Camilla Nøjgaard

Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

BACKGROUND/AIMS YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS Three hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS Serum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004). CONCLUSIONS Serum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information.

Serum levels of YKL-40 increases in patients with acute myocardial infarction.

ObjectivesYKL-40 is secreted by macrophages, including those in atherosclerotic plaques, neutrophils, and vascular smooth muscle cells. Circulating YKL-40 is elevated in patients with inflammation and increased tissue remodeling. The aim was to examine the sequential changes in serum YKL-40 in patients with acute myocardial infarction (AMI), with and without thrombolytic therapy, as compared with patients with stable coronary artery disease (CAD). MethodsYKL-40 was measured by radioimmunoassay in serum from 63 patients. A total of 47 patients had their first AMI [30 with ST segment elevation myocardial infarction (STEMI) were thrombolyzed, 17 with non-STEMI were not thrombolyzed] and 16 patients had CAD. ResultsSerum YKL-40 at the time of admission was higher in patients with AMI (median: 156 μg/l, range: 40–3000 μg/l) than in patients with CAD (median: 106 μg/l, range: 54–300 μg/l, P=0.048) and healthy participants (median: 102 μg/l, range: 38–514 μg/l, P<0.001). No difference in serum YKL-40 between CAD patients and healthy participants (P=0.89) was observed. No difference in serum YKL-40 between the AMI patients with or without ST-elevations (P=0.12) was observed. The maximum serum YKL-40 during the first 24 h after admission was higher in thrombolyzed STEMI patients than in the nonthrombolyzed, non-STEMI patients (P=0.01) and the CAD patients (P<0.0001). Serum YKL-40 declined consistently from the maximum value just after the AMI and during follow-up. Serum YKL-40 at 90, 180, and 360 days after AMI were significantly higher in nonthrombolyzed than in thrombolyzed patients (P=0.004, P=0.008, P=0.017, respectively). ConclusionThese results demonstrated that serum concentrations of YKL-40 are greatly increased in AMI patients with and without thrombolytic therapy.

Danish Patients With Chronic Pancreatitis Have a Four-Fold Higher Mortality Rate Than the Danish Population

BACKGROUND & AIMS We investigated mortality of patients with chronic pancreatitis (CP), compared with the Danish population and sought to determine whether clinical presentations of CP can be used in prognosis. We also investigated clinical factors associated with mortality and causes of death among these patients. METHODS The Copenhagen Pancreatitis Study is a prospective study of patients admitted from 1977 to 1982 to the 5 main hospitals in Copenhagen with a diagnosis of acute pancreatitis or CP. In 2008, follow-up data were collected from these patients from the Danish Registries; this subcohort comprised 290 patients with probable (n = 41) or definite CP (n = 249). RESULTS The mortality of patients with definite CP was 4-fold that of the Danish population and significantly higher than that of patients with probable CP (P = .003; 95% confidence interval [CI], 1.21-2.57); patients with probable CP had a 2- to 3-fold higher mortality rate than the population. In patients with definite CP, factors significantly associated with mortality included non-employment (P = .015; 95% CI, 0.53-0.93), and being underweight (P = .020; 95% CI, 0.52-0.95). Sex, alcohol use, smoking, single versus co-living, exocrine insufficiency, diabetes, pancreatic calcification, CP inheritance, painless CP, acute exacerbation of CP, or surgery for CP had no impact on survival. The most frequent causes of death were digestive diseases (19.5%), malignancies (19.5%), and cardiovascular diseases (11.3%). CONCLUSIONS Danish patients with definite CP had a 4-fold higher mortality rate compared with the background population and a higher mortality rate than patients with probable CP. Being nonemployed or underweight had significant impact on survival.

Meta‐analysis: nitroglycerin for prevention of post‐ERCP pancreatitis

Background  Acute pancreatitis after ERCP is a severe side effect.

Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial

OBJECTIVE Acute pancreatitis is the most dreaded complication of ERCP. Two studies have shown a significant effect of glyceryl nitrate (GN) in preventing post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a larger study with a realistically precalculated incidence of PEP. DESIGN/PATIENTS A randomized, double-blind, placebo-controlled multicenter study including patients from 14 European centers was performed. A total of 820 patients were entered; 806 were randomized. INTERVENTION The active drug was transdermal GN (Discotrine/Minitran, 3M Pharma) 15 mg/24 hours; placebo (PL) was an identical-looking patch applied before ERCP. A total of 401 patients received GN; 405 received PL. RESULTS Forty-seven patients had PEP (5.8%), 18 (4.5%) in the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in the GN group of 36% (95% CI, 11%-65%) compared with the PL group was not statistically significant (P = .11). Thirteen had mild pancreatitis (4 in the GN group, 9 in the PL group), 26 had moderate pancreatitis (9 in the GN group, 17 in the PL group), and 8 had severe pancreatitis (5 in the GN group, 3 in the PL group). Headache (P < .001) and hypotension (P = .006) were more common in the GN group. Significant variables predictive of PEP were not having biliary stones extracted; hypotension after ERCP; morphine, propofol, glucagon, and general anesthesia during the procedure; or no sufentanil during the procedure. CONCLUSIONS The trial showed no statistically significant preventive effect of GN on PEP. Because of a considerable risk of a type II error, an effect of GN may have been overlooked. (ClinicalTrials.gov ID: NCT00121901.).

Factors associated with long-term mortality in acute pancreatitis

Abstract Background and aims. Knowledge of the long-term prognosis of acute pancreatitis (AP) is limited. The aims were to investigate: (1) prognostic factors associated with long-term mortality in patients with AP; (2) whether or not the level of serum (S-)amylase at admission had an impact on the prognosis; (3) causes of death in these patients. Methods. During 1977–1982, patients who were admitted to the five main hospitals in Copenhagen with a diagnosis of AP or chronic pancreatitis (CP) were included in a prospective cohort, the Copenhagen Pancreatitis Study (CPS); in 2008, they were followed up by linkage to the Danish Registries. The analyzed subcohort consisted of 352 patients with probable AP (n = 54) or definite AP (n = 298). Results. Multivariate Cox regression analysis showed that significant factors associated with mortality were age, alcohol, and diabetes, whereas female gender, co-living and employment were associated with better survival. The S-amylase level had no impact on mortality. The most frequent causes of death were cardiovascular diseases, digestive diseases, and malignancies. Conclusions. Age, alcohol and diabetes had a significant impact on survival whereas the S-amylase level did not.

Update of exocrine functional diagnostics in chronic pancreatitis

Diagnostics of pancreatic insufficiency rely mainly on tests of pancreatic exocrine function based on either measurement of pancreatic secretion or the secondary effects resulting from lack of digestive enzymes or imaging modalities. These methods have been developing rapidly over the last decades, and the aims of this review were to describe exocrine functional testing and imaging of the pancreas in chronic pancreatitis..

The Scandinavian baltic pancreatic club (SBPC) database: design, rationale and characterisation of the study cohort

Abstract Objectives: Chronic pancreatitis (CP) is a multifaceted disease associated with several risk factors and a complex clinical presentation. We established the Scandinavian Baltic Pancreatic Club (SBPC) Database to characterise and study the natural history of CP in a Northern European cohort. Here, we describe the design of the database and characteristics of the study cohort. Methods: Nine centres from six different countries in the Scandinavian-Baltic region joined the database. Patients with definitive or probable CP (M-ANNHEIM diagnostic criteria) were included. Standardised case report forms were used to collect several assessment variables including disease aetiology, duration of CP, preceding acute pancreatitis, as well as symptoms, complications, and treatments. The clinical stage of CP was characterised according to M-ANNNHEIM. Yearly follow-up is planned for all patients. Results: The study cohort comprised of 910 patients (608 men: 302 women; median age 58 (IQR: 48–67) years with definite 848 (93%) or probable CP 62 (7%). Nicotine (70%) and alcohol (59%) were the most frequent aetiologies and seen in combination in 44% of patients. A history of recurrent acute pancreatitis was seen in 49% prior to the development of CP. Pain (69%) and exocrine pancreatic insufficiency (68%) were the most common complications followed by diabetes (43%). Most patients (30%) were classified as clinical stage II (symptomatic CP with exocrine or endocrine insufficiency). Less than 10% of the patients had undergone pancreatic surgery. Conclusion: The SBPC database provides a mean for future prospective, observational studies of CP in the Northern European continent.