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The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA 1 . As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities 2 . Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions 3,4 . Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel β-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: The association between body composition (BC) and cancer outcomes is complex and incompletely understood. Previous research in non-small-cell lung cancer (NSCLC) has been limited to small, single-institution studies and yielded promising, albeit heterogeneous, results., Objectives: To evaluate the association of BC with oncologic outcomes in patients receiving immunotherapy for advanced or metastatic NSCLC., Design, Setting, and Participants: This comprehensive multicohort analysis included clinical data from cohorts receiving treatment at the Dana-Farber Brigham Cancer Center (DFBCC) who received immunotherapy given alone or in combination with chemotherapy and prospectively collected data from the phase 1/2 Study 1108 and the chemotherapy arm of the phase 3 MYSTIC trial. Baseline and follow-up computed tomography (CT) scans were collected and analyzed using deep neural networks for automatic L3 slice selection and body compartment segmentation (skeletal muscle [SM], subcutaneous adipose tissue [SAT], and visceral adipose tissue). Outcomes were compared based on baseline BC measures or their change at the first follow-up scan. The data were analyzed between July 2022 and April 2023., Main Outcomes and Measures: Hazard ratios (HRs) for the association of BC measurements with overall survival (OS) and progression-free survival (PFS)., Results: A total of 1791 patients (878 women [49%]) with NSCLC were analyzed, of whom 487 (27.2%) received chemoimmunotherapy at DFBCC (DFBCC-CIO), 825 (46.1%) received ICI monotherapy at DFBCC (DFBCC-IO), 222 (12.4%) were treated with durvalumab monotherapy on Study 1108, and 257 (14.3%) were treated with chemotherapy on MYSTIC; median (IQR) ages were 65 (58-74), 66 (57-71), 65 (26-87), and 63 (30-84) years, respectively. A loss in SM mass, as indicated by a change in the L3 SM area, was associated with worse oncologic outcome across patient groups (HR, 0.59 [95% CI, 0.43-0.81] and 0.61 [95% CI, 0.47-0.79] for OS and PFS, respectively, in DFBCC-CIO; HR, 0.74 [95% CI, 0.60-0.91] for OS in DFBCC-IO; HR, 0.46 [95% CI, 0.33-0.64] and 0.47 [95% CI, 0.34-0.64] for OS and PFS, respectively, in Study 1108; HR, 0.76 [95% CI, 0.61-0.96] for PFS in the MYSTIC trial). This association was most prominent among male patients, with a nonsignificant association among female patients in the MYSTIC trial and DFBCC-CIO cohorts on Kaplan-Meier analysis. An increase of more than 5% in SAT density, as quantified by the average CT attenuation in Hounsfield units of the SAT compartment, was associated with poorer OS in 3 patient cohorts (HR, 0.61 [95% CI, 0.43-0.86] for DFBCC-CIO; HR, 0.62 [95% CI, 0.49-0.79] for DFBCC-IO; and HR, 0.56 [95% CI, 0.40-0.77] for Study 1108). The change in SAT density was also associated with PFS for DFBCC-CIO (HR, 0.73; 95% CI, 0.54-0.97). This was primarily observed in female patients on Kaplan-Meier analysis., Conclusions and Relevance: The results of this multicohort study suggest that loss in SM mass during systemic therapy for NSCLC is a marker of poor outcomes, especially in male patients. SAT density changes are also associated with prognosis, particularly in female patients. Automated CT-derived BC measurements should be considered in determining NSCLC prognosis.

Social determinants of health (SDoH) play a critical role in patient outcomes, yet their documentation is often missing or incomplete in the structured data of electronic health records (EHRs). Large language models (LLMs) could enable high-throughput extraction of SDoH from the EHR to support research and clinical care. However, class imbalance and data limitations present challenges for this sparsely documented yet critical information. Here, we investigated the optimal methods for using LLMs to extract six SDoH categories from narrative text in the EHR: employment, housing, transportation, parental status, relationship, and social support. The best-performing models were fine-tuned Flan-T5 XL for any SDoH mentions (macro-F1 0.71), and Flan-T5 XXL for adverse SDoH mentions (macro-F1 0.70). Adding LLM-generated synthetic data to training varied across models and architecture, but improved the performance of smaller Flan-T5 models (delta F1 + 0.12 to +0.23). Our best-fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models in the zero- and few-shot setting, except GPT4 with 10-shot prompting for adverse SDoH. Fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p < 0.05). Our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. These results demonstrate the potential of LLMs in improving real-world evidence on SDoH and assisting in identifying patients who could benefit from resource support., (© 2024. The Author(s).)

Biological agents known as anti-tumor necrosis factor (TNF) drugs are frequently utilized in the treatment of inflammatory bowel disease (IBD). In this study, we analyzed the shared processes of pyroptosis in Ulcerative colitis (UC) and Crohn's disease (CD), as well as explored the correlation between the burden of pyroptosis and the results of anti-TNF treatment based on bioinformatics analyses. We identified CAPS1, CASP5, GSDMD, AIM2, and NLRP3 as the hub genes, with AIM2 being the most effective indicator for predicting the response to anti-TNF therapy. We also noticed that non-responders received anti-TNF therapy exhibited elevated AIM2 protein expression. Subsequently, we conducted a cluster analysis based on AIM2-inflammasome-related genes and discovered that patients with a higher burden of AIM2 inflammasome displayed stronger immune function and a poor response to anti-TNF therapy. Overall, our study elucidates the pathway of pyroptosis in IBD and reveals AIM2 expression level as a potential biomarker for predicting the effectiveness of anti-TNF therapy., (© 2023. Springer Nature Limited.)

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8 + T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

Objectives: Cronkhite-Canada syndrome (CCS) is a rare nonhereditary gastrointestinal hamartomatous polyposis syndrome with a high risk of colorectal cancerogenesis. It is challenging to discriminate adenomas from nonneoplastic colorectal polyps macroscopically. This study aimed to explore the endoscopic features of different histopathological patterns of colorectal polyps in CCS., Methods: Sixty-seven lesions from 23 CCS patients were prospectively biopsied or resected during the colonoscopic examination for histopathological analysis. The Fisher's exact test and multivariate logistical analysis were conducted to reveal the predictive endoscopic features of CCS polyps with low-grade dysplasia (LGD) and adenomas., Results: There were seven (10.4%) adenomas, 20 (29.9%) CCS-LGD, and 40 (59.7%) nonneoplastic CCS polyps. Polyps were large (>20 mm) in none of the adenomas, 30.0% of CCS-LGD polyps, and 2.5% of nonneoplastic CCS polyps (P < 0.001). The color of the polyps was whitish for 71.4% of adenomas, 10.0% of CCS-LGD polyps, and 15.0% of nonneoplastic CCS polyps (P = 0.004). Pedunculated polyps were detected in 42.9% of adenomas, 45.0% of CCS-LGD polyps, and 5.0% of nonneoplastic CCS polyps (P < 0.001). The proportions of types IV and V I in the Kudo classification were 42.9%, 95.0%, and 35.0% in adenomatous, CCS-LGD, and nonneoplastic CCS polyps, respectively (P = 0.002). The endoscopic activity was in remission for 71.4% of adenomas, 5.0% of CCS-LGD polyps, and 10.0% of nonneoplastic CCS polyps (P < 0.001)., Conclusion: Endoscopic features, including the size, color, sessility, Kudo's pit pattern classification of polyps, and endoscopic activity, help identify the histopathological patterns of colorectal polyps in CCS., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Aim: Metabolic syndrome (MetS) increases the risk of colorectal cancer (CRC), and the impact of MetS on CRC prognosis remains controversial after the diagnosis of CRC has been established. This study aimed to explore the impact of the individual components and synergies of MetS on the prognosis of patients with CRC., Methods: We searched articles published before August 3, 2022, in four databases, including PubMed, Embase, Cochrane Library, and ScienceDirect. The random-effects model inverse variance method was used to estimate the summarized effect size., Results: Patients with CRC with MetS were 1.342 times more likely to experience all-cause mortality than those without MetS, and the 95% confidence interval (CI) of hazard ratio (HR) was 1.107-1.627 (P = 0.003). CRC-specific mortality in patients with CRC with MetS was 2.122 times higher than in those without MetS, and the 95% CI of HR was 1.080-4.173 (P = 0.029). CRC-specific mortality exhibited an increasing trend of risk with increased metabolic risk factors. The HR of CRC-specific mortality for one, two, and three metabolic risk factors was 1.206 (95% CI, 1.034-1.407; P = 0.017), 1.881 (95% CI, 1.253-2.824; P = 0.002), and 2.327 (95% CI, 1.262-4.291; P = 0.007), respectively., Conclusions: Metabolic syndrome increased all-cause and CRC-specific mortality in patients with CRC. As a single component of MetS, diabetes mellitus increased overall mortality in patients with CRC, while obesity increased CRC-specific mortality in patients with CRC, with a significant difference from non-MetS. Moreover, the risk of CRC-specific mortality increased with increasing number of metabolic risk factors., (© 2022 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

There is great heterogeneity among inflammatory bowel disease (IBD) patients in terms of pathogenesis, clinical manifestation, response to treatment, and prognosis, which requires the individualized and precision management of patients. Many studies have focused on prediction biomarkers and models for assessing IBD disease type, activity, severity, and prognosis. During the era of biologics, how to predict the response and side effects of patients to different treatments and how to quickly recognize the loss of response have also become important topics. Multiomics is a promising area for investigating the complex network of IBD pathogenesis. Integrating numerous amounts of data requires the use of artificial intelligence., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P <0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P <0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference ( P =0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) ( OR =3.39, 95% CI : 1.59-7.21), dual-marker ASCA (+) ANCA (-) ( OR =2.87, 95% CI : 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) ( OR =3.09, 95% CI : 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) ( OR =3.15, 95% CI : 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) ( OR =2.69, 95% CI : 1.42-5.12) and dual-marker ANCA (+) ASCA (-) ( OR =2.11, 95% CI : 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.

Objective: To investigate the prevalence and independent risk factors of non-alcoholic fatty liver disease (NAFLD) and advanced chronic liver disease among the type 2 diabetes mellitus (T2DM) population in the Shenyang community, so as to provide evidence for the prevention and control of T2DM combined with NAFLD. Methods: This cross-sectional study was conducted in July 2021. 644 T2DM cases from 13 communities in Heping District, Shenyang City were selected. All the surveyed subjects underwent physical examination (measurements of height, body mass index, neck circumference, waist circumference, abdominal circumference, hip circumference, and blood pressure), infection screening (excluding hepatitis B and C, AIDS, and syphilis), random fingertip blood glucose, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). The study subjects were divided into the non-advanced chronic liver disease group and the advanced chronic liver disease group according to whether the LSM value was greater than 10 kPa. Cirrhotic portal hypertension development was indicated in patients with LSM ≥ 15 kPa. The comparison of multiple mean values among the sample groups was performed by analysis of variance when the normal distribution was met. Results: In the T2DM community population, there were 401 cases (62.27%) combined with NAFLD, 63 cases (9.78%) combined with advanced chronic liver disease, and 14 cases (2.17%) combined with portal hypertension. There were 581 cases in the non-advanced chronic liver disease group and 63 cases (9.78%) in the advanced chronic liver disease group (LSM ≥10 kPa), including 49 cases (7.61%) with 10 kPa≤LSM<15 kPa, 11 cases (1.71%) with 15 kPa ≤LSM<25 kPa, and 3 cases (0.47%) with LSM ≥ 25 kPa. Age, body mass, body mass index, neck circumference, waist circumference, hip circumference, waist-to-height ratio, systolic blood pressure, and CAP were all statistically different between the non-advanced chronic liver disease group and the advanced chronic liver disease group ( F =-1.983,-2.598,-4.091,-2.062,-3.909, -4.581,-4.295,-2.474, and -5.191, respectively; P <0.05). There was a statistically significant difference in terms of whether or not there was combined cerebrovascular disease (2=4.632, P =0.031); however, there were no statistically significant differences in terms of lifestyle, diabetes complications, and other complications ( P >0.05). Conclusion: Patients with T2DM have a higher prevalence of NAFLD (62.27%) than those with advanced chronic liver disease (9.78%). 2.17% of T2DM cases in the community may not have had early diagnosis and early intervention, and they might have been combined with cirrhotic portal hypertension. So, the management of these patients should be strengthened.

Purpose: We retrospectively evaluated outcomes after radiation therapy for patients with oligoprogression on immune checkpoint inhibitors (ICI)., Methods and Materials: We identified patients irradiated to ≤5 progressive lesions while receiving ICI between 2010 and 2020. We excluded patients whose systemic therapy was switched after radiation but before progression. We evaluated predictors of local control (LC), progression-free survival (PFS) and overall survival (OS)., Results: We screened 1423 patients and identified 120 who were eligible; the most common histologies were lung cancer (n = 59) and melanoma (n = 36). The median number of oligoprogressive lesions was 1. For the median LC of irradiated oligoprogressive lesions, PFS and OS were not reached at 6.41 (4.67-7.66) and 29.80 (22.54-43.33) months, respectively. Tumor histology, radiated site, or radiation modality were not associated with LC, PFS, or OS. Local response to radiation (P < .0001) and radiation of newly developed lesions (P = .02) were associated with LC. Predictors of PFS on univariate and multivariate analyses were best response to radiation (P = .006) and high programmed death ligand 1 tumor proportion score (P = .02). On multivariate analyses, OS was associated with cumulative oligoprogressive lesion volumes (P = .02) and duration of ICI before oligoprogression (P = .03)., Conclusions: Promising outcomes were observed among patients irradiated for oligoprogression on ICI, especially those with a favorable local response, high tumor programmed death ligand 1 expression, and those receiving ICI for longer periods before oligoprogression. These data can help identify patients well suited for radiation therapy versus those who should switch systemic treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease (IBD). Methods: Patients with moderate and severe active IBD at the first use of vedolizumab from May 1 to October 31, 2021 were retrospectively enrolled. Then the clinical characteristics, and the efficacy and safety of vedolizumab were evaluated. Meanwhile, the clinical response rate, biological response rate and endoscopic response rate were calculated. Multivariate analysis was used to evaluate the independent influencing factors of short-term clinical efficacy and safety. Results: A total of 78 patients (44 males and 34 females) with IBD were enrolled, with a mean age of (40.5±11.9) years. The clinical remission rate, clinical response rate, biological remission rate, biological response rate and endoscopic remission rate was 60.3% (47/78), 85.9% (67/78), 70.5% (55/78), 43.6% (34/78) and 47.0% (31/66) respectively after 14 weeks of treatment. Body mass index (BMI) ≥ 18.5 kg/m 2 ( HR =5.04, 95% CI : 1.50-16.91, P =0.009) and biological remission at 6 weeks of treatment ( HR =15.22, 95% CI : 3.16-73.38, P =0.001) were predictors of endoscopic remission at 14 weeks of treatment. Adverse reactions occurred in 57 patients, with an incidence of 73.1%. The main manifestations were liver and kidney damage (37.2%) and infection (26.9%). Conclusions: More than half of patients with moderate and severe active IBD can achieve clinical remission after 14 weeks of vedolizumab treatment. Baseline BMI level and biological remission at 6 weeks of treatment are predictors of mucosal healing at 14 weeks. The incidence of adverse reactions is not low, although serious adverse reactions are rare in short-term treatment.

Immunotherapy has dramatically revolutionized the therapeutic landscape for patients with cancer. Although immune checkpoint inhibitors are now accepted as effective anticancer therapies, they introduce a novel class of toxicity, termed immune-related adverse events, which can lead to the temporary or permanent discontinuation of immunotherapy and life-threatening tumor progression. Therefore, the effective prevention and treatment of immune-related adverse events is a clinical imperative to maximize the utility of immunotherapies. Immune-related adverse events are related to the intestinal microbiota, baseline gut microbiota composition is an important determinant of immune checkpoint inhibitor-related colitis, and antibiotics exacerbate these undesirable side-effects. Supplementation with specific probiotics reduces immune checkpoint inhibitor-related colitis in mice, and fecal microbiota transplantation has now been shown to effectively treat refractory immune checkpoint inhibitor-related colitis in the clinic. Hence, modifying the microbiota holds great promise for preventing and treating immune-related adverse events. Microbiomes and their metabolites play important roles in the potential underlying mechanisms through interactions with both innate and adaptive immune cells. Here we review the gut microbiota and immune regulation; the changes occurring in the microbiota during immune checkpoint inhibitor therapy; the relationship between the microbiota and immune-related adverse events, antibiotics, probiotics/prebiotics, and fecal microbiota transplantation in immune checkpoint inhibitor-related colitis; and the protective mechanisms mediated by the microbiome and metabolites in immune-related adverse events., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The early prediction of intravenous corticosteroid (IVCS) resistance in acute severe ulcerative colitis (ASUC) patients remains an unresolved challenge. This study aims to construct and validate a model that accurately predicts IVCS resistance., Methods: A retrospective cohort was established, with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020. The primary outcome was IVCS resistance. Classification models, including logistic regression and machine learning-based models, were constructed. External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University., Results: A total of 129 patients were included in the derivation cohort. During index hospitalization, 102 (79.1%) patients responded to IVCS and 27 (20.9%) failed; 18 (14.0%) patients underwent colectomy in 3 months; 6 received cyclosporin as rescue therapy, and 2 eventually escalated to colectomy; 5 succeeded with infliximab as rescue therapy. The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and C-reactive protein (CRP) level at Day 3 are independent predictors of IVCS resistance. The areas under the receiver-operating characteristic curves (AUROCs) of the logistic regression, decision tree, random forest, and extreme-gradient boosting models were 0.873 (95% confidence interval [CI], 0.704-1.000), 0.648 (95% CI, 0.463-0.833), 0.650 (95% CI, 0.441-0.859), and 0.604 (95% CI, 0.416-0.792), respectively. The logistic regression model achieved the highest AUROC value of 0.703 (95% CI, 0.473-0.934) in the external validation., Conclusions: In patients with ASUC, UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance. We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC. A nomogram based on the logistic regression model might aid in the management of ASUC patients., (© The Author(s) 2022. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background/aims: Opportunistic infection in inflammatory bowel disease (IBD) has become a serious problem. However, its status of doctors' opinions and test equipment in hospitals are unclear. The aim of the study was to investigate these issues to improve the prognosis of IBD patients., Methods: This retrospective, multicenter study was conducted by 83 investigators who were members of the Asian Organization for Crohn's and Colitis. Data on opportunistic infection were collected from hospital databases between January 2017 and December 2017. The survey consisted of 11 items., Results: Most physicians appreciated the diagnostic value of tissue cytomegalovirus (CMV) DNA, accounting for 86.1% of members in China, 37.5% in Japan, 52.9% in South Korea, and 66.7% in Southeast Asia. Only 83.1% of hospitals had the ability to test for CMV immunohistochemistry in Asia. Hepatitis B surface antigen (HBsAg) screening was recommended by all members. However, only 66.7% in China, 70.6% in South Korea, and 66.7% in Southeast Asia agreed to routinely vaccinate IBD patients when HBsAg tested negative. Most members preferred metronidazole (74.7%) as the first choice for patients with Clostridium difficile infection. However, the proportion of stool C. difficile toxin test was lower in China than in other areas (75.0% in China vs 95.8% in Japan and 100% in South Korea and Southeast Asia, p<0.05)., Conclusions: Opportunistic infection from CMV, hepatitis B virus, and C. difficile should be of high concern for IBD patients. More efforts are needed, such as understanding consensus in clinical practice and improving testing facilities in hospitals.

Background: Artificial intelligence (AI) and deep learning have shown great potential in streamlining clinical tasks. However, most studies remain confined to in silico validation in small internal cohorts, without external validation or data on real-world clinical utility. We developed a strategy for the clinical validation of deep learning models for segmenting primary non-small-cell lung cancer (NSCLC) tumours and involved lymph nodes in CT images, which is a time-intensive step in radiation treatment planning, with large variability among experts., Methods: In this observational study, CT images and segmentations were collected from eight internal and external sources from the USA, the Netherlands, Canada, and China, with patients from the Maastro and Harvard-RT1 datasets used for model discovery (segmented by a single expert). Validation consisted of interobserver and intraobserver benchmarking, primary validation, functional validation, and end-user testing on the following datasets: multi-delineation, Harvard-RT1, Harvard-RT2, RTOG-0617, NSCLC-radiogenomics, Lung-PET-CT-Dx, RIDER, and thorax phantom. Primary validation consisted of stepwise testing on increasingly external datasets using measures of overlap including volumetric dice (VD) and surface dice (SD). Functional validation explored dosimetric effect, model failure modes, test-retest stability, and accuracy. End-user testing with eight experts assessed automated segmentations in a simulated clinical setting., Findings: We included 2208 patients imaged between 2001 and 2015, with 787 patients used for model discovery and 1421 for model validation, including 28 patients for end-user testing. Models showed an improvement over the interobserver benchmark (multi-delineation dataset; VD 0·91 [IQR 0·83-0·92], p=0·0062; SD 0·86 [0·71-0·91], p=0·0005), and were within the intraobserver benchmark. For primary validation, AI performance on internal Harvard-RT1 data (segmented by the same expert who segmented the discovery data) was VD 0·83 (IQR 0·76-0·88) and SD 0·79 (0·68-0·88), within the interobserver benchmark. Performance on internal Harvard-RT2 data segmented by other experts was VD 0·70 (0·56-0·80) and SD 0·50 (0·34-0·71). Performance on RTOG-0617 clinical trial data was VD 0·71 (0·60-0·81) and SD 0·47 (0·35-0·59), with similar results on diagnostic radiology datasets NSCLC-radiogenomics and Lung-PET-CT-Dx. Despite these geometric overlap results, models yielded target volumes with equivalent radiation dose coverage to those of experts. We also found non-significant differences between de novo expert and AI-assisted segmentations. AI assistance led to a 65% reduction in segmentation time (5·4 min; p<0·0001) and a 32% reduction in interobserver variability (SD; p=0·013)., Interpretation: We present a clinical validation strategy for AI models. We found that in silico geometric segmentation metrics might not correlate with clinical utility of the models. Experts' segmentation style and preference might affect model performance., Funding: US National Institutes of Health and EU European Research Council., Competing Interests: Declaration of interests AH reports consultancy fees for Altis Labs; and owning stock in Altis Labs. HJWLA reports being a scientific adviser and shareholder for Onc.Ai, Love Health, Health-AI, and Bristol Myers Squibb. RHM reports a research grant from ViewRay; honoraria from NewRT and ViewRay; is on an advisory board for AstraZeneca; and reports travel expenses from NewRT. DEK reports honoraria from RefleXion; and is a consultant and on an advisory board for Genentech. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To define endoscopic and histological remission in ulcerative colitis (UC) accurately, several scoring systems have been established. A novel virtual electronic chromoendoscopy score, the Paddington International Virtual ChromoendoScopy ScOre (PICaSSO), was developed, validated, and reproduced to assess inflammation grade and predict patient prognosis. We externally verified and validated the clinical value of PICaSSO in UC patients., Methods: This prospective study enrolled 63 UC patients. The Mayo endoscopic score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO were adopted for endoscopic evaluation. All biopsy samples were scored using the Robarts histological index (RHI), Nancy histological index (NHI), and "Extent, Chronicity, Activity, Plus additional findings" (ECAP) score. Patients with an endoscopic MES of 0-1 at baseline were followed up during a median time of 23.5 months., Results: PICaSSO was strongly correlated with other endoscopic and histological scoring systems. PICaSSO ≤3 had advantages in assessing histological remission (HR), with the highest accuracy of 88.9% for ECAP-HR. Relapse-free survival rates were significantly different between patients with MES 0 and MES 1 and patients with PICaSSO ≤3 and >3 (P = 0.010 and 0.018, respectively)., Conclusions: PICaSSO was externally validated with strong correlations with other endoscopic and histological scoring systems in UC, and PICaSSO-ER might potentially predict a better long-term clinical outcome in UC patients., (© 2022 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: The prediction of hepatocellular carcinoma (HCC) survival is challenging because of its rapid progression. In recent years, necroptosis was found to be involved in the progression of multiple cancer types. However, the role of necroptosis in HCC remains unclear., Methods: Clinicopathological parameters and transcriptomic data of 370 HCC patients were obtained from TCGA-LIHC dataset. Prognosis-related necroptosis genes (PRNGs) were identified and utilized to construct a LASSO risk model. The GEO cohorts (GSE54236 and GSE14520) were used for external validation. We evaluated the distribution of HCC patients, the difference in prognosis, and the accuracy of the prognostic prediction of the LASSO risk model. The immune microenvironment and functional enrichment of different risk groups were further clarified. Finally, we performed a drug sensitivity analysis on the PRNGs that constructed the LASSO model and verified their mRNA expression levels in vitro. Results: A total of 48 differentially expressed genes were identified, 23 of which were PRNGs. We constructed the LASSO risk model using nine genes: SQSTM1 , FLT3 , HAT1 , PLK1 , MYCN , KLF9 , HSP90AA1 , TARDBP , and TNFRSF21 . The outcomes of low-risk patients were considerably better than those of high-risk patients in both the training and validation cohorts. In addition, stronger bile acid metabolism, xenobiotic metabolism, and more active immune cells and immune functions were observed in low-risk patients, and high expressions of TARDBP , PLK1 , and FLT3 were associated with greater drug sensitivity. With the exception of FLT3 , the mRNA expression of the other eight genes was verified in Huh7 and 97H cells . Conclusions . The PRNG signature provides a novel and effective method for predicting the outcome of HCC as well as potential targets for further research., Competing Interests: There are no potential conflicts of interest for the authors to disclose., (Copyright © 2022 Xin Gao et al.)

Synovitis,acne,pustulosis,hyperostosis,and osteitis (SAPHO) syndrome is a rare disease. The previous literature demonstrated that about 10% of the patients with SAPHO syndrome were complicated with inflammatory bowel disease.So far,few cases of SAPHO syndrome complicated with inflammatory bowel disease have been reported in China.Herein,we reported a SAPHO syndrome case complicated with ulcerative colitis. The patient suffered from recurrent attacks of colitis following treatment of SAPHO syndrome with etanercept.

Identifying the presence of intravenous contrast material on CT scans is an important component of data curation for medical imaging-based artificial intelligence model development and deployment. Use of intravenous contrast material is often poorly documented in imaging metadata, necessitating impractical manual annotation by clinician experts. Authors developed a convolutional neural network (CNN)-based deep learning platform to identify intravenous contrast enhancement on CT scans. For model development and validation, authors used six independent datasets of head and neck (HN) and chest CT scans, totaling 133 480 axial two-dimensional sections from 1979 scans, which were manually annotated by clinical experts. Five CNN models were trained first on HN scans for contrast enhancement detection. Model performances were evaluated at the patient level on a holdout set and external test set. Models were then fine-tuned on chest CT data and externally validated. This study found that Digital Imaging and Communications in Medicine metadata tags for intravenous contrast material were missing or erroneous for 1496 scans (75.6%). An EfficientNetB4-based model showed the best performance, with areas under the curve (AUCs) of 0.996 and 1.0 in HN holdout ( n = 216) and external ( n = 595) sets, respectively, and AUCs of 1.0 and 0.980 in the chest holdout ( n = 53) and external ( n = 402) sets, respectively. This automated, scan-to-prediction platform is highly accurate at CT contrast enhancement detection and may be helpful for artificial intelligence model development and clinical application. Keywords: CT, Head and Neck, Supervised Learning, Transfer Learning, Convolutional Neural Network (CNN), Machine Learning Algorithms, Contrast Material Supplemental material is available for this article. © RSNA, 2022., Competing Interests: Disclosures of conflicts of interest: Z.Y. No relevant relationships. J.M.Q. No relevant relationships. A.H. Consultant for Altis Labs; shareholder in Altis Labs. R.Z. No relevant relationships. D.P. No relevant relationships. J.L. No relevant relationships. Z.Z. No relevant relationships. R.H.M. Contract/grant from ViewRay; consulting for ViewRay and AstraZeneca; payment for expert testimony from U.S. District Attorney's Office of New York. H.J.W.L.A. No relevant relationships. B.H.K. RSNA Research Scholar Award NIH K08DE030216., (© 2022 by the Radiological Society of North America, Inc.)

Objectives: Cronkhite-Canada syndrome (CCS) is a rare hamartomatous polyposis syndrome with a proposed association with chronic autoimmune inflammation. To date, genetic background of patients with CCS remains less investigated. In this study we aimed to explore the genomic landscape of CCS., Methods: Whole exome sequencing was performed on peripheral blood samples extracted from 18 patients with CCS. Potential function-impacting germline variants were filtered by R software. Through systematic data analysis, a number of genetic variants were identified. Enrichment analysis was performed using the R package ClusterProfiler., Results: Overall, 3960 low-frequency (<0.05 or not reported in the Exome Aggregation Consortium East Asian, 1000 Genomes, or ESP6500 database) potentially function-impacting germline variants were identified, with 18 genes (FDFT1, LOC400863, MUC3A, MUC4, ZNF806, GXYLT1, MUC6, PABPC3, PSPH, ZFPM1, CIC, LOC283710, ARSD, GOLGA6L2, LOC388282, SLC25A5, TMEM247, WDR89) involved over half the patients. Functional enrichment of these genes revealed several biological processes in relation to innate immune responses and glycosylation. Only one likely pathogenic germline variant of an hamartomatous polyposis syndrome-associated gene, PTCH1, was detected in one patient., Conclusions: CCS has genomic alteration patterns completely distinct from those of traditional hamartomatous polyposis syndrome. The germline mutation landscape indicates potential roles of innate immune responses and glycosylation in the pathogenesis of CCS., (© 2022 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden., Methods: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements., Results: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases., Conclusion: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Radiation therapy (RT)-associated lymphopenia may adversely affect treatment outcomes, particularly in the era of immunotherapy. We sought to determine dosimetric factors correlated with lymphopenia after palliative RT in a cohort of patients with advanced cancer treated with anti-PD-1 immune checkpoint inhibitors., Methods and Materials: We included patients with metastatic lung cancer, melanoma, or renal cell carcinoma who were treated with either pembrolizumab or nivolumab and received palliative RT to an extracranial site. Baseline and nadir absolute lymphocyte counts (ALCs) within 6 weeks of RT were recorded. Dosimetric factors were extracted from the corresponding dose-volume histograms and also used to model the dose to circulating lymphocytes via a whole-body blood flow model that simulates the spatiotemporal distribution of blood particles in major organs during RT., Results: We analyzed 55 patients who underwent 80 total courses of palliative RT; most (94%) were treated with 3-dimensional conformal RT. Doses to the whole body, bone, and large blood vessels (LBVs) were negatively correlated with the ALC nadir, with the strongest correlations seen at V15 (r s , -0.38, -0.43, and -0.37, and P  = .0004, .0001, and .0008, respectively). Doses to other organs were not significantly correlated with the ALC nadir. The modeled dose to circulating lymphocytes was also negatively correlated with the ALC nadir and percent ALC change (for D2%, r s , -0.31 and -0.44, and P  = .005 and .0001, respectively). Grade ≥3 lymphopenia was associated with LBV V15 (odds ratio [OR], 1.16; 95% CI, 1.07-1.26; P < .001), bone V15 (OR, 1.04; 95% CI, 1.01-1.08; P  = .03), body V15 (OR, 1.003; 95% CI, 1.001-1.006; P  = .008), and modeled lymphocyte dose (OR, 1.45; 95% CI, 1.16-1.82; P < .001)., Conclusions: The RT dose to the whole body, bone, and LBVs and the modeled dose to circulating lymphocytes were correlated with lymphopenia in patients treated with palliative RT and anti-PD-1 immune checkpoint inhibitors. These findings may inform future radiation planning in this setting., (© 2021 The Authors.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a pandemic worldwide. Although COVID-19 mainly affects the respiratory system, gastrointestinal (GI) manifestations have been frequently reported in such cases, even as initial symptoms. There have been several studies on different GI manifestations in patients with mild and severe disease or in remission. In this review article we summarized different GI manifestations of COVID-19 at various disease stages and the possible mechanisms based on published literatures, as well as the significance of GI manifestations in systemic inflammatory injury., (© 2021 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Auxin secreted by root-associated bacteria promotes plant growth, yet benefits to bacteria themselves are ill-defined. In this issue of Cell Host & Microbe, Tzipilevich et al. (2021) demonstrate that auxin and plant EFR-triggered response are essential for root colonization of B. velezensis, indicating potential co-evolution of plants and root commensal bacteria., (Copyright © 2021 Elsevier Inc. All rights reserved.)