Martin Floer

Background. Early recognition of sepsis and a prompt initiation of goal-directed therapy is important for sepsis survival. Little is known about the impact of early recognition of sepsis in the out-of-hospital setting when paramedics are the 1st medical professionals arriving on the scene. Objectives. To characterize the impact of sepsis recognition by paramedics in the 1st out-of-hospital contact and to establish a predictive model by combining preclinical patient characteristics. Materials and methods. In this retrospective single-center cohort study, we included a total of 263 patients diagnosed with sepsis after admission to the emergency department and correlated them to the emergency medical protocols of the paramedics who have seen the patient out-of-hospital. Results. Only 25 patients were correctly diagnosed by paramedics out-of-hospital. If sepsis was diagnosed, the median time to antibiotic administration was significantly lower (136.50 min compared to 206.98 min, p = 0.0069) and mortality was reduced from 22.8% to 8% (p = 0.0292). We have identified predictors for prognosis and calculated a predictive model with a modified quick Sepsis-related Organ Failure Assessment (qSOFA) score, which fits the needs for out-of-hospital usage and results in a better discrimination of vitally threatened patients (receiver operating characteristic (ROC) area under curve (AUC) of 0.641 compared to 0.719), as compared to the standard qSOFA. Conclusions, Sepsis recognition by paramedics at the 1st out-of-hospital contact significantly reduces sepsis mortality. The qSOFA and modified qSOFA are suitable tools for sepsis recognition, and have an impact on mortality and disease management when used.

Syndecan-1 (Sdc1) is a heparin sulfate proteoglycan expressed in intestinal epithelium, which plays a crucial role in inflammation and epithelial repair. Sdc1-knockout mice have a deteriorated course of dextran sulfate sodium-induced colitis as compared to controls. Syndecan-1 is also shed into the serum during inflammation of the epithelium. We hypothesized that an increased serum level of soluble Sdc1 is a biomarker of intestinal inflammation in ulcerative colitis (UC). To evaluate serum soluble Sdc1 as a biomarker of intestinal inflammation in UC. This is a proof-of-concept study. Patients were recruited by the University Hospital Münster and HELIOS Albert Schweitzer Klinik Northeim (Germany). Blood samples were collected from UC patients actively suffering from this condition and those in remission. The levels of Sdc1 were measured with Diaclone CD 138 ELISA kit (Diaclone Research, Besançon, France) and routine clinical data were collected (C-reactive protein (CRP) levels, calprotectin in stool samples). Data were analyzed using SPSS software. Soluble Sdc1 levels were significantly elevated in the active UC group as compared to the inactive UC group (94.5 ±68.1 ng/mL compared to 28.3 ±12.6 ng/mL, p = 0.0020). The levels of Sdc1 also significantly correlated with the severity of UC as measured with the Mayo score (p = 0.0248). Receiver operating characteristic (ROC) analysis showed a good correlation of Sdc1 with an endoscopic Mayo score ≥2, with a value of 0.7747 (95% confidence interval (95% CI) = 0.5775-0.9718). A cutoff value of 37.1 ng/mL of Sdc1 showed a sensitivity of 78% and a specificity of 77%. A panel of biomarkers including CRP, hemoglobin, hematocrit, and Sdc1 was able to precisely predict active UC with an area under the curve (AUC) = 0.9395 (95% CI = 0.8509-1.0000). Serum soluble Sdc1 correlates significantly with mucosa inflammation and Mayo score in UC. Clinical trials No. NCT02333526.

Background and aims: Adenoma detection rate (ADR) in colon cancer screening is most important for cancer prophylaxis. This work is the first three‐armed randomised controlled clinical trial aimed at comparing a head‐to‐head setting standard colonoscopy (SC) with Endocuff‐assisted colonoscopy (EC) and cap‐assisted colonoscopy (CAC) for improvement of ADR.Methods: Patients from Poland and Germany with independent indication for colonoscopy were randomised into three arms of this trial: EC, CAC and SC. Exclusion criteria were age p = 0.94). Withdrawal time was a mean of 7 min in all groups (p = 0.658), and bowel preparation did not differ between the groups. The time to reach the caecum was significantly reduced when using the cap (a mean of 6 min for CAC vs. 7 min for SC; p = 0.0001). There was no significant difference in the primary outcome of the ADR between the groups (EC 32%, CAC 30%, SC 30%; p = 0.815). EC proved to be superior (EC vs. SC) in the sigmoid colon and transverse colon for polyp detection.Conclusion: The use of EC increased the total number of polyps seen during colonoscopy. In contrast to recent studies, no significant improvement of the ADR was detected.

Tissue remodeling and mesenchymal cell accumulation accompanies chronic inflammatory disorders involving joints, lung, vasculature, and bowel. Chronic inflammation may alter DNA-mismatch repair (MMR) systems in mesenchymal cells, but is not defined in Crohn's disease (CD) and its associated intestinal remodeling and stricture formation. We determined whether DNA-MMR alteration plays a role in the pathogenesis of CD tissue remodeling. Control and CD bowel tissues were used to generate primary cultures of muscularis mucosa myofibroblasts, which were assessed directly or following stimulation with TNF-α/LPS or H₂O₂. MutS homolog (MSH)2, MSH3, and MSH6 expression in tissues and myofibroblasts was determined. Immunohistochemical staining revealed an increased expression of MSH2 in CD muscularis mucosa and submucosal tissues compared with controls or uninvolved CD tissue, and MSH2 expression was increased in CD myofibroblasts compared with control cells. TNF-α/LPS and H₂O₂ further enhanced MSH2 expression in both control and CD cells, which were decreased by simvastatin. There were no significant changes in MSH3 and MSH6 expression. Proliferating cell nuclear antigen and Ki67 staining of CD tissue revealed increased proliferation in the muscularis mucosa and submucosa of chronically inflamed tissues, and enhanced proliferation was seen in CD myofibroblasts compared with controls. Simvastatin reversed the effects of inflammatory stress on the DNA-MMR and inhibited proliferation of control and CD myofibroblasts. Gene silencing with MSH2 siRNA selectively decreased CD myofibroblast proliferation. These data demonstrate a potential role for MSH2 in the pathogenesis of nonneoplastic mesenchymal cell accumulation and intestinal remodeling in CD chronic inflammation.