Liquid biopsy of oesophageal squamous cell carcinoma: implications in diagnosis, prognosis, and treatment monitoring.

Oesophageal squamous cell carcinoma (ESCC) is a common malignant tumour of the gastrointestinal tract. Early detection and access to appropriate treatment are crucial for the long-term survival of patients. However, limited diagnostic and monitoring methods are available for identifying early stage ESCC. Endoscopic screening and surgical resection are commonly used to diagnose and treat early ESCC. However, these methods have disadvantages, such as high recurrence, lethality, and mortality rates. Therefore, methods to improve early diagnosis of ESCC and reduce its mortality rate are urgently required. In 1961, Gary et al. proposed a novel liquid biopsy approach for clinical diagnosis. This involved examining exosomes, circulating tumour cells, circulating free DNA, and circulating free RNA in body fluids. The ability of liquid biopsy to obtain samples repeatedly, wide detection range, and fast detection speed make it a feasible option for non-invasive tumour detection. In clinical practice, liquid biopsy technology has gained popularity for early screening, diagnosis, treatment efficacy monitoring, and prognosis assessment. Thus, this is a highly promising examination method. However, there have been no comprehensive reviews on the four factors of liquid biopsy in the context of ESCC. This review aimed to analyse the progress of liquid biopsy research for ESCC, including its classification, components, and potential future applications.

Pancreas-directed AAV8-hSPINK1 gene therapy safely and effectively protects against pancreatitis in mice.

OBJECTIVE: Currently, there is no cure for chronic pancreatitis (CP). Germline loss-of-function variants in SPINK1 (encoding trypsin inhibitor) are common in patients with CP and are associated with acute attacks and progression of the disease. This preclinical study was conducted to explore the potential of adeno-associated virus type 8 (AAV8)-mediated overexpression of human SPINK1 (hSPINK1) for pancreatitis therapy in mice. DESIGN: A capsid-optimised AAV8-mediated hSPINK1 expression vector (AAV8-hSPINK1) to target the pancreas was constructed. Mice were treated with AAV8-hSPINK1 by intraperitoneal injection. Pancreatic transduction efficiency and safety of AAV8-hSPINK1 were dynamically evaluated in infected mice. The effectiveness of AAV8-hSPINK1 on pancreatitis prevention and treatment was studied in three mouse models (caerulein-induced pancreatitis, pancreatic duct ligation and Spink1 c.194+2T>C mouse models). RESULTS: The constructed AAV8-hSPINK1 vector specifically and safely targeted the pancreas, had low organ tropism for the heart, lungs, spleen, liver and kidneys and had a high transduction efficiency (the optimal expression dose was 2×1011 vg/animal). The expression and efficacy of hSPINK1 peaked at 4 weeks after injection and remained at significant level for up to at least 8 weeks. In all three mouse models, a single dose of AAV8-hSPINK1 before disease onset significantly alleviated the severity of pancreatitis, reduced the progression of fibrosis, decreased the levels of apoptosis and autophagy in the pancreas and accelerated the pancreatitis recovery process. CONCLUSION: One-time injection of AAV8-hSPINK1 safely targets the pancreas with high transduction efficiency and effectively ameliorates pancreatitis phenotypes in mice. This approach is promising for the prevention and treatment of CP.

Self-expandable metallic stents may be more efficient than balloon dilatation alone for esophageal stricture after circumferential endoscopic submucosal dissection: a retrospective cohort study in China.

INTRODUCTION: Self-expandable metallic stents (SEMSs) can be used to treat esophageal stricture after circumferential endoscopic submucosal dissection (ESD), but its efficacy and placement timing remain to be determined. In this study, the treatment time and number of dilatations were compared between the SEMS placement group and the balloon dilatation (BD) group to clarify the efficacy and placement time of SEMSs in the treatment of esophageal stricture after circumferential esophageal ESD. METHODS: This was a retrospective cohort study. Patients with esophageal stricture after circumferential ESD between January 2015 and January 2020 were included. Data on the patients' demographic characteristics, esophageal lesion-related factors, esophageal stricture occurrence, and measures taken to treat the stricture were collected. The primary outcome was the treatment time, and the secondary outcome was the number of dilatations. RESULTS: The total number of dilatations was 30 in the SEMS group and 106 in the BD group. The average number of dilatations in the SEMS group (1.76 ± 1.64) was significantly lower than that in the BD group (4.42 ± 5.32) (P = 0.016). Among the patients who underwent SEMS placement first had a shorter treatment time (average 119 days) than those who underwent BD first (average 245 days) (P = 0.041), and the average number of dilatations inpatients who underwent SEMS placement first (0.71 ± 1.07) was significantly lower than that in the patients who underwent BD first (2.5 ± 1.54). CONCLUSION: SEMSs were more efficient in the treatment of esophageal stricture in a cohort of patients after circumferential esophageal ESD.

Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.

Microplastics are detected in human gallstones and have the ability to form large cholesterol-microplastic heteroaggregates.

Ubiquitous pollution due to microplastics through the food chain is a major cause of various deleterious effects on the human health. The aim of this study was to determine the existence of microplastics and the internal mechanism of microplastics as accelerators of cholelithiasis. Gallstones were collected from 16 patients after cholecystectomy, and microplastics in the gallstones were detected through laser direct infrared and pyrolysis gas chromatographymass spectrometry examinations. Mice model of gallstone were constructed with or without different diameters of microplastic (0.5, 5 and 50 µm). The affinity between microplastic and cholesterol or bilirubin was tested by co-culturing and qualified using molecular dynamics simulations. Finally, altered gut microbiota among the groups were identified using 16 s rRNA sequencing. The presence of microplastics in the gallstones of all the patients were confirmed. Microplastic content was significantly higher in younger chololithiasis patients (age<50 years). Mice fed a high-cholesterol diet with microplastic drinks showed more severe chololithiasis. In terms of the mechanism, microplastics showed a higher affinity for cholesterol than for bilirubin. Significant alterations in the gut microbiota have also been identified after microplastic intake in mice. Our study revealed the presence of microplastics in human gallstones, showcasing their potential to aggravate chololithiasis by forming large cholesterol-microplastic heteroaggregates and altering the gut microbiota.

Genetic Factors Associated With Adverse Pregnancy Outcomes in Chronic Pancreatitis.

INTRODUCTION: The effects of genetic factors on pregnancy outcomes in chronic pancreatitis (CP) patients remain unclear. We evaluated the impacts of clinical features and mutations in main CP-susceptibility genes ( SPINK1 , PRSS1 , CTRC , and CFTR ) on pregnancy outcomes in Chinese CP patients. METHODS: This was a prospective cohort study with 14-year follow-up. The sample comprised female CP patients with documented pregnancy and known genetic backgrounds. Adverse pregnancy outcomes were compared between patients with and without gene mutations. Univariate and multivariate analyses were performed to determine the impact factors for adverse pregnancy outcomes. RESULTS: Totally, 160 female CP patients with a pregnancy history were enrolled; 59.4% of patients carried pathogenic mutations in CP-susceptibility genes. Adverse pregnancy outcomes occurred in 38 patients (23.8%); the prevalence of adverse outcomes was significantly higher in those harboring gene mutations than those without (30.5% vs 13.8%, P = 0.015). Notably, the rates of preterm delivery (12.6% vs 3.1%, P = 0.036) and abortion (17.9% vs 4.6%, P = 0.013) were remarkably higher in patients with gene mutations (especially SPINK1 mutations) than those without. In multivariate analyses, both CP-susceptibility gene mutations (odds ratio, 2.52; P = 0.033) and SPINK1 mutations (odds ratio, 2.60; P = 0.037) significantly increased the risk of adverse pregnancy outcomes. Acute pain attack during pregnancy was another risk factor for adverse pregnancy outcomes. DISCUSSION: Pathogenic mutations in CP-susceptibility genes, especially SPINK1 , were independently related to adverse pregnancy outcomes in CP patients. Significant attention should be paid to pregnant females harboring CP-susceptibility gene mutations (ClinicalTrials.gov: NCT06055595).

pH-responsive CuS/DSF/EL/PVP nanoplatform alleviates inflammatory bowel disease in mice via regulating gut immunity and microbiota.

The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu2+. Further, the main in vivo metabolite of DSF can bind to Cu2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia-Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus, and Bifidobacterium, indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. STATEMENT OF SIGNIFICANCE: Our study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions.

Pirfenidone alleviates chronic pancreatitis via suppressing the activation of pancreatic stellate cells and the M1 polarization of macrophages.

In the realm of fibroinflammatory conditions, chronic pancreatitis (CP) stands out as a particularly challenging ailment, lacking a dedicated, approved treatment. The potential of Pirfenidone (PFD), a drug originally used for treating idiopathic pulmonary fibrosis (IPF), in addressing CP's fibrotic aspects has sparked new interest. This investigation focused on the role of PFD in diminishing fibrosis and immune response in CP, using a mouse model induced by caerulein. The research extended to in vitro studies examining the influence of PFD on pancreatic stellate cells' (PSCs) behavior and the polarization of macrophages into M1 and M2 types. Advanced techniques like RNA sequencing and comprehensive data analyses were employed to decode the molecular interactions of PFD with PSCs. Supplementary experiments using techniques such as quantitative real-time PCR, western blotting, and immunofluorescence were also implemented. Results showed a notable reduction in pancreatic damage in PFD-treated mice, manifested through decreased acinar cell atrophy, lower collagen deposition, and a reduction in macrophage presence. Further investigation revealed PFD's capacity to hinder PSCs' migration, growth, and activation, alongside a reduction in the production and secretion of extracellular matrix proteins. This effect is primarily achieved by interfering with signaling pathways such as TGF-ß/Smad, Wnt/ß-catenin, and JAK/STAT. Additionally, PFD selectively hampers M1 macrophage polarization through the STAT3 pathway, without impacting M2 polarization. These outcomes highlight PFD's dual mechanism in moderating PSC activity and M1 macrophage polarization, positioning it as a promising candidate for CP therapy.

A Novel Serum Exosomal miRNA Signature in the Early Prediction of Persistent Organ Failure in Patients with Acute Pancreatitis.

OBJECTIVE: Current study aims to investigate whether serum exosomal microRNAs (miRNAs) could be potential biomarkers in predicting APs with POF at early phase. BACKGROUND: Novel biomarkers are sorely needed for early prediction of persistent organ failure (POF) in acute pancreatitis (AP) patients. METHODS: In the discovery stage, exosomal miRNAs were profiled in sera from APs with or without POF (5 vs. 5) using microarrays. POF-associated miRNA signatures then were assessed in training cohort (n=227) and further validated in three independent cohorts (n=516), including one nested case-control cohort. RESULTS: A total of 743 APs were recruited in this large-scale biomarker identification study with a nested case-control study. Data from the discovery cohort demonstrated that 90 exosomal miRNAs were significantly dysregulated in APs with POF compared with controls. One miRNA classifier (Cmi) comprising 3 miRNAs (miR-4265, 1208, 3127-5p) was identified in the training cohort, and was further evaluated in two validation cohorts for their predictive value for POF. AUCs for Cmi ranged from 0.88 to 0.90, which was statistically superior to AUCs of APACHE-II and BISAP, and outperformed BUN and creatinine in POF prediction across all cohorts (P<.05). Higher levels of Cmi indicated increased need for ICU admission, prolonged hospitalization, and elevated mortality rate, thus poor prognosis. In the nested case-control study, Cmi could help identify prediagnostic POF in post-ERCP pancreatitis cases within "golden hours" after ERCP with high efficacy. CONCLUSIONS: Serum exosomal Cmi may be an early predictor for POF in AP, even within "golden hours" after AP onset. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02602808).

Serum urate is associated with an increased risk of inflammatory bowel disease: A bidirectional Mendelian randomization study.

BACKGROUND: Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). However, it remains unclear whether the observations are causal because of confounding factors. AIM: To investigate the causal associations between urate levels and IBD using bidirectional Mendelian randomization (MR). METHODS: Independent genetic variants for urate levels and IBD were selected as instrumental variables from published genome-wide association studies (GWASs). Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD (the UK Biobank, the FinnGen database and a large GWAS meta-analysis) and one for urate levels (a large GWAS meta-analysis). MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger and sensitivity analyses (MR-PRESSO). A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model. RESULTS: Genetically higher serum urate levels were strongly associated with an increased risk of UC [odds ratio (OR): 1.95, 95% confidence interval (CI): 1.86-2.05] after outlier correction, and the ORs (95%CIs) for IBD and CD were 0.94 (95%CI: 0.86-1.03) and 0.91 (95%CI: 0.80-1.04), respectively. Animal studies have confirmed the positive association between urate levels and UC. Moreover, genetically predicted IBD was inversely related to urate levels (OR: 0.97, 95%CI: 0.94-0.99). However, no association was observed between genetically influenced UC or CD and urate levels. CONCLUSION: Urate levels might be risk factors for UC, whereas genetically predicted IBD was inversely associated with urate levels. These findings provide essential new insight for treating and preventing IBD.

One-day versus three-day low-residue diet bowel preparation regimens before colonoscopy: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Although studies have shown that the quality of bowel preparation with low-residue diet (LRD) is as effective as that of clear fluid diet (CLD), there is currently no consensus on how long an LRD should last. The aim of this study was to compare a 1-day versus 3-day LRD on bowel preparation before colonoscopy. METHODS: A systematic review search was conducted in MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane database from inception to April 2023. We identified randomized controlled trials (RCTs) that compared 1-day with 3-day LRD bowel cleansing regiments for patients undergoing colonoscopy. The rate of adequate bowel preparation, polyp detection rate, adenoma detection rate, tolerability, willingness to repeat preparation, and adverse events were estimated using odds ratios (OR) and 95% confidence interval (CI). We also performed meta-analysis to identify risk factors and predictors of inadequate preparation. RESULTS: Four studies published between 2019 and 2023 with 1927 participants were included. The present meta-analysis suggested that 1-day LRD was comparable with 3-day LRD for adequate bowel preparation (OR 0.89; 95% CI, 0.65-1.21; P = 0.45; I2  = 0%; P = 0.52). The polyp detection rate (OR 0.94; 95% CI, 0.77-1.14; P = 0.52; I2  = 23%; P = 0.27) and adenoma detection rate (OR 0.87; 95% CI, 0.71-1.08; P = 0.21; I2  = 0%; P = 0.52) were similar between the groups. There were significantly higher odds of tolerability in patients consuming 1-day LRD compared with 3-day LRD (OR 1.64; 95% CI, 1.13-2.39; P < 0.01; I2  = 47%; P = 0.15). In addition, constipation was identified as the independent predictor of inadequate preparation (OR 1.98; 95% CI, 1.27-3.11; P < 0.01; I2  = 0%; P = 0.46). CONCLUSION: The present study demonstrated that a 1-day LRD was as effective as a 3-day CLD in the quality of bowel preparation before colonoscopy and significantly improved tolerability of patients. In addition, constipation is an independent risk factor of poor bowel preparation, and the duration of LRD in patients with constipation still needs further clinical trials.

A Human Adenovirus C Infection-Related Gene Panel for Predicting Survival and Treatment Responsiveness in Glioma Patients.

BACKGROUND: Viruses are critical for the regulation of cancer development and for therapy. Human adenovirus C (HadVC) has been detected in central nervous system and glioma tissue. The objective of the present study was the development of a robust prognostic model based on HadVC infection (HadVCi)-relevant genes. METHODS: The genome, transcriptome, and virome were systemically analyzed using The Cancer Genome Atlas dataset for training and 2 cohorts from the Chinese Glioma Genome Atlas and an immunotherapy trial cohort with 17 patients receiving anti-PD-1 treatment for validation. HadVCi-relevant gene selection from differentially expressed genes between HadVC-infected and non-HadVC-infected glioma patients using least absolute shrinkage and selection operator regression was followed by Cox regression modeling to establish a prognostic HadVCi score. Kaplan-Meier and receiver operating characteristic curve analyses were performed to estimate the predictive capacity of the HadVCi score. The χ2, Spearman, and Mann-Whitney U tests were used to identify the correlation with the clinicopathological parameters, treatment responsiveness, and immune landscape. Temozolomide-resistant glioma cells were established and analyzed at the transcriptional level using RNA sequencing data. RESULTS: The HadVCi score was (-0.2526673∗TRPC6) + (-0.2244276∗RNF207) + (-0.0894468∗SEC31B) + (-0.0190214∗ZCRB1) + (-0.017122∗DNPH1) + (0.0495818∗CCDC34) + (0.1196349∗PURG) + (0.1778997∗LILRA5). The score possesses a strong ability to predict overall survival. Further analysis revealed a higher HadVCi score correlated with a malignant phenotype and poorer treatment responsiveness to temozolomide-based chemotherapy and combined therapies. Additionally, transcriptomic analysis showed malignancy-, stemness-, and radioresistant-related gene activation in the HadVCi group, which characterized the poor outcomes and limited sensitivity to standard therapy. CONCLUSIONS: The HadVCi score could be an effective tool for survival prediction and treatment guidance for patients with glioma.

A pan-cancer analysis of the oncogenic role of Golgi transport 1B in human tumors.

Background: Owing to the aggressiveness and treatment-refractory nature of cancer, ideal candidates for early diagnosis and treatment are needed. Golgi transport 1B (GOLT1B) has been associated with cellular malignant behaviors and immune responses in colorectal and lung cancer, but a systematic pan-cancer analysis on GOLT1B has not been conducted. Methods: The expression status and clinical association of GOLT1B in The Cancer Genome Atlas (TCGA) were analyzed. Genetic and methylation alterations in GOLT1B were explored. The relationship between GOLT1B and immune cell infiltration was also investigated. Genes related to GOLT1B expression were selected and analyzed. Results: GOLT1B was highly expressed in most tumors, and there was a positive correlation between GOLT1B expression and clinical pathological parameters. High expression levels of GOLT1B have been associated with poor prognosis of most cancers. Copy number amplification was the primary type of GOLT1B genetic alterations, which was related to the prognosis of pan-cancer cases. There were different levels of GOLT1B promoter methylation across cancer types. The methylation level of the probe cg07371838 and cg25816357 was closely associated with prognosis in diverse cancers. There was also a positive correlation between GOLT1B genetic alterations and CD4+ T lymphocytes, especially the Th2 subset, as well as between GOLT1B expression and the estimated infiltration value of cancer-associated fibroblasts. Serine/threonine kinase receptor-associated protein (STRAP), integrator complex subunit 13 (INTS13), and ethanolamine kinase 1 (ETNK1) were the most relevant genes for GOLT1B expression, and their interactions with GOLT1B were involved in regulating the transforming growth factor (TGF)-ß receptor signaling pathway and epithelial-mesenchymal transition (EMT). Conclusions: This pan-cancer analysis provided a comprehensive understanding of the oncogenic role of GOLT1B, highlighting a potential mechanism whereby GOLT1B influences the tumor microenvironment, as well as cancer immunotherapy.

Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.

BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).

Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention: A Secondary Analysis of the OPT-PEACE Randomized Clinical Trial.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.