Lung diseases are one of the leading causes of death in Germany and the world. They often display a high disease burden and very few therapeutic options are available for chronic lung diseases at the moment. In order to treat lung diseases permanently successfully, researchers have to counter these challenges in a scientific and organized manner.

DZL- BREATH
In November 2011 Hannover was chosen from the Federal Ministry of Education and Research (BMBF) as one of five sites of the German Centre for Lung Research (DZL) in Germany. As network with the name BREATH, Hannover Medical School (MHH) applied together with the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) and the Leibniz Universität Hannover to the BMBF and convinced with their concept. (BREATH: Biomedical Research in Endstage And ObsTructive Lung Disease Hannover).

http://www.breath-hannover.de/en/ 

Biobanks analyze, collect and manage biomaterial from clinics and research under standardized conditions as part of the DZL.

DZL - Biobanking at BREATH
The Hannover Unified Biobank (HUB), the centralized, harmonized, modern and standardized biobank of the MHH, establishes sophisticated biobanking according to the DZL standard at the DZL location BREATH.

Standardized biobanking at the DZL sites enables sophisticated and secure storage of biomaterials. The biomaterial samples obtained in the clinic and research are analyzed, collected and administered in the biobanks of the respective locations. The DZL platform biobanking and data management unites the biobanks of the DZL and aims to network the existing biobanks of the individual sites and to make the collections accessible to the research projects of the DZL.

Furthermore, a DZL Biobanking Portal was created, which is available to all DZL members, has all relevant documents and information on sample collections available and is linked to existing Internet catalogs of biobanks. The DZL Platform Biobank and Data Management of the DZL also work on the harmonization of biomaterial collections. Through the harmonization and standardization of the "Standard Operating Procedures" and other guidelines and documents of biobanking in the field of ethics, data protection and quality assurance with the construction of a data warehouse structure, the DZL presents itself as an excellent research network in Germany.

Further information of German Centre for Lung Research (DZL):

https://www.dzl.de/en/

DZL – German Centre for Lung Research

The German Centre for Lung Research (DZL) is a BMBF-initiated network that aims to establish effective therapies for lung diseases and new options for prevention and diagnosis. Basic research, which is closely interconnected with clinical practice, is central. The results of basic research should be translated into clinical medicine quickly using a bidirectional process.

The DZL is a coalition of the leading university and non-university institutions for lung research that aims to thoroughly investigate the eight core diseases or groups of diseases:

• Asthma and allergies
• Chronic Obstructive Pulmonary Disease (COPD)
• Cystic Fibrosis (CF)
• Pneumonia and Acute Lung Injury
• Diffuse Parenchymal Lung Disease (DPLD)
• Pulmonary Hypertension (PH)
• End-Stage Lung Disease
• Lung Cancer (LC)

Although antibiotics and vaccines have been used successfully for decades, infections remain responsible for an immense number of illnesses and deaths worldwide. Among the major challenges are chronic and poverty-related infectious diseases and in particular emerging, microbial and viral infections, which spread quickly globally via modern ways of transportation. The rapid emergence of resistance against available anti-infectives is another serious threat. There are also infections in immunocompromised patients, which pave the way by the modern high-performance medicine in particular in the field of transplantation and oncology.

In order to combat pathogens and the associated threats to health, new, integrative and interdisciplinary approaches are needed in which experts work closely together in the fields of translational basic science, epidemiology and clinic. In 2011, the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) has established the German Centre for Infection Research, in which universities, university hospitals, Leibniz and Max Planck Institutes and the Helmholtz Centres and federal research facilities with a distinctive profile in the field of infectious diseases are brought together to counter the infectiological main challenges with an integrated approach.

http://www.dzif.de/en

Translational Infrastructure Biobanking

A comprehensive biobanking structure is indispensable to conduct infection research at many different locations and to transfer the research results into practice.

Biospecimen of high pertinence for DZIF partners are for example cultures of pathogens and so-called microbial producers, which are bacteria that are suitable for the production of compounds, as well as liquid biological samples like serum, plasma and urine or well characterized tissue samples of infected patients.

Within the DZIF unit “Biobanks”, a coordinator and a technology platform were established. The DZIF location in Heidelberg is coordinating the tissue biobank. The German Collection of Microorganisms and Cell Cultures (DSMZ) provides standards and protocols for the storage, maintenance, authentication and quality control of microbial pathogen strains and microbial producers. The DZIF location in Munich is responsible for biobanking of liquid samples.

The biobanking platform is a resource and technology platform for DZIF, which

• Provides biospecimen of high quality with associated clinical data
• Supports biobanking activities at partner locations with roll-out programs
• Promotes harmonization and standardization of work flows as well as ELSI-, IT-, QM- and IP-solutions

The biobanking platform is based on existing and future biobanks and collections within DZIF and their expertise and organizational structure.

They cooperate with national (TMF) and international (BBMRI, EMbaRC, GBRCN) actors in the field of biobanking and draw on generic concepts.

Aims of the DZIF biobanking platform

The DZIF biobanking platform has the aim to provide safe and high quality, authenticated and standardized biomaterials and their derivates to the DZIF-Projects and partners.

Aims in detail:

• Setup and coordination of a DZIF bio resource platform
• Establishment and characterization of collections of microbial pathogens and compound producer as well as human biomaterial and their derivatives (DNA, RNA, meta data, cell lines) for DZIF and other partners at the DZIF partner sites
• Setup of a method platform for the generation of derivatives and improved analysis
• Setup of a data base, a "virtual bio resource center", in which the corresponding meta data of the samples becomes available for the DZIF partners
• Development of structured ELSI, QM und IT solutions for DZIF biobanks and partners

https://www.dzif.de/en/infrastructure/biobanking

Strengthen research in the network

The German Biobank Node (GBN) is the central cooperation platform for German biobanks. Under the umbrella of GBN, eleven biobank locations work together in the biobank alliance German Biobank Alliance (GBA) to support biomedical research with high-quality biomaterial samples and data. Hannover Unified Biobank (HUB) is a partner of this biobank alliance.


Together, the GBA's biobanks develop uniform quality standards, build a networked IT structure and create legal and ethical guidelines for biobanking. In doing so, they lay the foundation for the further development and quality assurance of biobanking in Germany and Europe. The networking of German biobanks is funded by the Federal Ministry of Education and Research (BMBF).


GBN is still a partner in the European biobank network BBMRI-ERIC, which focuses on networking and the exchange of experiences of biobanks within Europe.



General

The German Biobank Alliance (GBA) was initiated in 2017 by the German Biobank Node (GBN). Funded by the Federal Ministry of Education and Research (BMBF), GBN sees itself as a central cooperation platform for the German biobank community. Under the umbrella of GBN, eleven BMBF-funded biobanks and two IT development centers work together in the German Biobank Alliance (GBA) to make existing biomaterials from various biobanks available for biomedical research across Europe.

Overview of the German Biobank Alliance
Eleven German biobanks have joined together in the German Biobank Alliance. Together, they store almost 14 million bio samples that are available for research. By 2020, they will work to ensure that these samples and data can be exchanged between biobanks in Germany and Europe. For this purpose, common IT infrastructures are developed, quality standards are implemented and legal and ethical standards are harmonized.

Biobanks - Essential for biomedical research

The future of hearing

The goal of the Cluster of Excellence "Hearing4all" is literally "hearing for everyone". By improving individualized hearing diagnostics and the appropriate provision of personal hearing aids, the scientists want to decisively improve the communication situation of those affected - whether at work, in traffic or at home. Basic, model-based work on diagnosis and the auditory profile of normal to hard-of-hearing people is carried out in order to gain a better understanding of the individual's hearing. In addition, these models are used to improve the individual supply of technical hearing aids and to optimize them for the respective situation.

Further Information: Hearing4All

Cluster of Excellence RESIST for infection research

The aim of the Resist excellence cluster is to better understand the individual's susceptibility to infections in order to be able to avoid, diagnose and treat infections "tailor-made" on this basis. "This is a great day for infection research and therefore for people who are particularly susceptible to infections - be it due to congenital immune deficiencies, an under-developed immune system or as a result of medical therapies. You can particularly harm infections and we look forward to to be able to improve the possibilities for diagnostics and therapy in the long term, "said Professor Dr. Thomas Schulz. The head of the MHH Institute for Virology is the spokesman for this regional network, to which the Helmholtz Center for Infection Research, the TWINCORE Center for Experimental and Clinical Infection Research, the University of Veterinary Medicine, the "Center for Structural Systems Biology" (CSSB) in Hamburg and the "Center for Chronic Immunodeficiencies" (CCI) in Freiburg belong.


For example, newborns and the elderly, whose immune system is not yet developed or very susceptible, and people whose immune system is dampened for therapeutic reasons, such as multiple sclerosis or after a transplant, are particularly susceptible to infections. However, infections can also be dangerous for wearers of implants.

In order to be able to fight infections better than before, the RESIST team will investigate the molecular basis of defenses against pathogens and develop diagnostic methods with which the individual's susceptibility to infection can be better assessed in order to make the therapy more individual.

Basic research is carried out in RESIST and new paths are to be shown that can be expanded in existing translational programs, for example in the German Centers for Infection and Lung Research, in the Clinical Research Center and in the Center for Individualized Infection Medicine. In the long term, the new knowledge gained in RESIST should be taken up in these centers and further developed for use on patients.

In the past 18 years, emerging coronaviruses have triggered two epidemics and recently a serious pandemic that has killed thousands. The extent of the current pandemic can not yet be predicted. Quick measures are required to mitigate the consequences of the current pandemic and, moreover, to better prepare ourselves for new corona viruses in the long term.

Together with scientists and physicians of the MHH and the Helmholtz Centre for Infection Research the HUB started to establish a cohort of COVID-19 patients in March 2020 with a comprehensive collection of biosamples and data. The project is funded by the federal ministry for science and culture. Patients are recruited from the MHH and KRH (Klinikum Region Hannover). Adult patients (over 18 years old) with a confirmed SARS-CoV-2 infection and different degrees of severity are included in the cohort. The cohort envisages weekly longitudinal follow-ups during the inpatient treatment as well as a follow up visit 6-8 weeks and 6 month after hospital discharge (post COVID). The collection of biosamples at each visit comprises plasma, urine, DNA, RNA (Paxgene) , salvia and viable PBMC. All samples can be connected to the clinical data collected in the MHH clinical data ware house. An intensive molecular characterization of this cohort is planned. Omics data (metabolomics , WGS, Genomic structural variations, Transcriptomics in blood, Epigenomics (Methylation), cytokine analysis, immune cell analysis)

It is planes to include a total of 1000 patients. Currently 38 patients are included. The future number of patients will be strongly influenced by the further course of the COVID pandemic. To involve a higher number of patients a cooperation with the local public health department for the recruitment of patients is planned.

Biomaterial:

Blood, PBMCs, Plasma, Serum, Buffy Coat, Salvia, and Bronchioalveolarlavage (BAL)

Patient account:

A total of 1000 patients with different degrees of severity of the disease course or control persons are planned.

A Use and Access Committee (UAC) decides on the allocation of samples.

TTRAC-19 Biobank

TRAC 19 - Transmissions Analytics Covid19

Lower Saxony school model project for the elucidation of SARS-CoV-2 infection pathways among schoolchildren in childhood and adolescence and their teachers as a function of time


The opening of the schools following the previous full lockdown according to the gradual plan of the Lower Saxony Ministry of Culture offers a unique opportunity to increase the prevalence and the increased incidence expected from the increased interaction of children and adolescents (pupils, students) with each other and with adults (teaching staff) by COVID-19 using selected Hanover school locations. For the first time, the study requested will be quality-assured, up-to-date and, in addition, very quickly (within 6-8 hours) real-time data on the infection chain and spread and thus provide the essential information for the establishment of knowledge-based decision-making aids. These important findings allow taking appropriate, effective measures and preparing for better crisis management in other cases.
This would make Lower Saxony an innovative model location and could provide important information not only for the entire Republic, but for other highly industrialized companies with a similar age structure and far beyond. The proposed project is an innovative model project for immediate effective support in the fight against Corona SARS-CoV-2 through trans- and interdisciplinary study cooperation between LUH, MHH, NIFE and HMTMH, which, when implemented, also promotes international visibility in science and society leads.

Kooperationspartner:

• Gottfried Wilhelm Leibniz Universität Hannover (LUH)
• Hochschule für Musik, Theater und Medien Hannover (HMTMH)
• Medizinische Hochschule Hannover (MHH), HAannover Unified Biobank (HUB)
• Niedersächsisches Zentrum für Biomedizintechnik, Implantatforschung und Entwicklung (NIFE)

Biomaterial:

• Plasma,
• Buffy Coat

Prospective Cohort study:

School children (5th to 12th grade), adult family members (1,000) and teachers (75) living in the house are taken blood samples and tested for SARS-CoV-2 antibodies or COVID-19. An initial examination is followed by up to 2 follow-ups. This is followed by a statistical evaluation of the prevalence and incidence of SARS-CoV-2 infections and the prevalence and incidence of antibodies against SARS-CoV-2 in all groups.

The project may be extended to other schools.

COVID 19 antibody cohort:

Analysis of  Sars-CoV-2 Antibody in normal population

• 60.000 participants
• Healthy  adults
• EDTA Plasma

National Research Network of University Medicine on COVID-19 (NFN) - National Pandemic Cohort Network (NAPKON)

National Pandemic Cohort Network:

The aim is to build a harmonized, expandable and interoperable National Pandemic Cohort Network (NAPKON) to support the fight against the current COVID-19 pandemic and its consequences, as well as future pandemics of any origin. The establishment of a uniform concept with infrastructure cores and 3 cohort platforms for the representative acquisition of fine-grained data and bio samples.

The 3 PLT consist of platform A (LEOSS), platform B (intensive examination of patients in the clinic) and platform C (population).

There is also an examination for the late effects of recovered COVID-19 patients, combined with a comprehensive, harmonized collection of data and bio samples under a common governance structure.

Patients:

• planned 12.000 patientes

Groups:

• asymptomatic and slightly ill

• seriously ill, hospitalized

• critically ill, intensive care unit

Building on the successes of NAPKON in 2020 and 2021, national collaboration will continue across the three NAPKON cohorts to fulfill the mission of establishing a national collaborative infrastructure and making relevant contributions to the understanding and long-term management of the current SARS-CoV-2 pandemic (see NAPKON). NAPKON and NUKLEUS will continue to develop close collaboration and synergies with the NUM projects COVerCHILD, COVIM, and the NAPKON Therapeutic Intervention Platform (NAPKON-TIP). The specific goals of NAPKON v2 are to consolidate infrastructure and generate new knowledge on COVID-19 and PCS (Post-COVID-19 syndrome). Data and biospecimens collected in the NAPKON cohorts will additionally be used for centrally performed multi-OMICs analyses to explore pathophysiological mechanisms of COVID-19 and signatures that predict and cause specific outcomes and phenotypes of COVID-19 and post-COVID-19 syndrome (PCS). To this end, the project was linked to the Sample Analysis for Post Covid Research in NAPKON (SAPCRiN) project (see SAPCRIN).

Any corona infection carries the risk of long-term health damage. However, there is a lack of precise diagnostic criteria, scientifically sound knowledge about the pathophysiology and risk factors as well as treatment options for Long Covid.
With the aim of finding prognostic markers as well as treatment options for the disease, the SAPCRiN project will start as part of a call for proposals on Long Covid.
SAPCRiN is based on NAPKON. NAPKON offers an ideal platform for research on Long Covid. Within three different Covid 19 patient cohorts, clinical data, biosamples and imaging data of acutely ill or recovered Covid 19 patients are collected nationwide according to uniform standards. In this way, the course of the disease of covid-19 can be recorded, the connection with comorbidities and other health parameters as well as the late effects can be examined. In NAPKON, COVID-19  patients* are recruited and followed longitudinally. Standardized biosamples will be collected at all participating university hospitals and will form the basis for systematic molecular characterization.

The NUM Clinical Epidemiology and Study Platform (NUKLEUS) provides an infrastructure and specific know-how for the planning, implementation and evaluation of multicentre clinical and epidemiological studies. It offers the scientific community optimal access to infrastructures for the provision of high-quality data and biosamples.
The Biosample Core Unit (BCU) is responsible for the quality of biospecimens and biospecimen associated data in NAPKON and future NUM studies. High quality biobanking, in particular the use of common standard operating procedures (SOPs) for biosample collection and processing, is an important prerequisite for multicentre studies and ensures successful and reproducible research based on the collected biosamples. The BCU is managed by Prof. Dr. Illig from the Hannover Unified Biobank (HUB) of the MHH and Dr. Anton from the HMGU in Munich. Furthermore, an audit programme was developed and implemented by the BCU to support the various university hospitals in implementing the uniform quality standards for the provision of high-quality data and biospecimens.

n order to meet the challenges of current and future pandemics as well as current research questions with high medical demands, a network is needed that can quickly focus the capabilities of university medicine on the particularly urgent and important tasks and carry out complex clinical studies itself.
To this end, a Therapeutic Intervention Platform (NAPKON-TIP) is to be established based on the recruitment network successfully established in the National Pandemic Cohort Network (NAPKON) and the NUM infrastructures, in particular the NUM Clinical Epidemiology and Studies Platform (NUKLEUS).
NAPKON-TIP is designed as a platform for adaptive clinical trials to facilitate the ongoing evaluation of new therapies for efficacy and safety in stratified populations. The focus of NAPKON-TIP is on adaptive trials, the specificity of which is that the therapies and subgroups included can be adjusted as new knowledge about the efficacy and safety of the treatments, as well as population stratification within or outside the platform study, suggests.

Refugees are particularly vulnerable to infectious diseases due to the living conditions caused by displacement and mass accommodation. Due to the generally low vaccination rates and the comparatively high prevalence of certain infectious diseases (e.g. COVID 19, HIV, HBV, HCV, TB, measles, chickenpox) in the Ukrainian population, infectious medicine expertise is particularly in demand here. Specifically, a total of 2,500 refugees will undergo a structured screening and vaccination programme in the participating NUM centres in close cooperation with the health offices. This also includes children who are particularly involved in the current wave of refugees and are at risk of infectious diseases. The data collected in this context will be systematically evaluated by NUM scientists in order to better identify care needs in the group of war refugees and to be able to formulate a corresponding recommendation.

A phase III randomized, double-blind, placebo-controlled, multi-center clinical trial to assess the efficacy and safety of VPM1002 (vaccine) in reducing hospital admissions and / or severe infectious respiratory disease in the elderly during the SARS-CoV-2 pandemic by modulating the Immune system.

The participation of 10 national centers is planned, a total of 2040 patients will be recruited, 300 of them in Hanover.

• 300 patients

• Male and female adults (≥ 60 Jahre)

• Serum

NEOCYST is a multidisciplinary network of clinicians, geneticists and scientists with the common goal of improving the quality of life of patients and their families who are affected by congenital and hereditary cystic kidney diseases.

The network aims to promote understanding of demography, phenotypes and consequences, genetic causes and the molecular pathomechanisms of childhood cystic kidney disease with / without extrarenal manifestations. The integration of several nationwide clinical registries under the common heading "Cystic Kidney Disease" provides the clinical information and molecular genetics required for validated genotype-phenotype correlation analysis and the search for new genes.

The parallel establishment of a biobank as a platform for disease-specific translational research and helps in the identification of general “pathways” in cyst formation and disease progression with a special focus on cilia length control, signal transduction and planar cell polarity through the use of human biomaterials.

The focus of the biomaterial biobank subproject is the establishment of a biomaterial collection of patients in the early beginning of the cystic kidney.

The collection includes body fluids such as EDTA blood for plasma, DNA, serum, urine and primary cells. Within 3 years approx. 200 patients will be involved in this project, 60 patients will be recruited annually in up to 6 clinical centers of the NEOCYST consortium and their cooperation centers. The patients come for follow-up examinations

Through harmonized SOPs, sample generation, processing, storage and sample dispatch are adapted to the standards of the German Center for Lung Research (DZL), the TMF and ISBER. The samples are aliquoted in 2D barcode cryotubes and frozen in clinical centers. The trial registration takes place in a web-based registration tool.

The frozen biomaterials from the clinical sites are sent to the MHH Hannover Unified Biobank (HUB). In the HUB, the samples are registered, checked and stored in an automatic -80 ° C warehouse. Two thirds of the samples are stored for long-term storage in the gas phase of liquid nitrogen tanks. The remaining third of the samples are left in the automated warehouse for quick sample access for the consortium's sub-projects.

All processes are supported by modern, secure IT systems and meet the requirements of the TMF data security concept. A central study register holds the patient-related phenotype data.

Further information: www.neocyst.de

The PROBASE study (Risk-adapted prostate cancer early detection study based on a “baseline” PSA value in young men - a prospective multicenter randomized trial) examines a modern concept for general PSA screening. With this risk-adapted strategy, the PSA tests are carried out depending on the individual risk of the man, which is determined on the basis of a basic PSA value at the age of 45 or 50 years.

The determination of the level of the prostate-specific antigen (PSA) in the blood plays an important role both in the diagnosis of prostate cancer - called prostate cancer by doctors - and in the control of prostate cancer therapy. In contrast, it is controversial in early detection. On the one hand, PSA screening, i.e. the determination of the PSA value in all men from a certain age at regular intervals, detection of prostate cancer earlier and therefore better treatment, which reduces mortality. On the other hand, men with prostate cancer have such a favorable prognosis that they do not necessarily need treatment. However, this often begins when prostate cancer is diagnosed. In addition, results are possible in the PSA measurement, which incorrectly speak for the presence of prostate cancer. For this reason, general PSA screening can result in further physical and psychological stressful examinations and treatments that would not have taken place without screening.

Further information: www.probase.de

The German multi-organ Auto-Immunity Network (GAIN) is an association of doctors and scientists from the universities of Freiburg, Hanover, Munich and Kiel with the aim of researching multi-organ autoimmune diseases.


Multi-organ autoimmune diseases are very rare diseases and are often triggered by monogenetic mutations in certain immunoregulatory genes.


The GAIN project aims to examine pathophysiology and identify new genetic causes. A patient registry and a biobank for multi-organ autoimmune diseases are also to be set up. The collected samples and data should also be available for internal and external scientific projects in the future.

The nationwide DIGIT-HF study starts in the 2nd funding period


Around three million people in Germany suffer from chronic advanced heart failure. The disease is one of the most common reasons why patients have to be admitted to hospital or die from the consequences. In this large, multi-center study, scientists at the Clinic for Cardiology and Angiology at the Hannover Medical School (MHH) are testing the effectiveness of the drug Digitoxin. More than 800 patients in around 40 centers have already been included in the DIGIT-HF study.

Further information: https://www.digit-hf.de/

2nd funding period of KFO311

In its assessment, the German Research Foundation (DFG) highlighted the excellent results of our Clinical Research Group (KFO) 311 and is funding our work for another three years with more than six million euros.

Our network, in which nine MHH clinics and institutes conduct research together, develops treatment strategies and reparative therapies for patients with severe heart and lung diseases. The aim is to further develop mechanical relief and also to identify new reparative therapies that help the heart and lungs to recover.

We are on the right track with the results of the first funding period and now want to further develop these approaches to therapies for our patients. The poor prognosis of these patients should improve sustainably, their lives extended and their quality of life increased.

Specifically, in the second funding period we would like to (i) better understand the biological effects of mechanical relief and the pathomechanisms of tissue repair in acute and (pre-) terminal heart and lung failure, (ii) define new reparative therapy approaches in model organisms and already identified therapy strategies translate towards clinical application and (iii) further develop relief therapy in the patient based on evidence. Structurally, the KFO311 bundles cardiological, pneumological, cardiac / thoracic surgery and pathological expertise as well as experience in multimodal imaging in experimental and clinical areas at the MHH. The KFO311 benefits from its networking with excellent associated institutes and the central facilities and core units of the MHH for preclinical research and clinical studies. We also support young academics in clinics with structured programs at the MHH.

Pathology platform for heart and lung tissue and liquid biobanking

In the second funding period, the KFO311 benefits from an already established and unique infrastructure for the rapid processing of fresh human tissue and body fluids as well as biobanking and long-term storage. Quickly available, expertly assessed and extremely valuable tissue from human and animal hearts and lungs as well as standardized liquid samples are generated and thus added value for the research groups belonging to KFO311.

In order to provide a comprehensive overview of available samples and sample quality, a sample platform is implemented in which all samples are visible.

Project Leader:

Prof. Dr. Thomas Illig

Prof. Dr. Danny Jonigk
 

ZIFCO - Integrierte Infektionsforschungskohorte des Deutschen Zentrums für Infektionsforschung (DZIF) in der NAKO Gesundheitsstudie

ZIFCO's goal is to use the infrastructures and data generated within the framework of the NAKO health study, using current eHealth developments, for translational infection research in Germany.

In ZIFCO, we prospectively examine risk factors for acute respiratory, gastrointestinal and urogenital infections as well as the susceptibility to such infections. Conversely, we will investigate to what extent acute infections and their susceptibility to them can represent a risk factor for other, non-communicable diseases (e.g. cardiovascular diseases).

Further infomation:

https://www.helmholtz-hzi.de/de/forschung/forschungsprojekte/ansicht/projekt/detail/zifco/

Sepsis ist eine lebensbedrohliche Wirtsreaktion auf eine Infektion mit konsekutivem Organversagen.
Hier ist sehr häufig die Lunge im Sinne eines ARDS (Adult Respiratory Distress Syndroms)
betroffen.

Es handelt sich beim ARDS-Register und Biobank um eine unizentrische, prospektive Registerstudie mit Asservierung von Biomaterial
(Plasma / Serum / DNA / Urin / BAL).

Die Transplantationskohorte des DZIF ist ein Bestandteil des Forschungsbereiches "Infektionen im immungeschwächten Wirt" im Deutschen Zentrum für Infektionsforschung (DZIF) und speziell auf die Belange von Patienten ausgerichtet, die ein Spenderorgan oder eine Stammzelltransplantation erhalten haben.

Hintergrund

Empfänger von Spenderorganen sind lebenslang auf die Einnahme von Medikamenten angewiesen, um eine Abstoßung des neuen Organes zu verhindern. Diese Immunsuppressiva schwächen einen Teil der körpereigenen Immunantwort. Dies schützt das neue Organ, führt jedoch zu einer erhöhten Anfälligkeit für Infektionen. Organempfänger sind somit in besonderem Maße durch Krankheitserreger gefährdet. Auch Empfänger von Stammzellen verfügen durch die zugrundeliegende Erkrankung und die Behandlung zunächst über eine stark reduzierte Immunabwehr.

Dies bedeutet, dass Infektionen schneller als üblich auftreten und zu Komplikationen führen können. Wurde ein Organ transplantiert, so können Infektionen die Funktion des Organes beeinträchtigen und im schlimmsten Fall auch zu einem Versagen des neuen Organes führen.

Das individuelle Risiko der Patienten, Komplikationen zu erfahren, ist von vielen verschiedenen Faktoren abhängig. Je besser die Zusammenhänge zwischen der Art der Transplantation, den Vorerkrankungen, der Medikation und auftretenden Infektionen verstanden sind, desto besser können in der Praxis die Prävention und die Behandlung erfolgen.

Ziele

Mit Hilfe der Transplantationskohorte können medizinische Daten und biologische Proben von transplantierten Patienten in ganz Deutschland gesammelt und verwaltet werden. Diese Daten und Proben bilden die Grundlage wissenschaftlicher Studien. Dabei werden Zusammenhänge zwischen den zahlreichen Faktoren untersucht, die einen Einfluss auf die Infektanfälligkeit und die Funktion der Organe haben können. In Zusammenarbeit mit den beteiligten Kliniken und Forschungseinrichtungen wollen wir den Austausch von Erfahrungen fördern und neues Wissen erlangen. Die Studienergebnisse können dazu führen, dass neue Erkenntnisse gewonnen und die Behandlung von transplantierten Patienten fortlaufend verbessert werden können.

Gesammelte Daten und Proben

Wesentlicher Bestandteil der Transplantationskohorte ist die Kohortendatenbank, die vom Institut für Medizinische Statistik und Epidemiologie des Klinikums rechts der Isar in München betrieben wird.

In dieser Datenbank werden Informationen gesammelt, die Aufschluss über das individuelle Infektionsrisiko transplantierter Patienten geben können. Dies beinhaltet Informationen zu Vorerkrankungen, bestehenden Infektionen, dem Verlauf der Transplantation, der Medikation und auftretenden infektiösen Ereignissen. Für jedes Organ wurde im Vorfeld eine spezielle Auswahl an Parametern festgelegt, so dass die relevanten Ereignisse für die Art der Transplantation berücksichtigt werden.

Als weitere wichtige Grundlage für spätere Studien dient Biomaterial der transplantierten Patienten. Hierbei werden ausschließlich Proben verwendet, die im Laufe der routinemäßigen Behandlung der Patienten anfallen und für weitere Untersuchungen nicht mehr benötigt werden. Die Biomaterialien werden in professionellen Biobanken gelagert. Zu diesem Zweck arbeitet die Transplantationskohorte eng mit der DZIF-Biobanken-Plattform zusammen.

Mit deutschlandweit 200.000 Teilnehmern und 18 Studienzentren ist die NAKO die größte Gesundheitsstudie der deutschen Geschichte. Im Studienzentrum Hannover wurden im Zeitraum 2014 bis 2018 10.000 TeilnehmerInnen aus dem Großraum Hannover in die Langzeitstudie eingeschlossen. Seit Dezember 2018 werden die TeilnehmerInnen zur zweiten Untersuchung ins Studienzentrum eingeladen.

link zur Nako Gesundheitsstudie Hannover

i.Vacc- individual vaccination

Paving the way for an individual vaccination

Research into multi-omics big data in the population based on a digital mHealth cohort

Further infomation: https://www.helmholtz-hzi.de/de/forschung/forschungsprojekte/ansicht/projekt/detail/ivacc-4/

Prof. Dr. Thomas Illig is here Principal Investigators.

Was ist Asthma – und wenn ja wie viele? Frei nach einem populären Buchtitel könnte man auch die Fragestellung der All Age Asthma Cohort (ALLIANCE) definieren. Denn tatsächlich kennen Mediziner nicht nur ein Asthma, sondern eine Vielzahl typischer Krankheitsverläufe. Bei gut einem Viertel aller Kinder tritt mindestens einmal in der frühen Kindheit Giemen auf. Dabei handelt es sich um ein typisches Geräusch beim Ausatmen, das durch verengte Atemwege hervorgerufen wird. Gleichwohl es Anzeichen für ein späteres Asthma sein kann, behalten nur 3-5% aller Kinder, die Giemen oder andere frühe Symptome zeigen, ihr Asthma bis zum Erwachsenenalter. In anderen Fällen tritt Asthma überhaupt erst im Erwachsenenalter auf, dann aber oft in schwerer Form.

Um vorhersagen zu können, wie eine Erkrankung verläuft und wie sie behandelt werden sollte, hat das DZL bereits in der ersten Förderperiode die ALLIANCE-Kohorte ins Leben gerufen. Sie umfasst mittlerweile mehr als 1000 Patienten und gesunde Probanden im Alter zwischen sechs Monaten und 84 Jahren. Nach einer umfassenden Basisuntersuchung kommen die Asthma-Patienten in der Regel jährlich in die jeweiligen Studienzentren. Gesunde Probanden, welche als Kontrollgruppe dienen, werden einmalig untersucht.

Im Rahmen des Untersuchungsprogramms misst das ALLIANCE-Studienteam Lungenfunktion und Atemwegsentzündung der Probanden und prüft, inwieweit sie gegen bestimmte Allergene sensibilisiert sind. Biomaterialien wie Blut, Nasenabstriche, Sputum und Ausatemluft werden gesammelt und analysiert. Strukturierte Fragebogen-Interviews und Daten aus den Patientenakten dokumentieren Symptome, Krankheitsverlauf, Lebensumstände und Umweltfaktoren. Um die Ergebnisse bei Kindern und Erwachsenen direkt vergleichen zu können, ist das Spektrum der Untersuchungen so ähnlich wie möglich gestaltet und die Abläufe standardisiert.

Mithilfe einer ganzen Reihe tiefgehender molekularbiologischer Analysemethoden (‚Deep Phenotyping‘) sollen Mechanismen der verschiedenen Verläufe aufgeklärt werden. Daten- und Biobanken der ALLIANCE-Kohorte umfassen mittlerweile hunderttausende an Datenpunkten und Patientenproben. Ihre Analyse hat bereits begonnen. Ziel der Studie ist es Biomarker (Signalgeber) zu identifizieren, die es zukünftig ermöglichen sollen, die jeweilige Unterform der Erkrankung möglichst früh zu erkennen. Das würde auch ermöglichen, die Behandlung auf jeden einzelnen Patienten viel individueller abzustimmen.

ALLIANCE ist eines der großen klinischen Flaggschiffprojekte des DZL. Beteiligt sind die Standorte ARCN (Kiel/Lübeck/Borstel/Großhansdorf), BREATH (Hannover), CPC-M (München) und UGMLC (Gießen/Marburg/Bad Nauheim) sowie die Uniklinik Köln als DZL-externer Partner. Im pädiatrischen Teil arbeiten das Universitätsklinikum Schleswig-Holstein (Campus Lübeck), die Medizinische Hochschule Hannover, das Universitätsklinikum Gießen-Marburg, das Klinikum der Universität München und die Uniklinik Köln zusammen. Erwachsene Patienten nehmen an der Studie in der LungenClinic Grosshansdorf und am Forschungszentrum Borstel teil.

Kompetenznetz Ambulant Erworbene Pneumonie

Die Ambulant Erworbene Pneumonie (CAP- Community Acquired Pneumonia) gilt als eine der weltweit bedeutendsten Infektionserkrankungen. Sie ist mit einem hohen Sterblichkeitsrisiko behaftet. Allein in Deutschland erkranken rund 680.000 Menschen pro Jahr an CAP, von denen ein erheblicher Anteil im Krankenhaus behandelt werden muss. Trotz der medizinischen und gesundheitsökonomischen Bedeutung dieser Erkrankung fehlten in Deutschland zuverlässige Daten zum Erregerspektrum, zur Resistenzsituation der Erreger und zum Verlauf der Erkrankung. Deshalb hat das BMBF im Jahr 2001 das Kompetenznetzwerk "Ambulant erworbene Pneumonie" (CAPNETZ) initiiert. Ziel von CAPNETZ ist es, dass weniger Menschen an Lungenentzündung erkranken und seltener daran sterben. Dazu müssen Diagnostik, Therapie und Patientenversorgung verbessert werden.

CAPNETZ vernetzt niedergelassene und klinisch tätige Ärzte sowie Mikrobiologen, Virologen, Epidemiologen und Informatiker. Führende Forschungseinrichtungen in Deutschland kooperieren in CAPNETZ. Alle klinischen und mikrobiologischen Daten werden zusammengeführt und in einer zentralen Material- und Datenbank verwaltet. Bis 2013 konnten so bereits über 10.000 Patienten erfasst werden. Etwa ein Drittel dieser Patienten befand sich in ambulanter Behandlung, etwa zwei Drittel wurden stationär aufgenommen. Die verantwortlichen Erreger werden angezüchtet und deren Empfindlichkeit gegenüber Antibiotika ermittelt. Alle klinischen und mikrobiologischen Daten werden zusammengeführt und in einer zentralen Material- und Datenbank verwaltet. CAPNETZ verfügt damit über die weltweit umfangreichste Datenbank zur ambulant erworbenen Pneumonie.

Vorhandene Proben:

• Serum

• Plasma

• PBMCs

• Rachenspülwasser

• Urin

• Bakterien Isolate

• Respirationsmaterial

• EDTA Blut

 Patients:

circa 11.000 CAP patients (1/2017)

(400 Patients/Year)

Further information:

www.capnetz.de

Die ABACOPD Studie ist eine randomisierte, doppelt blind, Placebo kontrollierte Studie, die zeigen soll, dass Antibiotika nicht erforderlich ist bei milden bis mäßig akuten Exazerbationen der COPD.

Multizentrische Studie (Deutschland)

etwa  25 Zentren

Krankheitsbild:

Chronische obstruktive Lungenerkrankung  (COPD)

Primärziel:
Die klinische Studie soll zeigen, dass es keine relevante Erhöhung der "Fehler-Rate" bei Patienten mit Placebo- anstelle einer Antibiotika-Behandlung als Standardtherapie gibt.

Population:

• Erwachsene, älter als 40 Jahre

• Rauchervorgeschichte von 10 Schachteln/Jahr oder mehr

• COPD Phasen I-IV, mit leichter bis mittelschwerer definierten akuten Exazerbation der COPD

• anhaltende Verschlechterung des Zustands des Patienten (darunter mindestens 2 der folgenden Symptome: erhöhte Atemnot, Auswurf und Sputum purulence)

• aus dem stabilen Zustand

• mit normalen Tag zu Tag Variationen.

Stichprobengröße:
Etwa 480 Patienten pro Behandlungsgruppe.

Proben:

• Plasma

• Serum

Further Information:

www.capnetz.de/html/abacopd/project

Fanconi-Anämie (FA) ist eine seltene, vererbte Erkrankung, die durch fortschreitendes Versagen des Knochenmarks, diverse angeborene Anomalien und einer Prädisposition für Malignität hervorgerufen wird. Es besteht einen phänotypische Heterogenität unter Patienten mit FA, die auf mindestens 16 Genemutationen zurückzuführen ist. Das FA Register wurde gegründet, um den natürlichen Verlauf der Erkrankung und die genetischen und umweltbedingten Modifikatoren besser zu definieren und verstehen zu können. Die Registrierung bemüht sich auch, um up-to-date Informationen über FA für Angehörende der Gesundheitsberufe, Patienten und ihrer Familien. 

Immune Safety Avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies

The vision of Immune Safety Avatar (imSAVAR) is to develop a platform for integrated nonclinical assessments of immunomodulatory therapy safety and efficacy. Existing nonclinical models do not adequately represent the complexity of the immune system and its interactions in both immunoncology and immunmediated diseases. They also do not accurately reflect the diversity of response to new therapies that is seen in clinical medicine.

We will, thus, constantly refine existing and develop new nonclinical models with the final goal of validation aiming at: (i) understanding the value of nonclinical models for predicting efficacy and safety of immunomodulators incorporating cellular high throughput assays, complex organisms models and micro physiological systems, (ii) developing new endpoints and better monitoring approaches for immune function tests, and (iii) designing cellular and molecular biomarkers for early detection of adverse effects. The platform imSAVAR will be based upon case studies for prioritized therapeutic modalities and has been built around institutes of the Fraunhofer-Gesellschaft which has strong track records in applied science and in particular toxicology.

The consortium will improve the prediction of the transferability of safety and efficacy of immunomodulators from pre-clinical models to first-in-human studies in collaboration with the private sector, pharma, regulators and technology providers. We will share experience on customized models that can be deployed (w.r.t. the 3Rs principles), establish the necessary infrastructure, conduct the analyses and provide wider disease domain expertise. This conjoint effort assures that the platform imSAVAR constantly benefits the field of immune safety evaluation, and will generate opportunities for European businesses. A guiding principle of this consortium is the meaningful engagement of multiple stakeholders including patients and regulators. A multi-stakeholder community will be established.

Innovation project to further develop care after kidney transplant

Further infomation: https://ntx360grad.de/

Information will follow

For patients with the most severe end-stage lung diseases, such as COPD, the only curative therapy option currently available is lung transplantation, which is, however, reserved for an extremely selected range of patients. Particularly in the case of lung transplantation, there is an increasing mismatch of potential organ recipients to organ donors, which leads to a progressive mortality of the patients on the waiting list.

Monocentric prospective open-armed phase IV study of the effects of hawthorn special extract WS® 1442 on arterial microvascular structure and macrovascular function, endurance performance and erectile ability in men with heart failure in stage NYHA II and erectile dysfunction.

Study participants
50 patients with diastolic heart failure NYHA II and erectile dysfunction

Post-pulmonary hypertension is pre-capillary pulmonary hypertension associated with liver disease or portal hypertension.

clinical research

Influenza Study in Cooperation with the TWINCORE and the HZI in Braunschweig.

After a completed pilot study with 34 subjects, the main study (beginning: autumn 2015) should include around 300 participants in the study. Individuals aged 60-80 years are included, since influenza vaccination is recommended for this age group in Germany. Excluded are (1) individuals who have a known allergy to chicken egg whites because the vaccine may contain traces of chicken egg whites and (2) individuals who cannot fully understand the consequences of taking part in the study due to limited cognition.

Participants:

• Pilot Study : 34 Participants
• Main study: 300 Participants
• Age 60-80 Years

Biomaterials:

• Plasma
• Serum
• PAXgene
• Buffy coat (DNA)

REBIRTH addresses major challenges to human health. Based both on known biological principles and those yet to be discovered, our vision is to explore and develop new therapeutic concepts that go beyond other contemporary approaches. For some of the most devastating disease entities in patients with heart, lung, liver and blood disorders (including immune disorders), our research develops new therapies in the field of regenerative science and medicine.

To realize our vision, we translate mechanisms of organogenesis, endogenous repair and stem cell biology into controllable in vitro systems and into disease models with potential clinical application. Certainly, elucidating the existence, the characteristics and the role of stem cells in their distinct niches in adult tissue will provide important cues for therapeutic strategies enhancing endogenous regeneration. REBIRTH scientists will continue to investigate novel tissue-specific stem cells and stem cell-supportive cytokines, and to characterize their role in pathology and organ regeneration. Similarly, novel insights into biological principles of mammalian development are identified within REBIRTH. These will allow investigators not only to improve current protocols for differentiation of stem cells into their specialized derivatives, but also to better understand and advance the generation of bioartificial tissue in vitro.

Of course, reprogramming of adult somatic cells into pluripotent cells represents an important aspect of REBIRTH’s stem cell research. It is now possible to induce full pluripotency in somatic cells of various species, including human cells, through transgenic overexpression of specific pluripotency factors. The technology of generating what are known as induced pluripotent stem (iPS) cells, introduced by the Yamanaka lab (Kyoto) in 2006, is considered a major breakthrough in stem cell research. REBIRTH scientists have substantially contributed to current knowledge and technological developments in this field, for instance concerning the development of methods for improved generation, characterization, expansion and differentiation of iPS cells. Current projects include risk assessment and strategies to produce clinically safe cell products, the development of novel tools for correction of genetic mutations in patient-specific stem cells and their use in disease modelling and tissue engineering.

Based on our philosophy of creating synergies by bringing together clinicians and biomedical researchers with physical and chemical scientists and engineers, the fields of materials engineering, chemistry and physics have complemented our biomedical discoveries by developing innovative technologies that create novel prospects for cell and tissue engineering. The structural and scientific set-up of our cluster helps conventional boundaries in medicine to be transcended, providing a future-oriented view of human health and disease by unravelling new interrelationships between disease entities, such as regeneration and inflammation, degeneration and infection, as well as senescence and tumour development.

Importantly, our programme integrates excellent training with innovative science and both experimental and clinical medicine. The existing wide range of certified/accredited facilities for Good Practice (laboratory, manufacturing and clinical) and close industrial collaborations will be further expanded with a view towards patient-focused, applied studies. Upscaling technologies and pro-active biosafety assessment complete our translational activities. REBIRTH focuses on disorders of the blood (including immunity), heart, lung (respiratory tract) and liver, developing synsergy by connecting experts with a broad range of background knowledge.

With this profile, REBIRTH is an ideal partner for other domestic and international centres in regenerative medicine. MHH’s long-standing commitment to bench-to-bedside solutions, our highly valued interactions with major academic, regulatory and industrial partners, and our previous achievements in the development of novel therapeutic concepts underline the role of REBIRTH as a leading centre for successful translation of basic regenerative sciences into advanced therapy.

To develop genuinely regenerative and reconstructive treatments, it is necessary to understand and exploit the self-healing capabi­li­ties and mechanisms of the human organism. Insights into regenerative processes and their underlying mechanisms will not only improve disease prevention, but also allow targeted interventions in the case of severe acute or chronic disease.

Further information: http://www.rebirth-hannover.de/de/home.html

COMBACTE: Combatting Bacterial Resistance in Europe

Antimicrobial resistance is a growing problem worldwide, and with few new antimicrobial drugs making it to the market, there is an urgent need for new medicines to treat resistant infections. Antibiotic-resistant bacteria cause approximately 33,000 deaths in the EU and the annual treatment and social costs have been estimated at approximately 1.5 billion euros. If no action is taken, we risk leaving society in a situation where doctors will have few, if any, options to treat resistant bacterial infections.

Networked biomedical research projects require a high degree of interoperability between universities, other academic organizations and non-academic institutions. The cooperation becomes even more complex in a decentralized infrastructure as pursued within the German Centres for Health Research (DZGs) or in collaborations between DZGs. Biomaterial samples are ideally collected centrally using harmonized infrastructure and processes. A number of national epidemiological studies exist (e.g. KORA, SHIP, PopGen, German National Cohort) built on a comprehensive, quality-assured sample pool and data on phenotypes. However, the phenotypic data of these cohorts are often insufficient for specific questions e. g. in pneumology. Such cohorts often have a small spectrum of specific sample types e. g. lavage fluid or others. Moreover, sample requests can often be expected with a perennial flow. The presented research project of BioMaterialBank (BMB) North in Borstel, the Leibniz Institute for Prevention Research and Epidemiology (BIPS) in Bremen, the Hannover Unified Biobank (HUB) in Hannover, the biobank PopGen in Kiel, the Interdisciplinary Center for Biobanking-Lübeck (ICB-L) in Lübeck, the Integrated Research Biobank (IRB) in Greifswald and the Integrated Biobank (IBBJ) in Jena is rooted in a cooperative grounding project of the Research Centre Borstel in pneumology. The initial motivation was the generation of reference values of healthy individuals. Within the project presented here, voluntary healthy subjects (n = 250) are recruited at five differently structured sites, using different recruitment strategies. Specimen collection, processing, management, storage and transport will be adapted to decentralize the infrastructure of differently equipped biobanks. Objectives of the research project are (I) the provision of high quality biomaterials facilitating inter-site comparability, (II) the central analysis of samples obtained decentrally through 4 different analysis methods. This results in the determination of reference values for scientific purposes, (III) the identification of critical factors for decentralized recruitment, extraction and processing of samples, followed by the development of recommendations, guidelines and standards, which will be published according to international standards. The project reflects current challenges of biobanks in research networks that are repeatedly discussed within the TMF working groups. This expertise in the TMF working groups will had been sought in order to optimize the proposed projects and its outcome. The high degree of interconnectivity of the project allows the participation and cooperation of all partners in the TMF working groups and DZGs that have a focus on pulmonary research. Project participants are members of biobanks and are cooperating within frameworks of the German Centre for Lung Research (DZL), the German Centre for Infection Research (DZIF), the German Centre for Cardiovascular Research (DZHK), of P2N and Northgerman Biobank Alliance (NBA) for many years.

Study examines the effect of delayed further processing of biosamples

The Q-Map study (Quality Markers to Access Processing Delay) aims to clarify the extent to which the delayed further processing of blood and urine samples has an impact on later analyzes, in particular whether metabolites can be used as markers for such delayed further processing ( Metabolites are metabolic products such as sugar, fats, amino acids etc.) and whether a delayed isolation of blood cells from blood samples, e.g. due to transport times, has an impact on the yield and viability of these cells. Overall, this study serves to continuously improve and test the quality of biomaterials. This is of great importance for future research questions..

20 Participants:

• healthy

• male

• 20-35 Years

• Normal weight according to DGE (Body Mass Index: 20-25)

• No long-term medication, no medication in the past 48 hours

• Sobriety at the time of the examination (8 hours beforehand no food and no liquids other than water)

Biomaterials:

• Plasma

• PBMCs

• Urin