Gall-bladder dysmotility - A risk factor for gall-stone formation in hypertriglyceridaemia and reversal on triglyceride-lowering therapy with bezafibrate and fish oil

Doel: Onderzoeken van de pathofysiologische mechanismen die de kans op galstenen verhogen bij hypertriglyceridemie (HTG) en het vergelijken van de effecten van triglycerideverlagende therapie met bezafibraat en visolie op determinanten van cholelithiasis (biliaire lipidesamenstelling en galblaasmotoriek) bij HTG-patiënten.Opzet: Gekruiste opzet met ‘random’-volgorde.Patiënten en methoden: De galblaasmotoriek werd postprandiaal en tijdens cholecystokinine(CCK)-infusie echografisch onderzocht. De determinanten van cholelithiasis en de serumlipiden werden vergeleken tussen 9 HTG-patiënten en 10 normolipidemische controlepersonen van hetzelfde geslacht, dezelfde leeftijd en ‘body mass’-index. Bij de HTG-patiënten werden de effecten van bezafibraat en gezuiverde omega-3-olie (‘visolie’) bepaald.Resultaten: De serumtriglyceride(TG)-spiegel van de HTG-patiënten was 14-voudig verhoogd, vergeleken met de controlepersonen. De lipidesamenstelling van de gal, de nuchtere galblaasvolumen en de serum-CCK-spiegels verschilden niet tussen HTG-patiënten en controlepersonen. De galblaaslediging was verminderd bij HTG-patiënten versus controlepersonen tijdens CCK-infusie (–22) en ook na een maaltijd (–37; beide p &lt; 0,001). De postprandiale serum-CCK-spiegels waren significant hoger bij HTG-patiënten. Zowel bezafibraat als visolie verlaagde de serum-TG-spiegel (–68 en –51 ten opzichte van de uitgangswaarde; beide: p &lt; 0,01). Nuchtere CCK-spiegels verschilden niet, terwijl de CCK-geïnduceerde galblaaslediging onder bezafibraat toenam met 29 (p &lt; 0,001) en met visolie met 13 (p = 0,07). De postprandiale galblaasmotoriek verbeterde tijdens zowel bezafibraat- (+47) als visoliebehandeling (+25; beide: p &lt; 0,02), waarschijnlijk gedeeltelijk door een toegenomen gevoeligheid van de galblaas voor CCK (voor beide: p &lt; 0,05 vergeleken met de uitgangsfase). Bezafibraat, in tegenstelling tot visolie, verhoogde de molaire cholesterol-galzuurratio (+40; p ≤ 0,05), terwijl beide behandelingen geen effect hadden op de cholesterolsaturatie-index.Conclusies: De verminderde galblaasmotoriek bij HTG-patiënten lijkt het gevolg te zijn van verminderde gevoeligheid voor CCK, wat kan bijdragen aan het verhoogde risico op galsteenvorming. Bij HTG-patiënten verbetert triglycerideverlagende therapie met visolie of bezafibraat de verminderde galblaasmotoriek zonder nadelig effect op de biliaire cholesterolverzadiging.Objective. To unravel the mechanisms responsible for the increased risk of gall-stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride-lowering therapy with bezafibrate and fish oil on determinants of cholelithiasis (biliary-lipid composition and gall-bladder motility) in HTG patients. Design. Randomised cross over. Patients and methods. Gall-bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between 9 HTG patients and 10 age, sex and body-mass index matched normolipidaemic controls. The effects of bezafibrate and purified omega-3-oil ('fish oil') in HTG patients were studied. Results. HTG patients showed 14-fold higher serum-triglyceride (TG) levels than controls. Biliary-lipid composition, fasting gall-bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall-bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p &lt; 0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68 and -51% versus baseline, respectively; both p &lt; 0.01). Fasting CCK levels were not affected whereas CCK-induced gall-bladder emptying increased during bezafibrate (+29%; p &lt; 0.001) and tended to increase upon fish-oil therapy (+13%; p = 0.07). Postprandial gall-bladder motility improved at least partly with bezafibrate and fish oil (+47 and +25% versus baseline, respectively; both p &lt; 0.02) due to increased gallbladder sensitivity to CCK (both p &lt; 0.05 versus baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p ≤ 0.05), but no effects on the cholesterol-saturation index were seen with either treatment. Conclusions. We suggest that impaired gall-bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall-stone disease in HTG patients. Triglyceride-lowering therapy by both fish oil and bezafibrate improves gall-bladder dysmotility without adversely affecting biliary-cholesterol saturation.</p

Gall-bladder dysmotility - A risk factor for gall-stone formation in hypertriglyceridaemia and reversal on triglyceride-lowering therapy with bezafibrate and fish oil

Doel: Onderzoeken van de pathofysiologische mechanismen die de kans op galstenen verhogen bij hypertriglyceridemie (HTG) en het vergelijken van de effecten van triglycerideverlagende therapie met bezafibraat en visolie op determinanten van cholelithiasis (biliaire lipidesamenstelling en galblaasmotoriek) bij HTG-patiënten.Opzet: Gekruiste opzet met ‘random’-volgorde.Patiënten en methoden: De galblaasmotoriek werd postprandiaal en tijdens cholecystokinine(CCK)-infusie echografisch onderzocht. De determinanten van cholelithiasis en de serumlipiden werden vergeleken tussen 9 HTG-patiënten en 10 normolipidemische controlepersonen van hetzelfde geslacht, dezelfde leeftijd en ‘body mass’-index. Bij de HTG-patiënten werden de effecten van bezafibraat en gezuiverde omega-3-olie (‘visolie’) bepaald.Resultaten: De serumtriglyceride(TG)-spiegel van de HTG-patiënten was 14-voudig verhoogd, vergeleken met de controlepersonen. De lipidesamenstelling van de gal, de nuchtere galblaasvolumen en de serum-CCK-spiegels verschilden niet tussen HTG-patiënten en controlepersonen. De galblaaslediging was verminderd bij HTG-patiënten versus controlepersonen tijdens CCK-infusie (–22) en ook na een maaltijd (–37; beide p &lt; 0,001). De postprandiale serum-CCK-spiegels waren significant hoger bij HTG-patiënten. Zowel bezafibraat als visolie verlaagde de serum-TG-spiegel (–68 en –51 ten opzichte van de uitgangswaarde; beide: p &lt; 0,01). Nuchtere CCK-spiegels verschilden niet, terwijl de CCK-geïnduceerde galblaaslediging onder bezafibraat toenam met 29 (p &lt; 0,001) en met visolie met 13 (p = 0,07). De postprandiale galblaasmotoriek verbeterde tijdens zowel bezafibraat- (+47) als visoliebehandeling (+25; beide: p &lt; 0,02), waarschijnlijk gedeeltelijk door een toegenomen gevoeligheid van de galblaas voor CCK (voor beide: p &lt; 0,05 vergeleken met de uitgangsfase). Bezafibraat, in tegenstelling tot visolie, verhoogde de molaire cholesterol-galzuurratio (+40; p ≤ 0,05), terwijl beide behandelingen geen effect hadden op de cholesterolsaturatie-index.Conclusies: De verminderde galblaasmotoriek bij HTG-patiënten lijkt het gevolg te zijn van verminderde gevoeligheid voor CCK, wat kan bijdragen aan het verhoogde risico op galsteenvorming. Bij HTG-patiënten verbetert triglycerideverlagende therapie met visolie of bezafibraat de verminderde galblaasmotoriek zonder nadelig effect op de biliaire cholesterolverzadiging.Objective. To unravel the mechanisms responsible for the increased risk of gall-stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride-lowering therapy with bezafibrate and fish oil on determinants of cholelithiasis (biliary-lipid composition and gall-bladder motility) in HTG patients. Design. Randomised cross over. Patients and methods. Gall-bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between 9 HTG patients and 10 age, sex and body-mass index matched normolipidaemic controls. The effects of bezafibrate and purified omega-3-oil ('fish oil') in HTG patients were studied. Results. HTG patients showed 14-fold higher serum-triglyceride (TG) levels than controls. Biliary-lipid composition, fasting gall-bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall-bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p &lt; 0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68 and -51% versus baseline, respectively; both p &lt; 0.01). Fasting CCK levels were not affected whereas CCK-induced gall-bladder emptying increased during bezafibrate (+29%; p &lt; 0.001) and tended to increase upon fish-oil therapy (+13%; p = 0.07). Postprandial gall-bladder motility improved at least partly with bezafibrate and fish oil (+47 and +25% versus baseline, respectively; both p &lt; 0.02) due to increased gallbladder sensitivity to CCK (both p &lt; 0.05 versus baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p ≤ 0.05), but no effects on the cholesterol-saturation index were seen with either treatment. Conclusions. We suggest that impaired gall-bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall-stone disease in HTG patients. Triglyceride-lowering therapy by both fish oil and bezafibrate improves gall-bladder dysmotility without adversely affecting biliary-cholesterol saturation.</p

Algorithm combining virtual chromoendoscopy features for colorectal polyp classification

Background and study aims Colonoscopy is considered the gold standard for decreasing colorectal cancer incidence and mortality. Optical diagnosis of colorectal polyps (CRPs) is an ongoing challenge in clinical colonoscopy and its accuracy among endoscopists varies widely. Computer-aided diagnosis (CAD) for CRP characterization may help to improve this accuracy. In this study, we investigated the diagnostic accuracy of a novel algorithm for polyp malignancy classification by exploiting the complementary information revealed by three specific modalities. Methods We developed a CAD algorithm for CRP characterization based on high-definition, non-magnified white light (HDWL), Blue light imaging (BLI) and linked color imaging (LCI) still images from routine exams. All CRPs were collected prospectively and classified into benign or premalignant using histopathology as gold standard. Images and data were used to train the CAD algorithm using triplet network architecture. Our training dataset was validated using a threefold cross validation. Results In total 609 colonoscopy images of 203 CRPs of 154 consecutive patients were collected. A total of 174 CRPs were found to be premalignant and 29 were benign. Combining the triplet network features with all three image enhancement modalities resulted in an accuracy of 90.6 %, 89.7 % sensitivity, 96.6 % specificity, a positive predictive value of 99.4 %, and a negative predictive value of 60.9 % for CRP malignancy classification. The classification time for our CAD algorithm was approximately 90 ms per image. Conclusions Our novel approach and algorithm for CRP classification differentiates accurately between benign and premalignant polyps in non-magnified endoscopic images. This is the first algorithm combining three optical modalities (HDWL/BLI/LCI) exploiting the triplet network approach

The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; A randomized double-blind placebo controlled trial

The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gut mucosal gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP104448, TIFN101 or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06 ± 0.04 to 0.10 ± 0.06, p = 0.001), but was not significantly affected by the bacterial interventions. However, analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated gene transcription pathways related to cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific gene transcriptional effects on repair processes in the compromised intestine of healthy subjects

Effect of domain-specific self-supervised pretraining on predictive uncertainty for colorectal polyp characterization

Colorectal polyps (CRPs) are potential precursors of colorectal cancer (CRC), one of the most common types of cancer worldwide. Computer-Aided Diagnosis (CADx) systems can play a crucial role as a second opinion for endoscopists in characterizing CRPs and contribute to the diagnostic performance of colonoscopies. Despite their potential, deep neural network-based systems often tend to overestimate the confidence about their decisions and provide predictive probabilities that are poorly related to their classification accuracy. Quantifying uncertainty of such supportive systems is crucial for optimal clinical workflow integration and physician's acceptance. Thus, a trustworthy CADx system is expected to provide accurate and well-calibrated classification confidence. Transfer learning from either natural image datasets, such as ImageNet, or other datasets with similar modalities, has been widely used for improving the accuracy of deep learning-based systems in medical image classification. In this paper, we study the impact of domain-specific pretraining on the calibration and the overall performance of a CADx system for CRP characterization. We evaluate our hypothesis on a fully deterministic and a hybrid Bayesian version of each approach using a generic ResNet50 architecture. Experimental results demonstrate the effectiveness of domain-specific pretraining in achieving a higher overall characterization AUC. Additionally, the in-domain and out-of-domain pretrained models portray similar calibration error rates, however, their corresponding hybrid Bayesian models offer higher robustness with improved calibration performance. A hybrid Bayesian version of a domain-specific pretraining approach has shown to significantly improve the accuracy and reliability of CADx systems used for CRP characterization and similar positive effects may be expected for other medical imaging applications

Sugar Beet Pectin Supplementation Did Not Alter Profiles of Fecal Microbiota and Exhaled Breath in Healthy Young Adults and Healthy Elderly

Aging is accompanied with increased frailty and comorbidities, which is potentially associated with microbiome perturbations. Dietary fibers could contribute to healthy aging by beneficially impacting gut microbiota and metabolite profiles. We aimed to compare young adults with elderly and investigate the effect of pectin supplementation on fecal microbiota composition, short chain fatty acids (SCFAs), and exhaled volatile organic compounds (VOCs) while using a randomized, double-blind, placebo-controlled parallel design. Fifty-two young adults and 48 elderly consumed 15 g/day sugar beet pectin or maltodextrin for four weeks. Fecal and exhaled breath samples were collected before and after the intervention period. Fecal samples were used for microbiota profiling by 16S rRNA gene amplicon sequencing, and for analysis of SCFAs by gas chromatography (GC). Breath was used for VOC analysis by GC-tof-MS. Young adults and elderly showed similar fecal SCFA and exhaled VOC profiles. Additionally, fecal microbiota profiles were similar, with five genera significantly different in relative abundance. Pectin supplementation did not significantly alter fecal microbiota, SCFA or exhaled VOC profiles in elderly or young adults. In conclusion, aside from some minor differences in microbial composition, healthy elderly and young adults showed comparable fecal microbiota composition and activity, which were not altered by pectin supplementation.</p

Test performance of immunological fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 +/- 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (/=55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies