Non-pancreatic hyperlipasemia: A puzzling clinical entity.

BACKGROUND: Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism. This non-pancreatic hyperlipasemia (NPHL) is puzzling for attending physicians during the diagnostic procedure for AP. It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it. A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking. AIM: To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes. METHODS: A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal (ULN) was prospectively evaluated over 31 months. Patients were identified using daily electronic laboratory reports developed to support an ongoing observational, multicenter, prospective cohort study called the EASY trial (ISRCTN10525246) to establish a simple, easy, and accurate clinical scoring system for early prognostication of AP. Diagnosis of NPHL was established based on ≥ 3 × ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis. RESULTS: A total of 808 patients [male, n = 420 (52%); median age (IQR): 65 (51-75) years] were diagnosed with ≥ 3 × ULN serum lipase levels. A total of 392 patients had AP, whereas 401 had NPHL with more than 20 different etiologies. Sepsis and acute kidney injury (AKI) were the most prevalent etiologies of NPHL (27.7% and 33.2%, respectively). The best discriminative cut-off value for lipase was ≥ 666 U/L (sensitivity, 71.4%; specificity, 88.8%). The presence of AKI or sepsis negatively affected the diagnostic performance of lipase. NPHL was associated with a higher in-hospital mortality than AP (22.4% vs 5.1%, P < 0.001). In multivariate binary logistic regression, not lipase but increased amylase level (> 244 U/L) and neutrophil-to-lymphocyte ratio (NLR) (> 10.37, OR: 3.71, 95%CI: 2.006-6.863, P < 0.001), decreased albumin level, age, and presence of sepsis were independent risk factors for in-hospital mortality in NPHL. CONCLUSION: NPHL is a common cause of lipase elevation and is associated with high mortality rates. Increased NLR value was associated with the highest mortality risk. The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.

Correction to: A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis.

In the Original article, the legend of Figures 3 and 4 are interchanged and line number 387 is incomplete.

A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis.

Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = - 0.4, p = 0.009) and between vWF:Ag and TH2 (R = - 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease.

AIM: To assess the prevalence and stability of different antiphospholipid antibodies (APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases (IBD) patients. METHODS: About 458 consecutive patients [Crohn's disease (CD): 271 and ulcerative colitis (UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course (development f complicated disease phenotype and need for surgery), occurrence of thrombotic events, actual state of disease activity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up, (median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls (HC) were tested on individual anti-ß2-Glycoprotein-I (anti-ß2-GPI IgA/M/G), anti-cardiolipin (ACA IgA/M/G) and anti-phosphatidylserine/prothrombin (anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies (ASCA IgA/G) by enzyme-linked immunosorbent assay (ELISA). In a subgroup of CD (n = 198) and UC patients (n = 103), obtaining consecutive samples over various arbitrary time-points during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally, we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed. RESULTS: Patients with CD had significantly higher prevalence of both ACA (23.4%) and anti-PS/PT (20.4%) antibodies than UC (4.8%, P < 0.0001 and 10.2%, P = 0.004) and HC (2.9%, P < 0.0001 and 15.5%, P = NS). No difference was found for the prevalence of anti-ß2-GPI between different groups (7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients. Occurrence of anti-ß2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-ß2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes. Changes in antibody status were more remarkable in CD than UC (ACA IgA: 49.9% vs 23.3% and ACA IgG: 21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis. CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However, presence of different APLAs were not associated with the clinical phenotype or disease course.