Methanogens, methane and gastrointestinal motility Triantafyllou, Konstantinos; Chang, Christopher; Pimentel, Mark
Journal of neurogastroenterology and motility,
01/2014, Volume:
20, Issue:
1
Journal Article
Peer reviewed
Open access
Anaerobic fermentation of the undigested polysaccharide fraction of carbohydrates produces hydrogen in the intestine which is the substrate for methane production by intestinal methanogens. Hydrogen ...and methane are excreted in the flatus and in breath giving the opportunity to indirectly measure their production using breath testing. Although methane is detected in 30%-50% of the healthy adult population worldwide, its production has been epidemiologically and clinically associated with constipation related diseases, like constipation predominant irritable bowel syndrome and chronic constipation. While a causative relation is not proven yet, there is strong evidence from animal studies that methane delays intestinal transit, possibly acting as a neuromuscular transmitter. This evidence is further supported by the universal finding that methane production (measured by breath test) is associated with delayed transit time in clinical studies. There is also preliminary evidence that antibiotic reduction of methanogens (as evidenced by reduced methane production) predicts the clinical response in terms of symptomatic improvement in patients with constipation predominant irritable bowel syndrome. However, we have not identified yet the mechanism of action of methane on intestinal motility, and since methane production does not account for all constipation associated cases, there is need for high quality clinical trials to examine methane as a biomarker for the diagnosis or as a biomarker that predicts antibiotic treatment response in patients with constipation related disorders.
Evidence is limited on the comparative diagnostic performance of newer end-cutting fine-needle biopsy (FNB) needles for tissue sampling of pancreatic masses. We performed a systematic review with ...network meta-analysis to compare the diagnostic accuracy of available FNB needles for sampling of solid pancreatic lesions.
A systematic literature review (Medline and Cochrane Database) was conducted for studies evaluating the accuracy of newer FNB needles in adults undergoing EUS-guided sampling of solid pancreatic masses. The primary outcome was diagnostic accuracy. Secondary outcomes were sample adequacy, diagnostic sensitivity, specificity, and adverse event rate. We performed pairwise and network meta-analyses and appraised the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation methodology.
Overall, 16 RCTs (1934 patients) were identified. On network meta-analysis, Franseen needles (Acquire; Boston Scientific, Marlborough, Mass, USA) significantly outperformed reverse-bevel needles (risk ratio RR, 1.21 95% confidence interval {CI}, 1.05-1.40 for accuracy and 1.31 95% CI, 1.05-1.22 for adequacy) and FNA needles (RR, 1.21 95% CI, 1.01-1.25 for accuracy and 1.07 95% CI, 1.02-1.13 for adequacy). Likewise, the Fork-tip needle (SharkCore; Medtronic, Dublin, Ireland) was significantly superior to the reverse-bevel needle (RR, 1.17 95% CI, 1.03-1.33 for accuracy and 1.09 95% CI, 1.02-1.16 for adequacy) and to the FNA needle (RR, 1.09 95% CI, 1.01-1.19 for accuracy and 1.03 95% CI, 1.01-1.07 for adequacy). Other comparisons did not achieve statistical significance. As a consequence, Franseen (surface under the cumulative ranking score, .89 for accuracy and .94 for adequacy) and Fork-tip needles (surface under the cumulative ranking score, .76 for accuracy and .73 for adequacy) ranked as the 2 highest-performing FNB needles. When considering different needle sizes, 25-gauge Franseen and 25-gauge Fork-tip needles were not superior to 22-gauge reverse-bevel needles (RR, 1.18 95% CI, .96-1.46 and 1.04 95% CI, .62-1.52). None of the tested needles was significantly superior to the other FNB devices or to FNA needles when rapid onsite cytologic evaluation was available.
Franseen and Fork-tip needles, particularly 22-gauge size, showed the highest performance for tissue sampling of pancreatic masses, with low confidence in estimates.
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Among various hormones, which are synthesized by intestinal cells and influence enteric function, neurotensin (NT) has gained scientific attention the last three decades. This neuropeptide, mainly ...located in neuronal synaptic vesicles of hypothalamus and in neuroendocrine cells of the small bowel, participates in enteric digestive processes, gut motility and intestinal inflammatory mechanisms by cooperating with other regulators such as histamine, substance P and somatostatin. NT plays an important role mainly in intestinal lipid metabolism by cooperating with cholecystokinin and establishes a hormonal brain–gut–adipose tissue connection, which could adjust appetite, weight status and generally eating behavior with the amount and the content (particularly fat) of food intake. Moreover, NT achieves a multi-level control of intestinal motility by cooperating with the enteric- and central nervous system, and other enteric hormones (such as somatostatin). NT regulates motility patterns related to the efficiency of the digestive process, stool emptying, transition from the fasted to the postprandial state and reestablishment of the fasted status. In addition, NT possesses a long-term enteroprotective role towards the intestinal tract, despite the fact that under certain circumstances NT may participate in short-term subcellular pathways promoting an acute inflammatory response. The aim of this review is two-fold. First, is to provide an up-to-date synopsis of the available knowledge regarding the involvement of neurotensin in enteric functional status, and highlight its significance in physiological and pathological conditions. Second, is to propose new research directions concerning the role of neurotensin and other intestinal regulatory peptides in the establishment of the brain–gut axis and in the development of functional disorders of the abdominal tract. Conclusively, to clarify the areas, in which an experimental therapeutic intervention, based on NT analogs, may lead to encouraging results.
► NT plays important role mainly in intestinal lipid metabolism and it participates in brain-gut-adipose tissue connection. ► NT achieves a multi-level control of intestinal motility. ► NT possesses a long-term enteroprotective role towards the intestinal tract. ► NT may be involved in acute subcellular pathways of inflammatory response. ► Indirect data imply a possible relation between NT and irritable bowel syndrome.
Abstract
Background
Risk stratification for sudden cardiac death in post‐myocardial infarction (post‐MI) patients remains a challenging task. Several electrocardiographic noninvasive risk factors ...(NIRFs) have been associated with adverse outcomes and were used to refine risk assessment. This study aimed to evaluate the performance of NIRFs extracted from 45‐min short resting Holter ECG recordings (SHR), in predicting ventricular tachycardia inducibility with programmed ventricular stimulation (PVS) in post‐MI patients with preserved left ventricular ejection fraction (LVEF).
Methods
We studied 99 post‐MI ischemia‐free patients (mean age: 60.5 ± 9.5 years, 86.9% men) with LVEF ≥40%, at least 40 days after revascularization. All the patients underwent PVS and a high‐resolution SHR. The following parameters were evaluated: mean heart rate, ventricular arrhythmias (premature ventricular complexes, couplets, tachycardias), QTc duration, heart rate variability (HRV), deceleration capacity, heart rate turbulence, late potentials, and T‐wave alternans.
Results
PVS was positive in 24 patients (24.2%). HRV, assessed by the standard deviation of normal‐to‐normal R–R intervals (SDNN), was significantly decreased in the positive PVS group (42 ms vs. 51 ms,
p
= .039). SDNN values <50 ms were also associated with PVS inducibility (OR 3.081,
p
= .032 in univariate analysis, and 4.588,
p
= .013 in multivariate analysis). No significant differences were identified for the other NIRFs. The presence of diabetes, history of ST‐elevation MI (STEMI) and LVEF <50% were also important predictors of positive PVS.
Conclusions
HRV assessed from SHR, combined with other noninvasive clinical and echocardiographic variables (diabetes, STEMI history, LVEF), can provide an initial, practical, and rapid screening tool for arrhythmic risk assessment in post‐MI patients with preserved LVEF.
Background
Electrocardiographic non‐invasive risk factors (NIRFs) have an important role in the arrhythmic risk stratification of post‐myocardial infarction (post‐MI) patients with preserved or ...mildly reduced left ventricular ejection fraction (LVEF). However, their specific relation to left ventricular systolic function remains unclear. We aimed to evaluate the association between NIRFs and LVEF in the patients included in the PRESERVE‐EF trial.
Methods
We studied 575 post‐MI ischemia‐free patients with LVEF≥40% (mean age: 57.0 ± 10.4 years, 86.2% men). The following NIRFs were evaluated: premature ventricular complexes, non‐sustained ventricular tachycardia (NSVT), late potentials (LPs), prolonged QTc, increased T‐wave alternans, reduced heart rate variability, and abnormal deceleration capacity with abnormal turbulence.
Results
There was a statistically significant relationship between LPs (Chi‐squared = 4.975; p < .05), nsVT (Chi‐squared = 5.749, p < .05), PVCs (r= −.136; p < .01), and the LVEF. The multivariate linear regression analysis showed that LPs (p = .001) and NSVT (p < .001) were significant predictors of the LVEF. The results of the multivariate logistic regression analysis indicated that LPs (OR: 1.76; 95% CI: 1.02–3.05; p = .004) and NSVT (OR: 2.44; 95% CI: 1.18–5.04; p = .001) were independent predictors of the mildly reduced LVEF: 40%–49% versus the preserved LVEF: ≥50%.
Conclusion
Late potentials and NSVT are independently related to reduced LVEF while they are independent predictors of mildly reduced LVEF versus the preserved LVEF. These findings may have important implications for the arrhythmic risk stratification of post‐MI patients with mildly reduced or preserved LVEF.
Background
NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β.
Aims
To investigate NLRP3 inflammasome ...activation in inflammatory bowel disease.
Methods
Peripheral blood mononuclear cells from Crohn’s disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1β, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1β was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1β production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of
IL
-
1β
,
TNFα
,
NLRP3
, and
CASP1
were measured by RT-PCR. DNA was isolated from CD patients for
ATG16L1
gene genotyping.
Results
NLRP3 inflammasome was activated in 60% of CD patients compared to 28.6% of controls (
p
= 0.042); no significant difference was detected between UC and controls. Among UC patients, NLRP3 activation was associated (
p
= 0.008) with long-standing disease (>1.5 years). IL-1β levels were significantly higher in CD patents in comparison with controls (
p
= 0.032). No difference was detected in the levels of IL-6, TNFα, pro-IL-1β and in the numbers
IL
-
1β
,
TNFα
,
NLRP3
, and
CASP1
transcripts among groups. IL-1β production was similar between carriers of wild-type and of SNP alleles of the rs2241880.
Conclusions
NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.
Background
In the PRESERVE‐EF study, a two‐step sudden cardiac death (SCD) risk stratification approach to detect post‐myocardial infarction (MI) patients with left ventricle ejection fraction (LVEF) ...≥40% at risk for major arrhythmic events (MAEs) was used. Seven noninvasive risk factors (NIRFs) were extracted from a 24‐h ambulatory electrocardiography (AECG) and a 45‐min resting recording. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS) and inducible patients received an Implantable Cardioverter ‐ Defibrillator (ICD).
Methods
In the present study, we evaluated the performance of the NIRFs, as they were described in the PRESERVE‐EF study protocol, in predicting a positive PVS. In the PRESERVE‐EF study, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analyzed.
Results
Among the NIRFs examined, the presence of signal averaged ECG‐late potentials (SAECG‐LPs) ≥ 2/3 and non‐sustained ventricular tachycardia (NSVT) ≥1 eposode/24 h cutoff points were important predictors of a positive PVS study, demonstrating in the logistic regression analysis odds ratios 2.285 (p = .027) and 2.867 (p = .006), respectively. A simple risk score based on the above cutoff points in combination with LVEF < 50% presented high sensitivity but low specificity for a positive PVS.
Conclusion
Cutoff points of NSVT ≥ 1 episode/24 h and SAECG‐LPs ≥ 2/3 in combination with a LVEF < 50% were important predictors of inducibility. However, the final decision for an ICD implantation should be based on a positive PVS, which is irreplaceable in risk stratification.
Background
Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety ...within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy.
Aims
We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes.
Methods
Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response.
Results
We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes.
Conclusions
Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.
Background Colon capsule endoscopy (CCE) could be an option to examine the colon after incomplete colonoscopy. Objective To investigate the extent that CCE complements incomplete colonoscopy and ...guides further workup. Design Prospective, follow-up study. Setting Three tertiary-care centers. Patients Consecutive outpatients after colonoscopy failure; 1-year study period. Intervention Patients underwent CCE either immediately after colonoscopy or were rescheduled. Further investigations were guided by the results of CCE. Patients were followed as long as 2 years. Results We studied 75 outpatients; 39 had a screening colonoscopy. One third of the patients underwent CCE immediately after colonoscopy. Overall, CCE reached or went beyond the colon segment at which colonoscopy stopped in 68 patients (91%). CCE technically complemented difficult colonoscopy independently of whether same-day CCE was performed (24 96%) or was not performed (44 88%). CCE detected additional significant findings in 36% of the same-day CCE cases and in 48% of the rescheduled ones. Two patients in the same-day group and 13 in the rescheduled CCE group underwent further colon examination that revealed additional significant findings in 3 of them. Ten percent of the patients reported mild adverse events (AE). If needed, 63 participants (84%) were willing to repeat CCE. Follow-up has not identified symptomatic missed colon cancers. Limitations Selected patient population, first-generation colon capsule, old preparation scheme. Conclusion CCE performed immediately or at a scheduled date after colonoscopy failure is feasible and safe. CCE after incomplete colonoscopy appears to yield significant findings, guide further workup, and has high patient acceptance.
Introduction: Irritable bowel syndrome (IBS) symptoms can be effectively managed with the low FODMAP diet. However, its efficacy in reducing inflammation is not yet proven. On the contrary, the ...Mediterranean diet has anti-inflammatory properties with proven efficacy in treating chronic low-grade inflammation-related diseases. Aim: To publicly share our protocol evaluating the efficacy of the Mediterranean low-FODMAP (MED-LFD) versus NICE recommendations (British National Institute for Health and Care Excellence) diet in managing IBS symptoms and quality of life. Materials and Methods: Participants meeting the Rome IV criteria will be randomly assigned to MED-LFD or NICE recommendations and they will be followed for six months. Efficacy, symptom relief, quality of life and mental health will be assessed using validated questionnaires. In addition, fecal samples will be analyzed to assess gut microbiota, and to measure branched and short-chain fatty acids, and volatile organic compounds (metabolic byproducts from bacteria). Expected results and discussion: By publicly sharing this clinical study protocol, we aim to improve research quality in the field of IBS management by allowing for peer review feedback, preventing data manipulation, reducing redundant research efforts, mitigating publication bias, and empowering patient decision-making. We expect that this protocol will show that MED-LFD can effectively alleviate IBS symptoms and it will provide pathophysiology insights on its efficacy. The new dietary pattern that combines the LFD and the MED approaches allows for the observation of the synergistic action of both diets, with the MED’s anti-inflammatory and prebiotic properties enhancing the effects of the LFD while minimizing its limitations. Identifier in Clinical Trials: NCT03997708
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