Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis

Summary Conclusions Urinary TAP obtained within the first 48 h of the onset of symptoms can distinguish patients with severe acute pancreatitis. Background Urinary trypsinogen activation peptide (TAP) has recently been described as an early marker of severity in acute pancreatitis. Methods In a multicenter study, urine samples were collected for TAP concentration at 6–12, 24, and 48 h after admission from 139 patients with acute pancreatitis (99 with mild disease, 40 with severe disease) and from 50 control patients. Severity of acute pancreatitis was defined by the presence of organ failure and/or pancreatic necrosis on dynamic contrast-enhanced computed tomography. Results Median urinary TAP in the 139 patients with acute pancreatitis compared to the 50 control patients was significantly higher at admission, 4.6 vs 0.8 ng/mL (p<0.001), and 6–12 h, 1.9 vs 0.55 ng/mL (p=0.04). Among patients who presented within 48h of the onset of symptoms, the median urinary TAP for severe pancreatitis (9 patients) compared to mild pancreatitis (40 patients) was significantly higher at admission, 29.6 vs. 3.6 ng/mL (p=0.001). Also, when obtained within 48h of the onset of symptoms, all patients with severe pancreatitis had an admission urinary TAP level>10 ng/mL. The sensitivity and specificity of an admission urinary TAP≥10 for severe pancreatitis was 100 and 85%, respectively. Given a cutoff of 10 ng/mL for an admission urinary TAP obtained within 48h of the onset of symptoms, the negative predictive value was 100% for mild pancreatitis.     

Prediction of the severity of acute pancreatitis on admission by urinary trypsinogen activation peptide: A meta-analysis

AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission. METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAPvs Acute Physiology and Chronic Health Evaluation Ⅱ within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27vs 4.61, respectively. CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis.     

Urinary excretion of trypsinogen activation peptide (TAP) in taurocholate-induced pancreatitis in rats

Trypsinogen activation peptide (TAP) is a useful marker of severe acute pancreatitis. However, it is sometimes difficult to detect an elevation of plasma TAP in patients with acute pancreatitis because TAP is rapidly cleared from plasma. Therefore, urine TAP has been evaluated to provide an accurate prediction of the outcome of pancreatitis. In the present study, we examined the time course of plasma and urine TAP simultaneously after induction of taurocholate-induced pancreatitis in rats. Plasma TAP levels peaked at 1 hour after the induction of pancreatitis and then gradually decreased, but was still higher than prepancreatitis levels at 48 hours. Significant increases in urine TAP levels were seen at 0-6, 6-12, and 30-36 hours after induction of pancreatitis. The peak level of urine TAP output and TAP/creatinine ratio was observed at 6-12 and 30-36 hours, respectively. Urine TAP concentration showed a significant correlation with both urine TAP/creatinine ratio and TAP output in urine (p < 0.01). In conclusion, plasma TAP increased immediately after the induction of pancreatitis, but excretion of TAP into urine was delayed several hours in taurocholate-induced pancreatitis in rats. The measurement of urine TAP concentration alone sufficiently can reflect the amount of TAP liberated in the pancreas at initial stage of acute pancreatitis.     

Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis:A multicenter study in Japan

BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide(TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis.AIM To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan.METHODS Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography(CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria.RESULTS A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis(sensitivity,73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis(specificity, 62.5%). The area under the curve(AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade.CONCLUSION We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.     

Fecal calprotectin is more accurate than fecal immunochemical test for predicting mucosal healing in quiescent ulcerative colitis: a prospective multicenter study

Abstract

Objective: Non-invasive stool tests, including the fecal immunochemical test (FIT) and fecal calprotectin (FC), are reliable biomarkers for mucosal healing (MH) in ulcerative colitis (UC). However, which fecal test is superior for predicting MH in inactive UC patients requires evaluation. We aimed to compare the accuracy of FIT and FC results for predicting MH in quiescent UC patients.

Methods: This prospective, multicenter study was conducted at three tertiary hospitals. UC patients in clinical remission for at least three?months underwent colonoscopy and MH was evaluated using the Mayo endoscopic sub-score (MES). The receiver operating characteristic (ROC) curve and cutoff value with the best accuracy for predicting MH were assessed.

Results: Among 127 patients, 65 (51.2%) showed MH (MES = 0). The area under the curve (AUC) for predicting MH (MES = 0) was significantly higher for FC than for FIT (AUC 0.858 (95% confidence interval (CI) 0.784–0.913) vs. 0.707 (95% CI 0.620–0.784), p?<?.001); there was no difference when MH included MES = 1 (MES ≤ 1) (AUC 0.820 (95% CI 0.742–0.883) vs. 0.813 (95% CI 0.734–0.877), p?=?.891). When the cutoff value was 70?μg/g for FC and 10?ng/mL for FIT, the sensitivity, specificity, positive predictive value and negative predictive value were 89.2, 71, 76.3, and 86.3, respectively, for FC and 92.3, 50, 65.9, and 86.1, respectively, for FIT.

Conclusion: FC is more accurate than FIT for predicting MH in quiescent UC patients. The superiority of FC might be related to the distinctive performance of FC in differentiating inflammatory levels, particularly in low-grade mucosal activity.     

Renal doppler changes in patients with acute pancreatitis: A prospective study

BackgroundRenal Doppler to assess renal resistive index (RRI) is an attractive option to prognosticate acute kidney injury (AKI) in acute pancreatitis (AP) as it is feasible within scope of point-of-care ultrasound. However, RRI has been infrequently evaluated in AP.ObjectiveProspectively study diagnostic and prognostic performance of RRI in patients with AP.Methodology75 patients with AP were prospectively enrolled and followed till recovery/death. All patients were subjected to renal Doppler and RRI was compared between patients with and without AKI.ResultsThirty six patients developed AKI and 39 patients did not develop AKI. AKI network stage 1, 2 and 3 AKI was seen in 7(19.4%), 12(33.3%) and 17 (47.2%) patients respectively. Prognostic scoring done at admission by SIRS, modified marshal score, and BISAP scores, as well as duration of hospitalization and mortality rates were significantly higher in patients with AKI. Mean peak systolic velocity and RRI at upper, middle and lower poles of bilateral kidneys were comparable between patients with and without AKI. The RRI was abnormal in 46 (66.6%) patients and it was <0.6 in 35/46 (76%) and >0.7 in 11/46 (24%) patients respectively. RRI <0.6 was observed in 16 (53.3%) and 19 (48.7%) patients with and without AKI respectively (p = 0.80). RRI >0.7 was observed in 4 (53.3%) and 7 (48.7%) patients with and without AKI respectively (p = 0.74).ConclusionsAKI is associated with poor prognosis in AP. RRI on renal Doppler at admission seems to have poor diagnostic as well as prognostic performance for AKI in patients with AP.     

Quality of life in elderly patients with acute myeloid leukemia: patients may be more accurate than physicians

Background

The aim of this study was to evaluate changes in quality of life scores and their association with therapy and survival in unselected elderly patients with acute myeloid leukemia.

Design and Methods

From February 2003 to February 2007, 113 patients aged more than 60 years with de novo acute myeloid leukemia were enrolled in a prospective observational study. Two different quality of life instruments were employed: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – C30 (EORTC QLQ-C30) and a health-related quality of life questionnaire for patients with hematologic diseases (QOL-E).

Results

Forty-eight patients (42.4%) received intensive chemotherapy and 65 (57.6%) were given palliative treatments. Age greater than 70 years (P=0.007) and concomitant diseases (P=0.019) had a significant impact on treatment allocation. At diagnosis, general quality of life was affected [median QOL-E standardized score 54, interquartile range 46–70; median EORTC global score 50, interquartile range 41–66]. Most patients were given a good ECOG Performance Status (< 2), which did not correlate with the patients’ perception of quality of life. At multivariate analysis, palliative approaches (P=0.016), age more than 70 years (P=0.013) and concomitant diseases (P=0.035) each had an independent negative impact on survival. In a multivariate model corrected for age, concomitant diseases and treatment option, survival was independently predicted by QOL-E functional (P=0.002) and EORTC QLQ-C30 physical function (P=0.030) scores.

Conclusions

Quality of life could have an important role in elderly acute myeloid leukemia patients at diagnosis as a prognostic factor for survival and a potential factor for treatment decisions.     

肥胖者重症急性胰腺炎发生率的多中心前瞻性对照研究

目的 观察肥胖的急性胰腺炎(AP)患者在基础内科治疗过程中发展为重症急性胰腺炎(SAP)的概率,探讨肥胖对AP病情发展的影响.方法 采用多中心、前瞻性研究,以APACHEⅡ评分评估AP严重程度,共纳入轻症急性胰腺炎(MAP)患者161例,以体重指数25 kg/m2为标准,分为肥胖组(79例)和非肥胖组(82例).在相同的基础内科治疗条件下观察两组患者血C-反应蛋白(CRP)和三酰甘油水平、并发症发生率、SAP的发生率及病死率.结果 肥胖组的CRP水平为(117±109)mg/L,显著高于非肥胖组的(35±36)mg/L(P＜0.01);肥胖组高三酰甘油血症患者的例数是非肥胖组的1倍,但无显著性差异.两组均无局部并发症,但肥胖组各系统并发症发生率(20.3%)显著高于非肥胖组(6.1%,P＜0.01).肥胖组有16例(20.3%)发展为SAP,显著高于非肥胖组(5例,6.1%,P＜0.01).肥胖组有1例(1.3%)病死,非肥胖组无病死.在APACHEⅡ4-7分的MAP患者中,肥胖组的SAP发生率(43.3%)明显高于非肥胖组(18.5%,P＜0.05).结论 肥胖且 APACHEⅡ评分为4-7分的MAP 患者更易进展为SAP,应给予更积极的临床干预措施.     

Hemoconcentration is a poor predictor of severity in acute pancreatitis

AIM: To determine whether the hematocrit (Hct) at admission or at 24 h after admission was associated with severe acute pancreatitis (AP), organ failure (OF), and pancreatic necrosis. METHODS: A total of 336 consecutive patients with a first AP episode were studied. Etiology, Hct values at admission and at 24 h, development of severe AP according to Atlanta's criteria, pancreatic necrosis, OF and mortality were recorded. Hemoconcentration was defined as Hct level >44% for males and >40% for females. The t-test and X2 test were used to assess the association of hemoconcentration to the severity, necrosis and OF. Diagnostic accuracy was also determined. RESULTS: Biliary disease was the most frequent etiology (n = 148). Mean Hct levels at admission were 41±6% for females and 46±7% for males (P<0.01). Seventy-eight (23%) patients had severe AP, and OF developed in 45 (13%) patients. According to contrast-enhanced computed tomography scan, 36% (54/150) patients showed pancreatic necrosis. Hct levels were elevated in 58% (55/96) and 61% (33/54) patients with interstitial and necrotizing pancreatitis, respectively. Neither Hct levels at admission nor hemoconcentration at 24 h were associated with the severity, necrosis or OF. Sensitivity, specificity and positive predictive values for both determinations were very low; and negative predictive values were between 61% and 86%, being the highest value for OF. CONCLUSION: Hct is not a useful marker to predict a worse outcome in acute pancreatitis. In spite of the high negative predictive value of hemoconcentration, the prognosis gain is limited due to an already high incidence of mild disease.     

APACHE system is better than Ranson system in the prediction of severity of acute pancreatitis

BACKGROUND: It has been suggested that addition of obesity score to the APACHE-Ⅱ system can lead to more accurate prediction of severity of acute pancreatitis. However there is scanty information on the usefulness of the combined APACHE-O scoring system in Asian patients. This study aimed to compare the accuracy of Ranson, APACHE-Ⅱ and APACHE-O systems in assessing severity of acute pancreatitis in a local Chinese population. METHODS: One hundred and one consecutive patients with acute pancreatitis were prospectively studied. Body mass index (BMI) was measured on admission. Ranson score, APACHE-Ⅱ and APACHE-O scores were recorded on admission and at 48 hours. By adopting the cut-off levels and definitions advocated in the Atlanta consensus for severe disease, the diagnostic accuracy of the three scoring systems was compared by the area under the curve (AUC) under the receiver operator characteristic curve. RESULTS: Of the 101 patients, 12 (11.9%) patients suffered from severe pancreatitis. Obesity was uncommon and only two patients (2.0%) had BMI >30. Eighty-two (81.2%) patients were normal weight (BMI≤25) whereas 17 (16.8%) were overweight ( BMI 25-30 ). Overweight or obesity (BMI >25) was not associated with severe pancreatitis (P= 0.40). The AUC for admission scores of Ranson, APACHE-Ⅱ, and APACHE-O systems was 0. 549, 0. 904 and 0. 904, respectively. The AUC for 48-hour scores of Ranson, APACHE-Ⅱ and APACHE-O systems was 0.808, 0.955 and 0.951, respectively. CONCLUSIONS: The APACHE-Ⅱ scoring system is more accurate than the Ranson scoring system of the prediction of severity in acute pancreatitis. Addition of obesity score does not significantly improve the predictive accuracy of the APACHE-Ⅱ system in our local population with a low prevalence of obesity.     

d-dimer as a marker of severity in patients with severe acute pancreatitis

Background/purpose

Coagulative disorder is known to occur in the early phase of severe acute pancreatitis (SAP) and d-dimer is a commonly used clinical parameter of hemostasis. The aim of this study was to assess the value of the plasma d-dimer level as a marker of severity in the first 3?days after admission in patients with SAP.

Methods

From January 2009 to February 2011, 45 patients admitted for SAP were included in this observational study. The d-dimer level was measured on a daily basis during days 1?C3 after admission and the acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and other clinical parameters were recorded at the same time. The maximum and the mean d-dimer values were used for analysis and compared with other prognostic factors of SAP.

Results

Both the maximum and mean levels of d-dimer were significantly different between patients with and without clinical variables such as multiple-organ dysfunction syndrome (MODS), need for surgical intervention, and the presence of pancreatic infection. The d-dimer level also showed great precision for the prediction of MODS and secondary infection. Additionally, the d-dimer level correlated well with two usual markers of SAP severity?Cthe APACHE II score and the C-reactive protein level.

Conclusion

d-dimer measurement is a useful, easy, and inexpensive early prognostic marker of the evolution and complications of SAP.     

Clinical value of rapid urine trypsinogen-2 test strip, urinary trypsinogen activation peptide, and serum and urinary activation peptide of carboxypeptidase B in acute pancreatitis

AIM: To assess the usefulness of urinary trypsinogen-2 test strip, urinary trypsinogen activation peptide (TAP), and serum and urine concentrations of the activation peptide of carboxypeptidase B (CAPAP) in the diagnosis of acute pancreatitis. METHODS: Patients with acute abdominal pain and hospitalized within 24 h after the onset of symptoms were prospectively studied. Urinary trypsinogen-2 was considered positive when a clear blue line was observed (detection limit 50 μg/L). Urinary TAP was measured using a quantitative solid-phase ELISA, and serum and urinary CAPAP by a radioimmunoassay method. RESULTS: Acute abdominal pain was due to acute pancreatitis in 50 patients and turned out to be extrapancreatic in origin in 22 patients. Patients with acute pancreatitis showed significantly higher median levels of serum and urinary CAPAP levels, as well as amylase and lipase than extrapancreatic controls. Median TAP levels were similar in both groups. The urinary trypsinogen-2 test strip was positive in 68% of patients with acute pancreatitis and 13.6% in extrapancreatic controls (P<0.01). Urinary CAPAP was the most reliable test for the diagnosis of acute pancreatitis (sensitivity 66.7%, specificity 95.5%, positive and negative predictive values 96.6% and 56.7%, respectively), with a 14.6 positive likelihood ratio for a cut-off value of 2.32 nmol/L. CONCLUSION: In patients with acute abdominal pain, hospitalized within 24 h of symptom onset, CAPAP in serum and urine was a reliable diagnostic marker of acute pancreatitis. Urinary trypsinogen-2 test strip showed a clinical value similar to amylase and lipase. Urinary TAP was not a useful screening test for the diagnosis of acute pancreatitis.