Zhiwu Hong

Nonthyroidal Illness Syndrome: Is It Far Away From Crohn’s Disease?

Goals: This study was designed to investigate the clinical features of nonthyroidal illness syndrome (NTIS) compared with euthyroid patients in Crohn’s disease (CD), to explore the etiology of NTIS in CD, to evaluate the clinical outcomes of NTIS patients, and to inspect the correlation of clinical variables and NTIS, and their ability of differentiating NTIS from euthyroid patients. Background: NTIS has been described for more than 30 years. However, only few studies focused on the relationship between NTIS and CD. The incidence, underlying pathogenesis, clinical outcomes, and correlation with other inflammatory disease severity and nutritional variables of NTIS in CD have not been completely established. Methods: Prospectively, 44 CD patients were enrolled. Medical records and various laboratory values (including thyroidal, nutritional, and inflammatory variables) were collected in all participants. Results: The incidence of NTIS in CD was 36.4%. Albumin, Acute Physiology and Chronic Health Evaluation II score, and Crohns Disease Activity Index score in NTIS group were statistically different from those in euthyroid group. A decreased sum activity of deiodinases and a reduced ratio of TT4/FT4 were observed in NTIS group. Duration of hospitalization was significantly longer for NTIS patients than euthyroid patients. Albumin was confirmed as a protective factor of NTIS in CD. Receiver operating characteristic curve analysis demonstrated the differentiating capacity of albumin, suggesting 37.6 g/L as optimal cut-off value with sensitivity and specificity of 81.3% and 79.2%, respectively. Conclusions: NTIS was a common complication in CD. NTIS patients showed worse nutrition status and clinical outcome, and more critical disease activity and severity compared with euthyroid patients. A hypodeiodination condition and a potential thyroid-hormone–binding dysfunction may play a role in the etiology of NTIS in CD. Albumin was a meaningful protective and distinguishing marker of NTIS in CD.

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.

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.

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.

Geographic Mapping of Crohn’s Disease and Its Relation to Affluence in Jiangsu Province, an Eastern Coastal Province of China

Background. Geographical variation in the incidence of Crohns disease (CD) has been reported in Europe and North American. However, there are no comparable data in mainland China. Methods. We retrospectively identified incident cases of CD patients registered in Jinling hospital during 2003 to 2012. The standardized incidence ratio (SIR) was calculated for each area of Jiangsu province and a thematic map of CD was made according to the local SIR. The association between incidence and local economic status was revealed by correlation between SIR of CD and different local economic indicators. Results. A total of 653 CD patients (male-to-female ratio, 1.8 : 1) from Jiangsu province were included. A steady increase was observed in the number of CD patients over the period of observation. Disease map of SIR showed a pronounced geographic concentration of CD in the south part of Jiangsu province. Spearman correlation analysis showed a positive correlation between local SIR of CD and local economic indicators. Conclusions. There is a marked geographic variability in CD incidence across Jiangsu province. CD incidence in affluent areas seems to be higher than that in less affluent areas. Further multicenter population-based studies are needed to assess the real disease map of CD.

Prevalence and risk factors of acute lower gastrointestinal bleeding in Crohn disease.

AbstractAcute lower gastrointestinal bleeding (ALGIB) is a rare but potentially life-threatening complication of Crohn disease (CD). Thus far, few studies of ALGIB in the context of CD have been published, most of which were case reports with limited value. We aimed to explore the prevalence of ALGIB in CD patients, evaluate risk factors for hemorrhagic CD and its recurrence, and analyze clinical data of the death cases.A total of 1374 CD patients registered from January 2007 to June 2013 were examined. Medical records of 73 patients with ALGIB and 146 matched as controls were reviewed and analyzed retrospectively. Logistic regression and Cox proportional hazards analyses were performed to identify risk factors for ALGIB and the cumulative probability of rebleeding. Kaplan–Meier curves with log-rank tests were used to demonstrate the cumulative survival rates of rebleeding.The prevalence of ALGIB was 5.31% (73/1374) in this study. In the univariate analysis, possible risk factors for ALGIB were duration of CD (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.33–1.09, P = 0.095), perianal disease (OR 1.96, 95% CI 0.92–4.20, P = 0.082), left colon involvement (OR 2.16, 95% CI 1.10–4.24, P = 0.025), azathioprine use ≥1 year (OR 0.46, 95% CI 0.23–0.90, P = 0.023), and previous hemorrhage history (OR 11.86, 95% CI 5.38–26.12, P < 0.0001). In the multivariate analysis, left colon involvement (OR 2.26, 95% CI 1.04–4.91, P = 0.039), azathioprine use ≥1 year (OR 0.44, 95% CI 0.20–0.99, P = 0.044), and previous hemorrhage history (OR 13.04, 95% CI 5.66–30.04, P < 0.0001) remained independent influencing factors. Older age (HR 0.23, 95% CI 0.07–0.77, P = 0.018), surgical treatment (HR 0.17, 95% CI 0.06–0.50, P < 0.001), and having bleeding episodes >3 months ago (HR 0.24, 95% CI 0.07–0.82, P = 0.022) resulted to be predictors associated with rebleeding after discharge. Patients who died often suffered severe concomitant diseases, and the overall mortality rate was 8.22% (6/73).We speculated that a special hemorrhagic phenotype of CD that was predisposed to rebleeding may exist. Further studies are warranted to investigate the pathogenesis and discover the optimum treatments of choice.

Value of Red Cell Distribution Width for Assessing Disease Activity in Crohn's Disease

Background:Correlation between red cell distribution width (RDW) and chronic inflammation was observed, although studies focused on value of RDW for assessing disease activity in Crohns disease (CD) are limited. Methods:This is a prospective study. RDW, C-reactive protein, erythrocyte sedimentation rate and white blood cell count were measured in 100 patients with CD on admission and 102 age- and gender-matched healthy volunteers. Value of these markers for assessing disease activity in CD was investigated. Results:RDW was significantly higher in patients with active CD than in inactive patients (P < 0.05). The optimal cutoff value for RDW was 15.6% in differentiating active from inactive disease, with sensitivity and specificity of 94.2% and 56.3%, respectively (area under the curve = 0.743). The overall accuracy of RDW in detecting active CD was 76.0%, which is higher than that of erythrocyte sedimentation rate (68.0%) and white blood cell count (51.0%) but lower than that of C-reactive protein (78.0%). Conclusions:RDW was elevated in patients with active CD in comparison with patients in remission. As a cost-effective tool, RDW may assist in determining the disease activity of CD.

Early Liver Dysfunction in Patients With Intra-Abdominal Infections

Abstract Liver dysfunction is commonly seen in patients with severe sepsis; however, few studies were reported in intra-abdominal infections (IAIs). This study was performed to assess the risk factors for early liver dysfunction (ELD) in patients with IAIs and to determine the effects of ELD on outcomes of these patients. From January 2011 to November 2014, a retrospective study that screened 421 patients with IAIs was performed. ELD was defined as an increase in serum total bilirubin (TB) >2 mg/dL or aminotransferases levels greater than twice the normal value within 48 hours after IAIs’ onset. Patients with pre-existing liver disease or major hepatobiliary injury were excluded. Risk factors for ELD and outcomes were compared by univariate and multivariate analyses. Subgroup analysis was performed for ELD patients within 24 to 48 hours. Of 353 enrolled patients admitted with IAIs, 147 (41.6%) developed ELD. Significant independent risk factors for ELD were trauma (odds ratio [OR] 1.770, 95% confidential interval [CI] 1.126–2.783, P = 0.01) and abdominal compartment syndrome (ACS) (OR 3.199, 95% CI 1.184–8.640, P = 0.02). Successful source control <24 hours was shown to exert protection against ELD after 24 hours during IAIs (OR 0.193, 95% CI 0.091–0.409, P < 0.001). ELD was associated with significantly worse outcomes, including longer ICU length of stay and higher in-hospital mortality. Multivariate analysis also showed that development of ELD was a predisposing factor of mortality in IAIs patients (P < 0.001). ELD was a common complication in patients with IAIs associated with worse outcomes. Trauma and ACS were relevant risk factors. Early successful source control appeared to be an important method to prevent and/or reduce ELD in patients with IAIs.