New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare. METHODS AND ANALYSIS: This is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19-9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM. ETHICS AND DISSEMINATION: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04164602.

[Changes in antibiotic resistance in cholangitis. Our clinical experience]. / Az antibiotikumrezisztencia változása cholangitisben. Klinikai tapasztalataink.

Introduction: Due to the inappropriate use of antibiotics (AB), more pathogens become multiresistant. One of the most severe sources of sepsis is cholangitis. To avoid fatal outcome, an effective AB policy plays a key role. Aim: To investigate the AB resistance of bacteria causing cholangitis and the efficacy of AB treatment. Patients and method: Microbiological tests of bile samples collected during cholangitis-indicated endoscopic retrograde cholangiopancreatographies were analysed at the First Department of Medicine, University of Szeged, in 2006 and in 2016. Results: 29 and 111 patients had bile sample collection in 2006 and in 2016, respectively. Of that, 22 (75%) and 106 (95%) were positive. Mean age: 61 ± 14 vs. 71 ± 14 years, no difference between men/women ratio. In 2006, 10 cases empirical AB (ciprofloxacine with metronidazole or imipenem) were used. In 9 cases (90%), the AB was adequate based on the microbiological results. In 2016, in 88 cases empirical AB was applied (ciprofloxacine and metronidazole, ceftriaxone with metronidazole or imipenem with metronidazole). In 29 cases, the empirical AB was ineffective. The efficacy of ciprofloxacine decreased to 64% in 2016. The profile of the most frequent cholangitis-causing pathogens (Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae) was the same, but their resistency against ciprofloxacine increased. The rates of polymicrobal infections were 73% and 63%, respectively. Conclusion: The rates of positive bile samples were significantly higher in 2016. The profile of the most frequent pathogens was the same. The efficacy of the first-choice empirical AB ciprofloxacine decreased in 2016. The types of the most frequent cholangitis-causing bacteria are in line with the ones included in the Tokyo Guideline. Orv Hetil. 2019; 160(36): 1437-1442.

In New-Onset Diabetes Mellitus, Metformin Reduces Fat Accumulation in the Liver, But Not in the Pancreas or Pericardium.

Background: Nonalcoholic fatty pancreas and liver disease (NAFPD and NAFLD) and pericardial adipose tissue (PAT) are often associated with type 2 diabetes mellitus (T2DM). Our aim was to evaluate the incidence rate of NAFLD and NAFPD, PAT size, and the effect of metformin treatment on NAFLD, NAFPD, and PAT in new-onset T2DM (NODM). Methods: Seventeen patients with NODM and 10 subjects used as a control group were involved in the study. Computed tomography (CT) and laboratory tests were performed before the beginning of metformin therapy and 4 months afterward. PAT and the amount of fat in the pancreas and liver were determined by X-ray attenuation during unenhanced CT examination and compared with the values for the control subjects. Results: Metabolic parameters improved significantly after metformin therapy. NAFLD was diagnosed in 64.7% of the patients with NODM and in 10% of the control subjects. The radiation absorption of the liver was significantly lower in the patients with NODM compared with the control group and significantly higher after metformin therapy compared with the baseline values. Only six patients (35.3%) had NAFLD after metformin therapy. NAFPD was diagnosed in 82.3% of the patients with NODM and in 20% of the control subjects. The radiation absorption of the pancreas was significantly lower in the patients with NODM compared with the control group but did not change significantly after treatment. PAT size was significantly larger in the patients with NODM and did not change significantly after metformin treatment. Conclusions: NAFLD, NAFPD, and increased PAT were detected in the majority of patients with NODM. Metformin therapy decreased the amount of fat in the liver in parallel with an improvement in the metabolic parameters and may, thus, be beneficial for preventing the late consequences of NAFLD.

The effect of serum triglyceride concentration on the outcome of acute pancreatitis: systematic review and meta-analysis.

Elevated serum triglyceride concentration (seTG, >1.7 mM or >150 mg/dL) or in other words hypertriglyceridemia (HTG) is common in the populations of developed countries. This condition is accompanied by an increased risk for various diseases, such as acute pancreatitis (AP). It has been proposed that HTG could also worsen the course of AP. Therefore, in this meta-analysis, we aimed to compare the effects of various seTGs on the severity, mortality, local and systemic complications of AP, and on intensive care unit admission. 16 eligible studies, including 11,965 patients were retrieved from PubMed and Embase. The results showed that HTG significantly elevated the odds ratio (OR = 1.72) for severe AP when compared to patients with normal seTG (<1.7 mM). Furthermore, a significantly higher occurrence of pancreatic necrosis, persistent organ failure and renal failure was observed in groups with HTG. The rates of complications and mortality for AP were significantly increased in patients with seTG >5.6 mM or >11.3 mM versus <5.6 mM or <11.3 mM, respectively. We conclude that the presence of HTG worsens the course and outcome of AP, but we found no significant difference in AP severity based on the extent of HTG.

Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review.

The exocrine and endocrine pancreata are very closely linked both anatomically and physiologically. Abdominal symptoms such as nausea, bloating, diarrhea, steatorrhea, and weight loss can often occur in diabetic patients. Impairments of the exocrine pancreatic function seem to be a frequent complication of diabetes mellitus; however, they are largely overlooked. The aim of this paper is to provide an overview of the current concepts of exocrine pancreatic insufficiency (PEI) in diabetes mellitus. The prevalence and symptoms of PEI in diabetes mellitus, the pathomechanism, and difficulties of diagnosis and therapy of PEI are summarized in this systematic review.