Abstract Expression patterns of the second SDF-1 receptor RDC1/CXCR7 were examined after focal ischemia in rats using in situ hybridization. CXCR7 mRNA was identified in the ventricle walls as well ...as neuronal, astroglial, and vascular cells. After ischemia, intact cortical regions showed a rapid, 4 days-lasting increase in neuronal CXCR7 expression. In the ischemic tissue CXCR7 expression was scarce and associated with blood vessels. Between days 2 and 10 after ischemia-onset, SDF-1 expression increased strongly in the peri-infarct and infarct region, which was accompanied by the appearance of numerous CXCR4-expressing but not CXCR7-expressing cells. These patterns suggest that SDF-1 may influence vascular, astroglial, and neuronal functions via CXCR7 and mediate cell recruitment to ischemic brain areas via CXCR4.
Gastrointestinal bleeding (GIB) is one of the most common emergencies in gastroenterology. The aim of this study was to investigate the association between the incidence of GIB and seasonal, ...circadian and meteorological patterns in the emergency department (ED) of a tertiary hospital.
From January 2007 until December 2012, we retrospectively evaluated patients presenting to the ED with respect to the number and location of GIB, season, time of day and weather.
Of 45 458 patients, 578 (1.3%) presented with a GIB. Of these, 62.5% were men compared with 54.7% of all patients in the ED (χ, P=0.0002). Patients with GIB were on average 4.4 years older than those without GIB (95% confidence interval 2.76-5.98, t-test, P<0.001). In addition, 304 (52.6%) patients had upper GIB and 138 (23.9%) had lower GIB. In total, 136 (23.5%) patients required no endoscopy because of initial laboratory and circulatory stability. In univariate analysis, meteorological parameters, including air temperature, cloud cover, relative humidity, vapour pressure, amount of precipitation, sunshine duration and snow height, were each associated with an increased risk of acute GIB (all P-values<0.05). In the 6-year study period, patients with GIB presented to the ED mainly during the winter months. Independent predictors of GIB on multivariate logistic regression were older age, male sex, season and daytime, all P less than 0.005. Emergency admissions during the night were associated with a 54 and 35% higher risk of GIB compared with daytime (8 a.m. to 4 p.m., P=0.0002) and late evening hours (4 p.m. to midnight, P=0.0142), respectively.
Presentation of patients with acute GIB in the ED is age and sex specific and shows seasonal and circadian differences in distribution, with an increased incidence in winter months and during night-time. This should be considered when determining possible emergency endoscopic interventions and the availability of emergency endoscopy services.
Differentiation of pancreatic cancer (PCA) from chronic pancreatitis (CP) is challenging. We searched for peptide markers in urine to develop a diagnostic peptide marker model.
Capillary ...electrophoresis-mass spectrometry was used to search for peptides in urine of patients with PCA (n = 39) or CP (n = 41). Statistical different peptides were included in a peptide multimarker model. Peptide markers were sequence identified and validated by immunoassay and immunohistochemistry (IHC).
Applied to a validation cohort of 54 patients with PCA and 52 patients with CP, the peptide model correctly classified 47 patients with PCA and 44 patients with CP (area under the curve, 0.93; 87% sensitivity; 85% specificity). All 5 patients with PCA with concomitant CP were classified positive. Urine proteome analysis outperformed carbohydrate antigen 19-9 (area under the curve, 0.84) by a 15% increase in sensitivity at the same specificity. From 99 healthy subjects, only four were misclassified. Fetuin-A was the most prominent peptide marker source for PCA as verified by immunoassay and IHC. In silico protease mapping of the peptide markers' terminal sequences pointed to increased meprin-A activity in PCA, which in IHC was associated with neoangiogenesis.
Urinary proteome analysis differentiates PCA from CP and may serve as PCA screening tool.
Background
Detection of cholangiocarcinoma (CC) remains a diagnostic challenge particularly in patients with primary sclerosing cholangitis (PSC). We recently established diagnostic peptide marker ...models in bile and urine to detect CC. Our aim was to combine both models to reach a higher diagnostic accuracy of CC diagnosis.
Methods
Bile (BPA) and urine (UPA) proteome analysis by capillary electrophoresis mass spectrometry was performed in a case-control phase II study on 87 patients (36 CC including 13 with CC on top of PSC, 33 PSC and 18 other benign disorders). A logistic regression model with both analyses was developed and subsequently validated in a prospective cohort of 45 patients.
Results
In the retrospective study, single BPA and UPA showed sensitivities of 83 and 89 % and specificities of 80 and 86 % with an area under the curve (AUC) value of 0.85 and 0.93. If CC was defined as positive UPA and BPA the combination resulted in a sensitivity of 72 % and a specificity of 96 %. The logistic regression model resulted in an increase in sensitivity to 92 % at 84 % specificity with an AUC of 0.96. Applied to the prospective study cohort, the logistic regression model was superior in its sensitivity (94%) and specificity (76%) over single BPA (63% sensitivity, 69% specificity) and UPA (81% sensitivity, 72% specificity) with an AUC of 0.84.
Conclusion
Our logistic regression model enables CC diagnosis with a higher accuracy than currently available diagnostic tools leading potentially to an earlier diagnosis.
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