| 1. |
- Fritz, N., et al.
(författare)
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The serotonin receptor 3E variant is a risk factor for female IBS-D
- 2022
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Ingår i: Journal of Molecular Medicine-Jmm. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 100:11, s. 1617-1627
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT(3)Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.
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| 2. |
- Mohr, S., et al.
(författare)
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The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome
- 2021
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Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 25:16, s. 8047-8061
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Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.
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| 3. |
- Manes, G, et al.
(författare)
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Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline
- 2019
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Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 1438-8812 .- 0013-726X. ; 51:5, s. 472-491
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Tidskriftsartikel (refereegranskat)abstract
- ESGE recommends offering stone extraction to all patients with common bile duct stones, symptomatic or not, who are fit enough to tolerate the intervention.Strong recommendation, low quality evidence.ESGE recommends liver function tests and abdominal ultrasonography as the initial diagnostic steps for suspected common bile duct stones. Combining these tests defines the probability of having common bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends endoscopic ultrasonography or magnetic resonance cholangiopancreatography to diagnose common bile duct stones in patients with persistent clinical suspicion but insufficient evidence of stones on abdominal ultrasonography.Strong recommendation, moderate quality evidence.ESGE recommends the following timing for biliary drainage, preferably endoscopic, in patients with acute cholangitis, classified according to the 2018 revision of the Tokyo Guidelines:– severe, as soon as possible and within 12 hours for patients with septic shock– moderate, within 48 – 72 hours– mild, elective.Strong recommendation, low quality evidence.ESGE recommends endoscopic placement of a temporary biliary plastic stent in patients with irretrievable biliary stones that warrant biliary drainage.Strong recommendation, moderate quality of evidence.ESGE recommends limited sphincterotomy combined with endoscopic papillary large-balloon dilation as the first-line approach to remove difficult common bile duct stones. Strong recommendation, high quality evidence.ESGE recommends the use of cholangioscopy-assisted intraluminal lithotripsy (electrohydraulic or laser) as an effective and safe treatment of difficult bile duct stones.Strong recommendation, moderate quality evidence.ESGE recommends performing a laparoscopic cholecystectomy within 2 weeks from ERCP for patients treated for choledocholithiasis to reduce the conversion rate and the risk of recurrent biliary events. Strong recommendation, moderate quality evidence.
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| 4. |
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| 5. |
- Scarpellini, E., et al.
(författare)
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International consensus on the diagnosis and management of dumping syndrome
- 2020
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Ingår i: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 16:8, s. 448-466
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Tidskriftsartikel (refereegranskat)abstract
- Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose. Dumping syndrome is a frequent complication of oesophageal and gastric surgery, as well as bariatric surgery; however, guidance on how to manage patients with this condition is lacking. In this Evidence-based guideline, the authors use a Delphi consensus process to develop uniform guidance for the definition, diagnosis and management of dumping syndrome.
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