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Trimodal prehabilitation for colorectal surgery attenuates post-surgical losses in lean body mass: A pooled analysis of randomized controlled trials.
Gillis, C, Fenton, TR, Sajobi, TT, Minnella, EM, Awasthi, R, Loiselle, SÈ, Liberman, AS, Stein, B, Charlebois, P, Carli, F
Clinical nutrition (Edinburgh, Scotland). 2019;(3):1053-1060
Abstract
BACKGROUND & AIMS Preservation of lean body mass is an important cancer care objective. The capacity for prehabilitation interventions to modulate the lean body mass (LBM) of colorectal cancer patients before and after surgery is unknown. METHODS A pooled analysis of two randomized controlled trials of trimodal prehabilitation vs. trimodal rehabilitation at a single university-affiliated tertiary center employing Enhanced Recovery After Surgery (ERAS) care was conducted. The prehabilitation interventions included exercise, nutrition, and anxiety-reduction elements that began approximately four weeks before surgery and continued for eight weeks after surgery. The rehabilitation interventions were identical to the prehabilitation interventions but were initiated only after surgery. Body composition, measured using multifrequency bioelectrical impedance analysis, was recorded at baseline, pre-surgery, 4 and 8 weeks after surgery. The primary outcome was change in LBM before and after colorectal surgery for cancer. A mixed effects regression model was used to estimate changes in body mass and body composition over time controlling for age, sex, baseline body mass index (BMI), baseline six-minute walk test (6MWT), and postoperative compliance to the interventions. NCT02586701 &NCT01356264. RESULTS Pooled data included 76 patients who followed prehabilitation and 63 patients who followed rehabilitation (n = 139). Neither group experienced changes in preoperative LBM. Compared to rehabilitated patients, prehabilitated patients had significantly more absolute and relative LBM at four and eight-weeks post-surgery in models controlling for age, sex, baseline BMI, baseline 6MWT, and compliance to the postoperative intervention. CONCLUSION Trimodal prehabilitation attenuated the post-surgical LBM loss compared to the loss observed in patients who received the rehabilitation intervention. Patients who receive neither intervention (i.e., standard of care) would be likely to lose more LBM. Offering a prehabilitation program to colorectal cancer patients awaiting resection is a useful strategy to mitigate the impact of the surgical stress response on lean tissue in an ERAS setting, and, in turn, might have a positive impact on the cancer care course. CLINICAL TRIAL REGISTRATION NCT02586701 &NCT01356264 (clinicaltrials.gov).
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Hyponatremia could identify patients with intrabdominal sepsis and anastomotic leak after colorectal surgery: a systematic review of the literature.
Alsaleh, A, Pellino, G, Christodoulides, N, Malietzis, G, Kontovounisios, C
Updates in surgery. 2019;(1):17-20
Abstract
Anastomotic leak (AL) is a serious post-operative complication in colorectal surgery. It can lead to devastating morbidity and mortality. Clinicians usually depend on a combination of clinical, biochemical and radiological findings to diagnose this problem. In our article, we tried to look if electrolyte disturbances could be indicators for intra-abdominal sepsis due to AL. Systematic review of the literature identifies a potential correlation between electrolyte alterations and AL in digestive surgery. The following databases were searched: PubMed, EMBASE and MIDLINE. The review adhered to the PRISMA statement for systematic review. Our literature search did not identify any articles linking any electrolyte disturbances-except for hyponatremia-to AL. Pathophysiology of these electrolyte disturbances does not seem to be linked to AL, except for hyponatremia which might be explained. Our review included 442 patients with intra-abdominal sepsis and 1133 controls. The mean specificity of hyponatremia being associated with intra-abdominal sepsis is 86%, whereas mean sensitivity is 28%. Hyponatremia seems to be a significant and clinically relevant marker for of intra-abdominal sepsis and AL.
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In vitro and human pharmacoscintigraphic evaluation of an oral 5-ASA delivery system for colonic release.
Foppoli, A, Maroni, A, Moutaharrik, S, Melocchi, A, Zema, L, Palugan, L, Cerea, M, Gazzaniga, A
International journal of pharmaceutics. 2019;:118723
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Abstract
5-aminosalicylic acid (5-ASA) is the most widely used drug for the treatment of ulcerative colitis. The benefits of targeted delivery of 5-ASA to the large intestine are well known, resulting in reduced systemic absorption and increased local concentrations at the disease site. In the present study, a 5-ASA colon delivery system based on the time-dependent strategy, exploiting the relatively consistent small intestinal transit time (SITT), was manufactured and evaluated in vitro as well as in vivo. The system was obtained by successive spray-coating of an immediate-release tablet core with low-viscosity HPMC and Eudragit® L. The enteric film was effective in preventing release during the acidic stage of the in vitro test, while the HPMC coating brought about reproducible lag phases prior to release in phosphate buffer medium. A γ-scintigraphy investigation pointed out that, following administration to fasted and fed volunteers, disintegration of the units never occurred prior to colon arrival. In all cases, a lag time preceded the appearance of the drug and its N-acetyl metabolite in the bloodstream, which was found to correlate with the time of disintegration in a linear mode. The plasma levels of the drug and metabolite as well as their cumulative urinary recovery were relatively low with respect to those reported when 5-ASA is delivered to the small bowel.
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Nanostructured Chitosan-Based Biomaterials for Sustained and Colon-Specific Resveratrol Release.
Iglesias, N, Galbis, E, Díaz-Blanco, MJ, Lucas, R, Benito, E, de-Paz, MV
International journal of molecular sciences. 2019;(2)
Abstract
In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box⁻Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1 w/w. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79⁻81%), and the CTS-NPs composites (29⁻34%).
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Flavanol Bioavailability in Two Cocoa Products with Different Phenolic Content. A Comparative Study in Humans.
Gómez-Juaristi, M, Sarria, B, Martínez-López, S, Bravo Clemente, L, Mateos, R
Nutrients. 2019;(7)
Abstract
Cocoa has beneficial health effects partly due to its high flavanol content. This study was aimed at assessing the absorption and metabolism of polyphenols in two soluble cocoa products: a conventional (CC) and a flavanol-rich product (CC-PP). A crossover, randomized, blind study was performed in 13 healthy men and women. On two different days, after an overnight fast, volunteers consumed one serving of CC (15 g) or CC-PP (25 g) in 200 mL of semi-skimmed milk containing 19.80 mg and 68.25 mg of flavanols, respectively. Blood and urine samples were taken, before and after CC and CC-PP consumption, and analyzed by high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QToF-MS). Up to 10 and 30 metabolites were identified in plasma and urine, respectively. Phase II derivatives of epicatechin were identified with kinetics compatible with small intestine absorption, although the most abundant groups of metabolites were phase II derivatives of phenyl-γ-valerolactone and phenylvaleric acid, formed at colonic level. 5-(4'-Hydroxyphenyl)-γ-valerolactone-sulfate could be a sensitive biomarker of cocoa flavanol intake. CC and CC-PP flavanols showed a dose-dependent absorption with a recovery of 35%. In conclusion, cocoa flavanols are moderately bioavailable and extensively metabolized, mainly by the colonic microbiota.
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NSAID administration post colorectal surgery increases anastomotic leak rate: systematic review/meta-analysis.
Modasi, A, Pace, D, Godwin, M, Smith, C, Curtis, B
Surgical endoscopy. 2019;(3):879-885
Abstract
BACKGROUND Current enhanced recovery guidelines suggest that opioid sparing medications should be used for analgesia whenever possible following colorectal surgery. The present study aims to assess whether post-operative NSAID use is associated with an increased anastomotic leak rate after a colonic or rectal anastomosis. METHODS A systematic review was performed for studies investigating anastomotic leak rate following NSAID use vs control after colonic or rectal anastomosis. Meta-analysis was performed to assess for overall risk of anastomotic leak with NSAID use, as well as sub-group analysis to compare selective vs non-selective NSAIDs and drug-specific NSAID safety profiles. RESULTS Seven studies were included in the final review. Use of an NSAID post-operatively was associated with an overall increased risk of anastomotic leakage [OR 1.58 (1.23, 2.03), P = 0.0003]. Non-selective NSAIDs were associated with an increased risk [OR 1.79 (1.47, 2.18), P < 0.00001], but selective NSAIDs were not. The non-selective NSAID diclofenac was associated with an increased leak rate [OR 2.79 (1.96, 3.96), P < 0.00001], but ketorolac was not [OR 1.36 (0.89, 2.06), P = 0.16]. CONCLUSIONS Great caution must be taken when prescribing NSAIDs following colonic or rectal anastomotic creation. The safety profile varies within the NSAID class and further research is needed to clarify which NSAIDs are safe for use and which are not.
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Improved high-quality colon cleansing with 1L NER1006 versus 2L polyethylene glycol + ascorbate or oral sulfate solution.
Repici, A, Coron, E, Sharma, P, Spada, C, Di Leo, M, Noble, CL, Gschossmann, J, Bargalló García, A, Baumgart, DC
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2019;(12):1671-1677
Abstract
BACKGROUND & AIMS Colonoscopy requires bowel cleansing for gut mucosa visualization; high-quality cleansing facilitates lesion detection. NER1006 is a 1L polyethylene glycol (PEG) bowel preparation. This post hoc analysis of two randomized trials investigated cleansing efficacy assessed, as in clinical practice, by site endoscopists. METHODS Patients received NER1006, 2L PEG + ascorbate (2LPEG), or oral sulfate solution (OSS) as a 2-day evening/morning regimen (N2D) or NER1006 morning-only dosing (N1D). Treatment-blinded site endoscopists assessed cleansing using the Harefield Cleansing Scale (HCS). Analyses were conducted in a modified full analysis set, including (mFAS; n = 1378) or excluding (mFAS2; n = 1319) imputed failures, and in patients with 100% treatment adherence (mFAS100; n = 1047). Overall cleansing success (HCS grade A/B), overall high-quality cleansing (HCS grade A), and high-quality segments (HCS 3-4) per treatment population were analyzed. RESULTS Overall cleansing success was higher with N2D than 2LPEG (92.7-97.5% vs. 87.9-93.0%), and more patients had overall high-quality cleansing with N2D and N1D than 2LPEG (68.0-72.1% and 64.0-68.4% vs. 50.7-56.0%). Without imputed failures, N2D delivered more overall high-quality cleansing than OSS (74.5-77.3% vs. 67.8-69.8%). More high-quality segments were demonstrated with N2D and N1D versus 2 LPEG (82.5-87.1% and 79.4-84.4% vs. 70.4-76.3%) and with N2D versus OSS (82.7-89.5% vs. 78.1-84.4%). CONCLUSION When assessed by site endoscopists, NER1006 delivers greater high-quality cleansing than 2LPEG or OSS.
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Lactose digestion in humans: intestinal lactase appears to be constitutive whereas the colonic microbiome is adaptable.
Forsgård, RA
The American journal of clinical nutrition. 2019;(2):273-279
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Abstract
Globally, ∼70% of adults are deficient in intestinal lactase, the enzyme required for the digestion of lactose. In these individuals, the consumption of lactose-containing milk and dairy products can lead to the development of various gastrointestinal (GI) symptoms. The primary solution to lactose intolerance is withdrawing lactose from the diet either by eliminating dairy products altogether or substituting lactose-free alternatives. However, studies have shown that certain individuals erroneously attribute their GI symptoms to lactose and thus prefer to consume lactose-free products. This has raised the question whether consuming lactose-free products reduces an individual's ability to absorb dietary lactose and if lactose-absorbers should thus avoid these products. This review summarizes the current knowledge regarding the acclimatization of lactose processing in humans. Human studies that have attempted to induce intestinal lactase expression with different lactose feeding protocols have consistently shown lack of enzyme induction. Similarly, withdrawing lactose from the diet does not reduce intestinal lactase expression. Evidence from cross-sectional studies shows that milk or dairy consumption is a poor indicator of lactase status, corroborating the results of intervention studies. However, in lactase-deficient individuals, lactose feeding supports the growth of lactose-digesting bacteria in the colon, which enhances colonic lactose processing and possibly results in the reduction of intolerance symptoms. This process is referred to as colonic adaptation. In conclusion, endogenous lactase expression does not depend on the presence of dietary lactose, but in susceptible individuals, dietary lactose might improve intolerance symptoms via colonic adaptation. For these individuals, lactose withdrawal results in the loss of colonic adaptation, which might lower the threshold for intolerance symptoms if lactose is reintroduced into the diet.
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Dietary quality and the colonic mucosa-associated gut microbiome in humans.
Liu, Y, Ajami, NJ, El-Serag, HB, Hair, C, Graham, DY, White, DL, Chen, L, Wang, Z, Plew, S, Kramer, J, et al
The American journal of clinical nutrition. 2019;(3):701-712
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Abstract
BACKGROUND Despite tremendous interest in modulating the microbiome to improve health, the association between diet and the colonic mucosa-associated gut microbiome in healthy individuals has not been examined. OBJECTIVE To investigate the associations between Healthy Eating Index (HEI)-2005 and the colonic mucosa-associated microbiota. METHODS In this cross-sectional observational study, we analyzed bacterial community composition and structure using 16S rRNA gene (V4 region) sequencing of 97 colonic mucosal biopsies obtained endoscopically from different colon segments of 34 polyp-free participants. Dietary consumption was ascertained using an FFQ. Differences in α- and β-diversity and taxonomic relative abundances between the higher and lower score of total HEI and its components were compared, followed by multivariable analyses. RESULTS The structure of the microbiota significantly differed by the scores for total HEI, total and whole fruits (HEI 1 and HEI 2), whole grains (HEI 6), milk products and soy beverages (HEI 7), and solid fat, alcohol, and added sugar (HEI 12). A lower score for total HEI and HEIs 2, 7, and 12 was associated with significantly lower richness. A lower score for total HEI was associated with significantly reduced relative abundance of Parabacteroides, Roseburia, and Subdoligranulum but higher Fusobacterium. A lower score for HEI 2 was associated with lower Roseburia but higher Bacteroides. A lower score for HEI 7 was associated with lower Faecalibacterium and Fusobacterium but higher Bacteroides. A lower score for HEI 12 was associated with lower Subdoligranulum but higher Escherichia and Fusobacterium (false discovery rate-adjusted P values <0.05). The findings were confirmed by multivariate analysis. Less abundant bacteria such as Alistipes, Odoribacter, Bilophila, and Tyzzerella were also associated with dietary quality. CONCLUSIONS A lower score for total HEI-2005 was significantly associated with reduced relative abundance of potentially beneficial bacteria but increased potentially harmful bacteria in the colonic mucosa of endoscopically normal individuals.
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Characteristics and associated risk factors of diverticular disease assessed by magnetic resonance imaging in subjects from a Western general population.
Storz, C, Rothenbacher, T, Rospleszcz, S, Linseisen, J, Messmann, H, De Cecco, CN, Machann, J, Lorbeer, R, Kiefer, LS, Wintermeyer, E, et al
European radiology. 2019;(3):1094-1103
Abstract
OBJECTIVES Diverticular disease represents an increasing pathology and healthcare burden worldwide. Our aim was to study the prevalence, extent and distribution of asymptomatic diverticular disease assessed by magnetic resonance imaging (MRI) in a sample of a Western population. METHODS Subjects from a population-based cohort study who underwent 3-T MRI were analyzed for the prevalence and extent of diverticula of the colon using an isotropic VIBE-Dixon gradient-echo sequence. The extent of diverticular disease was categorized according to the number of diverticula in each colonic segment. Univariate and adjusted analyses were performed to assess associated characteristics and risk factors. RESULTS Among 393 subjects included in the analysis (56.4 ± 9.2 years, 57.5% males), 164 (42%) had diverticular disease, with the highest prevalence in the left-sided colonic segments (93% diverticular disease in the descending and sigmoid segment). Subjects with advanced diverticular disease were older (62.1 vs. 54.4 years) and had a higher body mass index (BMI), LDL cholesterol levels and systolic blood pressure (30.2 ± 5.1 vs. 27.8 ± 4.9 kg/m2, 149.8 ± 29.3 vs. 135.2 ± 32.9 mg/dl and 128.2 ± 14.1 vs. 118.4 ± 16.1 mmHg, respectively; all p > 0.003) compared with subjects without diverticular disease. In contrast, no significant correlation could be found for gender, physical activity, smoking status and alcohol consumption (all p > 0.31). Intra-rater reliability was excellent for all colonic segments (intra-class correlation [ICC] = 0.99-1.00), and inter-rater reliability was excellent for left- and right-sided colonic segments (ICC = 0.84-0.97). CONCLUSIONS These findings provide insights into the disease mechanism of asymptomatic diverticular disease and may help to improve prevention of diverticulosis and its associated complications. KEY POINTS • Overall prevalence of asymptomatic diverticular disease assessed by MRI was 42%, affecting predominantly the left-sided colon. • Asymptomatic diverticular disease was associated with age and cardiometabolic risk factors. • Magnetic resonance imaging reveals insights into the pathophysiologic mechanism of asymptomatic diverticular disease.