Eosinophilia and Adverse Effects of Dupilumab for Respiratory Indications: A Real-World Setting.

BACKGROUND: Dupilumab has been used with significant benefit in the treatment of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Phase 3 clinical trials have demonstrated transient eosinophilia and rare eosinophil-related and other adverse effects. OBJECTIVE: To characterize dupilumab-associated eosinophilia (absolute eosinophil count [AEC] ≥ 1.5 x 103/µL within 36 weeks of dupilumab initiation) and adverse effects associated in real-world patients with asthma and CRSwNP in the United States. METHODS: Retrospective chart review of 251 patients on dupilumab for asthma and/or CRSwNP seen at a single institution. RESULTS: Among the 142 patients who had AECs checked before and after treatment, 16 (11.3%) patients had post-treatment eosinophilia, including 11 (7.7%) patients who had new eosinophilia upon dupilumab initiation. Thirteen patients with post-treatment eosinophilia remained on dupilumab, 10 of whom had resolution of eosinophilia. Eosinophil-related adverse effects were rare and cases of eosinophilic granulomatous polyangiitis (EGPA) were limited to 1 patient with eosinophilia and 1 patient with normal eosinophil levels on systemic steroids. Other adverse effects included arthralgias (13/251, 5.2%), rash (8/251, 3.2%), and conjunctivitis (7/251, 2.8%). All patients with pre-treatment eosinophilia and the majority of patients with post-treatment eosinophilia received significant treatment benefit for their respiratory disease with dupilumab. CONCLUSION: While dupilumab-associated eosinophilia is seen in a subset of patients, persistent eosinophilia or eosinophil-related adverse effects are rare. Furthermore, treatment benefit on dupilumab despite eosinophilia supports its continued use in both asthma and CRSwNP.

Advancing towards a unified eosinophil signature from transcriptional profiling.

Eosinophils are granulocytes that can accumulate in increased numbers in tissues and/or peripheral blood in disease. Phenotyping of eosinophils in health and disease has the potential to improve the precision of diagnosis and choice of therapies for eosinophilic-associated diseases. Transcriptional profiling of eosinophils has been plagued by cell fragility and difficulty isolating high quality RNA. With several technological advances, single-cell RNA sequencing (scRNA-seq) has become possible with eosinophils, at least from mice, while bulk RNA sequencing and microarrays have been performed in both murine and human samples. Anticipating more eosinophil transcriptional profiles in the coming years, we provide a summary of prior studies conducted on mouse and human eosinophils in blood and tissue, with a discussion of the advantages and potential pitfalls of various approaches. Common technical standards in studying eosinophil biology would help advance the field and make cross-study comparisons possible. Knowledge gaps and opportunities include identifying a minimal set of genes that define the eosinophil lineage, comparative studies between active disease and remission vs. homeostasis or development, especially in humans, and a comprehensive comparison between murine and human eosinophils at the transcriptional level. Characterizing such transcriptional patterns will be important to understanding the complex and diverse roles of eosinophils in both health and disease.

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.

Biologic therapy in rare eosinophil-associated disorders: remaining questions and translational research opportunities.

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.

Schottky heterojunction CeO2@MXene nanosheets with synergistic type I and type II PDT for anti-osteosarcoma.

Photodynamic therapy (PDT) has shown great potential for tumor treatment as the method is noninvasive, highly selective, and causes minimal side effects. However, conventional type II PDT, which relies on 1O2, presents poor therapeutic efficacy for hypoxic tumors due to its reliance on oxygen. Here, CeO2/Ti3C2-MXene (CeO2@MXene) hybrids were successfully designed by growing CeO2in situ using Ti3C2-MXene (MXene) nanosheets. CeO2@MXene serves as a reduction-oxidation (REDOX) center due to the presence of Ce in the lattice of CeO2 nanoparticles. This REDOX center reacts with H2O2 to generate oxygen and weakens the hypoxic tumor cell environment, achieving type II PDT. At the same time, many other ROS (such as ⋅O2- and ⋅OH) can be produced via a type I photodynamic mechanism (electron transfer process). The CeO2@MXene heterojunction performs nanoenzymatic functions for synergistic type I and type II PDT, which improves cancer treatment.

Post-Graphene 2D Materials: Structures, Properties, and Cancer Therapy Applications.

Cancer is one of the most serious diseases challenging human health and life span. Cancer has claimed millions of lives worldwide. Early diagnosis and effective treatment of cancer are very important for the survival of patients. In recent years, 2D nanomaterials have shown great potential in the development of anticancer treatment by combining their inherent physicochemical properties after surface modification. 2D nanomaterials have attracted great interest due to their unique nanosheet structure, large surface area, and extraordinary physicochemical properties. This article reviews the advantages and application status of emerging 2D nanomaterials for targeted tumor synergistic therapy compared with traditional therapeutic strategies. In order to investigate novel potential anticancer strategies, this paper focuses on the surface modification, cargo delivery capability, and unique optical properties of emerging 2D nanomaterials. Finally, the current problems and challenges in cancer treatment are summarized and prospected.

Prevalence and risk factors for persistent symptoms after COVID-19: a systematic review and meta-analysis.

BACKGROUND: Long-term physical and mental persistent symptoms after COVID-19 represent a growing global public health concern. However, there remains a substantial knowledge gap regarding their prevalence and risk factors. OBJECTIVES: To estimate the prevalence and risk factors for persistent symptoms after COVID-19. METHODS OF DATA SYNTHESIS: We used a random-effects model to pool persistent symptom prevalence and risk ratios comparing COVID-19 patients with non-COVID-19 individuals. DATA SOURCES: Electronic databases were searched for studies published from December 2019 to January 2023. STUDY ELIGIBILITY CRITERIA: Eligible studies that reported the prevalence and risk factors for persistent symptoms after COVID-19 were included. PARTICIPANTS: Patients who recovered from COVID-19. ASSESSMENT OF RISK OF BIAS: The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias in prevalence studies, whereas the risk of bias in cohort studies was evaluated with the Newcastle-Ottawa Scale. RESULTS: After screening 4359 studies, a total of 211 eligible studies were included, covering a population of 13 368 074 individuals. Fatigue, dyspnoea, post-traumatic stress disorder, anxiety, and depression were the most frequently reported persistent symptoms after COVID-19. Subgroup analyses revealed that individuals with more severe illness in the acute phase or from Europe exhibited a higher prevalence of certain symptoms, whereas children demonstrated a lower prevalence. Furthermore, COVID-19 patients had a significantly higher prevalence of most persistent symptoms compared with non-COVID-19 individuals. Factors frequently associated with a higher prevalence of persistent symptoms included female gender, advanced age, severe illness during the acute phase of COVID-19, multiple comorbidities, an extended duration of hospital stay, and a high body mass index. CONCLUSION: This meta-analysis provides a thorough review of the prevalence and risk factors for persistent symptoms following COVID-19. The findings underscore the importance of long-term monitoring and support for individuals recovering from COVID-19.

A Cell-Free Protein Synthesis Platform to Produce a Clinically Relevant Allergen Panel.

Allergens are used in the clinical diagnosis (e.g., skin tests) and treatment (e.g., immunotherapy) of allergic diseases. With growing interest in molecular allergy diagnostics and precision therapies, new tools are needed for producing allergen-based reagents. As a step to address this need, we demonstrate a cell-free protein synthesis approach for allergen production of a clinically relevant allergen panel composed of common allergens spanning a wide range of phylogenetic kingdoms. We show that allergens produced with this approach can be recognized by allergen-specific immunoglobulin E (IgE), either monoclonals or in patient sera. We also show that a cell-free expressed allergen can activate human cells such as peripheral blood basophils and CD34+ progenitor-derived mast cells in an IgE-dependent manner. We anticipate that this cell-free platform for allergen production will enable diagnostic and therapeutic technologies, providing useful tools and treatments for both the allergist and allergic patient.

Distinct CRTH2+CD161+ (peTh2) memory CD4+ T-cell cytokine profiles in food allergy and eosinophilic gastrointestinal disorders.

INTRODUCTION: Although IgE-mediated food allergy (FA) and eosinophilic gastrointestinal disorders (EGID) are clinically distinct and treated differently, pathogenic effector Th2 (peTh2) cells are implicated in the pathogenesis of both FA and EGID. The aim of this study was to better characterize peTh2 cells in the context of FA and EGID and the overlap between these two conditions. METHODS: Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7). Overnight peripheral blood mononuclear cell (PBMC) culture supernatants were assessed for cytokine production by multiplex analysis. RESULTS: CRTH2+CD161+ (peTh2) memory CD4+ T cells were significantly increased in both patients with FA and those with ALL_EGID (inclusive of EGID+FA+FT, EGID+FT and ONLY_EGID) when compared to HV. However, ALL_EGID patients, particularly those with EGID+FA+FT, had significantly elevated IL-5+IL-13+ peTh2 cells, whereas FA patients had significantly elevated IFN-γ or IL-17A-expressing peTh2 cells. This finding was supported by increased spontaneous IL-5 and IL-13 production in overnight cultures of PBMC from EGID+FA+FT patients compared to spontaneous IL-10 and IFN-γ production by PBMC from FA patients. FA patients had increased IL-9, IL-10, IL-17A, and IFN-γ production in overnight cultures of stimulated PBMC. CONCLUSIONS: EGID and IgE-mediated FA share a common cell subtype defined by specific surface markers and termed CRTH2+CD161+ (peTh2) memory CD4+ T cells. However, the cytokine profiles of these CRTH2+CD161+ (peTh2) memory CD4+ T cells are markedly different between the two disorders.

Biologics and Hypereosinophilic Syndromes: Knowledge Gaps and Controversies.

Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders defined by blood and/or tissue hypereosinophilia and clinical manifestations attributable to the eosinophilia. Although various clinical subtypes of HES have been described, the general approach to therapy in all subtypes has focused on the reduction of blood and tissue eosinophilia to improve symptoms and halt disease progression. Until recently, this typically involved the use of corticosteroids and/or other immunosuppressive or cytotoxic drugs with significant toxicity. Whereas imatinib, the first targeted therapy approved for treatment of HES, has dramatically changed the prognosis of patients with primary (myeloid) forms of HES, it is ineffective in patients with other HES subtypes. For these nonmyeloid patients with HES, the development of eosinophil-targeting biologics (most notably, mepolizumab, the first biologic approved for the treatment of HES) has been transformative. Nevertheless, important issues remain with respect to the efficacy and safety of these biologics in the treatment of the varied subtypes of HES. Moreover, with the increasing number of commercially available biologics with direct or indirect effects on eosinophils, questions related to the choice of initial biologic, potential reasons for biologic failure, and treatment options in the setting of incomplete response are becoming increasingly common.

Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients.

Patients on dialysis have dysfunctions of innate and adaptive immune system responses. The transcriptional factor IRF8 (interferon regulatory factor 8) is primarily expressed in plasmacytoid cells (pDCs) and myeloid dendritic cells (mDCs), playing a crucial role in the maturation of dendritic cells, monocytes, and macrophages, and contributing to protection against bacterial infections. The current study analyzed the expression patterns of IRF8 and assessed its association with the risk of infections in 79 dialysis patients compared to 44 healthy controls. Different subsets of leukocytes and the intracellular expression of IRF8 were measured using flow cytometry. Compared to the healthy controls, the dialysis patients showed significantly reduced numbers of pDCs and significantly increased numbers of natural killer cells and classical and intermediate monocytes. The dialysis patients exhibited decreased numbers of IRF8-positive dendritic cells (pDC p < 0.001, mDC1 p < 0.001, mDC2 p = 0.005) and increased numbers of IRF8-positive monocytes (p < 0.001). IRF8 expression in pDC, mDC, and classical monocytes was lower in the dialysis patients than in the controls. Dialysis patients who required hospitalization due to infections within one year of follow-up displayed significantly reduced IRF8 expression levels in pDCs compared to patients without such infections (p = 0.04). Our results suggest that reduced IRF8 expression in pDCs is a potential risk factor predisposing dialysis patients to serious infections.

False-Negative Testing for FIP1L1::PDGFRA by Fluorescence in situ Hybridization Is a Frequent Cause of Diagnostic Delay.

The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease.

Bulk T-cell receptor sequencing confirms clonality in pediatric eosinophilic esophagitis and identifies a food-specific repertoire.

BACKGROUND: Eosinophilic esophagitis (EoE) involves a chronic immune-mediated response to dietary antigens. Recent work identifies T-cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food-specific T-cell repertoire. We sought to confirm T-cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. METHODS: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non-EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V-J-CDR3s were assessed based on specific food triggers. RESULTS: Active EoE biopsies from children but not adults displayed decreased unique TCRα/ß clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non-EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre-diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). CONCLUSION: We confirmed relative clonality in children but not adults with active EoE and identified potential food-specific TCRs, particularly for milk-triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers.

Cholecystectomy and risk of liver disease: a systematic review and meta-analysis of 27 million individuals.

BACKGROUND: There is still a lack of knowledge on the association between cholecystectomy and liver disease. This study was conducted to summarize the available evidence on the association of cholecystectomy with liver disease and quantify the magnitude of the risk of liver disease after cholecystectomy. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched systematically from database inception to January 2023 to identify eligible studies that evaluated the association between cholecystectomy and the risk of liver disease. Meta-analysis was conducted to obtain a summary odds ratio (OR) and 95% confidence interval (CI) using a random-effects model. RESULTS: We identified 20 studies with a total of 27 320 709 individuals and 282 670 liver disease cases. Cholecystectomy was associated with an increased risk of liver disease (OR: 1.63, 95% CI: 1.34-1.98). In particular, cholecystectomy was found to be significantly associated with a 54% increased risk of nonalcoholic fatty liver disease (OR: 1.54, 95% CI: 1.18-2.01), a 173% increased risk of cirrhosis (OR: 2.73, 95% CI: 1.81-4.12), and a 46% increased risk of primary liver cancer (OR: 1.46, 95% CI: 1.18-1.82). CONCLUSIONS: There is an association between cholecystectomy and the risk of liver disease. Our results suggest that strict surgical indications should be implemented to reduce unnecessary cholecystectomy. Additionally, the routine assessment of liver disease is necessary for patients with a history of cholecystectomy. More prospective large-sample studies are required for better estimates of the risk.

Urine eosinophil-derived neurotoxin: A potential marker of activity in select eosinophilic disorders.

BACKGROUND: Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole. METHODS: Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay. RESULTS: Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups. CONCLUSIONS: Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.

Immunogenicity of COVID-19 vaccines in chronic liver disease patients and liver transplant recipients: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic liver disease (CLD) patients and liver transplant (LT) recipients have an increased risk of morbidity and mortality from coronavirus disease 2019 (COVID-19). The immunogenicity of COVID-19 vaccines in CLD patients and LT recipients is poorly understood. The present study aimed to evaluate the immunogenicity of COVID-19 vaccines in CLD patients and LT recipients. METHODS: We searched electronic databases for eligible studies. Two reviewers independently conducted the literature search, extracted the data and assessed the risk of bias of included studies. The rates of detectable immune response were pooled from single-arm studies. For comparative studies, we compared the rates of detectable immune response between patients and healthy controls. The meta-analysis was conducted using the Stata software with a random-effects model. RESULTS: In total, 19 observational studies involving 4191 participants met the inclusion criteria. The pooled rates of detectable humoral immune response after two doses of COVID-19 vaccination in CLD patients and LT recipients were 95% (95% confidence interval [CI] = 88%-99%) and 66% (95% CI = 57%-74%) respectively. After two doses of vaccination, the humoral immune response rate was similar in CLD patients and healthy controls (risk ratio [RR] = 0.96; 95% CI = 0.90-1.02; p = .14). In contrast, LT recipients had a lower humoral immune response rate after two doses of vaccination than healthy controls (RR = 0.68; 95% CI = 0.59-0.77; p < .01). CONCLUSIONS: Our meta-analysis demonstrated that COVID-19 vaccination induced strong humoral immune responses in CLD patients but poor humoral immune responses in LT recipients.

lncRNAs AC156455.1 and AC104532.2 as Biomarkers for Diagnosis and Prognosis in Colorectal Cancer.

Background: There have been countless studies to date assessing specific oncogenic pathways in a range of tumor classes, but the role of N6-methyladenosine- (m6A-) related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains to be defined. Methods: We analyzed such m6A-related lncRNAs by conducting analyses of the Pearson correlation with information originating from the databank of The Cancer Genome Atlas (TCGA). The prognostic relevance of these lncRNAs in CRC was then assessed through a series of univariate Cox regression analyses, leading to the identification of two different m6A modification patterns; they are associated with clinical outcomes and have been used to estimate tumor immune microenvironment (TIME) by the CIBERSORT and ESTIMATE algorithms. We tested the expression of m6A-related lncRNAs in twelve pairs of colorectal cancer tissues and adjacent normal tissues from patients by qRT-PCR. Results: We discovered the prognostic risk signature composed of six m6A-related lncRNAs based upon TCGA data. When the overall survival of cases in the dataset of TCGA was investigated, the low-risk cases survived longer than the high-risk CRC cases in both the training and testing cohorts. ROC curves further indicated that m6A-related lncRNA prognostic signature (m6A-LPS) can effectively estimate the survival outcomes of patients in both of these cohorts. We found that lncRNAs AC156455.1 and AC104532.2 were upregulated in twelve colorectal cancer tissues compared with adjacent normal tissues using qRT-PCR. Conclusions: This data highlights that the lncRNAs AC156455.1 and AC104532.2 in CRC can be used as biomarkers for diagnostics and prognosis in CRC, demonstrating their potential as targets when designing novel immunotherapeutic regimens.

Biomimetic FeCo@PDA nanozyme platform with Fenton catalytic activity as efficient antibacterial agent.

The multidrug resistance of bacteria caused by the abuse of traditional antibiotics poses a great threat to public health, so it is urgent to develop effective antibacterial agents to deal with this dilemma. Biomimetics and nanotechnology are expected to provide new strategies for solving this problem. This study takes inspiration from the adhesive protein properties of mussels to design and synthesise biomimetic polydopamine nanospheres (FeCo@PDA NPs), which have strong adhesion and catalytic Fenton reactive enzyme activity. The antibacterial activity of FeCo@PDA NPs against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) is significantly better than that of traditional antibiotics daptomycin (Dap) and vancomycin (Van). PDA NPs with an intrinsic hierarchical structure have the ability to adhere to bacterial surfaces and improve the loading rate of metal ions Fe2+/Co2+. In addition, due to the dual effects of strong adhesion and Co2+, FeCo@PDA NPs can destroy the bacterial membrane structure and release endogenous hydrogen peroxide, which increases the generation of reactive oxygen species by synergistic catalysis of bimetal ions Fe2+/Co2+ to further kill bacteria thoroughly. The cytotoxicity test results show that FeCo@PDA NPs have good cytocompatibility. The impressive antibacterial properties and good biocompatibility of FeCo@PDA NPs make them a potential antibacterial drug.

Artificial Intelligence-Assisted Endoscopic Diagnosis of Early Upper Gastrointestinal Cancer: A Systematic Review and Meta-Analysis.

Objective: The aim of this study was to assess the diagnostic ability of artificial intelligence (AI) in the detection of early upper gastrointestinal cancer (EUGIC) using endoscopic images. Methods: Databases were searched for studies on AI-assisted diagnosis of EUGIC using endoscopic images. The pooled area under the curve (AUC), sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) with 95% confidence interval (CI) were calculated. Results: Overall, 34 studies were included in our final analysis. Among the 17 image-based studies investigating early esophageal cancer (EEC) detection, the pooled AUC, sensitivity, specificity, PLR, NLR, and DOR were 0.98, 0.95 (95% CI, 0.95-0.96), 0.95 (95% CI, 0.94-0.95), 10.76 (95% CI, 7.33-15.79), 0.07 (95% CI, 0.04-0.11), and 173.93 (95% CI, 81.79-369.83), respectively. Among the seven patient-based studies investigating EEC detection, the pooled AUC, sensitivity, specificity, PLR, NLR, and DOR were 0.98, 0.94 (95% CI, 0.91-0.96), 0.90 (95% CI, 0.88-0.92), 6.14 (95% CI, 2.06-18.30), 0.07 (95% CI, 0.04-0.11), and 69.13 (95% CI, 14.73-324.45), respectively. Among the 15 image-based studies investigating early gastric cancer (EGC) detection, the pooled AUC, sensitivity, specificity, PLR, NLR, and DOR were 0.94, 0.87 (95% CI, 0.87-0.88), 0.88 (95% CI, 0.87-0.88), 7.20 (95% CI, 4.32-12.00), 0.14 (95% CI, 0.09-0.23), and 48.77 (95% CI, 24.98-95.19), respectively. Conclusions: On the basis of our meta-analysis, AI exhibited high accuracy in diagnosis of EUGIC. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier PROSPERO (CRD42021270443).