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1.	Andreasson, Jesper, et al. (författare) Exhaled phospholipid transfer protein and hepatocyte growth factor receptor in lung adenocarcinoma 2022 Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 23:1, s. 1-10 Tidskriftsartikel (refereegranskat)abstract 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 the particle flow rate (PFR) and collect exhaled breath particles (EBP) to diagnose primary lung adenocarcinoma (LUAD).METHODS: Seventeen patients listed for resection of LUAD stages IA-IIIA and 18 non-cancer surgical control patients were enrolled. EBP were collected before and after surgery for LUAD, and once for controls. Proteomic analysis was carried out using a proximity extension assay technology. Results were validated in both plasma from the same cohort and with microarray data from healthy lung tissue and LUAD tissue in the GSE10072 dataset.RESULTS: Of the 92 proteins analyzed, levels of five proteins in EBP were significantly higher in the LUAD patients compared to controls. Levels of phospholipid transfer protein (PLTP) and hepatocyte growth factor receptor (MET) decreased in LUAD patients after surgery compared to control patients. PFR was significantly higher in the LUAD cohort at all timepoints compared to the control group. MET in plasma correlated significantly with MET in EBP.CONCLUSION: Collection of EBP and measuring of PFR has never been performed in patients with LUAD. In the present study PFR alone could distinguish between LUAD and patients without LUAD. PLTP and MET were identified as potential biomarkers to evaluate successful tumor excision.
2.	Anesater, Erik, et al. (författare) A Rigid Disc for Protection of Exposed Blood Vessels During Negative Pressure Wound Therapy 2013 Ingår i: Surgical Innovation. - : SAGE Publications. - 1553-3506 .- 1553-3514. ; 20:1, s. 74-80 Tidskriftsartikel (refereegranskat)abstract Background. There are increasing reports of serious complications and deaths associated with negative pressure wound therapy (NPWT). Bleeding may occur when NPWT is applied to a wound with exposed blood vessels. Inserting a rigid disc in the wound may protect these structures. The authors examined the effects of rigid discs on wound bed tissue pressure and blood flow through a large blood vessel in the wound bed during NPWT. Methods. Wounds were created over the femoral artery in the groin of 8 pigs. Rigid discs were inserted. Wound bed pressures and arterial blood flow were measured during NPWT. Results. Pressure transduction to the wound bed was similar for control wounds and wounds with discs. Blood flow through the femoral artery decreased in control wounds. When a disc was inserted, the blood flow was restored. Conclusions. NPWT causes hypoperfusion in the wound bed tissue, presumably as a result of mechanical deformation. The insertion of a rigid barrier alleviates this effect and restores blood flow.
3.	Anesäter, Erik, et al. (författare) The influence on wound contraction and fluid evacuation of a rigid disc inserted to protect exposed organs during negative pressure wound therapy. 2011 Ingår i: International Wound Journal. - 1742-481X. ; 8, s. 393-399 Tidskriftsartikel (refereegranskat)abstract The use of a rigid disc as a barrier between the wound bed and the wound filler during negative pressure wound therapy (NPWT) has been suggested to prevent damage to exposed organs. However, it is important to determine that the effects of NPWT, such as wound contraction and fluid removal, are maintained during treatment despite the use of a barrier. This study was performed to examine the effect of NPWT on wound contraction and fluid evacuation in the presence of a rigid disc. Peripheral wounds were created on the backs of eight pigs. The wounds were filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. Wound contraction and fluid evacuation were measured after application of continuous NPWT at -80 mmHg. Wound contraction was similar in the presence and the absence of a rigid disc (84 ± 4% and 83 ± 3%, respectively, compared with baseline). Furthermore, the rigid disc did not affect wound fluid removal compared with ordinary NPWT (e.g. after 120 seconds, 71 ± 4 ml was removed in the presence and 73 ± 3 ml was removed in the absence of a disc). This study shows that a rigid barrier may be placed under the wound filler to protect exposed structures during NPWT without affecting wound contraction and fluid removal, which are two crucial features of NPWT.
4.	Anesäter, Erik, et al. (författare) The use of a rigid disc to protect exposed structures in wounds treated with negative pressure wound therapy: Effects on wound bed pressure and microvascular blood flow. 2012 Ingår i: Wound Repair and Regeneration. - 1524-475X. ; 20:4, s. 611-616 Tidskriftsartikel (refereegranskat)abstract There are increasing reports of deaths and serious complications associated with the use of negative pressure wound therapy (NPWT). Bleeding may occur in patients when NPWT is applied to a wound with exposed blood vessels or vascular grafts, possibly due to mechanical deformation and hypoperfusion of the vessel walls. Recent evidence suggests that using a rigid barrier disc to protect underlying tissue can prevent this mechanical deformation. The aim of this study was to examine the effect of rigid discs on the tissue exposed to negative pressure with regard to tissue pressure and microvascular blood flow. Peripheral wounds were created on the backs of eight pigs. The pressure and microvascular blood flow in the wound bed were measured when NPWT was applied. The wound was filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. The discs were created with or without channels (to accommodate exposed sensitive structures such as blood vessels and nerves), perforations, or a porous dressing that covered the underside of the discs (to facilitate pressure transduction and fluid evacuation). When comparing the results for pressure transduction to the wound bed, no significant differences were found using different discs covered with dressing, whereas pressure transduction was lower with bare discs. Microvascular blood flow in the wound bed decreased by 49 ± 7% when NPWT was applied to control wounds. The reduction in blood flow was less in the presence of a protective disc (e.g., -6 ± 5% for a dressing-covered, perforated disc, p = 0.006). In conclusion, NPWT causes hypoperfusion of superficial tissue in the wound bed. The insertion of a rigid barrier counteracts this effect. The placement of a rigid disc over exposed blood vessels or nerves may protect these structures from rupture and damage.
5.	Ansson, Cu, et al. (författare) Blood perfusion in Hewes tarsoconjunctival flaps in pigs measured by laser speckle contrast imaging 2018 Ingår i: JPRAS Open. - : Elsevier BV. - 2352-5878. ; 18, s. 98-103 Tidskriftsartikel (refereegranskat)abstract BackgroundHewes flap is a tarsoconjunctival eyelid flap, based at the lateral canthal tendon, and rotated and stretched to repair lateral defects in the lower eyelid commonly following tumor surgery. The aim of the present study was to monitor perfusion in a Hewes flap during reconstruction, which to the best of our knowledge, has not previously been done.MethodsA Hewes tarsoconjunctival eyelid flap was raised and the effects on blood perfusion of rotating the flaps by 90° and 180°, stretching the flaps with a force of 5 or 10 N, and repeated diathermic coagulation was monitored with laser speckle contrast imaging.ResultsRotating the flaps by 90° did not significantly affect perfusion, while further rotation to 180° reduced blood perfusion to 75% of the baseline value. When the tarsoconjunctival flaps were both rotated 90° and stretched with 5 N, the perfusion was reduced even further, to 63%. A further reduction in perfusion, to 36%, was seen when the higher force of 10 N was applied. Diathermy decreased blood perfusion to 56% after being applied once. Successive applications led to further decreases: 43%, 31%, and 15%, after the second, third and fourth applications.ConclusionsPerfusion in Hewes tarsoconjunctival flaps is affected by both rotation and stretching, but some perfusion is maintained despite these manipulations. Diathermy, however, has detrimental effects and should be avoided.
6.	Ansson, Cu Dybelius, et al. (författare) Perfusion in Upper Eyelid Flaps : Effects of Rotation and Stretching Measured With Laser Speckle Contrast Imaging in Patients 2020 Ingår i: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 36:5, s. 481-484 Tidskriftsartikel (refereegranskat)abstract PURPOSE: The aim of this study was to investigate how the blood perfusion in human upper eyelid skin flaps is affected by the length of the flap and the degree of stretching and rotation of the flap.METHODS: Twenty-nine upper eyelids were dissected as part of a blepharoplastic procedure in patients. The 1-cm wide proximal end of the flap remains attached, to mimic a random pattern skin flap (hereafter called a "skin flap"). Blood perfusion was measured with laser speckle contrast imaging before and after the flap was stretched with forces of 0.5, 1, and 2 N. The flap was then rotated 90°, and the same tensions were applied.RESULTS: Blood perfusion decreased gradually from the base to the tip of the flap. The flap was only well perfused in the proximal 1 cm (60% at 0.5 cm and 37% at 1.0 cm) and was minimally perfused beyond 2 cm (22% at 2.0 cm). Stretching the nonrotated flaps affected perfusion slightly (decreased to 43% at 0.5 cm). Simply rotating the flaps by 90° had no significant effect on the perfusion. The combination of rotation (90°) and stretching reduced the perfusion to 22% at 2 N, when measured 0.5 cm from the base.CONCLUSIONS: Blood perfusion in upper eyelid skin flaps decreases rapidly with distance from the base of the flap. Rotating and stretching the skin flap reduces blood perfusion even further, leading to minimal perfusion in this kind of flap at distances greater than 1.5 cm from the base.
7.	Augusto Silva, Iran, et al. (författare) A Semi-quantitative Scoring System for Green Histopathological Evaluation of Large Animal Models of Acute Lung Injury 2022 Ingår i: Bio-protocol. - 2331-8325. ; 12:16 Tidskriftsartikel (refereegranskat)abstract 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 typically associated with ARDS, animal models remain the most commonly used research tool for investigating potential new therapies. Experimental models of ALI/ARDS use different methods of injury to acutely induce lung damage in both small and large animals. These models have historically played an important role in the development of new clinical interventions, such as fluid therapy and the use of supportive mechanical ventilation (MV). However, failures in recent clinical trials have highlighted the potential inadequacy of small animal models due to major anatomical and physiological differences, as well as technical challenges associated with the use of clinical co-interventions [e.g., MV and extracorporeal membrane oxygenation (ECMO)]. Thus, there is a need for larger animal models of ALI/ARDS, to allow the incorporation of clinically relevant measurements and co-interventions, hopefully leading to improved rates of clinical translation. However, one of the main challenges in using large animal models of preclinical research is that fewer species-specific experimental tools and metrics are available for evaluating the extent of lung injury, as compared to rodent models. One of the most relevant indicators of ALI in all animal models is evidence of histological tissue damage, and while histological scoring systems exist for small animal models, these cannot frequently be readily applied to large animal models. Histological injury in these models differs due to the type and severity of the injury being modeled. Additionally, the incorporation of other clinical support devices such as MV and ECMO in large animal models can lead to further lung damage and appearance of features absent in the small animal models. Therefore, semi-quantitative histological scoring systems designed to evaluate tissue-level injury in large animal models of ALI/ARDS are needed. Here we describe a semi-quantitative scoring system to evaluate histological injury using a previously established porcine model of ALI via intratracheal and intravascular lipopolysaccharide (LPS) administration. Additionally, and owing to the higher number of samples generated from large animal models, we worked to implement a more sustainable and greener histopathological workflow throughout the entire process.
8.	Berggren, Johanna, et al. (författare) Reperfusion of Free Full-Thickness Skin Grafts in Periocular Reconstructive Surgery Monitored Using Laser Speckle Contrast Imaging 2021 Ingår i: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 37:4, s. 324-328 Tidskriftsartikel (refereegranskat)abstract 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 patients needing surgery due to tumor removal or cicatricial ectropion in the periocular region underwent reconstructive surgery using free skin grafts from either the contralateral upper eyelid or the upper inner arm. The free skin grafts measured 10-30 mm horizontally and 9-30 mm vertically. Blood perfusion was monitored using laser speckle contrast imaging immediately postoperatively (0 weeks) and at follow-up after 1, 3, and 7 weeks.RESULTS: All grafts were reperfused gradually during healing, the median value being 46% in the central part of the graft after 1 week and 79% after 3 weeks. The grafts were completely reperfused after 7 weeks. No difference was observed in the rate of reperfusion between the center and periphery of the grafts (p = not significant). The cosmetic and functional outcome was excellent in all but 1 patient, who developed ectropion that had to be surgically corrected.CONCLUSIONS: Skin grafts in the periorbital area are fully reperfused after 7 weeks. The periocular area is known to be well-vascularized and thus forgiving to reconstructive surgery. Future investigations of the reperfusion of free skin grafts in other parts of the body or in higher-risk populations should be carried out.
9.	Berggren, Johanna, et al. (författare) Revascularization After H-plasty Reconstructive Surgery in the Periorbital Region Monitored With Laser Speckle Contrast Imaging 2021 Ingår i: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 37:3, s. 269-273 Tidskriftsartikel (refereegranskat)abstract 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. The aim was to monitor perfusion in H-plasty flaps during surgery and during postoperative follow-up, using laser speckle contrast imaging.METHOD: H-plasty, i.e., bipedicle random advancement skin flaps, was used for reconstruction of the eyelids after tumor removal in 7 patients. The median length and width of the skin flaps were 13 mm (range, 8-20 mm) and 10 mm (range, 5-11 mm), respectively. Blood perfusion was measured using laser speckle contrast imaging during surgery and at follow up 1, 3, and 6 weeks postoperatively, to monitor revascularization.RESULTS: Immediately postoperatively, the perfusion in the distal end of the flaps had fallen to 54% (95% CI, 38%-67%). The perfusion then quickly increased during the healing process, being 104% (86%-124%) after 1 week, 115% (94%-129%) after 3 weeks, and 112% (96%-137%) after 6 weeks. There was no clinically observable ischemia or tissue necrosis.CONCLUSIONS: Revascularization of the H-plasty procedure flaps occurs quickly, within a week postoperatively, presumably due to the existing vascular network of the flap pedicle, and was not dependent on significant angiogenesis. This perfusion study confirms the general opinion that H-plasty is a good reconstructive technique, especially in the periorbital region with its rich vascular supply.
10.	Berggren, Johanna, et al. (författare) Revascularization of Free Skin Grafts Overlying Modified Hughes Tarsoconjunctival Flaps Monitored Using Laser-Based Techniques 2019 Ingår i: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 35:4, s. 378-382 Tidskriftsartikel (refereegranskat)abstract Purpose: It has recently been shown that the flap pedicle does not supply blood to a tarsoconjunctival graft in the modified Hughes procedure in patients. This raises questions concerning the rate of revascularization of the free skin graft commonly used to reconstruct the anterior lamella. The aim of this study was, thus, to monitor the course of revascularization in free skin grafts overlying modified Hughes tarsoconjunctival flaps, using laser-based techniques.Methods: Free skin grafts from the upper eyelid or upper arm in 9 patients were used to cover a tarsoconjunctival flap according to the modified Hughes procedure. Blood perfusion was monitored using laser speckle contrast imaging, and vascular reactivity was studied with laser Doppler velocimetry after heating the tissue to 44°C. Measurements were made at the time of surgery (baseline) and at 1, 3, 8, and 16 weeks postoperatively.Results: The gradual increase in perfusion of the free skin grafts during the healing process indicates revascularization. A slight increase in perfusion was seen already after 1 week. Perfusion reached 50% of the baseline after 3 weeks, and complete restoration of perfusion was seen after 8 weeks. The vascular function monitored with heat-induced hyperemia increased in a similar fashion.Conclusions: Full-thickness skin grafts revascularize within 3 to 8 weeks, despite overlying a tarsoconjunctival flap, which has recently been reported to be avascular. This provides further evidence that it should be possible to repair large eyelid defects using free full-thickness eyelid grafts.
11.	Berggren, Johanna V, et al. (författare) Blood Perfusion of Human Upper Eyelid Skin Flaps Is Better in Myocutaneous than in Cutaneous Flaps 2022 Ingår i: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 38:2, s. 166-169 Tidskriftsartikel (refereegranskat)abstract 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 design often used in reconstruction in the periocular area, a myocutaneous flap in which the blood supply follows the fibers of the orbicularis muscle and is thus parallel to the long axis of the flap. The muscle was thereafter dissected from the flap to create a cutaneous flap. Blood perfusion in the 2 types of flaps was compared using laser speckle contrast imaging.RESULTS: Blood perfusion decreased gradually from the base to the tip of all the flaps. Perfusion was significantly higher in the myocutaneous flaps than in the cutaneous flaps (p < 0.0004): 69% in the myocutaneous flaps and 43% in the cutaneous flaps, measured 5 mm from the base. Blood perfusion was preserved to a greater extent distally in the myocutaneous flaps (minimum value seen at 25 mm) than in the cutaneous flaps (minimum seen at 11 mm).CONCLUSIONS: Blood perfusion was better preserved in myocutaneous flaps, including both skin and the orbicularis oculi muscle, than in cutaneous flaps. This may be of clinical interest in patients with poor microcirculation in which a long flap is required for reconstructive surgery.
12.	Berggren, Johanna V, et al. (författare) Laser Speckle Contrast Imaging of the Blood Perfusion in Glabellar Flaps Used to Repair Medial Canthal Defects 2022 Ingår i: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 38:3, s. 274-279 Tidskriftsartikel (refereegranskat)abstract 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 monitoring techniques. The aim of this study was to use a modern imaging technique to assess blood perfusion in glabellar flaps.METHODS: Glabellar flaps were used to repair medial canthal defects following tumor excision in 7 patients. Blood perfusion was monitored using laser speckle contrast imaging: during surgery, immediately postoperatively (0 weeks), and at follow-up, 1, 3, and 6 weeks after surgery.RESULTS: Perfusion decreased gradually along the length of the flap, and reached a minimum 15 mm from the flap base. Perfusion in the proximal 20 mm of the flap was completely restored after 1 week, while the distal part of the flap was gradually reperfused over 6 weeks. Both the functional and esthetic surgical outcomes were excellent.CONCLUSIONS: The rapid reperfusion of the glabellar flap may be explained by its connection to the vascular network via the flap pedicle. In flaps longer than 20 mm, the distal part can be considered a free skin transplant, and a combination of a glabellar flap and a free skin graft could then be considered.
13.	Berggren, Johanna V, et al. (författare) The Effect of Canthotomy on Blood Perfusion During the Repair of Lower Eyelid Defects 2020 Ingår i: Ophthalmic Plastic and Reconstructive Surgery. - 1537-2677. ; 36:2, s. 135-138 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Canthotomy is frequently used to mobilize extra tissue when repairing larger lower eyelid defects. The aim of this study was to explore the effect of canthotomy on blood perfusion and oxygen tension.METHODS: Eight pigs underwent a wedge resection of the lower eyelid and canthotomy (with cantholysis involving the lateral palpebral artery). The wedge resection was performed 8, 6, and 4 mm from the canthotomy. Perfusion and oxygen tension were monitored in the eyelid between the wedge resection and canthotomy using laser Doppler velocimetry and a Clark electrode. Verapamil was administered, and measurements were also performed 12 hours after surgery, to investigate the possible effects of vasospasm RESULTS:: The wedge resection alone did not affect perfusion. Canthotomy led to a reduction in perfusion; being 60% when the length of remaining eyelid was 8 mm, 32% when it was 6 mm, and 24% when it was 4 mm. Similar results were observed for oxygen tension. Vasospasm did not affect the results.CONCLUSIONS: Canthotomy in combination with a wedge resection of the lower eyelid affects blood perfusion. A smaller length of remaining eyelid tissue will have less perfusion. This may not have any implications in cases of direct closure, but may play a role when the eyelid is to provide oxygen and nutrients to avascular grafts.
14.	Bergwik, Jesper, et al. (författare) Macrophage expressed tartrate-resistant acid phosphatase 5 promotes pulmonary fibrosis progression 2024 Ingår i: Immunology. - 0019-2805. ; 171:4, s. 583-594 Tidskriftsartikel (refereegranskat)abstract 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 perturbations of the bleomycin mouse model of IPF including genetic knockout, RANKL inhibition, and macrophage adoptive transfer to further understand ACP5's role in pulmonary fibrosis. Genetic ablation of Acp5 decreased immune cell recruitment to the lungs and reduced the levels of hydroxyproline (reflecting extracellular matrix-production) as well as histological damage. Additionally, gene expression profiling of murine lung tissue revealed downregulation of genes including Ccl13, Mmp13, and Il-1α that encodes proteins specifically related to immune cell recruitment and macrophage/fibroblast interactions. Furthermore, antibody-based neutralization of RANKL, an important inducer of Acp5 expression, reduced immune cell recruitment but did not decrease fibrotic lung development. Adoptive transfer of Acp5 -/- bone marrow-derived monocyte (BMDM) macrophages 7 or 14 days after bleomycin administration resulted in reductions of cytokine production and decreased levels of lung damage, compared to adoptive transfer of WT control macrophages. Taken together, the data presented in this study suggest that macrophage derived ACP5 plays an important role in development of pulmonary fibrosis and could present a tractable target for therapeutic intervention in IPF.
15.	Bjarnason, Thordur, et al. (författare) Pressure at the Bowel Surface during Topical Negative Pressure Therapy of the Open Abdomen: An Experimental Study in a Porcine Model. 2011 Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 35, s. 917-923 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Topical negative pressure (TNP) therapy is increasingly used in open abdomen management. It is not known to what extent this pressure propagates through the dressing to the bowel surface, potentially increasing the risk of bowel fistula formation. The present study in a porcine model was designed to evaluate pressure propagation. METHODS: A commercially available TNP therapy system (ABThera/VAC) was applied in six pigs after laparotomy. Pressure sensors were placed in predetermined positions in the dressing and in the abdominal cavity and the pressure was registered at TNP settings of -50, -75, -100, -125, and -150 mmHg. Next, after infusing 200 ml of saline into the abdomen through a catheter, the amount of fluid drained through the system during 10 min of TNP therapy was registered. Finally, pressure was measured above and below eight layers of paraffin gauzes during TNP therapy. RESULTS: Observed pressure within the outer two foams and the foam of the visceral protective layer correlated with preset TNP. The median pressure at the bowel surface was between -2 and -10 mmHg, regardless of preset TNP. Median fluid drainage was 95% of the infused fluid at -75 mmHg and 124% at -150 mmHg. Paraffin gauzes had a limited isolating effect, reducing the pressure by 13% in median. CONCLUSIONS: Negative pressure reaching the bowel surface during TNP therapy with the ABThera system is limited for all TNP levels. Reduced therapy pressure does not lead to reduced pressure at the bowel surface. The system drains the abdominal cavity completely of fluid. Paraffin gauzes are of limited value as a means of pressure isolation.
16.	Bodén, Embla, et al. (författare) A Systematic Review of Mesenchymal Epithelial Transition Factor (MET) and Its Impact in the Development and Treatment of Non-Small-Cell Lung Cancer. 2023 Ingår i: Cancers. - 2072-6694. ; 15:15 Forskningsöversikt (refereegranskat)abstract Lung cancer represents the leading cause of annual cancer-related deaths worldwide, accounting for 12.9%. The available treatment options for patients who experience disease progression remain limited. Targeted therapeutic approaches are promising but further understanding of the role of genetic alterations in tumorigenesis is imperative. The MET gene has garnered great interest in this regard. The aim of this systematic review was to analyze the findings from multiple studies to provide a comprehensive and unbiased summary of the evidence. A systematic search was conducted in the reputable scientific databases Embase and PubMed, leading to the inclusion of twenty-two articles, following the PRISMA guidelines, elucidating the biological role of MET in lung cancer and targeted therapies. The systematic review was registered in PROSPERO with registration ID: CRD42023437714. MET mutations were detected in 7.6-11.0% of cases while MET gene amplification was observed in 3.9-22.0%. Six studies showed favorable treatment outcomes utilizing MET inhibitors compared to standard treatment or placebo, with increases in PFS and OS ranging from 0.9 to 12.4 and 7.2 to 24.2 months, respectively, and one study reporting an increase in ORR by 17.3%. Furthermore, patients with a higher mutational burden may derive greater benefit from treatment with MET tyrosine kinase inhibitors (TKIs) than those with a lower mutational burden. Conversely, two studies reported no beneficial effect from adjunctive treatment with a MET targeted therapy. Given these findings, there is an urgent need to identify effective therapeutic strategies specifically targeting the MET gene in lung cancer patients.
17.	Bodén, Embla, et al. (författare) Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome 2022 Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:11 Tidskriftsartikel (refereegranskat)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.
18.	Borgquist, Ola, et al. (författare) Undertrycksbehandling av sår: Kunskap om verkningsmekanismer och komplikationer ger nya möjligheter. 2011 Ingår i: Läkartidningen. - 0023-7205. ; 108:46, s. 2372-2375 Forskningsöversikt (refereegranskat)
19.	Broberg, Ellen, et al. (författare) A new way of monitoring mechanical ventilation by measurement of particle flow from the airways using Pexa method in vivo and during ex vivo lung perfusion in DCD lung transplantation 2018 Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 6 Tidskriftsartikel (refereegranskat)abstract Background: Different mechanical ventilation settings are known to affect lung preservation for lung transplantation. Measurement of particle flow in exhaled air may allow online assessment of the impact of ventilation before changes in the tissue can be observed. We hypothesized that by analyzing the particle flow, we could understand the impact of different ventilation parameters. Methods: Particle flow was monitored in vivo, post mortem, and in ex vivo lung perfusion (EVLP) in six porcines with the Pexa (particles in exhaled air) instrument. Volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) were used to compare small versus large tidal volumes. The surfactant lipids dipalmitoylphosphatidylcholine (DPPC) and phosphatidylcholine (PC) were quantified by mass spectrometry. Results: In vivo the particle mass in VCV1 was significantly lower than in VCV2 (p= 0.0186), and the particle mass was significantly higher in PCV1 than in VCV1 (p= 0.0322). In EVLP, the particle mass in VCV1 was significantly higher than in PCV1 (p= 0.0371), and the particle mass was significantly higher in PCV2 than in PCV1 (p= 0.0127). DPPC was significantly higher in EVLP than in vivo. Conclusions: Here, we introduce a new method for measuring particle flow during mechanical ventilation and confirm that these particles can be collected and analyzed. VCV resulted in a lower particle flow in vivo but not in EVLP. In all settings, large tidal volumes resulted in increased particle flow. We found that DPPC was significantly increased comparing in vivo with EVLP. This technology may be useful for developing strategies to preserve the lung and has a high potential to detect biomarkers.
20.	Broberg, Ellen, et al. (författare) Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients 2020 Ingår i: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:1 Tidskriftsartikel (refereegranskat)abstract Introduction: In this cohort study, we evaluated whether the particles in exhaled air (PExA) device can be used in conjunction with mechanical ventilation during surgery. The PExA device consists of an optical particle counter and an impactor that collects particles in exhaled air. Our aim was to establish the feasibility of the PExA device in combination with mechanical ventilation (MV) during surgery and if collected particles could be analysed. Patients with and without nonsmall cell lung cancer (NSCLC) undergoing lung surgery were compared to normal breathing (NB) patients with NSCLC. Methods: A total of 32 patients were included, 17 patients with NSCLC (MV-NSCLC), nine patients without NSCLC (MV-C) and six patients with NSCLC and not intubated (NB). The PEx samples were analysed for the most common phospholipids in surfactant using liquid-chromatography-mass-spectrometry (LCMS). Results: MV-NSCLC and MV-C had significantly lower numbers of particles exhaled per minute ( particle flow rate; PFR) compared to NB. MV-NSCLC and MV-C also had a siginificantly lower amount of phospholipids in PEx when compared to NB. MV-NSCLC had a significantly lower amount of surfactant A compared to NB. Conclusion: We have established the feasibility of the PExA device. Particles could be collected and analysed. We observed lower PFR from MV compared to NB. High PFR during MV may be due to more frequent opening and closing of the airways, known to be harmful to the lung. Online use of the PExA device might be used to monitor and personalise settings for mechanical ventilation to lower the risk of lung damage.
21.	Broberg, Ellen, et al. (författare) Particle Flow Profiles From the Airways Measured by PExA Differ in Lung Transplant Recipients Who Develop Primary Graft Dysfunction 2019 Ingår i: Experimental and clinical transplantation. - : Baskent University. - 1304-0855 .- 2146-8427. ; 17:6, s. 803-812 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Primary graft dysfunction is a severe form of acute lung injury and a major cause of early morbidity and mortality encountered after lung transplant.We used a customized PExA 2.0 instrument (PExA, Gothenburg, Sweden) to measure particle flow in exhaled air during mechanical ventilation in the intensive care unit. Our objective was to discover whether patients who developed primary graft dysfunction had different particle flow patterns from the airways. We used volume-controlled ventilation and pressure-controlled ventilation to see whether changes in particle patterns could be observed in both mechanical ventilation settings.MATERIALS AND METHODS: First, we investigated whether it was safe to use a customized PExA 2.0 in conjunction with mechanical ventilation. Next, 12 lung transplant patients were randomized to either daily volumecontrolled ventilation or pressure-controlled ventilation as the first mode of treatment until extubation.RESULTS: In our study group, 6 patients did not develop primary graft dysfunction and 6 developed primary graft dysfunction. Patients with primary graft dysfunction underwent mechanical ventilation significantly longer; they also showed a stepwise increase in particle count from day 0 until extubation. We observed no adverse events related to the PExA 2.0 device.CONCLUSIONS: This study suggests that the PExA 2.0 device is safe to use in conjunction with mechanical ventilation in the intensive care unit. Lung transplant patients who developed primary graft dysfunction showed a different particle profile from the airways before clinical signs of primary graft dysfunction developed. Online assessment of ventilation impact before presentation of tissue changes may allow realtime detection of primary graft dysfunction, thus preventing or reducing its effects.
22.	Broberg, Ellen, et al. (författare) Releasing high positive end-expiratory pressure to a low level generates a pronounced increase in particle flow from the airways 2023 Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 11:1 Tidskriftsartikel (refereegranskat)abstract 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 particle flow while increasing and releasing positive end-expiratory pressure (PEEP). The aim of this study was to investigate the impact of different levels of PEEP on particle flow in exhaled air in an experimental setting. We hypothesized that gradually increasing PEEP will reduce the particle flow from the airways and releasing PEEP from a high level to a low level will result in increased particle flow. Methods: Five fully anesthetized domestic pigs received a gradual increase of PEEP from 5 cmH2O to a maximum of 25 cmH2O during volume-controlled ventilation. The particle count along with vital parameters and ventilator settings were collected continuously and measurements were taken after every increase in PEEP. The particle sizes measured were between 0.41 µm and 4.55 µm. Results: A significant increase in particle count was seen going from all levels of PEEP to release of PEEP. At a PEEP level of 15 cmH2O, there was a median particle count of 282 (154–710) compared to release of PEEP to a level of 5 cmH2O which led to a median particle count of 3754 (2437–10,606) (p < 0.009). A decrease in blood pressure was seen from baseline to all levels of PEEP and significantly so at a PEEP level of 20 cmH2O. Conclusions: In the present study, a significant increase in particle count was seen on releasing PEEP back to baseline compared to all levels of PEEP, while no changes were seen when gradually increasing PEEP. These findings further explore the significance of changes in particle flow and their part in pathophysiological processes within the lung.
23.	Bölükbas, Deniz, et al. (författare) Organ-Restricted Vascular Delivery of Nanoparticles for Lung Cancer Therapy 2020 Ingår i: Advanced Therapeutics. - : Wiley. - 2366-3987. ; 3:7 Tidskriftsartikel (refereegranskat)abstract 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 chemokine receptor type 2 is explored in lung tumors. The addition of active targeting ligands on MSNs enhances their uptake in vitro but fails to promote specific delivery to tumors in vivo, when administered systemically via the blood or locally to the lung into immunocompetent murine lung cancer models. Ineffective tumor targeting is due to efficient clearance of the MSNs by the phagocytic cells of the liver, spleen, and lung. These limitations, however, are successfully overcome using a novel organ-restricted vascular delivery (ORVD) approach. ORVD in isolated and perfused mouse lungs of Kras-mutant mice enables effective nanoparticle extravasation from the tumor vasculature into the core of solid lung tumors. In this study, ORVD promotes tumor cell-specific uptake of nanoparticles at cellular resolution independent of their functionalization with targeting ligands. Organ-restricted vascular delivery thus opens new avenues for optimized nanoparticles for lung cancer therapy and may have broad applications for other vascularized tumor types.
24.	De Santis, Martina M, et al. (författare) Extracellular-Matrix-Reinforced Bioinks for 3D Bioprinting Human Tissue 2021 Ingår i: Advanced Materials. - : Wiley. - 1521-4095 .- 0935-9648. ; 33:3 Tidskriftsartikel (refereegranskat)abstract 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 extracellular matrix derived from decellularized tissue (rECM). rECM has rheological and gelation properties beneficial for 3D bioprinting while retaining biologically inductive properties supporting tissue maturation ex vivo and in vivo. These bioinks are shear thinning, resist cell sedimentation, improve viability of multiple cell types, and enhance mechanical stability in hydrogels derived from them. 3D printed constructs generated from rECM bioinks suppress the foreign body response, are pro-angiogenic and support recipient-derived de novo blood vessel formation across the entire graft thickness in a murine model of transplant immunosuppression. Their proof-of-principle for generating human tissue is demonstrated by 3D bioprinting human airways composed of regionally specified primary human airway epithelial progenitor and smooth muscle cells. Airway lumens remained patent with viable cells for one month in vitro with evidence of differentiation into mature epithelial cell types found in native human airways. rECM bioinks are a promising new approach for generating functional human tissue using 3D bioprinting.
25.	De Santis, Martina M, et al. (författare) How to build a lung : latest advances and emerging themes in lung bioengineering 2018 Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52, s. 1-19 Forskningsöversikt (refereegranskat)abstract Chronic respiratory diseases remain a major cause of morbidity and mortality worldwide. The only option at end-stage disease is lung transplantation, but there are not enough donor lungs to meet clinical demand. Alternative options to increase tissue availability for lung transplantation are urgently required to close the gap on this unmet clinical need. A growing number of tissue engineering approaches are exploring the potential to generate lung tissue ex vivo for transplantation. Both biologically derived and manufactured scaffolds seeded with cells and grown ex vivo have been explored in pre-clinical studies, with the eventual goal of generating functional pulmonary tissue for transplantation. Recently, there have been significant efforts to scale-up cell culture methods to generate adequate cell numbers for human-scale bioengineering approaches. Concomitantly, there have been exciting efforts in designing bioreactors that allow for appropriate cell seeding and development of functional lung tissue over time. This review aims to present the current state-of-the-art progress for each of these areas and to discuss promising new ideas within the field of lung bioengineering.
26.	Dellgren, Goeran, et al. (författare) Effect of once-per-daytacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial 2024 Ingår i: LANCET RESPIRATORY MEDICINE. - 2213-2600. ; 12:1, s. 34-44 Tidskriftsartikel (refereegranskat)abstract Background Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation. Methods ScanCLAD is an investigator-initiated, open-label, multicentre, randomised, controlled trial in Scandinavia evaluating whether an immunosuppressive protocol based on anti-thymocyte globulin induction followed by tacrolimus (once per day), mycophenolate mofetil, and corticosteroids reduces the incidence of CLAD after de novo lung transplantation compared with a protocol using ciclosporin (twice per day), mycophenolate mofetil, and corticosteroids. Patients aged 18-70 years who were scheduled to undergo double lung transplantation were randomly allocated (1:1) to receive either oral ciclosporin (2-3 mg/kg before transplantation and 3 mg/kg [twice per day] from postoperative day 1) or oral tacrolimus (005-01 mg/kg before transplantation and 01-02 mg/kg from postoperative day 1). The primary endpoint was CLAD at 36 months post transplantation, determined by repeated lung function tests and adjudicated by an independent committee, and was assessed with a competing-risks analysis with death and re-transplantation as competing events. The primary outcome was assessed in the modified intention-to-treat (mITT) population, defined as those who underwent transplantation and received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02936505) and EudraCT (2015-004137-27). Findings Between Oct 21, 2016, and July 10, 2019, 383 patients were screened for eligibility. 249 patients underwent double lung transplantation and received at least one dose of study drug, and were thus included in the mITT population: 125 (50%) in the ciclosporin group and 124 (50%) in the tacrolimus group. The mITT population consisted of 138 (55%) men and 111 (45%) women, with a mean age of 552 years (SD 102), and no patients were lost to follow-up. In the mITT population, CLAD occurred in 48 patients (cumulative incidence 39% [95% CI 31-48]) in the ciclosporin group and 16 patients (13% [8-21]) in the tacrolimus group at 36 months post transplantation (hazard ratio [HR] 028 [95% CI 015-052], log-rank p<00001). Overall survival did not differ between groups at 3 years in the mITT population (74% [65-81] for ciclosporin vs 79% [70-85] for tacrolimus; HR 072 [95% CI 041-127], log-rank p=025). However, in the per protocol CLAD population (those in the mITT population who also had at least one post-baseline lung function test allowing assessment of CLAD), allograft survival was significantly better in the tacrolimus group (HR 049 [95% CI 026-091], log-rank p=0021). Adverse events totalled 1516 in the ciclosporin group and 1459 in the tacrolimus group. The most frequent adverse events were infection (453 events), acute rejection (165 events), and anaemia (129 events) in the ciclosporin group, and infection (568 events), anaemia (108 events), and acute rejection (98 events) in the tacrolimus group. 112 (90%) patients in the ciclosporin group and 108 (87%) in the tacrolimus group had at least one serious adverse event. Interpretation Immunosuppression based on use of tacrolimus once per day significantly reduced the incidence of CLAD compared with use of ciclosporin twice per day. These findings support the use of tacrolimus as the first choice of calcineurin inhibitor after lung transplantation.
27.	Edström, Dag, et al. (författare) Amniotic fluid derived mesenchymal stem cells reduce inflammation and improve lung function following transplantation in a porcine model Ingår i: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. - 1557-3117. Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Lung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and post-operative outcomes.METHODS: In a transplantation model, donor pigs were stratified to either the treated or the non-treated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion before transplantation. Treatment consisted of three doses of 2x10 6 cells/kg: one during ex vivo lung perfusion and two after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD). RESULTS: Repeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO 2/FiO 2 ratios and reduced incidence of PGD. CONCLUSIONS: Repeated injection of lung-specific cell treatment during EVLP and post-transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of post-operative outcomes.
28.	Edström, Dag, et al. (författare) Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome 2023 Ingår i: Respiratory Research. - 1465-9921. ; 24:1 Tidskriftsartikel (refereegranskat)abstract 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 adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 10 6 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.
29.	Engqvist, Linn, et al. (författare) Laser speckle contrast imaging enables perfusion monitoring of the anterior segment during strabismus surgery: a study on the horizontal rectus muscles 2023 Ingår i: British Journal of Ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 107, s. 1704-1708 Tidskriftsartikel (refereegranskat)abstract 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 measurements. There is no method available for perioperative, real-time perfusion measurements during ocular muscle surgery. The aims of this study were to investigate whether laser speckle contrast imaging (LSCI) could be used for such measurements, and to monitor perfusion during strabismus surgery on one or two horizontal rectus muscles.Methods Forty-four eyes in 44 patients with horizontal strabismus underwent corrective surgery involving medial and/or lateral rectus muscle detachment. Perfusion in the adjacent paralimbal and iris tissue was monitored with LSCI.Results When the first horizontal rectus muscle was detached perfusion in the adjacent paralimbal tissue decreased by 23% (p<0.0001), and by 12% (p<0.0001) when the second muscle was detached. The iris perfusion decreased by 5% (p<0.05) when the first muscle was detached but showed no significant decrease as the second muscle was cut.Conclusion This is the first study showing that perfusion of the anterior segment can be monitored non-invasively with LSCI during strabismus surgery. In this cohort, two horizontal rectus muscles were detached with only a small decrease in the anterior segment circulation. Future studies are required for complete mapping of the effect of surgery on multiple ocular muscles on the anterior segment circulation.Data are available upon request.
30.	Fakhro, Mohammed, et al. (författare) 25-year follow-up after lung transplantation at Lund University Hospital in Sweden : superior results obtained for patients with cystic fibrosis 2016 Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 23:1, s. 65-73 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: In Sweden, two centres perform lung transplantation for a population of about 9 million and the entire population is covered for lung transplantation by government health insurance. Lund University Hospital is one of these centres. This retrospective report reviews the 25-year experience of the Skåne University Hospital Lung Transplant Program with particular emphasis on short-term outcome and long-term survival but also between different subgroups of patients and types of transplant [single-lung transplantation (SLTx) versus double-lung transplantation (DLTx)] procedure performed.METHODS: Between January 1990 and June 2014, 278 patients underwent lung transplantation at the Skåne University Hospital Sweden. DLTx was performed in 172 patients, SLTx was performed in 97 patients and heart-lung transplantation was performed in 9 patients. In addition, 15 patients required retransplantation (7 DLTx and 8 SLTx).RESULTS: Overall 1-, 5-, 10-, 15- and 20-year survival rates were 88, 65, 49, 37 and 19% for the whole cohort. DLTx recipients showed 1-, 5-, 10- and 20-year survival rates of 90, 71, 60 and 30%, compared with SLTx recipients with 1-, 5-, 10- and 20-year survival rates of 83, 57, 34 and 6% (P < 0.05), respectively. Comparing the use of intraoperative extracorporeal membrane oxygenation, extracorporeal circulation (ECC) and no circulatory support in the aspect of survival, a significant difference in favour of intraoperative ECC was seen.CONCLUSIONS: Superior long-term survival rates were seen in recipients diagnosed with cystic fibrosis, α1-antitrypsin deficiency and pulmonary hypertension. DLTx showed better results compared with SLTx especially at 10 years post-transplant. In the present study, we present cumulative incidence rates of bronchiolitis obliterans syndrome of 15% at 5 years, 26% at 10 years and 32% at 20 years post-transplant; these figures are in line with the lowest rates presented internationally.
31.	Fakhro, Mohammed, et al. (författare) ABO-identical matching has no superiority in long-term survival in comparison to ABO-compatible matching in lung transplantation 2019 Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Background: Even though identical blood group matching between recipient and donor is preferred, it is still not clear by how much this improves the outcome for patients who received a lung transplant (LTx), or whether there is any survival benefit. Earlier studies have yielded ambiguous results and few have investigated long-term survival. The aim of this study is, therefore, to explore the different outcomes of identical and compatible recipient and donor blood group matching to determine whether identical matching is superior (LTx). Method: Between January 1990 to June 2016, 297 patients underwent primary LTx, 10 patients underwent heart and lung transplantation (HLTx), and 18 patients required re-transplantation (Re-LTx) at Skåne University Hospital in Lund. With a total of 325 transplantations at our center, 262 were ABO-identically matched while 53 were ABO-compatible. For survival analyses, the end-point used was retransplantation-free survival in addition to excluding HLTx (n = 10), assessed by Cox regression and Kaplan-Meier. Results: ABO-compatible patients had a median of 49 days (2-641), and ABO-identical patients had a median of 89 days (1-1717) (p = 0.048) on the transplant waiting list. Patients with a limited survival up to 1-year showed significant difference in survival rate for ABO-compatible recipients compared to ABO-identical recipients (p < 0.05), however no significant difference was shown in overall survival between the two groups (p > 0.05), with the same pattern shown in patients with a limited survival rate up to ten years, emphysema-patients, when excluding single-LTx and patients transplanted before 2005 and after 2005, respectively (p > 0.05). Conclusion: Recipients who received ABO-compatible matched grafts showed a similar survival rate to recipients who received ABO-identical matched grafts in the present study. Cytolomegalovirus and Ebstein Barr Virus mismatch were also identified as risk factors particular among emphysema patients. Since ABO-identical transplantations and ABO-compatible transplantations showed similar results, the present selection-bias of preferring ABO-identical lungs could be adjusted to increase organ allocation. It might also be possible to shorten recipient waiting list time, as an identical match showed over 80% higher time on the waiting list than a compatible, non-identical match.
32.	Fakhro, Mohammed, et al. (författare) ABO-Identical Matching Has No Superiority in Survival in Comparison to ABO-Compatible Matching in Lung Transplantation 2017 Ingår i: Journal of Heart and Lung Transplantation. - 1557-3117. ; 36:4, s. 315-315 Konferensbidrag (refereegranskat)
33.	Fakhro, Mohammed, et al. (författare) Double lung, unlike single lung transplantation might provide a protective effect on mortality and bronchiolitis obliterans syndrome 2017 Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 12:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Survival after lung transplantation (LTx) is often limited by bronchiolitis obliterans syndrome (BOS).METHOD: Survey of 278 recipients who underwent LTx. The endpoint used was BOS (BOS grade ≥ 2), death or Re-lung transplantation (Re-LTx) assessed by competing risk regression analyses.RESULTS: The incidence of BOS grade ≥ 2 among double LTx (DLTx) recipients was 16 ± 3% at 5 years, 30 ± 4% at 10 years, and 37 ± 5% at 20 years, compared to single LTx (SLTx) recipients whose corresponding incidence of BOS grade ≥ 2 was 11 ± 3%, 20 ± 4%, and 24 ± 5% at 5, 10, and 20 years, respectively (p > 0. 05). The incidence of BOS grade ≥ 2 by major indications ranked in descending order: other, PF, CF, COPD, PH and AAT1 (p < 0. 05). The mortality rate by major indication ranked in descending order: COPD, PH, AAT1, PF, Other and CF (p < 0. 05).CONCLUSION: No differences were seen in the incidence of BOS grade ≥ 2 regarding type of transplant, however, DLTx recipients showed a better chance of survival despite developing BOS compared to SLTx recipients. The highest incidence of BOS was seen among CF, PF, COPD, PH, and AAT1 recipients in descending order, however, CF and PF recipients showed a better chance of survival despite developing BOS compared to COPD, PH, and AAT1 recipients.
34.	Fakhro, Mohammed, et al. (författare) Ex-vivo Lung Perfusion - 10 Year Follow-up of the First Performed Double LTX With Marginal Donor Lungs Evaluated Using EVLP 2018 Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 37:4 Suppl, s. 149-149 Konferensbidrag (refereegranskat)
35.	Fakhro, Mohammed, et al. (författare) Impact of allograft ischemic time on short- and long-term survival in lung transplantation 2018 Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 37:4 Suppl, s. 247-248 Konferensbidrag (refereegranskat)
36.	Fakhro, Mohammed, et al. (författare) Impact of Forced Expiratory Volume in 1 Second (FEV1) and 6-Minute Walking Distance at 3, 6, and 12 Months and Annually on Survival and Occurrence of Bronchiolitis Obliterans Syndrome (BOS) After Lung Transplantation 2017 Ingår i: Annals of Transplantation. - 2329-0358. ; 22, s. 532-540 Tidskriftsartikel (refereegranskat)abstract BACKGROUND Development of bronchiolitis obliterans syndrome (BOS) is a great limitation for patient survival in lung transplantation (LTx). A curative treatment for BOS is still missing, and in terminal stages re-transplantation (Re-LTx) is the only salvation. It is possible to slow the progress of BOS if it is detected at an early stage. This might be possible by assessing pulmonary function pattern. MATERIAL AND METHODS Between 1990 and 2014, 278 patients underwent LTx at Skåne University Hospital, Sweden. Pulmonary function was followed using spirometry (FEV1) and 6-minute walking test (6MWT) measured at 3, 6, and 12 months and annually. The endpoint used was freedom from BOS (BOS grade ≤1), BOS (BOS grade ≥2), and death or Re-LTx. RESULTS Double-lung transplantation (DLTx) showed a hazard ratio (HR) of 0.514 (p=0.001) versus recipients who underwent single-lung transplantation (SLTx). Regarding freedom from BOS, FEV1 showed an HR of 0.597 and 6MWT an HR of 0.982 (p<0.001). Regarding combined endpoint BOS ≥2 and Re-LTx, FEV1 showed an HR of 0.618 and 6MWT an HR of 0.972 (p<0.001). CONCLUSIONS Recipients with higher FEV1 or 6MWT values had better chances of survival. Recipients with DLTx had a significant survival benefit and a protective effect against development of BOS. As the distance that the patient can walk in 6 minutes increases, risk for death or Re-LTx is significantly lower, as is incidence of developing BOS grade ≥2. Understanding changes within pulmonary function are probably key to understanding patient prognosis.
37.	Ghaidan, Haider, et al. (författare) Impact of allograft ischemic time on long-term survival in lung transplantation : a Swedish monocentric study 2020 Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 54:5, s. 322-329 Tidskriftsartikel (refereegranskat)abstract 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-point used was death/Re-LTx assessed by Cox regression and Kaplan–Meier survival. Results: Kaplan–Meier survival for mean IT (min) between subgroups ≤120, 121–240, 241–360 and 361+ showed significant difference for pairwise-comparisons with superior outcome for IT between ≤120 and 240 min. Cox regression analyses for each hour of IT in patients with a limited survival up to 1- and 5-year had a hazard ratio (HR) of 1.119 and 1.063 respectively (p <.05). Conclusions: In LTx, every 2-hour increase of IT is equivalent to an increased mortality of up to 24% within 5 years. LTx with an IT of ≤120 min had a superior survival in both 1- and 5 years in comparison to an IT of up to 360 min. Better application of IT provides a key role in improving LTx outcome.
38.	Ghaidan, Haider, et al. (författare) Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation 2022 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1 Tidskriftsartikel (refereegranskat)abstract 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 using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.
39.	Ghaidan, Haider, et al. (författare) Ten year follow-up of lung transplantations using initially rejected donor lungs after reconditioning using ex vivo lung perfusion 2019 Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Background: In 2006 and 2007 we performed double lung transplantation with marginal donor lungs assessed and reconditioned by Ex Vivo Lung Perfusion (EVLP), using a technique developed by Professor Stig Steen. Here we present a 10-year follow-up comparing the outcomes of lung transplantations performed at our clinic using EVLP lungs vs. conventional lungs. Method: Between 2006 and 2007, 21 patients (6 EVLP, 15 conventional) underwent double lung transplantation (LTx) with follow-up on May 2017 at Lund University Hospital, Sweden. Pulmonary function was measured at 3/6/12 months, and annually thereafter for a period of 10 years in addition to survival and freedom from chronic lung allograft dysfunction (CLAD) being analyzed. Results: Regarding Forced Expiratory Volume in 1 s (FEV1) and 6MWT at 3, 6, and 12 months and annually thereafter, no difference in median FEV1 nor 6MWT was found for EVLP-LTx vs. conventional-LTx (p > 0.05). No difference was shown in post-operative survival between EVLP-LTx vs. conventional LTx for patients with an overall survival up to 10-years (p > 0.05). The same pattern was shown in sub analyses for patients with a limited survival up to 1 and 5 years (p > 0.05). Conclusion: No superiority was found in conventional-LTx over EVLP-LTx, neither in long-term survival nor pulmonary function. No difference in CLAD-free survival was seen between the two groups. We believe that EVLP is a safe and effective method to use in LTx, greatly increasing the donor pool by improving marginal lungs and providing an objective assessment of the viability of marginal donor lungs.
40.	Hallgren, Filip, et al. (författare) Particle flow rate from the airways as fingerprint diagnostics in mechanical ventilation in the intensive care unit : A randomised controlled study 2021 Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:3 Tidskriftsartikel (refereegranskat)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.
41.	Haraldsen, Pernille, et al. (författare) A porcine model for acute ischaemic right ventricular dysfunction. 2014 Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 18:1, s. 43-48 Tidskriftsartikel (refereegranskat)abstract To establish an experimental model for acute ischaemic isolated right ventricular dysfunction and the subsequent haemodynamic changes.
42.	Haraldsen, Pernille, et al. (författare) Sevoflurane anesthesia during acute right ventricular ischemia in pigs preserves cardiac function better than propofol anesthesia. 2016 Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. Tidskriftsartikel (refereegranskat)abstract The intention of the present study was to evaluate possible cardioprotective properties of inhalation anesthesia with sevoflurane.
43.	Haraldsen, Pernille, et al. (författare) Sevoflurane provides better haemodynamic stability than propofol during right ventricular ischaemia-reperfusion 2020 Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285. ; 30:1, s. 129-135 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To assess whether sevoflurane provides better haemodynamic stability than propofol in acute right ventricular (RV) ischaemia-reperfusion. METHODS: Open-chest pigs (mean ± standard deviation, 68.8 ± 4.2 kg) anaesthetized with sevoflurane (n = 6) or propofol (n = 6) underwent 60 min of RV free wall ischaemia and 150 min of reperfusion. Haemodynamic parameters and blood flow in the 3 major coronary arteries were continuously monitored. Biomarkers of cardiac ischaemia were analysed. RESULTS: Mean arterial pressure and stroke volume decreased, whereas pulmonary vascular resistance increased equally in both groups. Heart rate increased 7.5% with propofol (P < 0.05) and 17% with sevoflurane (P < 0.05). At reperfusion, left atrial pressure and systemic vascular resistance decreased with sevoflurane. While RV stroke work (mmHg·ml) and cardiac output (l·min-1) decreased in the propofol group (4.2 ± 1.2 to 2.9 ± 1.7 and 2.65 ± 0.44 to 2.28 ± 0.56, respectively, P < 0.05 both), they recovered to baseline levels in the sevoflurane group (4.1 ± 1.5 to 4.0 ± 1.5 and 2.77 ± 0.6 to 2.6 ± 0.5, respectively, P > 0.05). Circumflex and left anterior descending coronary artery blood flow decreased in both groups. Right coronary artery blood flow (ml·min-1) decreased with propofol (38 ± 9 to 28 ± 9, P < 0.05), but not with sevoflurane (28 ± 11 to 28 ± 17, P > 0.05). Biomarkers of cardiac ischaemia increased in both groups. CONCLUSIONS: Compared to propofol, sevoflurane-anaesthetized pigs showed higher RV stroke work, cardiac output and right coronary artery blood flow during reperfusion. These findings warrant a clinical trial of sevoflurane in RV ischaemia in humans.
44.	Hirdman, Gabriel, et al. (författare) Proteomic characteristics and diagnostic potential of exhaled breath particles in patients with COVID-19 2023 Ingår i: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 20:1 Tidskriftsartikel (refereegranskat)abstract 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 analysis of exhaled breath particles (EBPs) in contrast, are non-invasive, sample directly from the pathological source and presents as a novel explorative and diagnostical tool.METHODS: Patients with PCR-verified COVID-19 infection (COV-POS, n = 20), and patients with respiratory symptoms but with > 2 negative polymerase chain reaction (PCR) tests (COV-NEG, n = 16) and healthy controls (HCO, n = 12) were prospectively recruited. EBPs were collected using a "particles in exhaled air" (PExA 2.0) device. Particle per exhaled volume (PEV) and size distribution profiles were compared. Proteins were analyzed using liquid chromatography-mass spectrometry. A random forest machine learning classification model was then trained and validated on EBP data achieving an accuracy of 0.92.RESULTS: Significant increases in PEV and changes in size distribution profiles of EBPs was seen in COV-POS and COV-NEG compared to healthy controls. We achieved a deep proteome profiling of EBP across the three groups with proteins involved in immune activation, acute phase response, cell adhesion, blood coagulation, and known components of the respiratory tract lining fluid, among others. We demonstrated promising results for the use of an integrated EBP biomarker panel together with particle concentration for diagnosis of COVID-19 as well as a robust method for protein identification in EBPs.CONCLUSION: Our results demonstrate the promising potential for the use of EBP fingerprints in biomarker discovery and for diagnosing pulmonary diseases, rapidly and non-invasively with minimal patient discomfort.
45.	Hirdman, Gabriel, et al. (författare) Taking a Deep Breath : an Examination of Current Controversies in Surgical Procedures in Lung Transplantation 2022 Ingår i: Current transplantation reports. - : Springer Science and Business Media LLC. - 2196-3029. ; 9:3, s. 160-172 Forskningsöversikt (refereegranskat)abstract 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, delayed chest closure, and ex vivo lung perfusion.Recent Findings: With the growing rate of lung transplantations worldwide and increasing numbers of patients placed on waiting lists, the importance of determining best practices has only increased in recent years. Factors which promote successful outcomes have been identified across all the topics, with certain approaches promoted, such as ambulation in bridge-to-transplant and widespread intraoperative ECMO as machine support.Summary: While great strides have been made in the operative procedures involved in lung transplantation, there are still key questions to be answered. The consensus which can be reached will be instrumental in further improving outcomes in recipients.
46.	Hlebowicz, Joanna, et al. (författare) Carotid atherosclerosis, changes in tissue remodeling and repair in patients with aortic coarctation 2021 Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 335, s. 47-52 Tidskriftsartikel (refereegranskat)abstract 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% men, mean age 47 ± 16 years) underwent ultrasound of their arteries. A multiplex platform to analyze circulating blood levels biomarkers reflecting inflammation, tissue remodeling and repair was used. Results: In men following CoA repair, a significantly increased carotid bulb IMT was observed in comparison to the control group (1.05 [0.72–1.24] vs. 0.67 [0.59–0.95] mm; p = 0.003). Median common carotid artery (CCA) IMT was increased in men compared to controls (0.82 [0.61–0.97] mm vs. 0.58 [0.53–0.76] mm, p < 0.003) and in women compared to controls (0.83 [0.70–0.92] vs. 0.60 [0.55–0.69], p < 0.004). CoA demonstrated an independent association with IMT in both men and women. Men with CoA were also more likely to have a plaque in their carotid arteries (p = 0.010). In women with CoA, we observed significantly lower levels of stem cell factor (SCF, p = 0.004) while in men with CoA we observed significantly lower levels of matrix metalloproteinase-3 (MMP-3, p = 0.048), tumor necrosis factor receptor 1 (TNF-R1, p = 0.032), tumor necrosis factor receptor superfamily member 10B (TRAIL-R2, p = 0.019) and monocyte chemotactic protein 1 (MCP-1, p = 0.015). Conclusions: This is the first study to show that despite successful CoA repair, patients have more carotid atherosclerosis than can be explained by changes in tissue remodeling and repair.
47.	Hlebowicz, Joanna, et al. (författare) Effect of commercial rye whole-meal bread on postprandial blood glucose and gastric emptying in healthy subjects 2009 Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 8 Tidskriftsartikel (refereegranskat)abstract Background: The intake of dietary fibre has been shown to reduce the risk of developing diabetes mellitus. The aim of this study was to compare the effects of commercial rye whole-meal bread containing whole kernels and white wheat bread on the rate of gastric emptying and postprandial glucose response in healthy subjects. Methods: Ten healthy subjects took part in a blinded crossover trial. Blood glucose level and gastric emptying rate (GER) were determined after the ingestion of 150 g white wheat bread or 150 g whole-meal rye bread on two different occasions after fasting overnight. The GER was measured using real-time ultrasonography, and was calculated as the percentage change in antral cross-sectional area 15 and 90 minutes after completing the meal. Results: No statistically significant difference was found between the GER values or the blood glucose levels following the two meals when evaluated with the Wilcoxon signed rank sum test. Conclusion: The present study revealed no difference in postprandial blood glucose response or gastric emptying after the ingestion of rye whole-meal bread compared with white wheat bread.
48.	Hlebowicz, Joanna, et al. (författare) Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and ghrelin concentrations in healthy subjects. 2009 Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 89, s. 815-821 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: A previous study of healthy subjects showed that intake of 6 g cinnamon with rice pudding reduced postprandial blood glucose and the gastric emptying rate (GER) without affecting satiety. OBJECTIVE: The objective was to study the effect of 1 and 3 g cinnamon on GER, postprandial blood glucose, plasma concentrations of insulin and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)], the ghrelin response, and satiety in healthy subjects. DESIGN: GER was measured by using real-time ultrasonography after ingestion of rice pudding with and without 1 or 3 g cinnamon. Fifteen healthy subjects were assessed in a crossover trial. RESULTS: The addition of 1 or 3 g cinnamon had no significant effect on GER, satiety, glucose, GIP, or the ghrelin response. The insulin response at 60 min and the area under the curve (AUC) at 120 min were significantly lower after ingestion of rice pudding with 3 g cinnamon (P = 0.05 and P = 0.036, respectively, after Bonferroni correction). The change in GLP-1 response (DeltaAUC) and the change in the maximum concentration (DeltaC(max)) were both significantly higher after ingestion of rice pudding with 3 g cinnamon (P = 0.0082 and P = 0.0138, respectively, after Bonferroni correction). CONCLUSIONS: Ingestion of 3 g cinnamon reduced postprandial serum insulin and increased GLP-1 concentrations without significantly affecting blood glucose, GIP, the ghrelin concentration, satiety, or GER in healthy subjects. The results indicate a relation between the amount of cinnamon consumed and the decrease in insulin concentration.
49.	Hlebowicz, Joanna, et al. (författare) Microvascular blood flow response in the intestinal wall and the omentum during negative wound pressure therapy of the open abdomen 2012 Ingår i: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 27:3, s. 397-403 Tidskriftsartikel (refereegranskat)abstract Higher closure rates of the open abdomen have been reported with negative pressure wound therapy (NPWT) compared with other wound therapy techniques. However, the method has occasionally been associated with increased development of intestinal fistulae. The present study measures microvascular blood flow in the intestinal wall and the omentum before and during NPWT. Six pigs underwent midline incision and application of NPWT to the open abdomen. The microvascular blood flow in the underlying intestinal loop wall and the omentum was recorded before and after the application of NPWT of -50, -70, -100, -120, -150, and -170 mmHg respectively, using laser Doppler velocimetry. A significant decrease in microvascular blood flow was seen in the intestinal wall during application of all negative pressures levels. The blood flow was 2.7 (+/- 0.2) Perfusion Units (PU) before and 2.0 (+/- 0.2) PU (p < 0.05) after application of -50 mmHg, and 3.6 (+/- 0.6) PU before and 1.5 (+/- 0.2) PU (*p < 0.01) after application of -170 mmHg. In the present study, we show that negative pressures between -50 and -170 mmHg induce a significant decrease in the microvascular blood flow in the intestinal wall. The decrease in blood flow increased with the amount of negative pressure applied. One can only speculate that a longstanding decreased blood flow in the intestinal wall may induce ischemia and secondary necrosis in the intestinal wall, which, theoretically, could promote the development of intestinal fistulae. We believe that NPWT of the open abdomen is a very effective treatment but could probably be improved.
50.	Hlebowicz, Joanna, et al. (författare) Relationship between postprandial changes in cardiac left ventricular function, glucose and insulin concentrations, gastric emptying, and satiety in healthy subjects 2011 Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 10 Tidskriftsartikel (refereegranskat)abstract Background: The digestion of food is known to alter the hemodynamics of the body significantly. The purpose of this study was to study the postprandial changes in stroke volume (SV), cardiac output (CO) and left ventricular (LV) longitudinal systolic and diastolic functions measured with tissue Doppler imaging, in relation to gastric emptying rate (GER), satiety, and glucose and insulin concentrations in healthy subjects. Methods: Twenty-three healthy subjects were included in this study. The fasting and postprandial changes at 30 min and 110 min in CO, heart rate (HR) and blood pressure were measured. Moreover, tissue Doppler imaging systolic (S'), early (E') and late (A') mitral annular diastolic velocities were measured in the septal (s) and lateral (l) walls. Glucose and insulin concentrations, and satiety were measured before and 15, 30, 45, 60, 90, and 120 min after the start of the meal. The GER was calculated as the percentage change in the antral cross-sectional area 1590 min after ingestion of the meal. Results: This study show that both CO, systolic longitudinal ventricular velocity of the septum (S's) and lateral wall (S'l), the early diastolic longitudinal ventricular velocity of the lateral wall (E'l), the late diastolic longitudinal ventricular velocity of the septum (A's) and lateral wall (A'l) increase significantly, and were concomitant with increased satiety, antral area, glucose and insulin levels. The CO, HR and SV at 30 min were significantly higher, and the diastolic blood pressure was significantly lower, than the fasting. The satiety was correlated to HR and diastolic blood pressure. The insulin level was correlated to HR. Conclusions: This study shows that postprandial CO, HR, SV and LV longitudinal systolic and diastolic functions increase concomitantly with increased satiety, antral area, and glucose and insulin levels. Therefore, patients should not eat prior to, or during, cardiac evaluation as the effects of a meal may affect the results and their interpretation.

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