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  1. Article ; Online: „Data-driven-Intensivmedizin“: Mangel an umfassenden Datensätzen.

    Hardenberg, Jan-Hendrik B

    Medizinische Klinik, Intensivmedizin und Notfallmedizin

    2024  

    Abstract: Intensive care units provide a data-rich environment with the potential to generate datasets in the realm of big data, which could be utilized to train powerful machine learning (ML) models. However, the currently available datasets are too small and ... ...

    Title translation Data-driven intensive care: a lack of comprehensive datasets.
    Abstract Intensive care units provide a data-rich environment with the potential to generate datasets in the realm of big data, which could be utilized to train powerful machine learning (ML) models. However, the currently available datasets are too small and exhibit too little diversity due to their limitation to individual hospitals. This lack of extensive and varied datasets is a primary reason for the limited generalizability and resulting low clinical utility of current ML models. Often, these models are based on data from single centers and suffer from poor external validity. There is an urgent need for the development of large-scale, multicentric, and multinational datasets. Ensuring data protection and minimizing re-identification risks pose central challenges in this process. The "Amsterdam University Medical Center database (AmsterdamUMCdb)" and the "Salzburg Intensive Care database (SICdb)" demonstrate that open access datasets are possible in Europe while complying with the data protection regulations of the General Data Protection Regulation (GDPR). Another challenge in building intensive care datasets is the absence of semantic definitions in the source data and the heterogeneity of data formats. Establishing binding industry standards for the semantic definition is crucial to ensure seamless semantic interoperability between datasets.
    Language German
    Publishing date 2024-04-26
    Publishing country Germany
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 2636018-4
    ISSN 2193-6226 ; 1435-1420 ; 0723-5003 ; 2193-6218 ; 0175-3851
    ISSN (online) 2193-6226 ; 1435-1420
    ISSN 0723-5003 ; 2193-6218 ; 0175-3851
    DOI 10.1007/s00063-024-01141-z
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  2. Article ; Online: Covid-19, ACE2 and the kidney.

    Hardenberg, Jan-Hendrik B / Luft, Friedrich C

    Acta physiologica (Oxford, England)

    2020  Volume 230, Issue 1, Page(s) e13539

    MeSH term(s) Angiotensins ; Animals ; Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Evolution, Molecular ; Genomics ; Humans ; Pandemics ; Peptidyl-Dipeptidase A ; Pneumonia, Viral ; SARS-CoV-2 ; Surveys and Questionnaires ; Vertebrates
    Chemical Substances Angiotensins ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Keywords covid19
    Language English
    Publishing date 2020-08-02
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 2218636-0
    ISSN 1748-1716 ; 1748-1708
    ISSN (online) 1748-1716
    ISSN 1748-1708
    DOI 10.1111/apha.13539
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  3. Article: Cocaine/Levamisole-Induced, Skin-Limited ANCA-Associated Vasculitis with Pyoderma Gangrenosum-like Presentation.

    Urosevic-Maiwald, Mirjana / Hardenberg, Jan-Hendrik B / Hafner, Jürg / Brüggen, Marie-Charlotte

    Dermatopathology (Basel, Switzerland)

    2022  Volume 9, Issue 3, Page(s) 207–211

    Abstract: The use of levamisole as the most frequent adulterant of cocaine has merged in previously unknown toxicities, notably a disease entity called cocaine/levamisole-associated autoimmune syndrome (CLAAS). Clinically, CLAAS can manifest with diverse cutaneous ...

    Abstract The use of levamisole as the most frequent adulterant of cocaine has merged in previously unknown toxicities, notably a disease entity called cocaine/levamisole-associated autoimmune syndrome (CLAAS). Clinically, CLAAS can manifest with diverse cutaneous and extracutaneous features sharing common laboratory findings (neutropenia, autoantibody patterns). We report the case of a cocaine-abusing female patient with relapsing episodes of painful ulcers, worsening and expanding over a three-year period. The case exhibited all features of a drug-induced, skin-limited, ANCA-associated vasculitis, evolving over time to PG-like findings. In both disease stages, the patient responded well to the cessation of cocaine exposure and systemic glucocorticosteroids. This case demonstrates the continuous nature of cutaneous CLAAS manifestations in a single patient. CLAAS has become a major public health issue in the at-risk group of cocaine users, and clinicians should be alert of this condition when treating cocaine users presenting with single or multiple skin ulcerations.
    Language English
    Publishing date 2022-06-29
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2777118-0
    ISSN 2296-3529
    ISSN 2296-3529
    DOI 10.3390/dermatopathology9030026
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  5. Article ; Online: Covid‐19, ACE2 and the kidney

    Hardenberg, Jan‐Hendrik B. / Luft, Friedrich C.

    Acta Physiologica

    2020  Volume 230, Issue 1

    Keywords Physiology ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2218636-0
    ISSN 1748-1716 ; 1748-1708
    ISSN (online) 1748-1716
    ISSN 1748-1708
    DOI 10.1111/apha.13539
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  6. Article ; Online: A Yin and Yang in Epithelial Immunology: The Roles of the α

    Hardenberg, Jan-Hendrik B / Braun, Andrea / Schön, Michael P

    The Journal of investigative dermatology

    2017  Volume 138, Issue 1, Page(s) 23–31

    Abstract: The proper function(s) of cell-surface receptors is crucial for the regulation of adaptive immune responses. One such receptor is the ... ...

    Abstract The proper function(s) of cell-surface receptors is crucial for the regulation of adaptive immune responses. One such receptor is the α
    MeSH term(s) Adaptive Immunity ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Epithelium/immunology ; Epithelium/metabolism ; Humans ; Immunologic Memory ; Integrins/immunology ; Integrins/metabolism ; Signal Transduction/immunology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Transforming Growth Factor beta/metabolism
    Chemical Substances Integrins ; Transforming Growth Factor beta ; integrin alphaEbeta7
    Language English
    Publishing date 2017-09-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2017.05.026
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  7. Article: COVID-19 und akute Nierenschädigung im Intensivbereich.

    Hardenberg, Jan-Hendrik B / Stockmann, Helena / Eckardt, Kai-Uwe / Schmidt-Ott, Kai M

    Der nephrologe

    2020  Volume 16, Issue 1, Page(s) 20–25

    Abstract: Acute kidney injury (AKI) is a frequent and severe complication in coronavirus disease 2019 (COVID-19) patients in the intensive care unit. The development of COVID-19 associated AKI is closely linked to the severity of the disease course. The main risk ... ...

    Title translation COVID-19 and acute kidney injury in the intensive care unit.
    Abstract Acute kidney injury (AKI) is a frequent and severe complication in coronavirus disease 2019 (COVID-19) patients in the intensive care unit. The development of COVID-19 associated AKI is closely linked to the severity of the disease course. The main risk factor for kidney failure requiring kidney replacement therapy is the necessity for invasive ventilation, whereby the onset of renal failure is often closely associated with the timing of intubation. Additionally, the risk factors for a severe course of COVID-19 have been shown to also be risk factors for renal failure. AKI in COVID-19 shows a high mortality and in some patients leads to chronic kidney disease; however, full recovery of kidney function in survivors who need dialysis is not uncommon. With respect to prevention and treatment of renal failure associated with COVID-19, the same recommendations as for AKI from other causes are valid (Kidney Disease: Improving Global Outcomes, KDIGO bundles). Due to the large numbers of patients in the setting of overwhelmed resources, the availability of extracorporeal renal replacement procedures can become critical, especially since hypercoagulation is frequent in COVID‑19. In order to avoid triage situations, in some centers acute peritoneal dialysis was used as an alternative to extracorporeal procedures.
    Language German
    Publishing date 2020-12-22
    Publishing country Germany
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 2274530-0
    ISSN 1862-0418 ; 1862-040X
    ISSN (online) 1862-0418
    ISSN 1862-040X
    DOI 10.1007/s11560-020-00471-1
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  8. Article ; Online: Critical Illness and Systemic Inflammation Are Key Risk Factors of Severe Acute Kidney Injury in Patients With COVID-19.

    Hardenberg, Jan-Hendrik B / Stockmann, Helena / Aigner, Annette / Gotthardt, Inka / Enghard, Philipp / Hinze, Christian / Balzer, Felix / Schmidt, Danilo / Zickler, Daniel / Kruse, Jan / Körner, Roland / Stegemann, Miriam / Schneider, Thomas / Schumann, Michael / Müller-Redetzky, Holger / Angermair, Stefan / Budde, Klemens / Weber-Carstens, Steffen / Witzenrath, Martin /
    Treskatsch, Sascha / Siegmund, Britta / Spies, Claudia / Suttorp, Norbert / Rauch, Geraldine / Eckardt, Kai-Uwe / Schmidt-Ott, Kai M

    Kidney international reports

    2021  Volume 6, Issue 4, Page(s) 905–915

    Abstract: Introduction: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters ... ...

    Abstract Introduction: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters reflecting disease processes and AKI development.
    Methods: We performed an observational cohort study of 223 consecutive COVID-19 patients treated at 3 sites of a tertiary care referral center to describe the evolvement of severe AKI (Kidney Disease: Improving Global Outcomes stage 3) and identify conditions promoting its development. Descriptive statistics and explanatory multivariable Cox regression modeling with clinical parameters as time-varying covariates were used to identify risk factors of severe AKI.
    Results: Severe AKI developed in 70 of 223 patients (31%) with COVID-19, of which 95.7% required kidney replacement therapy. Patients with severe AKI were older, predominantly male, had more comorbidities, and displayed excess mortality. Severe AKI occurred exclusively in intensive care unit patients, and 97.3% of the patients developing severe AKI had respiratory failure. Mechanical ventilation, vasopressor therapy, and inflammatory markers (serum procalcitonin levels and leucocyte count) were independent time-varying risk factors of severe AKI. Increasing inflammatory markers displayed a close temporal association with the development of severe AKI. Sensitivity analysis on risk factors of AKI stage 2 and 3 combined confirmed these findings.
    Conclusion: Severe AKI in COVID-19 was tightly coupled with critical illness and systemic inflammation and was not observed in milder disease courses. These findings suggest that traditional systemic AKI mechanisms rather than kidney-specific processes contribute to severe AKI in COVID-19.
    Language English
    Publishing date 2021-02-02
    Publishing country United States
    Document type Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2021.01.011
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  9. Article ; Online: High rates of long-term renal recovery in survivors of coronavirus disease 2019-associated acute kidney injury requiring kidney replacement therapy.

    Stockmann, Helena / Hardenberg, Jan-Hendrik Bernhard / Aigner, Annette / Hinze, Christian / Gotthardt, Inka / Stier, Britta / Eckardt, Kai-Uwe / Schmidt-Ott, Kai Martin / Enghard, Philipp

    Kidney international

    2021  Volume 99, Issue 4, Page(s) 1021–1022

    MeSH term(s) Acute Kidney Injury/etiology ; Acute Kidney Injury/mortality ; Acute Kidney Injury/physiopathology ; Acute Kidney Injury/therapy ; Aged ; COVID-19/complications ; COVID-19/mortality ; COVID-19/therapy ; Female ; Glomerular Filtration Rate ; Humans ; Kidney/physiopathology ; Male ; Recovery of Function ; Renal Replacement Therapy/adverse effects ; Renal Replacement Therapy/mortality ; Retrospective Studies ; Time Factors ; Treatment Outcome
    Language English
    Publishing date 2021-01-27
    Publishing country United States
    Document type Letter
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2021.01.005
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  10. Article ; Online: Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury.

    Hinze, Christian / Kocks, Christine / Leiz, Janna / Karaiskos, Nikos / Boltengagen, Anastasiya / Cao, Shuang / Skopnik, Christopher Mark / Klocke, Jan / Hardenberg, Jan-Hendrik / Stockmann, Helena / Gotthardt, Inka / Obermayer, Benedikt / Haghverdi, Laleh / Wyler, Emanuel / Landthaler, Markus / Bachmann, Sebastian / Hocke, Andreas C / Corman, Victor / Busch, Jonas /
    Schneider, Wolfgang / Himmerkus, Nina / Bleich, Markus / Eckardt, Kai-Uwe / Enghard, Philipp / Rajewsky, Nikolaus / Schmidt-Ott, Kai M

    Genome medicine

    2022  Volume 14, Issue 1, Page(s) 103

    Abstract: Background: Acute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood.: Methods: We performed ... ...

    Abstract Background: Acute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood.
    Methods: We performed single-nuclei transcriptomics, bulk transcriptomics, molecular imaging studies, and conventional histology on kidney tissues from 8 individuals with severe AKI (stage 2 or 3 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria). Specimens were obtained within 1-2 h after individuals had succumbed to critical illness associated with respiratory infections, with 4 of 8 individuals diagnosed with COVID-19. Control kidney tissues were obtained post-mortem or after nephrectomy from individuals without AKI.
    Results: High-depth single cell-resolved gene expression data of human kidneys affected by AKI revealed enrichment of novel injury-associated cell states within the major cell types of the tubular epithelium, in particular in proximal tubules, thick ascending limbs, and distal convoluted tubules. Four distinct, hierarchically interconnected injured cell states were distinguishable and characterized by transcriptome patterns associated with oxidative stress, hypoxia, interferon response, and epithelial-to-mesenchymal transition, respectively. Transcriptome differences between individuals with AKI were driven primarily by the cell type-specific abundance of these four injury subtypes rather than by private molecular responses. AKI-associated changes in gene expression between individuals with and without COVID-19 were similar.
    Conclusions: The study provides an extensive resource of the cell type-specific transcriptomic responses associated with critical illness-associated AKI in humans, highlighting recurrent disease-associated signatures and inter-individual heterogeneity. Personalized molecular disease assessment in human AKI may foster the development of tailored therapies.
    MeSH term(s) Acute Kidney Injury/genetics ; COVID-19/genetics ; Critical Illness ; Humans ; Kidney ; Transcriptome
    Language English
    Publishing date 2022-09-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-022-01108-9
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