Prediction of mortality in metastatic colorectal cancer in a real-life population: a multicenter explorative analysis.

BACKGROUND: Metastatic colorectal cancer (mCRC) remains a lethal disease. Survival, however, is increasing due to a growing number of treatment options. Yet due to the number of prognostic factors and their interactions, prediction of mortality is difficult. The aim of this study is to provide a clinical model supporting prognostication of mCRC mortality in daily practice. METHODS: Data from 1104 patients with mCRC in three prospective cancer datasets were used to construct and validate Cox models. Input factors for stepwise backward method variable selection were sex, RAS/BRAF-status, microsatellite status, treatment type (no treatment, systemic treatment with or without resection of metastasis), tumor load, location of primary tumor, metastatic patterns and synchronous or metachronous disease. The final prognostic model for prediction of survival at two and 3 years was validated via bootstrapping to obtain calibration and discrimination C-indices and dynamic time dependent AUC. RESULTS: Age, sidedness, number of organs with metastases, lung as only site of metastasis, BRAF mutation status and treatment type were selected for the model. Treatment type had the most prominent influence on survival (resection of metastasis HR 0.26, CI 0.21-0.32; any treatment vs no treatment HR 0.31, CI 0.21-0.32), followed by BRAF mutational status (HR 2.58, CI 1.19-1.59). Validation showed high accuracy with C-indices of 72.2 and 71.4%, and dynamic time dependent AUC's of 76.7 ± 1.53% (both at 2 or 3 years), respectively. CONCLUSION: The mCRC mortality prediction model is well calibrated and internally valid. It has the potential to support both, clinical prognostication for treatment decisions and patient communication.

Clinical Outcome in Patients with Carcinoma of the Esophagogastric Junction Treated with Neoadjuvant Radiochemotherapy or Perioperative Chemotherapy: A Two-Center Retrospective Analysis.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) is a rare but rising tumor entity in the Western world. Treatment is complex, as multimodality is key to optimal results. However, trials solely including AEG are rare, and the question if neoadjuvant radiochemotherapy (NRCT) or neoadjuvant/perioperative chemotherapy (NACT) is superior remains unanswered. PATIENTS AND METHODS: Patients with AEG I-III treated between October 2010 and August 2019 at the Ordensklinikum Linz or the Kepler University Hospital were identified either from a monitored tumor registry or by chart review. Time-to-event data were analyzed by Kaplan-Meier product limit estimation. The Kruskal-Wallis test and Fisher's exact test were used for comparing continuous and categorical data, respectively. RESULTS: A total of 85 patients (median age 63 years; median Charlson Comorbidity Index 3; 98.8% ECOG PS 0-1) were analyzed. Of these, 52 patients received NRCT (81% CROSS protocol) and 33 NACT (65% EOX and 35% FLOT protocol). There was a significantly higher pathological complete response rate in the NRCT group (30 vs. 12%; p = 0.010); distant relapse rates were higher in the NRCT group and local relapse rates were higher in the NACT group (both not significant). These differences, however, did not translate into a different disease-free survival (20 months; 95% CI: 13-34) or overall survival (44 months; 95% CI: 33-NA). Patients >65 years old had the same advantage from treatment as patients <65 years of age. CONCLUSIONS: Although treatment of AEG is complex, the progress documented over the last centuries can be reproduced in our real-life setting. Data regarding the superiority of either type of neoadjuvant/perioperative treatment are sparse. We assume no difference between EOX-based NACT and NRCT.

Shortening of treatment duration in patients with chronic hepatitis C genotype 2 and 3 - impact of ribavirin dose - a randomized multicentre trial.

BACKGROUND: Chronic hepatitis C (CHC) Patients, infected with genotype (GT) 2 or 3 are treated with Peg-IFN and ribavirin (RBV) (800 mg/day) for 24 weeks. Treatment duration can be shortened to 12-16 weeks if a higher dose of RBV (1.000/1.200 mg/day) was used without considerable loss of responsiveness or increased risk of relapse. Previously we have shown that in patients with CHC, GT 2/3 RBV can be reduced to 400 mg/day if administered for 24 weeks without an increase in relapse rates. Therefore we investigated the efficacy of a reduced RBV dosage of 400 mg/day with shorter treatment duration (16 weeks). METHODS: Treatment naïve patients with CHC, GT 2/3 were randomized to receive 180 µg peginterferonα2a/week in combination with either 800 (group C) or 400 mg/d (group D) for 16 weeks. The primary endpoint was SVR. RESULTS: 12 months after the first patient was randomized a inferior outcome of group D as compared to group C was noted, therefore the study was terminated. At study termination 89 patients were enrolled (group C: 31, D: 51). The SVR rate was statistically different in the two study groups with 51.6% in group C and 28.4% in group D (p = 0.038). Patients with low viral load had higher SVR rates (C: 67%, D: 33%) than those with high viral load (C: 33%, D: 21%). CONCLUSION: Both treatment duration and the dose of RBV play a major role to optimize outcome of patients with GT3. If one intends to shorten the treatment weight based RBV dose should be used, if lower RBV doses are used patients should be treated for at least 24 weeks as. A treatment regimen with a reduced RBV dosage and shortened treatment duration is associated with low SVR rates due to high relapse rates. TRIAL REGISTRATION: NCT01258101.

Antiviral treatment of chronic hepatitis C in clinical routine.

OBJECTIVE: Pegylated interferon plus ribavirin is the standard treatment for chronic hepatitis C. Sustained virological response (SVR) rates of up to 60% are reported in randomized controlled trials, but it is unclear whether the results from such trials are reproducible in the clinical routine setting. We investigated consecutive treatment-naïve chronic hepatitis C patients at our center to examine the efficacy of treatment with pegylated interferon plus ribavirin in clinical routine. MATERIALS AND METHODS: Between 2000 and 2006 we treated a total of 219 patients with pegylated interferon alpha (2a or 2b) and ribavirin (800-1200 mg/d). Among them, 34.8% of patients infected with HCV genotypes 1/4/6 and 18.4% of those with genotypes 2/3 had advanced fibrosis or cirrhosis (F3-F4). For analysis of outcome we subdivided our series into two groups of patients: those who fulfilled standard inclusion criteria in randomized controlled trials and those who did not. RESULTS: The overall SVR rate was 44.3%. In patients with F0-F2 an SVR was achieved in 52.5%; in those with F3-F4 the SVR rate was 20.8%. In patients infected with genotypes 1/4/6 the SVR rate was 35.4% (SVR: F0-F2 47.7%; F3-F4 19.6%); in those with genotypes 2/3 the rate was 67.8%. The SVR rate in patients with unfavorable baseline factors was significantly lower (32.4% vs. 50%; P = 0.017) and they were more likely to be non-responders (30.9% vs. 13.8%). CONCLUSION: In everyday clinical practice, up to one-third of patients show unfavorable baseline factors for antiviral therapy, resulting in worse therapeutic outcome. Differences in therapeutic outcome are influenced by patient selection and by the proportion and severity of the underlying liver disease.

Methicillin-Resistant Staphylococcus aureus ST398 from human patients, upper Austria.

Methicillin-resistant Staphylococcus aureus (MRSA) clonal type ST398 is usually associated with animals. We examined 1,098 confirmed MRSA samples from human patients and found that 21 were MRSA ST398. Most (16) patients were farmers. Increasing prevalence from 1.3% (2006) to 2.5% (2008) shows emergence of MRSA ST398 in humans in Austria.

Ten years of antibiotic consumption in ambulatory care: trends in prescribing practice and antibiotic resistance in Austria.

BACKGROUND: The primary aims of this study were (i) to determine the quantity and pattern of antibiotic use in Austria between 1998 and 2007 and (ii) to analyze antibiotic esistance rates in relation to antibiotic consumption in important clinical situations in order to provide data for empirical therapeutic regimens for key indications. METHODS: Consumption data and resistance data were obtained via the Austrian surveillance networks European Antimicrobial Resistance Surveillance System (EARSS) and European Surveillance on Antimicrobial Consumption (ESAC). The EARSS collects data on isolates from blood and cerebrospinal fluid obtained predominantly in the hospital setting. The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD) measurement units were assigned to the data. The number of DDDs and packages per 1,000 inhabitants (PID) were used to calculate the level of antibiotic consumption. Antibiotic resistance was expressed in resistance rates, i.e., the percentage of resistant isolates compared to all isolates of one bacterial species. RESULTS: The overall antibiotic consumption measured in DIDs increased by 10% between 1998 and 2007, whereas PIDs decreased by 3%. The consumption of substances within the drug utilization 90% segment (measured in PID) increased for ciprofloxacin (+118.9), clindamycin (+76.3), amoxicillin/clavulanic acid (+61.9%), cefpodoxime (+31.6), azithromycin (+24.7); and decreased for erythromycin (-79.5%), trimethoprim (-56,1%), norfloxacin (-48.8%), doxycycline (-44.6), cefaclor (-35.1%), penicillin (-34.0%), amoxicillin (-22.5), minocycline (-21.9%) and clarithromycin (-9.9%). Starting in 2001, an increase in the percentage of invasive E. coli isolates resistant to aminopenicillins (from 35% to 53%), fluoroquinolones (from 7% to 25.5%) and third-generation cephalosporins (from 0% to 8.8%) was observed. The percentage of nonsusceptible or intermediate penicillin-resistant pneumococcal isolates remained stable over this time period at around 5%. For macrolides, the rate of resistant isolates increased from 5% to 12.8%, with a peak in 2005 at 14.7%. CONCLUSION: The Austrian resistance data can not explain the fundamental change in prescribing practice. The more frequent use of ciprofloxacin has most likely contributed to rising resistance rates in E. coli in Austria. Penicillin G is still a highly effective substance for the treatment of invasive infections caused by pneumococci.

Methicillin-resistant Staphylococcus aureus: a new zoonotic agent?

Staphylococcus aureus is a major cause of infection in hospitals and the community. One third of the general population is colonized by the bacterium, constituting a risk factor for acquisition of infection with this pathogen. Worldwide, the increasing antibiotic resistance of S. aureus complicates treatment of infection and control measures. Soon after the introduction of methicillin, the first isolates resistant to this antibiotic were reported and named methicillin-resistant S. aureus (MRSA). During the past decade a major change in MRSA epidemiology has been observed: whereas in the past MRSA was almost exclusively regarded a hospital pathogen, the advent of community-acquired MRSA has led to infections in people without hospital-related risk factors. Recent evidence has also identified a link between colonization of livestock and MRSA carriage and infections in people who work with animals. Screening of pigs and pig farmers in the Netherlands revealed high prevalence of MRSA sequence type (ST) 398 and it has become clear that the emergence of ST398 is not just a Dutch problem, as reports on livestock colonization and human infections are appearing worldwide. In Austria, the ST398 lineage has been detected in dust samples from pig breeding facilities and in food samples. Since the first Austrian detection of this emerging lineage in 2006, 21 human isolates, partially associated with infections, have been observed. MRSA has to be regarded as a new emerging zoonotic agent and livestock may constitute a growing reservoir of the ST398 lineage. More information is needed so that control measures to reduce the impact of the emerging MRSA ST398 lineage on public health can be developed and implemented.

The European surveillance activities EARSS and ESAC in the context of ABS International.

Development of resistance obstructs the successful use of antimicrobial drugs, since shortly after each and every introduction of a new antibiotic resistant pathogens have emerged. The hope of being able to reverse or at least slow down the occurrence of antibiotic resistance has led to a number of actions and initiatives. The project "ABS International - Implementing antibiotic strategies for appropriate use of antibiotics in hospitals in member states of the European Union", together with the European Antimicrobial Resistance Surveillance System (EARSS) and the European Surveillance on Antimicrobial Consumption (ESAC), covers a large proportion of possible actions against antibiotic resistance. The data generated by EARSS and ESAC are an essential prerequisite for targeted interventions to cope with the problem of antibiotic resistance. The project ABS International constitutes an impressive initiative to optimize the situation in hospitals in nine European member states.