Intestinal ischemia-reperfusion injury leads to proinflammatory responses via gut-derived mediators, and accumulating evidence suggests that exosomes secreted by intestinal epithelial cells are ...involved in the development of systemic inflammation. Studies have reported changes in protein, lipid, and microRNA (miRNA) expression; however, considering the different experimental conditions, information on the relationships among these biomolecules remains insufficient. The aim of this study was to elucidate the multiple changes that simultaneously occur in exosomes after ischemic stimulation. Here, differentiated human intestinal Caco-2 cells were exposed to 95% air (normoxia group) or 5% O2 (hypoxia group) for 6 h. Cells in each group were subsequently incubated for 24 h in an atmosphere of 5% CO2 plus 95% air. The conditioned medium of each group was collected for isolating intestinal epithelial cell-derived exosomes. Together with proteome analyses, lipid analyses, and miRNA quantification, biological functional assays were performed using monocytic NF-κB reporter cells. Lipid metabolism-related protein expression was upregulated, miRNA levels were slightly altered, and unsaturated fatty acid-containing lysophosphatidylcholine concentration increased after hypoxia and reoxygenation injury; this suggested that the changes in exosomal components associated with ischemia-reperfusion injury activates inflammation, including the NF-κB pathway. This study elucidated the multiple changes that co-occur in exosomes after ischemic stimulation and partially clarified the mechanism underlying exosome-mediated inflammation after intestinal ischemic recanalization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intestinal ischemia-reperfusion injury leads to proinflammatory responses via gut-derived mediators, and accumulating evidence suggests that exosomes secreted by intestinal epithelial cells are ...involved in the development of systemic inflammation. Studies have reported changes in protein, lipid, and microRNA (miRNA) expression; however, considering the different experimental conditions, information on the relationships among these biomolecules remains insufficient. The aim of this study was to elucidate the multiple changes that simultaneously occur in exosomes after ischemic stimulation. Here, differentiated human intestinal Caco-2 cells were exposed to 95% air (normoxia group) or 5% O2 (hypoxia group) for 6 h. Cells in each group were subsequently incubated for 24 h in an atmosphere of 5% CO2 plus 95% air. The conditioned medium of each group was collected for isolating intestinal epithelial cell-derived exosomes. Together with proteome analyses, lipid analyses, and miRNA quantification, biological functional assays were performed using monocytic NF-κB reporter cells. Lipid metabolism-related protein expression was upregulated, miRNA levels were slightly altered, and unsaturated fatty acid-containing lysophosphatidylcholine concentration increased after hypoxia and reoxygenation injury; this suggested that the changes in exosomal components associated with ischemia-reperfusion injury activates inflammation, including the NF-κB pathway. This study elucidated the multiple changes that co-occur in exosomes after ischemic stimulation and partially clarified the mechanism underlying exosome-mediated inflammation after intestinal ischemic recanalization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The prediction of COVID-19 disease behavior in the early phase of infection is challenging but urgently needed. MuLBSTA score is a scoring system that predicts the mortality of viral pneumonia ...induced by a variety of viruses, including coronavirus, but the scoring system has not been verified in novel coronavirus pneumonia. The aim of this study was to validate this scoring system for estimating the risk of disease worsening in patients with COVID-19.
This study included the patients who were treated between April 1 st and March 13 th , 2020. The patients were classified into mild, moderate, and severe groups according to the extent of respiratory failure. MuLBSTA score was applied to estimate the risk of disease worsening in each severity group and we validated the utility of the scoring system.
A total of 72 patients were analyzed. Among the 46 patients with mild disease, 17 showed disease progression to moderate or severe disease after admission. The model showed a sensitivity of 100% and a specificity of only 34.5% with a cut-off value of 5 points. Among the 55 patients with mild or moderate disease, 6 deteriorated to severe disease, and the model showed a sensitivity of 83.3% and a specificity of 71.4% with a cut-off value of 11 points.
This study showed that MuLBSTA score is a potentially useful tool for predicting COVID-19 disease behavior. This scoring system may be used as one of the criteria to identify high-risk patients worsening to life-threatening status.
Pneumothorax (PTX) and pneumomediastinum (PM) have been reported as potential complications in patients with coronavirus disease 2019 (COVID-19); however, their risk factors and etiology remain ...unknown. Herein, we investigated the clinical characteristics of mechanically ventilated patients with COVID-19 with PTX or PM.
We examined patients with severe COVID-19 requiring mechanical ventilation who were admitted to the intensive care unit of a tertiary-level emergency medical center in Tokyo, Japan between April 1, 2020. and October 31, 2021. We collected and analyzed the clinical characteristics of the patients who presented with either PTX or PM during mechanical ventilation.
During the study period, a total of 165 patients required mechanical ventilation, and 15 patients with PTX/PM during mechanical ventilation were selected. Three patients with obvious causes were excluded, and the remaining 12 patients were analyzed (7.3%). The mortality rate in these patients was as high as 50%, demonstrating the difficulty of treatment in the presence of PTX/PM. PTX/PM occurred 14.5 days after intubation. A peak pressure of > 30 cmH
O was only apparent in one patient, suggesting that high positive pressure ventilation may be less involved than mentioned in the literature. In addition, the inspiratory effort was not strong in our group of patients. (P0.1 was 2.1 cm H2O 1.0-3.8).
Various factors are associated with the development of PTX/PM in patients on mechanical ventilation for COVID-19. We did not find a strong correlation between PTM/PM and barotrauma or strong inspiratory efforts, which have been identified as potential causes in previous studies.
Intestinal ischemia caused by hemorrhagic shock is known to induce systemic inflammatory responses. Previous studies have shown that mesenteric lymph (ML) plays a crucial role in gut-mediated ...inflammation. Lipid mediators, such as lysophosphatidylcholines (LPCs), which contain polyunsaturated fatty acids (PUFAs), are present in the postshock ML. Exosomes are also present in the ML and act as transcellular carriers of lipids; however, their role in postshock systemic inflammation has not been revealed. Here, we aimed to identify changes in lipid mediators in ML exosomes after intestinal ischemia.
Male Sprague-Dawley rats underwent laparotomy, followed by ML duct cannulation. Animals were subjected to 60 minutes of intestinal ischemia by superior mesenteric artery clamping, followed by 120 minutes of reperfusion. Mesenteric lymph was obtained before and after intestinal ischemia, and exosomes were isolated from ML by ultracentrifugation. The biological activity of ML exosomes was determined using the monocyte nuclear factor κB (NF-κB) activation assay. Lipids of ML exosomes were extracted and quantified by liquid chromatography/electrospray ionization mass spectrometry.
Mesenteric lymph exosome-induced NF-κB activation significantly increased after intestinal ischemia, and lipid analysis revealed a significant increase in the concentration of PUFA-containing LPCs. In addition, PUFA-containing LPCs also induced NF-κB activation.
Our results suggest that biologically active lipid mediators in ML exosomes may be involved in the inflammatory response after intestinal ischemia.
BACKGROUND
Inflammatory lipid mediators in mesenteric lymph (ML), including arachidonic acid (AA), are considered to play an important role in the pathogenesis of multiple-organ dysfunction after ...hemorrhagic shock. A previous study suggested that vagus nerve stimulation (VNS) could relieve shock-induced gut injury and abrogate ML toxicity, resulting in the prevention of multiple-organ dysfunction. However, the detailed mechanism of VNS in lymph toxicity remains unclear. The study aimed to investigate the relationship between VNS and inflammatory lipid mediators in ML.
METHODS
Male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery obstruction (SMAO) for 60 minutes to induce intestinal ischemia followed by reperfusion and observation. The ML duct was cannulated, and ML samples were obtained both before and after SMAO. The distal ileum was removed at the end of the observation period. In one group of animals, VNS was performed from 10 minutes before 10 minutes after SMAO (5 V, 0.5 Hz). Liquid chromatography–electrospray ionization–tandem mass spectrometry analysis of AA was performed for each ML sample. The biological activity of ML was examined using a monocyte nuclear factor κ-light-chain-enhancer of activated B cells activation assay. Western blotting of phospholipase A
2
group IIA (PLA
2
-IIA) was also performed for ML and ileum samples.
RESULTS
Vagus nerve stimulation relieved the SMAO-induced histological gut injury. The concentration of AA and level of nuclear factor κ-light-chain-enhancer of activated B cells activation in ML increased significantly after SMAO, whereas VNS prevented these responses. Western blotting showed PLA
2
-IIA expression in the ML and ileum after SMAO; however, the appearance of PLA2-IIA band was remarkably decreased in the samples from VNS-treated animals.
CONCLUSION
The results suggested that VNS could relieve gut injury induced by SMAO and decrease the production of AA in ML by altering PLA
2
-IIA expression in the gut and ML.
Gut damage after trauma/hemorrhagic shock contributes to multiple organ dysfunction syndrome. Electrical vagal nerve stimulation is known to prevent gut damage in animal models of trauma/hemorrhagic ...shock by altering the gut inflammatory response; however, the effect of vagal nerve stimulation on intestinal blood flow, which is an essential function of the vagus nerve, is unknown. This study aimed to determine whether vagal nerve stimulation influences the abdominal vagus nerve activity, intestinal blood flow, gut injury, and the levels of autonomic neuropeptides.
Male Sprague Dawley rats were anesthetized, and the cervical and abdominal vagus nerves were exposed. One pair of bipolar electrodes was attached to the cervical vagus nerve to stimulate it; another pair of bipolar electrodes were attached to the abdominal vagus nerve to measure action potentials. The rats underwent trauma/hemorrhagic shock (with maintenance of mean arterial pressure of 25 mmHg for 30 min) without fluid resuscitation and received cervical vagal nerve stimulation post-injury. A separate cohort of animals were subjected to transection of the abdominal vagus nerve (vagotomy) just before the start of cervical vagal nerve stimulation. Intestinal blood flow was measured by laser Doppler flowmetry. Gut injury and noradrenaline level in the portal venous plasma were also assessed.
Vagal nerve stimulation evoked action potentials in the abdominal vagus nerve and caused a 2-fold increase in intestinal blood flow compared to the shock phase (P < .05). Abdominal vagotomy eliminated the effect of vagal nerve stimulation on intestinal blood flow (P < .05). Vagal nerve stimulation protected against trauma/hemorrhagic shock -induced gut injury (P < .05), and circulating noradrenaline levels were decreased after vagal nerve stimulation (P < .05).
Cervical vagal nerve stimulation evoked abdominal vagal nerve activity and relieved the trauma/hemorrhagic shock–induced impairment in intestinal blood flow by modulating the vasoconstriction effect of noradrenaline, which provides new insight into the protective effect of vagal nerve stimulation.
Background
Coagulopathy induced by COVID-19 has received much attention. Arterial and venous thrombosis of multiple organs due to COVID-19-related coagulopathy is associated with a poor outcome.
Case ...presentation
A 67-year-female was transferred to our hospital in need of intensive care for severe COVID-19 pneumonia. On day 7 after admission, despite the treatments, her respiratory and hemodynamic status deteriorated. Computed tomography revealed massive ascites and free air as well as wall defects of the transverse colon. An emergency laparotomy was undertaken in the intensive-care unit, and 17 cm of the transverse colon was resected. Histopathological findings revealed two perforation sites of 25 and 7 mm in diameter, necrosis of the intestinal mucosa around the perforation sites, and the microcirculatory thrombosis in the mesentery vessels which was suspected of having been induced by COVID-19-related coagulopathy.
Conclusions
The case highlights the risk of intestinal ischemia and perforation induced by COVID-19 coagulopathy. Physicians treating COVID-19 should recognize the risk and evaluate patients carefully.
Factors associated with mortality are important in the treatment of coronavirus disease 2019 (COVID-19). Polymerase chain reaction (PCR) is the gold standard for diagnosing COVID-19, which reflects ...the viral load in the upper respiratory tract. In total, 523 patients were enrolled in this study; of them, 441 and 75 patients underwent PCR testing of nasopharyngeal swabs and sputum samples, respectively, within 20 days from onset of COVID-19. We investigated the association between RNA copy number and the COVID-19 severity and mortality rate and its effect on the predictive performance for severity and mortality. RNA copy numbers in nasopharyngeal swabs were higher in the non-survivor group than in the survivor group. Multivariate logistic regression analysis identified that the high RNA copy number (≥9 log10 /swab) in nasopharyngeal swabs was a factor associated with mortality (odds ratio, 4.50; 95% confidence interval, 1.510–13.100; P = 0.008). Furthermore, adding RNA copy number (≥9 log10 /swab) in severe cases, adjusted by duration from onset to PCR, improved mortality predictive performance based on known factors. The RNA copy number is a factor associated with the mortality of patients with COVID-19 and can improve the predictive performance of mortality in severe cases.
Background
Secondary aortoenteric fistula is a fatal cause of gastrointestinal bleeding after aortic reconstructive surgery with a prosthesis. In most cases, the proximal suture line is involved. We ...herein report a rare case in which the fistula formed between the suture line of inferior mesenteric artery reimplantation and the jejunum.
Case Presentation
An 82‐year‐old man was transferred to our hospital due to hematemesis with severe hypovolemic shock. Although he fell into cardiopulmonary arrest, immediate resuscitation achieved return of spontaneous circulation. As his surgical history of aortic reconstruction and computed tomography findings suggested potential secondary aortoenteric fistula, emergency surgery was carried out. The anastomosis between the inferior mesenteric artery and aortic graft was communicating with the jejunum. Partial jejunal resection was undertaken, and the aortic graft was replaced.
Conclusion
The anastomosis between the inferior mesenteric artery and aortic graft in the previous aortic replacement can become the site of secondary aortoenteric fistula.
A rare case of secondary aorto‐enteric fistula (SAFE), in which the fistula existed between a suture line of IMA reimplantation and jejunum. For treatments of SAFE, accurate and immediate diagnosis and surgery are required.
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