Pub Date : 2022-09-21DOI: 10.3389/fgstr.2022.989987
Ali A. Alali, A. Hashim, A. Alkandari
Background and objectives Gastric varices (GV) bleeding is a catastrophic complication of portal hypertension and is associated with significant morbidity and mortality. There are limited effective therapeutic interventions for the management of bleeding GV. Recently, EUS-guided therapy has been shown to be effective and safe intervention for such patients. However, there are no data to describe the feasibility and safety of EUS-guided therapy for GV in Arab population. The aim of this study is to describe our initial experience of EUS-guided therapy for GV in Kuwait. Methods A case-series of patients that underwent EUS-guided therapy for clinically significant GV. All patients underwent EUS-guided therapy including Cyanoacrylate (CYA) injection with or without coil embolization. Patients were followed post procedure to document GV obliteration and monitor for any adverse events. Results In total, 15 patients were included in this study (80% male) with mean age of 58 ± 12 years. The main indication for therapy was active GV bleeding (53.3%) followed by secondary prophylaxis (33.3%). Most patients had GOV-2 (80%) with mean GV size of 24.9 ± 7.9 mm. Combined EUS coil-CYA was used in most patients (80%), mean volume of CYA injected was 1.5 ± 0.74ml and mean number coils used of 1.5 ± 1.4. The technical success rate was 100% and all patients achieved GV obliteration after a median of 1 session (range 1-2). There were no major adverse events. Conclusion Among Arab population with portal hypertension, EUS-guided therapy is highly effective and safe option for the managements of clinically significant GV.
{"title":"Endoscopic ultrasound guided therapy of gastric varices: Initial experience in the Arab world (with video)","authors":"Ali A. Alali, A. Hashim, A. Alkandari","doi":"10.3389/fgstr.2022.989987","DOIUrl":"https://doi.org/10.3389/fgstr.2022.989987","url":null,"abstract":"Background and objectives Gastric varices (GV) bleeding is a catastrophic complication of portal hypertension and is associated with significant morbidity and mortality. There are limited effective therapeutic interventions for the management of bleeding GV. Recently, EUS-guided therapy has been shown to be effective and safe intervention for such patients. However, there are no data to describe the feasibility and safety of EUS-guided therapy for GV in Arab population. The aim of this study is to describe our initial experience of EUS-guided therapy for GV in Kuwait. Methods A case-series of patients that underwent EUS-guided therapy for clinically significant GV. All patients underwent EUS-guided therapy including Cyanoacrylate (CYA) injection with or without coil embolization. Patients were followed post procedure to document GV obliteration and monitor for any adverse events. Results In total, 15 patients were included in this study (80% male) with mean age of 58 ± 12 years. The main indication for therapy was active GV bleeding (53.3%) followed by secondary prophylaxis (33.3%). Most patients had GOV-2 (80%) with mean GV size of 24.9 ± 7.9 mm. Combined EUS coil-CYA was used in most patients (80%), mean volume of CYA injected was 1.5 ± 0.74ml and mean number coils used of 1.5 ± 1.4. The technical success rate was 100% and all patients achieved GV obliteration after a median of 1 session (range 1-2). There were no major adverse events. Conclusion Among Arab population with portal hypertension, EUS-guided therapy is highly effective and safe option for the managements of clinically significant GV.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45768356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-20DOI: 10.3389/fgstr.2022.1021050
A. Duarte Mendes, R. Vicente, M. Vitorino, Michelle Silva, D. Alpuim Costa
The treatment paradigm of neoplastic diseases has dramatically shifted with the introduction of immune checkpoint inhibitors (ICI). They induce a durable response in a wide variety of solid tumors, but this response depends on the infiltration of lymphocytes capable of recognizing and killing tumor cells. The primary predictor of intrinsic immune resistance to ICIs is the absence of lymphocytes in the tumor, the so-called “cold tumors”. Colorectal cancer (CRC) remains one of the most common and challenging cancer, but it is not traditionally considered a highly immunogenic tumor. In fact, immunotherapy showed a remarkable antitumoral activity only on a small subset of CRC patients – the ones with microsatellite instability-high/deficient DNA mismatch repair (MSI-H/dMMR). Most CRCs display a molecular microsatellite stability/proficient DNA mismatch repair (MSS/pMMR) profile, so strategies to improve tumor immunogenicity are crucial. Therefore, ongoing studies investigate new approaches to convert “cold” to “hot” tumors in MSS/pMMR CRCs. In addition, it has been described that gut microbiota influences tumor development and the host immune response. Hence, the microbiota may modulate the immune response, becoming a promising biomarker to identify patients who will benefit from ICIs. Future data will help to better understand microbiota mechanisms and their role in ICI efficacy. Precision medicine in cancer treatment could involve modulation of the microbiota through different strategies to improve tumor immunogenicity. In this review, we aim to present the potential relationship between gut microbiota and the modulation of the immune system and the hypothetical implications in CRC treatment, namely ICIs.
{"title":"Modulation of tumor environment in colorectal cancer – could gut microbiota be a key player?","authors":"A. Duarte Mendes, R. Vicente, M. Vitorino, Michelle Silva, D. Alpuim Costa","doi":"10.3389/fgstr.2022.1021050","DOIUrl":"https://doi.org/10.3389/fgstr.2022.1021050","url":null,"abstract":"The treatment paradigm of neoplastic diseases has dramatically shifted with the introduction of immune checkpoint inhibitors (ICI). They induce a durable response in a wide variety of solid tumors, but this response depends on the infiltration of lymphocytes capable of recognizing and killing tumor cells. The primary predictor of intrinsic immune resistance to ICIs is the absence of lymphocytes in the tumor, the so-called “cold tumors”. Colorectal cancer (CRC) remains one of the most common and challenging cancer, but it is not traditionally considered a highly immunogenic tumor. In fact, immunotherapy showed a remarkable antitumoral activity only on a small subset of CRC patients – the ones with microsatellite instability-high/deficient DNA mismatch repair (MSI-H/dMMR). Most CRCs display a molecular microsatellite stability/proficient DNA mismatch repair (MSS/pMMR) profile, so strategies to improve tumor immunogenicity are crucial. Therefore, ongoing studies investigate new approaches to convert “cold” to “hot” tumors in MSS/pMMR CRCs. In addition, it has been described that gut microbiota influences tumor development and the host immune response. Hence, the microbiota may modulate the immune response, becoming a promising biomarker to identify patients who will benefit from ICIs. Future data will help to better understand microbiota mechanisms and their role in ICI efficacy. Precision medicine in cancer treatment could involve modulation of the microbiota through different strategies to improve tumor immunogenicity. In this review, we aim to present the potential relationship between gut microbiota and the modulation of the immune system and the hypothetical implications in CRC treatment, namely ICIs.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45330501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-15DOI: 10.3389/fgstr.2022.988971
Katia E. Valdez, M. Javanbakht, Kori Keith, Roxanne Archer, John Z Deng, S. Marx, A. Kuznetsova, D. Dylla, J. Klausner
Background The objective of this study was to examine differences in healthcare utilization among patients receiving eight vs. 12-weeks of treatment for infection with the Hepatitis C Virus (HCV). Methods We conducted a retrospective cohort study among 282 treatment-naïve, HCV-infected patients. Those eligible were uninfected with the Human Immunodeficiency Virus, non-cirrhotic, and treated between 2016 and 2019 as part of an extensive, urban, university-affiliated healthcare system. Electronic medical data were abstracted starting from HCV treatment initiation and up to one year post-initiation or achievement of post-treatment sustained virologic response, whichever occurred first. The primary outcome of interest was healthcare utilization, defined by the number and type of healthcare encounters. Differences in healthcare utilization between those receiving eight vs. 12-weeks of treatment were examined using Student’s t-test, Fisher’s exact test, Pearson’s chi-square test, and the Wilcoxon rank-sum test. Results A total of 282 eligible patients were analyzed. At baseline, the average age was 59 years (standard deviation=12), and the majority were male (55%) and white/Caucasian (58%). There were no baseline demographic or clinical differences between those completing 8 (n=59) or 12 (n=223) weeks of treatment. While no overall difference in healthcare encounters was observed between those receiving the 8-weeks (median encounters 6; IQR 4-11) and 12-weeks of treatment (median encounters 8; IQR 5-12; P value=0.07), a notable difference was seen in the number of laboratory visits between the groups (median 1 vs. 2; P value=0.04). Conclusions Our findings indicate modest reductions in healthcare utilization among those receiving shorter treatment regimens for HCV infection, specifically regarding laboratory testing. These findings suggest that shorter treatment regimens may improve treatment expansion in settings that are otherwise too resource-constrained to deliver HCV care successfully.
{"title":"Healthcare resource utilization in Hepatitis C-infected patients completing eight versus twelve weeks of treatment: A retrospective cohort study","authors":"Katia E. Valdez, M. Javanbakht, Kori Keith, Roxanne Archer, John Z Deng, S. Marx, A. Kuznetsova, D. Dylla, J. Klausner","doi":"10.3389/fgstr.2022.988971","DOIUrl":"https://doi.org/10.3389/fgstr.2022.988971","url":null,"abstract":"Background The objective of this study was to examine differences in healthcare utilization among patients receiving eight vs. 12-weeks of treatment for infection with the Hepatitis C Virus (HCV). Methods We conducted a retrospective cohort study among 282 treatment-naïve, HCV-infected patients. Those eligible were uninfected with the Human Immunodeficiency Virus, non-cirrhotic, and treated between 2016 and 2019 as part of an extensive, urban, university-affiliated healthcare system. Electronic medical data were abstracted starting from HCV treatment initiation and up to one year post-initiation or achievement of post-treatment sustained virologic response, whichever occurred first. The primary outcome of interest was healthcare utilization, defined by the number and type of healthcare encounters. Differences in healthcare utilization between those receiving eight vs. 12-weeks of treatment were examined using Student’s t-test, Fisher’s exact test, Pearson’s chi-square test, and the Wilcoxon rank-sum test. Results A total of 282 eligible patients were analyzed. At baseline, the average age was 59 years (standard deviation=12), and the majority were male (55%) and white/Caucasian (58%). There were no baseline demographic or clinical differences between those completing 8 (n=59) or 12 (n=223) weeks of treatment. While no overall difference in healthcare encounters was observed between those receiving the 8-weeks (median encounters 6; IQR 4-11) and 12-weeks of treatment (median encounters 8; IQR 5-12; P value=0.07), a notable difference was seen in the number of laboratory visits between the groups (median 1 vs. 2; P value=0.04). Conclusions Our findings indicate modest reductions in healthcare utilization among those receiving shorter treatment regimens for HCV infection, specifically regarding laboratory testing. These findings suggest that shorter treatment regimens may improve treatment expansion in settings that are otherwise too resource-constrained to deliver HCV care successfully.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47109408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-31DOI: 10.3389/fgstr.2022.884507
J. Qian, Zemin Hu, Kun He, Y. He
Background Surgical resection combined with oral tyrosine kinase inhibitors(TKI) is the most effective treatment for gastrointestinal stromal tumor(GIST) liver metastases. Liver transplantation (LT) is the last resort for the treatment of terminal liver malignancy. Whether it can be a potential treatment option for liver metastases from unresectable GIST is worth exploring. Case presentation We report a 38-year-old woman who underwent jejunal stromal tumor resection and TKI(imatinib) therapy 15 years ago for jejunal stromal tumor liver metastases. During the period from 2015 to 2018, the liver metastases continued to grow after the patient stopped taking imatinib voluntarily, and the patient subsequently underwent multiple interventional surgeries and drug treatments, which were still poorly curative. The tumor was deemed unresectable because it filled the entire liver, and the patient subsequently underwent LT and was treated with imatinib post-operatively, which resulted in no recurrence of the tumor within 18 months of follow-up. Literature review There are few reports in the literature on LT for the treatment of liver metastases from GIST. A systematic review and summary of the current literature by literature search revealed that LT as a last resort for metastatic GIST of the liver remains a major challenge. Conclusions LT combined with TKI-targeted therapy is a potential therapy worth exploring for patients with unresectable metastatic GIST.
{"title":"Liver transplantation combined with tyrosine kinase inhibitors for the treatment of hepatic metastatic giant gastrointestinal stromal tumors: A case report and literature review","authors":"J. Qian, Zemin Hu, Kun He, Y. He","doi":"10.3389/fgstr.2022.884507","DOIUrl":"https://doi.org/10.3389/fgstr.2022.884507","url":null,"abstract":"Background Surgical resection combined with oral tyrosine kinase inhibitors(TKI) is the most effective treatment for gastrointestinal stromal tumor(GIST) liver metastases. Liver transplantation (LT) is the last resort for the treatment of terminal liver malignancy. Whether it can be a potential treatment option for liver metastases from unresectable GIST is worth exploring. Case presentation We report a 38-year-old woman who underwent jejunal stromal tumor resection and TKI(imatinib) therapy 15 years ago for jejunal stromal tumor liver metastases. During the period from 2015 to 2018, the liver metastases continued to grow after the patient stopped taking imatinib voluntarily, and the patient subsequently underwent multiple interventional surgeries and drug treatments, which were still poorly curative. The tumor was deemed unresectable because it filled the entire liver, and the patient subsequently underwent LT and was treated with imatinib post-operatively, which resulted in no recurrence of the tumor within 18 months of follow-up. Literature review There are few reports in the literature on LT for the treatment of liver metastases from GIST. A systematic review and summary of the current literature by literature search revealed that LT as a last resort for metastatic GIST of the liver remains a major challenge. Conclusions LT combined with TKI-targeted therapy is a potential therapy worth exploring for patients with unresectable metastatic GIST.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91170994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-17DOI: 10.3389/fgstr.2022.965982
O. Nyssen, L. Moreira, N. García-Morales, Anna Cano-Català, I. Puig, F. Mégraud, C. O'Morain, J. Gisbert
Background The ideal treatment approach for H. pylori infection has not yet been defined; therefore, the most effective management strategies for adult patients need to be identified to ensure clinical practice is aligned with the best standard of care. Our aim was to perform a review of research studies from the European Registry on H. pylori management (Hp-EuReg) by synthesizing the most clinically relevant information from each published manuscript. Methods All research studies published between 2013 and 2022, evaluating any information related to H. pylori infection management within the Hp-EuReg, a long-term registry of routine clinical practice by gastroenterologists in Europe, were included in the review. Results Overall, 26 studies have been published to date, where 12 evaluated the overall European data and the remaining were performed locally among the 28 participating countries. Eighteen studies evaluated the effectiveness of first- and/or second-line treatment, where one focused on penicillin allergic patients, six focused on specific treatment schemes, one evaluated the role of statins as a concomitant drug when combined with the eradication therapy, one assessed the adverse event profile of treatments, one evaluated the bacterial antibiotic resistance trends, and a last one reported on the common mistakes in routine clinical practice of European gastroenterologists. Conclusion The Hp-EuReg had a major influence on the routine clinical practice of European gastroenterologists, improving H. pylori eradication treatment success, allowing to make recommendations in line with the current consensus guidelines and potentially serving as a model for other diseases.
{"title":"European Registry on Helicobacter pylori Management (Hp-EuReg): Most relevant results for clinical practice","authors":"O. Nyssen, L. Moreira, N. García-Morales, Anna Cano-Català, I. Puig, F. Mégraud, C. O'Morain, J. Gisbert","doi":"10.3389/fgstr.2022.965982","DOIUrl":"https://doi.org/10.3389/fgstr.2022.965982","url":null,"abstract":"Background The ideal treatment approach for H. pylori infection has not yet been defined; therefore, the most effective management strategies for adult patients need to be identified to ensure clinical practice is aligned with the best standard of care. Our aim was to perform a review of research studies from the European Registry on H. pylori management (Hp-EuReg) by synthesizing the most clinically relevant information from each published manuscript. Methods All research studies published between 2013 and 2022, evaluating any information related to H. pylori infection management within the Hp-EuReg, a long-term registry of routine clinical practice by gastroenterologists in Europe, were included in the review. Results Overall, 26 studies have been published to date, where 12 evaluated the overall European data and the remaining were performed locally among the 28 participating countries. Eighteen studies evaluated the effectiveness of first- and/or second-line treatment, where one focused on penicillin allergic patients, six focused on specific treatment schemes, one evaluated the role of statins as a concomitant drug when combined with the eradication therapy, one assessed the adverse event profile of treatments, one evaluated the bacterial antibiotic resistance trends, and a last one reported on the common mistakes in routine clinical practice of European gastroenterologists. Conclusion The Hp-EuReg had a major influence on the routine clinical practice of European gastroenterologists, improving H. pylori eradication treatment success, allowing to make recommendations in line with the current consensus guidelines and potentially serving as a model for other diseases.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42854017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-15DOI: 10.3389/fgstr.2022.935447
Daniel A. DiLeo, C. Zenger, Giulio Quarta
Objectives Esophageal food bolus impaction is a medical emergency and 10-20% of impacted food boluses will require endoscopic removal. Emergent and prolonged procedures are associated with increased adverse events. We are interested in the relationship between the pre-endoscopic duration of esophageal food impaction and the duration of esophagogastroduodenoscopy (EGD) performed to remove the impacted food bolus. Methods Between 2010 and 2021, we examined EGD procedures performed for esophageal food impaction. Subjects were classified according to pre-endoscopic duration of food impaction. Results We found a positive correlation between pre-endoscopic duration of food impaction and procedure length (r=0.18). Esophageal impactions with mixed foods resulted in the longest procedure duration (p<0.05). Increasing age, male gender, and duration of impaction greater than 42 hours were significantly associated with increased procedure duration (p<0.05). Esophageal perforations, prolonged intubations, admissions following EGD, and readmissions were associated with EGD duration greater than 25.5 minutes. No adverse events occurred in patients who underwent EGD within 6 hours of symptom onset. Conclusions In the case of an esophageal food impaction, the time between symptom onset and endoscopy is positively correlated with procedure length and risk of adverse outcomes. We suggest that food impaction should remain an indication for emergent endoscopy. Prospective studies evaluating the safety and outcomes of prolonged time to endoscopy will further clarify the management of esophageal food impactions.
{"title":"Influence of pre-endoscopic duration of esophageal food impaction on endoscopy time and postprocedure adverse events","authors":"Daniel A. DiLeo, C. Zenger, Giulio Quarta","doi":"10.3389/fgstr.2022.935447","DOIUrl":"https://doi.org/10.3389/fgstr.2022.935447","url":null,"abstract":"Objectives Esophageal food bolus impaction is a medical emergency and 10-20% of impacted food boluses will require endoscopic removal. Emergent and prolonged procedures are associated with increased adverse events. We are interested in the relationship between the pre-endoscopic duration of esophageal food impaction and the duration of esophagogastroduodenoscopy (EGD) performed to remove the impacted food bolus. Methods Between 2010 and 2021, we examined EGD procedures performed for esophageal food impaction. Subjects were classified according to pre-endoscopic duration of food impaction. Results We found a positive correlation between pre-endoscopic duration of food impaction and procedure length (r=0.18). Esophageal impactions with mixed foods resulted in the longest procedure duration (p<0.05). Increasing age, male gender, and duration of impaction greater than 42 hours were significantly associated with increased procedure duration (p<0.05). Esophageal perforations, prolonged intubations, admissions following EGD, and readmissions were associated with EGD duration greater than 25.5 minutes. No adverse events occurred in patients who underwent EGD within 6 hours of symptom onset. Conclusions In the case of an esophageal food impaction, the time between symptom onset and endoscopy is positively correlated with procedure length and risk of adverse outcomes. We suggest that food impaction should remain an indication for emergent endoscopy. Prospective studies evaluating the safety and outcomes of prolonged time to endoscopy will further clarify the management of esophageal food impactions.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49219448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-12DOI: 10.3389/fgstr.2022.979314
Yuxi Guo, Zexie Li, N. Cheng, X. Jia, Jie Wang, Hongyu Ma, Runyuan Zhao, Bolin Li, Yanru Cai, Qian Yang
Objective To investigate the therapeutic effect and possible mechanism of artemisinin on ulcerative colitis (UC) induced by sodium glucan sulfate (DSS) in rats based on network pharmacology. Methods First, according to the 3D structure of artemisinin, the effective targets of the active compounds were obtained through the Swissstarge website (www.swisstargetprediction.ch/) and the TargetNet website (http://targetnet.scbdd.com/). With the aid of Genecards (https://www.genecards.org/), OMIM (https://omim.org/), TTD (http://db.idrblab.net/ttd/) to obtain effective targets of disease. The disease gene-drug target network was constructed by extracting the intersection targets of the two, and the visualization operation and analysis were performed by using Cytoscape 3.7.2. Gene function enrichment analysis and pathway analysis were performed on the intersection targets with the help of R language software. Autidock Vina was used for molecular docking of artemisinin to key targets. Then, 40 male Wistar rats were randomly divided into normal group, model group, mesalazine group (0.315 g/kg·d) and artemisinin group (0.1 g/kg·d), with 10 rats in each group. Except for the normal group, the rats in the other groups were given 3.5% DSS solution freely for 10 days to replicate the UC model. After the successful modeling, the rats were given intragastric administration. The normal group and the model group were given the same amount of 0.9% normal saline, once a day, for 14 days. The general condition of the rats was recorded every day and the disease activity index (DAI) score was performed. After the administration, the colonic mucosal damage index (CMDI) was scored, the histopathological changes of the colon were observed by HE staining, and the levels or activities of serum CRP, TNF-α, MDA, SOD, HIF-1α and T-AOC were detected by ELISA, and fecal and intestinal microbiota of rats were detected by 16S rDNA sequencing. Results Network pharmacology shows that, there were 98 key targets of artemisinin screening, 4853 effective targets of UC, and 43 intersection targets for artemisinin and UC, involving 48 signaling pathways. The molecular docking results showed that the binding energies of the key proteins to artemisinin were less than -5.0 kJ·mol-1, and the binding energy of PTGS2 NOS3 to artemisinin was the best. Animal experiments have shown that, Compared with the model group, the DAI and CMDI scores of the artemisinin group and the mesalazine group decreased, the levels and activities of serum CRP, TNF-α, MDA and HIF-1α decreased, the levels and activities of SOD and T-AOC increased, the abundance and diversity of inteatinal microbiota increased, and the abundance of p-Acidobacteria, p-Chloroflexi, p-Gemmatimonadetes, p-Nitrospirae in artemisinin group increased (P＜0.05), and there was no significant change in others. Conclusion Artemisinin intervenes with UC through key target proteins such as PTGS2 and ESR1, and involves various biological processes such
{"title":"To investigate the effects of artemisinin on inflammatory factors and intestinal microbiota in rats with ulcerative colitis based on network pharmacology","authors":"Yuxi Guo, Zexie Li, N. Cheng, X. Jia, Jie Wang, Hongyu Ma, Runyuan Zhao, Bolin Li, Yanru Cai, Qian Yang","doi":"10.3389/fgstr.2022.979314","DOIUrl":"https://doi.org/10.3389/fgstr.2022.979314","url":null,"abstract":"Objective To investigate the therapeutic effect and possible mechanism of artemisinin on ulcerative colitis (UC) induced by sodium glucan sulfate (DSS) in rats based on network pharmacology. Methods First, according to the 3D structure of artemisinin, the effective targets of the active compounds were obtained through the Swissstarge website (www.swisstargetprediction.ch/) and the TargetNet website (http://targetnet.scbdd.com/). With the aid of Genecards (https://www.genecards.org/), OMIM (https://omim.org/), TTD (http://db.idrblab.net/ttd/) to obtain effective targets of disease. The disease gene-drug target network was constructed by extracting the intersection targets of the two, and the visualization operation and analysis were performed by using Cytoscape 3.7.2. Gene function enrichment analysis and pathway analysis were performed on the intersection targets with the help of R language software. Autidock Vina was used for molecular docking of artemisinin to key targets. Then, 40 male Wistar rats were randomly divided into normal group, model group, mesalazine group (0.315 g/kg·d) and artemisinin group (0.1 g/kg·d), with 10 rats in each group. Except for the normal group, the rats in the other groups were given 3.5% DSS solution freely for 10 days to replicate the UC model. After the successful modeling, the rats were given intragastric administration. The normal group and the model group were given the same amount of 0.9% normal saline, once a day, for 14 days. The general condition of the rats was recorded every day and the disease activity index (DAI) score was performed. After the administration, the colonic mucosal damage index (CMDI) was scored, the histopathological changes of the colon were observed by HE staining, and the levels or activities of serum CRP, TNF-α, MDA, SOD, HIF-1α and T-AOC were detected by ELISA, and fecal and intestinal microbiota of rats were detected by 16S rDNA sequencing. Results Network pharmacology shows that, there were 98 key targets of artemisinin screening, 4853 effective targets of UC, and 43 intersection targets for artemisinin and UC, involving 48 signaling pathways. The molecular docking results showed that the binding energies of the key proteins to artemisinin were less than -5.0 kJ·mol-1, and the binding energy of PTGS2 NOS3 to artemisinin was the best. Animal experiments have shown that, Compared with the model group, the DAI and CMDI scores of the artemisinin group and the mesalazine group decreased, the levels and activities of serum CRP, TNF-α, MDA and HIF-1α decreased, the levels and activities of SOD and T-AOC increased, the abundance and diversity of inteatinal microbiota increased, and the abundance of p-Acidobacteria, p-Chloroflexi, p-Gemmatimonadetes, p-Nitrospirae in artemisinin group increased (P＜0.05), and there was no significant change in others. Conclusion Artemisinin intervenes with UC through key target proteins such as PTGS2 and ESR1, and involves various biological processes such","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48453322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-12DOI: 10.3389/fgstr.2022.971353
E. Gil, Kate M O'Neill, Elton Aleksi, J. Budrewicz, R. Melidone, L. Spirio
Objective To compare a RADA16-based self-assembling peptide hydrogel versus an inorganic powder-based spray device for controlling postoperative bleeding in upper and lower GI mucosal lesions in pigs. Methods Multiple mucosal lesions were endoscopically-created in the stomachs and lower colons of six Yorkshire swine on Day 0. Three animals’ wounds were treated with 2.5% RADA16 solution (PuraStat®), two animals were treated with an aerosolized mineral powder (Hemospray®), and one animal was an untreated control. Primary outcomes were test article applications required to control initial bleeding, time-to-hemostasis, and rebleeding incidence. Secondary outcomes included animal recovery, and clinical pathology at weekly endoscopic evaluations and the 4-week study terminus. Results Number of material administrations required and time-to-hemostasis was comparable between PuraStat and Hemospray groups. Rebleeding rates were comparable between treatments. Two of 12 (17%) Hemospray and none of 18 (0%) PuraStat stomach sites experienced rebleeding during the final 4 min of the 10-min observation period. No delayed bleeding was observed during weekly endoscopic follow-ups. Hematology and serology values remained normal in all animals. Histology showed expected healing responses at all PuraStat- and Hemospray-treated defects, with less inflammation than untreated sites. Histomorphological observations were comparable between different groups for both the stomach and colon for test and control materials, with lower inflammation scores than untreated sites. Performance and usability responses were generally good with both systems, although the Ability to Treat Intended Site score was significantly better with PuraStat in upper GI lesions. Conclusions PuraStat and Hemospray were effective topical hemostats for mild-to-moderate bleeding in upper and lower GI wounds. Rebleeding was observed in two of 12 Hemospray-treated sites and none of 18 PuraStat-treated sites. PuraStat and Hemospray were associated with better wound healing than untreated controls. The ability to treat upper GI lesions was easier with the PuraStat versus Hemospray system.
{"title":"Comparison of PuraStat self-assembling peptide hydrogel versus mineral-based Hemospray for endoscopic hemostasis of upper and lower gastrointestinal lesions in pigs","authors":"E. Gil, Kate M O'Neill, Elton Aleksi, J. Budrewicz, R. Melidone, L. Spirio","doi":"10.3389/fgstr.2022.971353","DOIUrl":"https://doi.org/10.3389/fgstr.2022.971353","url":null,"abstract":"Objective To compare a RADA16-based self-assembling peptide hydrogel versus an inorganic powder-based spray device for controlling postoperative bleeding in upper and lower GI mucosal lesions in pigs. Methods Multiple mucosal lesions were endoscopically-created in the stomachs and lower colons of six Yorkshire swine on Day 0. Three animals’ wounds were treated with 2.5% RADA16 solution (PuraStat®), two animals were treated with an aerosolized mineral powder (Hemospray®), and one animal was an untreated control. Primary outcomes were test article applications required to control initial bleeding, time-to-hemostasis, and rebleeding incidence. Secondary outcomes included animal recovery, and clinical pathology at weekly endoscopic evaluations and the 4-week study terminus. Results Number of material administrations required and time-to-hemostasis was comparable between PuraStat and Hemospray groups. Rebleeding rates were comparable between treatments. Two of 12 (17%) Hemospray and none of 18 (0%) PuraStat stomach sites experienced rebleeding during the final 4 min of the 10-min observation period. No delayed bleeding was observed during weekly endoscopic follow-ups. Hematology and serology values remained normal in all animals. Histology showed expected healing responses at all PuraStat- and Hemospray-treated defects, with less inflammation than untreated sites. Histomorphological observations were comparable between different groups for both the stomach and colon for test and control materials, with lower inflammation scores than untreated sites. Performance and usability responses were generally good with both systems, although the Ability to Treat Intended Site score was significantly better with PuraStat in upper GI lesions. Conclusions PuraStat and Hemospray were effective topical hemostats for mild-to-moderate bleeding in upper and lower GI wounds. Rebleeding was observed in two of 12 Hemospray-treated sites and none of 18 PuraStat-treated sites. PuraStat and Hemospray were associated with better wound healing than untreated controls. The ability to treat upper GI lesions was easier with the PuraStat versus Hemospray system.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46440766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-12DOI: 10.3389/fgstr.2022.914371
E. Stange
Inflammatory bowel diseases (IBD) have seen major progress in current concepts and treatment regimes. Based on the theory of an inadequate “overshoot” of the mucosal immune response to the intestinal microbiome, therapies have been developed to interfere with the key mediators of inflammation from cytokines, including TNF and IL12/23, to integrins such as α4ß7 and intracellular cytokine signal transducers such as janus kinases. Recently, sphingosine-1-receptor agonists were marketed to suppress mucosal inflammation by sequestering lymphocytes in peripheral lymph nodes. However, the aim of these regimes targeting immunity to induce a long-term deep remission, including mucosal healing, is missed in most patients. Contrasting these anti-inflammatory mechanisms of action, the pathogenic focus has finally shifted to the mucosal antibacterial barrier in both Crohn´s disease and ulcerative colitis. Translating this novel concept requires a completely different approach but, in the end, may come closer to a cure of these devastating diseases, in which an incomplete immune modulation fails to achieve the key endpoints: halting disease activity and progression. This review aims to give an overview of past, current, and future concepts in IBD, focusing on both pathogenesis and consequent therapy. A cure is in sight only if both reflect the actual key mechanisms of slow bacterial entry into the mucosa and are harmonized and in line.
{"title":"Current and future aspects of IBD research and treatment: The 2022 perspective","authors":"E. Stange","doi":"10.3389/fgstr.2022.914371","DOIUrl":"https://doi.org/10.3389/fgstr.2022.914371","url":null,"abstract":"Inflammatory bowel diseases (IBD) have seen major progress in current concepts and treatment regimes. Based on the theory of an inadequate “overshoot” of the mucosal immune response to the intestinal microbiome, therapies have been developed to interfere with the key mediators of inflammation from cytokines, including TNF and IL12/23, to integrins such as α4ß7 and intracellular cytokine signal transducers such as janus kinases. Recently, sphingosine-1-receptor agonists were marketed to suppress mucosal inflammation by sequestering lymphocytes in peripheral lymph nodes. However, the aim of these regimes targeting immunity to induce a long-term deep remission, including mucosal healing, is missed in most patients. Contrasting these anti-inflammatory mechanisms of action, the pathogenic focus has finally shifted to the mucosal antibacterial barrier in both Crohn´s disease and ulcerative colitis. Translating this novel concept requires a completely different approach but, in the end, may come closer to a cure of these devastating diseases, in which an incomplete immune modulation fails to achieve the key endpoints: halting disease activity and progression. This review aims to give an overview of past, current, and future concepts in IBD, focusing on both pathogenesis and consequent therapy. A cure is in sight only if both reflect the actual key mechanisms of slow bacterial entry into the mucosa and are harmonized and in line.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48697270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-12DOI: 10.3389/fgstr.2022.959082
C. Walker, A. Boland, A. Carroll, A. O’Connor
Approximately 25% of people with quiescent inflammatory bowel disease (IBD) have symptoms caused by a functional gastrointestinal disorder (FGID). The pathophysiology of FGIDs in IBD is multifactorial. The gut–brain axis plays an important role as a bidirectional pathway with reciprocal gastrointestinal and psychological symptoms. Other factors include altered gastrointestinal motility, microbiome dysbiosis, medication use, prior surgery, impaired intestinal permeability, immune-system activation, and visceral hypersensitivity. As both IBD and certain FGIDs can have similar symptoms, it can be difficult to determine which disorder is the precipitant of symptoms. However, a prompt diagnosis of an overlapping FGID helps avoid unnecessary corticosteroid use and escalations of IBD treatment. Despite their prevalence, there have been very few randomized controlled trials conducted on therapeutic interventions for overlapping FGIDs in IBD. Therefore, management usually follows those interventions recommended for FGIDs, with certain adaptations made to allow for an altered gastrointestinal anatomy and functioning, caused by IBD.
{"title":"Concurrent functional gastrointestinal disorders in patients with inflammatory bowel disease","authors":"C. Walker, A. Boland, A. Carroll, A. O’Connor","doi":"10.3389/fgstr.2022.959082","DOIUrl":"https://doi.org/10.3389/fgstr.2022.959082","url":null,"abstract":"Approximately 25% of people with quiescent inflammatory bowel disease (IBD) have symptoms caused by a functional gastrointestinal disorder (FGID). The pathophysiology of FGIDs in IBD is multifactorial. The gut–brain axis plays an important role as a bidirectional pathway with reciprocal gastrointestinal and psychological symptoms. Other factors include altered gastrointestinal motility, microbiome dysbiosis, medication use, prior surgery, impaired intestinal permeability, immune-system activation, and visceral hypersensitivity. As both IBD and certain FGIDs can have similar symptoms, it can be difficult to determine which disorder is the precipitant of symptoms. However, a prompt diagnosis of an overlapping FGID helps avoid unnecessary corticosteroid use and escalations of IBD treatment. Despite their prevalence, there have been very few randomized controlled trials conducted on therapeutic interventions for overlapping FGIDs in IBD. Therefore, management usually follows those interventions recommended for FGIDs, with certain adaptations made to allow for an altered gastrointestinal anatomy and functioning, caused by IBD.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47785953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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