Inhibition of SFTSV replication in humanized mice by a subcutaneously administered anti-PD1 nanobody.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective therapies or vaccines available, understanding the disease's mechanisms is crucial. Recent studies found increased expression of programmed cell death-1 (PD-1) on dysfunctional T cells in SFTS patients. However, the role of the PD-1/programmed cell death-ligand 1 (PD-L1) pathway in SFTS progression remains unclear. We investigated PD-1 blockade as a potential therapeutic strategy against SFTSV replication. Our study analyzed clinical samples and performed in vitro experiments, revealing elevated PD-1/PD-L1 expression in various immune cells following SFTSV infection. An anti-PD-1 nanobody, NbP45, effectively inhibited SFTSV infection in peripheral blood mononuclear cells (PBMCs), potentially achieved through the mitigation of apoptosis and the augmentation of T lymphocyte proliferation. Intriguingly, subcutaneous administration of NbP45 showed superior efficacy compared to a licensed anti-PD-1 antibody in an SFTSV-infected humanized mouse model. These findings highlight the involvement of the PD-1/PD-L1 pathway during acute SFTSV infection and suggest its potential as a host target for immunotherapy interventions against SFTSV infection.

Genomic and transcriptomic profiling of peripheral T cell lymphoma reveals distinct molecular and microenvironment subtypes.

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin's lymphomas varying in clinical, phenotypic, and genetic features. The molecular pathogenesis and the role of the tumor microenvironment in PTCL are poorly understood, with limited biomarkers available for genetic subtyping and targeted therapies. Through an integrated genomic and transcriptomic study of 221 PTCL patients, we delineate the genetic landscape of PTCL, enabling molecular and microenvironment classification. According to the mutational status of RHOA, TET2, histone-modifying, and immune-related genes, PTCL is divided into 4 molecular subtypes with discrete patterns of gene expression, biological aberrations, and vulnerabilities to targeted agents. We also perform an unsupervised clustering on the microenvironment transcriptional signatures and categorize PTCL into 4 lymphoma microenvironment subtypes based on characteristic activation of oncogenic pathways and composition of immune communities. Our findings highlight the potential clinical rationale of future precision medicine strategies that target both molecular and microenvironment alterations in PTCL.

Up-front autologous stem cell transplant in peripheral T-cell lymphoma patients achieving complete response after first-line treatment: A multicentre real-world analysis.

We conducted a retrospective, multicentre study to compare consolidation therapy with or without first-line autologous stem cell transplant (ASCT) for peripheral T-cell lymphoma (PTCL) patients in a real-world setting. We enrolled 347 PTCL patients who achieved complete response after first-line treatment. Of these, 257 received consolidation chemotherapy (non-ASCT group) and 90 received ASCT (ASCT group). Clinical outcomes were comparable between ASCT and non-ASCT groups. After propensity score matching, the 2-year cumulative incidence of treatment-related mortality and relapse remained similar between groups (1.9% vs. 2.0%, p = 0.985; 24.7% vs. 47.1%, p = 0.021). However, significant differences emerged in progression-free survival and overall survival probabilities. Within the T-cell lymphoma subgroup, ASCT patients exhibited favourable outcomes compared to non-ASCT patients: 2-year progression-free survival (73.4% vs. 50.8%, p = 0.024) and overall survival (92.1% vs. 73.5%, p = 0.021). Notably, no significant differences were observed for patients with NK/T-cell lymphoma. These real-world data suggest that up-front ASCT is a safe and effective consolidation option for PTCL patients in remission, particularly those with T-cell lymphoma.

Computed tomography-based radiomics model to predict adverse clinical outcomes in acute pulmonary embolism.

This preliminary study investigated the feasibility of a combined model constructed using radiomic features based on computed tomography (CT) and clinical features to predict adverse clinical outcomes in acute pulmonary embolism (APE). Currently, there is no widely recognized predictive model. Patients with confirmed APE who underwent CT pulmonary angiography were retrospectively categorized into good and poor prognosis groups. Seventy-four patients were randomized into a training (n = 51) or validation (n = 23) cohort. Feature extraction was performed using 3D-Slicer software. The least absolute shrinkage and selection operator regression was used to identify the optimal radiomics features and calculate the radiomics scores; subsequently, the radiomics model was developed. A combined predictive model was constructed based on radiomics scores and selected clinical features. The predictive efficacy of the three models (radiomics, clinical and combined) was assessed by plotting receiver operating characteristic curves. Furthermore, the calibration curves were graphed and the decision curve analysis was performed. Four radiomic features were screened to calculate the radiomic score. Right ventricular to left ventricular ratio (RV/LV) ≥ 1.0 and radiomics score were independent risk factors for adverse clinical outcomes. In the training and validation cohorts, the areas under the curve (AUCs) for the RV/LV ≥ 1.0 (clinical) and radiomics score prediction models were 0.778 and 0.833 and 0.907 and 0.817, respectively. The AUCs for the combined model of RV/LV ≥ 1.0 and radiomics score were 0.925 and 0.917, respectively. The combined and radiomics models had high clinical assessment efficacy for predicting adverse clinical outcomes in APE, demonstrating the clinical utility of both models. Calibration curves exhibited a strong level of consistency between the predictive and observed probabilities of poor and good prognoses in the combined model. The combined model of RV/LV ≥ 1.0 and radiomics score based on CT could accurately and non-invasively predict adverse clinical outcomes in patients with APE.

Selection and identification of a prohibitin 2-binding DNA aptamer for tumor tissue imaging and targeted chemotherapy.

Tumor cell-targeting molecules play a vital role in cancer diagnosis, targeted therapy, and biomarker discovery. Aptamers are emerging as novel targeting molecules with unique advantages in cancer research. In this work, we have developed several DNA aptamers through cell-based systematic evolution of ligands by exponential enrichment (Cell-SELEX). The selected SYL-6 aptamer can bind to a variety of cancer cells with high signal. Tumor tissue imaging demonstrated that SYL-6-Cy5 fluorescent probe was able to recognize multiple clinical tumor tissues but not the normal tissues, which indicates great potential of SYL-6 for clinical tumor diagnosis. Meanwhile, we identified prohibitin 2 (PHB2) as the molecular target of SYL-6 using mass spectrometry, pull-down and RNA interference assays. Moreover, SYL-6 can be used as a delivery vehicle to carry with doxorubicin (Dox) chemotherapeutic agents for antitumor targeted chemotherapy. The constructed SYL-6-Dox can not only selectively kill tumor cells in vitro, but also inhibit tumor growth with reduced side effects in vivo. This work may provide a general tumor cell-targeting molecule and a potential biomarker for cancer diagnosis and targeted therapy.

Cell Membrane-Anchored DNA Nanoinhibitor for Inhibition of Receptor Tyrosine Kinase Signaling Pathways via Steric Hindrance and Lysosome-Induced Protein Degradation.

Receptor tyrosine kinase (RTK) plays a crucial role in cancer progression, and it has been identified as a key drug target for cancer targeted therapy. Although traditional RTK-targeting drugs are effective, there are some limitations that potentially hinder the further development of RTK-targeting drugs. Therefore, it is urgently needed to develop novel, simple, and general RTK-targeting inhibitors with a new mechanism of action for cancer targeted therapy. Here, a cell membrane-anchored RTK-targeting DNA nanoinhibitor is developed to inhibit RTK function. By using a DNA tetrahedron as a framework, RTK-specific aptamers as the recognition elements, and cholesterol as anchoring molecules, this DNA nanoinhibitor could rapidly anchor on the cell membrane and specifically bind to RTK. Compared with traditional RTK-targeting inhibitors, this DNA nanoinhibitor does not need to bind at a limited domain on RTK, which increases the possibilities of developing RTK inhibitors. With the cellular-mesenchymal to epithelial transition factor (c-Met) as a target RTK, the DNA nanoinhibitor can not only induce steric hindrance effects to inhibit c-Met activation but also reduce the c-Met level via lysosome-mediated protein degradation and thus inhibition of c-Met signaling pathways and related cell behaviors. Moreover, the DNA nanoinhibitor is feasible for other RTKs by just replacing aptamers. This work may provide a novel, simple, and general RTK-targeting nanoinhibitor and possess great value in RTK-targeted cancer therapy.

Clinical application of two-port laparoscopic surgery in sigmoid colon and upper rectal cancer resection.

Background: In the field of minimally invasive surgery, the two-port laparoscopic surgery is on the rise. This study investigated the safety and efficacy of two-port laparoscopic surgery (TLS) for resecting sigmoid colon and upper rectal cancers compared with conventional laparoscopic surgery (CLS). Methods: The clinical data of patients undergoing laparoscopic sigmoid colon cancer and upper rectal cancer resection at the Department of General Surgery of the First Affiliated Hospital of Gannan Medical College between July 2019 and January 2022 were retrospectively collected. Grouped according to different laparoscopic surgery. Based on the inclusion and exclusion criteria,A total of 81 patients were enrolled, of the 25 patients from the TLS group,and of the 56 patients from the CLS group. We mainly compared whether there were statistical differences between the two groups in terms of operative time, intraoperative bleeding, incision length, time to first ambulation, time to first flatus, time to first defecation, postoperative complication rate, and other surgical outcomes. Results: There was no statistical difference between the two groups in terms of baseline clinical characteristics (P > 0.05). In terms of the surgical outcomes, there were statistical differences in the total incision length (TLS: 6.21 ± 0.67 cm, CLS: 8.64 ± 1.08 cm, P < 0.001)), time to first ambulation (TLS: 2.0 ± 0.7 d, CLS:3.1 ± 0.9 d, P < 0.001), time to first flatus (TLS: 2.5 ± 0.8 d, CLS: 3.0 ± 0.8 d, P = 0.028), time to first defecation (TLS: 3.8 ± 1.3 d, CLS: 5.1 ± 2.1 d, P = 0.010), and time for liquid diet (TLS: 4.3 ± 1.4 d, CLS: 5.3 ± 1.9 d, P = 0.021). There was no statistical difference between the two groups in terms of the pathology (P > 0.05). Conclusion: In terms of safety, TLS in sigmoid colon and upper rectal cancer resection is comparable to CLS. However, its incision is smaller and more aesthetic, and it causes lesser trauma than CLS. Additionally, it is also superior to CLS in postoperative recovery.

Sex-specific association between carotid atherosclerosis and fundus arteriosclerosis in a Chinese population: a retrospective cross-sectional study.

OBJECTIVES: Vascular stiffening is highly predictive of major adverse cardiovascular events. It is not clear whether microangiopathy, such as fundus arteriosclerosis, is related to carotid atherosclerosis. Hence, this study was designed to investigate the relationship between carotid atherosclerosis and fundus arteriosclerosis among individuals of different sexes in the Chinese health-examination population. METHODS: This retrospective cross-sectional study involved 20,836 participants, including 13050 males and 7786 females. All participants underwent a detailed health examination, including medical history assessment, physical examination, assessment of lifestyle factors, fundus photography, Doppler ultrasound examination of the neck, and laboratory examinations. Two trained ophthalmologists analysed fundus arteriosclerosis based on fundus photographs, while carotid atherosclerosis was diagnosed using colour Doppler sonography of the neck. Binary logistic regression was used to analyse the relationship between carotid atherosclerosis and fundus arteriosclerosis. RESULTS: In participants with fundus arteriosclerosis, the incidence of carotid atherosclerosis was higher than that of participants without fundus arteriosclerosis (52.94% vs. 47.06%). After adjustments for potential confounding factors, fundus arteriosclerosis was significantly associated with the risk of carotid atherosclerosis. The OR with 95% CI for fundus arteriosclerosis was 1.17 (1.02, 1.34) with p = 0.0262, and individuals who did not have fundus arteriosclerosis were used as a reference in the total population. Fundus arteriosclerosis was associated with the incidence of carotid atherosclerosis in males (p = 0.0005) but not in females (p = 0.0746). CONCLUSIONS: Fundus arteriosclerosis was closely associated with carotid atherosclerosis in the Chinese population. This association was found in males but not in females.

Associating Serum IgM, IgA Levels with Thoracic CT Indicators and Pulmonary Function Indexes in Acutely Exacerbated Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by acute exacerbations and reduced lung function. This study investigates the link between serum markers (Immunoglobulin M (IgM) and Immunoglobulin A (IgA)), thoracic computed tomography (CT) scan findings, and pulmonary function indexes during these episodes, aiming to improve our understanding and identify new diagnostic indicators. METHODS: From the First Affiliated Hospital of Hebei North University, we selected 89 COPD patients experiencing acute exacerbation within the past two years for our Acute Exacerbation Group (AG). Meanwhile, 96 COPD patients, initially treated at the same hospital and currently deemed stable, were chosen for the Stable Group (SG). Both groups underwent serum IgM and IgA tests, thoracic CT examinations, and pulmonary function assessments. RESULTS: In the AG Group, the serum IgM levels were marginally lower than in the Stable Group (SG), though the difference wasn't statistically significant (p = 0.097). Conversely, serum IgA levels in the AG were significantly lower than in the SG (p < 0.001). The AG also showed markedly reduced lung volume, inspiratory lung density, and pulmonary function indexes compared to the SG while having considerably higher values for emphysema index (EI) and air trapping index (ATI) (all p < 0.001). Pearson correlation analysis revealed that lung volume, average inspiratory lung density, and IgA levels had strong positive correlations with one-second forced expiratory volume (FEV1), FEV1/forced vital capacity (FVC), and diffuse carbon monoxide (DLCO) (with respective r-values of 0.824, 0.841, and 0.829; all p < 0.001). In contrast, EI and ATI exhibited significantly negative correlations with FEV1, FEV1/FVC, and DLCO (with r-values ranging from -0.837 to -0.885; all p < 0.001). CONCLUSIONS: The assessment of serum IgA combined with thoracic CT parameters offers valuable insights for diagnosing and evaluating acute exacerbations of COPD, presenting a straightforward clinical utility.

Clinical Usefulness of Speckle-Tracking Echocardiography in Patients with Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is defined as HF with left ventricular ejection fraction (LVEF) not less than 50%. HFpEF accounts for more than 50% of all HF patients, and its prevalence is increasing year to year with the aging population, with its prognosis worsening. The clinical assessment of cardiac function and prognosis in patients with HFpEF remains challenging due to the normal range of LVEF and the nonspecific symptoms and signs. In recent years, new echocardiographic techniques have been continuously developed, particularly speckle-tracking echocardiography (STE), which provides a sensitive and accurate method for the comprehensive assessment of cardiac function and prognosis in patients with HFpEF. Therefore, this article reviewed the clinical utility of STE in patients with HFpEF.

Disentangling age, gender, and racial/ethnic disparities in multiple myeloma burden: a modeling study.

Multiple myeloma (MM) is a hematological malignancy that is consistently preceded by an asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Disparities by age, gender, and race/ethnicity in both MGUS and MM are well-established. However, it remains unclear whether these disparities can be explained by increased incidence of MGUS and/or accelerated progression from MGUS to MM. Here, we fit a mathematical model to nationally representative data from the United States and showed that the difference in MM incidence can be explained by an increased incidence of MGUS among male and non-Hispanic Black populations. We did not find evidence showing differences in the rate of progression from MGUS to MM by either gender or race/ethnicity. Our results suggest that screening for MGUS among high-risk groups (e.g., non-Hispanic Black men) may hold promise as a strategy to reduce the burden and MM health disparities.

Ethnic differences of genetic risk and smoking in lung cancer: two prospective cohort studies.

BACKGROUND: The role of genetic background underlying the disparity of relative risk of smoking and lung cancer between European populations and East Asians remains unclear. METHODS: To assess the role of ethnic differences in genetic factors associated with smoking-related risk of lung cancer, we first constructed ethnic-specific polygenic risk scores (PRSs) to quantify individual genetic risk of lung cancer in Chinese and European populations. Then, we compared genetic risk and smoking as well as their interactions on lung cancer between two cohorts, including the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). We also evaluated the absolute risk reduction over a 5-year period. RESULTS: Differences in compositions and association effects were observed between the Chinese-specific PRSs and European-specific PRSs, especially for smoking-related loci. The PRSs were consistently associated with lung cancer risk, but stronger associations were observed in smokers of the UKB [hazard ratio (HR) 1.26 vs 1.15, P = 0.028]. A significant interaction between genetic risk and smoking on lung cancer was observed in the UKB (RERI, 11.39 (95% CI, 7.01-17.94)], but not in the CKB. Obvious higher absolute risk was observed in nonsmokers of the CKB, and a greater absolute risk reduction was found in the UKB (10.95 vs 7.12 per 1000 person-years, P <0.001) by comparing heavy smokers with nonsmokers, especially for those at high genetic risk. CONCLUSIONS: Ethnic differences in genetic factors and the high incidence of lung cancer in nonsmokers of East Asian ethnicity were involved in the disparity of smoking-related risk of lung cancer.

Integrative splicing-quantitative-trait-locus analysis reveals risk loci for non-small-cell lung cancer.

Splicing quantitative trait loci (sQTLs) have been demonstrated to contribute to disease etiology by affecting alternative splicing. However, the role of sQTLs in the development of non-small-cell lung cancer (NSCLC) remains unknown. Thus, we performed a genome-wide sQTL study to identify genetic variants that affect alternative splicing in lung tissues from 116 individuals of Chinese ancestry, which resulted in the identification of 1,385 sQTL-harboring genes (sGenes) containing 378,210 significant variant-intron pairs. A comprehensive characterization of these sQTLs showed that they were enriched in actively transcribed regions, genetic regulatory elements, and splicing-factor-binding sites. Moreover, sQTLs were largely distinct from expression quantitative trait loci (eQTLs) and showed significant enrichment in potential risk loci of NSCLC. We also integrated sQTLs into NSCLC GWAS datasets (13,327 affected individuals and 13,328 control individuals) by using splice-transcriptome-wide association study (spTWAS) and identified alternative splicing events in 19 genes that were significantly associated with NSCLC risk. By using functional annotation and experiments, we confirmed an sQTL variant, rs35861926, that reduced the risk of lung adenocarcinoma (rs35861926-T, OR = 0.88, 95% confidence interval [CI]: 0.82-0.93, p = 1.87 × 10-5) by promoting FARP1 exon 20 skipping to downregulate the expression level of the long transcript FARP1-011. Transcript FARP1-011 promoted the migration and proliferation of lung adenocarcinoma cells. Overall, our study provided informative lung sQTL resources and insights into the molecular mechanisms linking sQTL variants to NSCLC risk.

The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants.

The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.

Mortality in the US Populations With Monoclonal Gammopathy of Undetermined Significance.

This cohort study analyzes a nationally representative sample with a screening test for monoclonal gammopathy of undetermined significance (MGUS) to evaluate overall survival of populations with MGUS compared with those without MGUS among the general population in the US.

Association of psychological distress, smoking and genetic risk with the incidence of lung cancer: a large prospective population-based cohort study.

Background: Emerging evidence suggests a potential link between psychological distress (anxiety and depression) and lung cancer risk, however, it is unclear whether other factors such as tobacco smoking and genetic susceptibility modify the association. Methods: We included 405,892 UK Biobank participants free of cancer at baseline. Psychological distress was measured using the Patient Health Questionnaire-4 (PHQ-4). A polygenic risk score (PRS) was calculated using 18 lung cancer-associated genetic loci. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 7.13 years, 1754 lung cancer cases were documented. The higher score of psychological distress was associated with an increased risk of lung cancer (HRper 1-SD= 1.07, 95% CI: 1.02-1.11) after adjustment for smoking and other confounders. Mediation analysis revealed that 16.8% (95% CI: 13.0%-20.6%) of the distress-lung cancer association was mediated by smoking. Compared with never smokers with no distress, participants with heavy smoking and high distress had the highest risk of lung cancer (HR=18.57, 95% CI: 14.51-23.76). Both multiplicative and additive interactions were observed between smoking and psychological distress in lung cancer. Furthermore, the greatest relative increase in risk was observed among those with high genetic risk and high distress (HR=1.87, 95%CI: 1.50-2.33), and there was a significant additive interaction between the PRS and psychological distress. Conclusion: Our results indicate that psychological distress was associated with an elevated risk of incident lung cancer, and such relation was modified by tobacco smoking and genetic susceptibility.

Hif1α/Dhrs3a Pathway Participates in Lipid Droplet Accumulation via Retinol and Ppar-γ in Fish Hepatocytes.

Excessive hepatic lipid accumulation is a common phenomenon in cultured fish; however, its underlying mechanisms are poorly understood. Lipid droplet (LD)-related proteins play vital roles in LD accumulation. Herein, using a zebrafish liver cell line (ZFL), we show that LD accumulation is accompanied by differential expression of seven LD-annotated genes, among which the expression of dehydrogenase/reductase (SDR family) member 3 a/b (dhrs3a/b) increased synchronously. RNAi-mediated knockdown of dhrs3a delayed LD accumulation and downregulated the mRNA expression of peroxisome proliferator-activated receptor gamma (pparg) in cells incubated with fatty acids. Notably, Dhrs3 catalyzed retinene to retinol, the content of which increased in LD-enriched cells. The addition of exogenous retinyl acetate maintained LD accumulation only in cells incubated in a lipid-rich medium. Correspondingly, exogenous retinyl acetate significantly increased pparg mRNA expression levels and altered the lipidome of the cells by increasing the phosphatidylcholine and triacylglycerol contents and decreasing the cardiolipin, phosphatidylinositol, and phosphatidylserine contents. Administration of LW6, an hypoxia-inducible factor 1α (HIF1α) inhibitor, reduced the size and number of LDs in ZFL cells and attenuated hif1αa, hif1αb, dhrs3a, and pparg mRNA expression levels. We propose that the Hif-1α/Dhrs3a pathway participates in LD accumulation in hepatocytes, which induces retinol formation and the Ppar-γ pathway.

Patterns in Use and Transplant Outcomes Among Adult Recipients of Kidneys From Deceased Donors With COVID-19.

Importance: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown. Objective: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19. Design, Setting, and Participants: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs from March 1, 2020, to March 30, 2023. Exposure: The exposure was donor SARS-CoV-2 nucleic acid amplification test (NAT) results, with positive NAT results within 7 days before procurement defined as active COVID-19 and positive NAT results 1 week (>7 days) before procurement defined as resolved COVID-19. Main Outcomes and Measures: Primary outcomes were kidney nonuse, all-cause kidney graft failure, and all-cause patient death. Secondary outcomes were acute rejection (ie, rejection in the first 6 months after KT), transplant hospitalization length of stay (LOS), and delayed graft function (DGF). Multivariable logistic regression analyses were performed for kidney nonuse, rejection, and DGF; multivariable linear regression analyses were performed for LOS; and multivariable Cox regression analyses were performed for graft failure and all-cause death. All models were adjusted for inverse probability treatment weighting. Results: Among 35 851 deceased donors, the mean (SD) age was 42.5 (15.3) years; 22 319 (62.3%) were men and 23 992 (66.9%) were White. Among 45 912 recipients, the mean (SD) age was 54.3 (13.2) years; 27 952 (60.9%) were men and 15 349 (33.4%) were Black. The likelihood of nonuse of kidneys from active or resolved COVID-19-positive donors decreased over time. Overall, kidneys from active COVID-19-positive donors (adjusted odds ratio [AOR], 1.55; 95% CI, 1.38-1.76) and kidneys from resolved COVID-19-positive donors (AOR, 1.31; 95% CI, 1.16-1.48) had a higher likelihood of nonuse compared with kidneys from COVID-19-negative donors. From 2020 to 2022, kidneys from active COVID-19-positive donors (2020: AOR, 11.26 [95% CI, 2.29-55.38]; 2021: AOR, 2.09 [95% CI, 1.58-2.79]; 2022: AOR, 1.47 [95% CI, 1.28-1.70]) had a higher likelihood of nonuse compared with kidneys from donors without COVID-19. Kidneys from resolved COVID-19-positive donors had a higher likelihood of nonuse in 2020 (AOR, 3.87; 95% CI, 1.26-11.90) and 2021 (AOR, 1.94; 95% CI, 1.54-2.45) but not in 2022 (AOR, 1.09; 95% CI, 0.94-1.28). In 2023, kidneys from both active COVID-19-positive donors (AOR, 1.07; 95% CI, 0.75-1.63) and resolved COVID-19-positive donors (AOR, 1.18; 95% CI, 0.80-1.73) were not associated with higher odds of nonuse. No higher risk of graft failure or death was found in patients receiving kidneys from active COVID-19-positive donors (graft failure: adjusted hazard ratio [AHR], 1.03 [95% CI, 0.78-1.37]; patient death: AHR, 1.17 [95% CI, 0.84-1.66]) or resolved COVID-19-positive donors (graft failure: AHR, 1.10 [95% CI, 0.88-1.39]; patient death: AHR, 0.95 [95% CI, 0.70-1.28]). Donor COVID-19 positivity was not associated with longer LOS, higher risk of acute rejection, or higher risk of DGF. Conclusions and Relevance: In this cohort study, the likelihood of nonuse of kidneys from COVID-19-positive donors decreased over time, and donor COVID-19 positivity was not associated with worse KT outcomes within 2 years after transplant. These findings suggest that the use of kidneys from donors with active or resolved COVID-19 is safe in the medium term; further research is needed to assess longer-term transplant outcomes.