Prognostic Value of Postoperative Complication for Gastric Cancer.

Background: The incidence of complications in gastric cancer (GC) patients after surgery was increasing, and it was not clear whether postoperative complications would have an impact on prognosis. The current study attempted to investigate the role of postoperative complication for prognosis on GC patients undergoing radical resection. Materials and Methods: Eligible studies were searched in three databases, including PubMed, Embase, and the Cochrane Library, in accordance with the searching strategy on September 4th, 2022. The survival values were most concerned; then, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled up. All prognostic values, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and recurrence-free survival (RFS), were allowed. Subgroup analysis based on complication types was used for further in-depth research. Results: A total of 29 studies involving 33,858 patients were included in this study. Intra-abdominal abscess (19.4%) was the most common complications in the included studies, followed by anastomotic leakage (17.0%) and pneumonia (16.4%). There were 23, 4, 6, and 10 studies that reported OS, DFS, DSS, and RFS, respectively. After analysis, postoperative complication was found to be an independent prognostic factor for OS (HR = 1.52, I2 = 1.14%, 95% CI = 1.42-1.61, P = .00), DFS (HR = 1.71, I2 = 0.00%,95% CI = 1.44-1.98, P < .05), DSS (HR = 1.60, I2 = 54.58%, 95% CI = 1.26-1.93, P < .1), and RFS (HR = 1.26, I2 = 0.00%, 95% CI = 1.11-1.41, P < .05). Subgroup analysis found that noninfectious complication was not significantly associated with OS (HR = 1.39, I2 = 0.00%, 95% CI = 0.96-1.82, P > .05). Conclusion: Surgeons needed to pay more attention to GC patients who developed postoperative complications, especially infectious complications, and take proactive management to improve the prognosis.

Cerebral endothelial cells mediated enhancement of brain pericyte number and migration in oxygen-glucose deprivation involves the HIF-1α/PDGF-ß signaling.

The present study focused on whether hypoxia-inducible factor-1alpha (HIF-1α) and platelet-derived factor-beta (PDGF-ß) are involved in the crosstalk between brain microvascular endothelial cells (BMECs) and brain vascular pericytes (BVPs) under ischaemic-hypoxic conditions. Mono-cultures or co-cultures of BVPs and BMECs were made for the construction of the blood-brain barrier (BBB) model in vitro and then exposed to control and oxygen-glucose deprivation (OGD) conditions. BBB injury was determined by assessing the ability, apoptosis, and migration of BVPs and the transendothelial electrical resistance and horseradish peroxidase permeation of BMECs. Relative mRNA and protein levels of HIF-1α and PDGF-ß, as well as tight junction proteins ZO-1 and claudin-5 were analyzed by western blotting, reverse transcription quantitative PCR, and/or immunofluorescence staining. Dual-luciferase reporter assays assessed the relationship between PDGF-ß and HIF-1α. Co-culturing with BMECs alleviated OGD-induced reduction in BVP viability, elevation in BVP apoptosis, and repression in BVP migration. Co-culturing with BVPs protected against OGD-induced impairment on BMEC permeability. OGD-induced HIF-1α upregulation enhanced PDGF-ß expression in mono-cultured BMECs and co-cultured BMECs with BVPs. Knockdown of HIF-1α impaired the effect of BMECs on BVPs under OGD conditions, and PDGFR-ß silencing in BVPs blocked the crosstalk between BMECs and BVPs under OGD conditions. The crosstalk between BMECs and BVPs was implicated in OGD-induced BBB injury through the HIF-1α/PDGF-ß signaling.

Platelet-Derived Microvesicles Mediate Cardiomyocyte Ferroptosis by Transferring ACSL1 During Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is one of the critical health conditions often caused by the rupture of unstable coronary artery plaque, triggering a series of events, such as platelet activation, thrombus formation, coronary artery blockage, lasted severe ischemia, and hypoxia in cardiomyocytes, and culminating in cell death. Platelet-derived microvesicles (PMVs) act as intermediates for cellular communication. Nevertheless, the role of PMVs in myocardial infarction remains unclear. Initially, AMI-related messenger ribose nucleic acid (mRNA) and micro RNA (miRNA) datasets from the Gene Expression Omnibus (GEO) database were analyzed, specifically focusing on the expressed genes associated with Ferroptosis. Further, a miRNA-mRNA regulatory network specific to AMI was constructed. Then, the effect of PMVs on cardiomyocyte survival was further confirmed through in vitro experiments. High ACSL1 expression was observed in the platelets of AMI patients. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that ACSL1, located in the mitochondria, played a key role in the PPAR signaling pathway. The elevated ACSL1 expression in a co-culture model of PMVs and AC16 cardiomyocytes significantly increased the AC16 cell Ferroptosis. Further, we validated that the platelet ACSL1 expression could be regulated by hsa-miR-449a. Together, these findings suggested that platelet ACSL1 could trigger myocardial cell death via PMV transport. In addition, this research provided a theoretical framework for attenuating myocardial cell Ferroptosis in patients with acute myocardial infarction.

A multicenter single-arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer.

The objective of this multicenter, single-arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy-THPy) in the treatment of patients with stage II-III HER2-positive breast cancer. The present study enrolled patients with stage II-III HER2-positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21-day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention-to-treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7-75.8%), while the objective response rate was 89.1%. In the post-hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy-THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II-III HER2-positive breast cancer.

Glutamine addiction and therapeutic strategies in pancreatic cancer.

Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis, early metastasis, and poor prognosis. Because current therapeutic options are limited, there is an urgent need to investigate novel targeted treatment strategies. Pancreatic cancer faces significant metabolic challenges, principally hypoxia and nutrient deprivation, due to specific microenvironmental constraints, including an extensive desmoplastic stromal reaction. Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation. Increased glucose uptake and glycolytic pathway activity during this process have been extensively described. However, growing evidence suggests that pancreatic cancer cells are glutamine addicted. As a nitrogen source, glutamine directly (or indirectly via glutamate conversion) contributes to many anabolic processes in pancreatic cancer, including amino acids, nucleobases, and hexosamine biosynthesis. It also plays an important role in redox homeostasis, and when converted to α-ketoglutarate, glutamine serves as an energy and anaplerotic carbon source, replenishing the tricarboxylic acid cycle intermediates. The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer, focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.

Research and practice of the BOPPPS teaching model based on the OBE concept in clinical basic laboratory experiment teaching.

"Clinical basic inspection technology" is one of the essential courses in the medical laboratory profession. Combining the characteristics of the discipline itself, the research and practice of the BOPPPS model based on the OBE concept in clinical basic laboratory experiment teaching are discussed, and the reform of in teaching objectives, teaching contents, and teaching design path is implemented. The "student-centered" teaching process is divided into six stages: before, during, and after class, and the teaching process is continuously improved to achieve the desired teaching effect. Results of the experiment teaching show that the model has improved students' active participation and developed their clinical thinking skills, and more than 95% of students are satisfied with this teaching model.

Severe hypernatremia during postoperative care in patients with craniopharyngioma.

Purpose: We aimed to describe and predict the risk of severe hypernatremia after surgical resection of craniopharyngioma and to identify the association of water intake, urine output, and sodium level change in the patients. Method: The outcome was postoperative severe hypernatremia. We identified risk factors associated with hypernatremia using multivariable regression. We trained machine learning models to predict the outcome. We compared serum sodium change, intravenous input, oral input, total input, urine output, and net fluid balance according to different nurse shifts. Results: Among 234 included patients, 125 developed severe hypernatremia after surgery. The peak incidence occurred during day 0 and day 6 after surgery. The risk was increased in patients with gross total resection (odds ratio (OR) 2.41, P < 0.001), high Puget classification (OR 4.44, P = 0.026), preoperative adrenal insufficiency (OR 2.01, P = 0.040), and preoperative hypernatremia (OR 5.55, P < 0.001). The random forest algorithm had the highest area under the receiver operating characteristic curve (0.770, 95% CI, 0.727-0.813) in predicting the outcome and was validated in the prospective validation cohort. Overnight shifts were associated with the highest serum sodium increase (P = 0.010), less intravenous input (P < 0.001), and less desmopressin use (P < 0.001). Conclusion: The overall incidence of severe hypernatremia after surgical resection of craniopharyngioma was significant, especially in patients with gross total resection, hypothalamus distortion, preoperative adrenal insufficiency, and preoperative severe hypernatremia. Less intravenous input and less desmopressin use were associated with serum sodium increases, especially during overnight shifts.

Development of an Antiswelling Hydrogel System Incorporating M2-Exosomes and Photothermal Effect for Diabetic Wound Healing.

Diabetic wounds represent a persistent global health challenge with a substantial impact on patients' health and overall well-being. Herein, a hydrogel system that integrates functionalized gold nanorods (AuNRs) and M2 macrophage-derived exosomes (M2-Exos) was developed to achieve an efficient and synergistic therapy for diabetic wounds. We introduced an ion-cross-linked dissipative network into a prefabricated covalent cross-linked network (long-chain polymer network), which was prepared using AuNRs as a specific cross-linker. The ion network was then cross-linked with the long-chain polymer in situ to form a specific network structure, imparting antiswelling and photothermal effects to the hydrogel. This integrated hydrogel system effectively scavenged reactive oxygen species levels, inhibited inflammation, promoted angiogenesis, and stimulated photothermal antibacterial activity through near-infrared (NIR) irradiation. To demonstrate the potential of the hydrogel, we established experimental animal models of oral mucosa ulceration and full-thickness skin defects. In vivo results confirmed that M2-Exos released from the hydrogels played a crucial role in wound closure. Furthermore, the synergistic effect of AuNRs and NIR photothermal effects eradicated bacterial infections in the wound area. Overall, our integrated hydrogel system is a promising tool for accelerating chronic diabetic wound healing and tissue regeneration. This study highlights the potential benefits of combining bioactive M2-Exos and the photothermal effect of AuNRs into an antiswelling hydrogel platform to achieve satisfactory wound healing in patients with diabetes.

Role of Fast and Slow Inhibitors in Oscillatory Rhythm Design.

In biological or abiotic systems, rhythms occur, owing to the coupling between positive and negative feedback loops in a reaction network. Using the Semenov-Whitesides oscillatory network for thioester hydrolysis as a prototype, we experimentally and theoretically analyzed the role of fast and slow inhibitors in oscillatory reaction networks. In the presence of positive feedback, a single fast inhibitor generates a time delay, resulting in two saddle-node bifurcations and bistability in a continuously stirred tank reactor. A slow inhibitor produces a node-focus bifurcation, resulting in damped oscillations. With both fast and slow inhibitors present, the node-focus bifurcation repeatedly modulates the saddle-node bifurcations, producing stable periodic oscillations. These fast and slow inhibitions result in a pair of time delays between steeply ascending and descending dynamics, which originate from the positive and negative feedbacks, respectively. This pattern can be identified in many chemical relaxation oscillators and oscillatory models, e.g., the bromate-sulfite pH oscillatory system, the Belousov-Zhabotinsky reaction, the trypsin oscillatory system, and the Boissonade-De Kepper model. This study provides a novel understanding of chemical and biochemical rhythms and suggests an approach to designing such behavior.

Triglyceride-glucose index and cervical vascular function: outpatient-based cohort study.

OBJECTIVES: The purpose of this study was to investigate the correlation between triglyceride-glucose (TyG) index and cervical vascular function parameters in the general population without cerebrovascular disease. MATERIALS AND METHODS: This was a cross-sectional study that recruited a total of 1996 participants without cerebrovascular disease. TyG index was calculated based on fasting triglycerides and glucose. All patients were divided into two groups based on the median TyG index: the high TyG group and the low TyG group. The differences in basic clinical characteristics and neck vascular function parameters between the two groups of participants were compared, and then the correlation between TyG index and neck vascular function parameters was investigated. RESULTS: Participants with a high TyG index had lower systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries compared with those with a low TyG index. Participants with a high TyG index had higher pulsatility index in the left vertebral artery and right internal carotid artery, but this difference was not observed in the basilar artery. In addition, TyG index was significantly negatively correlated with systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries, and the correlation remained after adjusting for confounding factors. CONCLUSION: In the general population, there was a well-defined correlation between TyG index and cervical vascular function parameters, and increased TyG index was independently associated with reduced cervical vascular blood flow velocity.

Transitions of Collective Motions Driven by Phase Resetting.

The front cover artwork is provided by Prof. Gao's group. The image shows the motion patterns transition of the active gel group under the step light intensity, which describes the mechanism of a new collective emergence structure. Read the full text of the Research Article at 10.1002/cphc.202300054.

Association of Neutrophil to High-Density Lipoprotein Cholesterol Ratio with Cardiac Ultrasound Parameters and Cardiovascular Risk: A Cross-Sectional Study Based on Healthy Populations.

Background: Neutrophils and high-density lipoprotein cholesterol (HDL-C) are significantly linked to cardiovascular disease (CVD). This study investigates the correlation of neutrophil count to HDL-C ratio (NHR) with cardiac ultrasound parameters and cardiovascular risk in healthy populations. Materials and Methods: Firstly, NHR was calculated based on neutrophils and HDL-C. Then, the differences in basic clinical characteristics and cardiac ultrasound parameters were compared between the high and low NHR groups, males and females. Subsequently, cardiovascular risk was predicted according to the Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool for people aged 35-60 years. Finally, the correlation between NHR and cardiac ultrasound parameters and cardiovascular risk was calculated. Results: A total of 3020 healthy participants, 1879 males and 1141 females, were included. Participants in the high NHR group had significantly increased Aorta (AO), Left Atrium (LA), Right Atrium (RA), Right Ventricle (RV), End Systolic Diameter of Left Ventricle (ESD), End Diastolic Diameter of Left Ventricle (EDD), Main Pulmonary Artery (MPA), Right Ventricular Outflow Tract (RVOT), Interventricular Septum (IVS), Left Ventricular Posterior Wall (LVPW), and cardiovascular risk and decreased E/A values compared to those in the low NHR group. The same results were found in males participants compared to females. A total of 1670 participants underwent ICVD risk assessment tool. Cardiovascular risk was significantly higher in those with high NHR and in males than in those with low NHR and in females. Correlation analysis showed that NHR was positively correlated with AO, LA, RA, RV, ESD, EDD, MPA, RVOT, IVS, LVPW and cardiovascular risk, and negatively correlated with E/A values. Conclusion: Our study demonstrates that NHR is significantly associated with cardiac ultrasound parameters and cardiovascular risk in healthy populations. NHR may serve as a useful indicator for the early diagnosis and treatment of cardiovascular disease among healthy populations.

Update on diagnosis and treatment of early signet-ring cell gastric carcinoma: A literature review.

Gastric signet-ring cell gastric carcinoma (GSRC) is an unfavorable subtype of gastric cancer (GC) that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC. However, GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC. Therefore, the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients. In recent years, technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients. Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection (ESD), indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation. This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.

A Self-Healing Multifunctional Hydrogel System Accelerates Diabetic Wound Healing through Orchestrating Immunoinflammatory Microenvironment.

Developing an effective treatment strategy of drug delivery to improve diabetic wound healing remains a major challenge in clinical practice nowadays, due to multidrug-resistant bacterial infections, angiopathy, and oxidative damage in the wound microenvironment. Herein, an effective and convenient strategy was designed through a self-healing multiple-dynamic-bond cross-linked hydrogel with interpenetrating networks, which was formed by multiple-dynamic-bond cross-linking of reversible catechol-Fe3+ coordinate bonds, hydrogen bonding, and Schiff base bonds. The excellent autonomous healing of the hydrogel was initiated and accelerated by Schiff bonds with reversible breakage between 3,4-dihydroxybenzaldehyde containing catechol and aldehyde groups and chitosan chains, and further consolidated by the co-optation of other noncovalent interactions contributed of hydrogen bonding and Fe3+ coordinate bonds. Intriguingly, cathelicidin LL-37 was introduced and uniformly dispersed in the dynamic interpenetrating networks of the hydrogel as a bioactive molecular to orchestrate the diabetic wound healing microenvironment. This multifunctional wound dressing can significantly promote diabetic wound healing by antibacterial activity, immunomodulation, anti-inflammation, neovascularization, and antioxidant activity. Therefore, this study provided an effective and safe strategy for guiding the diabetic wound treatment in clinical applications.

Effects of High-Fat Diet on Cardiovascular Protein Expression in Mice Based on Proteomics.

Purpose: To investigate the effect of high-fat diet on protein expression in mouse heart and aorta using proteomic techniques. Methods: A high-fat diet was used to construct an obese mouse model, and body weight was checked regularly. After the experiment, serum lipid and oxidative stress levels were measured. Proteomic detection of cardiac and aortic protein expression. Cardiac and aortic common differentially expressed proteins (Co-DEPs) were screened based on proteomic results. Subsequently, functional enrichment analysis and screening of key proteins were performed. Results: A high-fat diet significantly increased body weight in mice. Obese mice had considerably higher levels of TC, TG, LDL-C, ROS, and MDA. In the heart and aorta, 17 Co-DEPs were discovered. The results of functional analysis of these proteins indicated that they were mainly related to lipid metabolism. Ech1, Decr1, Hsd17b4, Hsdl2 and Acadvl were screened as key proteins. In mice, a high-fat diet causes lipid metabolism to become disrupted, resulting in higher levels of oxidative stress and lipid peroxidation products. Conclusion: Ech1, Decr1, Hsd17b4, Hsdl2 and Acadvl as cardiac and aortic Co-DEPs are closely related to lipid metabolism and may serve as potential diagnostic and therapeutic targets for obesity-induced cardiovascular disease.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma.

OBJECTIVE: This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma (NHL). METHODS: We compared the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and the ASMR to ASIR ratio (MIR) at national and regional levels and studied the correlation between the MIR and the human development index (HDI) in 2012 and 2018. RESULTS: The highest ASIR was in North America in 2012 and in Australia in 2018, and the lowest ASIR was in Central and South Asia in both 2012 and 2018. The highest ASMR was in North Africa in both 2012 and 2018, and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018. The lowest MIR was in Australia in both 2012 and 2018, and the highest MIR was in Western Africa in both 2012 and 2018. HDI was strongly negatively correlated with MIR (r: -0.8810, P<0.0001, 2012; r: -0.8895, P<0.0001, 2018). Compared to the 2012 data, the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018. CONCLUSION: The MIR is negatively correlated with HDI. Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.

Transitions of Collective Motions Driven by Phase Resetting.

Abrupt (i. e. step) environmental changes, such as natural disasters or the intervention of predators, can alter the internal dynamics of groups with active units, leading to the rapid destruction and/or restructuring of the group, with the emergence of new collective structures that endow the system with adaptability. Few studies, to date, have considered the influence of abrupt environmental changes on emergent behavior. Here, we use a model of active matter, the Belousov-Zhabotinsky (BZ) self-oscillating gel, to study the mechanism of formation and transition between modes of collective locomotion caused by changes of illumination intensity in arrays of interacting photosensitive active units. New forms of collective motion can be generated by step changes of illumination intensity. These transformations arise from the phase resetting and wave-signal regeneration induced by the abrupt parameter variation, while gradual change results in different evolution of collective motion. Our results not only suggest a novel mechanism for emergence, but also imply that new collective behaviors could be accessible via discontinuous parameter changes.

Numerical Simulation on Laser Shock Peening of B4C-TiB2 Composite Ceramics.

The introduction of residual stresses using laser shock peening (LSP) is an effective means of improving the mechanical properties of ceramics. Numerical simulations offer greater convenience and efficiency than in-lab experiments when testing the effects of different processing techniques on residual stress distribution. In this work, a B4C-TiB2 ceramic model based on the extended Drucker-Prager model was established to investigate the effects of laser power density, the number of impacts and laser spot overlapping rate on the residual stress distribution, and the reliability of the simulation method was verified by experimental data. The following results are obtained: increasing the laser power density and the number of impacts can increase the surface residual compressive stress and reduce the depth of the residual compressive stress; the presence of multiple impacts will significantly reduce the depth of the residual compressive stress layer; with the increase in the laser spot overlapping rate, the compressive residual stress in the processed area gradually increases and is more uniformly distributed; the best processing effect can be achieved by using a spot overlapping rate of 50%.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.