Longitudinal ultrasound-based AI model predicts axillary lymph node response to neoadjuvant chemotherapy in breast cancer: a multicenter study.

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

Fecal microbiota transplantation for irritable bowel syndrome: Current evidence and perspectives.

In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology. We focus specifically on the mechanisms un-derlying the effects of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), the factors which affect the outcomes of FMT in IBS patients, and challenges. FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS. The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials, yielding divergent outcomes. The current frontier in this field seeks to elucidate these variations, underscore the existing knowledge gaps that necessitate exploration, and provide a guideline for successful FMT imple-mentation in IBS patients. At the same time, the application of FMT as a treatment for IBS confronts several challenges.

The impact of vedolizumab therapy on extraintestinal manifestations in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Extraintestinal manifestations (EIMs) pose a significant threat in inflammatory bowel disease (IBD) patients. Vedolizumab (VDZ) primarily affects the gastrointestinal tract. However, its impact on EIMs remains uncertain. Therefore, we conducted this meta-analysis to examine the effects of VDZ on EIMs during treatment. METHODS: Relevant studies were identified by conducting thorough searches across electronic databases, including PubMed, Ovid Embase, Medline, and Cochrane CENTRAL. Primary outcomes focused on the proportion of patients with resolution for pre-existing EIMs in IBD patients receiving VDZ. Secondary outcomes included the proportion of patients with EIM exacerbations and new onset EIMs during VDZ treatment. RESULTS: Our meta-analysis encompassed 21 studies. The proportion of patients with resolution of pre-existing EIMs in VDZ-treated IBD patients was 39% (150/386; 95% confidence interval [CI] 0.31-0.48). The proportion of patients with EIM exacerbations occurred at a rate of 28% (113/376; 95% CI 0.05-0.50), while new onset EIMs had a rate of 15% (397/2541; 95% CI 0.10-0.20). Subgroup analysis revealed a 40% (136/337) proportion of patients with resolution for articular-related EIMs and a 50% (9/18) rate for erythema nodosum. Exacerbation rates for arthritis/arthralgia, erythema nodosum/pyoderma gangrenosum, and aphthous stomatitis during VDZ use were 28% (102/328), 18% (7/38), and 11% (3/28), respectively. The incidence rate of newly developed EIMs during treatment was 11% (564/4839) for articular-related EIMs, with other EIMs below 2%. CONCLUSION: VDZ demonstrates efficacy in skin-related EIMs like erythema nodosum and joint-related EIMs including arthritis, arthralgia, spondyloarthritis, and peripheral joint diseases. Some joint and skin-related EIMs may experience exacerbation during VDZ therapy.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

[Research progress of traditional Chinese medicines as quorum sensing inhibitors in collaboration with antibiotics to inhibit drug-resistant bacteria].

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.

[Clinical metabolomics of Zicuiyin in treatment of diabetic kidney disease].

This study aimed to analyze the therapeutic effect of Zicuiyin on diabetic kidney disease(DKD) and explore the possible targets of this formula. Eighteen DKD patients treated in the endocrine department or nephrology department of Second Affilia-ted Hospital of Tianjin University of Traditional Chinese Medicine from January to December in 2019 were enrolled and assigned into a test group(n=10) and a control group(n=8). Both groups received routine chemical medicine treatment. In addition, the test group was treated with Zicuiyin and the control group with Huangkui Capsules for 8 weeks. The clinical trial was approved by the Ethics Committee of Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, with the ethical approval No. 2017-023-01, and all the patients signed the informed consent form. The results showed that the 8-week treatment with Zicuiyin lowered the level of glycosylated hemoglobin(HbA1c) and recovered the 24 h urinary protein(24hUP), 24 h urinary microalbumin(24hmAlb), urine albumin-to-creatinine ratio(UACR), and estimated glomerular filtration rate(eGFR) of the patients with 24hUP<3.5 g. According to the different levels in 24hUP, all the patients were divided into two subgroups(subgroup A with 24hUP<3.5 g and subgroup B with 24hUP≥3.5 g). The ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS)-based non-targeted metabolomics analysis was conducted on the baseline serum samples from diffe-rent subgroups of patients. Nineteen biomarker candidates were identified to distinguish the metabolic differences between the two subgroups, and their correlations with clinical indicators were analyzed. Zicuiyin lowered the levels of phenylalanine, pseudouridine, and adenosine [fold change(FC)<0.5, P<0.05] in subgroup A. The results indicated that Zicuiyin was more effective on the DKD patients with low urinary protein levels, and its targets were involved in phenylalanine metabolism and nucleoside metabolism.

Root-associated bacteria strengthen their community stability against disturbance of antibiotics on structure and functions.

Antibiotics affect bacterial community structure and functions in soil. However, the response and adaptation of root-associated bacterial communities to antibiotic stress remains poorly understood. Here, rhizobox experiments were conducted with maize (Zea mays L.) upon exposure to antibiotics ciprofloxacin or tetracycline. High-throughput sequencing analysis of bacterial community and quantitative PCR analysis of nitrogen cycling genes show that ciprofloxacin and tetracycline significantly shift bacterial community structure in bulk soil, whereas plant host may mitigate the disturbances of antibiotics on bacterial communities in root-associated niches (i.e., rhizosphere and rhizoplane) through the community stabilization. Deterministic assembly, microbial interaction, and keystone species (e.g., Rhizobium and Massilia) of root-associated bacterial communities benefit the community stability compared with those in bulk soil. Meanwhile, the rhizosphere increases antibiotic dissipation, potentially reducing the impacts of antibiotics on root-associated bacterial communities. Furthermore, rhizospheric effects deriving from root exudates alleviate the impacts of antibiotics on the nitrogen cycle (i.e., nitrification, organic nitrogen conversion and denitrification) as confirmed by functional gene quantification, which is largely attributed to the bacterial community stability in rhizosphere. The present study enhances the understanding on the response and adaptation of root-associated bacterial community to antibiotic pollution.

Development and validation of a nomogram to predict non-response to 5-aminosalicylic acid in patients with ulcerative colitis.

BACKGROUND: there are some patients with ulcerative colitis (UC) who have non-response (NR) to 5-aminosalicylic acid (5-ASA). To promote individualized treatment in UC patients, it is crucial to identify valid predictors to estimate NR to 5-ASA. Therefore, this study aimed to identify the predictive value of clinical and biochemical markers and to construct a nomogram model predicting NR to 5-ASA in patients with UC. METHODS: data of patients diagnosed with UC in the First Hospital of China Medical University between January 2012 and December 2020 were retrospectively analyzed. Primary outcome was the proportion of NR to 5-ASA. Multivariable logistic regression was used to construct prediction models. Area under the curve (AUC), calibration and decision curve analyses (DCA) were assessed in the validation cohort. RESULTS: of 284 UC patients who were treatment-naive, 86 (30.3 %) had NR to 5-ASA. Univariate regression analysis showed that disease classification (DC) (p = 0.008), monocytes (MONO) (p = 0.041), platelet distribution width (PDW) (p = 0.027), serum total cholesterol (TC) (p = 0.031) and α1 globulin (p < 0.001) were strongly associated with NR to 5-ASA. Receiver operating characteristics (ROC) analysis indicated the AUC was 0.852, it showed that this model has a good degree of discrimination. The DCA curve showed that the predicted probability is 0.0-96.0 %. CONCLUSION: this study developed a predictive model with good discrimination and calibration, and high clinical validity, which can effectively estimate the risk of NR to 5-ASA. DC, MONO, PDW, TC and α1 globulin can be used as predictors for NR to 5-ASA in UC patients.

Infliximab-induced psoriasis in an ulcerative colitis patient successfully treated with guselkumab.

Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract. Tumor necrosis factor (TNF) inhibitors such as infliximab (IFX) are used to treat UC. But TNF inhibitors can induce psoriasis, which was characterized by IL-17/IL-22 expressing Th17 cells and IFN-γ expressing Th1 cells, with increased expression of Th17 cells correlated with more severe skin lesions and a need for Ustekinumab (UST) therapy1. UST is a monoclonal antibody that binds to the p40 subunit of the interleukin (IL)-12 and IL-23. It has shown remarkable efficacy in psoriasis and UC2. Guselkumab, a subcutaneously administered fully human IgG1 monoclonal antibody that selectively inhibits the p19 subunit of IL-23, is approved for the treatment of patients with moderate-to-severe plaque psoriasis3. It was shown to be efficacious in patients with prior failure of other biologics such as UST and was also observed in the treatment of psoriasis localized in difficult-to-treat body regions including the scalp, palms, soles, and fingernails. We report a case of successful use of guselkumab to treat a UC patient with IFX-induced psoriasis that was refractory to UST therapy.

The incidence and predisposing factors for irritable bowel syndrome following COVID-19: a systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder. Several studies have analyzed the long-term GI symptoms and IBS following coronavirus disease 2019 (COVID-19). The purpose of this study is to evaluate the incidence and predisposing factors for IBS following COVID-19 by a systematic review and meta-analysis. METHODS: Electronic databases were searched to identify relevant studies. Primary outcomes were the pooled incidence rate of IBS following COVID-19 and the pooled relative risk (RR) for IBS in the COVID-19 group compared to the non-COVID-19 group. Secondary outcomes were the pooled RR and the standardized mean difference (SMD) for predisposing factors in the IBS group compared to the non-IBS group. Heterogeneity was evaluated using Cochran's Q test and I2 statistics. RESULTS: Ten studies were included in this study. The pooled incidence rate of IBS in COVID-19 patients was 12%. The pooled incidence rate of IBS-D, IBS-C and IBS-M was 5%, 2% and 1%. The pooled incidence rate of IBS in 6 and 12 months was 10% and 3%. The pooled RR for IBS in COVID-19 patients was 1.23 [95% confidence interval (CI) = 0.50-3.01] compared to non-COVID-19 patients. The pooled RR or SMD for mild, moderate, and severe disease activity, procalcitonin (PCT), depression or anxiety in IBS patients following COVID-19 was 0.94 (95% CI = 0.74-1.21), 1.19 (95% CI = 0.65-2.21), 1.30 (95% CI = 0.63-2.66), 6.73 (95% CI = 6.08-7.38) and 3.21 (95% CI = 1.79-5.75). CONCLUSION: The incidence of IBS following COVID-19 was 12%. But it was not higher than the general population. We also found some predisposing factors for IBS including depression or anxiety, PCT.

Effectiveness and safety of upadacitinib for inflammatory bowel disease: A systematic review and meta-analysis of RCT and real-world observational studies.

BACKGROUND: Upadacitinib, a novel and selective inhibitor of Janus kinase 1, has demonstrated promising efficacy in managing inflammatory bowel disease (IBD). In this systematic review and meta-analysis, our primary aim was to comprehensively assess the therapeutic effectiveness and safety profile of upadacitinib in the treatment of patients with IBD. METHODS: We conducted an extensive literature search across prominent databases, including Medline, Embase, Web of Science, and Cochrane Central, to identify pertinent studies providing insights into the efficacy and safety of upadacitinib in IBD. The primary endpoint was the achievement of clinical remission, while secondary endpoints encompassed clinical response, endoscopic response, endoscopic remission, and the evaluation of adverse events (AEs). RESULTS: In this meta-analysis of nine studies, we categorized results by study type. Clinical remission rates were: RCTs 36 % (95 % CI = 30-42 %), real-world studies 25 % (95 % CI = 1-49 %), retrospective studies 40 % (95 % CI = 24-56 %), cohort studies 55 % (95 % CI = 25-85 %). Clinical response rates were: RCTs 61 % (95 % CI = 55-67 %), real-world studies 42 % (95 % CI = 14-70 %), cohort studies 65 % (95 % CI = 57-73 %). Endoscopic remission rates were: RCTs 19 % (95 % CI = 15-24 %), cohort studies 29 % (95 % CI = 5-52 %). Endoscopic response rates were: RCTs 41 % (95 % CI = 36-47 %), cohort studies 57 % (95 % CI = 31-83 %). Incidence rate for any AEs: IBD 69 % (95 % CI = 63-76 %), UC 65 % (95 % CI = 57-74 %), CD 75 % (95 % CI = 67-82 %). CONCLUSION: Cumulative data from real-world studies and trials confirm the efficacy of upadacitinib in IBD induction and maintenance, with consistent safety. However, further long-term studies are needed to understand its sustained effectiveness and safety.

Development and validation of a nomogram to predict non-response to 5-aminosalicylic acid in patients with ulcerative colitis

Background: there are some patients with ulcerative colitis (UC) who have non-response (NR) to 5-aminosalicylic acid (5-ASA). To promote individualized treatment in UC patients, it is crucial to identify valid predictors to estimate NR to 5-ASA. Therefore, this study aimed to identify the predictive value of clinical and biochemical markers and to construct a nomogram model predicting NR to 5-ASA in patients with UC. Methods: data of patients diagnosed with UC in the First Hospital of China Medical University between January 2012 and December 2020 were retrospectively analyzed. Primary outcome was the proportion of NR to 5-ASA. Multivariable logistic regression was used to construct prediction models. Area under the curve (AUC), calibration and decision curve analyses (DCA) were assessed in the validation cohort. Results: of 284 UC patients who were treatment-naive, 86 (30.3 %) had NR to 5-ASA. Univariate regression analysis showed that disease classification (DC) (p = 0.008), monocytes (MONO) (p = 0.041), platelet distribution width (PDW) (p = 0.027), serum total cholesterol (TC) (p = 0.031) and α1 globulin (p < 0.001) were strongly associated with NR to 5-ASA. Receiver operating characteristics (ROC) analysis indicated the AUC was 0.852, it showed that this model has a good degree of discrimination. The DCA curve showed that the predicted probability is 0.0-96.0 %. Conclusion: this study developed a predictive model with good discrimination and calibration, and high clinical validity, which can effectively estimate the risk of NR to 5-ASA. DC, MONO, PDW, TC and α1 globulin can be used as predictors for NR to 5-ASA in UC patients. (AU)

Infliximab-induced psoriasis in an ulcerative colitis patient successfully treated with guselkumab

Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract. Tumor necrosis factor (TNF) inhibitors such as infliximab (IFX) are used to treat UC. But TNF inhibitors can induce psoriasis, which was characterized by IL-17/IL-22 expressing Th17 cells and IFN-γ expressing Th1 cells, with increased expression of Th17 cells correlated with more severe skin lesions and a need for Ustekinumab (UST) therapy1. UST is a monoclonal antibody that binds to the p40 subunit of the interleukin (IL)-12 and IL-23. It has shown remarkable efficacy in psoriasis and UC2. Guselkumab, a subcutaneously administered fully human IgG1 monoclonal antibody that selectively inhibits the p19 subunit of IL-23, is approved for the treatment of patients with moderate-to-severe plaque psoriasis3. It was shown to be efficacious in patients with prior failure of other biologics such as UST and was also observed in the treatment of psoriasis localized in difficult-to-treat body regions including the scalp, palms, soles, and fingernails. We report a case of successful use of guselkumab to treat a UC patient with IFX-induced psoriasis that was refractory to UST therapy. (AU)

Response and adaptation of rhizosphere microbiome to organic pollutants with enriching pollutant-degraders and genes for bioremediation: A critical review.

Phytoremediation largely involves microbial degradation of organic pollutants in rhizosphere for removing organic pollutants like polycyclic aromatic hydrocarbons, phthalates and polychlorinated biphenyls. Microbial community in rhizosphere experiences complex processes of response-adaptation-feedback up on exposure to organic pollutants. This review summarizes recent research on the response and adaptation of rhizosphere microbial community to the stress of organic pollutants, and discusses the enrichment of the pollutant-degrading microbial community and genes in the rhizosphere for promoting bioremediation. Soil pollution by organic contaminants often reduces the diversity of rhizosphere microbial community, and changes its functions. Responses vary among rhizosphere microbiomes up on different classes of organic pollutants (including co-contamination with heavy metals), plant species, root-associated niches (e.g., rhizosphere, rhizoplane and endosphere), geographical location and soil properties. Soil pollution can deplete some sensitive microbial taxa and enrich some tolerant microbial taxa in rhizosphere. Furthermore, rhizosphere enriches pollutant-degrading microbial community and functional genes including different gene clusters responsible for biodegradation of organic pollutants and their intermediates, which improve the adaptation of microbiome and enhance the remediation efficiency of the polluted soil. The knowledge gaps and future research challenges are highlighted on rhizosphere microbiome in response-adaptation-feedback processes to organic pollution and rhizoremediation. This review will hopefully update understanding on response-adaptation-feedback processes of rhizosphere microbiomes and rhizoremediation for the soil with organic pollutants.

Effectiveness of 4 L, 2 L, and 1 L PEG bowel preparation for colonoscopy in patients with ulcerative colitis: a retrospective study.

An adequate bowel preparation (BP) is essential for a high quality colonoscopy. Patients with ulcerative colitis (UC) show low compliance with BP due to the large volume of lavage solution to be ingested. We sought to evaluate the efficacy of 4 L, 2 L, and 1 L polyethylene glycol (PEG) for BP and identify the related factors of suboptimal BP (SOBP) in patients We conducted a retrospective analysis of UC patients who underwent colonoscopies from January 2017 to March 2022 at our hospital. Quality of BP was documented using the Boston Bowel Preparation Scale (BBPS). BBPS score ≤ 6 is considered SOBP. The related factors associated with SOBP were evaluated using logistic regression analyses. In total, 282 patients with UC were enrolled in our study. The bowel cleansing by BBPS was 8.44±0.84 in 4 L PEG-based BP, 8.29±0.95 in 2 L PEG-based BP, and 7.59±1.17 in 1 L PEG-based BP. On multivariable analysis, extensive colitis (E3), moderate disease activity (mayo score: 6-10) to severe disease activity (mayo score: 11-12), severe endoscopic activity (EMS: 3), biological therapies (infliximab and vedolizumab), and 1 L PEG-based BP were associated with an increased odds of SOBP. Our study demonstrated that 2 L-based and 4 L-based BP is highly effective in UC patients undergoing colonoscopy. Moderate to severe disease activity, severe endoscopic activity, and the use of biological therapies were associated with an increased risk of SOBP in UC patients undergoing colonoscopy.