Bettina Temmesfeld-Wollbrück

Adrenomedullin reduces intestinal epithelial permeability in vivo and in vitro

Leakage of the gut mucosal barrier in the critically ill patient may allow translocation of bacteria and their virulence factors, thereby perpetuating sepsis and inflammation. Present evidence suggests that adrenomedullin (AM) improves endothelial barrier function and stabilizes circulatory function in systemic inflammation. We tested the hypothesis that exogenously applied AM stabilizes gut epithelial barrier function. Infusion of Staphylococcus aureus alpha-toxin induced septic shock in rats. AM infusion in a therapeutic setting reduced translocation of labeled dextran from the gut into the systemic circulation in this model. AM also reduced alpha-toxin and hydrogen peroxide (H2O2)-related barrier disruption in Caco-2 cells in vitro and reduced H2O2-related rat colon barrier malfunction in Ussing chamber experiments. AM was shown to protect endothelial barrier function via cAMP elevation, but AM failed to induce cAMP accumulation in Caco-2 cells. cAMP is degraded via phosphodiesterases (PDE), and Caco-2 cells showed high activity of cAMP-degrading PDE3 and 4. However, AM failed to induce cAMP accumulation in Caco-2 cells even in the presence of sufficient PDE3/4 inhibition, whereas adenylyl cyclase activator forskolin induced strong cAMP elevation. Furthermore, PDE3/4 inhibition neither amplified AM-induced epithelial barrier stabilization nor affected AM cAMP-related rat colon short-circuit current, furthermore indicating that AM may act independently of cAMP in Caco-2 cells. Finally, experiments using chemical inhibitors indicated that PKC, phosphatidylinositide 3-kinase, p38, and ERK did not contribute to AM-related stabilization of barrier function in Caco-2 cells. In summary, during severe inflammation, elevated AM levels may substantially contribute to the stabilization of gut barrier function.

Outcomes of Endobronchial Valve Treatment Based on the Precise Criteria of an Endobronchial Catheter for Detection of Collateral Ventilation under Spontaneous Breathing.

Background: Endoscopic lung volume reduction with valves is a valid therapeutic option for COPD patients with severe emphysema. The exclusion of interlobar collateral ventilation (CV) is an important predictor of clinical success. Objectives: Recently, a catheter-based endobronchial in vivo measurement system (Chartis, Pulmonx, USA) has become routine in the clinical evaluation of CV status in target lobes, but the criteria for phenotyping CV by Chartis evaluation have not yet been defined. We asked the questions, how many phenotypes can be identified using Chartis, what are the exact criteria to distinguish them, and how do the Chartis phenotypes respond to valve insertionκ Methods: In a retrospective study, 406 Chartis assessments of 166 patients with severe COPD were analyzed. Four Chartis phenotypes, CV positive (CV+), CV negative (CV-), low flow (LF) and low plateau were identified. Fifty-two patients without CV were treated with valves and followed for 3 months. Results: The Chartis phenotypes were discriminated with respect to decline in expiratory peak flow, increase in resistance index and change in total exhaled volume after 1, 2, 3, 4 and 5 min of measurement time (p < 0.0001, ANOVA), and the cutoff criteria were defined accordingly. To examine the application of these phenotyping criteria, students applied them to 100 Chartis assessments, and they demonstrated almost perfect inter- and intraobserver agreements (κ > 0.9). Compared to baseline, CV- and LF patients with ipsilateral CV- lobe showed an improvement in FEV1 (p < 0.05), vital capacity (p < 0.05) and target lobe volume reduction (p < 0.005) after valve insertion. Conclusion: This study describes the most prevalent Chartis phenotypes.

Leptospirosis in travelers returning from the Dominican Republic.

Leptospirosis is probably the most widespread zoonosis in the world.1 Infection of humans occurs after indirect or direct exposure to urine of rodents, livestock, or a wide range of other mammals infected with Leptospira interrogans or other Leptospira species pathogenic to humans.2 Incidence of the disease is higher in warmer than in temperate countries,3 and in developing than in affluent countries.4,5 Leptospirosis predominates in rural areas, although urban epidemics are emerging, with larger outbreaks in various regions throughout the world.6 Human infection occurs through exposure to water and soil contaminated by infected animal urine. It is an occupational risk of farmers,veterinarians,miners, abattoir and sewer workers and has been associated with canoeing, wading,and swimming in contaminated lakes and rivers.7,8 In many tropical countries, dogs are a significant reservoir for isolated human infections and outbreaks.7 Occasional outbreaks in a recreational setting have been described among certain high-risk groups, such as whitewater rafters and athletes.8,9 In the early phase of illness when initiation of appropriate chemotherapy is most successful, it can be easily mistaken for a range of other infectious diseases, sometimes with severe consequences.6

Local ablative treatment for synchronous single organ oligometastatic lung cancer—A propensity score analysis of 180 patients

INTRODUCTIONnLocal ablative treatment (LAT) improves outcome in lung cancer with oligometastatic disease (OMD) and potentially leads to long term survival. The aim of this retrospective study was to evaluate and quantify the additional benefit of LAT in synchronous OMD and to further identify prognostic factors for survival.nnnPATIENTS AND METHODSnA propensity score-matched pairs analysis was performed on a set of patient and disease variables in 180 patients, treated for synchronous single organ OMD including non small-cell and neuroendocrine lung cancer with ≤4 metastases between 2000 and 2016 in 3 lung cancer centers in Berlin, Germany. Patients either received LAT for all sites of disease (intervention group) by means of surgery or stereotactic radiotherapy, or standard chemotherapy, if necessary combined with a local treatment with palliative intent (control group).nnnRESULTSnMedian follow-up time was 32.2 and 18.8 months for the intervention and control group, respectively. Substantial benefits in median progression-free survival (PFS, 25.1 vs. 8.2 months; HR, 0.30; 95% CI, 0.21-0.43; pu2009<u20090.001) and overall survival (OS, 60.4 vs. 22.5 months; HR, 0.42; 95% CI, 0.28-0.62; pu2009<u20090.001) were associated with LAT. Histology of adenocarcinoma and T1a primaries also predicted a favorable prognosis concerning PFS and OS. More favorable nodal stage (N0-2 vs. 3) and solitary metastases were associated with an extended PFS, whereas initial ECOG-PS (0-1 vs. 2) predicted OS.nnnCONCLUSIONSnLAT was the strongest predictor for PFS and OS in OMD with ≤4 metastases. Survival in the control group identifies OMD as a subset of lung cancer with a generally more favorable prognosis.

Infektiologische Differenzialdiagnosen bei granulomatösen Lungenerkrankungen

Infections are the most common cause of granulomatous lung diseases. A variety of different pathogens can cause granuloma formation. The diagnosis requires consideration of endemic characteristics, patients predispositions as well as specific requirements for pathogen detection. The aim of this review is to give a short overview of the most important causative pathogens and facilitate the differential diagnostic approach of granulomatous lung diseases.