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Nature Communications May 2024Cell plasticity theoretically extends to all possible cell types, but naturally decreases as cells differentiate, whereas injury-repair re-engages the developmental...
Cell plasticity theoretically extends to all possible cell types, but naturally decreases as cells differentiate, whereas injury-repair re-engages the developmental plasticity. Here we show that the lung alveolar type 2 (AT2)-specific transcription factor (TF), CEBPA, restricts AT2 cell plasticity in the mouse lung. AT2 cells undergo transcriptional and epigenetic maturation postnatally. Without CEBPA, both neonatal and mature AT2 cells reduce the AT2 program, but only the former reactivate the SOX9 progenitor program. Sendai virus infection bestows mature AT2 cells with neonatal plasticity where Cebpa mutant, but not wild type, AT2 cells express SOX9, as well as more readily proliferate and form KRT8/CLDN4+ transitional cells. CEBPA promotes the AT2 program by recruiting the lung lineage TF NKX2-1. The temporal change in CEBPA-dependent plasticity reflects AT2 cell developmental history. The ontogeny of AT2 cell plasticity and its transcriptional and epigenetic mechanisms have implications in lung regeneration and cancer.
Topics: Animals; Cell Plasticity; Mice; Alveolar Epithelial Cells; Thyroid Nuclear Factor 1; SOX9 Transcription Factor; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Epigenesis, Genetic; Mice, Inbred C57BL; Lung Injury; Regeneration; Sendai virus; Cell Proliferation; Mice, Knockout; Lung
PubMed: 38755149
DOI: 10.1038/s41467-024-48632-3 -
BMJ Open May 2024Lung isolation is primarily accomplished using a double-lumen tube (DLT) or bronchial blocker. A precise and accurate size of the DLT is a prerequisite for ensuring its... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of a 3D-printed reconstruction automated matching system for selecting the size of a left double-lumen tube: a study protocol for a prospective randomised controlled trial.
INTRODUCTION
Lung isolation is primarily accomplished using a double-lumen tube (DLT) or bronchial blocker. A precise and accurate size of the DLT is a prerequisite for ensuring its accurate placement. Three-dimensional (3D) reconstruction technology can be used to accurately reproduce tracheobronchial structures to improve the accuracy of DLT size selection. Therefore, we have developed automatic comparison software for 3D reconstruction based on CT data (3DRACS). In this study, we aimed to evaluate the efficiency of using 3DRACS to select the DLT size for endobronchial intubation in comparison with using the 'blind' DLT intubation method to determine the DLT size, which is based on height and sex.
METHODS AND ANALYSIS
This is a prospective, single-centre, double-blind randomised controlled trial. In total, 200 patients scheduled for lung resection using a left DLT will be randomly allocated to the 3D group or the control group at a 1:1 ratio. A 3DRACS will be used for the 3D group to determine the size of the DLT, while in the case of the control group, the size of the DLT will be determined according to patient height and sex. The primary outcome is the success rate of placement of the left DLT without fibreoptic bronchoscopy (FOB). The secondary outcomes include the following: successful intubation time, degree of pulmonary atrophy, grade of airway injury, oxygenation during one-lung ventilation, postoperative sore throat and hoarseness, and number of times FOB is used.
ETHICS AND DISSEMINATION
Ethical approval has been obtained from our local ethics committee (approval number: SCCHEC-02-2022-155). Written informed consent will be obtained from all participants before randomisation, providing them with clear instructions about the purpose of the study. The results will be disseminated through peer-reviewed publications and conferences.
TRIAL REGISTRATION NUMBER
NCT06258954.
Topics: Humans; Prospective Studies; Intubation, Intratracheal; Double-Blind Method; Printing, Three-Dimensional; Female; Male; Randomized Controlled Trials as Topic; Bronchoscopy; Tomography, X-Ray Computed; Adult; One-Lung Ventilation; Equipment Design
PubMed: 38754878
DOI: 10.1136/bmjopen-2024-085503 -
Aorta (Stamford, Conn.) May 2024Conventional elephant trunk (cET) and frozen elephant trunk (FET) are two distinct approaches to the surgical treatment of thoracic aortic aneurysms and dissections....
Conventional elephant trunk (cET) and frozen elephant trunk (FET) are two distinct approaches to the surgical treatment of thoracic aortic aneurysms and dissections. With the advent and growing uptake of endovascular technologies, FET is becoming increasingly popular for its potential to be performed as a single-stage operation with better aortic remodeling and less risk of graft kinking than the traditional two-stage cET procedure. However, FET has been associated with a higher risk of spinal cord ischemia and its use in patients with connective tissue disorder remains controversial. The current review aimed to reflect on recent evidence surrounding the application of cET and FET to different types of aortic pathology in both acute and elective settings. Another scope of this review was to compare the characteristics of the currently available FET commercial devices on the global market. Our findings highlight that when the pathology is confined to the proximal descending aorta, such as in Dsine, intervention is often single-staged and false lumen (FL) thrombosis is achieved with good effect. FET remains limited by spinal cord injury and applicability in patients with connective tissue disorder, although some groups have started to circumvent associated complications, likely due to growing surgical expertise. Many other aortic diseases do require second-stage intervention, and even in these cases, there appears to be lower in-hospital mortality when using FET over cET. This is possibly due to the higher rate of endovascular completion facilitated by the completed landing zones created during FET. FET is trending toward becoming the universal treatment modality for extending repair to the descending aorta.
PubMed: 38754437
DOI: 10.1055/s-0044-1786352 -
BMC Research Notes May 2024Pulmonary air leaks (PALs) due to visceral pleura injury during surgery is frequently observed after pulmonary resections and the complication is difficult to avoid in...
BACKGROUND
Pulmonary air leaks (PALs) due to visceral pleura injury during surgery is frequently observed after pulmonary resections and the complication is difficult to avoid in thoracic surgery. The development of postoperative PALs is the most common cause of prolonged hospitalization. Previously, we reported that PALs sealants using autologous dermal fibroblast sheets (DFSs) harvested from temperature-responsive culture dishes successfully closed intraoperative PALs during lung resection.
OBJECTIVE
In this study, we investigated the fate of human DFSs xenogenetically transplanted onto lung surfaces to seal PALs of immunocompromised rat. Dual-color FISH analyses of human fibroblast was employed to detect transplantation human cells on the lung surface.
RESULTS
One month after transplantation, FISH analyses revealed that transplanted human fibroblasts still composed a sheet-structure, and histology also showed that beneath the sheet's angiogenesis migrating into the sheets was observed from the recipient tissues. FISH analyses revealed that even at 3 months after transplantation, the transplanted human fibroblasts still remained in the sheet. Dual-color FISH analyses of the transplanted human fibroblasts were sparsely present as a result of the cells reaching the end of their lifespan, the cells producing extracellular matrix, and remained inside the cell sheet and did not invade the lungs of the host.
CONCLUSIONS
DFS-transplanted human fibroblasts showed that they are retained within cell sheets and do not invade the lungs of the host.
Topics: Animals; Fibroblasts; Humans; Rats; Lung; Immunocompromised Host; Pleura; In Situ Hybridization, Fluorescence; Transplantation, Heterologous; Male; Disease Models, Animal
PubMed: 38750547
DOI: 10.1186/s13104-024-06792-x -
Nature Communications May 2024Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation...
Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.
Topics: Animals; Jagged-1 Protein; Homeostasis; Esophageal Neoplasms; Esophagus; Stem Cells; Mice; Jagged-2 Protein; Humans; Carcinogenesis; Esophageal Squamous Cell Carcinoma; Mice, Knockout; Signal Transduction; Carcinoma, Squamous Cell; Receptors, Notch; Cell Differentiation; Male; Female
PubMed: 38750026
DOI: 10.1038/s41467-024-48347-5 -
PloS One 2024Since the 19th century, underwater explosions have posed a significant threat to service members. While there have been attempts to establish injury criteria for the...
Since the 19th century, underwater explosions have posed a significant threat to service members. While there have been attempts to establish injury criteria for the most vulnerable organs, namely the lungs, existing criteria are highly variable due to insufficient human data and the corresponding inability to understand the underlying injury mechanisms. This study presents an experimental characterization of isolated human lung dynamics during simulated exposure to underwater shock waves. We found that the large acoustic impedance at the surface of the lung severely attenuated transmission of the shock wave into the lungs. However, the shock wave initiated large bulk pressure-volume cycles that are distinct from the response of the solid organs under similar loading. These pressure-volume cycles are due to compression of the contained gas, which we modeled with the Rayleigh-Plesset equation. The extent of these lung dynamics was dependent on physical confinement, which in real underwater blast conditions is influenced by factors such as rib cage properties and donned equipment. Findings demonstrate a potential causal mechanism for implosion injuries, which has significant implications for the understanding of primary blast lung injury due to underwater blast exposures.
Topics: Humans; Lung; Blast Injuries; Explosions; Lung Injury; Male; Pressure; High-Energy Shock Waves
PubMed: 38748668
DOI: 10.1371/journal.pone.0303325 -
Frontiers in Immunology 2024Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs...
BACKGROUND
Researchers are focusing on cellular therapy for chronic obstructive pulmonary disease (COPD) using mesenchymal stem cells (MSCs), with human bone marrow-derived MSCs (hBM-MSCs) leading the way. However, BM-MSCs may not be as optimal as therapeutic cells owing to their low growth potential, invasive harvesting, and high expression of aging-related genes with poor differentiation potential. Consequently, umbilical cord-derived MSCs (hUC-MSCs), which have many excellent features as allogeneic heterologous stem cells, have received considerable attention. Allogeneic and heterologous hUC-MSCs appear to be promising owing to their excellent therapeutic properties. However, MSCs cannot remain in the lungs for long periods after intravenous infusion.
OBJECTIVE
To develop designer hUC-MSCs (dUC-MSCs), which are novel therapeutic cells with modified cell-adhesion properties, to aid COPD treatment.
METHODS
dUC-MSCs were cultured on type-I collagen gels and laminin 411, which are extracellular matrices. Mouse models of elastase-induced COPD were treated with hUC-MSCs. Biochemical analysis of the lungs of treated and control animals was performed.
RESULTS
Increased efficiency of vascular induction was found with dUC-MSCs transplanted into COPD mouse models compared with that observed with transplanted hUC-MSCs cultured on plates. The transplanted dUC-MSCs inhibited apoptosis by downregulating pro-inflammatory cytokine production, enhancing adhesion of the extracellular matrix to alveolar tissue via integrin β1, promoting the polarity of M2 macrophages, and contributing to the repair of collapsed alveolar walls by forming smooth muscle fibers. dUC-MSCs inhibited osteoclastogenesis in COPD-induced osteoporosis. hUC-MSCs are a promising cell source and have many advantages over BM-MSCs and adipose tissue-derived MSCs.
CONCLUSION
We developed novel designer cells that may be involved in anti-inflammatory, homeostatic, injury repair, and disease resistance processes. dUC-MSCs repair and regenerate the alveolar wall by enhancing adhesion to the damaged site. Therefore, they can contribute to the treatment of COPD and systemic diseases such as osteoporosis.
Topics: Animals; Mice; Disease Models, Animal; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Humans; Regeneration; Pulmonary Disease, Chronic Obstructive; Pulmonary Alveoli; Umbilical Cord; Cells, Cultured; Cell Differentiation; Cord Blood Stem Cell Transplantation; Mice, Inbred C57BL; Male
PubMed: 38745668
DOI: 10.3389/fimmu.2024.1384718 -
BMC Medical Imaging May 2024Spinal deformations, except for acute injuries, are among the most frequent reasons for visiting an orthopaedic specialist and musculoskeletal treatment in adults and...
BACKGROUND
Spinal deformations, except for acute injuries, are among the most frequent reasons for visiting an orthopaedic specialist and musculoskeletal treatment in adults and adolescents. Data on the morphology and anatomical structures of the spine are therefore of interest to orthopaedics, physicians, and medical scientists alike, in the broad field from diagnosis to therapy and in research.
METHODS
Along the course of developing supplementary methods that do not require the use of ionizing radiation in the assessment of scoliosis, twenty CT scans from females and males with various severity of spinal deformations and body shape have been analysed with respect to the transverse distances between the vertebral body and the spinous process end tip and the skin, respectively, at thoracic and lumbar vertebral levels. Further, the locations of the vertebral bodies have been analysed in relation to the patient's individual body shape and shown together with those from other patients by normalization to the area encompassed by the transverse body contour.
RESULTS
While the transverse distance from the vertebral body to the skin varies between patients, the distances from the vertebral body to the spinous processes end tips tend to be rather similar across different patients of the same gender. Tables list the arithmetic mean distances for all thoracic and lumbar vertebral levels and for different regions upon grouping into mild, medium, and strong spinal deformation and according to the range of spinal deformation.
CONCLUSIONS
The distances, the clustering of the locations of the vertebral bodies as a function of the vertebral level, and the trends therein could in the future be used in context with biomechanical modeling of a patient's individual spinal deformation in scoliosis assessment using 3D body scanner images during follow-up examinations.
Topics: Humans; Male; Female; Thoracic Vertebrae; Tomography, X-Ray Computed; Lumbar Vertebrae; Adult; Adolescent; Scoliosis; Middle Aged; Aged; Young Adult
PubMed: 38745329
DOI: 10.1186/s12880-024-01293-6 -
Critical Care (London, England) May 2024Hypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in...
BACKGROUND
Hypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAF) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype.
METHODS
We studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAF in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support.
RESULTS
The PAF was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004).
CONCLUSIONS
The PAF is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.
Topics: Humans; Sepsis; Respiratory Distress Syndrome; Male; Female; Middle Aged; Aged; Phenotype; Prospective Studies; Cause of Death; Cohort Studies; Inflammation
PubMed: 38745253
DOI: 10.1186/s13054-024-04943-x -
Scandinavian Journal of Trauma,... May 2024For trauma patients with subsequent immediate surgery, it is unclear which surgical disciplines are most commonly required for treatment, and whether and to what extend...
BACKGROUND
For trauma patients with subsequent immediate surgery, it is unclear which surgical disciplines are most commonly required for treatment, and whether and to what extend this might depend on or change with "hypotension on arrival". It is also not known how frequently damage control protocols are used in daily practice and whether this might also be related to "hypotension on arrival".
METHODS
A retrospective analysis of trauma patients from a German level 1 trauma centre and subsequent "immediate surgery" between 01/2017 and 09/2022 was performed. Patients with systolic blood pressure > 90 mmHg (group 1, no-shock) and < 90 mmHg (group 2, shock) on arrival were compared with regard to (a) most frequently required surgical disciplines, (b) usage of damage control protocols, and (c) outcome. A descriptive analysis was performed, and Fisher's exact test and the Mann‒Whitney U test were used to calculate differences between groups where appropriate.
RESULTS
In total, 98 trauma patients with "immediate surgery" were included in our study. Of these, 61 (62%; group 1) were normotensive, and 37 (38%, group 2) were hypotensive on arrival. Hypotension on arrival was associated with a significant increase in the need for abdominal surgery procedures (group 1: 37.1 vs. group 2: 54.5%; p = 0.009), more frequent usage of damage control protocols (group 1: 59.0 vs. group 2: 75.6%; p = 0.019) and higher mortality (group 1: 5.5 vs. group 2: 24.3%; p 0.027).
CONCLUSION
Our data from a German level 1 trauma centre proof that abdominal surgeons are most frequently required for the treatment of trauma patients with hypotension on arrival among all surgical disciplines (> thoracic surgery > vascular surgery > neurosurgery). Therefore, surgeons from these specialties must be available without delay to provide optimal trauma care.
Topics: Humans; Hypotension; Retrospective Studies; Male; Female; Trauma Centers; Adult; Middle Aged; Germany; Injury Severity Score; Wounds and Injuries
PubMed: 38745198
DOI: 10.1186/s13049-024-01187-0