Huajian Ren

Preliminary case-control study to evaluate diagnostic values of C-reactive protein and erythrocyte sedimentation rate in differentiating active Crohn's disease from intestinal lymphoma, intestinal tuberculosis and Behcet's syndrome.

Background:There are few evidences of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) in differentiating active Crohn’s disease (CD) from intestinal lymphoma (IL), intestinal tuberculosis (ITB) and Behcet’s syndrome (BD). This study is designed to investigate potential differential capacity of the 3 biomarkers between these disorders. Methods:A hospital-based case-control study was performed. A total of 29 active CD, 25 IL, 30 ITB and 17 BD patients were collected. Laboratory parameters were drawn from the first blood test results on admission. Results:In active CD group, the level of CRP was 20.2 ± 4.26 mg/dL, which was statistically lower than IL (59.9 ± 10.8 mg/dL, P < 0.0001). Similarly, the level of ESR reached its lowest point in active CD group (23.8 ± 3.18 mm/hr), compared with 46.6 ± 6.46 mm/hr in IL group (P = 0.0002). CRP showed a possible diagnostic value in differentiation of IL from active CD (odds ratio = 1.028, P = 0.046). CRP also exhibited a superior ability (area under curve [AUC] = 0.821) than ESR (AUC = 0.797) and CRP+ESR (AUC = 0.800) in distinguishing active CD from IL. The optimal cutoff value was 19.7 mg/dL, and the sensitivity and specificity were 62.1% and 96.0%, respectively. Conclusions:A significant decreased level of CRP and ESR was confirmed in active CD compared with IL. Current study demonstrated a possible differential value of CRP between active CD and IL. Further studies would be performed to validate their clinical significances.

Prevention of postoperative recurrence of Crohn’s disease: Tripterygium wilfordii polyglycoside versus mesalazine

Objectives To explore effectiveness and safety of polyglycosides of Tripterygium wilfordii (GTW) and mesalazine (5-aminosalicylic acid [5-ASA]) in preventing postoperative clinical and endoscopic recurrence of Crohn’s disease. Methods In this prospective, single-centre, single-blind study, postoperative Crohn’s disease patients in remission were randomized to receive 1 mg/kg GTW daily, orally, or 4 g 5-ASA daily, orally, for 52 weeks. Patients underwent physical examinations, ileocolonoscopies and biochemical analyses at baseline and weeks 13, 26 and 52, or when clinical recurrence was suspected. Outcome measures were proportion of patients showing clinical or endoscopic recurrence at week 52, and changes in Rutgeerts’ and Crohn’s Disease Activity Index (CDAI) scores. Results Twenty-one patients were assigned to receive GTW and 18 to 5-ASA; two patients on GTW and one on 5-ASA were withdrawn. Clinical and endoscopic recurrences were less common in the GTW group (n = 4) versus the 5-ASA group (n = 9). There were improvements in Rutgeerts’ scores for those taking GTW. Mean between-group CDAI scores were similar. No serious adverse events were reported. Conclusion These findings indicate that GTW appears to be an effective, well-tolerated prophylactic regimen, superior to oral 5-ASA, for preventing clinical and endoscopic recurrence in postsurgical Crohn’s disease.

Diagnostic delay in Crohn's disease is associated with increased rate of abdominal surgery: A retrospective study in Chinese patients

BACKGROUND Diagnostic delay of Crohns disease presents a challenge, and may increase the abdominal surgery rate. There have been no reports regarding diagnostic delay in Chinese patients. AIMS We aimed to evaluate the impact of diagnostic delay on outcomes of Chinese Crohns disease patients, and identify potential risk factors for the delay. METHODS Altogether, 343 Crohns disease patients from our hospital were retrospectively included. We assessed the effects of diagnostic delay on the outcomes, and identified the underlying risk factors. RESULTS Diagnostic interval was defined as the interval between the first symptoms and the diagnosis of Crohns disease. Diagnostic delay was defined according to the time interval in which the 76th to 100th percentiles of patients were diagnosed. The rates of subsequent surgery for diagnostic-delay and non-diagnostic-delay patients were 84.7% and 62.4%, respectively (odds ratio=1.108, P<0.0001). We found statistical differences between the two groups regarding age >40 years at diagnosis (35.3% versus 18.2%, P=0.004), basic educational level (48.2% versus 30.6%, P=0.005), and no family history of Crohns disease (0 versus 1.6%, P=0.045). CONCLUSIONS Diagnostic delay of Crohns disease was significantly associated with increased rates of intestinal surgery. Risk factors for diagnostic delay were age >40 years at diagnosis, basic educational level, and no family history of Crohns disease.

Efficacy of Erythropoietin Combined With Enteral Nutrition for the Treatment of Anemia in Crohn’s Disease: A Prospective Cohort Study

BACKGROUND Anemia is a common and serious complication in patients with inflammatory bowel disease. The present study was dedicated to evaluate the therapeutic efficacy of erythropoietin (EPO) combined with enteral nutrition (EN) in anemic Crohns disease (CD) patients, in terms of hemoglobin level, treatment success rate, adverse events, and predictor of this therapy. MATERIALS AND METHODS We performed a prospective study in CD patients. On the basis of hemoglobin level, all enrolled patients were divided into anemic and nonanemic groups. The anemic group was further divided into EPO and non-EPO subgroups, depending on whether EPO was prescribed. Hematological and other parameters were measured initially and in the first 4 weeks after starting treatment. RESULTS In total, 109 patients (49 nonanemic and 60 anemic, including 38 EPO and 22 non-EPO) were included. The prevalence of anemia in CD was 55.05%. Age, disease behavior, Crohns Disease Activity Index scores, C-reactive protein, and erythrocyte sedimentation rate were significantly different between anemic and nonanemic groups. An increase in hemoglobin level and a significant decrease in C-reactive protein level were observed in the EPO treatment group. Treatment success rate was 63.16% in the EPO group, whereas none of patients achieved treatment success in the non-EPO group. CONCLUSION EPO combined with EN can improve the hemoglobin level in anemic CD patients.

Autologous platelet rich fibrin glue for sealing of low-output enterocutaneous fistulas: An observational cohort study

BACKGROUND Glue sealing has become an alternative option for occlusion of enterocutaneous fistula (ECF) because of it minimal invasiveness and simplicity. This study aimed to determine efficacy and safety of autologous, platelet-rich fibrin glue (PRFG) in promoting closure of ECFs. METHODS This was a nonrandomized cohort study, recruiting patients who had low-output ECFs (<200 mL/24 h). Beside standard of care, patients were assigned to either the PRFG or control group. Clinical efficacy and safety were determined prospectively. Moreover, a well-balanced subcohort was generated by propensity score (PS) matching. Unadjusted and adjusted Cox proportional hazard models were employed to determine hazard ratios (HRs) of ECF closure in both cohorts. RESULTS From January 2008 to January 2012, 145 patients were enrolled initially, with 70 in the control group and 75 in the PRFG-treated group. Compared with the control group, patients in the PRFG group had lesser median time of fistula closure (7 vs 23 days; P = .0010). In addition, PRFG healed more fistulas within the first 28 days (77% vs 57%; P = .0127). For all fistulas included, PRFG-treated fistulas were 3.13 (95% confidence interval [CI], 1.82-5.36) times more likely to achieve closure than those with the non-PRFG approach in the adjusted Cox model. In a PS-matched cohort with 28 paired fistulas, HRs were 3.41 (95% CI, 1.91-6.07) for all fistulas regardless of location. No adverse events related to glue applications were observed. CONCLUSION Autologous PRFG seems to be safe and effective in the treatment of low-output ECFs, and can lessen closure times and promote closure rates.

Nonthyroidal illness syndrome in enterocutaneous fistulas

BACKGROUND The aim of this study was to investigate the incidence, etiology, clinical outcomes, and prognosis of nonthyroidal illness syndrome (NTIS) in patients with enterocutaneous fistulas. METHODS We prospectively collected 226 patients with enterocutaneous fistulas. Demographics, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment scores, C-reactive protein, body mass index, albumin, and thyroidal hormones were evaluated for each patient. RESULTS The incidence of NTIS was 57.5% in patients with enterocutaneous fistulas. Age and the APACHE II and Sequential Organ Failure Assessment scores were significantly higher, whereas albumin was lower in the NTIS group compared with those in the euthyroid group. A decreased sum activity of deiodinases and a reduced ratio of total thyroxin/free thyroxin and total triiodothyronine/free triiodothyronine were observed in the NTIS group. Patients with NTIS suffered longer durations in the intensive care unit and higher possibilities of mechanical ventilation. The cumulative survival rate was significantly lower in the NTIS group. CONCLUSIONS NTIS was common, and patients with NTIS displayed worse clinical outcome and prognosis. A hypodeiodination condition and a potential thyroid hormone-binding dysfunction may play a role in the etiology of NTIS. A low serum albumin concentration and a high APACHE II score were risk factors of NTIS in enterocutaneous fistulas.

Urinary Mitochondrial DNA Levels Identify Acute Kidney Injury in Surgical Critical Illness Patients.

Background: Recent studies showed that mitochondrial injury and mitochondrial DNA (mtDNA) damage are associated with the initiation and progression of acute kidney injury (AKI). However, practical limitations of existing assays of mitochondrial function have limited our ability to study the link between mitochondrial dysfunction and renal injury. Therefore, we evaluated urinary mtDNA (UmtDNA) as a biomarker of AKI in critical illness patients. Methods: DNA was isolated from urine samples in surgical intensive care unit (SICU) patients and quantified by quantitative polymerase chain reaction (PCR). Correlation analyses showed the relationships between the UmtDNA and several biomarkers of renal dysfunction. Moreover, we evaluated the predictive and diagnostic values of UmtDNA in newly developed AKI, renal replacement therapy (RRT), and hospital mortality using receiver operating characteristics curves. Results: MtDNA were expressed as PCR threshold cycle (Tc) number. Lower Tc indicated increased urinary mtDNA concentration. The baseline UmtDNA levels were elevated in SICU patients especially in AKI patients, compared with that in healthy controls. UmtDNA Tc number inversely correlated with serum creatine and urinary neutrophil gelatinase-associated lipocalin and directly with estimated glomerular filtration rate. Furthermore, baseline UmtDNA levels had high effectiveness in predicting development of AKI, initiation of RRT, and hospital mortality. Conclusions: Elevated UmtDNA levels could identify newly developed AKI and predict RRT or hospital mortality in SICU patients. UmtDNA Tc number correlated with markers of renal injury and dysfunction, suggesting the involvement of mitochondrial injury in kidney damage among surgical critical illness patients.

3D-printed “fistula stent” designed for management of enterocutaneous fistula: An advanced strategy

Enterocutaneous fistulas (ECFs) are great challenges during the open abdomen. The loss of digestive juice, water-electrolyte imbalance and malnutrition are intractable issues during management of ECF. Techniques such as “fistula patch” and vacuum-assisted closure therapy have been applied to prevent contamination of open abdominal wounds by intestinal fistula drainage. However, failures are encountered due to high-output fistula and anatomical complexity. Here, we report 3D-printed patient-personalized fistula stent for ECF treatment based on 3D reconstruction of the fistula image. Subsequent follow-up demonstrated that this stent was well-implanted and effective to reduce the volume of enteric fistula effluent.

T2 enhances in situ level of Foxp3+ regulatory cells and modulates inflammatory cytokines in Crohn's disease.

BACKGROUND Acting via IL-10 and transforming growth factor-β (TGF-β), t regulatory cells (Tregs) that express the Forkhead Box P3 (Foxp3) play a vital role in maintaining intestinal immune homeostasis. Many studies have found correlation between Foxp3(+) Treg cells and Crohns disease (CD). T2, extracted from the medicinal plant Tripterygium wilfordii Hook F, has already been proved to be therapeutically effective in inducing the remission of CD. However, the mechanisms in human studies remain largely unknown. AIM We aimed to explore the effect of T2 on the in situ levels of inflammatory cytokines and the number of Foxp3(+) Tregs in inflamed mucosa of CD. METHODS Mucosal biopsies from 20 patients treated with T2 were taken by colonoscopy. The changes of Foxp3(+) Tregs as well as TNF-α and IL-10 in diseased tissue were visualized by immunochemistry. Western blot and ELISA were used to quantify levels of Foxp3 protein expression and inflammatory cytokines. RESULTS T2 treatment ameliorated the pathological inflammation of CD. We observed that the significantly elevated Foxp3(+) Tregs and IL-10 levels in the mucosa of CD patients after T2 treatment concurred with the down-regulation of proinflammatory TNF-α. CONCLUSION We confirmed the efficacy of T2 treatment in CD and showed that microscopic inflammation was attenuated by the modulation of in situ levels of inflammatory cytokines. The therapeutic mechanisms might involve the up-regulation of Foxp3(+) Tregs.

The mitochondrially targeted antioxidant MitoQ protects the intestinal barrier by ameliorating mitochondrial DNA damage via the Nrf2/ARE signaling pathway

Disruption of the mucosal barrier following intestinal ischemia reperfusion (I/R) is life threatening in clinical practice. Mitochondrial dysfunction and oxidative stress significantly contribute to the early phase of I/R injury and amplify the inflammatory response. MitoQ is a mitochondrially targeted antioxidant that exerts protective effects following I/R injury. In the present study, we aimed to determine whether and how MitoQ protects intestinal epithelial cells (IECs) from I/R injury. In both in vivo and in vitro studies, we found that MitoQ pretreatment downregulated I/R-induced oxidative stress and stabilized the intestinal barrier, as evidenced by MitoQ-treated I/R mice exhibiting attenuated intestinal hyperpermeability, inflammatory response, epithelial apoptosis, and tight junction damage compared to controls. Mechanistically, I/R elevated mitochondrial 8-hydroxyguanine content, reduced mitochondrial DNA (mtDNA) copy number and mRNA transcription levels, and induced mitochondrial disruption in IECs. However, MitoQ pretreatment dramatically inhibited these deleterious effects. mtDNA depletion alone was sufficient to induce apoptosis and mitochondrial dysfunction of IECs. Mitochondrial transcription factor A (TFAM), a key activator of mitochondrial transcription, was significantly reduced during I/R injury, a phenomenon that was prevented by MitoQ treatment. Furthermore, we observed that thee protective properties of MitoQ were affected by upregulation of cellular antioxidant genes, including HO-1, NQO-1, and γ-GCLC. Transfection with Nrf2 siRNA in IECs exposed to hypoxia/reperfusion conditions partially blocked the effects of MitoQ on mtDNA damage and mitochondrial oxidative stress. In conclusion, our data suggest that MitoQ exerts protective effect on I/R-induced intestinal barrier dysfunction.