IntroductionPredicting severity of pancreatitis is an important goal. Clinicians are still searching for novel and simple biomarkers that can better predict persistent organ failure (OF). Lipoproteins, especially high-density lipoprotein (HDL), and apolipoprotein A-I (APO A-I), have been shown to have anti-inflammation effects in various clinical settings. Severe acute pancreatitis (SAP) is associated with hypo-lipoproteinemia. We studied whether the concentrations of HDL and APO A-I can predict persistent OF in patients with predicted SAP admitted to the ICU.MethodsIn 66 patients with predicted SAP, we prospectively evaluated the relationship between lipid levels, inflammatory cytokines and clinical outcomes, including persistent OF and hospital mortality. Blood samples were obtained within 24 hours of admission to the ICU.ResultsHDL and APO A-I levels were inversely correlated with various disease severity scores. Patients with persistent OF had lower levels of HDL and APO A-I, while those with transient OF had lower levels of interleukin-6, tumor necrosis factor-α and lower rates of hospital mortality. Meanwhile, hospital non-survivors had lower concentrations of HDL, and APO A-I compared to the survivors. By using the area under the receiver operating characteristic (AUROC) curve, both HDL and APO A-I demonstrated an excellent discriminative power for predicting persistent OF among all patients (AUROC 0.912 and 0.898 respectively) and among those with OF (AUROC 0.904 and 0.895 respectively). Pair-wise comparison of AUROC showed that both HDL and APO A-I had better discriminative power than C-reactive protein to predict persistent OF.ConclusionsSerum levels of HDL and APO A-I at admission to the ICU are inversely correlated with disease severity in patients with predicted SAP and can predict persistent OF in this clinical setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0832-x) contains supplementary material, which is available to authorized users.

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Key points Diabetic kidney disease (DKD) is a major complication of diabetes. We found that UTX (ubiquitously transcribed tetratricopeptide repeat on chromosome X, also known as KDM6A), a histone demethylase, was upregulated in the renal mesangial and tubular cells of diabetic mice and DKD patients. In cultured renal mesangial and tubular cells, UTX overexpression promoted palmitic acid‐induced elevation of inflammation and DNA damage, whereas UTX knockdown or GSK‐J4 treatment showed the opposite effects. We found that UTX demethylase activity‐dependently regulated the transcription of inflammatory genes and apoptosis; moreover, UTX bound with p53 and p53‐dependently exacerbated DNA damage. Administration of GSK‐J4, an H3K27 demethylase inhibitor, ameliorated the diabetes‐induced renal abnormalities in db/db mice, an animal model of type 2 diabetes. These results revealed the possible mechanisms underlying the regulation of histone methylation in DKD and suggest UTX as a potential therapeutic target for DKD. Abstract Diabetic kidney disease (DKD) is a microvascular complication of diabetes and the leading cause of end‐stage kidney disease worldwide without effective therapy available. UTX (ubiquitously transcribed tetratricopeptide repeat on chromosome X, also known as KDM6A), a histone demethylase that removes the di‐ and tri‐methyl groups from histone H3K27, plays important biological roles in gene activation, cell fate control and life span regulation in Caenorhabditis elegans. In the present study, we report upregulated UTX in the kidneys of diabetic mice and DKD patients. Administration of GSK‐J4, an H3K27 demethylase inhibitor, ameliorated the diabetes‐induced renal dysfunction, abnormal morphology, inflammation, apoptosis and DNA damage in db/db mice, comprising an animal model of type 2 diabetes. In cultured renal mesanglial and tubular cells, UTX overexpression promoted palmitic acid induced elevation of inflammation and DNA damage, whereas UTX knockdown or GSK‐J4 treatment showed the opposite effects. Mechanistically, we found that UTX demethylase activity‐dependently regulated the transcription of inflammatory genes; moreover, UTX bound with p53 and p53‐dependently exacerbated DNA damage. Collectively, our results suggest UTX as a potential therapeutic target for DKD.

BackgroundTuberculosis is one of the major infectious diseases in Taiwan. It has an especially high prevalence in diabetes patients, in whom it is usually asymptomatic and are more likely to result in drug-resistant tuberculosis. The aim of the study was to aggressively screen high risk diabetic elderly, identify the prevalence of tuberculosis and its determinants.MethodsType 2 diabetes patients aged over 65 years were enrolled. They received chest X-rays, blood tests and the questionnaires to assess their medical history and symptoms. Suspicious cases were referred to the pulmonary or infectious disease outpatient clinics. Pulmonary tuberculosis was confirmed by sputum culture. Variables between groups were analyzed by Student t test, Chi-square test or Fisher’s exact test. Risk factors were assessed using univariate logistic regression and multiple logistic regression.ResultsA total of 3,087 patients participated this screening program and 7 patients screened positive for pulmonary tuberculosis. Another 5 patients were being under treatment when participating screening program. The prevalence rate was 3.89 per thousand people. The patients with male gender, smoking, liver cirrhosis or subjective body weight loss were associated with an increased risk of tuberculosis significantly. Subjective body weight loss (OR: 6.635 [95% CI: 2.096-21.007]), liver cirrhosis (OR: 10.307 [95% CI: 2.108-50.395]) and history of smoking (OR: 3.981 [95% CI: 1.246-12.718]) are independent risk factors. Among all 73 patients with active tuberculosis or tuberculosis history, they tended to be male, lower body mass index (BMI), more smoking history, more alcohol consumption, more family history of tuberculosis, higher low density lipoprotein (LDL), and less hypertension. However, there was no significant difference in the glycated hemoglobin (HbA1c) levels between the tuberculosis group and non-tuberculosis group.ConclusionsActive screening program is helpful in detecting pulmonary tuberculosis in elderly diabetes patients. Subjective body weight loss, smoking and liver cirrhosis are independent risk factors.