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Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer 解决胰腺癌早期诊断中未满足的低容量检测的临床需求
Pub Date : 2023-09-19 DOI: 10.3389/fgstr.2023.1258998
Daniel A. Sheik, Kaleb Byers, Mini Thomas, Ummadisetti Chinna Rajesh, Kelli Ifuku, Kimberly Kirkwood, Mohammed Al-Haddad, Charles S. Craik, V. Jo Davisson
The incidental detection of pancreatic cysts, an opportunity for the early detection of pancreatic cancer, is increasing, owing to an aging population and improvements in imaging technology. The classification of pancreatic cystic precursors currently relies on imaging and cyst fluid evaluations, including cytology and protein and genomic analyses. However, there are persistent limitations that obstruct the accuracy and quality of information for clinicians, including the limited volume of the complex, often acellular, and proteinaceous milieu that comprises pancreatic cyst fluid. The constraints of currently available clinical assays lead clinicians to the subjective and inconsistent application of diagnostic tools, which can contribute to unnecessary surgery and missed pancreatic cancers. Herein, we describe the pathway toward pancreatic cyst classification and diagnosis, the volume requirements for several clinically available diagnostic tools, and some analytical and diagnostic limitations for each assay. We then discuss current and future work on novel markers and methods, and how to expand the utility of clinical pancreatic cyst fluid samples. Results of ongoing studies applying SERS as a detection mode suggest that 50 µL of pancreatic cyst fluid is more than sufficient to accurately rule out non-mucinous pancreatic cysts with no malignant potential from further evaluation. This process is expected to leave sufficient fluid to analyze a follow-up, rule-in panel of markers currently in development that can stratify grades of dysplasia in mucinous pancreatic cysts and improve clinical decision-making.
由于人口老龄化和成像技术的进步,胰腺囊肿的偶然发现是早期发现胰腺癌的一个机会,正在增加。胰腺囊性前体的分类目前依赖于影像学和囊肿液评估,包括细胞学、蛋白质和基因组分析。然而,持续存在的限制阻碍了临床医生信息的准确性和质量,包括由胰腺囊肿液组成的复杂的、通常是脱细胞的和蛋白质的环境的有限体积。目前可用的临床分析的限制导致临床医生主观和不一致的诊断工具的应用,这可能导致不必要的手术和漏诊胰腺癌。在此,我们描述了胰腺囊肿分类和诊断的途径,几种临床可用诊断工具的体积要求,以及每种检测的一些分析和诊断局限性。然后,我们讨论了当前和未来在新的标记物和方法方面的工作,以及如何扩大临床胰腺囊肿液样本的效用。正在进行的以SERS为检测模式的研究结果表明,50µL的胰腺囊肿液足以准确地排除无恶性潜能的非粘液性胰腺囊肿。这一过程有望留下足够的液体来分析一个随访的、规则的、目前正在开发的标志物小组,该小组可以对粘液性胰腺囊肿的发育不良等级进行分层,并改善临床决策。
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引用次数: 0
Efficacy and safety of Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 as an adjuvant for Helicobacter pylori eradication: a double-blind, randomized, placebo-controlled study 鼠李糖乳杆菌R0011和helveticus乳杆菌R0052作为根除幽门螺杆菌的佐剂的有效性和安全性:一项双盲、随机、安慰剂对照研究
Pub Date : 2023-09-14 DOI: 10.3389/fgstr.2023.1245993
Anya Kiattiweerasak, Natsuda Aumpan, Soonthorn Chonprasertsuk, Bubpha Pornthisarn, Sith Siramolpiwat, Patommatat Bhanthumkomol, Pongjarat Nunanan, Navapan Issariyakulkarn, Varocha Mahachai, Yoshio Yamaoka, Ratha-korn Vilaichone
Background Helicobacter pylori eradication is recommended as a way of providing symptomatic relief for dyspepsia. The limited efficacy of triple therapy is a major problem in many countries, including Thailand. Some probiotics have been shown to improve the H. pylori eradication rate and reduce side effects. This study aimed at evaluating the efficacy of probiotic (Lacidofil ® STRONG) as adjuvant to standard triple therapy. Methods This randomized, double-blind, placebo-controlled study was conducted between July 2020 and June 2022. Eligible patients with H. pylori gastritis (i.e., n =90 out of the 160 patients screened) were randomized to receive 14-day standard triple therapy either with probiotics or with a placebo (N=45/group). The treatment regimen entailed 30 mg lansoprazole administered twice daily, 1,000 mg amoxicillin administered twice daily, and 1 g clarithromycin modified-release formulation administered once daily. A probiotic capsule containing Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 (Lacidofil ® STRONG) or placebo were given twice daily during the eradication therapy and for an additional 4 weeks. Successful H. pylori eradication was defined as a negative 13 C-urea breath test at least 4 weeks after complete eradication. Results As per-protocol analysis, eradication rates after the 14-day regimen with probiotic or placebo were 90.9% and 75.0% ( p =0.047), respectively. Antibiotic susceptibility testing demonstrated high clarithromycin resistance (24%). For clarithromycin-resistant strains, there was no statistical difference in eradication rates between the probiotic and placebo groups. Furthermore, probiotic supplementation significantly reduced treatment side effects, including bloating (OR 0.27 [95% CI 0.10 to 0.75], p =0.012), diarrhea (OR 0.23 [95% CI 0.28 to 0.65], p =0.006), nausea (OR 0.05 [95% CI 0.01 to 0.36], p =0.003), and bitter taste (OR 0.14 [95% CI 0.03 to 0.69], p =0.015). In addition, the probiotic group had lower gastrointestinal symptom rating scale (GSRS) scores (1.46 ± 0.36 vs. 2.65 ± 0.66, p <0.001) and higher SF-36 health-related quality-of-life scores (63.3 ± 10.2 vs. 57.3 ± 13.4, p =0.020) after treatment than the placebo group. Conclusion The probiotic adjuvant with 14-day standard triple therapy improved the H. pylori eradication rate. Supplementation with Lacidofil ® STRONG during the 2-week eradication treatment and 4-week follow-up phase can help to reduce the gastrointestinal side effects of eradication therapy and increase patients’ general health-related quality of life.
背景:根除幽门螺杆菌被推荐为缓解消化不良症状的一种方法。三联疗法疗效有限是包括泰国在内的许多国家的一个主要问题。一些益生菌已被证明可以提高幽门螺杆菌的根除率并减少副作用。本研究旨在评估益生菌(Lacidofil®STRONG)作为标准三联疗法辅助治疗的疗效。该研究于2020年7月至2022年6月进行,为随机、双盲、安慰剂对照研究。符合条件的幽门螺杆菌胃炎患者(即160名筛选患者中的90名)随机接受14天的标准三联治疗,其中包括益生菌或安慰剂(n =45/组)。治疗方案包括30毫克兰索拉唑,每天两次,1000毫克阿莫西林,每天两次,1克克拉霉素缓释制剂,每天一次。在根除治疗期间,每天两次给予含有鼠李糖乳杆菌R0011和helveticus乳杆菌R0052 (Lacidofil®STRONG)的益生菌胶囊或安慰剂,并再持续4周。成功根除幽门螺杆菌被定义为在完全根除后至少4周的13 c -尿素呼气试验阴性。结果根据方案分析,益生菌和安慰剂治疗14天后的根除率分别为90.9%和75.0% (p =0.047)。抗生素药敏试验显示克拉霉素高耐药性(24%)。对于克拉霉素耐药菌株,益生菌组和安慰剂组在根除率上没有统计学差异。此外,益生菌补充显著减少了治疗副作用,包括腹胀(OR 0.27 [95% CI 0.10至0.75],p =0.012)、腹泻(OR 0.23 [95% CI 0.28至0.65],p =0.006)、恶心(OR 0.05 [95% CI 0.01至0.36],p =0.003)和苦味(OR 0.14 [95% CI 0.03至0.69],p =0.015)。此外,治疗后益生菌组胃肠道症状评定量表(GSRS)评分较低(1.46±0.36比2.65±0.66,p <0.001), SF-36健康相关生活质量评分较高(63.3±10.2比57.3±13.4,p =0.020)。结论益生菌佐剂配合14 d标准三联治疗可提高幽门螺杆菌的根除率。在2周根除治疗和4周随访期间补充Lacidofil®STRONG有助于减少根除治疗的胃肠道副作用,并提高患者的总体健康相关生活质量。
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引用次数: 0
The relations between constipation and characteristics of intestinal morphologies by colonoscopy 结肠镜下便秘与肠道形态特征的关系
Pub Date : 2023-09-11 DOI: 10.3389/fgstr.2023.1255129
Yuting Xu, Qili Xiao
Background Constipation is commonly diagnosed throughout the world, and it is typically associated with various factors. However, data on the characteristics of intestinal morphologies linked with constipation are scarce. We examined the association between the characteristics of different intestinal morphologies and constipation. Patients and methods Between March 2020 and February 2021, we enrolled 510 patients from the Affiliated Zhongshan Hospital of Guangzhou University of Chinese Medicine into two groups: 260 in the constipation group and 250 in the control group. Of these patients, intestinal morphology characteristics obtained via colonoscopy were compared and analyzed. Results There were meaningful differences between the cohorts based on the intestinal morphology characteristics of tortuousness ( p &lt; 0.001) and dissociation ( p &lt; 0.001). In addition, a significant difference in characteristics was determined for either both intestinal morphologies ( p &lt; 0.001) or only tortuousness without any other conditions ( p =0.015), but there was no significant difference between the two groups with respect to only dissociation without any other conditions ( p = 0.077). A subgroup analysis was performed on statistically significant variables—gender ( p &lt; 0.001), age ( p = 0.002), and operation time ( p &lt; 0.001)—and the results showed that regardless of the subgroup analysis, there was a statistically significant difference in tortuousness between the two groups. In addition, there were significantly differences in dissociation between the groups for elderly men and those with a longer operation time. Conclusion Compared with the general population, people with the intestinal morphologies of dissociation and, in particular, tortuousness seem to experience constipation more frequently.
背景:便秘在世界范围内是一种常见的疾病,它通常与多种因素有关。然而,与便秘相关的肠道形态特征的数据很少。我们研究了不同肠道形态特征与便秘之间的关系。患者和方法2020年3月至2021年2月,我们将广州中医药大学附属中山医院的510例患者分为两组:便秘组260例,对照组250例。对这些患者进行结肠镜检查获得的肠道形态学特征的比较和分析。结果各组间肠扭曲的形态学特征有显著性差异(p <0.001)和解离(p <0.001)。此外,两种肠道形态的特征也存在显著差异(p <(p =0.015),但两组在分离性方面无显著性差异(p = 0.077)。对具有统计学意义的变量——性别(p <0.001)、年龄(p = 0.002)、手术时间(p <0.001) -结果表明,无论亚组分析如何,两组之间的扭曲程度在统计学上存在显著差异。此外,老年男性组和手术时间较长的男性组在解离上有显著差异。结论与一般人群相比,肠道形态分离,特别是扭曲的人群似乎更容易出现便秘。
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引用次数: 0
Effects of a sucralfate-containing ointment on quality of life and symptoms associated with hemorrhoidal disease: patient-reported results of a Slovakian, pharmacist-led observational survey 含三硫酸软膏对生活质量和痔疮相关症状的影响:一项斯洛伐克药剂师主导的观察性调查的患者报告结果
Pub Date : 2023-09-05 DOI: 10.3389/fgstr.2023.1213433
Miroslava Snopková, Ondrej Sukel‘, Jan Micanko
This pharmacist-led study evaluated the effect of a rectal ointment containing sucralfate on quality of life, symptom frequency and time to relief of symptoms in Slovakian individuals with hemorrhoidal disease (HD).The multicenter prospective survey was conducted at 45 community pharmacies in Slovakia. Pharmacists invited adults (≥18 years) using sucralfate-containing ointment for their HD-related symptoms to participate.241 patients completed the HEMO-FISS-QoL questionnaire and a survey of symptom frequency at the beginning and end of the 14-day survey period. The primary endpoint was the change in HEMO-FISS-QoL scores in patients with hemorrhoidal symptoms during the 7 days before the initial pharmacy visit. Of the 241 patients enrolled in the survey, 144 had experienced hemorrhoidal symptoms within the preceding 7 days (mean age 51 years; 59.0% female). For these 144 patients, the total HEMO-FISS-QoL score decreased (i.e., quality of life was improved) from baseline by a mean of –8.7 (95% confidence interval –12.6, –6.2; P<0.001) at day 14. The frequency of hemorrhoidal symptoms was significantly reduced (P<0.001 vs baseline). Symptom relief was rapid; at 1-hour post-treatment 54.6% of patients had relief from pain and 56.3% from itching, and by 24 hours post-treatment most patients had relief from these symptoms (77.2% and 73.0%, respectively). No incidents nor adverse events related to sucralfate-containing ointment were reported to pharmacists.The results of this pharmacist-led observational survey suggest that the sucralfate-containing ointment could improve quality of life in patients with HD, providing rapid relief with a good safety profile. To confirm these results in a larger, well-defined patient population, randomized controlled trials in patients with clinically diagnosed HD are warranted.
这项以药剂师为主导的研究评估了一种含有硫硫酸盐的直肠软膏对斯洛伐克痔疮病(HD)患者的生活质量、症状频率和症状缓解时间的影响。在斯洛伐克的45个社区药房进行了多中心前瞻性调查。药剂师邀请使用含蔗糖酸软膏治疗hd相关症状的成年人(≥18岁)参与。在为期14天的调查开始和结束时,241例患者完成了HEMO-FISS-QoL问卷和症状频率调查。主要终点是首次药房就诊前7天有痔疮症状患者的HEMO-FISS-QoL评分的变化。在参与调查的241名患者中,144名患者在前7天内出现过痔疮症状(平均年龄51岁;59.0%的女性)。对于这144名患者,总的HEMO-FISS-QoL评分比基线平均下降了-8.7(95%可信区间-12.6,-6.2;P<0.001)。痔疮症状的发生频率显著降低(与基线相比P<0.001)。症状缓解迅速;治疗后1小时,54.6%的患者疼痛缓解,56.3%的患者瘙痒缓解,治疗后24小时,大多数患者症状缓解(分别为77.2%和73.0%)。药师未见与含三硫酸软膏相关的事故或不良事件报告。这项由药剂师主导的观察性调查结果表明,含三硫酸盐软膏可以改善HD患者的生活质量,提供快速缓解和良好的安全性。为了在更大、定义明确的患者群体中证实这些结果,有必要对临床诊断为HD的患者进行随机对照试验。
{"title":"Effects of a sucralfate-containing ointment on quality of life and symptoms associated with hemorrhoidal disease: patient-reported results of a Slovakian, pharmacist-led observational survey","authors":"Miroslava Snopková, Ondrej Sukel‘, Jan Micanko","doi":"10.3389/fgstr.2023.1213433","DOIUrl":"https://doi.org/10.3389/fgstr.2023.1213433","url":null,"abstract":"This pharmacist-led study evaluated the effect of a rectal ointment containing sucralfate on quality of life, symptom frequency and time to relief of symptoms in Slovakian individuals with hemorrhoidal disease (HD).The multicenter prospective survey was conducted at 45 community pharmacies in Slovakia. Pharmacists invited adults (≥18 years) using sucralfate-containing ointment for their HD-related symptoms to participate.241 patients completed the HEMO-FISS-QoL questionnaire and a survey of symptom frequency at the beginning and end of the 14-day survey period. The primary endpoint was the change in HEMO-FISS-QoL scores in patients with hemorrhoidal symptoms during the 7 days before the initial pharmacy visit. Of the 241 patients enrolled in the survey, 144 had experienced hemorrhoidal symptoms within the preceding 7 days (mean age 51 years; 59.0% female). For these 144 patients, the total HEMO-FISS-QoL score decreased (i.e., quality of life was improved) from baseline by a mean of –8.7 (95% confidence interval –12.6, –6.2; P<0.001) at day 14. The frequency of hemorrhoidal symptoms was significantly reduced (P<0.001 vs baseline). Symptom relief was rapid; at 1-hour post-treatment 54.6% of patients had relief from pain and 56.3% from itching, and by 24 hours post-treatment most patients had relief from these symptoms (77.2% and 73.0%, respectively). No incidents nor adverse events related to sucralfate-containing ointment were reported to pharmacists.The results of this pharmacist-led observational survey suggest that the sucralfate-containing ointment could improve quality of life in patients with HD, providing rapid relief with a good safety profile. To confirm these results in a larger, well-defined patient population, randomized controlled trials in patients with clinically diagnosed HD are warranted.","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43771385","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}
引用次数: 0
Case Report: Primary small bowel adenocarcinoma with peritoneal metastasis responded well to a CapeOX + bevacizumab regimen 病例报告:原发性小肠腺癌伴腹膜转移对CapeOX +贝伐单抗治疗方案反应良好
Pub Date : 2023-08-21 DOI: 10.3389/fgstr.2023.1187194
Guang-bo Fu, Z. Tang, Zishun Xu, Shenmin Zhang
Small bowel adenocarcinoma (SBA) is a rare condition often presenting with various non-specific gastrointestinal symptoms, making its diagnosis challenging. Delayed diagnosis is common, as patients may not receive the correct diagnosis until complications arise, necessitating further investigations. Furthermore, the management of SBA patients poses difficulties due to the scarcity of high-quality evidence.In this report, we present the case of an elderly man with SBA in the ileum who arrived at our emergency room with acute abdominal pain. The diagnosis was not made until the SBA caused a perforation, leading to acute abdominal pain. An emergent exploratory laparotomy revealed a 3 cm × 3 cm perforated tumor in the ileum, along with widespread metastatic nodules on the omentum, ascending colon, descending colon, and rectum. Postoperative pathological evaluation confirmed the diagnosis of SBA with peritoneal metastasis (pT4N2M1, stage IV). Following surgery, the patient received palliative systemic chemotherapy, which included the CapeOX regimen and the anti-VEGF monoclonal antibody bevacizumab. Remarkably, the patient responded well to this therapy, displaying good tolerance, and we observed no signs of disease progression. As of now, the patient is in good health and continuing with regular follow-up.The early diagnosis of small bowel adenocarcinoma remains a challenge. Delayed diagnosis can lead to a poor prognosis, underscoring the importance of considering SBA as a potential diagnosis for patients with unexplained abdominal pain and gastrointestinal symptoms. This case also highlights the efficacy of palliative chemotherapy with the CapeOX regimen combined with bevacizumab in controlling SBA.
小肠腺癌(SBA)是一种罕见的疾病,通常表现为各种非特异性胃肠道症状,使其诊断具有挑战性。延迟诊断是常见的,因为患者可能无法得到正确的诊断,直到出现并发症,需要进一步的调查。此外,由于缺乏高质量的证据,对SBA患者的管理也存在困难。在这篇报告中,我们提出一个老年男性回肠SBA的病例,他因急性腹痛来到我们的急诊室。直到SBA引起穿孔,导致急性腹痛,才做出诊断。急诊剖腹探查发现回肠有一个3cm × 3cm的穿孔肿瘤,同时在网膜、升结肠、降结肠和直肠有广泛的转移性结节。术后病理诊断为SBA伴腹膜转移(pT4N2M1, IV期)。术后患者接受姑息性全身化疗,包括CapeOX方案和抗vegf单克隆抗体贝伐单抗。值得注意的是,患者对这种治疗反应良好,表现出良好的耐受性,我们没有观察到疾病进展的迹象。截至目前,患者健康状况良好,并将继续定期随访。小肠腺癌的早期诊断仍然是一个挑战。延迟诊断可能导致预后不良,这强调了将SBA作为无法解释的腹痛和胃肠道症状患者的潜在诊断的重要性。该病例也强调了姑息性化疗与CapeOX方案联合贝伐单抗在控制SBA中的疗效。
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引用次数: 0
Editorial: Gastrointestinal and bilio-pancreatic stenting: when, which stent and why 社论:胃肠道和胆胰支架植入术:何时,使用哪种支架以及原因
Pub Date : 2023-08-21 DOI: 10.3389/fgstr.2023.1271139
A. Tringali, T. Voiosu, M. F. Y. Viesca, C. Gerges
{"title":"Editorial: Gastrointestinal and bilio-pancreatic stenting: when, which stent and why","authors":"A. Tringali, T. Voiosu, M. F. Y. Viesca, C. Gerges","doi":"10.3389/fgstr.2023.1271139","DOIUrl":"https://doi.org/10.3389/fgstr.2023.1271139","url":null,"abstract":"","PeriodicalId":73085,"journal":{"name":"Frontiers in gastroenterology (Lausanne, Switzerland)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41768415","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}
引用次数: 0
The effect of novel antimicrobial agents on the normal functioning of human intestinal microbiota: a systematic review 新型抗菌剂对人类肠道微生物群正常功能的影响:系统综述
Pub Date : 2023-08-16 DOI: 10.3389/fgstr.2023.1159352
Abayeneh Girma
Antimicrobial agents have significant effects on the ecological balance of the human microbiota through incomplete absorption (e.g., orally administered antimicrobial agents) or secretion (e.g., by the salivary glands, in the bile, or from the intestinal mucosa) of the agents. This study aimed to examine the effects of novel antimicrobial agents on the normal functioning of the intestinal microbiota. The articles, written in English, were recovered from PubMed, ScienceDirect, Web of Science, Google Scholar, and DOAJ, as well as from manual searches using a reference list. “Microbiota”, “Intestinal Microbiota”, “Eubiotic Microbiota”, “Ecological Impact”, “Antimicrobial Agents,”, “Antibiotics”, “Dysbiosis”, “Gut Microbiota”, and “Probiotics” were the search terms used to retrieve the articles. The PRISMA 2009 checklist was applied for article search strategy, article selection, data extraction, and result reporting for the review process. A total of eight original research articles were included from a total of 379 articles obtained in different search strategies. The eight new antimicrobial agents demonstrated significant impacts on the ecological balance of the human intestinal microbiota. Therefore, eubiosis is crucial in preventing the establishment of exogenous antimicrobial-resistant strains as well as their gene transfer.[PRISMA], identifier [2009].
抗菌剂通过不完全吸收(如口服抗菌剂)或分泌(如通过唾液腺、胆汁或肠粘膜)对人类微生物群的生态平衡有显著影响。本研究旨在探讨新型抗菌药物对肠道微生物群正常功能的影响。这些英文文章是从PubMed、ScienceDirect、Web of Science、b谷歌Scholar和DOAJ,以及使用参考文献列表进行人工搜索中恢复的。“微生物群”、“肠道微生物群”、“益生菌群”、“生态影响”、“抗菌剂”、“抗生素”、“生态失调”、“肠道微生物群”和“益生菌”是用于检索文章的搜索词。PRISMA 2009检查表应用于文章检索策略、文章选择、数据提取和审查过程的结果报告。从不同检索策略获得的379篇论文中,共纳入8篇原创研究论文。这8种新型抗菌药物对人体肠道菌群的生态平衡有显著影响。因此,益生菌是至关重要的,在防止建立外源性抗菌素耐药菌株及其基因转移。[PRISMA],标识符[2009]。
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引用次数: 0
Molecular medicine-based IBD treatment strategies—we take it personally! 基于分子医学的IBD治疗策略——我们将其个人化!
Pub Date : 2023-08-09 DOI: 10.3389/fgstr.2023.1226048
Viktoria Hentschel, J. Klaus
In light of potentially aggressive disease courses of either IBD type—CD or UC—marked by frequent flareups or non-subsiding inflammatory activity, effective immunosuppression is key to preventing progressive tissue destruction and permanent disability. However, over-treating patients with a high probability of an indolent disease course ought to be avoided. To solve this therapeutic dichotomy, there is a pressing need for a reliable classification of patients based on their biosignature to rate their individual prognosis and likelihood of response to a given therapy. This need for pinpoint therapeutic strategies is addressed by the concepts of PreM and the more stringently defined PerM. In this review we summarize the most pivotal study results published so far in the field of individualized IBD care with a special focus on molecular diagnostics and their applicability in the clinical setting.
鉴于IBD型cd或uc的潜在侵袭性疾病病程以频繁发作或不消退的炎症活动为特征,有效的免疫抑制是防止进行性组织破坏和永久性残疾的关键。然而,过度治疗的病人很可能是一个惰性的疾病过程应该避免。为了解决这种治疗上的二分法,迫切需要根据患者的生物特征对患者进行可靠的分类,以评估他们的个体预后和对给定治疗的反应可能性。PreM的概念和更严格定义的PerM解决了对精确治疗策略的需求。在这篇综述中,我们总结了迄今为止在IBD个体化治疗领域发表的最关键的研究结果,特别关注分子诊断及其在临床环境中的适用性。
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引用次数: 0
Genomic landscape in Saudi patients with hepatocellular carcinoma using whole-genome sequencing: a pilot study 使用全基因组测序的沙特肝细胞癌患者基因组景观:一项试点研究
Pub Date : 2023-08-04 DOI: 10.3389/fgstr.2023.1205415
M. Hassanain, Yang Liu, W. Hussain, Albandri Binowayn, Duna Barakeh, Ebtehal A. Alsolme, Faisal A Alsaif, Ghaida Almasaad, Mohammed Alswayyed, Maram Alaqel, Rana Aljunidel, Sherin Abdelrahman, C. Hauser, S. Alqahtani, R. Hoehndorf, M. Abedalthagafi
Hepatocellular carcinoma (HCC) is the third most prevalent cancer in Saudi Arabia. HCC poses a significant clinical challenge due to the presence of resistance among certain patients to the standard therapeutic agent sorafenib. This study aims to unravel the genomic characteristics of HCC patients in Saudi Arabia, investigate the genetic makeup of tumors in both sorafenib-sensitive and sorafenib-resistant patients, and analyze the functional implications of genomic abnormalities observed in these individuals. The resistance displayed by some HCC patients toward sorafenib underscores the need for alternative treatment approaches to effectively combat this formidable disease burden.Whole-genome sequencing (WGS) was performed on 16 HCC samples and targeted sequencing was performed on seven additional tumors. We identified and validated somatic and germline genetic aberrations. Employing a prize-collecting Steiner tree algorithm, we identified important altered genetic modules and potential biomarkers for each patient. Furthermore, we analyzed non-synonymous germline and somatic mutations, specifically in patients who underwent sorafenib treatment.Out of the 13 patients who received sorafenib, three exhibited sorafenib sensitivity, while the others showed resistance to the drug. Notably, 3 out of 16 individuals carried cancer-predisposing mutations. Additionally, 8 out of 16 patients displayed non-synonymous somatic alterations in genes associated with cancer. In the targeted-sequencing samples, rare non-synonymous variants were observed across all seven cases. The study also revealed the presence of specific somatic aberrations, including TP53, PIK3CA, APOB, CTNNB1, DPYD, LRP1B, MYC, and NFE2L2, which were identified in two patients. Among the 42 genes linked to sorafenib treatment, 4 out of 10 resistant patients carried somatic non-synonymous variants. Furthermore, when analyzing the 5,000 genes most relevant to the 42 genes, 7 out of 10 resistant individuals exhibited rare non-synonymous germline variants. Interestingly, none of the three sorafenib-sensitive patients displayed any concerning variants in those genes.Our findings indicate that most of the HCC patients possess cancer-related genetic variants, and the altered pathways in these patients exhibit similarities. Notably, resistant patients exhibit a higher frequency of aberrations in sorafenib-related genes than do sensitive patients. Specifically, 4 out of 10 resistant individuals demonstrated 13 somatic mutations, whereas none of the three sensitive patients exhibited any. Similarly, 7 out of 10 resistant patients possessed 30 germline mutations, while none were observed in the sensitive group (two-sided Fisher’s exact test; somatic: p=0.50, germline: 0.07). These results contribute to our understanding of the genetic landscape of HCC and highlight potential therapeutic targets that could aid in overcoming treatment resistance.
肝细胞癌(HCC)是沙特阿拉伯第三大常见癌症。由于某些患者对标准治疗药物索拉非尼存在耐药性,HCC提出了重大的临床挑战。本研究旨在揭示沙特阿拉伯HCC患者的基因组特征,研究索拉非尼敏感和索拉非尼耐药患者肿瘤的基因组成,并分析这些个体中观察到的基因组异常的功能意义。一些HCC患者对索拉非尼的耐药性强调了需要替代治疗方法来有效对抗这一可怕的疾病负担。对16个HCC样本进行了全基因组测序(WGS),并对另外7个肿瘤进行了靶向测序。我们鉴定并验证了体细胞和种系遗传畸变。采用获奖的斯坦纳树算法,我们确定了每个患者重要的改变的遗传模块和潜在的生物标志物。此外,我们分析了非同义种系和体细胞突变,特别是在接受索拉非尼治疗的患者中。在接受索拉非尼治疗的13名患者中,3名患者表现出索拉非尼敏感性,而其他患者则表现出耐药性。值得注意的是,16个人中有3人携带易患癌症的突变。此外,16名患者中有8名在与癌症相关的基因中表现出非同义的体细胞改变。在目标测序样本中,在所有7例中都观察到罕见的非同义变异。该研究还揭示了在两例患者中发现的特异性体细胞畸变,包括TP53、PIK3CA、APOB、CTNNB1、DPYD、LRP1B、MYC和NFE2L2。在与索拉非尼治疗相关的42个基因中,10个耐药患者中有4个携带体细胞非同义变体。此外,当分析与42个基因最相关的5000个基因时,10个抗性个体中有7个表现出罕见的非同义种系变异。有趣的是,三位对索拉非尼敏感的患者都没有在这些基因中显示出任何相关的变异。我们的研究结果表明,大多数HCC患者具有与癌症相关的遗传变异,并且这些患者的改变通路具有相似性。值得注意的是,耐药患者比敏感患者在索拉非尼相关基因中表现出更高的畸变频率。具体来说,10个耐药个体中有4个表现出13个体细胞突变,而3个敏感患者都没有表现出任何突变。同样,10名耐药患者中有7名具有30种生殖系突变,而在敏感组中没有观察到任何突变(双侧Fisher精确检验;体细胞:p=0.50,种系:0.07)。这些结果有助于我们了解HCC的遗传景观,并强调可能有助于克服治疗耐药的潜在治疗靶点。
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引用次数: 0
Cryptogenic chronic hepatitis: looking for an ideal diagnostic algorithm 隐源性慢性肝炎:寻找理想的诊断算法
Pub Date : 2023-08-01 DOI: 10.3389/fgstr.2023.1209000
G. G. L. Cançado, Aline Coelho Rocha Candolo, M. J. Nardelli, P. M. Zitelli, D. Mazo, C. Oliveira, M. Cunha-Silva, R. D. Greca, R. C. Araújo, Amanda Sacha Paulino Tolentino Alustau, C. Couto, Gabriel Rezende de Lima Roque, A. Farias, F. Carrilho, M. Pessoa
Cryptogenic chronic hepatitis is a growing cause of liver transplants, affecting 5%–15% of patients with chronic liver diseases. This study aimed to identify underlying causes of cryptogenic liver disease in a Brazilian cohort and propose a new diagnostic algorithm, including investigation for metabolic-dysfunction-associated fatty liver disease (MAFLD) and lysosomal acid lipase deficiency (LAL-D).A retrospective analysis was conducted on 326 patients with presumed cryptogenic hepatitis.Using Czaja’s algorithm, non-alcoholic fatty liver disease was diagnosed in 21.3% of patients, while alpha-1 antitrypsin deficiency, alcoholic liver disease, autoimmune hepatitis, hemochromatosis, biliary-related hepatitis, viral hepatitis, Budd–Chiari syndrome, glycogenosis, drug-induced liver injury, and Wilson’s disease were diagnosed in smaller proportions (< 3.5% each). LAL-D was found in 1% of patients, and 53.6% of patients remained with cryptogenic hepatitis. The etiology of the liver disease in a subset of patients undergoing liver transplantation was updated post hoc based on explant histology, and non-alcoholic steatohepatitis was found in 52.5% of patients. By incorporating the concept of MAFLD, the new algorithm could diagnose 49.1% of patients, reducing the number of individuals without an etiological diagnosis by 11.4%.One-third of patients with initially presumed cryptogenic liver disease were diagnosed with MAFLD. LAL-D should be considered in patients with chronic liver disease of unknown etiology. The updated diagnostic algorithm proposed in this study could improve diagnostic accuracy and aid in the management of patients with cryptogenic hepatitis.
隐源性慢性肝炎是肝移植的一个日益严重的原因,影响5%-15%的慢性肝病患者。本研究旨在确定巴西队列中隐源性肝病的潜在原因,并提出一种新的诊断算法,包括代谢功能障碍相关脂肪肝(MAFLD)和溶酶体酸性脂肪酶缺乏症(LAL-D)的调查。对326例推测为隐源性肝炎的患者进行了回顾性分析。使用Czaja算法,21.3%的患者被诊断为非酒精性脂肪性肝病,而α-1抗胰蛋白酶缺乏症、酒精性肝病、自身免疫性肝炎、血色素沉着症、胆道相关肝炎、病毒性肝炎、布-加综合征、糖原生成病、药物性肝损伤和Wilson病的诊断比例较小(各<3.5%)。在1%的患者中发现LAL-D,53.6%的患者仍患有隐源性肝炎。根据外植体组织学,对接受肝移植的一部分患者的肝病病因进行了事后更新,52.5%的患者发现了非酒精性脂肪性肝炎。通过引入MAFLD的概念,新算法可以诊断49.1%的患者,将没有病因诊断的患者数量减少11.4%。三分之一的最初推测为隐源性肝病的患者被诊断为MAFLD。病因不明的慢性肝病患者应考虑LAL-D。本研究中提出的更新诊断算法可以提高诊断准确性,并有助于管理隐源性肝炎患者。
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Frontiers in gastroenterology (Lausanne, Switzerland)
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