One-year Safety and Effectiveness of Ustekinumab in Patients With Crohn's Disease: The K-STAR Study.

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 index ≥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 response + 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, P < .001; 47.7% vs 36.0% at week 52-66, P = .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.

Autoinhibited Protein Database: a curated database of autoinhibitory domains and their autoinhibition mechanisms.

Autoinhibition, a crucial allosteric self-regulation mechanism in cell signaling, ensures signal propagation exclusively in the presence of specific molecular inputs. The heightened focus on autoinhibited proteins stems from their implication in human diseases, positioning them as potential causal factors or therapeutic targets. However, the absence of a comprehensive knowledgebase impedes a thorough understanding of their roles and applications in drug discovery. Addressing this gap, we introduce Autoinhibited Protein Database (AiPD), a curated database standardizing information on autoinhibited proteins. AiPD encompasses details on autoinhibitory domains (AIDs), their targets, regulatory mechanisms, experimental validation methods, and implications in diseases, including associated mutations and post-translational modifications. AiPD comprises 698 AIDs from 532 experimentally characterized autoinhibited proteins and 2695 AIDs from their 2096 homologs, which were retrieved from 864 published articles. AiPD also includes 42 520 AIDs of computationally predicted autoinhibited proteins. In addition, AiPD facilitates users in investigating potential AIDs within a query sequence through comparisons with documented autoinhibited proteins. As the inaugural autoinhibited protein repository, AiPD significantly aids researchers studying autoinhibition mechanisms and their alterations in human diseases. It is equally valuable for developing computational models, analyzing allosteric protein regulation, predicting new drug targets, and understanding intervention mechanisms AiPD serves as a valuable resource for diverse researchers, contributing to the understanding and manipulation of autoinhibition in cellular processes. Database URL: http://ssbio.cau.ac.kr/databases/AiPD.

The Impairment of Endothelial Autophagy Accelerates Renal Senescence by Ferroptosis and NLRP3 Inflammasome Signaling Pathways with the Disruption of Endothelial Barrier.

Autophagy is a cellular process that degrades damaged cytoplasmic components and regulates cell death. The homeostasis of endothelial cells (ECs) is crucial for the preservation of glomerular structure and function in aging. Here, we investigated the precise mechanisms of endothelial autophagy in renal aging. The genetic deletion of Atg7 in the ECs of Atg7flox/flox;Tie2-Cre mice accelerated aging-related glomerulopathy and tubulointerstitial fibrosis. The EC-specific Atg7 deletion in aging mice induced the detachment of EC with the disruption of glomerular basement membrane (GBM) assembly and increased podocyte loss resulting in microalbuminuria. A Transwell co-culture system of ECs and kidney organoids showed that the iron and oxidative stress induce the disruption of the endothelial barrier and increase vascular permeability, which was accelerated by the inhibition of autophagy. This resulted in the leakage of iron through the endothelial barrier into kidney organoids and increased oxidative stress, which led to ferroptotic cell death. The ferritin accumulation was increased in the kidneys of the EC-specific Atg7-deficient aging mice and upregulated the NLRP3 inflammasome signaling pathway. The pharmacologic inhibition of ferroptosis with liproxstatin-1 recovered the disrupted endothelial barrier and reversed the decreased expression of GPX4, as well as NLRP3 and IL-1ß, in endothelial autophagy-deficient aged mice, which attenuated aging-related renal injury including the apoptosis of renal cells, abnormal structures of GBM, and tubulointerstitial fibrosis. Our data showed that endothelial autophagy is essential for the maintenance of the endothelial barrier during renal aging and the impairment of endothelial autophagy accelerates renal senescence by ferroptosis and NLRP3 inflammasome signaling pathways. These processes may be attractive therapeutic targets to reduce cellular injury from renal aging.

Senescent Astrocytes Derived from Human Pluripotent Stem Cells Reveal Age-Related Changes and Implications for Neurodegeneration.

Astrocytes play a crucial role in maintaining brain homeostasis by regulating synaptic activity, providing metabolic support to neurons, and modulating immune responses in the central nervous system (CNS). During aging, astrocytes undergo senescence with various changes that affect their function and frequently lead to neurodegeneration. This study presents the first evidence of senescent astrocytes derived from human pluripotent stem cells (hPSCs). These senescent hPSC-derived astrocytes exhibited altered cellular and nuclear morphologies, along with increased expression of senescence-associated markers. Additionally, nuclear localization of NFκB, telomere shortening, and frequent signs of DNA damage were observed in these cells. Furthermore, senescent astrocytes showed defects in various critical functions necessary for maintaining a healthy CNS environment, including a reduced ability to support neuronal survival and clear neurotransmitters, synaptic debris, and toxic protein aggregates. Altered structural dynamics and reduced mitochondrial function were also observed in senescent astrocytes. Notably, treating hPSC-derived senescent astrocytes with chemicals targeting reactive oxygen species or an enzyme that regulates mitochondrial function can reverse senescence phenotypes. Thus, this study offers a valuable cellular model that can be utilized to investigate the mechanisms of brain aging and may present new avenues for discovering innovative therapeutic approaches for neurodegenerative diseases.

Dietary supplementation with Lacticaseibacillus rhamnosus IDCC3201 alleviates sarcopenia by modulating the gut microbiota and metabolites in dexamethasone-induced models.

Probiotics can exert direct or indirect influences on various aspects of health claims by altering the composition of the gut microbiome and producing bioactive metabolites. The aim of this study was to examine the effect of Lacticaseibacillus rhamnosus IDCC3201 on skeletal muscle atrophy in dexamethasone-induced C2C12 cells and a mouse animal model. Dexamethasone treatment significantly reduced C2C12 muscle cell viability, myotube diameter, and levels of muscle atrophic markers (Atrogin-1 and MuRF-1). These effects were alleviated by conditioned media (CM) and cell extract (EX) derived from L. rhamnosus IDCC3201. In addition, we assessed the in vivo therapeutic effect of L. rhamnosus IDCC3201 in a mouse model of dexamethasone (DEX)-induced muscle atrophy. Supplementation with IDCC3201 resulted in significant enhancements in body composition, particularly in lean mass, muscle strength, and myofibril size, in DEX-induced muscle atrophy mice. In comparison to the DEX-treatment group, the normal and DEX + L. rhamnosus IDCC3201 groups showed a higher transcriptional level of myosin heavy chain family genes (MHC1, MHC1b, MHC2A, 2bB, and 2X) and a reduction in atrophic muscle makers. These analyses revealed that L. rhamnosus IDCC3201 supplementation led to increased production of branched-chain amino acids (BCAAs) and improved the Allobaculum genus within the gut microbiota of muscle atrophy-induced groups. Taken together, our findings suggest that L. rhamnosus IDCC3201 represents a promising dietary supplement with the potential to alleviate sarcopenia by modulating the gut microbiome and metabolites.

Metabolic Regulation of Longevity and Immune Response in Caenorhabditis elegans by Ingestion of Lacticaseibacillus rhamnosus IDCC 3201 Using Multi-Omics Analysis.

Probiotics, specifically Lacticaseibacillus rhamnosus, have garnered attention for their potential health benefits. This study focuses on evaluating the probiotic properties of candidate probiotics L. rhamnosus IDCC 3201 (3201) using the Caenorhabditis elegans surrogate animal model, a well-established in vivo system for studying host-bacteria interactions. The adhesive ability to the host's gastrointestinal tract is a crucial criterion for selecting potential probiotic bacteria. Our findings demonstrated that 3201 exhibits significantly higher adhesive capabilities compared with Escherichia coli OP50 (OP50), a standard laboratory food source for C. elegans and is comparable with the widely recognized probiotic L. rhamnosus GG (LGG). In lifespan assay, 3201 significantly increased the longevity of C. elegans compared with OP50. In addition, preconditioning with 3201 enhanced C. elegans immune response against four different foodborne pathogenic bacteria. To uncover the molecular basis of these effects, transcriptome analysis elucidated that 3201 modulates specific gene expression related to the innate immune response in C. elegans. C-type lectin-related genes and lysozyme-related genes, crucial components of the immune system, showed significant upregulation after feeding 3201 compared with OP50. These results suggested that preconditioning with 3201 may enhance the immune response against pathogens. Metabolome analysis revealed increased levels of fumaric acid and succinic acid, metabolites of the citric acid cycle, in C. elegans fed with 3201 compared with OP50. Furthermore, there was an increase in the levels of lactic acid, a well-known antimicrobial compound. This rise in lactic acid levels may have contributed to the robust defense mechanisms against pathogens. In conclusion, this study demonstrated the probiotic properties of the candidate probiotic L. rhamnosus IDCC 3201 by using multi-omics analysis.

Corydalis ternata Nakai Alleviates Cognitive Decline in Alzheimer's Disease by Reducing ß-Amyloid and Neuroinflammation.

Recently, natural herbs have gained increasing attention owing to their comparatively low toxicity levels and the abundance of historical medical documentation regarding their use. Nevertheless, owing to a lack of knowledge regarding these herbs and their compounds, attempts to find those that could be beneficial for treating diseases have often been ad hoc; thus, there is now a growing demand for an in silico method to identify beneficial herbs. In this study, we present a computational approach for identifying natural herbs specifically effective in treating cognitive decline in Alzheimer's disease (AD) sufferers, which analyzes the similarities between herbal compounds and known drugs targeting AD-related proteins. Our in silico method suggests that Corydalis ternata can improve cognitive decline in AD sufferers. Behavioral tests with an AD mouse model for the confirmation of the in silico prediction reveals that C. ternata significantly alleviated the cognitive decline (memory and motor functions) caused by neurodegeneration. Further pathology analyses reveal that C. ternata decreases the level of Aß plaques, reduces neuroinflammation, and promotes autophagy flux, and thus C. ternata can be clinically effective for preventing mild cognitive impairment during the early stages of AD. These findings highlight the potential utility of our in silico method and the potential clinical application of the identified natural herb in treating and preventing AD.

Fermented mixed grain ameliorates chronic stress-induced depression-like behavior and memory deficit.

Fermented mixed grain (FG) has beneficial anti-cancer, antioxidant, and anti-inflammatory effects. In this study, we investigated the effects of FG on gut inflammation, brain dysfunction, and anxiety/depression-like behavior induced by unpredictable chronic mild stress (UCMS) in mice. Mice were administered mixed grain or FG for 3 weeks and were then exposed to UCMS for 4 weeks. FG administration ameliorated stress-induced anxiety/despair-like behavior. FG administration also prevented UCMS-induced memory impairment. Additionally, the mRNA levels of 5-HTR1A and IL-6 were restored to normal levels in the brains of FG-administered mice. FG administration also inhibited intestinal damage in stressed mice compared with that in the UCMS (without FG) group. These results suggest that FG can alleviate stress-induced intestinal damage, brain dysfunction, and cognitive impairment.

Effectiveness and safety of adalimumab in patients with intestinal Behçet's disease: a real-world prospective observational study in South Korea.

BACKGROUND: Intestinal Behçet's disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. METHODS: This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet's disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). RESULTS: A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953-0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). CONCLUSION: Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.

Protective Effects of Lacticaseibacillus rhamnosus IDCC3201 on Motor Functions and Anxiety Levels in a Chronic Stress Mouse Model.

Growing evidence indicates a crucial role of the gut microbiota in physiological functions. Gut-brain axis imbalance has also been associated with neuropsychiatric and neurodegenerative disorders. Studies have suggested that probiotics regulate the stress response and alleviate mood-related symptoms. In this study, we investigated the effects of the probiotic Lacticaseibacillus rhamnosus IDCC3201 (L3201) on the behavioral response and fecal metabolite content in an unpredictable chronic mild stress (UCMS) mouse model. Our study shows that chronic stress in mice for three weeks resulted in significant changes in behavior, including lower locomotor activity, higher levels of anxiety, and depressive-like symptoms, compared to the control group. Metabolomic analysis demonstrated that disrupted fecal metabolites associated with aminoacyl-tRNA biosynthesis and valine, leucine, and isoleucine biosynthesis by UCMS were restored with the administration of L3201. Oral administration of the L3201 ameliorated the observed changes and improved the behavioral alterations along with fecal metabolites, suggesting that probiotics play a neuroprotective role.

A multi-layered network model identifies Akt1 as a common modulator of neurodegeneration.

The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases (NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi-layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK-3ß), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell-based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long-term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.

24-h urine collection in patients with urolithiasis: perspective on renal function.

A prospective observational study involving consecutive patients diagnosed with symptomatic urolithiasis was conducted to evaluate the serial change of urinary protein and 24-h urine chemistry with time after surgical procedures for urolithiasis. A consecutive 24-h urine samples, including calcium, uric acid and citrate were collected before surgical treatments, 4 ~ 8 weeks after surgery and 6 months after surgery. The urinary protein to creatinine ratio was also repeated at each timepoint. Forty-seven patients completed the study. The quantity of 24-h urine chemistry, including calcium, uric acid and citrate, changed over time and tended to increase (p = 0.013, 0.076 and 0.004, respectively), but the changes were not prominent during short-term follow-up. In contrast, the urinary protein to creatinine ratio decreased (p < 0.001) after surgical treatment for symptomatic renal stones, and the change was reflected in short-term follow-up. However, the serial changes in the urinary protein to creatinine ratio were significantly related to the serial changes in the 24-h urinary chemistry (p < 0.001). Surgical decompression for symptomatic urolithiasis could decrease the urinary protein to creatinine ratio, indicating improvement from renal damage, which may be reflected in the increase in 24-h urinary chemistry, including calcium, uric acid and citrate. These results strengthen the previous guidelines for the timing of 24-h urine collection and provide new insight into the optimal timing from the perspective of renal function.

A machine learning-based quantitative model (LogBB_Pred) to predict the blood-brain barrier permeability (logBB value) of drug compounds.

MOTIVATION: Efficient assessment of the blood-brain barrier (BBB) penetration ability of a drug compound is one of the major hurdles in central nervous system drug discovery since experimental methods are costly and time-consuming. To advance and elevate the success rate of neurotherapeutic drug discovery, it is essential to develop an accurate computational quantitative model to determine the absolute logBB value (a logarithmic ratio of the concentration of a drug in the brain to its concentration in the blood) of a drug candidate. RESULTS: Here, we developed a quantitative model (LogBB_Pred) capable of predicting a logBB value of a query compound. The model achieved an R2 of 0.61 on an independent test dataset and outperformed other publicly available quantitative models. When compared with the available qualitative (classification) models that only classified whether a compound is BBB-permeable or not, our model achieved the same accuracy (0.85) with the best qualitative model and far-outperformed other qualitative models (accuracies between 0.64 and 0.70). For further evaluation, our model, quantitative models, and the qualitative models were evaluated on a real-world central nervous system drug screening library. Our model showed an accuracy of 0.97 while the other models showed an accuracy in the range of 0.29-0.83. Consequently, our model can accurately classify BBB-permeable compounds as well as predict the absolute logBB values of drug candidates. AVAILABILITY AND IMPLEMENTATION: Web server is freely available on the web at http://ssbio.cau.ac.kr/software/logbb_pred/. The data used in this study are available to download at http://ssbio.cau.ac.kr/software/logbb_pred/dataset.zip.

Preventive effect of peptides derived from fermented milk on chronic stress-induced brain damage and intestinal dysfunction in mice.

This study investigated the preventive effects of peptides derived from milk fermented with the probiotic strain Lactobacillus gasseri 505 (505) against stress-related brain damage and anxiety-like behavior. The peptides MKPWIQPKTKVIPYVRYL (Pep14) and VYQHQKAMKPWIQPKTKVIPYVRYL (Pep21), which exhibit high antioxidant and anti-inflammatory activities, were administered to stressed mice. The results showed that the stress mechanism in the gut-brain axis was regulated by pretreatment with both peptides, leading to inhibition of neurodevelopment and neuroinflammation through the hypothalamic-pituitary-adrenal (HPA) axis, based on the expression of related mRNA and proteins. The expression of colonic inflammation-related mRNA and proteins was also reduced. Moreover, anxiety-like behavior was significantly reduced in mice treated with Pep14 and Pep21. These results indicate that the bioactive peptides Pep14 and Pep21, derived from milk fermented with 505, may prevent stress-induced brain damage and anxiety-like behavior via regulation of the HPA axis.

Clinical outcomes of esophageal granular cell tumors with different endoscopic resection methods.

Esophageal granular cell tumors (GCTs), the second most common subepithelial tumors (SETs) of the esophagus, are potentially malignant with no definite management guidelines available. We retrospectively enrolled 35 patients with endoscopically resected esophageal GCTs between December 2008 and October 2021 and evaluated the clinical outcomes from the various methods performed. Several modified endoscopic mucosal resections (EMRs) were performed for treating esophageal GCTs. Clinical and endoscopic outcomes were evaluated. Mean age of patients was 55.8 ± 8.2, with majority being men (57.1%). Mean tumor size was 7.2 ± 2.6 mm, most (80.0%) were asymptomatic and present in the distal third of the esophagus (77.1%). Endoscopic characteristics predominantly included broad-based (85.7%) and whitish-to-yellowish color changes (97.1%). Endoscopic ultrasound (EUS) of 82.9% of the tumors revealed homogeneous hypoechoic SETs originating from the submucosa. The five endoscopic treatment methods used were: ligation-assisted (77.1%), conventional (8.7%), cap-assisted (5.7%), and underwater (5.7%) EMRs and ESD (2.9%). Mean procedure time was 6.6 ± 2.1 min, and no procedure-associated complications were noted. The en-bloc and complete histologic resection rates were 100% and 94.3%, respectively. No recurrences were noted during follow-up, and no significant differences in the clinical outcomes of the different methods of endoscopic resection were found. Based on tumor characteristics and therapeutic outcomes, modified EMR methods can be effective and safe. However, there were no significant differences in the clinical outcomes of the different methods of endoscopic resection.

Enhanced Cholesterol-Lowering and Antioxidant Activities of Soymilk by Fermentation with Lactiplantibacillus plantarum KML06.

This study aimed to evaluate the cholesterol-lowering and antioxidant activities of soymilk fermented with probiotic Lactobacillaceae strains and to investigate the production of related bioactive compounds. Lactiplantibacillus plantarum KML06 (KML06) was selected for the fermentation of soymilk because it has the highest antioxidant, cholesterol-lowering, and ß-glucosidase activities among the 10 Lactobacillaceae strains isolated from kimchi. The genomic information of strain KML06 was analyzed. Moreover, soymilk fermented with KML06 was evaluated for growth kinetics, metabolism, and functional characteristics during the fermentation period. The number of viable cells, which was similar to the results of radical scavenging activities and cholesterol assimilation, as well as the amount of soy isoflavone aglycones, daidzein, and genistein, was the highest at 12 h of fermentation. These results indicate that soymilk fermented with KML06 can prevent oxidative stress and cholesterol-related problems through the production of soy isoflavone aglycones.

Differentiation of astrocytes with characteristics of ventral midbrain from human embryonic stem cells.

Molecular and functional diversity among region-specific astrocytes is of great interest in basic neuroscience and the study of neurological diseases. In this study, we present the generation and characterization of astrocytes from human embryonic stem cells with the characteristics of the ventral midbrain (VM). Fine modulation of WNT and SHH signaling during neural differentiation induced neural precursor cells (NPCs) with high expression of EN1 and NKX6.1, but less expression of FOXA2. Overexpression of nuclear factor IB in NPCs induced astrocytes, thereby maintaining the expression of region-specific genes acquired in the NPC stage. When cocultured with dopaminergic (DA) precursors or DA neurons, astrocytes with VM characteristics (VM-iASTs) promoted the differentiation and survival of DA neurons better than those that were not regionally specified. Transcriptomic analysis showed that VM-iASTs were more closely related to human primary midbrain astrocytes than to cortical astrocytes, and revealed the upregulation of WNT1 and WNT5A, which supports their VM identity and explains their superior activity in DA neurons. Taken together, we hope that VM-iASTs can serve to improve ongoing DA precursor transplantation for Parkinson's disease, and that their transcriptomic data provide a valuable resource for investigating regional diversity in human astrocyte populations.

Prediction of intradialytic hypotension using pre-dialysis features-a deep learning-based artificial intelligence model.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning-based artificial intelligence (AI) model to predict IDH using pre-dialysis features. METHODS: Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost). RESULTS: IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. CONCLUSIONS: Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Clinical outcomes and risk factors associated with poor prognosis after endoscopic resection of 10-20 mm rectal neuroendocrine tumors: a multicenter, retrospective study of 10-year experience.

BACKGROUND: The efficacy of endoscopic resection for of 10-20 mm rectal neuroendocrine tumor (NET) remains controversial. We aimed to evaluate the clinical outcomes and risk factors associated with poor prognosis after endoscopic resection of 10-20 mm rectal NET and to determine the optimal treatment. METHODS: Patients who underwent endoscopic resection for rectal NET in four tertiary hospitals were enrolled, and data on with the clinical outcomes and risk factors related to poor prognosis were retrospectively analyzed. RESULTS: A total of 105 patients who underwent endoscopic submucosal resection (ESD; n = 65, 61.9%), modified endoscopic mucosal resection (mEMR; n = 31, 29.5%), and conventional EMR (cEMR; n = 9, 8.6%) were enrolled. The mean follow-up period was 41.2 ± 21.9 months. In the morphologic findings, the mean diameter was 11.6 mm (range 10-19); the shape was sessile (50.5%) and mixed type (49.5%), and surface depression was observed in 41.9% of patients. In the histologic findings, 87.6% of patients had G1 and 12.4% G2 tumor grade, and 3.8% of patients had lymphovascular invasion. The overall en bloc and histologically complete (R0) resections were 99.1% and 76.2%, respectively. cEMR was a less-frequently developed R0 resection. In the univariate and multivariate analyses for R0 resection, only surface depression was significantly associated. Regional or distant organs metastasis during follow-up developed in three patients (2.9%) and was significantly associated with female sex, redness, G2 tumor grade, and non-ESD methods. CONCLUSION: Patients who underwent endoscopic resection of 10-20 mm rectal NET had good prognosis; therefore, endoscopic resection can be considered as the first-line treatment, particularly for 10-14 mm rectal NET. However, the risk factors, such as female sex, redness, G2 tumor grade and non-ESD methods, were associated with regional or distant metastases during follow-up. Therefore, patients with these risk factors should be carefully monitored.

Clinical and endoscopic characteristics of sessile serrated lesions with dysplasia/carcinoma.

BACKGROUND/AIMS: Some sessile serrated lesions (SSLs) progress into dysplasia and colorectal cancer, however, the clinical and endoscopic characteristics of SSLs with dysplasia remain to be determined. In this study, we elucidated these characteristics in SSLs with dysplasia/carcinoma, compared with those of SSLs without dysplasia. METHODS: We retrospectively collected the clinical, endoscopic, and pathological data of 254 SSLs from 216 patients endoscopically resected between January 2009 and December 2020. RESULTS: All SSLs included 179 without dysplasia and 75 with dysplasia/carcinoma, including 55 with low-grade dysplasia, 10 with high-grade dysplasia, and 10 with submucosal cancer. In clinical characteristics, SSLs with dysplasia/carcinoma were significantly associated with advanced age, metabolic diseases, and high-risk adenomas. In endoscopic characteristics, SSLs with dysplasia/carcinoma were significantly associated with the distal colon, large size, polypoid morphology, surface-changes, no mucus cap, and narrow-band imaging international colorectal endoscopic classification (NICE) type 2/3. In the multivariate analysis, high-risk adenomas (odds ratio [OR], 2.98; p = 0.01), large size (OR, 1.18; p < 0.01), depression (OR, 11.74; p = 0.03), and NICE type 2/3 (OR, 14.97; p < 0.01) were significantly associated with SSLs with dysplasia/carcinoma. CONCLUSION: SSLs had a higher risk of dysplasia in the distal colon than in the proximal colon. SSLs with large size, depression, and adenomatous surface-patterns, as well as those in patients with high-risk adenomas, increased the risk of dysplasia/ carcinoma. This suggests that the clinical and endoscopic characteristics can aid in the diagnosis and management of SSLs with dysplasia/carcinoma.