The proliferation marker Ki-67 is one of the most controversially discussed parameters for treatment decisions in breast cancer patients. The purpose of this study was to evaluate the routine use and value of Ki-67 as a prognostic marker, and to analyze the associations between Ki-67 and common histopathological parameters in the routine clinical setting. Data from the clinical cancer registry Regensburg (Bavaria, Germany) were analyzed. Within the total data pool of 4,692 female patients, who had been diagnosed between 2005 and 2011, in 3,658 cases Ki-67 was routinely determined. Thus, a total of 3,658 patients with invasive breast cancer were included in the present study and used for statistical analysis. Ki-67 expression was associated with the common histopathological parameters. The strongest correlation was found between grading and Ki-67 (P < 0.001). In terms of survival analyses, Ki-67 was categorized into five categories (reference category Ki-67 ≤15 %) due to a nonlinear relationship to overall survival (OS). In multivariable analysis, Ki-67 was an independent prognostic parameter both for disease-free survival (DFS) (Ki-67 > 45 %, HR = 1.96, P = 0.001) as well as for OS (Ki-67: 26–35 %, HR = 1.71, P = 0.017; Ki-67: 36–45 %, HR = 2.05, P = 0.011; Ki-67 > 45 %, HR = 2.06, P = 0.002) independent of common clinical and histopathological factors. The 5-year DFS (OS) rate was 86.7 % (89.3 %) in patients with a Ki-67 value ≤15 % compared to 75.8 % (82.8 %) in patients with a Ki-67 value >45 %. Based on the data from a large cohort of a clinical cancer registry, it was demonstrated that Ki-67 is frequently determined in routine clinical work. Ki-67 expression is associated with common histopathological parameters, but is an additional independent prognostic parameter for DFS and OS in breast cancer patients. Future work should focus on standardization of Ki-67 assessment and specification of its role in treatment decisions.

Early biomarker-based prediction of imminent AKI followed by implementation of KDIGO care bundle reduced AKI severity, postoperative creatinine increase, length of ICU, and hospital stay in patients after major noncardiac surgery.

Two different methods yielded comparable results in identifying a reduction in the THI score of 6 and 7 points, respectively, as the minimal clinically relevant change. This study provides a first orientation for sample size calculations and for planning the design of future studies.

No abstract

Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity and treatment is elusive. A large variety of different treatment options have been proposed and from most of them some patients benefit. However, a particular treatment that helps one patient may fail for others. This suggests that there are different forms of tinnitus which differ in their pathophysiology and their response to specific treatments. Therefore, it is a major challenge for tinnitus treatment to identify the most promising therapy for a specific patient.However, most published clinical treatment studies have enrolled only relatively small patient samples, making it difficult to identify predictors of treatment response for specific approaches. Furthermore, inter-study comparability is limited because of varying methods of tinnitus assessment and different outcome parameters. Performing clinical trials according to standardized methodology and pooling the data in a database should facilitate both clinical subtypisation of different forms of tinnitus, and identification of promising treatments for different types of tinnitus. This would be an important step towards the goal of individualized treatment of tinnitus.For these reasons, an international database of tinnitus patients, who undergo specific treatments, and are assessed during the course of this treatment with standardized instruments (e.g., psychoacoustic measures, questionnaires) has been established. The primary objectives of this database are (1) collecting a standardized set of data on patient characteristics, treatments, and outcomes from tinnitus patients consulting specialized tinnitus clinics all over the world (at present 13 centers in 8 countries), (2) delineating different subtypes of tinnitus based on data that has been systematically collected and (3) identifying predictors for individual treatment response based on the clinical profile. Starting in 2008, the database currently contains data from more than 400 patients. It is expected that more centers will join the project and that the patient numbers will rapidly grow, so that this international database will further facilitate future research and contribute to the development of evidence based on individualized treatment.

Chronic tinnitus is a common condition with a high burden of disease. While many different treatments are used in clinical practice, the evidence for the efficacy of these treatments is low and the variance of treatment response between individuals is high. This is most likely due to the great heterogeneity of tinnitus with respect to clinical features as well as underlying pathophysiological mechanisms. There is a clear need to find effective treatment options in tinnitus, however, clinical trials differ substantially with respect to methodological quality and design. Consequently, the conclusions that can be derived from these studies are limited and jeopardize comparison between studies. Here, we discuss our view of the most important aspects of trial design in clinical studies in tinnitus and make suggestions for an international methodological standard in tinnitus trials. We hope that the proposed methodological standard will stimulate scientific discussion and will help to improve the quality of trials in tinnitus.

Prospective controlled cohort study, Level II.

The aim of the study was to explore the prevalence and risk factors for technical-induced hemolysis in adults supported with veno-venous extracorporeal membrane oxygenation (vvECMO) and to analyze the effect of hemolytic episodes on outcome. This was a retrospective, single-center study that included 318 adult patients (Regensburg ECMO Registry, 2009–2014) with acute respiratory failure treated with different modern miniaturized ECMO systems. Free plasma hemoglobin (fHb) was used as indicator for hemolysis. Throughout a cumulative support duration of 4,142 days on ECMO only 1.7% of the fHb levels were above a critical value of 500 mg/l. A grave rise in fHb indicated pumphead thrombosis (n = 8), while acute oxygenator thrombosis (n = 15) did not affect fHb. Replacement of the pumphead normalized fHb within two days. Neither pump or cannula type nor duration on the first system was associated with hemolysis. Multiple trauma, need for kidney replacement therapy, increased daily red blood cell transfusion requirements, and high blood flow (3.0–4.5 L/min) through small-sized cannulas significantly resulted in augmented blood cell trauma. Survivors were characterized by lower peak levels of fHb [90 (60, 142) mg/l] in comparison to non-survivors [148 (91, 256) mg/l, p≤0.001]. In conclusion, marked hemolysis is not common in vvECMO with modern devices. Clinically obvious hemolysis often is caused by pumphead thrombosis. High flow velocity through small cannulas may also cause technical-induced hemolysis. In patients who developed lung failure due to trauma, fHb was elevated independantly of ECMO. In our cohort, the occurance of hemolysis was associated with increased mortality.