Necessity of transnasal gastroscopy in routine diagnostics: a patient-centred requirement analysis.

INTRODUCTION: Numerous indications require regular upper gastrointestinal endoscopy (oesophagogastroduodenoscopy; EGD) in outpatients. In most cases, peroral gastroscopy is performed. The aim of this study was to evaluate the need of transnasal gastroscopy (nEGD) in outpatients. METHODS: A questionnaire was used to assess patients' preferred choice of method, previous experience with EGD, psychological aspects and sociodemographic data. Furthermore, patient satisfaction with and potentially perceived discomfort during the examination as well as preference for a method in regard to future examinations was evaluated. RESULTS: From September 2016 to March 2017, a total of 283 outpatients at endoscopy of the University Hospital of Leipzig were approached to participate in the study. 196 patients were eligible, of whom 116 (60%) chose nEGD. For 87 patients (87/283, 31%) nEGD had to be excluded for medical reasons. The average age in the total sample was 53 (±17) years. 147 (77%) have had previous experience with peroral EGD (oEGD). Of the nEGD examined patients 83% were fairly up to extremely satisfied with the procedure. Satisfaction significantly predicted the choice of future EGD examinations. Nasal pain experienced during nEGDs was associated with rejection of nEGD in further EGD examinations (p<0.01). Patients who did choose a specific procedure were more likely to select the same procedure as their future preference (χ²= 73.6, df=1, p<0.001); this preference was unaffected by the procedure that had been chosen previously (reselecting nEGD: 84%, oEGD: 89%, p=0.874). CONCLUSION: nEGD without sedation is a viable alternative. Patient satisfaction with nEGD is high, and reselection rate for nEGD is similar to that for oEGD. As a result of this study nEGD is now offered as a routine procedure at the University of Leipzig. TRIAL REGISTRATION NUMBER: NCT03663491.

Severe ileocecal inflammatory syndrome in adult patients with cystic fibrosis.

The relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.

Early detection of cardiotoxicity by 2D and 3D deformation imaging in patients receiving chemotherapy.

The aim of the present study was to find out whether early cardiac changes in patients receiving chemotherapy can be detected by the conventional and deformation parameters of 2D and 3D echocardiography. Twenty-five healthy subjects with normal regional left ventricular function (group 1) and 25 patients receiving chemotherapy (group 2) underwent 2D and 3D transthoracic echocardiography (Toshiba Artida Medical System). All patients (group 2) were examined before and during cardiotoxic chemotherapy at a 3-month follow-up. Left ventricular volumes, ejection fraction, muscle mass, global longitudinal, global radial, global circumferential strain, and rotation were analyzed with 2D and 3D echocardiography, while twist and time-to-peak-intervals were analyzed with 3D echocardiography. For left ventricular volumes and muscle mass, no significant differences were seen between the two study groups (P<0.05). According to our results, myocardial dysfunction induced by cardiotoxic chemotherapy can be detected by 2D global radial strain. Detecting myocardial dysfunction by global longitudinal and circumferential strain requires more than 3 months follow-up. Changes in rotation, twist or time-to-peak intervals could not be verified at the 3-month follow-up in the present study. 2D global radial strain seems to be the most sensitive and robust parameter to detect early myocardial damage during chemotherapy. 3D echocardiography is not yet an established method to detect myocardial damage in clinical practice due to lower spatial and temporal resolution.

Loss of Bace1 in mice does not alter the severity of caerulein induced pancreatitis.

CONTEXT: Beta-site alpha-amyloid protein cleaving enzyme1 (BACE1) plays a key role in the pathogenesis of Alzheimer's disease. Additional to its moderate expression in the brain, high levels of BACE1 mRNA were found in the pancreas. Murine Bace1 has been immunohistochemicaly detected at the apical pole of acinar cells within the exocrine pancreas of mice and Bace1 activity was observed in pancreatic juice. In vitro experiments revealed enteropeptidase as a putative substrate for Bace1 suggesting a role in acute pancreatitis. OBJECTIVE: The aim of this study was to address a protective mechanism of Bace1 in acute experimental pancreatitis in mice. METHODS: Acute experimental pancreatitis was induced by intraperitoneal injection of caerulein in homozygote Bace1-/- mice and wild type mice. Serum and tissue analyses were carried out after 4 h, 8 h and 24 h. Measurement of plasma amylase and lipase was performed to confirm pancreatitis induction. In order to assess the severity of pancreatitis H&E stained pancreatic sections were examined regarding edema, inflammation and apoptosis. Immunohistochemical detection of myeloperoxidase (MPO) positive cells was carried out to further quantify the extent of inflammation. Expression of Bace2 within the pancreas was analyzed by immunohistochemistry and RT-qPCR. RESULTS: We demonstrate that total loss of Bace1 in mice leads to no alterations in the course of acute experimental caerulein-pancreatitis. Bace1-/- mice develop a moderate pancreatitis that is comparable in histomorphological and serological features with those seen in wild type mice. DISCUSSION: We discuss the results in the context of the applied caerulein induced edematous pancreatitis model and possible compensatory mechanisms via Bace2 that might be responsible for the observed results.

Genetic and biochemical evidence for a functional role of BACE1 in the regulation of insulin mRNA expression.

OBJECTIVE: Beta-site amyloid precursor protein cleaving enzyme (BACE1) is highly expressed in pancreatic ß-cells. The BACE1 gene is located in a region associated with a high diabetes risk in PIMA Indians. DESIGN AND METHODS: INS-1E cells were used to study the impact of siRNA-mediated BACE1 knockdown and glucose metabolism was characterized in Bace1(-/-) mice. BACE1 gene was sequenced in DNA samples from 48 subjects and 13 representative single nucleotide polymorphisms (SNPs) were then genotyped for association studies in 1,527 Caucasians. RESULTS: Reduction of Bace1 expression results in a significant decrease in insulin mRNA expression in INS-1E cells. Bace1(-/-) mice display significantly lower body weight, lower plasma insulin concentrations, but normal glucose tolerance and insulin sensitivity. In a case-control study including 538 healthy controls and 989 patients with type 2 diabetes (T2D), one SNP (rs535860) was significantly associated with T2D (P < 3.5 × 10(-5) , adjusted for age, sex, and BMI). CONCLUSIONS: Reduced Bace1 expression causes impaired insulin expression in pancreatic ß-cells of Bace1(-/-) mice, suggesting that BACE1 plays a role in the regulation of insulin biogenesis. The functionally relevant rs535860 SNP may decrease BACE1 expression by creating a new miR-661 binding site and could therefore contribute to T2D development.