Changes in source contributions to the oxidative potential of PM2.5 in urban Xiamen, China.

The toxicity of PM2.5 does not necessarily change synchronously with its mass concentration. In this study, the chemical composition (carbonaceous species, water-soluble ions, and metals) and oxidative potential (dithiothreitol assay, DTT) of PM2.5 were investigated in 2017/2018 and 2022 in Xiamen, China. The decrease rate of volume-normalized DTT (DTTv) (38%) was lower than that of PM2.5 (55%) between the two sampling periods. However, the mass-normalized DTT (DTTm) increased by 44%. Clear seasonal patterns with higher levels in winter were found for PM2.5, most chemical constituents and DTTv but not for DTTm. The large decrease in DTT activity (84%-92%) after the addition of EDTA suggested that water-soluble metals were the main contributors to DTT in Xiamen. The increased gap between the reconstructed and measured DTTv and the stronger correlations between the reconstructed/measured DTT ratio and carbonaceous species in 2022 were observed. The decrease rates of the hazard index (32.5%) and lifetime cancer risk (9.1%) differed from those of PM2.5 and DTTv due to their different main contributors. The PMF-MLR model showed that the contributions (nmol/(min·m3)) of vehicle emission, coal + biomass burning, ship emission and secondary aerosol to DTTv in 2022 decreased by 63.0%, 65.2%, 66.5%, and 22.2%, respectively, compared to those in 2017/2018, which was consistent with the emission reduction of vehicle exhaust and coal consumption, the adoption of low-sulfur fuel oil used on board ships and the reduced production of WSOC. However, the contributions of dust + sea salt and industrial emission increased.

Gut microbiome pattern impacts treatment response in primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease. An inadequate response to ursodeoxycholic acid (UDCA) poses a high risk of progression toward end-stage liver disease. Gut dysbiosis has been implicated in PBC. Here, we aimed to investigate microbial signatures that permit risk stratification and provide mechanistic insights into novel therapies for PBC. METHODS: We prospectively recruited UDCA treatment-naive patients with PBC and performed metagenomic sequencing and metabolomic profiling using stool and serum samples obtained before (n = 132) and after (n = 59) treatment. PBC microbiome subtypes were identified using unsupervised machine learning methods and validated in two independent cohorts. FINDINGS: PBC baseline metagenomes clustered into two community subtypes characterized by varying abundances of Clostridia taxa. Compared with Clostridialow microbiomes, Clostridiahigh microbiomes were more similar to healthy controls. Notably, patients in the Clostridialow subtype exhibited a 2-fold higher UDCA non-response rate compared to those in the Clostridiahigh subtype (41% vs. 20%, p = 0.015). Integrative analysis of metagenomic and metabolomic data revealed divergent functional modules and metabolic activities between the two metacommunities. In particular, anaerobic fermentation and the production of bioactive metabolites, including tryptophan derivatives and secondary bile acids, crucial for immune regulation and gut barrier maintenance, were markedly diminished in the Clostridialow subtype. Moreover, UDCA administration reconfigured the fecal microbial and metabolic profiles only in the Clostridiahigh group. Importantly, the microbiome subtypes and their associations with UDCA response were reproducible in two independent treatment-naive PBC cohorts. CONCLUSIONS: Characterizing baseline microbiota patterns may enable the prediction of treatment outcomes in PBC and facilitate personalized treatment strategies. FUNDING: This research was mainly supported by the National Natural Science Foundation of China.

Leveraging the One Health concept for arsenic sustainability.

Arsenic (As) is a naturally occurring chemical element widely distributed in the Earth's crust. Human activities have significantly altered As presence in the environment, posing significant threats to the biota as well as human health. The environmental fates and adverse outcomes of As of various species have been extensively studied in the past few decades. It is imperative to summarize these advances as a whole to provide more profound insights into the As cycle for sustainable development. Embracing the One Health concept, we systematically reviewed previous studies in this work and explored the following three fundamental questions, i.e., what the trends and associated changes are in As contamination, how living organisms interact and cope with As contamination, and most importantly what to do to achieve a sustainable future with As. By focusing on one critical question in each section, this review aims to provide a full picture of the complexity of environmental As. To tackle the significant research challenges and gaps in As pollution and mitigation, we further proposed a One Health framework with potential coping strategies, guiding a coordinated agenda on dealing with legacy As in the environment and ensuring a sustainable As future.

A study on the methylation patterns of DIO3 in patients with heart failure and its correlation with key clinical parameters.

Objective: This study aimed to analyze the methylation pattern of deoxyribonucleic acid (CpG) sites in the DIO3_FA26 promoter region of patients with heart failure (HF) and explore the correlation between differential CpG methylation levels and various clinical parameters. Methods: Peripheral blood specimens were collected from 20 patients with HF and 20 healthy individuals. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to identify and detect the CpG sites in the DIO3_FA26 promoter region. CpG methylation levels were compared between patients with HF and healthy controls and patients with HF with different levels of cardiac function. Results: The methylation level of DIO3_FA26_CpG_17.18 in patients with HF was significantly lower than that in the healthy control group (P = 0.0002). Among patients with HF and cardiac function levels of I/II and III/IV, methylation levels of DIO3_FA26_CpG_24.25.26.27 (P = 0.0168) were significantly lower in those with III/IV cardiac function compared to those with I/II cardiac function. Conclusion: The methylation level of DIO3_FA26_CpG_17.18 is significantly reduced in patients with HF, and that of DIO3_FA26_CpG_24.25.26.27 is significantly decreased in patients with III/IV cardiac function. Variations in DIO3_FA26 methylation levels influence coagulation, liver and kidney functions, and routine blood indexes, including D-dimer, albumin, calcium, and hemoglobin. This study provides clinical evidence for the involvement of DIO3_FA26 methylation in the occurrence and development of HF and proposes novel targets for HF prevention and treatment.

Efficacy and safety of early prone position in postoperative cardiac surgery adults with acute respiratory distress syndrome: a single-center retrospective cohort study.

Background: Acute respiratory distress syndrome (ARDS) is a leading cause of postoperative respiratory failure after cardiac surgery, and the mortality rate is extremely high. Although prone positioning (PP) may be safe and effective for ARDS, it is still not widely adopted in cardiac surgery patients. We aimed to assess the efficacy and safety of early PP in ARDS after cardiac surgery. Methods: This is a single-center retrospective cohort study. We included adult intensive care unit (ICU) patients who developed ARDS with arterial pressure of oxygen to fraction of oxygen ratio (P/F) ≤200 mmHg within 72 hours after cardiac surgery between 1 January 2019 and 1 August 2023. The outcomes were P/F after 1 session of PP, duration of mechanical ventilation (MV) and ICU stay, and adverse events. Results: In total, 79 patients who underwent PP and 87 patients who underwent supine position (SP) were included. The mean time to perform PP after ICU admission was 38.0 hours. The P/F improved significantly after 1 session of PP treatment [160.0 (127.8-184.3) vs. 275.0 (220.0-325.0) mmHg, P<0.001], the duration of MV and ICU stay in the PP group were significantly shorter than those in the SP group [84.0 (64.0-122.0) vs. 120.0 (97.0-182.0) h, P<0.001; 6.0 (5.0-8.0) vs. 8.0 (6.0-12.0) days, P<0.001, respectively]. No adverse events were observed during the PP even in patients with intra-aortic balloon pump (IABP). Conclusions: Early PP treatment is effective and safe for patients with moderate to severe ARDS after cardiac surgery and it is even safe in a subgroup placed with IABP.

Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.

Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune cells with strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM activity of NK cells engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 NK cells were superior to IL-15 NK cells both in terms of safety and long-term anti-tumor activity, with locoregionally administered IL-15 NK cells proving toxic and ineffective at tumor control. IL-21 NK cells displayed a unique chromatin accessibility signature, with CCAAT/enhancer-binding proteins (C/EBP), especially CEBPD, serving as key transcription factors regulating their enhanced function. Deletion of CEBPD resulted in loss of IL-21 NK cell potency while its overexpression increased NK cell long-term cytotoxicity and metabolic fitness. These results suggest that IL-21, through C/EBP transcription factors, drives epigenetic reprogramming of NK cells, enhancing their anti-tumor efficacy against GBM.

CSAM: A 2.5D Cross-Slice Attention Module for Anisotropic Volumetric Medical Image Segmentation.

A large portion of volumetric medical data, especially magnetic resonance imaging (MRI) data, is anisotropic, as the through-plane resolution is typically much lower than the in-plane resolution. Both 3D and purely 2D deep learning-based segmentation methods are deficient in dealing with such volumetric data since the performance of 3D methods suffers when confronting anisotropic data, and 2D methods disregard crucial volumetric information. Insufficient work has been done on 2.5D methods, in which 2D convolution is mainly used in concert with volumetric information. These models focus on learning the relationship across slices, but typically have many parameters to train. We offer a Cross-Slice Attention Module (CSAM) with minimal trainable parameters, which captures information across all the slices in the volume by applying semantic, positional, and slice attention on deep feature maps at different scales. Our extensive experiments using different network architectures and tasks demonstrate the usefulness and generalizability of CSAM. Associated code is available at https://github.com/aL3x-O-o-Hung/CSAM.

Application of a simplified transesophageal echocardiography examination sequence in high-risk cardiac surgery.

BACKGROUND: In cardiac surgical procedures, patients carrying high-risk profiles are prone to encompass complicated cardiopulmonary bypass (CPB) separation. Intraoperative transesophageal echocardiography (TEE), a readily available tool, is utilized to detect cardiac structural and functional pathologies as well as to facilitate clinical management of CPB separation, especially in the episodes of hemodynamic compromise. However, the conventional TEE examination, always performed in a liberal fashion without any restriction of view acquisition, is relatively time-consuming; there appear its flaws in the context of critically severe status. We therefore developed the perioperative rescue transesophageal echocardiography (PReTEE), a simplified three-view TEE protocol consisting of midesophageal four chamber, midesophageal left ventricular long axis, and transgastric short axis. METHODS: This is a single-center and randomized controlled trial which will be implemented in Peking Union Medical College Hospital, Beijing, China. A total of 46 TEE scans are schemed to be performed by 6 operators participating in and randomly assigned to either the PReTEE or the conventional TEE group. This study is purposed to investigate whether the efficiency of discriminating leading causes of difficult CPB wean-off can be significantly improved via an abbreviated sequence of TEE views. The primary outcome of interest is the difference between the groups of PReTEE and the conventional TEE in the successful discrimination of etiologies in specified 120 s. Cox proportional hazards model will be further employed to calculate the outcome difference. DISCUSSION: The estimated results of this trial are oriented at verifying whether a simplified TEE exam sequence can improve the efficiency of etiologies discrimination during CPB separation in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05960552. Registered on 6 July 2023.

Nanocrystalline transition metal tetraborides as efficient electrocatalysts for hydrogen evolution reaction at the large current density.

While great efforts have been made to improve the electrocatalytic activity of existing materials toward hydrogen evolution reaction (HER), it is also importance for searching new type of nonprecious HER catalysts to realize the practical hydrogen evolution. Herein, we firstly report nanocrystalline transition metal tetraborides (TMB4, TM=W and Mo) as an efficient HER electrocatalyst has been synthesized by a single-step solid-state reaction. The optimized nanocrystalline WB4 exhibits an overpotential as low as 172 mV at 10 mA/cm2 and small Tafel slope of 63 mV/dec in 0.5 M H2SO4. Moreover, the nanocrystalline WB4 outperforms the commercial Pt/C at high current density region, confirming potential applications in industrially electrochemical water splitting. Theoretical study reveals that high intrinsic HER activity of WB4 is originated from its large work function that contributes to the weak hydrogen-adsorption energy. Therefore, this work provides new insights for development of robust nanocrystalline electrocatalysts for efficient HER.

Soil organic carbon formation efficiency from straw/stover and manure input and its drivers: Estimates from long-term data in global croplands.

New soil organic carbon (SOC) formation in cropland from straw/stover or manure input is a vital source of SOC for climate change mitigation. However, location and variations in the efficiency, specifically the ratio of new SOC formation to organic C input (NCE), remain unquantified globally. In this study, the spatial variability of cropland NCE from straw/stover or manure input and explanatory factors were determined by analyzing 897 pairs of long-term field measurements from 404 globally distributed sites and by mapping grid-level cropland NCEs. The global NCE for paddy and upland averaged 13.8% (8.7%-25.1%, 5th-95th percentile) and 10.9% (6.8%-17.3%), respectively. The initial SOC and the clay content of soil, rather than temperature, were the most important factors regulating NCE. A parabola with an apex at approximately 17 g kg-1 between the initial SOC and NCE was resolved, and a positive correlation between soil clay content and NCE was observed. High-resolution mapping of the global NCE derived from manure/straw and insight into NCE dynamics provide a benchmark for diagnosing cropland soil C dynamics under climate change and identifying priority regions and actions for C management.

Epidemiologic and genetic associations between primary biliary cholangitis and extrahepatic rheumatic diseases.

Patients with primary biliary cholangitis (PBC) commonly experience extrahepatic rheumatic diseases. However, the epidemiologic and genetic associations as well as causal relationship between PBC and these extrahepatic conditions remain undetermined. In this study, we first conducted systematic review and meta-analyses by analyzing 73 studies comprising 334,963 participants across 17 countries and found strong phenotypic associations between PBC and rheumatic diseases. Next, we utilized large-scale genome-wide association study summary data to define the shared genetic architecture between PBC and rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Sjögren's syndrome (SS). We observed significant genetic correlations between PBC and each of the four rheumatic diseases. Pleiotropy and heritability enrichment analysis suggested the involvement of humoral immunity and interferon-associated processes for the comorbidity. Of note, we identified four variants shared between PBC and RA (rs80200208), SLE (rs9843053), and SSc (rs27524, rs3873182) using cross-trait meta-analysis. Additionally, several pleotropic loci for PBC and rheumatic diseases were found to share causal variants with gut microbes possessing immunoregulatory functions. Finally, Mendelian randomization revealed consistent evidence for a causal effect of PBC on RA, SLE, SSc, and SS, but no or inconsistent evidence for a causal effect of extrahepatic rheumatic diseases on PBC. Our study reveals a profound genetic overlap and causal relationships between PBC and extrahepatic rheumatic diseases, thus providing insights into shared biological mechanisms and novel therapeutic interventions.

ZDHHC9-mediated Bip/GRP78 S-palmitoylation inhibits unfolded protein response and promotes bladder cancer progression.

Recent studies have highlighted palmitoylation, a novel protein post-translational modification, as a key player in various signaling pathways that contribute to tumorigenesis and drug resistance. Despite this, its role in bladder cancer (BCa) development remains inadequately understood. In this study, ZDHHC9 emerged as a significantly upregulated oncogene in BCa. Functionally, ZDHHC9 knockdown markedly inhibited tumor proliferation, promoted tumor cell apoptosis, and enhanced the efficacy of gemcitabine (GEM) and cisplatin (CDDP). Mechanistically, SP1 was found to transcriptionally activate ZDHHC9 expression. ZDHHC9 subsequently bound to and palmitoylated the Bip protein at cysteine 420 (Cys420), thereby inhibiting the unfolded protein response (UPR). This palmitoylation at Cys420 enhanced Bip's protein stability and preserved its localization within the endoplasmic reticulum (ER). ZDHHC9 might become a novel therapeutic target for BCa and could also contribute to combination therapy with GEM and CDDP.

Development and interpretation of a multimodal predictive model for prognosis of gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal original tumor in gastrointestinal (GI) tract and is considered to have varying malignant potential. With the advancement of computer science, radiomics technology and deep learning had been applied in medical researches. It's vital to construct a more accurate and reliable multimodal predictive model for recurrence-free survival (RFS) aiding for clinical decision-making. A total of 254 patients underwent surgery and pathologically diagnosed with GIST in The First Hospital of China Medical University from 2019 to 2022 were included in the study. Preoperative contrast enhanced computerized tomography (CE-CT) and hematoxylin/eosin (H&E) stained whole slide images (WSI) were acquired for analysis. In the present study, we constructed a sum of 11 models while the multimodal model (average C-index of 0.917 on validation set in 10-fold cross validation) performed the best on external validation cohort with an average C-index of 0.864. The multimodal model also reached statistical significance when validated in the external validation cohort (n = 42) with a p-value of 0.0088 which pertained to the recurrence-free survival (RFS) comparison between the high and low groups using the optimal threshold on the predictive score. We also explored the biological significance of radiomics and pathomics features by visualization and quantitative analysis. In the present study, we constructed a multimodal model predicting RFS of GIST which was prior over unimodal models. We also proposed hypothesis on the correlation between morphology of tumor cell and prognosis.

Bacterial and fungal communities regulated directly and indirectly by tobacco-rape rotation promote tobacco production.

Tobacco continuous cropping is prevalent in intensive tobacco agriculture but often leads to microbial community imbalance, soil nutrient deficiency, and decreased crop productivity. While the tobacco-rape rotation has demonstrated significant benefits in increasing tobacco yield. Microorganisms play a crucial role in soil nutrient cycling and crop productivity. However, the internal mechanism of tobacco-rape rotation affecting tobacco yield through microbe-soil interaction is still unclear. In this study, two treatments, tobacco continuous cropping (TC) and tobacco-rape rotation (TR) were used to investigate how planting systems affect soil microbial diversity and community structure, and whether these changes subsequently affect crop yields. The results showed that compared with TC, TR significantly increased the Shannon index, Chao1 index, ACE index of bacteria and fungi, indicating increased microbial α-diversity. On the one hand, TR may directly affect the bacterial and fungal community structure due to the specificity of root morphology and root exudates in rape. Compared with TC, TR significantly increased the proportion of beneficial bacterial and fungal taxa while significantly reduced soil-borne pathogens. Additionally, TR enhanced the scale and complexity of microbial co-occurrence networks, promoting potential synergies between bacterial OTUs. On the other hand, TR indirectly changed microbial community composition by improving soil chemical properties and changing microbial life history strategies. Compared with TC, TR significantly increased the relative abundance of copiotrophs while reduced oligotrophs. Notably, TR significantly increased tobacco yield by 39.6% compared with TC. The relationships among yield, microbial community and soil chemical properties indicated that planting systems had the greatest total effect on tobacco yield, and the microbial community, particularly bacteria, had the greatest direct effect on tobacco yield. Our findings highlighted the potential of tobacco-rape rotation to increase yield by both directly and indirectly optimizing microbial community structure.

Pre-operative prediction of histopathological growth patterns of colorectal cancer liver metastasis using MRI-based radiomic models.

PURPOSE: Histopathological growth patterns (HGPs) of colorectal liver metastases (CRLMs) have prognostic value. However, the differentiation of HGPs relies on postoperative pathology. This study aimed to develop a magnetic resonance imaging (MRI)-based radiomic model to predict HGP pre-operatively, following the latest guidelines. METHODS: This retrospective study included 93 chemotherapy-naïve patients with CRLMs who underwent contrast-enhanced liver MRI and a partial hepatectomy between 2014 and 2022. Radiomic features were extracted from the tumor zone (RTumor), a 2-mm outer ring (RT+2), a 2-mm inner ring (RT-2), and a combined ring (R2+2) on late arterial phase MRI images. Analysis of variance method (ANOVA) and least absolute shrinkage and selection operator (LASSO) algorithms were used for feature selection. Logistic regression with five-fold cross-validation was used for model construction. Receiver operating characteristic curves, calibrated curves, and decision curve analyses were used to assess model performance. DeLong tests were used to compare different models. RESULTS: Twenty-nine desmoplastic and sixty-four non-desmoplastic CRLMs were included. The radiomic models achieved area under the curve (AUC) values of 0.736, 0.906, 0.804, and 0.794 for RTumor, RT-2, RT+2, and R2+2, respectively, in the training cohorts. The AUC values were 0.713, 0.876, 0.785, and 0.777 for RTumor, RT-2, RT+2, and R2+2, respectively, in the validation cohort. RT-2 exhibited the best performance. CONCLUSION: The MRI-based radiomic models could predict HGPs in CRLMs pre-operatively.

Advanced gene nanocarriers/scaffolds in nonviral-mediated delivery system for tissue regeneration and repair.

Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration.

Low estimated glomerular filtration rate and high body mass index are risk factors for acute kidney injury in systemic lupus erythematosus patients after cardiac surgery.

Objective: The occurrence of acute kidney injury (AKI) is common following cardiac surgery, especially among patients characterized with systemic lupus erythematosus (SLE), but studies on this clinical scenario have been limited by the rarity of SLE. We aimed to explore the risk predictors and outcomes with regards to postoperative AKI among cardiac-surgical patients concomitant with SLE. Methods: This was a single-center retrospective study performed in a tertiary hospital. Adult patients diagnosed with SLE who underwent cardiac surgery within the last 22 years were enrolled. Essential variables, including patient-, surgery- and anesthesia-related information, were collected from the medical record system. The definition of AKI was derived from the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Risk predictors suspected to be linked with post-surgical AKI were calculated using the univariable and multivariable analyses. Results: Of all 59 SLE patients undergoing cardiac surgery, 57 were ultimately enrolled into the analysis. AKI occurred in 29 patients (50.9%), who had significantly longer extubation time (median difference 1.0 day, P < 0.001), ICU length of stay (median difference 2.0 days, P = 0.001), postoperative length of stay (median difference 5.0 days, P = 0.026), and more postoperative major complications (odds ratio 10.29, P = 0.025) than the others. Preoperative estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 (odds ratio 5.31, P = 0.021) and body mass index (BMI) ≥ 24 kg/m2 (odds ratio 4.32, P = 0.043) were the only two factors in the multivariable analysis that were significantly correlated with the development of postoperative AKI in patients with SLE after cardiac surgery. Conclusion: AKI in SLE patients after cardiac surgery is common and requires scrutiny, especially in overweight patients with moderate to severe preoperative renal dysfunction.

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.