Characterization of volatile compounds from healthy and citrus black spot-infected Valencia orange juice and essential oil by using gas chromatography-mass spectrometry.

Citrus black spot (Phyllosticta citricarpa, CBS) is an important fungal disease that causes rind blemishes and affects quality of citrus fruits. The response of citrus to CBS in terms of volatiles was evaluated using molecular sensory science approaches. Fifty and twenty-one volatiles were identified in the orange juice and essential oil samples, respectively, via gas chromatography-mass spectrometry (GC-MS). The total volatile content in the samples increased after CBS infection, especially in the severe-infection group (SEG) juice and moderate-infection group (MOG) essential oil, which reached the highest levels. CBS enhanced floral, fruity, and off-flavor aromas and decreased the green aroma in citrus juice. Citrusy, floral, and green aromas increased in the CBS-infected essential oil. Six/five potential markers were screened in citrus juice/essential oil, respectively using the orthogonal partial least-square discriminant analysis (OPLS-DA) model. The changes in aroma profile and the difference in infection levels in citrus were attributed to these odorants.

Prophylactic Intra-abdominal Drainage is Associated With Lower Postoperative Complications in Patients With Crohn's Disease: A Randomized Controlled Trial.

BACKGROUND: Prophylactic intraoperative drains have been shown not superior for patients underwent intestinal surgery. However, for patients with Crohn's disease (CD), this needs further exploration. METHODS: In this pilot study, CD patients were randomly assigned to drain (n = 50) and no-drain (n = 50) groups. The primary endpoint was the rate of postoperative prolonged ileus (PPOI). The secondary endpoints were postoperative abdominal ascites, postoperative systemic inflammatory response syndrome (SIRS) and C-reactive protein (CRP) levels. RESULTS: The incidences of PPOI and postoperative abdominal ascites were significantly lower in the drain group (12% vs 44%; 0% vs 24%, both P < .05). Postoperative SIRS incidence and CRP levels were significantly increased in the no-drain group [36% vs 10%; 54.9 vs 34.3 mg/L, both P < .05]. In multivariate analysis, prophylactic drainage was the independent protective factor for PPOI and postoperative LOS. CONCLUSIONS: Prophylactic drainage may be associated with improved clinical outcomes in CD patients.

Pouchitis Is Associated with Paneth Cell Dysfunction and Ameliorated by Exogenous Lysosome in a Rat Model Undergoing Ileal Pouch Anal Anastomosis.

BACKGROUND: Pouchitis is a common complication of restorative proctocolectomy and ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC), significantly affecting the postoperative quality of life. Paneth cells play an important role in the maintenance of gut homeostasis. This study aimed to investigate the role of Paneth cells in the pathogenesis of pouchitis. METHOD: Endoscopic biopsies from the pouch body and terminal ileum of UC patients undergoing IPAA with or without pouchitis were obtained to analyze Paneth cell function. Acute pouchitis was induced with 5% dextran sulfate sodium (DSS) for seven consecutive days in a rat model of IPAA. The Paneth cell morphology was examined by immunofluorescence and electron microscopy. The effect of exogenous lysozyme supplementation on pouchitis was also investigated. The fecal microbiota profile after DSS and lysozyme treatment was determined by 16s rRNA ITS2 sequence analysis. RESULT: Abnormal mucosal lysozyme expression was observed in patients with pouchitis. The rat model of pouchitis showed increased pouch inflammation, increased CD3+ and CD45+ T cell infiltration, and decreased tight junction proteins, including ZO-1 and Occludin. There is a significant deficiency of Paneth cell-derived lysozyme granules in the rat model of pouchitis. Supplementation with exogenous lysozyme significantly ameliorated pouchitis, lowering the levels of inflammatory cytokines such as TNF-α and IL-6 in the pouch tissue. 16s rRNA analysis revealed a higher Lachnospiraceae level after lysosome treatment. CONCLUSIONS: Paneth cell dysfunction is prominent in patients and rat models of pouchitis and may be one of its causes. The decrease in Lachnospiraceae, a characteristic of dysbiosis in pouchitis, could be reserved by lysosome treatment. Lysozyme supplementation shows promise as a novel treatment strategy for pouchitis.

Interleukin-6 promotes skeletal muscle catabolism by activating tryptophan-indoleamine 2,3-dioxygenase 1-kynurenine pathway during intra-abdominal sepsis.

BACKGROUND: Inflammatory cytokine interleukin-6 (IL-6) plays a pivotal role in skeletal muscle degradation after intra-abdominal sepsis (IAS), with mechanism remained to be elucidated. Indoleamine 2,3-dioxygenase 1 (IDO-1), a key enzyme in converting tryptophan into kynurenine, could be activated by IL-6, and kynurenine has been shown to be involved in muscle degradation. We hypothesized that IL-6 could promote muscle degradation via tryptophan-IDO-1-kynurenine pathway in IAS patients. METHODS: Serum and rectus abdominis (RA) were obtained from IAS or non-IAS patients. Mouse model of IAS-induced muscle wasting was generated by caecal ligation and puncture (CLP) and lipopolysaccharide (LPS) injection. IL-6 signalling was blocked by anti-mouse IL-6 antibody (IL-6-AB), and the IDO-1 pathway was blocked by navoximod. To elucidate the role of kynurenine in muscle mass and physiology, kynurenine was administered to IAS mice treated with IL-6-AB. RESULTS: Compared to non-IAS patients, kynurenine levels in serum (+2.30-fold vs. non-IAS, P < 0.001) and RA (+3.11-fold vs. non-IAS, P < 0.001) were elevated, whereas tryptophan levels in serum (-53.65% vs. non-IAS, P < 0.01) and RA (-61.39% vs. non-IAS, P < 0.01) were decreased. Serum IL-6 level of the IAS group was significantly higher compared to non-IAS patients (+5.82-fold vs. non-IAS, P = 0.01), and muscle cross-sectional area (MCSA) was markedly reduced compared to non-IAS patients (-27.73% vs. non-IAS, P < 0.01). In animal experiments, IDO-1 expression was up-regulated in the small intestine, colon and blood for CLP or LPS-treated mice, and there was correlation (R2  = 0.66, P < 0.01) between serum and muscle kynurenine concentrations. Navoximod significantly mitigated IAS-induced skeletal muscle loss according to MCSA analysis (+22.94% vs. CLP, P < 0.05; +23.71% vs. LPS, P < 0.01) and increased the phosphorylated AKT (+2.15-fold vs. CLP, P < 0.01; +3.44-fold vs. LPS, P < 0.01) and myosin heavy chain (+3.64-fold vs. CLP, P < 0.01; +2.13-fold vs. LPS, P < 0.01) protein expression in myocytes. In the presence of anti-IL-6 antibody, a significantly decreased IDO-1 expression was observed in the small intestine, colon and blood in CLP or LPS mice (all P < 0.01), whereas the decrease of MCSA was alleviated (+37.43% vs. CLP + IgG, P < 0.001; +30.72% vs. LPS + IgG, P < 0.001). In contrast, additional supplementation of kynurenine decreased the MCSA in septic mice treated with IL-6-AB (both P < 0.01). CONCLUSIONS: This study provided novel insights into the tryptophan-IDO-1-kynurenine-dependent mechanisms that underlie inflammatory cytokine-induced skeletal muscle catabolism during intra-abdominal sepsis.

Microbiota DNA Translocation Into Mesentery Lymph Nodes Is Associated With Early Development of Pouchitis After IPAA for Ulcerative Colitis.

BACKGROUND: The role of bacterial translocation in Crohn's disease has been extensively studied. However, data regarding bacterial translocation into the mesentery in patients with ulcerative colitis were scarce. OBJECTIVE: This study aimed to explore the relationship between bacterial translocation and postoperative outcome by comparing the microbiome profile of different anatomical sites in patients with ulcerative colitis who underwent proctocolectomy and IPAA. DESIGN: A prospective study. SETTING: This study was conducted at the Jinling Hospital from August 2017 to May 2018. PATIENTS: Samples of 27 patients with ulcerative colitis who had IPAA and 15 healthy controls who underwent routine colonoscopy were collected. MAIN OUTCOME MEASURES: The microbiome profile of different tissue sites and short- and long-term outcomes after IPAA in patients with ulcerative colitis. RESULTS: Bacterial DNA was detected in mesenteric lymph nodes of 51.9% of patients with ulcerative colitis (14/27) and in mesenteric adipose tissue of 66.7% of patients (18/27). The microbiome in mesenteric lymph nodes and mesenteric adipose tissue resembled the mucosal microbiome to a greater extent than the fecal microbiome. Positive bacterial DNA in mesenteric lymph nodes (8/14 vs 0/13; p = 0.002) was associated with pouchitis within 12 months after IPAA, whereas Bray-Curtis distance in mesenteric lymph nodes was significantly different between patients with pouchitis and without ( p = 0.009). LIMITATIONS: This study was limited by its small sample size and lacked situ experiment to confirm the true bacterial translation. CONCLUSIONS: Bacterial translocation was highly prevalent in patients with ulcerative colitis. The translocated bacteria DNA in mesenteric adipose tissue and mesenteric lymph nodes was highly correlated and more likely to originate from mucosal than fecal microbiome. Also, the extent of bacterial translocation and translocation of certain bacteria might be associated with the early development of pouchitis after IPAA. This might represent an unprecedented technique to predict pouchitis using mesenteric lymph node bacterial profiles. See Video Abstract at http://links.lww.com/DCR/C119 . LA TRANSLOCACIN DEL ADN DE LA MICROBIOTA EN LOS GANGLIOS LINFTICOS DEL MESENTERIO SE ASOCIA CON EL DESARROLLO TEMPRANO DE POUCHITIS DESPUS DE IPAA PARA LA COLITIS ULCEROSA: ANTECEDENTES:El papel de la translocación bacteriana en la enfermedad de Crohn se ha estudiado ampliamente en los últimos años. Sin embargo, los datos sobre la translocación bacteriana en el mesenterio en pacientes con colitis ulcerosa fueron escasos.OBJETIVO:El objetivo de este estudio fue explorar la relación entre la translocación bacteriana y el resultado postoperatorio comparando el perfil del microbioma de diferentes sitios anatómicos en pacientes con colitis ulcerosa que se sometieron a proctocolectomía y anastomosis ileoanal con bolsa.DISEÑO:Estudio prospectivo.AJUSTE:Este estudio se realizó en el Hospital Jinling desde agosto de 2017 hasta mayo de 2018.PACIENTES:Se recogieron muestras de 27 pacientes con colitis ulcerosa que tenían anastomosis de bolsa ileoanal y 15 controles sanos que se sometieron a una colonoscopia de rutina.PRINCIPALES MEDIDAS DE RESULTADO:El perfil del microbioma de diferentes sitios de tejido y los resultados a corto y largo plazo después de la anastomosis ileoanal con bolsa en pacientes con colitis ulcerosa.RESULTADOS:Se detectó ADN bacteriano en los ganglios linfáticos mesentéricos del 51,9 % (14/27) de los pacientes con colitis ulcerosa y en el tejido adiposo mesentérico del 66,7 % (18/27) de los pacientes, respectivamente. El microbioma en los ganglios linfáticos mesentéricos y el tejido adiposo mesentérico se parecía más al microbioma de la mucosa que al microbioma fecal. El ADN bacteriano translocado en los ganglios linfáticos mesentéricos y el tejido adiposo mesentérico estaban altamente correlacionados. El ADN bacteriano positivo en los ganglios linfáticos mesentéricos (8/14 frente a 0/13, p = 0,002) se asoció con reservoritis dentro de los 12 meses posteriores a la anastomosis ileoanal con reservorio, mientras que la distancia de Bray-Curtis en los ganglios linfáticos mesentéricos fue significativamente diferente entre reservoritis y no reservorios. -pacientes con reservorio (p = 0,009). Ruminococcus, Bacteroides y Clostridiales se encontraron exclusivamente en los ganglios linfáticos mesentéricos de pacientes con reservoritis.LIMITACIÓN:Este estudio estuvo limitado por el pequeño tamaño de la muestra y la falta de un experimento in situ para confirmar la verdadera traducción bacteriana.CONCLUSIÓN:La translocación bacteriana fue altamente prevalente en pacientes con colitis ulcerosa. El ADN bacteriano translocado en el tejido adiposo mesentérico y los ganglios linfáticos mesentéricos estaba altamente correlacionado y era más probable que se originara en el microbioma de la mucosa que en el fecal. Además, la extensión de la translocación bacteriana y la translocación de ciertas bacterias podría estar asociada con el desarrollo temprano de reservoritis después de la anastomosis del reservorio ileoanal. Esto podría representar una técnica sin precedentes para predecir la reservoritis utilizando perfiles bacterianos de los ganglios linfáticos mesentéricos. Consulte Video Resumen en. http://links.lww.com/DCR/C119(Traducción-Dr. Felipe Bellolio ).

Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study.

AIM: This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal association between inflammatory bowel disease (IBD) and periodontitis. MATERIALS AND METHODS: We used genetic instruments from the genome-wide association study summary statistics of European descent for IBD (12,882 cases and 21,770 controls) to investigate the association with periodontitis (3046 cases and 195,395 controls) and vice versa. The radial inverse-variance weighted method was carried out to obtain the primary causal estimates, and the robustness of the results was assessed by a series of sensitivity analyses. Due to multiple testing, associations with p values <.008 were considered as statistically significant, and p values ≥.008 and <.05 were considered as suggestively significant. RESULTS: In the primary causal estimates, IBD as a whole was associated with an increased risk of periodontitis (odds ratio [OR], 1.060; 95% confidence interval [CI], 1.017; 1.105; p = .006). Subtype analyses showed that ulcerative colitis (UC) was associated with periodontitis (OR, 1.074; 95% CI 1.029; 1.122; p = .001), while Crohn's disease (CD) was not. Regarding the reverse direction, periodontitis showed a suggestive association with IBD as a whole (OR, 1.065; 95% CI 1.013; 1.119; p = .014). Subtype analyses revealed that periodontitis was associated with CD (OR, 1.100; 95% CI 1.038; 1.167; p = .001) but not UC. The final models after outlier removal showed no obvious pleiotropy, indicating that our primary analysis results were reliable. CONCLUSIONS: The present MR study provides moderate evidence on the bidirectional causal relationship between IBD and periodontitis. The bidirectional increased risk found in our study was marginal and, possibly, of limited clinical relevance. More studies are needed to support the findings of our current study.

Ileoanal Pouch Syndrome Is Common and Associated With Significant Disability in Patients With Ulcerative Colitis Undergoing IPAA.

BACKGROUND: Recently, ileoanal pouch syndrome (IPS) has been proposed and defined according to a series of patient-centered bowel symptoms and consequences after ileoanal pouch surgery. OBJECTIVE: The purpose of this study was to investigate the prevalence of IPS and the related disability in UC patients undergoing IPAA. DESIGN: This was a cross-sectional study. SETTING: This study was conducted in a tertiary center. PATIENTS: Data of 128 UC-related IPAA from October 2014 to May 2021 were collected. MAIN OUTCOME MEASURES: Primary outcomes were prevalence of IPS. RESULTS: One hundred twenty-eight patients were enrolled with a median postoperative follow-up of 2.64 (IQR, 1.31-3.80) years. The prevalence of IPS and its constituent symptoms and consequences are lower for patients with longer follow-up after ileostomy reversal. Fecal incontinence and pad usage had the greatest impact on the quality of life affecting 29% and 31% of patients. IPS group had a significantly higher IBD-Disability Index score compared to the non-IPS group (27.25 vs 12.15, p < 0.001). Multivariate analysis showed that 4 symptoms (fecal incontinence, clustering, fragmentation and incomplete evacuation, and nocturnal symptoms) and 2 consequences (pad usage and negative mental alterations) were associated with increased IBD-Disability Index (p < 0.05). For patients followed-up for >2 years, multivariate analysis showed that male gender (OR, 4.485; 95% CI, 1.354-14.857; p = 0.014), preoperative duration of disease (OR, 1.013; 95% CI, 1.001-1.025; p = 0.031), and postoperative follow-up (OR, 0.462; 95% CI, 0.244-0.876; p = 0.049) were independently associated with IPS. LIMITATIONS: This is a single-center cross-sectional study rather than a prospective multicenter large longitudinal study. CONCLUSIONS: IPS is a common situation negatively affecting the quality of life for patients with ulcerative colitis undergoing IPAA, and its rate decreased over time from ileal pouch surgery. See Video Abstract at http://links.lww.com/DCR/C41. EL SNDROME DEL RESERVORIO ILEOANAL ES COMN Y EST ASOCIADO CON UNA DISCAPACIDAD SIGNIFICATIVA EN PACIENTES CON CU CON RESERVORIO ILEAL Y ANASTOMOSIS RESERVORIOANAL: ANTECEDENTES:Recientemente se propuso y definió el síndrome del reservorio ileoanal de acuerdo con una serie de síntomas intestinales centrados en el paciente y las consecuencias después de la cirugía del reservorio ileoanal.OBJETIVO:El propósito de este estudio fue investigar la prevalencia del síndrome del reservorio ileoanal y la discapacidad relacionada en pacientes con colitis ulcerosa con reservorio ileal y anastomosis reservorio-anal.DISEÑO:Este fue un estudio transversal.ESCENARIO:Este estudio se realizó en un centro terciario.PACIENTES:Se recopilaron datos de 128 pacientes con reservorio ileal por colitis ulcerosa desde octubre de 2014 hasta mayo de 2021.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la prevalencia del síndrome del reservorio ileoanal.RESULTADOS:Ciento veintiocho pacientes fueron reclutados con una mediana de seguimiento postoperatorio de 2,64 (IQR, 1,31-3,80) años. La prevalencia del síndrome del reservorio ileoanal y sus síntomas y consecuencias constituyentes es menor para los pacientes con un seguimiento más prolongado después de la reversión de la ileostomía. La incontinencia fecal y el uso de compresas tuvieron el mayor impacto en la calidad de vida, afectando al 29% y al 31% de los pacientes. El grupo con síndrome del reservorio ileoanal tuvo una puntuación del índice de discapacidad por enfermedad inflamatoria intestinal significativamente más alta en comparación con el grupo sin síndrome del reservorio ileoanal (27,25 frente a 12,15, p <0,001). El análisis multivariado mostró que 4 síntomas (incontinencia fecal, agrupamiento, fragmentación y evacuación incompleta y síntomas nocturnos) y 2 consecuencias (uso de toallas higiénicas y alteraciones mentales negativas) se asociaron con un aumento del índice de discapacidad por enfermedad inflamatoria intestinal (p <0,05). Para los pacientes seguidos durante más de dos años, el análisis multivariado mostró que el sexo masculino (OR, 4,485; IC 95%, 1,354-14,857; p = 0,014), la duración preoperatoria de la enfermedad (OR, 1,013; IC 95%, 1,001-1,025; p = 0,031) y el seguimiento postoperatorio (OR, 0,462; IC 95%, 0,244-0,876; p = 0,049) se asociaron de forma independiente con el síndrome del reservorio ileoanal.LIMITACIONES:Este es un estudio transversal de un solo centro en lugar de un gran estudio longitudinal prospectivo multicéntrico.CONCLUSIONES:El síndrome del reservorio ileoanal es una situación común que afecta negativamente la calidad de vida de los pacientes con colitis ulcerosa sometidos a anastomosis del reservorio ileal-anal, y su tasa disminuyó con el tiempo a partir de la cirugía del reservorio ileal. El sexo masculino y la mayor duración preoperatoria de la enfermedad son factores de riesgo importantes para el síndrome del reservorio ileoanal. Consulte Video Resumen en http://links.lww.com/DCR/C41. (Traducción-Dr. Felipe Bellolio).

Targeted Metabolomics With a Chemometric Study of Oxygenated Heterocyclic Aglycones as a Tool for Preliminary Authenticity Assessment of Orange and Grapefruit Juices.

Profiles of citrus juice oxygenated heterocyclic aglycones (OHAs), which are notable marker secondary metabolites, were used to assess the authenticity of sweet orange and grapefruit juices in situations where mandarin and pomelo juices might be adulterants. Thirty-nine known OHAs, including 10 methoxyflavones, 13 coumarins, and 16 furanocoumarins, as well as 13 tentatively screened OHAs, were analyzed in orange, mandarin, grapefruit and pomelo juices using our newly developed high-resolution HPLC-UV and fluorescence detection method. Quantitative OHA profiles from 158 pure juice samples were obtained to establish a purity discriminant model using an omics strategy. Reduction of OHA variables showed that three important methoxyflavones, i.e. isosinensetin, tangeretin and sinensetin provided the best discrimination ability between sweet orange and mandarin juices. There are two subtypes of pomelos, Shatianyou Group and Wendan Group, of which juices should be separately compared to grapefruit juice. Five OHAs, namely meranzin, 3,5,6,7,8,3',4'-heptamethoxyflavone, osthole, 6',7'-epoxybergamottin, and bergamottin were found to discriminate Shatianyou Group of pomelo juice from grapefruit juice; whereas three OHAs, namely bergaptol, isomeranzin, and 6',7'-dihydroxybergamottin were able to discriminate Wendan Group of pomelo juice from grapefruit juice. The established partial least squares discriminant analysis (PLS-DA) models were capable of detecting as little as 10% mandarin juice in sweet orange juice and 10% pomelo juice in grapefruit juice, allowing for fast prescreening of excess addition with good reliability (root mean square error of prediction, RMSEP < 5%).

Perioperative parenteral fish oil supplementation improves postoperative coagulation function and outcomes in patients undergoing colectomy for ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC) is an independent risk factor for thromboembolism, especially during the perioperative period. This study aimed to determine the effects of perioperative parenteral nutrition (PN) supplemented with fish oil (FO) on coagulation function and postoperative outcomes in patients with UC. METHODS: This retrospective cohort included 92 consecutive patients who underwent colectomy for UC. Postoperative coagulation indices and outcomes, including thromboelastography (TEG) findings and comprehensive complication index (CCI), were compared. The relative change in serum D-dimer (ΔD-dimer) levels and maximal amplitude (ΔMA) on TEG were also determined. RESULTS: Patients receiving PN supplemented with FO (n = 48) had lower D-dimer (P = .036) levels on postoperative day (POD) 5 and a higher MA (P < 0.001) on POD 1 than those who did not receive it (n = 44). A lower ΔD-dimer level (P = .048) and ΔMA (P < 0.001) were also observed in patients receiving FO. The incidence of major postoperative complications (6.3 vs 22.7%; P = .017) and CCI (20.9 vs 23.4%; P = .044) were significantly lower in patients receiving FO. In multivariate analysis, FO (odds ratio, 0.231; 95% confidence interval, 0.055-0.971; P = .046) was a positive protector of major postoperative complications. CONCLUSION: Perioperative PN supplemented with FO improved coagulation function and reduced major postoperative complications in patients with UC requiring colectomy. These results may provide cues in formulating management strategies for preventing thromboembolisms and postoperative complications in patients with UC.

H19 Overexpression Improved Efficacy of Mesenchymal Stem Cells in Ulcerative Colitis by Modulating the miR-141/ICAM-1 and miR-139/CXCR4 Axes.

Overexpression of C-X-C motif chemokine receptor 4 (CXCR4) and intercellular cell adhesion molecule-1 (ICAM-1) may promote homing of mesenchymal stem cells (MSC). In this study, we treated ulcerative colitis animals with MSC preconditioned with or without H19 and compared the therapeutic effect of MSC and MSC-H19. We evaluated the regulatory relationship of H19 vs. miR-141/miR-139 and miR-141/miR-139 vs. ICAM-1/CXCR4. We established an ulcerative colitis mouse model to assess the effect of MSC and MSC-H19. H19 was found to bind to miR-141 and miR-139. The activity of H19 was strongly decreased in cells c-transfected with miR-141/miR-139 and WT H19. ICAM-1 was confirmed to be targeted by miR-141 and CXCR4 was targeted by miR-139. The H19 expression showed a negative regulatory relationship with the miR-141 and miR-139 expression but a positive regulatory relationship with the ICAM-1 and CXCR4 expression. In summary, the overexpression of H19 in MSC downregulated miR-139 and miR-141, thus increasing the activity of their targets ICAM-1 and CXCR4, respectively, to exhibit therapeutic effects in ulcerative colitis.

Characterization of Oxygenated Heterocyclic Compounds and in vitro Antioxidant Activity of Pomelo Essential Oil.

PURPOSE: Citrus essential oils are widely used for aromatherapy and the alternative treatment of chronic diseases. Beyond the aroma substances, they are known to contain bioactive nonvolatile components; however, little knowledge has been gained about nonvolatiles in the essential oil of pomelo (Citrus grandis Osbeck), the largest citrus fruit. The purpose of this study was to analyze the nonvolatile oxygenated heterocyclic compounds (OHCs) of pomelo essential oils and evaluate their in vitro antioxidant activities for further development. METHODS: Cold-pressed essential oil (CPEO) and distilled essential oil (DEO) were obtained from the peel of the Liangping pomelo cultivar. High-performance liquid chromatography (HPLC) coupled with a photodiode array and fluorescence detection method was developed to identify and quantify the OHCs of the two essential oils. Ferric reducing antioxidant power and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl 3-oxide (PTIO) radical scavenging assays were used to determine the antioxidative capabilities. RESULTS: Thirteen OHCs were identified in CPEO. Coumarins such as meranzin (2.0 mmol L-1) and furanocoumarins such as isoimperatorin (1.3 mmol L-1) composed the majority of nonvolatiles in CPEO. These OHCs were characterized by high proportion (58%) of side chain epoxides. Five OHCs, namely, auraptenol, 6',7'-dihydroxybergamottin (6',7'-DHB), imperatorin, isoimperatorin and 8-geranyloxypsoralen were first identified in pomelo CPEO. Eight OHCs were detected at trace amounts in pomelo DEO. Antioxidant assays showed that CPEO was multiple times more potent than DEO regarding the total reducing power and radical scavenging capacity. Clearance of PTIO, a stable reactive oxygen species, followed slow kinetics. CONCLUSION: Coumarins and furanocoumarins, two families of OHCs, constituted most of the nonvolatile components in CPEO. The nonvolatiles contributed significantly to the in vitro antioxidant activity of CPEO. Pomelo CPEO showed good prospects as a potential long-lasting natural antioxidant.

Randomized Controlled Trial: Perioperative Dexamethasone Reduces Excessive Postoperative Inflammatory Response and Ileus After Surgery for Inflammatory Bowel Disease.

BACKGROUND: An excessive postoperative inflammatory response is common after surgery for inflammatory bowel disease (IBD) and may be associated with an increased incidence of postoperative ileus. This study assessed the role of perioperative dexamethasone in postoperative ileus after IBD surgery. METHOD: Patients undergoing elective IBD surgery were randomized to either an intravenous 8-mg dose of dexamethasone (n = 151) or placebo (n = 151) upon induction of anesthesia. The primary outcome was the incidence of prolonged postoperative ileus. Secondary outcomes included incidence of reported nausea or vomiting, time to first passage of flatus and stool, GI-2 recovery, postoperative pain, length of stay, and surgical complications. RESULTS: An intention-to-treat analysis revealed that patients who received dexamethasone exhibited a lower incidence of prolonged postoperative ileus (22.5% vs 38.4%; P = 0.003), shorter time to first passage of stool (28 vs 48 h, P < 0.001), GI-2 recovery (72 vs 120 h; P < 0.001), reduced postoperative length of stay (9.0 vs 10.0 d; P = 0.002), and less postoperative pain (P < 0.05) compared with controls. Moreover, there were no significant differences in postoperative nausea or vomiting (P = 0.531), major postoperative complications (P = 0.165), or surgical site infections (P = 0.337) between the groups. A benefit was only observed in patients with Crohn's disease, restored bowel continuity, colon/rectal resections, and those who underwent open operations. CONCLUSION: A single, intravenous 8-mg dose of dexamethasone upon induction of anesthesia reduced the incidence of prolonged postoperative ileus, the intensity of postoperative pain, and shortened the postoperative length of stay for IBD patients undergoing elective surgery. ClinicalTrials.gov: NCT03456752.

Fungal Dysbiosis Aggravates Pouchitis in a Rat Model of Ileal Pouch Anal Anastomosis.

BACKGROUND: Although the interaction between gut microbiota and pouchitis after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) has been confirmed, evidence of commensal mycobiota in the etiology of pouchitis is still lacking. This study aimed to investigate the role of fungi in the pathogenesis of pouchitis. METHODS: Fecal samples were collected from UC patients with or without pouchitis after IPAA. Experimental pouchitis was induced by 5% dextran sulfate sodium for 7 consecutive days in a rat model of IPAA. Fungal dysbiosis was induced by 0.5% fluconazole (Flu), and commensal fungal recognition through dectin-1 was blocked by 5% laminarin. Fecal fungal composition was analyzed using internal transcribed spacer 2 sequencing. Severity of pouchitis and activation of the CARD9-nuclear factor kappa-B pathway was determined among different groups. RESULTS: Patients with pouchitis had a lower alpha (α) diversity in mycobiota composition and a higher abundance of Saccharomyces at the genus level compared with those with a normal pouch. In the rat model of pouchitis, Flu treatment decreased fungal burden but induced fungal dysbiosis, characterized by increased α diversity, a decreased relative abundance of Kazachstania, and increased Polythrincium and Saccharomyces. In addition, Flu treatment worsened dextran sulfate sodium pouchitis, as indicated by increased mortality, weight loss, higher histological score, and CD4+ cell infiltration. Laminarin also increased the severity of pouchitis. In the Flu and laminarin groups, the expression of interferon-γ, tumor necrosis factor-α, CARD9, and phosphorylated nuclear factor kappa-B inhibitor alpha was decreased. CONCLUSIONS: Patients with pouchitis had altered fungal composition. Fungal dysbiosis or recognition deficiency by the host may exacerbate experimental pouchitis. Strategies targeting commensal mycobiota may provide therapeutic potential against pouchitis, especially for antibiotic-refractory patients.

Nomogram to Predict Postoperative Intra-abdominal Septic Complications After Bowel Resection and Primary Anastomosis for Crohn's Disease.

BACKGROUND: Postoperative intra-abdominal septic complications of Crohn's disease substantially increase the healthcare expenditure and prolong hospitalization. OBJECTIVE: We aimed to develop and validate a prediction model for intra-abdominal septic complications after bowel resection and primary anastomosis for Crohn's disease. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted in a tertiary center. PATIENTS: Data of 949 Crohn's disease-related primary bowel resections and anastomosis from January 2011 to December 2017 were collected. MAIN OUTCOME MEASURES: Primary outcomes were prevalence of intra-abdominal septic complications. RESULTS: Overall prevalence of intra-abdominal septic complications after Crohn's disease surgery was 11.6%. Predictors included preoperative C-reactive protein level ≥40 mg/L (OR = 3.545), preoperative glucocorticoids (OR = 1.829) and infliximab use (OR = 3.365), upper GI involvement (OR = 2.072), and hypoalbuminemia (albumin level <30 g/L, OR = 2.406). Preoperative exclusive enteral nutrition was a protector for postoperative septic complications (OR = 0.192) compared with partial enteral nutrition/parenteral nutrition/straight to surgery. A nomogram was computed to facilitate risk calculation; this had a predictive discrimination, measured as area under the receiver operating characteristic curve, of 0.823. LIMITATIONS: This model is generated from retrospective data. A major limitation of this model is the lack of external validation. CONCLUSIONS: A new model to predict postoperative intra-abdominal septic complications was developed, which may guide preoperative optimization and candidate selection for primary anastomosis after bowel resection for Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B178. NOMOGRAMA PARA PREDECIR COMPLICACIONES SéPTICAS INTRAABDOMINALES POSTOPERATORIAS DESPUéS DE RESECCIóN INTESTINAL Y ANASTOMOSIS PRIMARIA EN ENFERMEDAD DE CROHN: Las complicaciones sépticas intraabdominales postoperatorias en la enfermedad de Crohn aumentan sustancialmente los costos de atención médica y prolongan la hospitalización.Nuestro objetivo fue desarrollar y validar un modelo de predicción para las complicaciones sépticas intraabdominales después de resección intestinal y anastomosis primaria en enfermedad de Crohn.Este fue un estudio de cohorte retrospectivo.Este estudio se realizó en un centro de tercer nivel.Se recopilaron datos de 949 resecciones intestinales primarias con anastomosis por enfermedad de Crohn de enero de 2011 a diciembre de 2017.El resultado primario fue la prevalencia de complicaciones sépticas intraabdominales.La prevalencia general de complicaciones sépticas intraabdominales después de cirugía por enfermedad de Crohn fue 11.6%. Los predictores incluyeron un nivel preoperatorio de proteína C reactiva ≥ 40 mg / L (odds ratio = 3.545), glucocorticoides preoperatorios (odds ratio = 1.829) y uso de infliximab (odds ratio = 3.365), compromiso gastrointestinal superior (odds ratio = 2.072) e hipoalbuminemia (albúmina <30g / L, odds ratio = 2.406). La nutrición enteral exclusiva preoperatoria fue un protector para las complicaciones sépticas postoperatorias (odds ratio = 0.192, en comparación con la nutrición enteral parcial / nutrición parenteral / envío directo a cirugía. Se calculó un nomograma para facilitar el cálculo del riesgo; esto tuvo una discriminación predictiva, medida como área bajo la curva de la característica de operación del receptor, de 0.823.Este modelo se generó a partir de datos retrospectivos. Una limitación importante de este modelo es la falta de validación externa.Se desarrolló un nuevo modelo para predecir complicaciones sépticas intraabdominales postoperatorias, que puede guiar la optimización preoperatoria y la selección de candidatos para anastomosis primaria después de resección intestinal en enfermedad de Crohn. Consulte Video Resumen en http://links.lww.com/DCR/B178. (Traducción-Dr. Jorge Silva Velazco).

Altered uric acid metabolism in isolated colonic Crohn's disease but not ulcerative colitis.

BACKGROUND AND AIM: Patients with inflammatory bowel disease (IBD) have higher incidence of developing nephrolithiasis. Increased uric acid production induced by Saccharomyces cerevisiae exacerbates colitis in mice. We aimed to evaluate the association between serum uric acid level and disease activity in IBD population. METHODS: Four hundred and thirty-five patients enrolled in Jinling Hospital from January 1, 2015 to August 31, 2017 were included in the retrospective study. Clinical parameters were collected and compared with non-IBD matched controls (n = 51). Serum uric acid to creatinine ratio (UA/Cr) was used as a biomarker for uric acid metabolism. Sixty-five active IBD patients were longitudinally studied to investigate the UA/Cr before and after therapy. Linear mixed models were estimated for Crohn's disease (CD) group to explore the relationship between UA/Cr and other parameters. RESULTS: Uric acid to creatinine ratio was significantly correlated with Crohn's disease activity index (ρ = 0.184, P = 0.002) and Harvey Bradshaw index (ρ = 0.154, P = 0.010) and C-reactive protein (ρ = 0.591, P < 0.001) in CD group. Colonic CD and anti-Saccharomyces cerevisiae antibody (ASCA) positive CD had an increased UA/Cr compared with L1, L3, and ASCA negative CD (P = 0.027, P = 0.0013, and P = 0.043, respectively). A significant decrease in UA/Cr was observed after induction therapy in active CD (P = 0.0002) but not in ulcerative colitis (P = 0.076). CONCLUSION: Uric acid to creatinine ratio correlated with disease activity in CD. Colonic CD and ASCA positive CD had an increased UA/Cr. Effective treatment for CD patients lowered UA/Cr. Uric acid metabolism might be a novel aspect to investigate disease activity of IBD.

High Visceral to Subcutaneous Fat Ratio Is Associated with Increased Postoperative Inflammatory Response after Colorectal Resection in Inflammatory Bowel Disease.

AIM: Excessive postoperative inflammatory response, which is characterized by overproduction of cytokines, often leads to complications after colorectal surgery. However, the impact of body composition on postoperative inflammatory response is largely unknown. The aim of this study is to elucidate whether body fat amount and its distribution affects postoperative inflammation after colorectal surgery in IBD patients. METHODS: Eighty-six patients undergoing colorectal resection for IBD from June 2014 to Jan 2017 were enrolled. Abdominal CT images within one week prior to surgery were assessed for visceral fat, subcutaneous fat, and muscle mass. Postoperative inflammatory response was evaluated using serum CRP, PCT, and IL-6 levels on postoperative days 1, 3, and 5. Univariate analysis was conducted to identify risk factors for infectious complications. The correlation between body composition and postoperative plasma concentration of inflammatory markers was analyzed using a linear regression model. ROC curve was applied to analyze the effect of different body composition parameters on postoperative infectious complications and to determine the relationship between inflammatory markers and infectious complications. RESULTS: Neither volume of fat or muscle was related to postoperative plasma concentrations of CRP, IL-6, and PCT. However, visceral to subcutaneous fat ratio was associated with PCT levels on postoperative days (POD) 1, 3, and 5, with the highest regression coefficient on POD1 (ß = 0.360; 95% CI, 0.089-0.631; P = 0.010). Body composition did not predict postoperative infectious complications, while CRP on POD 3 was predictive of infectious complications. CONCLUSION: Increased visceral to subcutaneous fat ratio was associated with postoperative inflammatory response in IBD patients undergoing colorectal resection. This may partly explain the increased incidence of postoperative complications in patients with visceral obesity.

Toward a More Sensitive Endpoint for Assessing Postoperative Complications in Patients with Inflammatory Bowel Disease: a Comparison Between Comprehensive Complication Index (CCI) and Clavien-Dindo Classification (CDC).

BACKGROUND: The comprehensive complication index (CCI) is a novel approach to evaluate complications. However, application of the CCI in inflammatory bowel disease (IBD) population is scarce and the difference between the CCI and the Clavien-Dindo classification (CDC) remains unknown. The aim of this study was to compare the CCI to the conventional CDC by applying the CCI among the IBD patients. METHODS: The data of 426 IBD patients who underwent surgery between September 1, 2015 and August 31, 2017 were collected. Univariate and multivariate analyses were conducted to identify risk factors for postoperative complications. The efficacy of CCI and CDC was compared using correlation analysis and logistic regression. Cumulative sum control (CUSUM) models were applied to monitor the CCI continuously. RESULTS: Totally, 297 complications occurred in 144 (33.8%) patients. The rate of severe complications (CDC grade ≥ III) was 12.9% and the mean CCI was 9.8 ± 15.5. Preoperative glucocorticoids usage and previous abdominal surgery were related to higher CCI value (p = 0.002, p = 0.006, respectively) but not related to higher incidence of severe complications (CDC grade ≥ III) (p = 0.117, p = 0.177, respectively). In patients with multiple complications, the CCI demonstrated a stronger correlation with hospital stay (ρ = 0.604, p < 0.001) than CDC (ρ = 0.508, p < 0.001). Higher CCI value (p < 0.001, OR 1.161, 95% CI 1.093-1.234) and the CDC grade (p < 0.001, OR 3.811, 95% CI 2.283-6.362) were risk factors for prolonged LOS. In the CUSUM-CCI model of IBD surgery, a gradual decrease was observed over time. CONCLUSIONS: The CCI and the CDC are both risk factors for prolonged postoperative LOS after surgery for IBD patients. The CCI is more strongly correlated with postoperative LOS than is the conventional CDC. The CUSUM-CCI model is effective in monitoring surgical quality.

Ulcerative Colitis Endoscopic Index of Severity (UCEIS) versus Mayo Endoscopic Score (MES) in guiding the need for colectomy in patients with acute severe colitis.

BACKGROUND: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the Mayo Endoscopic Score (MES) were developed as an objective method of the endoscopic severity in ulcerative colitis (UC); however, it was still unclear whether UCEIS vs MES could guide the need for colectomy in acute severe colitis (ASC). METHODS: Consecutive ASC patients between January 2012 and May 2016 were retrospectively evaluated. Demographic data, previous therapy, clinical observations, laboratory parameters, medical therapy and endoscopic assessments were documented. The primary outcome was the need for colectomy during admission and follow-up. RESULTS: Ninety-two patients were enrolled. 37 (40.2%) needed colectomy. UCEIS score is a predictor of requirement for colectomy in multivariate analysis (OR, 3.25; 95% CI, 1.77-5.97; P < 0.001). Receiver-operator characteristic (ROC) area of UCEIS is 0.85, with a sensitivity of 60.3% and specificity of 85.5% using cut-off value of 7, which outperforms MES with the ROC area of 0.65; When UCEIS score ≥7, 80% of patients eventually need colectomy. CONCLUSION: UCEIS outperformed MES as a predictor for need for colectomy in ASC patients. The high probability of medical treatment failure and benefits of early colectomy should be discussed in patients with baseline UCEIS ≥ 7.Acute severe colitis; colectomy; Ulcerative Colitis Endoscopic Index of Severity; Mayo Endoscopic Score.

Validation and optimization of the Systemic Inflammation-Based modified Glasgow Prognostic Score in predicting postoperative outcome of inflammatory bowel disease: preliminary data.

Systemic Inflammation-Based modified Glasgow Prognostic Score (mGPS) was developed as an objective tool to grade state of inflammation. However, the association between mGPS and postoperative complications for inflammatory bowel disease (IBD) patients was still unknown. In our study, 270 IBD patients [Crohn's disease (CD), n = 186; Ulcerative colitis (UC), n = 84] from January 2013 and January 2016 who underwent elective bowel resection were retrospectively analyzed, and, the levels of preoperative C-reactive protein (CRP) and albumin were included as parameters of mGPS. The incidence of overall postoperative complications was 44.81% (121/270), including 46.77% (87/186) of CD and 40.48% (34/84) of UC. According to multivariate analysis, mGPS (CD: OR = 3.47, p = 0.003; UC: OR = 3.28, p = 0.019) was independently associated with an increased risk of postoperative complications. Patients with a higher mGPS also suffered longer postoperative stay and increased SSIs (both p < 0.05). Combining mGPS with neutrophil ratio improved its prognostic value with a better area under the curve (AUC), using receiver operating characteristic (ROC) method. Then we confirmed that mGPS was associated with postoperative complications in IBD patients undergoing elective bowel resection and the addition of neutrophil ratio enhanced its prognostic value.