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BACKGROUND: This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD). METHODS: Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120). RESULTS: Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity indexâ ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical responseâ +â biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, Pâ <â .001; 47.7% vs 36.0% at week 52-66, Pâ =â .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment. CONCLUSIONS: Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea.
Ustekinumab was well-tolerated and safe for Koran patients with Crohn's disease with no new safety signal as induction and maintenance therapy. Biologic-naïve patients exhibited better effectiveness outcomes, whereas combination therapy with immunomodulators was not superior to ustekinumab monotherapy.
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BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.
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BACKGROUND: Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerability of the MTX combination therapy in patients with Crohn's disease (CD). METHODS: We performed a multicenter observational study with 185 patients with CD with MTX and biologics combination therapy; the patients were recruited from three IBD Clinics in Korea. We evaluated the outcomes of the MTX combination therapy and examined the predictive factors of clinical and endoscopic remission. RESULTS: MTX was administered orally to 62.7% of patients; the mean dose was 15.5 mg per week, and the mean treatment duration was 36 months. Of the 169 patients treated with MTX combination therapy for over 6 months, the steroid-free clinical remission rates were 34.3%, 26.0%, 29.8%, and 32.7% at 4, 12, 18, and 24 months, respectively. Previous thiopurine use was a significant negatively associated independent factor (p < 0.001), and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of steroid-free clinical remission (p = 0.035). Ninety-six patients underwent follow-up endoscopy after 28 months, and 36 (37.5%) achieved endoscopic remission. Longer disease duration (p = 0.006), ileocolonic type of Montreal location (p = 0.036), and baseline C-reactive protein (CRP) level of more than 5 mg/L (p = 0.035) were significant negatively associated independent factors and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of endoscopic remission (p = 0.037). CONCLUSIONS: MTX combination therapy with biologics was effective and tolerable in patients with CD.
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Produtos Biológicos , Doença de Crohn , Humanos , Produtos Biológicos/uso terapêutico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Small rectal neuroendocrine tumors (NETs) can be treated with modified endoscopic mucosal resection (EMR). However, an optimal EMR method remains to be established. We aimed to assess the non-inferiority of Tip-in EMR versus precut EMR (EMR-P) for treating rectal NETs. METHODS: This prospective, multicenter, randomized controlled trial enrolled patients with rectal NETs of < 10 mm in diameter. The patients were randomly assigned to EMR-P and Tip-in EMR groups in a 1:1 ratio. Primary outcome was margin-negative (R0) resection rate between the two methods, with a noninferiority margin of 10%. RESULTS: Seventy-five NETs in 73 patients, including 64 eligible lesions (32 lesions in each, EMR-P and Tip-in EMR groups), were evaluated. In a modified intention-to-treat analysis, R0 resection rates of the EMR-P and Tip-in EMR groups were 96.9% and 90.6%, respectively, which did not demonstrate non-inferiority (risk difference, -6.3 [95% confidence interval: -18.0 to 5.5]). Resection time in the EMR-P group was longer than that in the Tip-in EMR group (p < 0.001). One case of intraprocedural bleeding was reported in each group. CONCLUSION: We did not demonstrate the non-inferiority of Tip-in EMR compared to EMR-P for treating small rectal NETs. However, the R0 resection rates for both techniques were high enough for clinical application.
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Ressecção Endoscópica de Mucosa , Tumores Neuroendócrinos , Neoplasias Retais , Humanos , Ressecção Endoscópica de Mucosa/efeitos adversos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Estudos Prospectivos , Resultado do Tratamento , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/cirurgia , Mucosa Intestinal/patologia , Estudos Retrospectivos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologiaRESUMO
Creeping fat (CrF) is an extraintestinal manifestation observed in patients with Crohn's disease (CD). It is characterized by the accumulation of mesenteric adipose tissue (MAT) that wraps around the intestinal wall. Although the role of CrF in CD is still debated, multiple studies have highlighted a correlation between CrF and inflammation, as well as fibrostenosais of the intestine, which contributes to the worsening of CD symptoms. However, the mechanism underlying the potential role of CrF in the development of Crohn's fibrosis remains an enigma. This study aimed to analyze CrF comprehensively using single-cell RNA sequencing analysis. The data was compared with transcriptomic data from adipose tissue in other disease conditions, such as ulcerative colitis, lymphedema, and obesity. Our analysis classified two lineages of preadipocyte (PAC) clusters responsible for adipogenesis and fibrosis in CrF. Committed PACs in CrF showed increased cytokine expression in response to bacterial stimuli, potentially worsening inflammation in patients with CD. We also observed an increase in fibrotic activity in PAC clusters in CrF. Co-analyzing the data from patients with lymphedema, we found that pro-fibrotic PACs featured upregulated pentraxin-3 expression, suggesting a potential target for the treatment of fibrosis in CrF. Furthermore, PACs in CrF exhibited a distinct increase in cell-to-cell communication via cytokines related to inflammation and fibrosis, such as CCL, LIGHT, PDGF, MIF, and SEMA3. Interestingly, these interactions also increased in PACs of the lymphedema, whereas the increased MIF signal of PACs was found to be a distinct characteristic of CrF. In immune cell clusters in CrF, we observed high immune activity of pro-inflammatory macrophages, antigen-presenting macrophages, B cells, and IgG+ plasma cells. Finally, we have demonstrated elevated IgG+ plasma cell infiltration and increased pentraxin-3 protein levels in the fibrotic regions of CrF in CD patients when compared to MAT from both UC patients and healthy individuals. These findings provide new insights into the transcriptomic features related to the inflammation of cells in CrF and suggest potential targets for attenuating fibrosis in CD.
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Doença de Crohn , Linfedema , Humanos , Adipogenia , Tecido Adiposo/metabolismo , Inflamação/metabolismo , Citocinas/metabolismo , Fibrose , Imunoglobulina G/metabolismoRESUMO
Single-cell genomics has the potential to map cell states and their dynamics in an unbiased way in response to perturbations like disease. However, elucidating the cell-state transitions from healthy to disease requires analyzing data from perturbed samples jointly with unperturbed reference samples. Existing methods for integrating and jointly visualizing single-cell datasets from distinct contexts tend to remove key biological differences or do not correctly harmonize shared mechanisms. We present Decipher, a model that combines variational autoencoders with deep exponential families to reconstruct derailed trajectories (https://github.com/azizilab/decipher). Decipher jointly represents normal and perturbed single-cell RNA-seq datasets, revealing shared and disrupted dynamics. It further introduces a novel approach to visualize data, without the need for methods such as UMAP or TSNE. We demonstrate Decipher on data from acute myeloid leukemia patient bone marrow specimens, showing that it successfully characterizes the divergence from normal hematopoiesis and identifies transcriptional programs that become disrupted in each patient when they acquire NPM1 driver mutations.
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We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.
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Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Doença de Crohn/metabolismo , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , RNA/metabolismo , Fibroblastos/metabolismo , Necrose/metabolismoRESUMO
Background: Methotrexate monotherapy is recommended as a maintenance therapy for Crohn's disease (CD). However, long-term follow-up data are scarce. Objectives: We aimed to examine the effectiveness and tolerability of methotrexate monotherapy in 94 CD patients from three inflammatory bowel disease Clinics in Korea. Design: This was a multicenter retrospective observational study. Methods: Patients with active CD treated with methotrexate monotherapy were included. Clinical characteristics, laboratory indicators, endoscopy indices were evaluated at baseline, 6, 12, and 24 months. Independent factors associated with long-term clinical and endoscopic outcomes were determined. Results: Methotrexate was administered orally (70.2%) or parenterally (29.8%). The mean methotrexate induction dose was 15.3 ± 0.4 mg/week, and the mean duration of therapy was 26.2 months. Of 76 patients who were treated for >6 months, the clinical remission rates were 76.3%, 74.6%, and 80.0% at 6, 12, and 24 months, respectively, by per-protocol analysis. The mean CRP levels were 7.5 ± 1.3, 5.3 ± 1.2, 3.8 ± 0.7, and 2.6 ± 0.5 mg/L at 0, 6, 12, and 24 months, respectively. Of 31 patients who underwent follow-up endoscopy after 27.5 months, the endoscopic remission rate was 38.7%. Baseline hemoglobin level <10 g/dL was a significant independent factor negatively associated with clinical remission at 6 [odds ratio (OR): 0.023, 95% confidence interval (CI): 0.003-0.206, p = 0.001] and 12 (OR: 0.079, 95% CI: 0.009-0.699, p = 0.023) months. Parenteral administration was a significant independent factor positively associated with clinical remission (OR: 11.231, 95% CI: 1.027-122.811, p = 0.047) and endoscopic remission (hazard ratio: 4.711, 95% CI: 1.398-15.874, p = 0.012) at 12 months. Conclusions: Methotrexate monotherapy was effective and tolerable as a maintenance therapy in CD patients.
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Objective: Immune-mediated inflammatory disease (IMID) is associated with an increased risk of mortality. It is unclear whether the higher mortality is attributable to the IMIDs themselves or to the higher prevalence of comorbidities in IMIDs. We aimed to investigate whether IMIDs per se confer a higher risk of mortality. Methods: From the Korean National Health Insurance Service-National Sample Cohort database, this population-based cohort study included 25,736 patients newly diagnosed with IMIDs between January 2007 and December 2017, and 128,680 individuals without IMIDs who were matched for age, sex, income, hypertension, type 2 diabetes, dyslipidemia, and the Charlson comorbidity index. All individuals were retrospectively observed through December 31, 2019. The outcomes included all-cause and cause-specific mortalities. Adjustments for age, sex, and comorbidities were performed using multivariable Cox proportional hazard regression analyses, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the outcomes were estimated. Results: The adjusted risk of all-cause mortality was significantly lower in patients with IMIDs than that in those without (aHR, 0.890; 95% CI, 0.841-0.942). Regarding cause-specific mortality, cancer-specific (aHR, 0.788; 95% CI, 0.712-0.872) and cardiovascular disease-specific (aHR, 0.798; 95% CI, 0.701-0.908) mortalities were the two causes of death that showed significantly lower risks in patients with IMIDs. A similar trend was observed when organ based IMIDs were analyzed separately (i.e., gut, joint, and skin IMIDs). Conclusion: After adjusting for comorbidities, IMIDs were associated with a lower risk of all-cause mortality compared to those without IMIDs. This was attributable to the lower risks of cancer-and cardiovascular disease-specific mortalities.
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Objective: Patients with type 2 diabetes (T2DM) are at a high risk of developing depression and anxiety. To better stratify the risk, we aimed to assess whether the presence of immune-mediated inflammatory diseases (IMIDs) confers a higher risk of depression and anxiety in these patients. Methods: Patients with T2DM without prior depression or anxiety who underwent national health examination between 2009 and 2012 (n = 1,612,705) were enrolled from the nationwide health check-up data from Korean National Health Insurance Service. The outcome events were incident depression and anxiety, defined as International Classification of Diseases, 10th Revision codes F32-F33 and F40-F41, respectively. Multivariable Cox proportional hazard regression analyses were conducted to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) according to the existence of IMIDs. Results: Over an average follow-up time of 6.4 years, existence of gut IMIDs was associated with a higher risk of depression (aHR: 1.28 [95% CI: 1.08-1.53]) and anxiety (1.22 [1.06-1.42]). Existence of joint IMIDs was associated with a higher risk of depression (1.34 [1.31-1.37]) and anxiety (1.31 [1.29-1.34]). Existence of skin IMID was associated with a higher risk of depression (1.18 [1.14-1.23]) and anxiety (1.13 [1.09-1.16]). The effect sizes of IMIDs on depression and anxiety were larger in those with ≥ 2 IMIDs (1.42 [1.19-1.69] and 1.49 [1.29-1.72], respectively) than in those with one IMID (1.30 [1.27-1.32] and 1.26 [1.24-1.28], respectively). Conclusion: In patients with T2DM, presence of IMIDs was associated with a higher risk of depression and anxiety. More stringent attention and screening for anxiety and depression should be encouraged in patients with T2DM and comorbid IMIDs due to clinical implications of psychological distress on patient-reported outcomes and prognosis.
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Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: adenoma ≥10 mm in size; 3 to 5 (or more) adenomas; tubulovillous or villous adenoma; adenoma containing high-grade dysplasia; traditional serrated adenoma; sessile serrated lesion containing any grade of dysplasia; serrated polyp of at least 10 mm in size; and 3 to 5 (or more) sessile serrated lesions. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.
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BACKGROUND: Non-curative resection (non-CR) after endoscopic submucosal dissection (ESD) requires additional surgery due to the possibility of lymph node metastasis (LNM). Therefore, it is important to accurately predict the risk of non-CR to avoid unnecessary preoperative procedures. Thus, we aimed to develop and verify a nomogram to predict the risk of non-CR prior to ESD. METHODS: Patients who underwent ESD for early gastric cancer (EGC) were divided into CR and non-CR groups based on the present ESD criteria. The pre-procedural factors, such as endoscopic features, radiologic findings, and pathology of the lesion, were compared between the groups to identify the risk factors associated with non-CR. A nomogram was developed using multivariate analysis, and its predictive value was assessed using an external validation group. RESULTS: Among 824 patients, 682 were curative (82.7%) and 142 were non-curative (17.3%). By comparing two groups, endoscopic features including redness, whitish mucosal change, fold convergence, and large lesion size; histologic features such as moderately or poorly differentiated or signet ring cell carcinoma; and abnormal CT findings including non-specific lymph node enlargement and fold thickening were identified as significant predictors of non-CR. The nomogram was developed based on these predictors and showed good predictive performance in the external validation, with an area under the curve of 0.87. CONCLUSIONS: We developed a nomogram to predict the risk of non-CR prior to ESD. These predictive factors in addition to the existing ESD criteria can help provide the best treatment option for patients with EGC.
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Carcinoma de Células em Anel de Sinete , Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Nomogramas , Endoscopia , Fatores de Risco , Carcinoma de Células em Anel de Sinete/cirurgia , Carcinoma de Células em Anel de Sinete/patologia , Mucosa Gástrica/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Endoscopic procedures can cause anxiety, which can lead to more uncomfortable, difficult, and incomplete procedures, in addition to greater use of sedative medication. Here, we investigate whether exposing patients to virtual reality (VR) prior to endoscopic procedures can reduce their anxiety levels. MATERIALS AND METHODS: Forty patients at Gangnam Severance Hospital were enrolled and divided into the VR group and the control group. Patients in the VR group were exposed to VR prior to their procedure to alleviate anxiety. The primary data outcomes were State-Trait Anxiety Inventory (STAI), pain score, satisfaction with sedation, and satisfaction with the procedure. RESULTS: The mean STAI-state and STAI-trait did not differ significantly between the control group and the VR group. While defining a high anxiety STAI score as ≥45 in an STAI-state, the proportion of patients with high anxiety at baseline was 35% and increased to 50% prior to the procedure in the control group. However, in the VR group, the proportion of patients with high anxiety at baseline was 60% and decreased to 50% prior to the procedure. The proportion changes of patients with high anxiety in the STAI-state exhibited a significant difference between the control and VR groups (p=0.007). Furthermore, patients' satisfaction with sedation was significantly greater in the VR group compared to the control group (p=0.017). CONCLUSION: VR exposure may relieve patients' anxiety levels prior to endoscopic procedures, but further well-designed placebo-controlled studies are needed. VR, an inexpensive, easily available, and non-invasive method, also improved the satisfaction with sedation of endoscopic procedures.
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Anestesia , Realidade Virtual , Humanos , Ansiedade , Endoscopia , Satisfação do PacienteRESUMO
BACKGROUND AND AIMS: Insufficient validation limits the generalizability of deep learning in diagnosing Helicobacter pylori infection with endoscopic images. The aim of this study was to develop a deep learning model for the diagnosis of H pylori infection using endoscopic images and validate the model with internal and external datasets. METHODS: A convolutional neural network (CNN) model was developed based on a training dataset comprising 13,403 endoscopic images from 952 patients who underwent endoscopy at Seoul National University Hospital Gangnam Center. Internal validation was performed using a separate dataset comprised of images of 411 individuals of Korean descent and 131 of non-Korean descent. External validation was performed with the images of 160 patients in Gangnam Severance Hospital. Gradient-weighted class activation mapping was performed to visually explain the model. RESULTS: In predicting H pylori ever-infected status, the sensitivity, specificity, and accuracy of internal validation for people of Korean descent were .96 (95% confidence interval [CI], .93-.98), .90 (95% CI, .85-.95), and .94 (95% CI, .91-.96), respectively. In the internal validation for people of non-Korean descent, the sensitivity, specificity, and accuracy in predicting H pylori ever-infected status were .92 (95% CI, .86-.98), .79 (95% CI, .67-.91), and .88 (95% CI, .82-.93), respectively. In the external validation cohort, sensitivity, specificity, and accuracy were .86 (95% CI, .80-.93), .88 (95% CI, .79-.96), and .87 (95% CI, .82-.92), respectively, when performing 2-group categorization. Gradient-weighted class activation mapping showed that the CNN model captured the characteristic findings of each group. CONCLUSIONS: This CNN model for diagnosing H pylori infection showed good overall performance in internal and external validation datasets, particularly in categorizing patients into the never- versus ever-infected groups.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/diagnóstico , Redes Neurais de Computação , Endoscopia Gastrointestinal/métodosRESUMO
BACKGROUND AND AIMS: Metabolic syndrome may share the pathophysiology of adipose tissue dysregulation and inadequate immune response with inflammatory bowel disease [IBD]. We determined the association of abdominal obesity [AO] with the risk of developing IBD. METHODS: We conducted a nationwide population-based cohort study using the Korean National Health Insurance Services database. A total of 10 082 568 participants of the 2009 national health screening programme were enrolled. Newly diagnosed Crohn's disease [CD] and ulcerative colitis [UC] were identified using the International Classification of Diseases 10th Revision and specialized national codes for rare intractable diseases. Waist circumference [WC] was classified into six groups and compared with the reference values of 85.0-89.9 cm for men and 80.0-84.9 cm for women. AO was defined as a WC of ≥90 cm for men and ≥85 cm for women. RESULTS: During a median follow-up of 9.3 years, the incidence rates of CD and UC were 2.11 and 8.40 per 100 000 person-years, respectively. After adjustment for age, sex, lifestyle behaviours, income and body mass index [BMI], the increase in baseline WC was significantly associated with the risk of developing CD, but not UC, compared to the references. The risk of developing CD in subjects with AO increased significantly compared to those without AO [adjusted hazard ratio, 1.40; 95% confidence interval, 1.21-1.61], regardless of obesity based on BMI. CONCLUSIONS: Individuals with AO bore an increased risk of developing CD proportional to WC, but not UC, suggesting that visceral adiposity is related to the pathophysiology of CD.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Masculino , Humanos , Feminino , Estudos de Coortes , Circunferência da Cintura , Fatores de Risco , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Doença de Crohn/complicações , Colite Ulcerativa/complicações , Obesidade/complicações , Incidência , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Ustekinumab was recently approved for the treatment of moderate to severe Crohn's disease (CD). Although the ustekinumab Clinical Decision Support Tool (UST-CDST) was able to predict ustekinumab responsiveness in a clinical trial, it is not clear whether UST-CDST can also predict a future clinical relapse following ustekinumab therapy in the real-life setting. METHODS: We enrolled patients with moderate to severe CD who were refractory to conventional therapies and who showed a clinical response after induction therapy with ustekinumab and monitored them until the relapse. We performed a Cox proportional hazard analysis to investigate the predictive capability of UST-CDST for a clinical disease relapse. RESULTS: Clinical remission rates at week 20 were 25.0% for low-probability responders, 66.7% for intermediate-probability responders, and 75.0% for high-probability responders. The high-probability responders were more likely to achieve clinical remission at week 20 compared with the low-probability responders. Among 99 patients with moderate to severe CD, 37 (37.4%) experienced a clinical relapse during the median follow-up period of 18.0 months of ustekinumab treatment. The cumulative relapse rates were 70.0% in the low-probability responders, 35.9% in the intermediate-probability responders, and 22.5% in the high-probability responders (Pâ =â .001). In a multivariable Cox proportional hazard analysis, the high-probability responders and intermediate-probability responders had a lower risk of clinical relapse than the low-probability responders. Receiver operating characteristic analysis using UST-CDST to predict relapse revealed an area under the curve of 0.698. CONCLUSIONS: The UST-CDST can predict clinical relapse in patients with moderate to severe CD subjected to ustekinumab therapy.
Clinical decision tools are useful in stratifying patients for optimal treatment. Here, we validate the capacity of Ustekinumab Clinical Decision Support Tool to predict clinical remission and relapse in Korean patients with moderate to severe Crohn's disease.
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Doença de Crohn , Sistemas de Apoio a Decisões Clínicas , Humanos , Ustekinumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Estudos de Viabilidade , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (µg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.
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Medicamentos Biossimilares , Colite Ulcerativa , Doença de Crohn , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Infliximab/uso terapêutico , Estudos Prospectivos , Fármacos Gastrointestinais/uso terapêutico , Resultado do Tratamento , Indução de Remissão , Medicamentos Biossimilares/uso terapêuticoRESUMO
The triglyceride-glucose (TyG) index was proposed as a useful marker of metabolic syndrome. Insulin resistance, the main mechanism underlying metabolic syndrome, is related to gastroesophageal reflux disease (GERD). This study aimed to elucidate the association between the TyG index and GERD/erosive reflux disease (ERD). We retrospectively reviewed the electronic medical records of patients who underwent gastroduodenoscopy at a checkup center. The calculation of TyG index used following formula: ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). We divided the patients into four groups according to the TyG index quartile (Q). We evaluated the relationship between the alteration of the TyG index and GERD in patients who received health checkups two times. Among the 52,605 enrolled patients, 3073 (5.8%) and 434 (0.8%) were diagnosed with GERD and ERD, respectively. The odds ratios (ORs) for GERD in the TyG index progressively increased across quartiles (P < 0.001): Q2 (OR = 2.477), Q3 (OR = 3.013), and Q4 (OR = 4.027) compared with Q1, which was used as a reference, respectively. Those for ERD also progressively increased across quartiles (P < 0.001): Q2 (OR = 4.264), Q3 (OR = 4.841), and Q4 (OR = 7.390) compared with Q1, respectively. Moreover, the degree of TyG index increase during the first and second tests in the GERD group was more prominent than in the control group (P = 0.001). In conclusion, the higher TyG index was significantly associated with GERD. The TyG index may be a novel predictive biomarker of GERD and ERD.
Assuntos
Refluxo Gastroesofágico , Resistência à Insulina , Síndrome Metabólica , Humanos , Triglicerídeos , Glucose , Estudos de Coortes , Glicemia/metabolismo , Estudos Retrospectivos , Síndrome Metabólica/epidemiologia , Fatores de Risco , BiomarcadoresRESUMO
We previously constructed a VGG-16 based artificial intelligence (AI) model (image classifier [IC]) to predict the invasion depth in early gastric cancer (EGC) using endoscopic static images. However, images cannot capture the spatio-temporal information available during real-time endoscopy-the AI trained on static images could not estimate invasion depth accurately and reliably. Thus, we constructed a video classifier [VC] using videos for real-time depth prediction in EGC. We built a VC by attaching sequential layers to the last convolutional layer of IC v2, using video clips. We computed the standard deviation (SD) of output probabilities for a video clip and the sensitivities in the manner of frame units to observe consistency. The sensitivity, specificity, and accuracy of IC v2 for static images were 82.5%, 82.9%, and 82.7%, respectively. However, for video clips, the sensitivity, specificity, and accuracy of IC v2 were 33.6%, 85.5%, and 56.6%, respectively. The VC performed better analysis of the videos, with a sensitivity of 82.3%, a specificity of 85.8%, and an accuracy of 83.7%. Furthermore, the mean SD was lower for the VC than IC v2 (0.096 vs. 0.289). The AI model developed utilizing videos can predict invasion depth in EGC more precisely and consistently than image-trained models, and is more appropriate for real-world situations.
RESUMO
Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for the management of advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: (1) adenoma ≥10 mm in size; (2) 3 to 5 (or more) adenomas; (3) tubulovillous or villous adenoma; (4) adenoma containing high-grade dysplasia; (5) traditional serrated adenoma; (6) sessile serrated lesion (SSL) containing any grade of dysplasia; (7) serrated polyp of at least 10 mm in size; and (8) 3 to 5 (or more) SSLs. More studies are needed to fully comprehend the patients most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.