Case study observational research: inflammatory cytokines in the bronchial epithelial lining fluid of COVID-19 patients with acute hypoxemic respiratory failure.

BACKGROUND: In this study, the concentrations of inflammatory cytokines were measured in the bronchial epithelial lining fluid (ELF) and plasma in patients with acute hypoxemic respiratory failure (AHRF) secondary to severe coronavirus disease 2019 (COVID-19). METHODS: We comprehensively analyzed the concentrations of 25 cytokines in the ELF and plasma of 27 COVID-19 AHRF patients. ELF was collected using the bronchial microsampling method through an endotracheal tube just after patients were intubated for mechanical ventilation. RESULTS: Compared with those in healthy volunteers, the concentrations of interleukin (IL)-6 (median 27.6 pmol/L), IL-8 (1045.1 pmol/L), IL-17A (0.8 pmol/L), IL-25 (1.5 pmol/L), and IL-31 (42.3 pmol/L) were significantly greater in the ELF of COVID-19 patients than in that of volunteers. The concentrations of MCP-1 and MIP-1ß were significantly greater in the plasma of COVID-19 patients than in that of volunteers. The ELF/plasma ratio of IL-8 was the highest among the 25 cytokines, with a median of 737, and the ELF/plasma ratio of IL-6 (median: 218), IL-1ß (202), IL-31 (169), MCP-1 (81), MIP-1ß (55), and TNF-α (47) were lower. CONCLUSIONS: The ELF concentrations of IL-6, IL-8, IL-17A, IL-25, and IL-31 were significantly increased in COVID-19 patients. Although high levels of MIP-1 and MIP-1ß were also detected in the blood samples collected simultaneously with the ELF samples, the results indicated that lung inflammation was highly compartmentalized. Our study demonstrated that a comprehensive analysis of cytokines in the ELF is a feasible approach for understanding lung inflammation and systemic interactions in patients with severe pneumonia.

Point-of-care testing for tranexamic acid efficacy: a proof-of-concept study in cardiac surgical patients.

BACKGROUND: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001). CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.

Effect of acute normovolemic hemodilution in patients undergoing cardiac surgery with remimazolam anesthesia.

PURPOSE: The reduced effects of allogeneic transfusion with acute normovolemic hemodilution (ANH) have been reported. Harvesting a large volume of blood may maximize the effect in patients with low body weight, and the prevention of hypotension is important. Remimazolam is an anesthetic with few circulatory responses. Our aim was to evaluate whether high-volume ANH reduces the need for transfusion in cardiac patients under remimazolam anesthesia. METHODS: In this retrospective single-center study, we enrolled cardiopulmonary bypass (CPB) patients who received remimazolam anesthesia. Changes in hemodynamic parameters were assessed. The numbers of blood transfusions and chest tube outputs were also evaluated. RESULTS: In a total of 51 patients, ANH was performed in 27 patients with a mean body mass index of 23.2 (ANH volume: 740 ± 222 mL). No significant differences were observed in mean blood pressure during blood collection. The intraoperative amount of red blood cell (RBC) transfusion was significantly lower in the ANH group than in the control group (431 ± 678 and 1260 ± 572 mL, p < 0.001). The avoidance rates of RBC were 66.7 and 4.2%, respectively. The multivariate analysis result revealed that ANH correlated with RBC, with an odds ratio of 0.067 (95% confidence interval 0.005-0.84, p < 0.05). The postoperative bleeding at 24 h was significantly lower in the ANH group (455 ± 228 and 797 ± 535 mL, p < 0.01). CONCLUSION: In patients undergoing CPB, ANH reduced intraoperative transfusion amount and postoperative bleeding. Hemodynamic changes during blood collection were minimal under remimazolam anesthesia and high-volume ANH was feasible.

Pulmonary vein stump thrombosis and organ infarction after lung lobectomy.

Lung resection surgery, which is performed as a treatment for lung cancer and metastatic lung tumors, is currently conducted via minimally invasive techniques such as video-assisted thoracoscopic surgery and robot-assisted methods. Postoperative complications related to this surgery, such as pulmonary vein thrombosis and cerebral and other organ infarctions, have been increasingly reported. The primary cause of these complications is thrombus formation in the pulmonary vein stump. Statistical data on the site of lung lobectomy have indicated that surgeries involving the left upper lobe are most frequently associated with embolic complications. Although this issue has not received considerable attention in anesthesiology, the importance of prevention and treatment in postoperative management is growing. The role of anesthesiologists in preventing these complications is critical. These roles involve careful fluid management to avoid hypercoagulable states, consideration of early postoperative anticoagulation therapy, assessment of the suitability of epidural anesthesia for postoperative anticoagulation, and improvement of hospital-wide safety systems and monitoring of high-risk patients. Anesthesiologists need to understand the pathology and risk factors involved and play an active role in preventing and treating these complications through effective collaboration with thoracic surgeons and the in-hospital stroke team.

Tracheal injury diagnosed by a sudden increase in end-tidal carbon dioxide levels during mediastinoscopic subtotal esophagectomy: a case report.

BACKGROUND: Mediastinoscopic surgery for esophageal cancer facilitates early postoperative recovery. However, it can occasionally cause serious complications. Here, we present the case of a patient with a tracheal injury diagnosed by a sudden increase in end-tidal carbon dioxide (EtCO2) during mediastinoscopic subtotal esophagectomy. CASE PRESENTATION: A 52-year-old man diagnosed with esophageal cancer was scheduled to undergo mediastinoscopic subtotal esophagectomy. During the mediastinoscopic procedure, the EtCO2 level suddenly increased above 200 mmHg, and the blood pressure dropped below 80 mmHg. We immediately asked the operator to stop insufflation and found a tracheal injury on the right side of the trachea near the carina by bronchoscopy. The endotracheal tube was replaced with a double-lumen tube, and the trachea was repaired via right thoracotomy. There were no further intraoperative complications. After surgery, the patient was extubated and admitted to the intensive care unit. CONCLUSIONS: Monitoring EtCO2 levels and close communication with the operator is important for safely managing sudden tracheal injury during mediastinoscopic esophagectomy.

Remimazolam for general anesthesia in a patient with aortic stenosis and severe obesity undergoing transcatheter aortic valve implantation.

INTRODUCTION: There is currently limited research on the clinical use of remimazolam in severely obese patients. In this report, we describe the anesthesia management of transcatheter aortic valve implantation (TAVI) in a severely obese patient using remimazolam. CASE DESCRIPTION: A 76-year-old woman (height 1.54 m; total body weight 104 kg; body mass index 43.9 kg/m2) was scheduled for TAVI via the femoral artery approach for aortic valve stenosis. Preoperative echocardiography showed an aortic valve peak flow of 4.0 m/s and an effective orifice area of 0.75 cm2. Anesthesia induction was performed with a bolus dose of 100 µg fentanyl, 15 mg remimazolam, 60 mg rocuronium, and a continuous infusion of remifentanil at 0.4 mg/h. Intraoperatively, remimazolam was administered at a rate of 35 mg/h. General anesthesia management was completed without any complications, although the patient required temporary catecholamine and inhalation anesthesia assistance due to hemodynamic changes. CONCLUSION: Owing to its pharmacological advantages, remimazolam may be an option for anesthesia induction and maintenance in severely obese patients with unstable circulation.

Anesthetic Management of Thoracoscopic Pulmonary Cystectomy in a Patient With Fontan Circulation and Disturbed Lung Inflation During Leakage Testing: A Case Report.

Congenital heart disease may require multiple cardiac surgeries during childhood. Subsequent non-cardiac surgeries increase the perioperative bleeding and hypoxia because of changes in circulation. An 18-year-old male patient with a history of multiple cardiac interventions, including Fontan surgery, underwent a thoracoscopic right lung suture and coverage for recurrent right spontaneous pneumothorax under general anesthesia with one lung ventilation (OLV). The superior dorsal and inferior lobes, which were inflatable before surgery, failed to expand during leakage testing. The trachea's condition was examined using a flexible bronchoscope, and no obstructions were found. A thoracic drainage catheter was inserted, and the lower lobe was dilated from outside the body using negative pressure control in a sealed environment. In the patient with previously treated Fontan circulation, both lungs were expanded by inserting a thoracic catheter during thoracoscopic right lung suture and maintaining negative external pressure.

Immunological Response to Subcutaneous and Intranasal Administration of SARS-CoV-2 Spike Protein in Mice.

In novel coronavirus infection (COVID-19), the outbreak of acute lung injury due to trans-airway infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the starting point of severe disease. The COVID-19 pandemic highlights the need for a vaccine that prevents not only the disease but also its infection. Currently, the SARS-CoV-2 vaccine is administered via intramuscular injection and is generally not immunogenic to the mucosa. As a result, current vaccinations fail to reduce viral shedding and transmission and ultimately do not prevent infection. We established a mouse vaccine model in which a single dose of S1 protein and aluminum oxide gel (alum) subcutaneous vaccine was followed by a booster dose of S1 protein and CpG oligodeoxynucleotide intranasal vaccine. The group that received two doses of the intranasal vaccine booster showed a significant increase in IgG and IgA antibody titers against S1 and RBD in serum and BAL, and a significant difference in neutralizing antibody titers, particularly in BAL. One intranasal vaccine booster did not induce sufficient immunity, and the vaccine strategy with two booster intranasal doses produced systemic neutralizing antibodies and mucus-neutralizing antibodies against SARS-CoV-2. It will be an important tool against the emergence of new viruses and the next pandemic.

Potential marker subset of blood-circulating cytokines on hematopoietic progenitor-to-Th1 pathway in COVID-19.

In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of the proteins analyzed in COVID-19, approximately 70% were detected with Bonferroni-corrected significant differences in comparison with disease severity, clinical outcome, long-term hospitalization, and disease progression and recovery. Specifically, IP-10, sTNF-R1, sTNF-R2, sCD30, sCD163, HGF, SCYB16, IL-16, MIG, SDF-1, and fractalkine were found to be major components of the COVID-19 cytokine storm. Moreover, the 11 cytokines (i.e., SDF-1, SCYB16, sCD30, IL-11, IL-18, IL-8, IFN-γ, TNF-α, sTNF-R2, M-CSF, and I-309) were associated with the infection, mortality, disease progression and recovery, and long-term hospitalization. Increased expression of these cytokines could be explained in sequential pathways from hematopoietic progenitor cell differentiation to Th1-derived hyperinflammation in COVID-19, which might also develop a novel strategy for COVID-19 therapy with recombinant interleukins and anti-chemokine drugs.

Antibody Response Following the Intranasal Administration of SARS-CoV-2 Spike Protein-CpG Oligonucleotide Vaccine.

The new coronavirus infection causes severe respiratory failure following respiratory tract infection with severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). All currently approved vaccines are administered intramuscularly; however, intranasal administration enhances mucosal immunity, facilitating the production of a less invasive vaccine with fewer adverse events. Herein, a recombinant vaccine combining the SARS-CoV-2 spike protein receptor-binding domain (RBD), or S1 protein, with CpG-deoxyoligonucleotide (ODN) or aluminum hydroxide (alum) adjuvants was administered intranasally or subcutaneously to mice. Serum-specific IgG titers, IgA titers in the alveolar lavage fluid, and neutralizing antibody titers were analyzed. The nasal administration of RBD protein did not increase serum IgG or IgA titers in the alveolar lavage fluid. However, a significant increase in serum IgG was observed in the intranasal group administered with S1 protein with CpG-ODN and the subcutaneous group administered with S1 protein with alum. The IgA and IgG levels increased significantly in the alveolar lavage fluid only after the intranasal administration of the S1 protein with CpG-ODN. The neutralizing antibody titers in serum and bronchoalveolar lavage were significantly higher in the intranasal S1-CpG group than in every other group. Hence, the nasal administration of the S1 protein vaccine with CpG adjuvant might represent an effective vaccine candidate.