SUMMARY BackgroundMethotrexate-induced liver damage in psoriasis has led to dermatologic guidelines that stipulate monitoring of liver injury by means of serial liver biopsies. Recent literature data suggest that methotrexate may be considerably less hepatotoxic than previously assumed.

SUMMARYImmunoglobulin D (IgD) is normally present in only low concentrations in serum. In the hyper-IgD and periodic fever syndrome (HIDS), however, serum levels exceed 140 mg/l. This syndrome is further characterized by recurrent inflammatory febrile attacks together with an acute phase response and appearance of cytokines in the circulation. The role of IgD in the pathogenesis of HIDS and its relation to the increased cytokine concentrations is unclear. Therefore, we tested whether IgD, IgG and a 1 -acid glycoprotein (AGP) isolated from human serum influence the synthesis of interleukin-1b (IL-1b), tumour necrosis factor-a (TNF-a), and IL-1ra, as measured by specific radioimmunoassays, in human peripheral blood mononuclear cells (PBMC). Incubation of PBMC with IgD and AGP for 24 hr led to increased release of IL-1b, TNF-a, and IL-1ra. The magnitude of stimulation of IgD exceeded that of AGP; the effect by IgD was dose-dependent and showed a 30-fold (TNF-a) to almost 150-fold (IL-1b) increase at the highest concentration (50 mg/l), while AGP (750 m g/ml) only increased the cytokine secretion fourfold (TNF-a) to almost 30-fold (IL-1b). The effect of IgD on IL-1ra was less dramatic but a fivefold increase was observed at 50 mg/l compared with a 2 . 5-fold increase with AGP. IgD potentiated the effect of lipopolysaccharide (LPS) on secretion of both IL-1b and TNF-a, although the effect was most apparent for TNF-a. Apart from inducing IL-1ra synthesis, IgG did not influence cytokine release in human PBMC. These data indicate that IgD is a potent inducer of TNF-a, IL-1b and IL-1ra and thus may contribute to the pathogenesis of HIDS.

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These results may explain the higher risk of amyloidosis in patients with a SAA1.1/1.1 genotype vs SAA1.5/1.5 or SAA1.1/1.5 genotype. In addition, the impaired degradation of SAA1.5 by MMP-1 could also explain the higher serum SAA concentrations in persons with a SAA1.5 genotype.

Background and objective: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most prevalent complication after ERCP with an incidence of 3.5%. PEP severity is classified according to either the consensus criteria or the revised Atlanta criteria. In this international cohort study we investigated which classification is the strongest predictor of PEP-related mortality. Methods: We reviewed 13,384 consecutive ERCPs performed between 2012 and 2017 in eight hospitals. We gathered data on all pancreatitis-related adverse events and compared the predictive capabilities of both classifications. Furthermore, we investigated the correlation between the two classifications and identified reasons underlying length of stay. Results: The total sample consisted of 387 patients. The revised Atlanta criteria have a higher sensitivity (100 vs. 55%), specificity (98 vs. 72%) and positive predictive value (58 vs. 5%). There is a significant difference (p < 0.001) between the two classifications. In 124 patients (32%), the length of stay was influenced by concomitant diseases. Conclusion: The revised Atlanta classification is superior in predicting mortality and better reflects PEP severity. This has important implications for researchers, clinicians and patients. For the diagnosis of PEP pancreatitis, the consensus criteria remain the golden standard. However, the revised Atlanta criteria are preferable for defining PEP severity. Key summary Established knowledge. Post-ERCP pancreatitis (PEP) is the most prevalent complication of ERCP, with an incidence rate of 3.5%. /home/ueg . Adequate assessment of PEP severity is necessary for researchers and clinicians to predict prognosis and compare efficacy of prophylactic measures for PEP. . Two classification systems for PEP severity exist: the consensus criteria and the revised Atlanta criteria. New findings. Our study shows that the diagnostic performance of the revised Atlanta criteria for PEP-related mortality is better than the consensus criteria, because of its focus on necrosis and organ failure. . In that way, use of the revised Atlanta criteria allows for a better and more objective evaluation of PEP prophylaxis efficacy. . However, the consensus criteria, with its focus on length of hospital stay, could still be useful in light of patient-reported outcome measures and patient-centered care.