Sandra Lindstedt

• Lund University

Lung transplantation remains the definitive treatment for end‐stage lung disease, but several critical challenges persist. Key issues include the limited availability of donor organs, ongoing debates over optimal preservation methods, and the controversy surrounding the best intraoperative support systems. Additionally, the efficacy of bridging str...

Background Lung transplantation remains hampered by a scarcity of viable donor lungs, partially attributed to donor lung injuries. Methods Three porcine lung injury models were studied: infection-induced using lipopolysaccharide (n = 7), aspiration-induced using endotracheal gastric content (n = 7), and injury using lavage and harmful ventilation...

Objective Patients on direct-acting oral anticoagulants (DOACs) are at high risk of perioperative bleeding complications. Intraoperative hemoadsorption is a novel strategy to reduce perioperative bleeding in patients on DOACs undergoing non-deferable cardiac surgery. The international STAR-registry reports real-world clinical outcomes associated wi...

Background/Objectives: A novel patient group with chronic pulmonary fibrosis is emerging post COVID-19. To identify patients at risk of developing post-COVID-19 lung fibrosis, we here aimed to identify systemic proteins that overlap with fibrotic markers identified in patients with idiopathic pulmonary fibrosis (IPF) and may predict COVID-19-induce...

Objective Patients on direct-acting oral anticoagulants (DOACs) are at high risk of perioperative bleeding complications. Intraoperative hemoadsorption is a novel strategy to reduce perioperative bleeding in patients on DOACs undergoing non-deferable cardiac surgery. The international STAR-registry reports real-world clinical outcomes associated wi...

Solid organ transplantation has progressed rapidly over the decades from the first experimental procedures to its role in the modern era as an established treatment for end-stage organ disease. Solid organ transplantation including liver, kidney, pancreas, heart, and lung transplantation, is the definitive option for many patients, but despite the...

Background Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or...

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recomme...

Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the dise...

Acute lung injury (ALI) represents an aetiologically diverse form of pulmonary damage. Part of the assessment and diagnosis of ALI depends on skilled observer-based scoring of brightfield microscopy tissue sections. Although this readout is sufficient to determine gross alterations in tissue structure, its categorical scores lack the sensitivity to...

The microscopic observation of lung tissue is challenging due to its fragile nature. Xylene and isopropanol are common tissue-clearing reagents used before paraffin embedding, yet no studies have compared these two reagents in lung tissue processing. Due to the well-known health risks xylene could introduce to operators, as well as its environmenta...

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder involving scarring of pulmonary tissue and a subsequent decrease in respiratory capacity, ultimately resulting in death. Tartrate resistant acid phosphatase 5 (ACP5) plays a role in IPF but the exact mechanisms are yet to be elucidated. In this study, we have utilized various pertur...

Background Despite advancements, cardiopulmonary bypass-assisted cardiac surgery still carries a significant risk for morbidity and mortality, often related to postoperative hyperinflammation. Hemoadsorption of cytokines and various exogenous and endogenous inflammation triggers has been increasingly used in cardiac surgery to mitigate the risk of...

Background Despite advancements, cardiopulmonary bypass-assisted cardiac surgery still carries a significant risk for morbidity and mortality, often related to postoperative hyperinflammation. Hemoadsorption of cytokines and various exogenous and endogenous inflammation triggers has been increasingly used in cardiac surgery to mitigate the risk of...

IntroductionIn recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and clinical studies, with the potential to improve graft...

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-base...

Background: Lung transplantation is the only treatment option for end stage lung disease. Despite improvements, in LTx, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the mainchief factor in late mortality after lung transplantationLtx. Primary graft dysfunctionPGD...

BACKGROUND Lung 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 oxy...

Simple Summary Lung cancer is the type of cancer that kills the most people in the world each year. It is difficult to diagnose lung cancer in the early stages and there are only few treatment options available once the cancer has spread. The mesenchymal epithelial transition factor (MET) gene is of importance in lung cancer development, and mutati...

Elevated levels of neutrophil extracellular traps (NETs) have been reported in primary graft dysfunction, making methods to reduce or remove them highly valuable. The mechanisms behind primary graft dysfunction remain rudimentarily understood but its relation to higher rates of acute and chronic rejection necessitates the development of preventativ...

Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adip...

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...

Extracorporeal membrane oxygenation (ECMO) occupies an increasingly important position in the clinic for the management of cardiac and/or pulmonary failure. As a rescue therapy, ECMO can support patients following respiratory or cardiac compromise to act as a bridge to recovery, to decision, or to transplant. This chapter reviews briefly the histor...

Background SARS-CoV-2 has been shown to predominantly infect the airways and the respiratory tract and too often have an unpredictable and different pathologic pattern compared to other respiratory diseases. Current clinical diagnostical tools in pulmonary medicine expose patients to harmful radiation, are too unspecific or even invasive. Proteomic...

Objectives Detecting particle flow from the airways by a non-invasive analyzing technique might serve as an additional tool to monitor mechanical ventilation. In the present study, we used a customized particles in exhaled air (PExA) technique, which is an optical particle counter for the monitoring of particle flow in exhaled air. We studied parti...

Background Screening decreases mortality among lung cancer patients but is not widely implemented, thus there is an unmet need for an easily accessible non-invasive method to enable early diagnosis. Particles in exhaled air offer a promising such diagnostic tool. We investigated the validity of a particles in exhaled air device (PExA) to measure th...

Aims Exhaled breath particles have been explored for diagnosing different lung diseases. We recently showed in an experimental model that different cardiac output results in different particle flow rate (PFR) from the airways. Given the well‐known close relationship between impaired cardiac function and respiratory failure, we hypothesized that PFR...

Background The structure of alveoli is critical for normal lung function and when maintenance of the underlying extracellular matrix (ECM) that forms these delicate structures fails, patients may develop emphysema or lung fibrosis via pathological processes that are not fully understood. The alveolar walls are lined by alveolar epithelial cells (AE...

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...

Background A dreaded complication of strabismus surgery is anterior segment ischaemia (ASI), caused by damage to the anterior ciliary arteries. To avoid ASI, a maximum of two rectus muscles are operated on at a time. However, these surgical protocols are based on empirical observations of clinical outcome, rather than objective perfusion measuremen...

Purpose of Review This article reviews controversial questions within the field of lung transplantation, with a focus on data generated within the last 3 years. We aim to summarize differing opinions on a selection of topics, including bridge-to-transplantation, intraoperative machine circulatory support, bronchial anastomosis, size mismatch, delay...

Acute respiratory distress syndrome (ARDS) is a life-threatening, high mortality pulmonary condition characterized by acute lung injury (ALI) resulting in diffuse alveolar damage. Despite progress regarding the understanding of ARDS pathophysiology, there are presently no effective pharmacotherapies. Due to the complexity and multiorgan involvement...

Background The mast cell-specific metalloprotease CPA3 has been given important roles in lung tissue homeostasis and disease pathogenesis. However, the dynamics and spatial distribution of mast cell CPA3 expression in lung diseases remain unknown. Methods Using a histology-based approach for quantitative spatial decoding of mRNA and protein single...

Background The risk of adults with a congenital heart defect (ACHD) developing heart failure, stroke, arrhythmias, and need for valve replacement is increased compared to healthy peers. Evidence for the use of novel oral anticoagulants (NOAC) in this patient group is still lacking and vitamin K antagonists (VKA) are the primary choice for patients...

Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS usin...

Introduction Atopic asthma and allergic rhinitis are common chronic inflammatory diseases affecting lower airways and nasal mucosa, respectively. Several reports demonstrated frequent co-occurrence of these two diseases, however, the exact molecular mechanism has not been described. The present study aimed to investigate if small non-coding RNA mig...

Objectives: Detecting particle flow from the airways by none invasively online analysing technique might serve as an additional tool to monitor mechanical ventilation. In the present study we used a customised Pexa (Particles in Exhaled Air), which is an optical particle counter for airway monitoring of particle flow in exhaled air. Positive end ex...

Purpose: The aim of this study was to monitor how the blood perfusion in human upper eyelids is affected during full-thickness blepharotomy. Methods: Seven eyelids in 5 patients with upper eyelid retraction due to Graves' disease underwent full-thickness blepharotomy. Perfusion was measured using laser speckle contrast imaging in the eyelid marg...

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 d...

Background: Asthma is the most frequent chronic disease in children. One of the most replicated genetic findings in childhood asthma is the ORMDL3 gene confirmed in several GWA studies in several paediatric populations. Objectives: The purpose of this study was to analyse ORMDL3 variants and expression in childhood asthma in the Polish populatio...

Background Primary graft dysfunction (PGD) is still a major complication in patients undergoing lung transplantation (LTx). Much is unknown about the effect of postoperative mechanical ventilation on outcomes, with debate on the best approach to ventilation. Aim/Purpose The goal of this study is to generate hypotheses on the association between po...

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...

Background: The glabellar flap is a common technique for surgical repair after tumor excision in the medial canthal area. However, the outcome may be affected by partial flap necrosis. Little is known about the impact of surgery on blood perfusion and the postoperative course of reperfusion due to the absence of reliable and noninvasive perfusion...

Introduction Adults with congenital heart disease (ACHD) are a group with an increased risk of thromboembolic complications and arrhythmias. Vitamin K antagonists (VKA) are the most commonly used thromboprophylaxis therapy in this population. Studies on the efficacy and safety of novel oral anticoagulants (NOAC) are scare, but emerging together wit...

There have been a few reports of successful lung transplantation (LTx) in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS); however, all reports were with rather short follow-up. Here we present a 62-year-old man without prior lung diseases. Following SARS-CoV-2-induced ARDS and 6 months of extracorporeal membrane oxygena...

Background and aims: After aortic coarctation (CoA) repair, patients still suffer from cardiovascular complications. The aim of this study was to measure cardiovascular markers, intima-media thickness (IMT) and plaques in controls and patients with CoA. Methods: Sixty-four patients with CoA (66% male, mean age 48 ± 15 years) and controls (54% me...

Background: The aim of this study was to monitor blood perfusion in human upper eyelid skin flaps and examine how the perfusion is affected by the thickness of the flap. Methods: Twenty upper eyelids were dissected as part of a blepharoplasty procedure in patients. The medial end of the blepharoplasty flap remained attached to mimic a flap desig...

In severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) is a life-prolonging treatment, especially among COVID-19 patients. Evaluation of lung injury progression is challenging with current techniques. Diagnostic imaging or invasive diagnostics are risky given the difficulties of intra-hospital transportatio...

Introduction Mechanical ventilation (MV) 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 ventilat...

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....

Airway basal cells are crucial for regeneration of the human lung airway epithelium, and are thought to be important contributors to Chronic Obstructive Pulmonary Disease (COPD) and other lung disorders. In order to reveal how basal cells contribute to disease, and to discover novel therapeutic targets, these basal cells need to be further characte...

Patients with arteriolosclerosis have impaired microvascular perfusion leading to impaired wound healing. Aged garlic extract has shown to have a positive impact on vascular elasticity. The present study aimed to assess the effect of long-term treatment with AGE on peripheral tissue perfusion in patients with confirmed atherosclerosis. Ninety three...

Despite improvements, lung transplantation (LTx) remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine filtration as a means of restoring ARDS donor lungs. We induced mild to moderate AR...

Recent advances in 3D bioprinting allow for generating intricate structures with dimensions relevant for human tissue, but suitable bioinks for producing translationally relevant tissue with complex geometries remain unidentified. Here, a tissue-specific hybrid bioink is described, composed of a natural polymer, alginate, reinforced with extracellu...

Precision-cut lung slices (PCLS) have gained increasing interest as a model to study lung biology/disease and screening novel therapeutics. In particular, PCLS derived from human tissue can better recapitulate some aspects of lung biology/disease as compared to animal models. Several experimental readouts have been established for use with PCLS, bu...

Purpose: Free skin grafts are frequently used in reconstructive surgery. However, little is known about the course of reperfusion due to the previous lack of reliable perfusion monitoring techniques. The aim of this study was to use state-of-the-art laser speckle contrast imaging to monitor free skin grafts in the periocular area. Methods: Seven...

Background: H-plasty reconstructive surgery is commonly used to close defects after tumor excision in the periorbital region. Revascularization of the bipedicle skin flaps is essential for healing. However, it has not previously been possible to study this revascularization in humans due to the lack of noninvasive perfusion monitoring techniques....

Precision-cut lung slices (PCLS) have gained increasing interest as a model to study lung biology and disease, as well as for screening novel therapeutics. In particular, PCLS derived from human tissue can better recapitulate some aspects of lung biology and disease as compared to PCLS derived from animals (e.g. clinical heterogeneity), but access...

Despite their immense potential, clinical translation of nanomedicines is hampered by physicochemical and biological barriers impairing cell‐specific targeting especially in solid tumors. In article number 2000017 Darcy E. Wagner, Silke Meiners and co‐workers report a novel approach using organ‐restricted vascular delivery (ORVD) with direct admini...

Purpose: The influence of allograft ischemic time (IT) on short- and long-term mortality remains under debate in lung transplantation (LTx). Due to a scarcity in donors, better understanding of IT might improve the outcome after LTx. Methods: Between January 1990 and June 2016; 307 patients underwent LTx at Lund university hospital, Sweden. The end...

Purpose: It is generally believed that large eyelid defects must be repaired using a vascularized flap for 1 lamella, while the other can be a free graft. Recent studies indicate that the pedicle of a tarsoconjunctival flap does not contribute to blood perfusion. The purpose of this study was to explore whether large eyelid defects can be repaired...

Nanoparticle‐based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C─C ch...

Abstract Background One of the most serious secondary manifestations of Cardiovascular Disease (CVD) is coronary atherosclerosis. This study aimed to evaluate whether aged garlic extract (AGE) can influence coronary artery calcification (CAC) and to predict the individual effect of AGE using a standard process for data mining (CRISP–DM). Method Thi...

Fibrotic disorders account for over one third of mortalities worldwide. Despite great efforts to study the cellular and molecular processes underlying fibrosis, there are currently few effective therapies. Dual-stage polymerization reactions are an innovative tool for recreating heterogeneous increases in extracellular matrix (ECM) modulus that are...