Pub Date : 2024-04-02DOI: 10.3389/fgstr.2024.1359002
G. Rizzo, M. Traina, I. Tarantino
The utilization of graphic novels in the realm of clinical medicine is an infrequent occurrence. However, there is a burgeoning interest in their application across a spectrum of pathological conditions with the ultimate aim of enhancing patient care. This study is a prospective pilot designed to assess the influence of graphic novels on the stress levels and behavioral responses of patients diagnosed with pancreatic lesions and who are to undergo endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). Patients exhibiting radiological and clinical pancreatic lesions needing biopsy will be evaluated consecutively. The inclusion criteria encompass the presence of a solid pancreatic mass or a partially solid mass in the event of a cystic component. The exclusion criteria include patients with cognitive impairments, those currently on benzodiazepines or other psychotropic medications, and those with a prior diagnosis of cancer. The authors have developed a comic panel comprising a sequence of six vibrant vignettes, which delineate the standard procedure of EUS-FNB to the patient. Following hospital admission, patients who meet the enrolment criteria and consent to participate in the study will be randomly assigned to either the test or the control group. A graphic novel will be distributed to all patients in the test group, who will have the opportunity to peruse it while awaiting the procedure. Subsequent to the EUS-FNB, all enrolled patients will complete the Beck Anxiety Inventory (BAI) and a modified version of the Depression Anxiety Stress Scales-21 (termed mDASS-21 or mASS-14). The BAI, a 21-item self-report inventory, is employed to gauge the severity of anxiety in adults. The other questionnaire is a modified rendition of the DASS-21, which originally comprised 21 items segregated into three subscales (anxiety, stress, and depression) with seven items each. The anxiety subscale measures physiological arousal, situational anxiety, and the subjective experience of the effects of anxiety, while the stress subscale assesses chronic non-specific arousal, difficulty relaxing, nervous tension, irritability, agitation, and impatience.
{"title":"The impact of a graphic novel on anxiety and stress in patients undergoing endoscopic ultrasound with fine needle biopsy for pancreatic lesions: a pilot study protocol","authors":"G. Rizzo, M. Traina, I. Tarantino","doi":"10.3389/fgstr.2024.1359002","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1359002","url":null,"abstract":"The utilization of graphic novels in the realm of clinical medicine is an infrequent occurrence. However, there is a burgeoning interest in their application across a spectrum of pathological conditions with the ultimate aim of enhancing patient care. This study is a prospective pilot designed to assess the influence of graphic novels on the stress levels and behavioral responses of patients diagnosed with pancreatic lesions and who are to undergo endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). Patients exhibiting radiological and clinical pancreatic lesions needing biopsy will be evaluated consecutively. The inclusion criteria encompass the presence of a solid pancreatic mass or a partially solid mass in the event of a cystic component. The exclusion criteria include patients with cognitive impairments, those currently on benzodiazepines or other psychotropic medications, and those with a prior diagnosis of cancer. The authors have developed a comic panel comprising a sequence of six vibrant vignettes, which delineate the standard procedure of EUS-FNB to the patient. Following hospital admission, patients who meet the enrolment criteria and consent to participate in the study will be randomly assigned to either the test or the control group. A graphic novel will be distributed to all patients in the test group, who will have the opportunity to peruse it while awaiting the procedure. Subsequent to the EUS-FNB, all enrolled patients will complete the Beck Anxiety Inventory (BAI) and a modified version of the Depression Anxiety Stress Scales-21 (termed mDASS-21 or mASS-14). The BAI, a 21-item self-report inventory, is employed to gauge the severity of anxiety in adults. The other questionnaire is a modified rendition of the DASS-21, which originally comprised 21 items segregated into three subscales (anxiety, stress, and depression) with seven items each. The anxiety subscale measures physiological arousal, situational anxiety, and the subjective experience of the effects of anxiety, while the stress subscale assesses chronic non-specific arousal, difficulty relaxing, nervous tension, irritability, agitation, and impatience.","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":"138 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140755826","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 : 2024-03-22DOI: 10.3389/fgstr.2024.1372191
Neil O’Morain, R. Stack, J. Doherty, B. Nolan, P. Girod, Lakshman Kumar, M. Mccrossan, Elaine Joy, Orlaith Casey, G. Horgan, Glen Doherty
Colonoscopy following a positive FIT test in an average risk population is effective in reducing CRC incidence and mortality. While lower gastrointestinal symptoms remain a common cause for referral for colonoscopy, symptoms are poor predictors of clinically significant disease. The study was performed to compare neoplasia detection FIT +ve individuals and age-matched symptomatic cohorts. A single centre retrospective observational study was performed including all index colonoscopies performed on patients aged 60-70 from January 2015 to September 2021. Diagnostic yield was reported as adenoma detection rate, SSL detection rate, detection of high risk finding or adenocarcinoma. 8,106 colonoscopies were performed on patients aged 60-70 years. 3,695 (45.6%) originated from screening (FIT +ve). With exclusion criteria applied, 2,640 (59.9%) for screening and 1,767 (40.1%) for symptomatic patients were included. Median age in screening was 65 years (IQR 62-67) and 64 years in the symptomatic group (IQR 62-68), with male predominance in both groups (n=1,536, 58.1%, n=944, 53.4%). There were significant differences in both the ADR (56% vs 26.3%, p<0.01) and the SSLDR (10.4% vs. 8.1%, p=0.05) in the screening cohort compared to the symptomatic group. High risk findings (21.3% vs. 7.5%, p<0.01) were significantly more prevalent in the screening group with a considerably higher colorectal cancer (4.7% vs. 0.9%, p=<0.001) detection rate. FIT based triage significantly outperforms symptom based investigation for individuals in the 60-70 age group. Patients should be preferentially referred to organised colorectal cancer screening. FIT can be performed on symptomatic patients, to identify low risk individuals.
{"title":"Neoplasia detection in FIT positive screening colonoscopies compared with an age-controlled symptomatic cohort: a retrospective review","authors":"Neil O’Morain, R. Stack, J. Doherty, B. Nolan, P. Girod, Lakshman Kumar, M. Mccrossan, Elaine Joy, Orlaith Casey, G. Horgan, Glen Doherty","doi":"10.3389/fgstr.2024.1372191","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1372191","url":null,"abstract":"Colonoscopy following a positive FIT test in an average risk population is effective in reducing CRC incidence and mortality. While lower gastrointestinal symptoms remain a common cause for referral for colonoscopy, symptoms are poor predictors of clinically significant disease. The study was performed to compare neoplasia detection FIT +ve individuals and age-matched symptomatic cohorts. A single centre retrospective observational study was performed including all index colonoscopies performed on patients aged 60-70 from January 2015 to September 2021. Diagnostic yield was reported as adenoma detection rate, SSL detection rate, detection of high risk finding or adenocarcinoma. 8,106 colonoscopies were performed on patients aged 60-70 years. 3,695 (45.6%) originated from screening (FIT +ve). With exclusion criteria applied, 2,640 (59.9%) for screening and 1,767 (40.1%) for symptomatic patients were included. Median age in screening was 65 years (IQR 62-67) and 64 years in the symptomatic group (IQR 62-68), with male predominance in both groups (n=1,536, 58.1%, n=944, 53.4%). There were significant differences in both the ADR (56% vs 26.3%, p<0.01) and the SSLDR (10.4% vs. 8.1%, p=0.05) in the screening cohort compared to the symptomatic group. High risk findings (21.3% vs. 7.5%, p<0.01) were significantly more prevalent in the screening group with a considerably higher colorectal cancer (4.7% vs. 0.9%, p=<0.001) detection rate. FIT based triage significantly outperforms symptom based investigation for individuals in the 60-70 age group. Patients should be preferentially referred to organised colorectal cancer screening. FIT can be performed on symptomatic patients, to identify low risk individuals.","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":" 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140212225","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 : 2024-03-18DOI: 10.3389/fgstr.2024.1292226
Geoanna Bautista, Genia Dubrovsky, Nicolle K. Sweeney, R. Solórzano-Vargas, Daniel J. Tancredi, Michael Lewis, Mattias Stelzner, Martín G. Martín, J. C. Dunn
Severe forms of short bowel syndrome (SBS) resulting in chronic intestinal failure (IF) have limited therapeutic options, all of which are associated with significant morbidities. Spring-mediated distraction enterogenesis (SMDE) uses an intraluminal self-expanding spring to generate mechanical force to induce intestinal stretching and sustained axial growth, providing a promising novel approach for patients with SBS. Previous studies have established this method to be safe and effective in small and large animal models. However, SMDE has previously not been implemented in a large, clinically relevant animal model.Juvenile mini-Yucatan pigs with 75% of their small intestine resected had intraluminal springs placed after an initial adaptive period. Morphological and histological assessments were performed on SMDE segments compared to the control region of the intestine undergoing normal adaptive responses to resection.While the initial histologic adaptive response observed following resection was attenuated after a month, the SMDE segments instead augmented these adaptive changes. Specifically, intestinal length increased 2-fold in SMDE segments, and the widths of the epithelial, muscularis, and serosal layers were enhanced in SMDE compared with control segments of the same animal. This data suggests that morphologic intestinal adaptation may be enhanced with SMDE in the setting of SBS.Here we demonstrate the successful and reproducible implementation of SMDE in a large animal model in the setting of prior intestinal resection, making SMDE a viable and novel approach for SBS to be explored further.
严重的短肠综合征（SBS）会导致慢性肠功能衰竭（IF），但目前的治疗方法有限，而且所有这些治疗方法都与严重的发病率有关。弹簧介导的牵张肠道生成术（SMDE）利用腔内自膨胀弹簧产生机械力，诱导肠道伸展和持续的轴向生长，为SBS患者提供了一种前景广阔的新方法。以往的研究已证实这种方法在小型和大型动物模型中安全有效。切除了 75% 小肠的幼年小尤卡坦猪在最初的适应期后被放置了腔内弹簧。对 SMDE 区段进行了形态学和组织学评估，并将其与正常适应切除反应的肠道对照区进行了比较。一个月后，切除后观察到的最初组织学适应反应有所减弱，但 SMDE 区段反而增强了这些适应性变化。具体来说，与同一动物的对照组相比，SMDE 节段的肠道长度增加了 2 倍，上皮、肌层和浆膜层的宽度也增加了。这些数据表明，在 SBS 的情况下，SMDE 可增强肠道的形态适应性。在此，我们证明了在大型动物模型中，在先前进行过肠道切除的情况下，SMDE 的成功实施和可重复性，使 SMDE 成为治疗 SBS 的一种可行的新方法，有待进一步探索。
{"title":"Spring-mediated distraction enterogenesis may alter the course of adaptation in porcine short bowel syndrome","authors":"Geoanna Bautista, Genia Dubrovsky, Nicolle K. Sweeney, R. Solórzano-Vargas, Daniel J. Tancredi, Michael Lewis, Mattias Stelzner, Martín G. Martín, J. C. Dunn","doi":"10.3389/fgstr.2024.1292226","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1292226","url":null,"abstract":"Severe forms of short bowel syndrome (SBS) resulting in chronic intestinal failure (IF) have limited therapeutic options, all of which are associated with significant morbidities. Spring-mediated distraction enterogenesis (SMDE) uses an intraluminal self-expanding spring to generate mechanical force to induce intestinal stretching and sustained axial growth, providing a promising novel approach for patients with SBS. Previous studies have established this method to be safe and effective in small and large animal models. However, SMDE has previously not been implemented in a large, clinically relevant animal model.Juvenile mini-Yucatan pigs with 75% of their small intestine resected had intraluminal springs placed after an initial adaptive period. Morphological and histological assessments were performed on SMDE segments compared to the control region of the intestine undergoing normal adaptive responses to resection.While the initial histologic adaptive response observed following resection was attenuated after a month, the SMDE segments instead augmented these adaptive changes. Specifically, intestinal length increased 2-fold in SMDE segments, and the widths of the epithelial, muscularis, and serosal layers were enhanced in SMDE compared with control segments of the same animal. This data suggests that morphologic intestinal adaptation may be enhanced with SMDE in the setting of SBS.Here we demonstrate the successful and reproducible implementation of SMDE in a large animal model in the setting of prior intestinal resection, making SMDE a viable and novel approach for SBS to be explored further.","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":"28 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140231768","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 : 2024-01-25DOI: 10.3389/fgstr.2024.1363016
Sean Benson, Frauke Alves
{"title":"Editorial: In vivo and in situ imaging for characterization of colorectal cancer","authors":"Sean Benson, Frauke Alves","doi":"10.3389/fgstr.2024.1363016","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1363016","url":null,"abstract":"","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140496103","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 : 2024-01-24DOI: 10.3389/fgstr.2024.1333988
Georgia Zeng, Benjamin R. Holmes, Saleh A. Alqahtani, U. Gill, Patrick T. F. Kennedy
Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are leading causes of liver-related morbidity and mortality. The interaction between these two disease processes is poorly defined and the impact of NAFLD on HBV-related cirrhosis and HCC remains unclear. The aim of this study was to evaluate the impact of NAFLD on response to antiviral CHB therapy to inform the debate on changing CHB treatment thresholds for these comorbid patients.Studies with a minimum of 50 adult CHB patients on nucleoside analogue therapy with or without concurrent NAFLD were identified from PubMed/Medline and EMBASE to February 21, 2023. Data extraction from each study included HBeAg and treatment status, diagnostic method of NAFLD, frequency of monitoring intervals, patient age, gender, grade of hepatic steatosis, BMI and metabolic comorbidities. The outcomes of interest, complete virological response (CVR), biochemical response (BR) and HBeAg loss/seroconversion, were recorded at each available monitoring interval. Comparing CHB-NAFLD and CHB-only groups, pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using random- or fixed-effects models depending on heterogeneity.From a search of 470 citations, we identified 32 potentially relevant papers. Overall, 11 studies, comprising 2580 unique patients, met the inclusion criteria of the meta-analysis. CHB-NAFLD patients exhibited significantly lower rates of CVR compared to CHB-only patients. This was demonstrated by an OR of 0.59 (0.38-0.93, p=0.001, I2 = 72%) at 12 months, which tapered off to an OR of 0.67 (0.48-0.95, p=0.02) at 60 months. CHB-NAFLD patients also exhibited significantly lower rates of BR compared to CHB-only patients, as demonstrated by ORs of 0.39 (0.24-0.62, p<0.0001, I2 = 53%) at 12 months and 0.33 (0.17-0.63, p=0.0008) at 24 months.Patients with concurrent CHB and NAFLD experience delayed CVR to antiviral therapy and more persistent biochemical abnormalities in comparison to patients with CHB only. This supports the argument for earlier antiviral therapy in order to avert CHB complications in these multi-morbid patients, as the global disease burden of NAFLD continues to increase.
{"title":"The co-existence of NAFLD and CHB is associated with suboptimal viral and biochemical response to CHB antiviral therapy: a systematic review and meta-analysis","authors":"Georgia Zeng, Benjamin R. Holmes, Saleh A. Alqahtani, U. Gill, Patrick T. F. Kennedy","doi":"10.3389/fgstr.2024.1333988","DOIUrl":"https://doi.org/10.3389/fgstr.2024.1333988","url":null,"abstract":"Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are leading causes of liver-related morbidity and mortality. The interaction between these two disease processes is poorly defined and the impact of NAFLD on HBV-related cirrhosis and HCC remains unclear. The aim of this study was to evaluate the impact of NAFLD on response to antiviral CHB therapy to inform the debate on changing CHB treatment thresholds for these comorbid patients.Studies with a minimum of 50 adult CHB patients on nucleoside analogue therapy with or without concurrent NAFLD were identified from PubMed/Medline and EMBASE to February 21, 2023. Data extraction from each study included HBeAg and treatment status, diagnostic method of NAFLD, frequency of monitoring intervals, patient age, gender, grade of hepatic steatosis, BMI and metabolic comorbidities. The outcomes of interest, complete virological response (CVR), biochemical response (BR) and HBeAg loss/seroconversion, were recorded at each available monitoring interval. Comparing CHB-NAFLD and CHB-only groups, pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using random- or fixed-effects models depending on heterogeneity.From a search of 470 citations, we identified 32 potentially relevant papers. Overall, 11 studies, comprising 2580 unique patients, met the inclusion criteria of the meta-analysis. CHB-NAFLD patients exhibited significantly lower rates of CVR compared to CHB-only patients. This was demonstrated by an OR of 0.59 (0.38-0.93, p=0.001, I2 = 72%) at 12 months, which tapered off to an OR of 0.67 (0.48-0.95, p=0.02) at 60 months. CHB-NAFLD patients also exhibited significantly lower rates of BR compared to CHB-only patients, as demonstrated by ORs of 0.39 (0.24-0.62, p<0.0001, I2 = 53%) at 12 months and 0.33 (0.17-0.63, p=0.0008) at 24 months.Patients with concurrent CHB and NAFLD experience delayed CVR to antiviral therapy and more persistent biochemical abnormalities in comparison to patients with CHB only. This supports the argument for earlier antiviral therapy in order to avert CHB complications in these multi-morbid patients, as the global disease burden of NAFLD continues to increase.","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":"49 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139601203","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 : 2024-01-24DOI: 10.3389/fgstr.2023.1304944
Jon Florholmen, R. Goll, Kay-Martin Johnsen
Moderate to severe ulcerative colitis (UC) is generally treated with a step-up algorithm from 5-aminosalicylic acid (5-ASA) to biological agents. There is no general recommendation if or when to de-escalate or discontinue biological therapy. In this study, we performed biological therapy with anti-tumor necrosis factor (TNF) treatment to endoscopic remission followed by discontinuation of therapy. This is a 13- year follow-up study performed for this treatment algorithm.This study aimed to assess whether the treatment algorithm outlined above influences the UC phenotype toward a milder form and identify potential biomarkers for altering the disease phenotype.Patients with moderate to severe UC were enrolled from 2004 to 2015 and followed up until 2023 to evaluate disease outcomes. Patients were categorized into subgroups based on the highest treatment level required to attain remission: non-biological therapy, biological therapy, or colectomy. Mucosal TNF mRNA expression levels were measured using real-time PCR.Out of the 116 patients from the original cohort, 71 individuals who had previously undergone anti-TNF treatment to endoscopic remission and subsequently discontinued anti-TNF therapy were included in the present study. Disease outcomes were registered until 2023. By the end of the observation period, 62% of participants were in remission without biological treatment. Among the 71 patients, 39% never experienced a relapse, 23% relapsed but successfully attained remission with untargeted treatment, 18% relapsed and subsequently received a new sequence of biological therapy, and 20% had colectomy. Normalized mucosal TNF mRNA expression was identified as a significant predictor for clinical outcomes.Most UC patients transitioned to a milder disease phenotype without requiring biological therapy. Treating to normalize mucosal TNF expression emerges as a potential biomarker, predicting the downregulation of disease severity.
{"title":"Intensified anti-TNF treatment downregulates the phenotype in ulcerative colitis: a 13-year prospective follow-up study","authors":"Jon Florholmen, R. Goll, Kay-Martin Johnsen","doi":"10.3389/fgstr.2023.1304944","DOIUrl":"https://doi.org/10.3389/fgstr.2023.1304944","url":null,"abstract":"Moderate to severe ulcerative colitis (UC) is generally treated with a step-up algorithm from 5-aminosalicylic acid (5-ASA) to biological agents. There is no general recommendation if or when to de-escalate or discontinue biological therapy. In this study, we performed biological therapy with anti-tumor necrosis factor (TNF) treatment to endoscopic remission followed by discontinuation of therapy. This is a 13- year follow-up study performed for this treatment algorithm.This study aimed to assess whether the treatment algorithm outlined above influences the UC phenotype toward a milder form and identify potential biomarkers for altering the disease phenotype.Patients with moderate to severe UC were enrolled from 2004 to 2015 and followed up until 2023 to evaluate disease outcomes. Patients were categorized into subgroups based on the highest treatment level required to attain remission: non-biological therapy, biological therapy, or colectomy. Mucosal TNF mRNA expression levels were measured using real-time PCR.Out of the 116 patients from the original cohort, 71 individuals who had previously undergone anti-TNF treatment to endoscopic remission and subsequently discontinued anti-TNF therapy were included in the present study. Disease outcomes were registered until 2023. By the end of the observation period, 62% of participants were in remission without biological treatment. Among the 71 patients, 39% never experienced a relapse, 23% relapsed but successfully attained remission with untargeted treatment, 18% relapsed and subsequently received a new sequence of biological therapy, and 20% had colectomy. Normalized mucosal TNF mRNA expression was identified as a significant predictor for clinical outcomes.Most UC patients transitioned to a milder disease phenotype without requiring biological therapy. Treating to normalize mucosal TNF expression emerges as a potential biomarker, predicting the downregulation of disease severity.","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":"43 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139599684","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 : 2024-01-16DOI: 10.3389/fgstr.2023.1323471
S. Koester, Naisi Li, Neelendu Dey
Ret is implicated in colorectal cancer (CRC) as both a proto-oncogene and a tumor suppressor. We asked whether RET signaling regulates tumorigenesis in an Apc-deficient preclinical model of CRC. We observed a sex-biased phenotype: ApcMin/+Ret+/- females had significantly greater tumor burden than ApcMin/+Ret+/- males, a phenomenon not seen in ApcMin/+ mice, which had equal distributions by sex. Dysfunctional RET signaling was associated with gene expression changes in diverse tumor signaling pathways in tumors and normal-appearing colon. Sex-biased gene expression differences mirroring tumor phenotypes were seen in 26 genes, including the Apc tumor suppressor gene. Ret and Tlr4 expression were significantly correlated in tumor samples from female but not male ApcMin/+Ret+/- mice. Antibiotics resulted in reduction of tumor burden, inverting the sex-biased phenotype such that microbiota-depleted ApcMin/+Ret+/- males had significantly more tumors than female littermates. Reconstitution of the microbiome rescued the sex-biased phenotype. Our findings suggest that RET represents a sexually dimorphic microbiome-mediated “switch” for regulation of tumorigenesis.
Ret 与结直肠癌（CRC）有关，它既是原癌基因，也是肿瘤抑制因子。我们想知道，在 Apc 缺失的 CRC 临床前模型中，RET 信号是否调控肿瘤发生。我们观察到了一种具有性别差异的表型：ApcMin/+Ret+/-雌性小鼠的肿瘤负荷明显大于ApcMin/+Ret+/-雄性小鼠，这种现象在ApcMin/+小鼠中并没有出现，因为ApcMin/+小鼠的肿瘤负荷在性别上分布相同。RET信号传导失调与肿瘤和正常结肠中多种肿瘤信号通路的基因表达变化有关。在26个基因（包括Apc肿瘤抑制基因）中发现了反映肿瘤表型的性别基因表达差异。在雌性而非雄性ApcMin/+Ret+/-小鼠的肿瘤样本中，Ret和Tlr4的表达明显相关。抗生素减轻了肿瘤负荷，逆转了性别差异表型，即微生物群缺失的ApcMin/+Ret+/-雄性小鼠的肿瘤明显多于雌性小鼠。微生物群的重建挽救了性别差异表型。我们的研究结果表明，RET代表了微生物组介导的肿瘤发生调控的性别二态 "开关"。
{"title":"RET is a sex-biased regulator of intestinal tumorigenesis","authors":"S. Koester, Naisi Li, Neelendu Dey","doi":"10.3389/fgstr.2023.1323471","DOIUrl":"https://doi.org/10.3389/fgstr.2023.1323471","url":null,"abstract":"Ret is implicated in colorectal cancer (CRC) as both a proto-oncogene and a tumor suppressor. We asked whether RET signaling regulates tumorigenesis in an Apc-deficient preclinical model of CRC. We observed a sex-biased phenotype: ApcMin/+Ret+/- females had significantly greater tumor burden than ApcMin/+Ret+/- males, a phenomenon not seen in ApcMin/+ mice, which had equal distributions by sex. Dysfunctional RET signaling was associated with gene expression changes in diverse tumor signaling pathways in tumors and normal-appearing colon. Sex-biased gene expression differences mirroring tumor phenotypes were seen in 26 genes, including the Apc tumor suppressor gene. Ret and Tlr4 expression were significantly correlated in tumor samples from female but not male ApcMin/+Ret+/- mice. Antibiotics resulted in reduction of tumor burden, inverting the sex-biased phenotype such that microbiota-depleted ApcMin/+Ret+/- males had significantly more tumors than female littermates. Reconstitution of the microbiome rescued the sex-biased phenotype. Our findings suggest that RET represents a sexually dimorphic microbiome-mediated “switch” for regulation of tumorigenesis.","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":" 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139618956","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 : 2024-01-11DOI: 10.3389/fgstr.2023.1355275
Ravi Kumar Sharma, P. Chhabra, S. Rana
{"title":"Editorial: Pancreatic cystic lesions: aiding in the early diagnosis of pancreatic cancer","authors":"Ravi Kumar Sharma, P. Chhabra, S. Rana","doi":"10.3389/fgstr.2023.1355275","DOIUrl":"https://doi.org/10.3389/fgstr.2023.1355275","url":null,"abstract":"","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":" 39","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139626858","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 : 2024-01-04DOI: 10.3389/fgstr.2023.1299182
Valentina Medici, Nehemiah Kebede, Jennifer Stephens, Mary Kunjappu, John M. Vierling
There are limited data from the United States regarding the real-world signs and symptoms of Wilson disease (WD). This retrospective, observational medical chart review was conducted to identify real-world characteristics of patients with WD in the United States, as well as WD signs and symptoms at diagnosis and over time.De-identified clinical data were abstracted from medical charts of US patients diagnosed with WD between January 1, 2012, and June 30, 2017. Hepatic, neurologic, and psychiatric biochemical findings, signs, and symptoms were characterized at diagnosis and follow-up/during treatment.In total, 225 WD patients were included in the study. The mean (SD) age at diagnosis was 24.7 (9.8) years, and 65.3% were male. Median (Q1–Q3) follow-up after diagnosis was 39.5 (33.8–60.4) months. The most common disease presentation at WD diagnosis was combined neurologic/psychiatric and hepatic (52.9%), followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Common clinical characteristics at diagnosis were Kayser-Fleischer rings (77.2%), low ceruloplasmin levels (95.2%), high hepatic copper (97.8%), elevated 24-hour urinary copper excretion (90.2%), and abnormal liver function tests (38.7%–85.1%). At diagnosis, the most common biochemical findings or hepatic sign/symptoms were abnormal liver enzymes (50.7%), abdominal pain (16.6%), and fatigue (15.7%). The most common neurologic signs/symptoms were headache (18.3%), dysarthria (17.4%), and ataxia (17.0%). Common psychiatric signs/symptoms included anxiety/depression/other mood changes (36.2%), emotional lability (12.8%), and increased irritability/anger outbursts (9.2%). Prevalence of biochemical abnormalities or signs/symptoms among patients at diagnosis and after ~1-year follow-up were neurologic (60.1% and 44.0%), hepatic (69.6% and 37.8%), and psychiatric (53.7% and 37.6%), respectively. Common new onset symptoms at ~1-year post-WD diagnosis were abnormal liver enzymes (5.6%), headache (6.2%), and anxiety/depression/other mood changes (7.2%).These real-world, descriptive data highlight the clinical complexity and heterogeneity of WD and the need for better education about diagnostic testing and multidisciplinary support. Although rare, the neurologic, psychiatric, and hepatic signs/symptoms of WD have a substantial clinical impact.
{"title":"Clinical signs and symptoms of Wilson disease in a real-world cohort of patients in the United States: a medical chart review study","authors":"Valentina Medici, Nehemiah Kebede, Jennifer Stephens, Mary Kunjappu, John M. Vierling","doi":"10.3389/fgstr.2023.1299182","DOIUrl":"https://doi.org/10.3389/fgstr.2023.1299182","url":null,"abstract":"There are limited data from the United States regarding the real-world signs and symptoms of Wilson disease (WD). This retrospective, observational medical chart review was conducted to identify real-world characteristics of patients with WD in the United States, as well as WD signs and symptoms at diagnosis and over time.De-identified clinical data were abstracted from medical charts of US patients diagnosed with WD between January 1, 2012, and June 30, 2017. Hepatic, neurologic, and psychiatric biochemical findings, signs, and symptoms were characterized at diagnosis and follow-up/during treatment.In total, 225 WD patients were included in the study. The mean (SD) age at diagnosis was 24.7 (9.8) years, and 65.3% were male. Median (Q1–Q3) follow-up after diagnosis was 39.5 (33.8–60.4) months. The most common disease presentation at WD diagnosis was combined neurologic/psychiatric and hepatic (52.9%), followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Common clinical characteristics at diagnosis were Kayser-Fleischer rings (77.2%), low ceruloplasmin levels (95.2%), high hepatic copper (97.8%), elevated 24-hour urinary copper excretion (90.2%), and abnormal liver function tests (38.7%–85.1%). At diagnosis, the most common biochemical findings or hepatic sign/symptoms were abnormal liver enzymes (50.7%), abdominal pain (16.6%), and fatigue (15.7%). The most common neurologic signs/symptoms were headache (18.3%), dysarthria (17.4%), and ataxia (17.0%). Common psychiatric signs/symptoms included anxiety/depression/other mood changes (36.2%), emotional lability (12.8%), and increased irritability/anger outbursts (9.2%). Prevalence of biochemical abnormalities or signs/symptoms among patients at diagnosis and after ~1-year follow-up were neurologic (60.1% and 44.0%), hepatic (69.6% and 37.8%), and psychiatric (53.7% and 37.6%), respectively. Common new onset symptoms at ~1-year post-WD diagnosis were abnormal liver enzymes (5.6%), headache (6.2%), and anxiety/depression/other mood changes (7.2%).These real-world, descriptive data highlight the clinical complexity and heterogeneity of WD and the need for better education about diagnostic testing and multidisciplinary support. Although rare, the neurologic, psychiatric, and hepatic signs/symptoms of WD have a substantial clinical impact.","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":"55 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139384621","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 : 2024-01-04DOI: 10.3389/fgstr.2023.1296048
Silvia Cruchet, Sandra Hirsch, Diana Villa-López, Mucio Moreno-Portillo, Juan C. Palomo, Ana T. Abreu-Abreu, J. Abdo-Francis, C. Jiménez-Gutiérrez, Martin Rojano, G. López-Velázquez, P. Gutiérrez-Castrellón
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder in adults. Systematic reviews with meta-analyses have demonstrated the efficacy and safety of probiotics in improving symptoms of IBS.The aim of the study was to demonstrate the efficacy and safety of Limosilactobacillus reuteri (L. reuteri) DSM 17938 combined with L. reuteri ATCC PTA 6475 regarding improving the symptoms associated with IBS in adults.A randomized, double-blind, placebo-controlled clinical trial was conducted in 140 adults aged 18 years to 65 years with a diagnosis of IBS (based on the Rome IV criteria). After 2 weeks of washout, subjects were randomized to receive either 2 × 108 colony-forming units (CFUs) of L. reuteri DSM 17938 combined with L. reuteri ATCC PTA 6475 plus standard of care or placebo plus standard of care for 14 weeks, followed by a post-intervention period of 2 additional weeks. Changes in gastrointestinal symptoms (as measured with the GSRS-IBS), stool pattern (as measured with the Bristol scale), quality of life, depression and anxiety, frequency of adverse events, and fecal calprotectin concentrations were evaluated.In total, 70 subjects were allocated to receive L. reuteri and 70 were allocated to receive placebo. During the pre-randomization phase, no differences were observed between the groups in terms of IBS-associated symptoms and stool consistency. Starting at week 6 of the intervention, subjects in group L. reuteri showed a significant improvement in IBS-associated symptoms (p < 0.01). A significant improvement was also observed in fecal calprotectin concentration in the L. reuteri group at the end of interventions (30.2 ± 11.8 mg/g of stool in the L. reuteri group and 41.6 mg/g ± 10.7 mg/g in the placebo group; p = 0.019). The frequency of adverse events was similar between groups.A twice-a-day intervention for 14 weeks is safe and effective, reduces the symptoms associated with IBS in adults aged 18 years to 65 years, improves stool consistency, and reduces symptoms associated with anxiety after 6 weeks.
{"title":"Limosilactobacillus reuteri DSM 17938 and ATCC PTA 6475 for the treatment of moderate to severe irritable bowel syndrome in adults: a randomized controlled trial","authors":"Silvia Cruchet, Sandra Hirsch, Diana Villa-López, Mucio Moreno-Portillo, Juan C. Palomo, Ana T. Abreu-Abreu, J. Abdo-Francis, C. Jiménez-Gutiérrez, Martin Rojano, G. López-Velázquez, P. Gutiérrez-Castrellón","doi":"10.3389/fgstr.2023.1296048","DOIUrl":"https://doi.org/10.3389/fgstr.2023.1296048","url":null,"abstract":"Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder in adults. Systematic reviews with meta-analyses have demonstrated the efficacy and safety of probiotics in improving symptoms of IBS.The aim of the study was to demonstrate the efficacy and safety of Limosilactobacillus reuteri (L. reuteri) DSM 17938 combined with L. reuteri ATCC PTA 6475 regarding improving the symptoms associated with IBS in adults.A randomized, double-blind, placebo-controlled clinical trial was conducted in 140 adults aged 18 years to 65 years with a diagnosis of IBS (based on the Rome IV criteria). After 2 weeks of washout, subjects were randomized to receive either 2 × 108 colony-forming units (CFUs) of L. reuteri DSM 17938 combined with L. reuteri ATCC PTA 6475 plus standard of care or placebo plus standard of care for 14 weeks, followed by a post-intervention period of 2 additional weeks. Changes in gastrointestinal symptoms (as measured with the GSRS-IBS), stool pattern (as measured with the Bristol scale), quality of life, depression and anxiety, frequency of adverse events, and fecal calprotectin concentrations were evaluated.In total, 70 subjects were allocated to receive L. reuteri and 70 were allocated to receive placebo. During the pre-randomization phase, no differences were observed between the groups in terms of IBS-associated symptoms and stool consistency. Starting at week 6 of the intervention, subjects in group L. reuteri showed a significant improvement in IBS-associated symptoms (p < 0.01). A significant improvement was also observed in fecal calprotectin concentration in the L. reuteri group at the end of interventions (30.2 ± 11.8 mg/g of stool in the L. reuteri group and 41.6 mg/g ± 10.7 mg/g in the placebo group; p = 0.019). The frequency of adverse events was similar between groups.A twice-a-day intervention for 14 weeks is safe and effective, reduces the symptoms associated with IBS in adults aged 18 years to 65 years, improves stool consistency, and reduces symptoms associated with anxiety after 6 weeks.","PeriodicalId":512079,"journal":{"name":"Frontiers in Gastroenterology","volume":"58 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139385985","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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