Macrophage expressed tartrate-resistant acid phosphatase 5 promotes pulmonary fibrosis progression.

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.

Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath.

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 disease at the proteomic level. In total, 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on postoperative day 3. Exhaled breath particles (EBPs) were evaluated by mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Recipients with PGD had significantly higher PFR [686.4 (449.7-8,824.0) particles per minute (ppm)] compared to recipients without PGD [116.6 (79.7-307.4) ppm, p = 0.0005]. Porcine and human EBP proteins recapitulated proteins found in the BAL, demonstrating its utility instead of more invasive techniques. Furthermore, adherens and tight junction proteins were underexpressed in PGD tissue. Histological and proteomic analysis found significant changes to the alveolar-capillary barrier explaining the high PFR in PGD. Exhaled breath measurement is proposed as a rapid and non-invasive bedside measurement of PGD.

The role of hemoadsorption in cardiac surgery - a systematic review.

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 for postoperative complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess the role of perioperative hemoadsorption in cardiac surgery, by summarizing the current knowledge in this clinical setting. METHODS: A literature search of PubMed, Cochrane library, and the database provided by CytoSorbents was conducted on June 1st, 2023. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search, including language variations of terms "cardiac surgery" and "hemoadsorption". The screening and selection process followed scientific principles (PRISMA statement). Abstracts were considered for inclusion if they were written in English and published within the last ten years. Publications were eligible for assessment if reporting on original data from any type of study (excluding case reports) in which a hemoadsorption device was investigated during or after cardiac surgery. Results were summarized according to sub-fields and presented in a tabular view. RESULTS: The search resulted in 29 publications with a total of 1,057 patients who were treated with hemoadsorption and 988 control patients. Articles were grouped and descriptively analyzed due to the remarkable variability in study designs, however, all reported exclusively on CytoSorb® therapy. A total of 62% (18/29) of the included articles reported on safety and no unanticipated adverse events have been observed. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability. CONCLUSIONS: The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery in patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Future large randomized controlled trials are needed to better define proper patient selection, dosing, and timing of the therapy.

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry.

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 recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.

Proteomic characteristics and diagnostic potential of exhaled breath particles in patients with COVID-19.

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.

Integrin α10ß1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome.

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 α10ß1-selected adipose tissue-derived MSCs (integrin α10ß1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10ß1 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 × 106 cells/kg integrin α10ß1-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 α10ß1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.

Increased expression of ORMDL3 in allergic asthma: a case control and in vitro study.

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 pediatric populations. OBJECTIVES: The purpose of this study was to analyze ORMDL3 variants and expression in childhood asthma in the Polish population. METHODS: In the study we included 416 subject, 223 asthmatic children and 193 healthy control subjects. The analysis of two SNPs (rs3744246 and rs8076131) was performed using genotyping with TaqMan probes. The methylation of the ORMDL3 promoter was examined with Methylation Sensitive HRM (MS-HRM), covering 9 CpG sites. The expression of ORMDL3 was analyzed in PBMCs from pediatric patients diagnosed with allergic asthma and primary human bronchial epithelial cells derived from healthy subjects treated with IL-13, IL-4, or co-treatment with both cytokines to model allergic airway inflammation. RESULTS: We found that ORMDL3 expression was increased in allergic asthma both in PBMCs from asthmatic patients as well as in human bronchial epithelial cells stimulated with the current cytokines. We did not observe significant differences between cases and controls either in the genotype distribution of analyzed SNPs (rs3744246 and rs8076131) nor in the level of promoter methylation. CONCLUSIONS: Increased ORMDL3 expression is associated with pediatric allergic asthma and upregulated in the airways upon Th2-cytokines stimulation, but further functional studies are required to fully understand its role in this disease.

Extracorporeal Membrane Oxygenation: Set-up, Indications, and Complications.

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 history of ECMO implementation as well as device modes, from veno-arterial, veno-venous, veno-arterial-venous, and veno-venous-arterial set-ups. The importance of acknowledging complications that can arise in each of these modes cannot be overlooked. Both bleeding and thrombosis are inherent risks to the use of ECMO and the existing strategies for management are reviewed. The device also elicits an inflammatory response, and the use of extracorporeal approaches can lead to infection, both of which are important to examine when reflecting how ECMO can be successfully implemented in patients. This chapter both discusses the understanding of these various complications and highlights the need for future research.

Exhaled phospholipid transfer protein and hepatocyte growth factor receptor in lung adenocarcinoma.

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.

The role of mechanical ventilation in primary graft dysfunction in the postoperative lung transplant recipient: A single center study and literature review.

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 was to generate hypotheses on the association between postoperative mechanical ventilation settings and allograft size matching in PGD development. METHOD: This is a retrospective study of LTx patients between September 2011 and September 2018 (n = 116). PGD was assessed according to the International Society of Heart and Lung Transplantation (ISHLT) criteria. Data were collected from medical records, including chest x-ray assessments, blood gas analysis, mechanical ventilator parameters and spirometry. RESULTS: Positive end-expiratory pressures (PEEP) of 5 cm H2 O were correlated with lower rates of grade 3 PGD. Graft size was important as tidal volumes calculated according to the recipient yielded greater rates of PGD when low volumes were used, a correlation that was lost when donor metrics were used. CONCLUSION: Our results highlight a need for greater investigation of the role donor characteristics play in determining post-operative ventilation of a lung transplant recipient. The mechanical ventilation settings on postoperative LTx recipients may have an implication for the development of acute graft dysfunction. Severe PGD was associated with the use of a PEEP higher than 5 and lower tidal volumes and oversized lungs were associated with lower long-term mortality. Lack of association between ventilatory settings and survival may point to the importance of other variables than ventilation in the development of PGD.

Mapping of Perfusion During Full-Thickness Blepharotomy Using Laser Speckle Contrast Imaging.

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 margin and in the conjunctival pedicle. RESULTS: Immediately following the procedure, a nonsignificant reduction in perfusion was observed in the skin of the pretarsal eyelid margin, being 66% of the initial value ( p = n.s.). However, a statistically significant decrease in perfusion, to 53% of the initial value ( p < 0.01), was seen in the central pedicle of the conjunctiva. There were no surgical complications such as infection, signs of ischemia, or bleeding. CONCLUSIONS: In this study, eyelid perfusion was mapped during full-thickness blepharotomy for the first time using laser speckle contrast imaging. The results showed that perfusion is sufficiently preserved during surgery, probably due to the rich vascular supply in the periocular region, which may explain the low risk of postoperative complications such as ischemia and infection.

Laser Speckle Contrast Imaging of the Blood Perfusion in Glabellar Flaps Used to Repair Medial Canthal Defects.

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.

Blood Perfusion of Human Upper Eyelid Skin Flaps Is Better in Myocutaneous than in Cutaneous Flaps.

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.

Human Primary Airway Basal Cells Display a Continuum of Molecular Phases from Health to Disease in Chronic Obstructive Pulmonary Disease.

Airway basal cells are crucial for regeneration of the human lung airway epithelium and are believed to be important contributors to chronic obstructive pulmonary disease (COPD) and other lung disorders. To reveal how basal cells contribute to disease and to discover novel therapeutic targets, these basal cells need to be further characterized. In this study, we optimized a flow cytometry-based cell sorting protocol for primary human airway basal cells dependent on cell size and NGFR (nerve-growth factor receptor) expression. The basal cell population was found to be molecularly and functionally heterogeneous, in contrast to cultured basal cells. In addition, significant differences were found, such as KRT14 expression exclusively existing in cultured cells. Also, colony-forming capacity was significantly increased in cultured cells showing a clonal enrichment in vitro. Next, by single-cell RNA sequencing on primary basal cells from healthy donors and patients with Global Initiative for Chronic Obstructive Lung Disease stage IV COPD, the gene expression revealed a continuum ranging from healthy basal cell signatures to diseased basal cell phenotypes. We identified several upregulated genes that may indicate COPD, such as stress response-related genes GADD45B and AHSA1, together with with genes involved in the response to hypoxia, such as CITED2 and SOD1. Taken together, the presence of healthy basal cells in stage IV COPD demonstrates the potential for regeneration through the discovery of novel therapeutic targets. In addition, we show the importance of studying primary basal cells when investigating disease mechanisms as well as for developing future cell-based therapies in the human lung.

Isolation of high-yield and -quality RNA from human precision-cut lung slices for RNA-sequencing and computational integration with larger patient cohorts.

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 with animal models. Several experimental readouts have been established for use with PCLS, but obtaining high-yield and -quality RNA for downstream analysis has remained challenging. This is particularly problematic for utilizing the power of next-generation sequencing techniques, such as RNA-sequencing (RNA-seq), for nonbiased and high-throughput analysis of PCLS human cohorts. In the current study, we present a novel approach for isolating high-quality RNA from a small amount of tissue, including diseased human tissue, such as idiopathic pulmonary fibrosis. We show that the RNA isolated using this method has sufficient quality for RT-qPCR and RNA-seq analysis. Furthermore, the RNA-seq data from human PCLS could be used in several established computational pipelines, including deconvolution of bulk RNA-seq data using publicly available single-cell RNA-seq data. Deconvolution using Bisque revealed a diversity of cell populations in human PCLS, including several immune cell populations, which correlated with cell populations known to be present and aberrant in human disease.

Reperfusion of Free Full-Thickness Skin Grafts in Periocular Reconstructive Surgery Monitored Using Laser Speckle Contrast Imaging.

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.

Successful Free Bilamellar Eyelid Grafts for the Repair of Upper and Lower Eyelid Defects in Patients and Laser Speckle Contrast Imaging of Revascularization.

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 using a free bilamellar eyelid autograft alone. METHODS: Ten large upper and lower eyelid defects resulting from tumor excision were reconstructed using bilamellar grafts harvested from the contralateral or opposing eyelid. Revascularization of the flap was monitored during healing using laser speckle contrast imaging, and the surgical outcome was assessed. RESULTS: The functional and cosmetic results were excellent. All grafts survived and there was no tissue necrosis. Only 1 patient underwent revision after 4 days as the sutures came loose. Two patients developed minimal ectropion but needed no reoperation. All patients were satisfied with the surgical results. Perfusion monitoring showed that the grafts were gradually revascularized, exhibiting 50% perfusion after 4 weeks and 90% perfusion after 8 weeks. CONCLUSIONS: A free bilamellar eyelid graft appears to be an excellent alternative to the tarsoconjunctival flap procedure in the reconstruction of both upper and lower eyelid defects, especially in patients who cannot tolerate visual axis occlusion or the 2-stage procedure of the conventional staged flap procedure.

Revascularization After H-plasty Reconstructive Surgery in the Periorbital Region Monitored With Laser Speckle Contrast Imaging.

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.

Successful improved peripheral tissue perfusion was seen in patients with atherosclerosis after 12 months of treatment with aged garlic extract.

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 patients with a CT-scan confirmed coronary artery arteriolosclerosis were randomised in a double-blind manner to placebo or 2400 mg AGE daily for 1 year. Peripheral tissue perfusion was evaluated at 0- and 12-months using Laser Speckle Contrast Imaging. Measurement of post occlusive reactive hyperemia (PORH) and cutaneous vascular conductance (CVC) using acetylcholine iontophoresis (Ach) was conducted. After 12 months a significant increase of 21.6% (95% CI 3.2%-40.0%, P < .05) was seen in the relative change of PORH in the AGE compared with the placebo group. The same response was seen for CVC and Ach with an increase of 21.4% (95% CI 3.4%-39.4%, P < .05) in the AGE group compared with the placebo group. Aged garlic extract regenerated peripheral tissue perfusion and increase microcirculation in patients with arteriolosclerosis. Adequate peripheral tissue perfusion and tissue oxygen tension are important prerequisites for successful tissue repair. Restored microcirculation in patients could hypothetically facilitate wound healing.

Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury.

Acute respiratory distress syndrome (ARDS) is a common cause of death in the intensive care unit, with mortality rates of ~30-40%. To reduce invasive diagnostics such as bronchoalveolar lavage and time-consuming in-hospital transports for imaging diagnostics, we hypothesized that particle flow rate (PFR) pattern from the airways could be an early detection method and contribute to improving diagnostics and optimizing personalized therapies. Porcine models were ventilated mechanically. Lipopolysaccharide (LPS) was administered endotracheally and in the pulmonary artery to induce ARDS. PFR was measured using a customized particles in exhaled air (PExA 2.0) device. In contrast to control animals undergoing mechanical ventilation and receiving saline administration, animals who received LPS developed ARDS according to clinical guidelines and histologic assessment. Plasma levels of TNF-α and IL-6 increased significantly compared with baseline after 120 and 180 min, respectively. On the other hand, the PFR significantly increased and peaked 60 min after LPS administration, i.e., ~30 min before any ARDS stage was observed with other well-established outcome measurements such as hypoxemia, increased inspiratory pressure, and lower tidal volumes or plasma cytokine levels. The present results imply that PFR could be used to detect early biomarkers or as a clinical indicator for the onset of ARDS.