CD71 expressing circulating neutrophils serve as a novel prognostic biomarker for metastatic spread and reduced outcome in pancreatic ductal adenocarcinoma patients.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, presenting a persisting global health burden. Neutrophils have a double-edged role in tumor progression exhibiting both pro-tumor and anti-tumor functions. CD71, also known as transferrin receptor 1, performs a critical role in cellular iron uptake and is highly expressed on proliferating cells, and especially on activated immune cells. CD71 is known to be elevated in various types of solid cancers and is associated with poor prognosis, however, the expression of CD71 on neutrophils in PDAC and its potential clinical impact is still unknown. Therefore, we analyzed CD71 on circulating neutrophils in PDAC and clinical control patients and found a significant increased expression in PDAC patients. High expression of CD71 on neutrophils in PDAC patients was associated with reduced outcome compared to low expression. CD71 on neutrophils correlated positively with the levels of proinflammatory cytokines IL-6, IFN-γ, and growth factor ligands CD40-L, and BAFF in plasma of PDAC patients. Finally, we have demonstrated that high expression of CD71 on neutrophils was also associated with an increased expression of CD39 and CD25 on circulating T-cells. Based on our findings, we hypothesize that CD71 on neutrophils is associated with tumor progression in PDAC. Further studies are required to investigate the distinct functionality of CD71 expressing neutrophils and their potential clinical application.

Effect of Circular Stapler Diameter on Anastomotic Leakage Rate and Stenosis After Open Total Gastrectomy With Esophagojejunostomy: A Substantive Retrospective Propensity Score Matched Series.

Background: Anastomotic leakage (AL) and stenosis (AS) are two of the most severe postoperative complications after total gastrectomy with esophagojejunostomy. The stapler diameter can be chosen by the surgeon. Therefore, this study aims to assess the correlation between the stapler size as main independent variable as well as other different risk factors and AL and AS. Methods: We conducted a retrospective analysis of data from 356 patients who underwent open total gastrectomy between 2000 and 2018, mostly due to gastric cancer (96.9%). After propensity score matching the outcome parameters AL and AS were compared between the two stapler size groups. We also assessed different risk factors for AL and AS in cancer patients using multivariate analysis. Results: Small circular stapler diameter (21/25 mm; n = 147 vs 28/29/31 mm; n = 209) was identified as a significant risk factor for the occurrence of AL (10% vs 4% for smaller vs larger staplers; P = 0.042). In multivariate analysis for the occurrence of AL an ASA score ≥ 3 could be identified as a risk factor (OR 2.85; 95% CI = 1.13-7.15; P = 0.026). Additionally, smaller stapler size could be identified as a risk factor for AS (OR small 1.00, OR large 0.24; 95% CI: 0.06-0.97; P = 0.045). AL was associated with lower survival (18.1 vs 38.16 months; P = 0.0119). Conclusion: The application of a larger circular stapler for esophagojejunostomy in open total gastrectomy shows significantly lower rates of AL and stenosis. Therefore, the largest possible stapler diameter should be applied.

[Cold Plasma to Treat Therapy-Refractive Corneal Ulcers]. / Kaltplasma zur Behandlung therapierefraktärer Hornhautulzera.

BACKGROUND: The integrity of the ocular surface and the transparency of the cornea is crucial to obtain a good visual acuity - a requirement to actively participate in both social and professional environments. The homeostasis of the ocular surface is constantly endangered by microbes and by intrinsic factors with negative influence on wound healing. Furthermore, widespread use of contact lenses obtain a risk of corneal infection even resulting in corneal perforation and loss of the eye. Current therapies include topical and systemic antibiotics and antimycotics, often applied in an in-ward setting. PATIENTS/MATERIALS AND METHODS: Some microbes can be therapy-resistent or -refractory and therefore cause a deterioration of the clinical aspect. In this study, the effects of cold plasma treatment of corneal ulcers on reduction of microbial load in vitro, in tissue ex vivo and in a therapy-refractory ulcer. RESULTS: In vitro, ex vivo and in the patient microbial load could be reduced or the clinical findings improved. CONCLUSIONS: Plasma medicine and its disinfective properties could open a novel approach to treat microbial infections of the cornea. The can result in reduced treatment times, a faster demission of the patients and overall in a reduction of health care costs.

Argon Cold Plasma-A Novel Tool to Treat Therapy-resistant Corneal Infections.

PURPOSE: To test whether therapy-resistant corneal infections can be successfully treated with argon cold plasma to reduce or eliminate pathogen microorganisms without affecting corneal cell viability. DESIGN: First-in-human case series and experimental study. METHODS: Cold plasma effects on viability of primary human corneal limbal epithelial cells were studied using exposure times from 0.5 to 10 minutes (metabolic activity, oxidative stress, apoptosis). Disinfective potential of cold plasma was tested against common pathogens (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans) on culture medium and evaluated by counting colony-forming units and optical density measurements, as well as against S aureus in a human cornea infection model. Additionally, in a first-in-human trial 4 patients with therapy-resistant corneal ulcers were treated to evaluate the clinical potential of cold plasma. RESULTS: Cells treated for 0.5-5 minutes completely recovered within 24 hours without changes in morphology; only 10-minute treatment impaired the cells permanently. No evident oxidative stress, apoptosis, or damage to the corneal structure could be found. All pathogens were susceptible to cold plasma treatments, with different levels of sensitivity. The condition of all 4 patients significantly improved after cold plasma treatment combined with antibiotic therapy. CONCLUSIONS: Our results indicate that argon cold plasma treatment reduces or eliminates common pathogens without impairing corneal epithelial cells in vitro, ex vivo, and in direct application on patients' eyes. We conclude that argon cold plasma therapy offers a potential supplement or alternative therapy for therapy-resistant corneal infections. A larger, comparative study is necessary to further confirm these findings.