Systemic Immune-Inflammation Index (SII) Predicts Poor Survival in Pancreatic Cancer Patients Undergoing Resection

Background: The systemic immune-inflammation index based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in several malignancies. The aim of this study was to determine the prognostic role of systemic immune-inflammation index in patients with pancreatic ductal adenocarcinoma undergoing resection. Methods: Consecutive patients who underwent surgical resection at the department of surgery at the Medical University of Vienna between 1995 and 2014 were included into this study. The systemic immune-inflammation index was calculated by the formula platelet*neutrophil/lymphocyte. Optimal cutoffs were determined using Youden's index. Uni-and multivariate analyses were calculated by the Cox proportional hazard regression model for overall survival. Results Three hundred twenty-one patients were included in this study. Clinical data was achieved from a prospective patient database. In univariate survival analysis, elevated systemic immune-inflammation index was found to be significantly associated with shortened patients' overall survival (p = 0.007). In multivariate survival analysis, systemic immune-inflammation index remained an independent prognostic factor for overall survival (p = 0.004). No statistical significance could be found for platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in multivariate analysis. Furthermore, area under the curve analysis showed a higher prognostic significance for systemic immune-inflammation index, compared to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio. Conclusion: A high systemic immune-inflammation index is an independent, preoperative available prognostic factor in patients with resectable pancreatic ductal adenocarcinoma and is superior to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio for predicting overall survival in pancreatic ductal adenocarcinoma patients

Gastroesophageal Adenocarcinomas and the Expression of FGF8, FGF18 and FGFR4

Das Adenokarzinom des gastroösophagealen Übergangs zeigt weltweit eine Zunahme in der Inzidenz, jedoch konnten trotz Fortschritten in Diagnostik und chirurgischer und multimodaler Therapie kaum Verbesserungen der Überlebenszeit erzielt werden. Fibroblast Growth Factors (FGFs) und ihre Rezeptoren (FGFRs) konnten in einer Reihe von malignen Erkrankungen als prognostische Marker und mögliche neue therapeutische Angriffspunkte identifiziert werden (1). Bis heute hat noch keine Studie den Einfluss von FGF8, FGF18 und FGFR4 beim Adenokarzinom des gastroösophagealen Übergangs untersucht. Daher befasst sich diese Diplomarbeit mit der Analyse der Expression von FGF8, FGF18 und FGFR4 beim Adenokarzinom des gastroösophagealen Übergangs und deren potentieller prognostischen Wertigkeit. Insgesamt wurden 155 PatientInnen in diese Studie inkludiert, 69 (44,5%) PatientInnen wurden mittels neoadjuvanter Chemotherapie behandelt. Hohe Expression von FGF8, FGF18 und FGFR4 wurden in 60,7% (n=94), 31,6% (n=49) und 54,2% (n=84) der PatientInnen beobachtet. Sowohl für primär resezierte als auch für neoadjuvant behandelte PatientInnen erwies sich die Überexpression von FGF8 als unabhängiger prognostischer Faktor für das Gesamtüberleben. Weiter konnte eine Korrelation der Überexpression von FGF8 mit dem Ansprechen auf die neoadjuvante Therapie gezeigt werden. In der Subgruppe der neoadjuvant behandelten PatientInnen war die Überexpression von FGF18 mit einem signifikant verlängertem Gesamtüberleben vergesellschaftet. Für FGFR4 konnte keine signifikante Korrelation zwischen Expression und Überleben gezeigt werden. Daher sind FGF8 und FGF18 potentiell vielversprechende prognostische Faktoren und mögliche therapeutische Angriffspunkte für zukünftige Therapien.Adenocarcinomas of the gastroesophageal junction show a worldwide increase in incidence but even though advances in diagnostic accuracy, surgical treatment and multimodal therapy, prognosis remains poor. Fibroblast growth factors (FGFs) and their receptors (FGFRs) were identified as promising prognostic biomarkers and therapeutic targets in multiple tumor entities (1), however, no data on expression of FGF8, FGF18 and FGFR4 in adenocarcinomas of the esophagus exist. Therefore, this thesis claims to investigate the protein expression of the three markers mentioned above. For investigation immunohistochemistry targeting FGF8, FGF18 and FGFR4 was performed on tissue specimens of 155 patients, including samples of 69 patients who received neoadjuvant treatment (samples were taken before and after the applied therapy regimen). High protein expression levels of FGF8, FGF18 and FGFR4 were observed in 60.7% (n=94), 31.6% (n=49) and 54.2% (n=84) patients, respectively. Overexpression of FGF8 was revealed to be an independent prognostic factor for overall survival for both, primary resected and neoadjuvantly treated patients. Furthermore, FGF8 expression levels were correlating with Mandard regression rates, therefore indicating its potential as a prognostic factor. In contradiction, FGF18 was found to be significantly associated with prolonged overall survival in patients who received neoadjuvant therapy. No significant correlations for FGFR4 for overall survival in adenocarcinomas of the gastroesophageal junction could be observed. In conclusion, FGF8 and FGF18 are promising markers for prognosis, survival and possible targets for prospective therapy.Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersArbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftMedizinische Universität Wien, Diplomarb., 2020(VLID)512134

Identification of Filamentous Fungi by MALDI-TOF Mass Spectrometry: Evaluation of Three Different Sample Preparation Methods and Validation of an In-House Species Cutoff

Invasive infections caused by filamentous fungi constitute a leading cause of morbidity and mortality in immunocompromised patients. Rapid and reliable identification of filamentous fungi is essential for the early initiation of appropriate treatment. In the present study, 230 filamentous fungi isolates identified by conventional methods were investigated using MALDI-TOF MS (Bruker Daltonics, Bremen, Germany) in combination with the Filamentous Fungi Library 3.0 provided by the manufacturer. Three different sample preparation methods were applied as recommended by the manufacturer and identification rates were compared using the criteria provided by the manufacturer. Application of the more time-consuming sample preparation methods clearly improved identification at the species level. Thus, the identification rate increased from 48.9% using the simplest method to 76.1% with the most laborious procedure. Misidentifications did not occur. Furthermore, the reliability of an in-house threshold for species identification was investigated. The reduced threshold increased the rate of isolates correctly identified at the species level by up to 86.4%. As no misidentification was made at the genus level and only one misidentification of minor significance occurred at the species level, this threshold could be validated for routine use in our laboratory. In conclusion, regarding the high identification rates achieved, this commercial platform proved suitable for implementation in routine diagnosis

Oncotarget / The modified glasgow prognostic score is an independent prognostic indicator in neoadjuvantly treated adenocarcinoma of the esophagogastric junction

The modified Glasgow Prognostic Score (mGPS) combines the indicators of decreased plasma albumin and elevated CRP. In a number of malignancies, elevated mGPS is associated with poor survival. Aim of this study was to investigate the prognostic role of mGPS in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction 256 patients from a prospective database undergoing surgical resection after neoadjuvant treatment between 2003 and 2014 were evaluated. mGPS was scored as 0, 1, or 2 based on CRP (>1.0 mg/dl) and albumin (<35 g/L) from blood samples taken prior (preNT-mGPS) and after (postNT-mGPS) neoadjuvant therapy. Scores were correlated with clinicopathological patients characteristics. From 155 Patients, sufficient data was available. Median follow-up was 63.8 months (33.389.5 months). In univariate analysis, Cox proportional hazard model shows significant shorter patients OS (p = 0.04) and DFS (p = 0.02) for increased postNT-mGPS, preNT-hypoalbuminemia (OS: p = 0.003; DFS: p = 0.002) and post-NT-CRP (OS: p = 0.03; DFS: p = 0.04). Elevated postNT-mGPS and preNT-hypoalbuminemia remained significant prognostic factors in multivariate analysis for OS (p = 0.02; p = 0.005,) and DFS (p = 0.02, p = 0.004) with tumor differentiation and tumor staging as significant covariates. PostNT-mGPS and preNT-hypoalbuminemia are independent prognostic indicators in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction and significantly associated with diminished OS and DFS.(VLID)471339

A multi-omics based anti-inflammatory immune signature characterizes long COVID-19 syndrome

Summary: To investigate long COVID-19 syndrome (LCS) pathophysiology, we performed an exploratory study with blood plasma derived from three groups: 1) healthy vaccinated individuals without SARS-CoV-2 exposure; 2) asymptomatic recovered patients at least three months after SARS-CoV-2 infection and; 3) symptomatic patients at least 3 months after SARS-CoV-2 infection with chronic fatigue syndrome or similar symptoms, here designated as patients with long COVID-19 syndrome (LCS). Multiplex cytokine profiling indicated slightly elevated pro-inflammatory cytokine levels in recovered individuals in contrast to patients with LCS. Plasma proteomics demonstrated low levels of acute phase proteins and macrophage-derived secreted proteins in LCS. High levels of anti-inflammatory oxylipins including omega-3 fatty acids in LCS were detected by eicosadomics, whereas targeted metabolic profiling indicated high levels of anti-inflammatory osmolytes taurine and hypaphorine, but low amino acid and triglyceride levels and deregulated acylcarnitines. A model considering alternatively polarized macrophages as a major contributor to these molecular alterations is presented