Coronary Arteries (INOCA).

Up to 65% of women and approximately 30% of men have ischemia with no obstructive coronary artery disease (CAD; commonly known as INOCA) on invasive coronary angiography performed for stable angina. INOCA can be due to coronary microvascular dysfunction or coronary vasospasm. Despite the absence of obstructive CAD, those with INOCA have an increased risk of all-cause mortality and adverse outcomes, including recurrent angina and cardiovascular events. These patients often undergo repeat testing, including cardiac catheterization, resulting in lifetime healthcare costs that rival those for obstructive CAD. Patients with INOCA often remain undiagnosed and untreated. This review discusses the symptoms and prognosis of INOCA, offers a systematic approach to the diagnostic evaluation of these patients, and summarizes therapeutic management, including tailored therapy according to underlying pathophysiological mechanisms.

Jusqu'à 65 % des femmes et environ 30 % des hommes présentent une ischémie sans coronaropathie obstructive (INOCA [ischemia with no obstructive coronary artery disease]) révélée à la faveur d'une angiographie coronarienne invasive réalisée pour une angine stable. L'INOCA peut être attribuable à une dysfonction microvasculaire coronaire ou à un vasospasme coronaire. Malgré l'absence de coronaropathie obstructive, les patients atteints d'une INOCA présentent un risque accru de décès toutes causes confondues et d'événements indésirables, notamment l'angine récurrente et des événements cardiovasculaires. Ces patients sont souvent soumis à des examens répétés, dont le cathétérisme cardiaque, ce qui représente des dépenses de santé à vie qui rivalisent avec celles associées aux coronaropathies obstructives. Dans bien des cas, l'INOCA échappe au diagnostic et n'est pas traité. Dans le présent article de synthèse, nous nous penchons sur les symptômes et le pronostic de l'INOCA. Nous proposons une méthode systématique d'évaluation diagnostique de ces patients et résumons les modalités de sa prise en charge thérapeutique, notamment un traitement adapté aux mécanismes physiopathologiques sous-jacents.

Mutant KRAS regulates transposable element RNA and innate immunity via KRAB zinc-finger genes.

RAS genes are the most frequently mutated oncogenes in cancer, yet the effects of oncogenic RAS signaling on the noncoding transcriptome remain unclear. We analyzed the transcriptomes of human airway and bronchial epithelial cells transformed with mutant KRAS to define the landscape of KRAS-regulated noncoding RNAs. We find that oncogenic KRAS signaling upregulates noncoding transcripts throughout the genome, many of which arise from transposable elements (TEs). These TE RNAs exhibit differential expression, are preferentially released in extracellular vesicles, and are regulated by KRAB zinc-finger (KZNF) genes, which are broadly downregulated in mutant KRAS cells and lung adenocarcinomas in vivo. Moreover, mutant KRAS induces an intrinsic IFN-stimulated gene (ISG) signature that is often seen across many different cancers. Our results indicate that mutant KRAS remodels the repetitive noncoding transcriptome, demonstrating the broad scope of intracellular and extracellular RNAs regulated by this oncogenic signaling pathway.

Neural Network Detection of Pacemakers for MRI Safety.

Flagging the presence of cardiac devices such as pacemakers before an MRI scan is essential to allow appropriate safety checks. We assess the accuracy with which a machine learning model can classify the presence or absence of a pacemaker on pre-existing chest radiographs. A total of 7973 chest radiographs were collected, 3996 with pacemakers visible and 3977 without. Images were identified from information available on the radiology information system (RIS) and correlated with report text. Manual review of images by two board certified radiologists was performed to ensure correct labeling. The data set was divided into training, validation, and a hold-back test set. The data were used to retrain a pre-trained image classification neural network. Final model performance was assessed on the test set. Accuracy of 99.67% on the test set was achieved. Re-testing the final model on the full training and validation data revealed a few additional misclassified examples which are further analyzed. Neural network image classification could be used to screen for the presence of cardiac devices, in addition to current safety processes, providing notification of device presence in advance of safety questionnaires. Computational power to run the model is low. Further work on misclassified examples could improve accuracy on edge cases. The focus of many healthcare applications of computer vision techniques has been for diagnosis and guiding management. This work illustrates an application of computer vision image classification to enhance current processes and improve patient safety.

LncRNA Biomarkers of Inflammation and Cancer.

Long noncoding RNAs (lncRNAs) are promising candidates as biomarkers of inflammation and cancer. LncRNAs have several properties that make them well-suited as molecular markers of disease: (1) many lncRNAs are expressed in a tissue-specific manner, (2) distinct lncRNAs are upregulated based on different inflammatory or oncogenic stimuli, (3) lncRNAs released from cells are packaged and protected in extracellular vesicles, and (4) circulating lncRNAs in the blood are detectable using various RNA sequencing approaches. Here we focus on the potential for lncRNA biomarkers to detect inflammation and cancer, highlighting key biological, technological, and analytical considerations that will help advance the development of lncRNA-based liquid biopsies.

Many heart transplant biopsies currently diagnosed as no rejection have mild molecular antibody-mediated rejection-related changes.

BACKGROUND: The Molecular Microscope (MMDx) system classifies heart transplant endomyocardial biopsies as No-rejection (NR), Early-injury, T cell-mediated (TCMR), antibody-mediated (ABMR), mixed, and possible rejection (possible TCMR, possible ABMR). Rejection-like gene expression patterns in NR biopsies have not been described. We extended the MMDx methodology, using a larger data set, to define a new "Minor" category characterized by low-level inflammation in non-rejecting biopsies. METHODS: Using MMDx criteria from a previous study, molecular rejection was assessed in 1,320 biopsies (645 patients) using microarray expression of rejection-associated transcripts (RATs). Of these biopsies, 819 were NR. A new archetypal analysis model in the 1,320 data set split the NRs into NR-Normal (N = 462) and NR-Minor (N = 359). RESULTS: Compared to NR-Normal, NR-Minor were more often histologic TCMR1R, with a higher prevalence of donor-specific antibody (DSA). DSA positivity increased in a gradient: NR-Normal 24%; NR-Minor 34%; possible ABMR 42%; ABMR 66%. The top 20 transcripts distinguishing NR-Minor from NR-Normal were all ABMR-related and/or IFNG-inducible, and also exhibited a gradient of increasing expression from NR-Normal through ABMR. In random forest analysis, TCMR and Early-injury were associated with reduced LVEF and increased graft loss, but NR-Minor and ABMR scores were not. Surprisingly, hearts with MMDx ABMR showed comparatively little graft loss. CONCLUSIONS: Many heart transplants currently diagnosed as NR by histologic or molecular assessment have minor increases in ABMR-related and IFNG-inducible transcripts, associated with DSA positivity and mild histologic inflammation. These results suggest that low-level ABMR-related molecular stress may be operating in many more hearts than previously estimated. (ClinicalTrials.gov #NCT02670408).

Bobolink (Dolichonyx oryzivorus) Declines Follow Bison (Bison bison) Reintroduction on Private Conservation Grasslands.

Among the most rapidly declining birds in continental North America, grassland birds evolved with American bison (Bison bison) until bison nearly became extinct due to overhunting. Bison populations have subsequently rebounded due to reintroductions on conservation lands, but the impacts of bison on grassland nesting birds remain largely unknown. We investigated how bison reintroduction, together with other land management and climate factors, affected breeding populations of a grassland bird species of conservation concern, the Bobolink (Dolichonyx oryzivorus). We quantified population changes in Bobolinks over an 18-year period in conservation grasslands where bison were reintroduced, compared with adjacent grasslands grazed by cattle and where hay was harvested after the bird breeding season. Four years after bison reintroduction, the bison population in the study area had doubled, while Bobolink abundance declined 62% and productivity declined 84%. Our findings suggest that bison reintroduction as a conservation strategy may be counterproductive in grassland fragments where overgrazing, trampling, and other negative impacts drive declines in grassland breeding birds. Where bird conservation is an objective, small grassland reserves may therefore be inappropriate sites for bison reintroduction. To maximize conservation benefits to birds, land managers should prioritize protecting grassland birds from disturbance during the bird breeding season.