Clinical characteristics of pneumothorax and pneumomediastinum in mechanical ventilated patients with coronavirus disease 2019: a case series.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 cmH2O 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]). CONCLUSION: 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.

Profiles of lipid, protein and microRNA expression in exosomes derived from intestinal epithelial cells after ischemia-reperfusion injury in a cellular hypoxia model.

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.

Association of SARS-CoV-2 RNA Copy Number with the COVID-19 Mortality Rate and Its Effect on the Predictive Performance of Mortality in Severe Cases.

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.

Life-saving case of cardiopulmonary arrest by secondary aortoenteric fistula formed in the anastomotic site between the inferior mesenteric artery and aortic graft.

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.

Arterial and Venous Thrombosis Complicated in COVID-19: A Retrospective Single Center Analysis in Japan.

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients. Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests. Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08-42.3, and 1.06-9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics. Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.

Colon perforation as a complication of COVID-19: a case report.

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.

Vagus nerve stimulation modulates arachidonic acid production in the mesenteric lymph following intestinal ischemia-reperfusion injury.

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 A2 group IIA (PLA2-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 PLA2-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 PLA2-IIA expression in the gut and ML.

An Experience of Multiple Hematomas in a Coronavirus Disease-19 Patient Administered with ART-123 and Heparin.

BACKGROUND: Anticoagulant therapy for patients with severe coronavirus disease (COVID-19) pneumonia is considered to improve the hypercoagulable and inflammatory state. However, bleeding complications should also be considered. CASE PRESENTATION: A 77-year-old man with a history of falls was diagnosed with COVID-19. Owing to his severe condition, he was intubated and transferred to our hospital for intensive care. Favipiravir, tocilizumab, unfractionated heparin, and ART-123 were administered to treat COVID-19 and manage the antithrombotic prophylaxis for paroxysmal atrial fibrillation (Af). On the 6th day after admission, a hematoma was noted on the left chest wall. Computed tomography (CT) revealed multiple hematomas, including hematomas on his chest wall and obturatorius internus muscle. Emergency angiography transcatheter embolization (TAE) was performed. The patient was transferred to another hospital 23 days after TAE, without complications. CONCLUSION: Our findings show that anticoagulation therapy and a history of falls induced multiple hematomas in a COVID-19 patient and that the condition was managed with TAE. When anticoagulants are considered in the management of Af and COVID-19 associated coagulopathy, it is necessary to closely monitor potential bleeding complications.

Predictors associated with clinical improvement of SARS-CoV-2 pneumonia.

BACKGROUND: There are few agents that have been proven effective for COVID-19. Predicting clinical improvement as well as mortality or severity is very important. OBJECTIVES: This study aimed to investigate the factors associated with the clinical improvement of COVID-19. METHODS: Overall, 74 patients receiving treatment for COVID-19 at Tokyo Medical and Dental University Hospital from April 6th to May 15th, 2020 were included in this study. Clinical improvement was evaluated, which defined as the decline of two levels on a six-point ordinal scale of clinical status or discharge alive from the hospital within 28 days after admission. The clinical courses were particularly investigated and the factors related to time to clinical improvement were analyzed with the log-rank test and the Cox proportional hazard model. RESULTS: Forty-nine patients required oxygen support during hospitalization, 22 patients required invasive mechanical ventilation, and 5 patients required extracorporeal membrane oxygenation. A total of 83% of cases reached clinical improvement. Longer period of time from onset to admission (≥10 days) (HR, 1.057; 95% CI, 1.002-1.114), no hypertension (HR, 2.077; 95% CI, 1.006-4.287), and low D-dimer levels (<1 µg/ml) (HR, 2.372; 95% CI, 1.229-4.576) were confirmed to be significant predictive factors for time to clinical improvement. Furthermore, a lower SARS-CoV-2 RNA copy number was also a predictive factor for clinical improvement. CONCLUSIONS: Several predictors for the clinical improvement of COVID-19 pneumonia were identified. These results may be important for the management of COVID-19 pneumonia.

MuLBSTA score is a useful tool for predicting COVID-19 disease behavior.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A successful case of extracorporeal membrane oxygenation treatment for intractable pneumothorax in a patient with COVID-19.

BACKGROUND: Some patients with coronavirus disease 2019 (COVID-19) develop pneumothorax. Tube thoracotomy and bulla resection could generate aerosols and cause virus transmission; the optimal treatment strategy remains unclear. CASE PRESENTATION: A 57-year-old male was transferred as a severe COVID-19 pneumonia case. On the 16th day after admission, the patient's respiratory condition deteriorated, and the chest X-ray revealed the presence of severe right-sided pneumothorax. A chest drain was immediately inserted; however, a significant air leak continued, and severe ventilator settings were required. Thus, veno-venous extracorporeal membrane oxygenation (VV-ECMO) treatment was initiated to allow the lungs to rest. After 10 days of lung-protective ventilation, the patient was weaned from ECMO and the chest drain was removed on the following day with no major comorbidities. CONCLUSION: The combination of ECMO with lung rest strategy could be a treatment option for intractable pneumothorax with COVID-19 to avoid unnecessary surgical procedures and aerosol generation.

COVID-19 pneumonia complicated by bilateral pneumothorax: A case report.

BACKGROUND: Pneumothorax is a rare but life-threatening complication associated with pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CASE PRESENTATION: Informed consent was obtained from the patient himself.A 50-year-old man presented with a 9-day history of fever, cough, and dyspnoea. He was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia and was admitted to the Medical Hospital, Tokyo Medical and Dental University. Chest CT showed diffuse patchy ground-glass opacities (GGOs). His state of oxygenation deteriorated, and mechanical ventilation was initiated on day 4 after admission (12th day from onset). He improved gradually and was weaned from ventilation on day 15. Sudden onset of bilateral pneumothorax occurred on day 21 with severe respiratory failure, and chest CT revealed pneumatocele formation on both lower lobes. CONCLUSIONS: Pneumothorax is a notable complication in cases of severe COVID-19 pneumonia, especially in those who require positive-pressure ventilation.

The role of mesenteric lymph exosomal lipid mediators following intestinal ischemia-reperfusion injury on activation of inflammation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our results suggest that biologically active lipid mediators in ML exosomes may be involved in the inflammatory response after intestinal ischemia.

Electrical stimulation of the vagus nerve improves intestinal blood flow after trauma and hemorrhagic shock.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Novel role of group VIB Ca2+-independent phospholipase A2γ in leukocyte-endothelial cell interactions: An intravital microscopic study in rat mesentery.

BACKGROUND: Phospholipase A2 (PLA2) is associated with a variety of inflammatory processes related to polymorphonuclear neutrophil (PMN)-endothelial cell interactions. However, the cellular and molecular mechanisms underlying the interactions and the causative isoform(s) of PLA2 remain elusive. In addition, we recently showed that calcium-independent PLA2γ (iPLA2γ), but not cytosolic PLA2 (cPLA2), is responsible for the cytotoxic functions of human PMN including respiratory bursts, degranulation, and chemotaxis. We therefore hypothesized that iPLA2γ is a prerequisite for the PMN recruitment cascade into the site of inflammation. The aim of this study was to elucidate the roles of the three major phospholipases A2, iPLA2, cPLA2 and secretory PLA2, in leukocyte rolling and adherence and in the surface expression of ß2-integrins in vivo and in vitro in response to well-defined stimuli. METHODS: Male Wistar rats were pretreated with PLA2 inhibitors selective for iPLA2ß, iPLA2γ, cPLA2, or secretory PLA2. Leukocyte rolling/adherence in the mesenteric venules superfused with platelet-activating factor (PAF) were quantified by intravital microscopy. Furthermore, isolated human PMNs or whole blood were incubated with each PLA2 inhibitor and then activated with formyl-methionyl-leucyl-phenylalanine (fMLP) or PAF. PMN adherence was assessed by counting cells bound to purified fibrinogen, and the surface expression of lymphocyte function-associated antigen 1 and macrophage antigen 1 (Mac-1) was measured by flow cytometry. RESULTS: The iPLA2γ-specific inhibitor almost completely inhibited the fMLP/PAF-induced leukocyte adherence in vivo and in vitro and also decreased the fMLP/PAF-stimulated surface expression of Mac-1 by 60% and 95%, respectively. In contrast, the other inhibitors did not affect these cellular functions. CONCLUSION: iPLA2γ seems to be involved in leukocyte/PMN adherence in vivo and in vitro as well as in the up-regulation of Mac-1 in vitro in response to PAF/fMLP. This enzyme is therefore likely to be a major regulator in the PMN recruitment cascade.

Discrete roles of intracellular phospholipases A2 in human neutrophil cytotoxicity.

BACKGROUND: The role of calcium-independent phospholipase A2 (iPLA2), a component of the three major PLA2 families, in acute/chronic inflammatory processes remains elusive. Previous investigations have documented iPLA2-mediated respiratory burst of neutrophils (PMNs); however, the causative isoform of iPLA2 is unidentified. We also demonstrated that the iPLA2γ-specific inhibitor attenuates trauma/hemorrhagic shock-induced lung injury. Therefore, iPLA2γ may be implicated in acute inflammation. In addition, arachidonic acid (AA), which is primarily produced by cytosolic PLA2 (cPLA2), is known to display PMN cytotoxicity, although the relationship between AA and the cytotoxic function is still being debated on. We therefore hypothesized that iPLA2γ regulates PMN cytotoxicity via AA-independent signaling pathways. The study aim was to distinguish the role of intracellular phospholipases A2, iPLA2, and cPLA2, in human PMN cytotoxicity and explore the possibility of the presence of signaling molecule(s) other than AA. METHODS: Isolated human PMNs were incubated with the PLA2 inhibitor selective for iPLA2ß, iPLA2γ, or cPLA2 and then activated with formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate (PMA). Superoxide production was assayed according to the superoxide dismutase-inhibitable cytochrome c reduction method, and the degree of elastase release was measured using a p-nitroanilide-conjugated elastase-specific substrate. In addition, chemotaxis toward platelet activating factor/fMLP was determined with a modified Boyden chamber system. RESULTS: The iPLA2γ-specific inhibitor reduced the fMLP/PMA-stimulated superoxide generation by 90% and 30%, respectively; in addition, the inhibitor completely blocked the fMLP/PMA-activated elastase release. However, the cPLA2-specific inhibitor did not abrogate these effects to any degree at all concentrations. Likewise, the inhibitor for iPLA2γ, but not iPLA2ß or cPLA2, completely inhibited the platelet activating factor/fMLP-induced chemotaxis. CONCLUSION: iPLA2 is involved in extracellular reactive oxygen species production, elastase release, and chemotaxis in response to well-defined stimuli. In addition, the ineffectiveness of the cPLA2 inhibitor suggests that AA may not be relevant to these cytotoxic functions.

A case of purpura fulminans caused by Hemophilus influenzae complicated by reversible cardiomyopathy.

Here, we report a case of a 41-year-old male diagnosed as septic shock with purpura fulminans (PF) infection. The causative organism was ß-lactamase-negative ampicillin-resistant Hemophilus influenzae. He developed fulminant cardiac dysfunction approximately 1 h after admission, and the cause was considered to be septic cardiomyopathy. Blood pressure and oxygenation were maintained at adequate levels with the aid of extracorporeal membrane oxygenation (ECMO). The cardiac dysfunction was reversible, and he was successfully weaned from ECMO on day 12 of hospitalization. However, he needed amputation for all extremities because the infection spread to his limbs and eventually, succumbed to sepsis caused by empyema on day 34 of hospitalization. To the best of our knowledge, this is only the second case of PF caused by H. influenzae in an adult to be reported worldwide.

Group VIB Ca(2+)-independent phospholipase A(2γ) is associated with acute lung injury following trauma and hemorrhagic shock.

BACKGROUND: Gut-derived mediators are carried via mesenteric lymph duct into systemic circulation after trauma/hemorrhagic shock (T/HS), thus leading to acute lung injury (ALI)/multiple-organ dysfunction syndrome. Phospholipase A2 (PLA(2)) is a key enzyme for the production of lipid mediators in posthemorrhagic shock mesenteric lymph (PHSML). However, the precise functions of PLA(2) subtype, such as cytosolic PLA(2), secretory PLA(2), and Ca-independent PLA(2), in the acute phase of inflammation have remained unclear. Our previous study has suggested that the activation of Group VIB Ca-independent PLA(2γ) (PLA(2γ)) may be associated with increased lyso-phosphatidylcholines (LPCs) in the PHSML. Therefore, our purpose was to verify the role of iPLA(2γ) on the production of 2-polyunsaturated LPC species and the pathogenesis of T/HS-induced ALI using an iPLA(2γ)-specific inhibitor, R-(E)-6-(bromoethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (R-BEL). METHODS: Male Sprague-Dawley rats were anesthetized and cannulated in blood vessels and mesenteric lymph duct. Animals in the T/HS group underwent a midline laparotomy plus hemorrhagic shock (mean arterial pressure, 35 mm Hg, 30 minutes) and 2-hour resuscitation with shed blood and 2× normal saline. Trauma/sham shock rats were performed the identical procedure without hemorrhage. R-BEL or DMSO was administered 30 minutes before T/HS or trauma/sham shock. Polyunsaturated LPCs and arachidonic acid in the PHSML were analyzed with a liquid chromatography/electrospray ionization-mass spectrometry. Furthermore, ALI was assessed by lung vascular permeability, myeloperoxidase activity, and histology. RESULTS: T/HS increased 2-polyunsaturated LPCs and arachidonic acid in the PHSML. The R-BEL pretreatment significantly decreased these lipids and also inhibited ALI. CONCLUSION: The iPLA(2γ) enzyme is possibly involved in the pathogenesis of ALI following T/HS through the mesenteric lymph pathway.

Needs for disaster medicine: lessons from the field of the Great East Japan Earthquake.

PROBLEM: The Great East Japan Earthquake, which occurred in Tohoku, Japan on 11 March 2011, was followed by a devastating tsunami and damage to nuclear power plants that resulted in radiation leakage. CONTEXT: The medical care, equipment and communication needs of four Disaster Medical Assistance Teams (DMAT) during four missions are discussed. DMATs are medically trained mobile teams used in the acute phase of disasters. ACTION: The DMATs conducted four missions in devastated areas from the day of the earthquake to day 10. The first and second missions were to triage, resuscitate and treat trauma victims in Tokyo and Miyagi, respectively. The third mission was to conduct emergency medicine and primary care in Iwate. The fourth was to assist with the evacuation and screening of inpatients with radiation exposure in Fukushima. OUTCOME: Triage, resuscitation and trauma expertise and equipment were required in Missions 1 and 2. Emergency medicine in hospitals and primary care in first-aid stations and evacuation areas were required for Mission 3. In Mission 4, the DMAT assisted with evacuation by ambulances and buses and screened people for radiation exposure. Only land phones and transceivers were available for Missions 1 to 3 although they were ineffective for urgent purposes. DISCUSSION: These DMAT missions showed that there are new needs for DMATs in primary care, radiation screening and evacuation after the acute phase of a disaster. Alternative methods for communication infrastructure post-disaster need to be investigated with telecommunication experts.

Lipidomics analysis of mesenteric lymph after trauma and hemorrhagic shock.

BACKGROUND: After trauma and hemorrhagic shock (T/HS), a variety of inflammatory mediators enter the systemic circulation through mesenteric lymph ducts, leading to acute lung injury and multiple-organ dysfunction syndrome. Recent studies have demonstrated that post-HS mesenteric lymph (PHSML) activates polymorphonuclear leukocytes (PMNs) and causes vascular endothelial cell and red blood cell dysfunction. Furthermore, PHSML contains proinflammatory mediators, such as biologically active lipids. The purpose of this study was to identify the lipid mediators in PHSML and plasma by liquid chromatography/electrospray ionization mass spectrometry and then estimate the biologic activities of the identified lipids on PMNs. METHODS: PHSML was collected from male Sprague-Dawley rats undergoing trauma (laparotomy) plus HS (40 mm Hg, 30 minutes) or sham shock (SS). The lipids in PHSML and plasma were extracted using the methods of Bligh and Dyer, and liquid chromatography/electrospray ionization mass spectrometry was performed. The biologic activities (superoxide production and elastase release) of identified lipids on human PMNs were tested. RESULTS: Phosphatidylcholine, lysophosphatidylcholine (LPC), phosphatidylethanolamine, lysophosphatidylethanolamine (LPE), and sphingomyelin were detected in the PHSML. Furthermore, linoleoyl, arachidonoyl, and docosahexaenoyl LPCs and LPEs significantly increased in the PHSML of the T/HS group as compared with those of the T/SS group. In the plasma, arachidonoyl and docosahexaenoyl LPCs of the T/HS group also significantly increased in comparison with that of the T/SS group. Linoleoyl and arachidonoyl LPCs and LPEs showed the priming activity on N-formyl-methionyl-leucyl-phenylalanine-activated PMNs. The elastase release was also induced by linoleoyl and arachidonoyl LPCs. CONCLUSION: Mesenteric lymph after T/HS contains biologically active lipids, such as LPCs and LPEs with polyunsaturated fatty acids, which may be involved in the pathogenesis of acute lung injury/multiple-organ dysfunction syndrome.