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Pradiktive Biomarker sind ein integraler Bestandteil in der Diagnostik von Lungenkarzinomen. Neben molekularen Analysen spielt die Immunhistochemie eine bleibende und offenbar auch zunehmende Rolle. Die Bedeutung liegt hier vorrangig in der Selektion von Tumoren, die weiterfuhrend molekularpathologisch untersucht werden. Bei niedriger Pravalenz molekularer Subtypen kann die Immunhistochemie somit einen wertvollen Beitrag zur ressourcensparenden Diagnostik leisten. Einige Assays erlauben auch eine unmittelbare, nur auf Immunhistochemie beruhende pradiktive Einordnung. Mit neuen Medikamentenzulassungen fur Lungenkarzinome kommen weitere immunhistochemiebasierte pradiktive Biomarker hinzu. Durch die Auswahl geeigneter diagnostischer Primarantikorper, die sorgfaltige Validierung der Farbeprotokolle und standardisierte Auswertungen muss eine hohe Sensitivitat der Assays sichergestellt werden.

Background Uromodulin-associated Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD-UMOD) belongs to a group of autosomal dominant inherited diseases caused by mutations in the UMOD gene, which codes for uromodulin, a protein exclusively expressed in renal tubular cells of the ascending limb of the loop of Henle. The diagnosis is hampered by non-specific clinical, laboratory and histological findings. In this study, we evaluated serum uromodulin as diagnostic marker for ADTKD-UMOD in a family with a novel mutation in UMOD. Methods We investigated a family with five members suffering from chronic kidney disease of unknown origin (CKD) and three healthy members using whole exome sequencing. Serum uromodulin was measured by ELISA. The uromodulin concentration of each CKD family member was compared to reference CKD groups with similar eGFR and to non-CKD individuals in case of the healthy family members, respectively. Results Whole exome sequencing revealed novel missense mutation c.457T>G, p.(Cys153Gly) in UMOD. Serum uromodulin concentration was lower in all affected patients compared to all patients of the reference CKD groups, while healthy family members showed normal values comparable to those of the non-CKD reference group. Conclusions The mutation detected in our family leads to severely reduced serum uromodulin concentrations, distinguishing these patients clearly from CKD patients with comparable eGFR. Therefore, serum uromodulin could serve as a simple, new diagnostic marker to identify patients with ADTKD-UMOD.

Background Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. Method The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). Results All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. Conclusions It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.

New lines of evidence suggest that less than 10% of neurodegenerative diseases have a strict genetic aetiology and other factors may be prevalent. Environmental exposures to potentially toxic elements appear to be a risk factor for Parkinson’s, Alzheimer’s and sclerosis diseases. This study proposes a multidisciplinary approach combining neurosciences, psychology and environmental sciences while integrating socio-economic, neuropsychological, environmental and health data. We present the preliminary results of a neuropsychological assessment carried out in elderly residents of the industrial city of Estarreja. A battery of cognitive tests and a personal questionnaire were administered to the participants. Multivariate analysis and multiple linear regression analysis were used to identify potential relationships between the cognitive status of the participants and environmental exposure to potentially toxic elements. The results suggest a relationship between urinary PTEs levels and the incidence of cognitive disorders. They also point towards water consumption habits and profession as relevant factors of exposure. Linear regression models show that aluminium (R2 = 38%), cadmium (R2 = 11%) and zinc (R2 = 6%) are good predictors of the scores of the Mini-Mental State Examination cognitive test. Median contents (µg/l) in groundwater are above admissible levels for drinking water for aluminium (371), iron (860), manganese (250), and zinc (305). While the World Health Organization does not provide health-based reference values for aluminium, results obtained from this study suggest that it may have an important role in the cognitive status of the elderly. Urine proved to be a suitable biomarker of exposure both to elements with low and high excretion rates.

Hintergrund. Das Kompetenznetz Demenzen (KND) ist ein akademischer Verbund mehrheitlich psychiatrischer Gedächtnissprechstunden und verfolgt drei Ziele: (1) Die Weiterentwicklung der Demenzdiagnostik einschließlich Neuropsychologie, Biomarker, Bildgebung und Genetik. (2) Die Durchführung von Therapiestudien bei kognitiven Störungen und Demenzen. (3) Die Verbesserung der Versorgung von Demenzerkrankten in Deutschland. Ziel der Arbeit. In diesem Beitrag werden die bisherigen Ergebnisse einzelner Teilprojekte des KND zusammengefasst sowie Ausblicke über die laufende Forschung gegeben. Methoden. Es wurden zwei multizentrische Kohorten aufgebaut. In einer ersten Kohorte wurden Menschen mit einer leichten kognitiven Störung und Menschen mit einer beginnenden Demenz klinisch, neuropsychologisch sowie hinsichtlich verschiedener Biomarker untersucht. Ein Teil dieser Kohorte wurde im Rahmen einer Beobachtungsstudie über Jahre nachverfolgt, ein weiterer Teil im Rahmen von zwei Behandlungsstudien untersucht. In der zweiten Kohorte wurden Menschen ohne Demenz klinisch, neuropsychologisch und genetisch untersucht, und es wurden psychosoziale Faktoren erhoben. In den verschiedenen Teilprojekten des KND werden Daten über Follow-up-Zeiträume bis zu zehn Jahren ausgewertet. Ergebnisse und Diskussion. Das Kompetenznetz Demenzen hat zahlreiche Publikationen zur Diagnostik und Therapie von kognitiven Störungen und Demenzen sowie zur Versorgung von Demenzerkrankten in Deutschland ermöglicht. Der Verbund hat Strukturen sowie eine Daten- und Biomaterialbank geschaffen, die auch weiterhin die Grundlage für nationale und internationale Kooperationen sind. Darüber hinaus hat das KND zur Entstigmatisierung von Demenzerkrankungen beigetragen. Background. The Dementia Competence Network (DCN) is represented by academic memory clinics and has three major aims: (1) To facilitate the development of diagnostic tools including neuropsychology, biomarkers, imaging and genetics. (2) To implement clinical trials in mild cognitive impairment and dementia and (3) to improve standard care for dementia in Germany. Aims. This article summarizes the achievements of the DCN so far and highlights future perspectives. Methods. The DCN has built up two multicentre cohorts. Within the first cohort, patients with mild cognitive impairment or mild dementia were examined longitudinally using multiple neuropsychological assessments and numerous different biomarkers. In a subgroup of the first cohort, patients were treated with antidementive drugs in two placebo-controlled clinical trials. The second cohort included cognitively healthy older people and examined repetitively clinical, neuropsychological and psychosocial parameters for ten years. Results and discussion. The DCN has generated a large data and biomaterial bank. Numerous publications have helped to develop further diagnostic procedures and treatment of cognitive disorders and dementia. The DCN has contributed to end stigmatisation of dementia. peerReviewed

Hintergrund Die Entwicklung der individualisierten Medizin fordert eine bessere Risikopradiktion der aortalen Ereignisse und eine differenzierte Behandlung der erweiterten Aorta ascendens.

BACKGROUND: The diagnosis and treatment of periprosthetic joint infection (PJI) remain true clinical challenges. PJI diminishes therapeutic success, causes dissatisfaction for the patient and medical staff, and often requires extensive surgical revision(s). At the present time, an extensive multimodal algorithmic approach is used to avoid time- and cost-consuming diagnostic aberrations. However, especially in the case of the frequent and clinically most relevant "low-grade" PJI, the current diagnostic "gold standard" has reached its limits.EVALUATION: Synovial biomarkers are thought to close this diagnostic gap, hopefully enabling the safe differentiation among aseptic, (chronic) septic, implant allergy-related and the arthrofibrotic genesis of symptomatic arthroplasty. Therefore, joint aspiration for obtaining synovial fluid is preferred over surgical synovial tissue biopsy because of the faster results, greater practicability, greater patient safety, and lower costs. In addition to the parameters synovial IL-6, CRP, and leukocyte esterase, novel biomarkers such as antimicrobial peptides and other proinflammatory cytokines are currently highlighted because of their very high to excellent diagnostic accuracy.CONCLUSION: Independent multicenter validation studies are required to show whether a set of different innovative synovial fluid biomarkers rather than a few single parameters is favorable for a safe "one-stop shop" differential diagnosis of PJI.

A mixed hidden Markov model (HMM) was developed for predicting breeding values of a biomarker (here, somatic cell score) and the individual probabilities of health and disease (here, mastitis) based upon the measurements of the biomarker. At a first level, the unobserved disease process (Markov model) was introduced and at a second level, the measurement process was modeled, making the link between the unobserved disease states and the observed biomarker values. This hierarchical formulation allows joint estimation of the parameters of both processes. The flexibility of this approach is illustrated on the simulated data. Firstly, lactation curves for the biomarker were generated based upon published parameters (mean, variance, and probabilities of infection) for cows with known clinical conditions (health or mastitis due to Escherichia coli or Staphylococcus aureus). Next, estimation of the parameters was performed via Gibbs sampling, assuming the health status was unknown. Results from the simulations and mathematics show that the mixed HMM is appropriate to estimate the quantities of interest although the accuracy of the estimates is moderate when the prevalence of the disease is low. The paper ends with some indications for further developments of the methodology.

Zusammenfassung: Biomarker, ein inzwischen geradezu inflationär verwendeter Begriff! Während in den vergangenen Jahrzehnten die Bezeichnung „Marker“ vor allem mit Tumorerkrankungen und deren klinisch-chemischer Diagnostik verbunden war, hat die „-omics“-Welle der letzten Dekade eine Unmenge an neuen „Markern“ für alles und jedes in die medizinische Literatur gespült. Insbesondere der unkritische Umgang mit jenen Markern und die Unerfahrenheit derjenigen, die durch neue Techniken in vormals rein naturwissenschaftlichen Fachgebieten in die Lage versetzt wurden, diese neuen Marker zu messen, haben nicht nur zu einer großen Verunsicherung in bezug auf die Wertigkeit von Biomarkern an sich, sondern auch zu einer großen Enttäuschung in den wie Strohfeuer aufflammenden „-omics“-Disziplinen geführt. Kaum einer der oft hervorragend publizierten Biomarker hat den Weg in die Klinik gefunden, hochzitierten Wissenschaftlern konnten elementarste Fehler in (Prä-)analytik und Interpretation nachgewiesen werden und selbst die bisher als anerkannt angesehenen „klassischen“ Tumormarker sind vielfach in Misskredit geraten. Zu Unrecht! Denn mit alten wie neuen Markern hat die Labormedizin hervorragende Werkzeuge in der Hand, die, richtig angewandt, nicht nur das Potential haben, die Labordiagnostik zu revolutionieren, sondern auch das Gesicht des Faches verändern werden, weg von einer in vitro quantifizierenden Hilfsdisziplin hin zu einer integrativen und interpretativen Wissenschaft.

Zusammenfassung: In den letzten Jahren wurden neben genetischen Studien immer mehr Analysen von Veränderungen im epigenetischen Code durchgeführt. Epigenetische Mechanismen bestimmen, welche Gene in welcher Zelle transkribiert werden. Damit formen sie den Phänotyp. Der epigenetische Code kann durch Umwelteinflüsse modifiziert werden. Dies ermöglicht den Zellen, sich an lang anhaltende Veränderungen in ihrer Umgebung anzupassen. Daher liegt der Schluss nahe, dass epigenetische Veränderungen die Grundlage für langfristige Auswirkungen von Umwelteinflüssen auf die Gesundheit sein können. Vor allem bei Tumoren und chronisch-entzündlichen Erkrankungen zeigen immer mehr Studien, dass mit dem Krankheitsverlauf epigenetische Veränderungen einhergehen. Das Wissen um epigenetische Veränderungen könnte zukünftig in der Praxis genutzt werden, sowohl als Biomarker und prognostischer Faktor wie auch als therapeutischer Ansatz.

Background miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. Methods We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. Results We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 (95% CI: 0.703–0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. Conclusions Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers. Electronic supplementary material The online version of this article (doi:10.1186/s12916-014-0224-0) contains supplementary material, which is available to authorized users.

New guidelines of the "Kidney Disease: Improving Global Outcome" (KDIGO) working group standardize the definition of acute kidney injury (AKI) and acute kidney disease (AKD) allowing the assessment of prognosis and efficacy of prophylactic and therapeutic measures in different patient cohorts. The degree of severity and the duration of acute kidney injury are critical factors for the development of chronic kidney disease and mortality. The achievement of optimal fluid volumes is a cornerstone in the treatment during the early phase of AKI, while volume overload should be avoided in the late phase of established AKI. Recently employed biomarkers are promising for the early detection and prognosis of AKI, but cannot yet be used as routine tests. Microscopic urinalysis, a very old and cost-effective diagnostic measure, provides valuable informations about the severity and the course of AKI.

Classical prognostic factors for squamous cell carcinoma of the head and neck (HNSCC) are based on general parameters such as tumor stage or histological grading and only allow for a rough estimation of the clinical course. However, predicting individual responses to treatment remains challenging and diverging clinical courses of same-stage HNSCC stage remain obscure. The need for a better understanding of the individual genomic or proteomic signature of HNSCC resulted in a great number of publications on novel biomarkers. Still, in most cancer centres therapy planning and risk appraisal are solely based on the classical factors with only a few exceptions such as HPV status in oropharyngeal carcinoma. Future improvements in biomarker research will probably be achieved with sets of various genomic and proteomic markers as provided by microarray technology. This review highlights the criteria for a successful biomarker candidate, gives an overview on the most important new biomarkers, and introduces the principles of genomic and proteomic biomarker chips.