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Article ; Online: Current Status and Future Perspectives on Machine Perfusion

Anna Niroomand / Gabriel Hirdman / Franziska Olm / Sandra Lindstedt

Cells, Vol 11, Iss 91, p

A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy

2022 Volume 91

Abstract: Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to ... ...

Abstract	Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal lungs viable for transplantation. This ultimately aligns with the need of the lung transplant field to increase the number of available donor organs given critical shortages. As transplantation is the only option for patients with end-stage lung disease, advancements in technology are needed to decrease wait-list time and mortality. This review summarizes the results from the application of EVLP as a therapeutic intervention and focuses on the use of the platform with regard to cell therapies, cell product therapies, and cytokine filtration among other technologies. This review will summarize both the clinical and translational science being conducted in these aspects and will highlight the opportunities for EVLP to be developed as a powerful tool to increase the donor lung supply.
Keywords	lung transplantation ; EVLP ; machine perfusion ; cell therapy ; mesenchymal stromal cells ; extracellular vesicles ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome

Embla Bodén / Jesper Andreasson / Gabriel Hirdman / Malin Malmsjö / Sandra Lindstedt

Biomedicines, Vol 10, Iss 2738, p

2022 Volume 2738

Abstract: Non-small cell lung cancer (NSCLC) is associated with low survival rates, often due to late diagnosis and lack of personalized medicine. Diagnosing and monitoring NSCLC using blood samples has lately gained interest due to its less invasive nature. In ... ...

Abstract	Non-small cell lung cancer (NSCLC) is associated with low survival rates, often due to late diagnosis and lack of personalized medicine. Diagnosing and monitoring NSCLC using blood samples has lately gained interest due to its less invasive nature. In the present study, plasma was collected at three timepoints and analyzed using proximity extension assay technology and quantitative real-time polymerase chain reaction in patients with primary NSCLC stages IA–IIIA undergoing surgery. Results were adjusted for patient demographics, tumor, node, metastasis (TNM) stage, and multiple testing. Major histocompatibility (MHC) class 1 polypeptide-related sequence A/B (MIC-A/B) and tumor necrosis factor ligand superfamily member 6 (FASLG) were significantly increased post-surgery, suggesting radical removal of cancerous cells. Levels of hepatocyte growth factor (HGF) initially increased postoperatively but were later lowered, potentially indicating radical removal of malignant cells. The levels of FASLG in patients who later died or had a relapse of NSCLC were lower at all three timepoints compared to surviving patients without relapse, indicating that FASLG may be used as a prognostic biomarker. The biomarkers were confirmed using microarray data. In conclusion, quantitative proteomics could be used for NSCLC identification but may also provide information on radical surgical removal of NSCLC and post-surgical prognosis.
Keywords	non-small cell lung cancer ; biomarkers ; proteomics ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Design and Rationale of Cytokine Filtration in Lung Transplantation (GLUSorb)

Sandra Lindstedt / Martin Silverborn / Lukas Lannemyr / Leif Pierre / Hillevi Larsson / Edgars Grins / Snejana Hyllen / Goran Dellgren / Jesper Magnusson

JMIR Research Protocols, Vol 12, p e

Protocol for a Multicenter Clinical Randomized Controlled Trial

2023 Volume 52553

Abstract: BackgroundLung transplantation (LTx) is the only treatment option for end-stage lung disease. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the main ...

Abstract	BackgroundLung transplantation (LTx) is the only treatment option for end-stage lung disease. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the main factor in late mortality after LTx. PGD develops within the first 72 hours and impairs the oxygenation capacity of the lung, measured as partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2). Increasing the PaO2/FiO2 ratio is thus critical and has an impact on survival. There is a general lack of effective treatments for PGD. When a transplanted lung is not accepted by the immune system in the recipient, a systemic inflammatory response starts where cytokines play a critical role in initiating, amplifying, and maintaining the inflammation leading to PGD. Cytokine filtration can remove these cytokines from the circulation, thus reducing inflammation. In a proof-of-concept preclinical porcine model of LTx, cytokine filtration improved oxygenation and decreased PGD. In a feasibility study, we successfully treated patients undergoing LTx with cytokine filtration (ClinicalTrials.gov; NCT05242289). ObjectiveThe purpose of this clinical trial is to demonstrate the superiority of cytokine filtration in improving LTx outcome, based on its effects on oxygenation ratio, plasma levels of inflammatory markers, PGD incidence and severity, lung function, kidney function, survival, and quality of life compared with standard treatment with no cytokine filtration. MethodsThis study is a Swedish national interventional randomized controlled trial involving 116 patients. Its primary objective is to investigate the potential benefits of cytokine filtration when used in conjunction with LTx. Specifically, this study aims to determine whether the application of cytokine filtration, administered for a duration of 12 hours within the initial 24 hours following a LTx procedure, can lead to improved patient outcomes. This study seeks to assess various aspects of patient ...
Keywords	Medicine ; R ; Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	610
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	JMIR Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Aged Garlic Extract Reduces IL-6

Martiné Wlosinska / Ann-Christin Nilsson / Joanna Hlebowicz / Mohammed Fakhro / Malin Malmsjö / Sandra Lindstedt

Evidence-Based Complementary and Alternative Medicine, Vol

A Double-Blind Placebo-Controlled Trial in Females with a Low Risk of Cardiovascular Disease

2021 Volume 2021

Abstract: Background. Chronic inflammation is a risk factor for cardiovascular disease. The aim of the study was to evaluate whether a daily supplementation of aged garlic extract (AGE) could reduce inflammation in females with low risk for cardiovascular disease. ...

Abstract	Background. Chronic inflammation is a risk factor for cardiovascular disease. The aim of the study was to evaluate whether a daily supplementation of aged garlic extract (AGE) could reduce inflammation in females with low risk for cardiovascular disease. The study was conducted at a single center, as a parallel randomized placebo-controlled trial. Method. 63 females with a Framingham risk score over 10 underwent cardiac computed tomography (CT) scan. Of those, patients with a coronary artery calcium (CAC) scores less than 5 (n = 31) met the inclusion criteria and were randomized, in a double-blind manner to an intake of placebo or AGE (2400 mg daily) for 1 year. Results. Main outcome measure was changes in inflammatory biomarkers, blood pressure, fastening blood glucose, and blood lipids. A total of 29 patients (14 in the AGE group and 15 in the placebo group) completed the study and were analyzed. Females treated with AGE showed lower levels of inflammatory marker IL-6 after 12 months of treatment compared to females receiving placebo (p<0.05). The blood lipids had a trend towards a lowering effect in females treated with AGE; however, this trend was not significant. Conclusion. The present study concludes that AGE lowers IL-6 in females with a risk profile of cardiovascular disease. We could also conclude that risk prediction with cardiac CT scan turned out to be superior in estimating the risk of cardiac disease compared to Framingham risk score. This trial is registered with NCT03860350.
Keywords	Other systems of medicine ; RZ201-999
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Particle flow rate from the airways as fingerprint diagnostics in mechanical ventilation in the intensive care unit

Filip Hallgren / Martin Stenlo / Anna Niroomand / Ellen Broberg / Snejana Hyllén / Malin Malmsjö / Sandra Lindstedt

ERJ Open Research, Vol 7, Iss

a randomised controlled study

2021 Volume 3

Abstract: Introduction Mechanical ventilation can be monitored by analysing particles in exhaled air as measured by particle flow rate (PFR). This could be a potential method of detecting ventilator-induced lung injury (VILI) before changes in conventional ... ...

Abstract	Introduction Mechanical ventilation can be monitored by analysing particles in exhaled air as measured by particle flow rate (PFR). This could be a potential method of detecting ventilator-induced lung injury (VILI) before changes in conventional parameters can be detected. The aim of this study was to investigate PFR during different ventilation modes in patients without lung pathology. Method A prospective study was conducted on patients on mechanical ventilation in the cardiothoracic intensive care unit (ICU). A PExA 2.0 device was connected to the expiratory limb on the ventilator for continuous measurement of PFR in 30 patients randomised to either volume-controlled ventilation (VCV) or pressure-controlled ventilation (PCV) for 30 min including a recruitment manoeuvre. PFR measurements were continued as the patients were transitioned to pressure-regulated volume control (PRVC) and then pressure support ventilation (PSV) until extubation. Results PRVC resulted in significantly lower PFR, while those on PSV had the highest PFR. The distribution of particles differed significantly between the different ventilation modes. Conclusions Measuring PFR is safe after cardiac surgery in the ICU and may constitute a novel method of continuously monitoring the small airways in real time. A low PFR during mechanical ventilation may correlate to a gentle ventilation strategy. PFR increases as the patient transitions from controlled mechanical ventilation to autonomous breathing, which most likely occurs as recruitment by the diaphragm opens up more distal airways. Different ventilation modes resulted in unique particle patterns and could be used as a fingerprint for the different ventilation modes.
Keywords	Medicine ; R
Subject code	690
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Corticotropin releasing hormone as an identifier of bronchiolitis obliterans syndrome

Anna Niroomand / Haider Ghaidan / Oskar Hallgren / Lennart Hansson / Hillevi Larsson / Darcy Wagner / Martina Mackova / Kieran Halloran / Snejana Hyllén / Sandra Lindstedt

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 11

Abstract: Abstract Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a ... ...

Abstract	Abstract Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a minimally invasive biomarker of BOS. Here, 644 different proteins were analyzed to detect biomarkers that distinguish BOS grade 0 from grades 1–3. The plasma of 46 double lung transplant patients was analyzed for proteins using a high-component, multiplex immunoassay that enables analysis of protein biomarkers. Proximity Extension Assay (PEA) consists of antibody probe pairs which bind to targets. The resulting polymerase chain reaction (PCR) reporter sequence can be quantified by real-time PCR. Samples were collected at baseline and 1-year post transplantation. Enzyme-linked immunosorbent assay (ELISA) was used to validate the findings of the PEA analysis across both time points and microarray datasets from other lung transplantation centers demonstrated the same findings. Significant decreases in the plasma protein levels of CRH, FERC2, IL-20RA, TNFB, and IGSF3 and an increase in MMP-9 and CTSL1 were seen in patients who developed BOS compared to those who did not. In this study, CRH is presented as a novel potential biomarker in the progression of disease because of its decreased levels in patients across all BOS grades. Additionally, biomarkers involving the remodeling of the extracellular matrix (ECM), such as MMP-9 and CTSL1, were increased in BOS patients.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Alveolar epithelial cells are competent producers of interstitial extracellular matrix with disease relevant plasticity in a human in vitro 3D model

Oskar Rosmark / Måns Kadefors / Göran Dellgren / Christofer Karlsson / Anders Ericsson / Sandra Lindstedt / Johan Malmström / Oskar Hallgren / Anna-Karin Larsson-Callerfelt / Gunilla Westergren-Thorsson

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 17

Abstract: Abstract Alveolar epithelial cells (AEC) have been implicated in pathological remodelling. We examined the capacity of AEC to produce extracellular matrix (ECM) and thereby directly contribute towards remodelling in chronic lung diseases. Cryopreserved ... ...

Abstract	Abstract Alveolar epithelial cells (AEC) have been implicated in pathological remodelling. We examined the capacity of AEC to produce extracellular matrix (ECM) and thereby directly contribute towards remodelling in chronic lung diseases. Cryopreserved type 2 AEC (AEC2) from healthy lungs and chronic obstructive pulmonary disease (COPD) afflicted lungs were cultured in decellularized healthy human lung slices for 13 days. Healthy-derived AEC2 were treated with transforming growth factor ß1 (TGF-β1) to evaluate the plasticity of their ECM production. Evaluation of phenotypic markers and expression of matrisome genes and proteins were evaluated by RNA-sequencing, mass spectrometry and immunohistochemistry. The AEC2 displayed an AEC marker profile similar to freshly isolated AEC2 throughout the 13-day culture period. COPD-derived AECs proliferated as healthy AECs with few differences in gene and protein expression while retaining increased expression of disease marker HLA-A. The AEC2 expressed basement membrane components and a complex set of interstitial ECM proteins. TGF-β1 stimuli induced a significant change in interstitial ECM production from AEC2 without loss of specific AEC marker expression. This study reveals a previously unexplored potential of AEC to directly contribute to ECM turnover by producing interstitial ECM proteins, motivating a re-evaluation of the role of AEC2 in pathological lung remodelling.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Global longitudinal strain correlates to systemic right ventricular function.

Samarai, Daniel / Ingemansson, Sandra Lindstedt / Gustafsson, Ronny / Thilén, Ulf / Hlebowicz, Joanna

Cardiovascular ultrasound

2020 Volume 18, Issue 1, Page(s) 4

Abstract: Background: The aim of this retrospective study was to evaluate the relationship between right ventricular function derived from cardiac magnetic resonance imaging (CMR), echocardiography and exercise stress test performance, NT-proBNP (N-terminal proB- ... ...

Abstract	Background: The aim of this retrospective study was to evaluate the relationship between right ventricular function derived from cardiac magnetic resonance imaging (CMR), echocardiography and exercise stress test performance, NT-proBNP (N-terminal proB-type natriuretic peptide) level and NYHA class in patients with a systemic right ventricle. Methods: All patients with congenitally corrected transposition of the great arteries (ccTGA), or transposition of the great arteries after Mustard or Senning procedures, (TGA) followed at our centre who had undergone CMR, echocardiography, an exercise stress test and blood sampling, were included in the study. Results: We examined 11 patients (six after the Senning procedure, one after the Mustard procedure, and four ccTGA) who have a median age of 32 years (22-67 years). A significant correlation was observed between the systemic ventricular function, expressed as the CMR-derived right ventricular ejection fraction and the right ventricular global longitudinal strain (r= -0.627; p=0.039). Conclusion: We have demonstrated that in patients with ccTGA or TGA right ventricular global longitudinal strain may be useful in the evaluation of the systemic right ventricular function.
MeSH term(s)	Adolescent ; Adult ; Aged ; Congenitally Corrected Transposition of the Great Arteries/diagnosis ; Congenitally Corrected Transposition of the Great Arteries/physiopathology ; Echocardiography/methods ; Female ; Heart Ventricles/diagnostic imaging ; Heart Ventricles/physiopathology ; Humans ; Magnetic Resonance Imaging, Cine/methods ; Male ; Middle Aged ; Myocardial Contraction/physiology ; Retrospective Studies ; Stroke Volume/physiology ; Ventricular Function, Right/physiology ; Young Adult
Language	English
Publishing date	2020-01-27
Publishing country	England
Document type	Journal Article
ISSN	1476-7120
ISSN (online)	1476-7120
DOI	10.1186/s12947-020-0186-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Publisher Correction

Ganna Petruk / Manoj Puthia / Firdaus Samsudin / Jitka Petrlova / Franziska Olm / Margareta Mittendorfer / Snejana Hyllén / Dag Edström / Ann-Charlotte Strömdahl / Carl Diehl / Simon Ekström / Björn Walse / Sven Kjellström / Peter J. Bond / Sandra Lindstedt / Artur Schmidtchen

Nature Communications, Vol 14, Iss 1, Pp 1-

Targeting Toll-like receptor-driven systemic inflammation by engineering an innate structural fold into drugs

2023 Volume 1

Keywords	Science ; Q
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeting Toll-like receptor-driven systemic inflammation by engineering an innate structural fold into drugs

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 20

Abstract: Abstract There is a clinical need for conceptually new treatments that target the excessive activation of inflammatory pathways during systemic infection. Thrombin-derived C-terminal peptides (TCPs) are endogenous anti-infective immunomodulators ... ...

Abstract	Abstract There is a clinical need for conceptually new treatments that target the excessive activation of inflammatory pathways during systemic infection. Thrombin-derived C-terminal peptides (TCPs) are endogenous anti-infective immunomodulators interfering with CD14-mediated TLR-dependent immune responses. Here we describe the development of a peptide-based compound for systemic use, sHVF18, expressing the evolutionarily conserved innate structural fold of natural TCPs. Using a combination of structure- and in silico-based design, nuclear magnetic resonance spectroscopy, biophysics, mass spectrometry, cellular, and in vivo studies, we here elucidate the structure, CD14 interactions, protease stability, transcriptome profiling, and therapeutic efficacy of sHVF18. The designed peptide displays a conformationally stabilized, protease resistant active innate fold and targets the LPS-binding groove of CD14. In vivo, it shows therapeutic efficacy in experimental models of endotoxin shock in mice and pigs and increases survival in mouse models of systemic polymicrobial infection. The results provide a drug class based on Nature´s own anti-infective principles.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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