Trocar Puncture With a Sump Drain for Crohn's Disease With Intra-Abdominal Abscess: A 10-Year Retrospective Cohort Study.

Background: Traditional percutaneous catheter drainage (PCD) and surgical intervention could not always achieve satisfactory results for patients with Crohn's disease (CD) who have complications with intra-abdominal abscess. We proposed a trocar puncture with sump drainage for the treatment of CD with intra-abdominal abscess and compared it with the conventional PCD and surgical intervention. Methods: Crohn's disease patients with intra-abdominal abscess and admitted to our hospital from 2011 to 2020 were identified by reviewing the electronic medical records. We divided them into Trocar, PCD, and fecal diverting (FD) groups, according to the ways of treating an abscess. Outcomes, risk factors for abscess recurrence, and postoperative complications were compared among the three groups. Results: A total of 69 patients were included and they were divided into Trocar (n = 18), PCD (n = 29), and FD (n = 22) groups. Four patients in the PCD group were transferred to receive the FD surgery due to the failure of initial treatment. The incidence of abscess recurrence was significantly higher in the PCD (48%) and FD (50%) groups compared to the patients using the trocar puncture with the sump drain (Trocar group) (16.7%). There were 8 patients in Trocar, 22 in PCD, and 20 s in the FD group who received enterectomy. None of the patients in the Trocar had an ultimate stoma and the incidence of postoperative complications was statistically lower [0% (Trocar) vs. 31.8% (PCD) vs. 45% (FD), P < 0.05]. The way of initial treating of the abscess was significantly correlated with the abscess recurrence and postoperative complications. Conclusions: Trocar puncture with a sump drain had a lower incidence of abscess recurrence, abdominal adhesions, postdrainage, and postoperative complications compared to the conventional PCD or surgical intervention.

STING-mediated Syk Signaling Attenuates Tumorigenesis of Colitis­associated Colorectal Cancer Through Enhancing Intestinal Epithelium Pyroptosis.

BACKGROUND: Stimulator of interferon genes (STING) has essential functions in the immune responses and can induce cancer cell apoptosis. However, it is not completely clear how STING plays a role in colitis-associated colorectal cancer (CAC) and whether it can trigger pyroptosis during the tumorigenesis of CAC. METHODS: To investigate the role of STING-modulated pyroptosis in the development of CAC, STING knockout and Wild type mice were challenged with azoxymethane (AOM) and dextran sodium sulfate (DSS) to establish a murine CAC model. STING pharmacological agonist was used to further study the functions of STING signaling in the tumorigenesis. Moreover, STING endogenous ligand was employed to verify the effects of STING in human colon cancer cells. RESULTS: STING deficiency mice were more susceptible to CAC by reducing pyroptosis of tumor cells, whereas overactivation of STING with the agonist suppressed tumorigenesis of CAC. STING also managed CAC development by modulating tumor cells proliferation, adhesion, and invasion, as well as inflammatory response. The ex vivo studies indicated that STING could induce pyroptosis via spleen tyrosine kinase (Syk), and Syk knockdown weakened such pyroptotic tumor cells death. In addition, the visible physical interaction between STING and Syk was observed in colorectal tumor samples of CAC patients. CONCLUSIONS: STING-mediated Syk signaling may regulate the tumorigenesis of CAC by modulating pyroptosis of tumor cells, and modulation of STING/Syk serves as a novel therapeutic strategy for CAC therapy.

Intestinal mucosa-derived DNA methylation signatures in the penetrating intestinal mucosal lesions of Crohn's disease.

The purpose of this study was to evaluate genome-wide DNA methylation changes in intestinal mucosa tissue of adult patients with Crohn's disease comprehensively. DNA methylation chip was used to analyze abnormal methylation sites among penetrating and non-penetrating intestinal mucosa tissue of Crohn's disease and normal intestinal mucosa tissue of healthy controls. Methylation abnormalities of different locus were verified by pyrosequencing and quantitative polymerase chain reaction. Differential DNA methylation sites were participated in the positive regulation of apoptosis and the positive regulation of IL-8 production and were enriched in signaling pathways related to inflammatory bowel disease and extracellular matrix receptor interaction signaling pathways. Correlation analysis showed that the methylation abnormalities of HLA-DRB1 (r = - 0.62, P < 0.001), MUC1 (r = - 0.45, P = 0.01), YPEL5 (r = - 0.55, P = 0.001) and CBLB (r = - 0.62, P < 0.001) were significantly negatively correlated with their relative expression levels. The degree of methylation abnormality of MUC1 was negatively correlated with the disease activity score of Crohn's disease (r = - 0.50, P = 0.01). Apoptosis, interleukin-8 production and abnormal extracellular matrix might be involved in the mechanism of penetrating intestinal mucosal lesions in Crohn's disease. The degree of abnormal methylation of MUC1 was negatively correlated with the disease activity of Crohn's disease.

JINLING (Judicious INdex of Luminal INflammation Grade) score, an effective indicator to assess inflammation severity in Crohn's disease.

BACKGROUND: With the increasing demand for individualized treatment in Crohn's disease, a score for accurate evaluation of inflammation grade will be of great significance. We have developed the JINLING score to assess inflammation severity for Crohn's disease, which incorporates an endoscopic score (SES-CD) and a 2-item patient-reported outcome (PRO2). The aim of this study was to examine the performance of JINLING score in evaluating inflammation grade and the correlation with the clinical outcomes. METHODS: The correlation between JINLING score and Global Histologic Disease Activity Score (GHAS), fecal calprotectin (FCP), and C-reactive protein (CRP) level was performed in an exploration phase with a retrospective data set. The data on clinical outcomes including medication effects, Crohn's disease-related surgery and biochemical results were collected from a single-center prospective validation cohort. RESULTS: JINLING score correlated significantly with FCP, CRP, and hemoglobin in the exploration cohort (all P < 0.05). The receiver operating characteristic (ROC) curves based on a threshold Crohn's disease activity index value of 150, GHAS of 4, and FCP of 60 µg/g to identify disease activity, all showed a higher area under the curve with JINLING score than SES-CD or PRO2 alone. In the validation cohort, patients with high inflammation grade (JINLING ≥4) had higher GHAS, CRP, and FCP than low inflammation grade patients. High JINLING score was associated with an increased risk of treatment failure (hazard ratio 2.93; 95% confidence interval 1.13-7.61, P = 0.021). CONCLUSION: This newly developed index served well for quantifying inflammation grade and predicting clinical outcomes. JINLING score has the potential to facilitate clinical decision-making and personalized therapy for Crohn's disease patients.

Early Enteral Nutrition Preserves Intestinal Barrier Function through Reducing the Formation of Neutrophil Extracellular Traps (NETs) in Critically Ill Surgical Patients.

BACKGROUND: The gut was suggested as the driver of critical illness and organ injury. Recently, excessive formation of neutrophil extracellular traps (NETs) was associated with mucosal inflammation. Direct investigation of intestinal mucosa is essential to illuminate the potential mechanism of gut barrier in critically ill patients. We hypothesized that early enteral nutrition (EN) could decrease intestinal NETs and maintain the gut barrier. METHODS: Intestinal biopsies were obtained using biopsy forceps from critically ill surgical patients complicated with enterocutaneous fistula. Expressions of tight junction (TJ) proteins, mucosal inflammation, and apoptosis were evaluated. Moreover, NET-associated proteins were evaluated in intestinal specimens of patients by Western blot and immunofluorescence analysis. RESULTS: The intestinal barrier was significantly impaired in critically ill patients receiving early total parenteral nutrition (TPN), evidenced by intestinal villi atrophy, inflammatory infiltration, increased enterocyte apoptosis, and abnormal TJ expressions. Early EN significantly alleviated these intestinal injuries. In addition, we observed increased formation of the NET structure and elevated expressions of NET-associated proteins in intestines of critically ill surgical patients. Early EN was associated with the diminished presence of NETs and reduced expression of NET-associated proteins. Mechanically, analysis of the TLR4 pathway showed a significant increase in TLR4, NFκB, and MAPK signaling in patients receiving TPN when compared to those receiving early EN. CONCLUSION: The intestinal barrier is disrupted in the human gut during critical illness. Our data suggests that an increased NET structure was showed in the gut of critically ill surgical patients, and early EN treatment was associated with the reduction of NET formation and the preservation of mucosal immunity.

Current progress of source control in the management of intra-abdominal infections.

Intra-abdominal infection (IAI) is a deadly condition in which the outcome is associated with urgent diagnosis, assessment and management, including fluid resuscitation, antibiotic administration while obtaining further laboratory results, attaining precise measurements of hemodynamic status, and pursuing source control. This last item makes abdominal sepsis a unique treatment challenge. Delayed or inadequate source control is an independent predictor of poor outcomes and recognizing source control failure is often difficult or impossible. Further complicating issue in the debate is surrounding the timing, adequacy, and procedures of source control. This review evaluated and summarized the current approach and challenges in IAI management, which are the future research directions.

Mincle/Syk Signalling Promotes Intestinal Mucosal Inflammation Through Induction of Macrophage Pyroptosis in Crohn's Disease.

BACKGROUND: Macrophage-inducible C-type lectin [Mincle] signalling plays a proinflammatory role in different organs such as the brain and liver, but its role in intestinal inflammation, including Crohn's disease [CD], remains unknown. METHODS: The characteristics of Mincle signalling expression in CD patients and experimental colitis were examined. The functional role of Mincle signalling in the intestine was addressed in experimental colitis models in vivo by using Mincle knock-out [Mincle-/-] mice. In addition, neutralising anti-Mincle antibody, downstream spleen tyrosine kinase [Syk] inhibitor, and Mincle pharmacological agonist were used to study the Mincle signalling in intestine. Bone marrow-derived macrophages were collected from mice and used to further verify the effect of Mincle signalling in macrophages. RESULTS: This study has shown that Mincle signalling was significantly elevated in active human CD and experimental colitis, and macrophages were the principal leukocyte subset that upregulate Mincle signalling. Mincle deficiency and Syk pharmacological inhibition ameliorated the colitis by reducing induced macrophage pyroptosis, and activation of Mincle with the agonist aggravated the intestinal inflammation. The ex vivo studies demonstrated that activation of Mincle signalling promoted the release of proinflammatory cytokines, whereas its absence restricted release of proinflammatory cytokines from pyroptosis of macrophages. In addition, Mincle/Syk signalling in macrophages could promote the production of chemokines to recruit neutrophils by activating mitogen-activated protein kinase [MAPK] during intestinal inflammation. CONCLUSIONS: Mincle signalling promotes intestinal mucosal inflammation by inducing macrophage pyroptosis. Modulation of the Mincle/Syk axis emerges as a potential therapeutic strategy to target inflammation and treat CD.

Follistatin like protein-1 modulates macrophage polarization and aggravates dextran sodium sulfate-induced colitis.

Follistatin-like protein 1 (FSTL1) is a pleiotropic cytokine involved in multiple processes including organ development, carcinogenesis, metastasis and so on. Some recent studies have suggested a possible role of FSTL1 in the inflammatory diseases. We for the first time tried to unravel its effect on the colitis, and explore the possible mechanisms. Here we found that FSTL1 was upregulated in active human and murine colitis. It facilitated proinflammatory M1 polarization of macrophages and inhibited the M2 anti-inflammatory phenotype, leading to excessive production of multiple inflammatory cytokines in vitro and in vivo. Haplodeletion of FSTL1 in mice significantly reduced the clinical and histological activity of colitis. Most importantly, macrophage depletion diminished the difference between DSS-treated WT and FSTL1+/- mice. Altogether, our results suggested that FSTL1 may also serve as an important contributor in the colonic inflammation. The possible mechanism may be related to its modulation on macrophage polarization.

Preliminary exploration of the potential of spliceosome-associated protein 130 for predicting disease severity in Crohn's disease.

The role of spliceosome-associated protein 130 (SAP130) in gut inflammation, particularly in Crohn's disease (CD), remains unclear. The aim of our study was to analyze correlations between serum SAP130 levels and CD severity, and to assess its predictive value for the clinical efficacy of exclusive enteral nutrition (EEN) in CD. Correlations between the SAP130 levels and CD severity were evaluated. SAP130 and its receptor Mincle (macrophage-inducible C-type lectin) in the colon tissue in active CD were measured. Furthermore, the serum SAP130 level was investigated as a predictor of clinical efficacy in patients treated with EEN. The serum SAP130 levels significantly increased in patients with active CD compared with patients in remission for CD (P < 0.001) and control individuals (P < 0.001), and they varied according to clinical activity and significantly correlated with disease severity. In parallel, the expression of both SAP130 and Mincle in colon tissue was elevated in active CD. Additionally, the serum SAP130 level declined in patients with active CD who achieved efficacy at week 8 after EEN therapy. This preliminary evidence shows that SAP130 might be a potential noninvasive biomarker that correlates well with CD severity and the clinical efficacy of EEN in CD.

Clinical parameters and outcomes of necrotizing soft tissue infections secondary to gastrointestinal fistulas.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) is severe surgical infections which can occur following trauma or abdominal surgery. NSTIs secondary to gastrointestinal (GI) fistula is a rare but severe complication. METHODS: A retrospective cohort study was performed on all subjects presenting with GI fistulas associated NSTIs were included. Clinical characteristics, microbiological profile, operations performed, and outcomes of patients were analyzed. RESULTS: Between 2014 and 2017, 39 patients were finally enrolled. The mean age were 46.9 years and male were the dominant. For the etiology of fistula, 25 (64.1%) of the patients was due to trauma. Overall, in-hospital death occurred in 15 (38.5%) patients. Microbiologic findings were obtained from 31 patients and Klebsiella pneumoniae was the most common species (41.0%). Eight patients were treated with an open abdomen; negative pressure wound therapy was used in 33 patients and only 2 patients received hyperbaric oxygen therapy. Younger age and delayed abdominal wall reconstruction repair were more common in trauma than in non-trauma. Non-survivors had higher APACHE II score, less source control< 48 h and lower platelet count on admission than survivors. Multiple organ dysfunction syndrome, multidrug-resistant organisms and source control failure were the main cause of in-hospital mortality. CONCLUSIONS: Trauma is the main cause of GI fistulas associated NSTIs. Sepsis continues to be the most important factor related to mortality. Our data may assist providing enlightenment for quality improvement in these special populations.

Mitochondrial DNA in liver inflammation and oxidative stress.

The function of liver is highly dependent on mitochondria producing ATP for biosynthetic and detoxifying properties. Accumulating evidence indicates that most hepatic disorders are characterized by profound mitochondrial dysfunction. Mitochondrial dysfunction not only exhibits mitochondrial DNA (mtDNA) damage and depletion, but also releases mtDNA. mtDNA is a closed circular molecule encoding 13 of the polypeptides of the oxidative phosphorylation system. Extensive mtDNA lesions could exacerbate mitochondrial oxidative stress and subsequently cause damage to hepatocytes. When mtDNA leaves the confines of mitochondria to the cytosolic and extracellular environment, it can act as damage-associated molecular patterns (DAMPs) to trigger the inflammatory response through the Toll-like receptor 9, inflammasomes, and stimulator of interferon genes (STING) pathways and further exacerbate hepatocellular damage and even remote organs injury. In addition, mtDNA also plays a vital role in hepatitis B virus (HBV)-related liver injury and hepatocellular carcinoma (HCC). In this review, we describe mtDNA alterations during liver injury, focusing on the mechanisms of mtDNA-mediated liver inflammation and oxidative stress injury.

Correlation between endoscopic and histological validated scoring indices in Crohn's disease.

BACKGROUND: It is of crucial importance to evaluate disease activity by means of endoscopy and histopathology in Crohn's disease (CD). Nonetheless, correlation between endoscopic and histological validated indices has not been verified. AIMS: We aim to correlate the Simple Endoscopic Score for Crohns disease (SES-CD) with two validated widely used histological indices in patients with established CD. METHODS: The SES-CD at the worst affected area was scored and histological disease activity using Global Histologic Disease Activity Score (GHAS or D'Haens score) and the Naini and Cortina Score (NCS) was scored independently by two pathologists blinded to the clinical information and endoscopic results. Spearman correlation between the SES-CD, GHAS and NCS were performed. RESULTS: 143 patients, 32 with SES-CD scores 0-2, 57 with 3-6, 37 with 7-15, and 17 with ≥16. Correlation coefficients between SES-CD and GHAS were r = 0.86 (95% CI 0.80-0.91, p < 0.001) and between SES-CD and NCS r = 0.85 (95% CI 0.81-0.88, p < 0.001). There was a strong correlation between the two histological indices (r = 0.70, 95% CI 0.59-0.78, p < 0.001). Mucosal healing without histological disease activity was most correlated with SES-CD score 0 or 1. CONCLUSIONS: The SES-CD strongly correlates with both GHAS and NCS. The SES-CD of 0 to 1 best represents histological remission that correlates with quiescent disease activity.

Early Active Drainage by Fine Tube Bundles Improves the Clinical Outcome of Anastomotic Leak after Abdominal Surgery: A Pilot Randomized, Controlled Trial in Two Tertiary Hospitals in China.

BACKGROUND: Post-operative anastomotic leak (PAL) is the most feared complication after abdominal surgery. Timely drainage of enteric effluent is beneficial in the healing of PAL. METHODS: We introduced a new and feasible approach for early active drainage of PAL using fine tube bundles (FTBs). The therapeutic effects of FTBs were observed prospectively and compared with the traditional drainage tube without FTBs in a non-blinded randomized controlled trial. RESULTS: Sixty patients with PAL in two tertiary hospitals in China from 2010 to 2016 were included in this study. Of these patients, 30 received FTBs and 30 were treated with a traditional drainage tube. The implantation failure rate was zero in the FTB group. No statistical difference was observed between the two groups in terms of demographic data. After these interventions, patients in the FTB group showed a faster decline in infection-related indictors, a higher ratio of spontaneous PAL closure, and shorter treatment duration of antibacterial agents compared with those in the traditional drainage tube group. Fatal complications and financial cost were also reduced in the FTB group. CONCLUSION: Fine tube bundles may contribute to the healing of PAL through active drainage. This method should be validated by further clinical trials for wider use.

Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction.

Ischemia-reperfusion (I/R) injury is a challenging clinical problem, especially injuries involving the gastrointestinal tract. Mitochondrial DNA (mtDNA) is released upon cell death and stress, and can induce the inflammatory response. We aimed to investigate the role of mtDNA in the pathogenesis of intestinal I/R. Intestinal I/R model was established with clamping of the superior mesenteric artery, and IEC-6 cells were incubated under hypoxia/reoxygenation (H/R) conditions to simulate I/R injury. Using in vitro models, H/R up-regulated oxidative stress, disrupted mitochondrial activity and the mitochondrial membrane potential, induced apoptosis and elevated the mtDNA levels in the supernatant of intestinal epithelial cells, and the co-culture of mtDNA with human primary dendritic cells significantly elevated TLR9-MyD88 expression and enhanced the production of inflammatory cytokines and chemokines. MtDNA was also released in a mouse model of intestinal I/R and was associated with the increased secretion of inflammatory cytokines and increased gut barrier injury compared with that of the sham group. We concluded that mtDNA contributes to I/R injury and may serve as a biomarker of intestinal I/R. We further suggest that oxidized mtDNA originated from IECs during intestinal I/R exacerbates the acute proinflammatory process by eliciting the production of proinflammatory cytokines and chemokines.

Impaired Coagulation Status in the Crohn's Disease Patients Complicated with Intestinal Fistula.

BACKGROUND: Intestinal fistula is one of the common complications of Crohn's disease (CD) that might require surgical treatment. The clinical characteristics and outcomes of CD with intestinal fistula are much different from CD alone. This study was to investigate whether the coagulation status of CD is changed by intestinal fistula. METHODS: Data were retrospectively analyzed for 190 patients with a definitive diagnosis of CD who were registered at the Jinling Hospital between January 2014 and September 2015. Baseline clinical characteristics and laboratory indices of initial admission and 7 days after intestinal fistula resections were collected. Student's t-test and the Wilcoxon rank-sum test were used to compare differences between the two groups. RESULTS: Compared with CD patients without intestinal fistula, prothrombin time (PT) in patients with intestinal fistula was significantly longer (12.13 ± 1.27 s vs. 13.18 ± 1.51 s, P < 0.001 in overall cohort; 11.56 ± 1.21 s vs. 12.61 ± 0.73 s, P = 0.001 in females; and 12.51 ± 1.17 s vs. 13.37 ± 1.66 s, P = 0.003 in males). Platelet (PLT) count was much lower in intestinal fistula group than in nonintestinal fistula group (262.53 ± 94.36 × 109/L vs. 310.36 ± 131.91 × 109/L, P = 0.009). Multivariate logistic regression showed that intestinal fistula was significantly associated with a prolonged PT (odds ratio [OR] = 1.900, P < 0.001), a reduced amount of PLT (OR = 0.996, P = 0.024), and an increased operation history (OR = 5.408, P < 0.001). Among 65 CD patients receiving intestinal fistula resections, PT was obviously shorter after operation than baseline (12.28 ± 1.16 s vs. 13.02 ± 1.64 s, P = 0.006). CONCLUSIONS: Intestinal fistula was significantly associated with impaired coagulation status in patients complicated with CD. Coagulation status could be improved after intestinal fistula resections.

The non-thyroidal illness syndrome is associated with postoperative surgical site infections in enterocutaneous fistulae.

BACKGROUND: Non-thyroidal illness syndrome (NTIS) is common in critically ill patients and associated with adverse outcomes. Many enterocutaneous fistula (ECF) patients still suffer NTIS prior to definitive surgery. This study was designed to explore the association between preoperative NTIS and postoperative outcomes in ECF patients. METHODS: A total of 264 ECF patients who underwent definitive surgery from April 2014 to November 2016 were studied. Thyroid hormones were tested for each patient before surgery, and the patients were divided into two groups (NTIS group and euthyroid group) according to the presence of NTIS. Demographics, surgery-related data, and complications during the first 30 days after surgery were recorded and analyzed. RESULTS: Among ECF patients accepted for definitive surgery, the prevalence of NTIS was 31.4% (83/264). The most common presentation of NTIS was a single low free triiodothyronine (FT3) 28.0% (74/264), followed by low FT3 combined with low thyrotropin (TSH) 1.9% (5/264), and low free thyroxine (FT4) combined with low TSH 1.5% (4/264). Compared to the euthyroid group, more patients with NTIS had multiple ECF, received more than three months of enteral nutrition pre-operatively, and developed surgical site infections (SSI). FT3 levels correlated with risk of SSI. Receiver operating characteristic curve (ROC) analysis revealed the diagnostic effectiveness of FT3, suggesting that the optimal cut-off value was 3.5 pmol/L. Area under the curve, sensitivity and specificity were 0.75, 72.6% and 68.7%, respectively. CONCLUSIONS: ECF patients with NTIS before definitive surgery appear to have a greater risk for poor outcomes. The benefit of thyroid hormone replacement therapy or delaying definitive surgery deserves further study.

Effects of Changes in the Levels of Damage-Associated Molecular Patterns Following Continuous Veno-Venous Hemofiltration Therapy on Outcomes in Acute Kidney Injury Patients With Sepsis.

Background: We investigated the association of damage-associated molecular pattern (DAMP) removal with mortality in sepsis patients undergoing continuous veno-venous hemofiltration (CVVH). Methods: Circulating levels of DAMPs [mitochondrial DNA (mtDNA); nuclear DNA (nDNA); heat shock protein 70 (HSP70); and high mobility group box 1 (HMGB1)] and cytokines were measured at baseline, 6 and 12 h after initiation of CVVH. Urinary DNA levels were analyzed at baseline and end of CVVH. The expression of human leukocyte antigen (HLA)-DR was assayed at 0, 3, and 7 days after initiation of CVVH. Moreover, the effects of HSP70 and HMGB1 clearance on survival were analyzed. Results: We evaluated 43 patients with acute kidney injury (AKI) (33 sepsis patients). Twenty-two sepsis patients (67%) and three non-sepsis patients (30%) expired (P = 0.046). Significant reductions in the levels of circulating interleukin-6 (P = 0.046) and tumor necrosis factor-α (P = 0.008) were found in the sepsis group. The levels of mtDNA were increased (ND2, P = 0.035; D-loop, P = 0.003), whereas that of HSP70 was reduced (P = 0.000) in all patients during the first 12 h. The levels of DAMPs in the plasma were markedly increased after blood passage from the inlet through the dialyzer in survivor sepsis patients. The clearance rates of HSP70 and HMGB1 were good predictors of mortality [area under the curve (AUC) = 0.937, P = 0.000; AUC = 0.90, P = 0.001, respectively]. The level of HLA-DR was increased in response to higher HSP70 clearance (P = 0.006). Survival was significantly worse in groups with higher clearance rates of HSP70 and HMGB1 than the cut-off value (log-rank test: P = 0.000 for both). Higher HSP70 clearance was a significant independent predictor of mortality (odds ratio = 1.025, 95% confidence interval [CI]: 1.012-1.039, P = 0.000). The urinary nDNA (ß-globin) level before CVVH was an independent risk factor for the duration of CVVH in patients with sepsis (sRE = 0.460, 95% CI: 1.720-8.857, P = 0.005). Conclusion: CVVH removes inflammatory factors, reduces urinary DAMPs, and removes plasma DAMPs. However, survival decreases in response to higher HSP70 clearance.

The utility of food antigen test in the diagnosis of Crohn's disease and remission maintenance after exclusive enteral nutrition.

BACKGROUND: Crohn's disease (CD) involves intensive immunologic responses to food antigens. Exclusive enteral nutrition (EEN) showed efficacy in inducing disease remission. However, relapse commonly occurred when normal diet was reintroduced. We aimed to investigate the food-specific IgG antibodies of CD, and clarify the effects of exclusion diet guided by food-specific antibodies on remission maintenance after EEN. METHODS: All available data of food-specific antibodies were retrieved from the database and analyzed for the diagnostic value. Thereafter, we retrospectively recruited qualified patients who reintroduced their diet excluding the moderately and strongly immunoreactive foods with prospective follow-up data. Matched patients without diet intervention after EEN served as control. CD activity index (CDAI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and endoscopic score were compared. RESULTS: A significantly enhanced immune response to rice, tomato, egg white/egg yolk and maize was observed in CD patients. The number of IgG-positive items had the greatest power to discriminate CD from ulcerative colitis and the control group with area under the curve of 0.819 and 0.828. Each diet group included 32 patients, and disease relapsed in 12.5% of the exclusion group compared with 25% of the control. The increase of CDAI and ESR was more remarkable in the control group than in the exclusion diet group (P<0.05). CONCLUSIONS: CD patients presented intensive immune responses to food antigens. The number of IgG-positive food items had potential to be a diagnostic marker of CD. Diet guided by food antibody test might help maintain disease remission.

Delayed Diagnosis is Associated with Early and Emergency Need for First Crohn's Disease-Related Intestinal Surgery.

BACKGROUND Increasing evidence suggests that delayed diagnosis in Crohn's disease is associated with a complicated disease course. The aim of this study was to explore the association between delayed diagnosis and the timing of the first Crohn's disease-related intestinal surgery. MATERIAL AND METHODS A retrospective study included 215 Crohn's disease patients with previous surgical history in the Department of General Surgery of Jinling Hospital, China, between January 2013 and March 2016. Data were collected on demographics, clinical characteristics, medication history, and operation history. RESULTS The time from the first appearance of Crohn's disease-related symptoms to the first intestinal surgery in the delayed diagnosis group was obviously shorter than in the non-delayed diagnosis group (26.4±28.7 months vs. 42.6±58.4 months, respectively, p=0.032). Patients in the delayed diagnosis group tended to receive more ileal resections (47.8% vs. 26.4%, respectively, p=0.002) and less ileocecal resections (22.4% vs. 37.2%, respectively, p=0.032). More patients in the delayed diagnosis group received the first Crohn's disease-related intestinal surgery as an emergency one (20.9% vs. 4.7%, respectively, p=0.001). CONCLUSIONS Delayed diagnosis is associated with early and emergency need for the first Crohn's disease-related intestinal surgery.

[Predictive value of procalcitonin in postoperative intra-abdominal infections after definitive operation of intestinal fistulae].

OBJECTIVE: To investigate the predictive value of procalcitonin(PCT) in postoperative intra-abdominal infections (IAI) after definitive operation of intestinal fistulae(IF). METHODS: With the exclusion of emergence operation, preoperative clinical infection, preoperative renal or hepatic dysfunction, and age less than 18 years, a total of 356 consecutive patients who underwent elective digestive tract reconstruction of intestinal fistulae from February 2012 to December 2015 at Intestinal Fistula Center of Jinling Hospital were prospectively enrolled in the study. All the patients were divided into IAI group (26 cases, 21 of anastomosis leakage and 5 of peritoneal abscess) and non-IAI group (330 cases) based on the existence of postoperative IAI. The non-IAI group was then divided into two subgroups of other infection (93 cases) and non-infection(237 cases) according to the presence of other infections. Plasma PCT level, serum CRP concentration and WBC count were assessed preoperatively and on postoperative days (PODs) 1, 3, 5, 7 by immunofluorescence, turbidimetry and automatic blood analyzer, respectively. The predictive value of each marker for IAI was calculated by receiver operating characteristic (ROC) curve. RESULTS: There was no significant difference in general clinical data between IAI and non-IAI group (all P>0.05). The proportions of multi-IF (53.8%, 14/26) and colectomy (61.5%, 16/26) in IAI group were higher than those of non-IAI group [20.0% (66/330), χ2=15.847, P=0.000 and 31.2%(103/330), χ2=9.961, P=0.002]. Differences of preoperative PCT, CRP and WBC levels among IAI, other infection and non-infection groups were not significant. These three markers all increased obviously and immediately after surgery. PCT and WBC values reached the peak point on POD 1, whereas CRP on POD 3. In IAI group, mean PCT values were (5.4±4.2) µg/L, (2.9±1.9) µg/L and (1.6±1.8) µg/L on POD 1, POD 3 and POD 5, respectively, which were higher than those of other infection group [(4.2±8.7) µg/L, (1.9±3.8) µg/L and (0.6±0.8) µg/L] and non-infection group [(2.7±5.8) µg/L, (1.1±1.7) µg/L and (0.5±0.7) µg/L, all P<0.05]. Mean CRP values in IAI group were 99.4 mg/L and 183.9 mg/L respectively on POD 1 and POD 3,and mean WBC values of IAI group on POD 1, POD 3 and POD 5 were 16.0×109/L, 10.8×109/L and 8.7×109/L, respectively, which were all significantly higher than those in the other 2 groups (all P<0.05). No significant differences were obtained between other infection group and non-infection group in all these three markers (all P>0.05). ROC curve demonstrated that PCT had the biggest area under the curve (AUC) of 0.86 and 0.84 on POD 3 and POD 5, with the cut-off value of 0.98 µg/L and 0.83 µg/L, 92.0% sensitivity and 74.0% specificity, 91.0% sensitivity and 73.0% specificity, respectively. The highest AUC was 0.72 on POD 3 for CRP and 0.71 on POD 3 for WBC, with 80.0% sensitivity and 54.0% specificity, 56.0% sensitivity and 73.0% specificity, respectively. CONCLUSION: The value of procalcitonin above 0.98 µg/L on POD 3 and 0.83 µg/L on POD 5 can predict the occurrence of IAI after definitive operations of intestinal fistulae.