MicroRNA-320a Monitors Intestinal Disease Activity in Patients With Inflammatory Bowel Disease.

OBJECTIVES: In patients with inflammatory bowel disease (IBD), a treat-to-target treatment strategy requires tight monitoring of disease activity. Noninvasive biomarkers may help to monitor the intestinal disease activity. We demonstrated recently that peripheral microRNA (miR)-320a expression in mice follows the course of experimental colitis. The aim of this study was to evaluate the potential of miR-320a to monitor the disease activity in patients with IBD, to predict the course of disease, and to distinguish IBD from infectious colitis. METHODS: The miR-320a levels were prospectively assessed by quantitative real-time polymerase chain reaction analysis of peripheral blood samples from 40 patients with Crohn's disease (CD) and 37 patients with ulcerative colitis (UC) as well as from 19 healthy control individuals and 7 patients with infectious colitis. Disease activity was quantified by appropriate clinical disease indices and endoscopic scoring systems. RESULTS: When compared with healthy controls, miR-320a blood levels were significantly increased in patients with active CD and UC (16.1 ± 2.6 vs 2,573 ± 941; vs 434 ± 96; both P < 0.001) and patients with IBD in remission (316 ± 251 [CD] and 91 ± 29 [UC]; both P < 0.001). In patients with CD, miR-320a levels showed a strong correlation with the endoscopic disease activity (r = 0.76; P < 0.001). Similarly, in patients with UC, we detected a significantly enhanced miR-320a expression, which was highest in patients with severe endoscopic disease activity (eMayo = 0-1: 66 ± 16 vs eMayo = 2: 352 ± 102; vs eMayo = 3: 577 ± 206; both P < 0.001). Finally, miR-320a blood expression in patients with active CD and UC significantly increased compared with patients with infectious colitis (63 ± 13, P < 0.001). DISCUSSION: MiR-320a expression in peripheral blood from patients with IBD follows the clinical and endoscopic disease activities and may help to distinguish IBD from infectious colitis.

Therapeutic effects of Ginkgo biloba extract against acute ischemic colitis.

Ginkgo biloba extract (GBE) is a plant extract obtained from the leaves of G biloba tree. The aim of this study was to evaluate the clinicopathologic characteristics and therapeutic effects of GBE on ischemic colitis (IC).Forty-seven patients with IC were divided as GBE group (n = 30) and routine group (n = 17). The routine group was given routine therapy, and the GBE group was given routine therapies plus GBE intravenous injection. Clinicopathologic characteristics, endoscopy findings, serum antioxidant enzymes, and inflammatory mediators were evaluated.About 89.3% initial symptom was acute-onset abdominal cramping and abdominal pain followed with hematochezia. The lesions were mainly located in sigmoid colon (80.8%). Serum level of superoxide dismutase (SOD) in patients with IC was significantly decreased (P < .05), while methane dicarboxylic aldehyde (MDA), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) levels were significantly increased (P < .05). However, serum procalcitonin (PCT) level showed no significant change. Treatment of GBE resulted in quick remittance of abdominal pain and hematochezia, and significant attenuation of colon macroscopic and histologic damage in all patients. Furthermore, the treatment also significantly increased SOD levels, decreased MDA, TNF-α, and IL-6 levels (P < .05).Acute-onset abdominal cramping or abdominal pain followed with hematochezia was the mainly initial symptom of IC, and sigmoid and descending colons were the common vulnerable sites. GBE exerted a beneficial effect on IC with faster symptom relief and better mucosal healing, possibly through scavenging oxidative-free radicals and downregulating inflammatory mediators. GBE may be a promising candidate for protection against IC.

Serum procalcitonin correlates with colonoscopy findings and can guide therapeutic decisions in postoperative ischemic colitis.

BACKGROUND: Postoperative ischaemic colitis (POIC) is a life-threatening vascular gastrointestinal condition. Serum procalcitonin (PCT) levels be of value in the detection of necrosis. AIMS: To evaluate the correlation between serum PCT levels and the colonoscopic assessment of the severity of POIC. METHODS: Between January 2007 and November 2014, 150 patients with POIC and PCT data were included in the study. The main outcome measure was the correlation between serum PCT and the colonoscopy-based assessment of the severity of POIC (according to Favier's classification: stage 1/2 without multi-organ failure vs. stage 2/3 with multi-organ failure). RESULTS: Eighty-five percent of the stage 1 cases (n=22) had a serum PCT level ≤2µg/L; 63% (n=19) of the stage 2 cases with multi-organ failure had a PCT level between 4 and 8µg/L, and 70% (n=52) of the stage 3 cases had a PCT level ≥8µg/L. The PCT level was strongly correlated with the Favier stage (Spearman's rho: 0.701; p<0.0001). PCT levels were similar in stage 2 cases with multi-organ failure and in stage 3 cases (16.06µg/L vs. 7.79µg/L, respectively; p=0.35). CONCLUSION AND RELEVANCE: Serum PCT is correlated with stage 2/3 POIC requiring surgery. If PCT ≥5µg/L, surgery should be considered.

Ischemic Colitis after Cardiac Surgery: Can We Foresee the Threat?

INTRODUCTION: Ischemic colitis (IC) remains a great threat after cardiac surgery with use of extracorporeal circulation. We aimed to identify predictive risk factors and influence of early catecholamine therapy for this disease. METHODS: We prospectively collected and analyzed data of 224 patients, who underwent laparotomy due to IC after initial cardiac surgery with use of extracorporeal circulation during 2002 and 2014. For further comparability 58 patients were identified, who underwent bypass surgery, aortic valve replacement or combination of both. Age ±5 years, sex, BMI ± 5, left ventricular function, peripheral arterial disease, diabetes and urgency status were used for match-pair analysis (1:1) to compare outcome and detect predictive risk factors. Highest catecholamine doses during 1 POD were compared for possible predictive potential. RESULTS: Patients' baseline characteristics showed no significant differences. In-hospital mortality of the IC group with a mean age of 71 years (14% female) was significantly higher than the control group with a mean age of 70 (14% female) (67% vs. 16%, p<0.001). Despite significantly longer bypass time in the IC group (133 ± 68 vs. 101 ± 42, p = 0.003), cross-clamp time remained comparable (64 ± 33 vs. 56 ± 25 p = 0.150). The majority of the IC group suffered low-output syndrome (71% vs. 14%, p<0.001) leading to significant higher lactate values within first 24h after operation (55 ± 46 mg/dl vs. 31 ± 30 mg/dl, p = 0.002). Logistic regression revealed elevated lactate values to be significant predictor for colectomy during the postoperative course (HR 1.008, CI 95% 1.003-1.014, p = 0.003). However, Receiver Operating Characteristic Curve calculates a cut-off value for lactate of 22.5 mg/dl (sensitivity 73% and specificity 57%). Furthermore, multivariate analysis showed low-output syndrome (HR 4.301, CI 95% 2.108-8.776, p<0.001) and vasopressin therapy (HR 1.108, CI 95% 1.012-1.213, p = 0.027) significantly influencing necessity of laparotomy. CONCLUSION: Patients who undergo laparotomy for IC after initial cardiac surgery have a substantial in-hospital mortality risk. Early postoperative catecholamine levels do not influence the development of an IC except vasopressin. Elevated lactate remains merely a vague predictive risk factor.

Predictive Factors for Severe Outcomes in Ischemic Colitis.

BACKGROUND/AIMS: Ischemic colitis includes a wide clinical spectrum ranging from mild to severe forms. This study aimed to determine the factors that are related to the occurrence of severe ischemic colitis. METHODS: This multicenter study was conducted retrospectively in Korea. The patients were divided into mild and severe groups. This study surveyed clinical characteristics, blood tests, endoscopic findings, and imaging studies. RESULTS: In the comparison of comorbidities, the severe group had a higher ratio of chronic kidney disease than the mild group (p=0.001). In the blood test, the severe group had a reduced number of platelets (p=0.018) and a higher C-reactive protein value (p=0.001). The severe group had a higher ratio of involvement of the right colon (p=0.026). The Eastern Cooperative Oncology Group (ECOG) performance status score of the patients showed that the severe group had higher scores than the mild group (p=0.003). A multivariate analysis showed that chronic kidney disease and high ECOG performance status scores were significant risk factors. CONCLUSIONS: If patients diagnosed with ischemic colitis are also treated for chronic kidney disease or have poor performance status, more attention and early intervention are necessary.

Clinical Characteristics of Ischemic Colitis in Elderly Patients.

BACKGROUND/AIMS: The aim of this study was to retrospectively analyze the endoscopy findings, clinical symptoms, signs and biochemical data of elderly patients with ischemic colitis (IC). METHODOLOGy: A retrospective study of 58 patients diagnosed with IC in the endoscopy center of Jinan Central Hospital from October 2008 to October 2013 was carried out. The patients were divided into two groups based on the age: elderly group (≥ 65 years) versus young group (< 65 years). Symptoms, signs, biochemical data, endoscopic findings and the length of hospitalization were compared. RESULTS: Of the 58 patients with IC (43 women and 15 men), the median age was 72.5 years (range 30-84 years), and 70.69% (41/58) were over the age of 65 years. Compared with the young group, the elderly group had a less frequent hyperactive bowel sounds, a higher baseline levels of C-reactive protein(CRP) and a longer average periods of hospitalization. CONCLUSION: Clinical characteristics of IC in the elderly were similar to those in the young group. CRP may be involved in the development of IC in the elderly patients. By considering the basic dieases combined with CRP levels, it is possible to more effectively predict and prevent the development of IC.

Predictors of severity in ischaemic colitis.

PURPOSE: Ischaemic colitis (IC) is an inadequate perfusion leading to potentially life-threatening colonic inflammation. The aim was to identify patient characteristics that predict severity in biopsy-confirmed IC. METHODS: A retrospective study of consecutive patients admitted with a robust diagnosis of IC over a 5-year period was performed. As IC is often misdiagnosed, strict inclusion criteria including supporting histopathology, exclusion of inflammatory bowel disease, absence of recent antibiotics or negative stool sampling with testing for Clostridium difficile were adhered to. Due to differing pathophysiology involved, patients suffering IC due to injury to colonic perfusion from vascular procedures or tumours were also excluded. Patients were divided by outcomes into a severe IC group including those that needed surgery or suffered mortality and a non-severe IC group that included patients managed medically with good evolution during their index admission. Patient characteristics were analysed to identify statistically significant predictors of severity (p < 0.05). RESULTS: Thirty-two patients (11 males, 21 females; mean age 72.5) met the inclusion criteria. Medical management was adopted in 23 patients with a single mortality (4.3%). Nine patients were managed surgically with two mortalities (22.2%), giving an overall mortality of 9.4% and a severe IC group consisting of ten patients. Significant prognostic predictors of severity included: right-sided IC (p = 0.0002), guarding (p = 0.001), lack of bleeding per rectum (p = 0.005) and chronic constipation (p = 0.02). CONCLUSIONS: The majority of patients with IC can be managed conservatively. Right-sided IC, guarding, lack of bleeding per rectum and chronic constipation are associated with severe IC.

Rebamipide enema therapy for left-sided ischemic colitis patients accompanied by ulcers: open label study.

AIM: To attempt rectal administration of rebamipide in the treatment of ischemic colitis patients with ulcers, and evaluate its effects. METHODS: We compared 9 ischemic colitis patients (2 men, 7 women) with ulcers treated by bowel rest only from 2000 to 2005 (conventional therapy group), with 6 patients (2 men, 4 women) treated by rebamipide enema therapy in 2006 (rebamipide enema therapy group) and analyzed the mean duration of fasting and hospitalization, degree of ulcer healing, and decrease in WBC count for the two groups. RESULTS: The mean duration of fasting and hospitalization were 2.7+/-1.8 d and 9.2+/-1.5 d in the rebamipide group and 7.9+/-4.1 d and 17.9+/-6.8 d in the control group, respectively, and significantly reduced in the rebamipide group (t= -2.915; P=0.0121 and t= -3.054; P=0.0092). As for the degree of ulcer healing at 7 d after admission, the ulcer score was reduced by 3.5+/-0.5 (points) in the rebamipide group and 2.8+/-0.5 (points) in the control group (t=1.975; P=0.0797), while the decrease in WBC count was 120.0+/-55.8 (x 10(2)/microL) in the rebamipide group and 85.9+/-56.8 (x 10(2)/microL) in the control group (t=1.006; P=0.3360). CONCLUSION: In left-sided ischemic colitis patients with ulcers, rebamipide enema therapy significantly reduced the duration of fasting and hospitalization, recommending its use as a new and effective therapeutic alternative.

Serum procalcitonin (PCT) as a negative screening test for colonic ischemia after open abdominal aortic surgery.

BACKGROUND AND AIM: We assessed serum procalcitonin (PCT) as a screening test for early detection of ischemic colitis. PATIENTS AND METHODS: Ninety-three patients (81 men and 12 women) undergoing elective aortic surgery were enrolled in this study. Their mean age was 70.3+/-8.1 years old. Serum procalcitonin was measured postoperatively. RESULTS: Four patients suffered from colon ischemia. Based on a cut off value of serum PCT>/=2.0 ng/ml, fourteen patients had a false positive but none had a false negative result. Sensitivity was 100%, and specificity was 83.9% in detecting ischemic colitis. Negative predictive vale was 100%. CONCLUSION: Serum PCT is a non-invasive test that has a high negative predictive vale in ruling out colon ischemia after aortic surgery.

Use of serologic markers as a screening tool in inflammatory bowel disease compared with elevated erythrocyte sedimentation rate and anemia.

OBJECTIVES: The purpose of this work was to evaluate the use of serologic testing as a screening test for inflammatory bowel disease compared with erythrocyte sedimentation rate and hemoglobin in a referred patient population with suspected inflammatory bowel disease. PATIENTS AND METHODS: A retrospective study was performed, reviewing medical charts of patients who had inflammatory bowel disease serology performed at Prometheus Laboratories from September 2002 to September 2004. Patients were divided into 4 categories: ulcerative colitis, Crohn disease, indeterminate colitis, and noninflammatory bowel disease groups. Patients were categorized based on clinical evaluation by board-certified pediatric gastroenterologists. RESULTS: A total of 227 patients seen at the Lucile Packard Children's Hospital Gastroenterology Clinic had inflammatory bowel disease serology performed at or before the time of diagnosis. Seventeen charts were excluded secondary to inadequate information. Forty children were found to have inflammatory bowel disease, a prevalence of 19%. Overall, serologic testing for inflammatory bowel disease had 60% sensitivity and 92% specificity. A positive laboratory test for anemia or an elevated erythrocyte sedimentation rate had 83% sensitivity, whereas the combination of anemia and elevated erythrocyte sedimentation rate had 96% specificity. The positive predictive value of serologic testing was 60% compared with 79% in patients with anemia and elevated erythrocyte sedimentation rate. The positive predictive value of serologic testing in the subgroup of subjects without rectal bleeding (139 subjects) was only 35% compared with 60% using routine tests. Almost one third of all positive serologic tests were in patients with no demonstrable inflammatory bowel disease. CONCLUSIONS: As a pediatric inflammatory bowel disease screening strategy for the general pediatrician or gastroenterologist, the measurement of the combination of erythrocyte sedimentation rate and hemoglobin has a higher positive predictive value and is more sensitive, more specific, and less costly than commercial serologic testing.

The effect of transient intestinal ischemia on inflammatory parameters.

BACKGROUND AND AIMS: To determine the early biological changes occurring in intestinal ischemia in vivo. PATIENTS AND METHODS: We studied the effects of acute transient intestinal ischemia in 15 patients undergoing elective open surgery for the treatment of abdominal subrenal aortic aneurysm induced by clamping of the aorta at subrenal level and above the branching of the inferior mesenteric artery. Blocking the blood flow results in hypoperfusion of the inferior mesenteric artery and then to rectal mucosal ischemia. RESULTS: With the introduction of a mucosal ischemic period the basal intestinal mucosal pH decreased during ischemia, and showed a rapid increase during reperfusion to the level preceding ischemia. Parameters were evaluated in blood taken from inferior mesenteric vein. A rectal dialysis was put into the rectum to evaluate eicosanoid concentrations in rectal fluid collected before and during clamping and after declamping. Significant enhancement in plasma level of xanthine, a marker for tissue damage, was observed during reperfusion. Interleukin-6 levels were significantly elevated from 11.28+/-3.4 pg/ml (preischemic) to 109+/-85.9 pg/ml (ischemic) and to 189.33+/-120.24 pg/ml (reperfusion); and tromboxane B(2) levels from 141.57+/-51.20 pg/ml preoperation to 473.01+/-319.01 pg/ml during the surgical procedure. CONCLUSION: These observations indicate that even transient ischemia modifies the inflammatory pattern.

Ischemic colitis during pregnancy and contraceptive medication.

Ischemic bowel disease is generally considered a disease of the elderly and usually consists of reversible colopathy. Nonocclusive causes of ischemic colitis include low-flow states due to cardiac dysfunction and hypovolemia and use of certain medications including progestational medication. We report 2 cases of ischemic colitis in young women. The first one occurred in a young patient who developed three consecutive episodes of ischemic colitis during her pregnancy, whereas the second woman presented with ischemic colitis in relation with the estrogen use. Each episode had a favorable outcome. Having ruled out an infectious cause, or a low blood flow state and in the absence of known thrombogenic disease, we hypothesized the etiology of these ischemic episodes to a high level of circulating estrogens due to pregnancy in the first case and oral contraceptive medication in the second. Physicians treating hemorrhagic colitis in young women should consider the use of contraceptive medication containing estrogens or pregnancy as possible causes.

[Role of coagulation disorders in mesenteric ischemia]. / Place des anomalies de la coagulation dans l'ischémie mésentérique.

Mesenteric ischemic process can lead to bowel infarction or indolent low-grade ischemia. Inherited thrombophilia represents about 30 to 40% of mesenteric vein thrombosis. Analysis of thromboembolism sites occurring during genetic defect of coagulant factors showed that mesenteric thrombosis is the third localization after lung and legs, in equal incidence with cerebral thrombosis. The genetic defects known to be associated with thrombophilia, as deficiencies of protein C, protein S, antithrombin III, and dysfibrinogenemia, are discussed. A special interest is devoted to resistance to activated protein C. Acquired diseases, as myeloproliferative disease or paroxysmal nocturnal hemoglobinemia, inducing thrombosis are also discussed. Recent advances in both basic and clinical research have provided new insights that may be integrated into diagnostic and therapeutic practices.

Effects of perioperative granulocyte colony-stimulating factor on horses with ascending colonic ischemia.

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that regulates the proliferation and maturation of hematopoietic progenitor cells and modulates the function of mature neutrophils. The responses to administration of G-CSF alone, and in combination with antimicrobials, were studied in an equine model of ascending colon ischemia. Complete segmental colonic ischemia (3.75 hours) with pelvic flexure enterotomy was created in four treatment groups. Group 1 horses received recombinant canine G-CSF (10 micrograms/kg, every 24 hours, intramuscularly), gentamicin sulfate (2.2 mg/kg, every 8 hours, intravenously), and potassium penicillin G (40,000 IU/kg, every 6 hours, intravenously). Group 2 horses were treated with the G-CSF vehicle and antimicrobials as for group 1. Group 3 horses received G-CSF and the antimicrobial drug vehicles, and group 4 horses served as the untreated control receiving G-CSF vehicle and antimicrobial vehicles. The results for 20 horses, five horses in each group, were compared. Treatment with G-CSF was associated with an increased concentration of white blood cells, band neutrophils, neutrophils, lymphocytes, and monocytes in the peripheral blood after surgery. Antimicrobial administration had no detectable effect on cell concentrations after surgery. Administration of G-CSF was associated with an increased concentration of nucleated cells in the peritoneal fluid including neutrophils, small mononuclear cells and large mononuclear cells. Horses that developed incisional infections had lower neutrophil concentrations in the peripheral blood on postoperative day 2 than horses without infected incisions. These results suggested that the prophylactic administration of G-CSF may be useful in the treatment of patients at risk for developing neutropenia after surgery.