Background: Antibacterial agents play important roles in the treatment of bacterial infections. However, the development of antimicrobial resistance (AMR) and carry-over of substances into the environment are several problems arising during oral treatment of bacterial infections. We assessed AMR development in commensal Escherichia coli (E. coli) in enrofloxacin treated and untreated animals. In addition, we examined fluoroquinolone in the plasma and urine of treated and untreated animals, and in sedimentation dust and aerosol. Methods: In each trial, six pigs were treated with enrofloxacin via powder, granulate or pellet forms in two time periods (days 1–5 and 22–26). Four pigs served as untreated controls. The minimum inhibitory concentration (MIC) was determined to evaluate AMR development. Analysis of enro- and ciprofloxacin was performed with high performance liquid chromatography. Results: Non-wildtype E. coli (MIC > 0.125 µg/mL) was detected in the pellet treated group after the first treatment period, whereas in the other groups, non-wildtype isolates were found after the second treatment period. E. coli with MIC > 4 µg/mL was found in only the pellet trial. Untreated animals showed similar susceptibility shifts several days later. Bioavailability differed among the treatment forms (granulate > pellet > powder). Enro- and ciprofloxacin were detected in aerosols and sedimentation dust (granulate, powder > pellet). Conclusions This study indicates that the kind of the oral dosage form of antibiotics affects environmental contamination and AMR development in commensal E. coli in treated and untreated pigs.

BACKGROUNDChronic heart failure is a significant cause of cardiovascular morbidity and mortality. This study tested the hypothesis that restrictive filling pattern may provide useful prognostic data for identifying patients with chronic heart failure at high risk of all-cause cardiac death.

METHODSNinety patients with chronic heart failure [70 men and 20 women, mean age (58.1 +/- 11.6) years] were investigated and followed for (18.8 +/- 7.9) months. During this period, 14 patients died of progressive pump failure, 12 patients underwent heart transplantation, 5 patients died suddenly, and 2 patients died of acute myocardial infarction. A new criterion, the restrictive filling index (RFI), was designed to subgroup patients into a restrictive and a nonrestrictive group.

RESULTSPatients with restrictive filling pattern had a more severe left ventricular dysfunction and a higher cardiac mortality. Analysis by the Kaplan-Meier method revealed that patients in the RFI > or = 1 and RFI < 1 groups had a cardiac events-free survival rate of 52% versus 94% at 1 year, and 27.5% versus 92% at 2 years, respectively. The multivariate Cox proportional hazard model selected RFI as the most powerful prognostic factor (chi(2) = 8.8017, P = 0.0030) for all-cause cardiac death.

CONCLUSIONThese results indicate that RFI is a simple, noninvasive, and specific clinical predictor for adult chronic heart failure patients who are at a high risk for all-cause cardiac death.

Chronic Disease ; Echocardiography, Doppler ; Heart Failure ; diagnostic imaging ; mortality ; Humans ; Male ; Middle Aged ; Prognosis ; Ventricular Dysfunction, Left ; physiopathology

BACKGROUND: The treatment of different skin conditions with spa waters is a long tradition dating back to at least late Hellenism. Interestingly, independent scientific examinations studying the effect of spa waters are scarce. OBJECTIVE: In the present in vitro study, we compared the effect of culture media supplemented with (a) thermal spa waters (La Roche-Posay, Avene) and (b) two natural mineral drinking waters (Heppinger, Adelholzener) on physiological parameters in HaCaT keratinocytes. METHODS: The different medium preparations were investigated with regard to cell proliferation and cell damage. Moreover, the impact on inflammation parameters with and without ultraviolet B (UVB) irradiation was examined. RESULTS: Two popular thermal spring waters were found to suppress cell proliferation and cell damage. Moreover, these waters reversed the induction of interleukin-6, as measured using enzyme-linked immunosorbent assay and promoter transactivation, and the formation of reactive oxygen species after UVB stimulation. Of note, the two natural mineral waters, which are distributed as drinking waters, had some effect on the above-mentioned parameters but to a lesser extent. CONCLUSION: In summary, our results show that spa waters, and particularly those derived from thermal springs, reduce parameters associated with inflammation. It seems likely that trace elements such as selenium and zinc are critical for the observed effects.
Cell Proliferation ; Culture Media ; Drinking ; Enzyme-Linked Immunosorbent Assay ; Humans* ; Inflammation* ; Interleukin-6 ; Keratinocytes* ; Mineral Waters ; Reactive Oxygen Species ; Selenium ; Skin ; Trace Elements ; Transcriptional Activation ; Water* ; Zinc

Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.
Humans ; CTLA-4 Antigen ; Immune Checkpoint Inhibitors/therapeutic use* ; Liver ; Prospective Studies ; Skin Neoplasms