Multicenter Cohort Research Articles

Global Differences and Risk Factors Influencing Drug Hypersensitivity Quality of Life: A Multi-Centre, Multi-ethnic Study of Drug Allergy Across Three Continents

BackgroundPenicillin allergy labels are associated with many adverse outcomes. Fear and restriction of future medication use also impact health-related quality of life (HR-QoL). However, the impact of a drug allergy on HR-QoL and its associated factors remain unknown. ObjectiveTo investigate the impact of penicillin allergy labels and compare the factors associated with HR-QoL impairment among an international multi-center and multi-ethnic cohort. MethodsHR-QoL was measured using the 6-item Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) and compared among patients labelled with penicillin allergy, before their allergy evaluation, from eight adult allergy/immunology clinics across Asia, Australasia, and North America. ResultsWe recruited 643 patients labelled with penicillin allergy (median age: 56 [IQR 39-67] years, male: female ratio: 1:2.2), with 273 (42.5%), 186 (28.9%) and 184 (28.6%) from Asia, North America and Australia; respectively. The median DrHy-Q score was 8.3 (IQR 0.0–29.2). All patients underwent penicillin allergy evaluation, and 96.0% (617/643) were delabelled following negative provocation tests. Patients who were female (8.3 vs. 4.2, p=0.003), had other concomitant antimicrobial allergy labels (20.8 vs. 4.2, p=0.004), and from Asia (33.3 vs. 4.2 [North America] vs. 0 [Australia], p<0.001) had significantly higher DrHy-Q scores, reflecting a reduced HR-QoL. Ethnicity, as well as other allergy variables, were not significant in multivariate analysis. ConclusionRegional differences, ethnicity, and other risk factors influence HR-QoL impairment among patients labelled with penicillin allergy. Future studies are needed to understand the contributions of regional socio-demographic factors and identify interventions to improve HR-QoL.

New ultrasound features in diagnosing fetal anal atresia: a multicenter prospective cohort study

This research aimed to assess the validity of ultrasound scans with new features in detecting fetal anal atresia and verify the effectiveness of these new features. Additionally, we aimed at investigating the perinatal incidence of anal atresia. This multicenter prospective study recruited 94,617 normal gravidas and 84 gravidas with anal atresia fetuses. The gold standard for diagnosing perinatal anal atresia is routine neonatal anus examinations. The incidence calculation was based on the results of the gold standard. The validity of our new approach was evaluated via a diagnostic test involving all 94,701 subjects. The effectiveness of our new features was assessed through an ablation study in a randomly established new dataset, with the ratio of anal atresia to non-anal atresia cases of 1:4. The annual perinatal incidence of anal atresia between 2019 and 2023 ranges from 0.57‰ to 1.29‰. Our new method performed great regarding the Youden index, diagnostic odds ratio (DOR), area under the curve (AUC) of the receiver operating characteristic curve (ROCC), AUC of the precision-recall curve (PRC), F1-score, and Cramer’s V. In the ablation study, our new approach surpassed its competitors concerning Youden index, DOR, AUC of the ROCC, and AUC of the PRC. Ultrasound scans show high validity and clinical value in detecting fetal anal atresia. Our new ultrasound features significantly promote the detection of fetal anal atresia.

Longitudinal transcriptional immune profiles and persistent wheezing in moderate-to-late preterm infants.

Prematurity is associated with an increased risk of persistent wheezing but the underlying mechanisms are not well defined. The aim of this study was to identify blood transcriptional profiles associated with the development of wheezing in a cohort of moderate to late preterm infants and to define immune gene expression changes associated with wheezing. A convenience sample of a multicenter birth cohort (SAREPREM) of moderate-late preterm children followed during the first 3 years of life was analyzed. Children were enrolled in the first 2 weeks of life (Y0) and longitudinally evaluated at 1 (Y1), 2 (Y2), and 3 years (Y3) of age, for the presence of wheezing and to obtain samples for transcriptional profile analysis. Samples were processed on Illumina HT12 chips and genomic expression analyses performed with R programming, modular analysis for biological function, and QuSAGE for quantitative gene expression. Seventy-six children were included in the study; 33 were classified as non-wheezing and 43 (56.6%) in the wheezing group. At Y0, children who developed wheezing had decreased expression of interferon genes and increased expression of B cell genes compared with the non-wheezing group. These changes in IFN and B cell gene expression were especially significant in children with late/persistent wheezing compared with transient wheezers. Changes in IFN and B lymphocyte gene expression identified in early life suggest the existence of specific immunological mechanisms that play an important role in the development of wheezing in late-preterm infants.

Oncologic outcomes based on lymphovascular space invasion in node-negative FIGO 2009 stage I endometrioid endometrial adenocarcinoma: a multicenter retrospective cohort study

BackgroundThe 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system includes lymphovascular invasion quantification as a staging criterion for endometrioid endometrial carcinomas; no lymphovascular invasion and focal invasion (≤4...

Evaluation of the effects of a Chinese herb in nonoperative bone fractures in Taiwan: A Retrospective multi-central database Cohort Study

IntroductionBone fracture is a critical issue worldwide, affecting daily activities and increasing living expenses. The effect of Chinese herbs on bone union has been evaluated in recent years. However, its clinical efficacy in the unionization of bone fractures is not completely elucidated. Zheng-Gu-Zi-Jin-Dang (ZGZJD) is a famous formula in Chinese medicine traumatology that has been widely used in patients with fractures in previous studies. MethodsWe used the Chang Gung Research Database and retrospectively reviewed patients at Chang Gung Memorial Hospital who suffered from bone fractures to evaluate the efficacy of ZGZJD intervention on bone union within three months after bone fractures and we used the frequency matching method in a 1:5 ratio for further analysis. ResultsBetween 2004 and 2016, 291,851 fractures were diagnosed at Chang Gung Memorial Hospital. A total of 544 patients received ZGZJD, and 2720 patients were match as control which do not use the herbs. However, we adjusted the comorbidities affecting the bone union, sex, age and different body extremities and there were no better healing rate in ZGZJD patient. ConclusionsAlthough ZGZJD is a common formula used in bone fractures, there is no direct clinical evidence that it enhances bone union. However, according to ingredients analysis in ZGZJD, this famous Chinese traumatology medicine may be useful during the inflammatory phase of bone healing.

Increased choroidal stromal area in patients with active Graves’ ophthalmopathy based on binarisation method of optical coherence tomographic images

ObjectiveTo investigate the change in choroidal components of patients with Graves’ ophthalmopathy (GO) with different degrees of disease activity and severity by using the image binarisation method of optical coherence...

Real-world data for marginal zone lymphoma patients in the French REALYSA cohort: The REALMA study.

Marginal Zone Lymphoma (MZL) comprises three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since clinical trials have limited representativeness, there is a need for real-world data (RWD) evidence in MZL. Real-world data in Lymphoma and survival in Adults (REALYSA) is a prospective multicentric French cohort of newly diagnosed lymphoma patients. This study consists of the first abstraction of MZL patients prospectively included in REALYSA between 12/2018 and 01/2021 with at least 1year of follow-up. It provides a landscape description of clinical characteristics, initial workup, quality of life and first-line therapy performed in routine practice. Among 207 included patients, 122 presented with EMZL, 51 with SMZL and 34 with NMZL. At baseline, median age was 67years (range 28-96), and patients reported a favorable global health status (75/100 (IQR 58,83)) - which was higher in NMZL and lower in SMZL patients (p=0.006). 18FDG-PET/CT was frequently performed at initial workup (EMZL 72%, SMZL 73%, NMZL 85%). Active surveillance was the initial management for 58 (28%) patients. The most prescribed therapies were rituximab-chlorambucil in the EMZL population (30%), rituximab monotherapy in the SMZL population (37%) and R-CHOP (24%)/bendamustine-rituximab (15%) in the NMZL population. At end of first line, overall response rate was 93% among treated patients with 75% of complete response. This French nationwide study provided for the first time prospective RWD on clinical characteristics, initial management and treatment response of MZL patients.

Plasma exchange does not improve overall survival in patients with acute liver failure in a real world cohort

Background and AimsTherapeutic plasma exchange (PEX) has emerged as a potential treatment option for patients with acute liver failure (ALF). The effect of PEX on survival outcomes outside of clinical trials is not yet well established. In this study we aimed to evaluate the real-world use and outcomes of PEX for the treatment of ALF. MethodsThis multicentre retrospective cohort study included consecutive patients with ALF admitted to all 7 tertiary liver transplant centres in the United Kingdom (UK) between June 2013 and December 2021. Changes in clinical variables following PEX treatment was assessed and overall survival and transplant free survival (TFS) to hospital discharge of patients receiving PEX were compared to those receiving standard medical therapy (SMT). Propensity score matching was performed to control for intergroup covariates and selection bias. ResultsWe included 378 patients with ALF (median (IQR) age 36 (28-48), 64% (n=242) female) of which 120 received PEX. There was a significant improvement in most clinical variables following PEX, including median dose of noradrenaline (reduction from 0.35 μg/kg/min (0.19 - 0.70 μg/kg/min) to 0.16 μg/kg/min (0.08 - 0.49) (p = 0.001). There was no significant difference between PEX and SMT groups in overall survival (51.4 % v 62.6 % respectively, p = 0.12) or TFS (42.6 % v 53.1 %, p = 0.24). ConclusionPEX is now frequently used in the management of ALF patients in the UK. It is associated with significant improvement in haemodynamic parameters but there is no survival benefit. Impact and implicationsPEX is frequently used in the management of patients with ALF in the UK. This real-world study demonstrates significant improvement in haemodynamic status but has not confirmed the survival benefit seen in previous published literature. These results should help inform future use of PEX.

Protocol for a phase 2 study of bosutinib for amyotrophic lateral sclerosis using real-world data: induced pluripotent stem cell-based drug repurposing for amyotrophic lateral sclerosis medicine (iDReAM) study

IntroductionAmyotrophic lateral sclerosis (ALS) is a progressive, severe neurodegenerative disease caused by motor neuron death. Development of a medicine for ALS is urgently needed, and induced pluripotent cell-based drug repurposing...

Baseline characteristics of the first 302 patients included for acute malignant hypertension crisis in the prospective multidisciplinary HAMA cohort.

Malignant hypertension has not disappeared and remains the most severe form of hypertension. More than 100 years after its description, many points remain unanswered. Mechanisms, definitions, and optimal treatment are still controversial. In 2019, we decided to launch a prospective multicentre multidisciplinary cohort in France to try to fill these gaps. This study aimed to describe the baseline characteristics of the first 302 included patients and compared these data to already published cohorts. We included patients with severe hypertension associated with severe hypertensive retinopathy and patients filling the HYP MOD (HYPertension MultiOrgan Damage) definition from a broad range of departments (cardiology, nephrology, neurology intensive care unit, emergency department, internal medicine). We collected clinical, biological, imaging, and target organ damage data at admission, along with social and demographic data. We also recorded diagnostic and therapeutic management, adverse events during hospitalization, and characteristics at discharge. We enrolled 302 patients in 32 months (105/year) among 40 centres and different specialties. They mainly included young men (68%, mean age 48.7 ± 14.5 years). Target organ damage involved the eye in 86.7% of patients, kidney in 58.6%, heart in 50%, brain in 32.8%, and Thrombotic Microangiopathy stigmata in 15.6%. Patients with severe retinopathy shared characteristics similar to those included in the most important cohorts already published. We also reported several additional subgroups of interest: one-third of our patients were less than 40 years old, one-third were of non-European origin, 14.3% were included through the multiorgan damage definition, without fundus severe injuries, 22.8% were treated without the use of IV therapy, 40.9% had normal or low renin level, and almost all patients were not on antihypertensive therapy at the time of the enrolment. These preliminary findings already challenge long-standing dogma, raise numerous questions, and provide a solid basis to address them in ancillary studies of the cohort.

Aetiology of Pleural Effusions in a Large Multicentre Cohort: Variation Between Outpatients and Inpatients.

This multi-centre retrospective cohort study aimed to determine whether the cause of an undiagnosed pleural effusion differed depending on if a patient presented as an outpatient or inpatient. A total of 1080 adult patients (556 inpatients and 524 outpatients) presenting primarily with an undiagnosed pleural effusion from 1 January 2021 to 31 December 2022 from four UK hospitals were included. We found malignant effusions were more common in outpatients compared to inpatients (48.3% vs. 36.0% p < 0.0001). Infection was common in inpatients but uncommon in outpatients (36.2% vs. 5.0% p < 0.0001). Other causes in all patients included heart and/or renal failure (13.1%) and non-specific pleuritis (5.6%). No diagnosis was possible in 11.8% of patients referred. Investigative pathways should vary depending on whether patients present as an inpatient or outpatient.

A-150 Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG)

A-150 Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG)

Relationship between the albumin-corrected anion gap and short-term prognosis among patients with cardiogenic shock: a retrospective analysis of the MIMIC-IV and eICU databases

ObjectivesWe aimed to investigate the association between the albumin-corrected anion gap (ACAG) and the prognosis of cardiogenic shock (CS).DesignA multicentre retrospective cohort study.SettingData were collected from the Medical Information Mart...

Stress CMR Perfusion Imaging in the Medicare-Eligible Population: Insights From the SPINS Study.

Patients aged ≥65 years account for a disproportionately large portion of cardiovascular (CV) events and pose a challenge for noninvasive detection of coronary artery disease. This study sought to determine the prognostic value of stress cardiac magnetic resonance (CMR) in a Medicare-eligible group of patients in a multicenter setting in the United States. From a multicenter U.S. registry, the study identified patients aged≥65 years who were referred for stress CMR for evaluation of myocardial inducible ischemia. The primary outcome was defined as CV death or nonfatal myocardial infarction, whereas the secondary outcome was defined as any primary outcome, hospitalization for unstable angina, hospitalization for congestive heart failure, and unplanned late coronary artery bypass grafting. The associations of CMR findings with CV outcomes adjusted to clinical risk markers and health care cost spending were determined. Among 1,780 patients (aged 73 ± 5.7 years; 46% female), study investigators observed 144 primary eventsand 323 secondary events, over a median follow-up of 4.8 years. The presence of inducible ischemia and late gadolinium enhancement (LGE) was associated with incrementally higher event rates. Patients with neither inducible ischemia nor LGE experienced a<1% annualized rate of primary outcome. In a multivariable model adjusted for CV risk factors, inducible ischemia and LGE maintained an independent association with primary (HR: 2.80 [95%CI: 1.93-4.05]; P< 0.001; and HR: 1.85 [95%CI: 1.21-2.82]; P = 0.004, respectively) and secondary (HR: 2.46 [95%CI: 1.90-3.19]; P< 0.001; and HR: 1.72 [95%CI: 1.30-2.27]; P< 0.001, respectively) outcomes. Rates of revascularization, as well as downstream costs for patients without CMR-detected inducible ischemia, remained low throughout the follow-up period. In a multicenter cohort of Medicare-eligible older patients, stress CMR was effective in providing risk stratification. (Stress CMR Perfusion Imaging in the United States [SPINS] study; NCT03192891).

Development and Portability of a Text Mining Algorithm for Capturing Disease Progression in Electronic Health Records of Patients With Stage IV Non-Small Cell Lung Cancer.

The objective was to develop and evaluate the portability of a text mining algorithm for prospectively capturing disease progression in electronic health record (EHR) data of patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunochemotherapy. This study used EHR data from patients with mNSCLC receiving immunochemotherapy (between October 1, 2018, and December 31, 2022) in four Dutch hospitals. A text mining algorithm for capturing disease progression was developed in hospitals 1 and 2 and then transferred to hospitals 3 and 4 to evaluate portability. Performance metrics were calculated by comparing its outcomes with manual chart review. In addition, data were simulated to come available over time to assess performance in real-time applications. Median progression-free survival (PFS) was calculated using the Kaplan-Meier method to compare text mining with manual chart review. During development and portability, the text mining algorithm performed well in capturing disease progression, with all performance scores >90%. When real-time performance was simulated, the performance scores in all four hospitals exceeded 90% from week 15 after the start of follow-up. Although the exact progression dates varied in 46 patients of 157 patients with progressive disease, the number of patients labeled with progression too early (n = 24) and too late (n = 22) was well balanced with discrepancies ranging from -116 to 384 days. Nevertheless, the PFS curves constructed with text mining and manual chart review were highly similar for each hospital. In this study, an accurate text mining algorithm for capturing disease progression in the EHR data of patients with mNSCLC was developed. The algorithm was portable across different hospitals, and the performance over time was good, making this an interesting approach for prospective follow-up of multicenter cohorts.

Real-world antithrombotic strategies in patients with atrial fibrillation and recently developed acute coronary syndrome

BackgroundThe antithrombotic strategy for patients with atrial fibrillation (AF) and coronary artery disease following percutaneous coronary intervention is shifting towards less intensive. Nevertheless, for patients with AF and acute coronary syndrome (ACS), an optimal antithrombotic strategy is yet to be established. Methods and resultsWe conducted a multi-center cohort study involving 146 Japanese centers that had prospectively registered 460 patients with AF and ACS followed for 2 years. Primary endpoint was the composite of thrombotic and bleeding events, and secondary endpoints included heart failure hospitalization. At the time of study registration, 86% of participants had received direct oral anticoagulants (DOACs) and 75% had received aspirin-based triple antithrombotic therapy (TAT) between March 2017 and August 2019. Apixaban was the most frequently used DOAC (29%). While the proportion of anticoagulants did not change according to the time course, the intensity of antiplatelets significantly attenuated over time (dual antiplatelet at baseline: 75%, and at 2-years: 7%). The cumulative incidence of the primary outcome measure was similar in patients with warfarin and DOACs. However, the risk of heart failure hospitalization was significantly higher in those with warfarin compared to DOACs (Hazard ratio: 2.8, 95% confidence interval: 1.1-5.8, p=0.022). ConclusionsThe present findings suggest the appropriate optimization of antithrombotic medication balancing in patients with AF and ACS in Japan by reducing the intensity of antiplatelets during the study period.

Multi-site DNA methylation alterations of peripheral blood mononuclear cells serve as novel biomarkers for the diagnosis of AIS/stage I lung adenocarcinoma: A multi-center cohort study.

Early diagnosis remains an obstacle for improving the outcome of lung adenocarcinoma (LUAD). DNA methylation changes in peripheral blood mononuclear cells (PBMCs) could reflect immune response to tumorigenesis, providing the theoretical basis for early cancer diagnosis based on immune cell profiling. This multi-center study evaluated the DNA methylation patterns based on PBMCs samples from 1115 individuals at nine medical centers. Genome-wide DNA methylation profiling of PBMCs in a discovery cohort (35 LUAD patients and 50 healthy controls) was performed using Illumina 850K microarray. Candidate differentially methylated CpG positions (DMPs) were selected and validated in a two-step DMPs screening cohort (65 LUAD patients and 80 healthy controls) by pyrosequencing and multiple target region methylation enrichment sequencing (MTRMES). Then, an early LUAD Diagnostic Panel (LDP score) based on multi-site methylation-specific chip-based digital PCR was constructed in a training set and then confirmed in a validation set from the LDP score development cohort (389 AIS/stage I LUAD patients and 293 healthy controls). Besides, we included 157 other cancer patients, including 52 gastric cancer (GC) patients, 50 breast cancer (BC) patients, and 55 colorectal cancer (CRC) patients to assess the specificity of LDP score. In addition, we also evaluated the early warning ability of LDP score for LUAD in a prospective cohort (46 people who were at high-risk of developing LC). A total of 1415 LUAD-specific DMPs were identified. Then, six DMPs were selected for validation and three DMPs were finally verified. The LDP score was constructed by combining the three DMPs, age, and gender, and showed an AUC of 0.916, sensitivity of 88.17%, and specificity of 80.20% in combined set, outperforming traditional methods, such as CEA and CT (detection rate: 87.79% vs. 4.69%; 87.79% vs. 35.21%). This diagnostic performance was confirmed in sub-types of LUAD with clinical challenges, such as 6-20mm LUAD (AUC: 0.914, 95%CI: 0.889-0.934) and ground-glass nodules (AUC: 0.916, 95%CI: 0.889-0.938). Importantly, our LDP score had significant improvement in terms of selecting high-risk individuals who should receive low-dose computed tomography (87.80% vs. 9.28%). Remarkably, LDP score could predict LUAD around two years before clinical diagnosis in our prospective cohort. The novel developed LDP score represented a convenient and effective assay for the detection of AIS/stage I LUAD with high sensitivity and specificity, and had demonstrated unique advantages over traditional detection methods.

The Prognostic Impact of Minimally Invasive Esophagectomy on Survival After Esophagectomy Following a Delayed Interval After Chemoradiotherapy: A Secondary Analysis of the DICE Study.

To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12wk) following chemoradiotherapy (CRT). Previously, we established that a prolonged interval after CRT before esophagectomy was associated with poorer long-term survival. This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approaches. A total of 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and 2 years after CRT. Significant differences were observed in American Society of Anesthesiologists grade, radiation dose, clinical T stage, and histologic subtype. There were no significant differences between the groups in age, sex, body mass index, pathologic T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate ( P =0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI: 1.14-2.5) and propensity-matched analysis ( P =0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE in 40 to 50Gy dose groups (HR=1.9; 95% CI: 1.2-3.0) and in patients having surgery within 6 months of CRT (HR=1.6; 95% CI: 1.1-2.2). MIE was associated with improved overall survival compared with OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

Young-onset type 2 diabetes mellitus enhances proteinuria, but not glomerular filtration rate decline: A Japanese cohort study.

The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline.

Intravenous thrombolysis versus dual antiplatelet therapy in minor ischemic stroke within the thrombolytic window (TAMIS): a multicenter cohort study.

Intravenous thrombolysis (IVT) and dual antiplatelet therapy (DAPT) have been widely used in minor ischemic stroke (MIS) treatment. However, the clinical outcomes and safety of these two treatments have not been compared within the early thrombolytic time window. Here, we conducted a multicenter, ambispective cohort study involving patients with MIS presenting within 4.5 h of symptom onset at 3 affiliated hospitals of Jinan University from 2018-2022. The patients were divided into the IVT group and DAPT group. The primary outcome was a 90-day excellent outcome (mRS ≤ 1). A total of 1,026 patients were enrolled, of whom 492 were assigned to the IVT group and 534 were assigned to the DAPT group. The IVT group had better 90-day excellent outcomes (mRS ≤ 1) than the DAPT group (OR 1.69, 95% CI 1.14-2.52, P = 0.010). Among the 623 patients with nondisabling stroke, the proportion of mRS ≤ 1 in the IVT group was higher than the DAPT group (P = 0.009). In the subtypes of MIS with large vessel occlusion/stenosis and with isolated symptoms, the 90-day outcomes of the IVT group and DAPT group were not different (P > 0.05). In conclusion, compared with DAPT, IVT was associated with better 90-day clinical outcomes in patients with MIS (in particular, for those with mRS > 1), including earlier clinical improvement.IVT also benefited the early neurological improvement of patients with severe stenosis/occlusion of intracranial large vessels, nondisabling mild stroke, nondisabling mild stroke with isolated symptoms.