Kohshi Hattori

Tracheal intubation is an essential procedure in the induction of general anesthesia; however, it is also a main source of infectious aerosols such as severe acute respiratory virus 2 (SARS-CoV-2). For protection from infectious aerosols, an air conditioning system which provides continuous laminar air flow from the ceiling and a local isolating device are widely used in typical operating rooms. However, how aerosols spread in an actual operating room has not been visualized, especially during tracheal intubation. In this study, we observed the spread of aerosols under several circumstances. To recreate the scenario of general anesthesia induction, we substituted aerosol spray with smoke from a smoke tester device in the mouth of a human body model placed on the operating table. Then we measured the maximum height of aerosol spread every second for 9 seconds. To verify the contribution of air conditioning and an isolating device, we compared four situations based on their presence or absence. The maximum height of aerosol spread was significantly lower in the presence of laminar air flow from the ceiling. An isolating device contributed to initially enclosing the aerosol; however, some aerosol leaked and diffused depending on the air flow outside the device. During tracheal intubation in typical operating room, air-conditioned laminar air flow can contribute to prevent infectious aerosol spread, and an isolating device can provide supplementary protection.

The purinergic P2Y12 receptor regulates microglial activation, resulting in persistence and aggravation of pain in neuropathic and nociceptive pain models. We conducted a retrospective chart review to explore the analgesic potency of the P2Y12 receptor-specific antagonist, clopidogrel, for clinical management of postoperative pain in patients who underwent abdominal surgery. Twenty-seven patients with cardiovascular comorbidities, who underwent laparoscopic abdominal surgery and had ceased aspirin (ASP, n = 17) or clopidogrel (CLP, n = 10) for 14 days pre-operatively, were enrolled retrospectively. In both groups, the number of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) consumed for managing postoperative pain was compared using the chi-square test and Mann–Whitney test. Our results showed that from postoperative day (POD) 0 to POD 3, the average numerical rating reflecting the postoperative pain was comparable between the two groups (CLP: 4.0 ± 1.4 vs. ASP: 3.7 ± 0.8, P-value = 0.56). However, at POD 7, opioid consumption in the CLP-treated group (fentanyl-equivalent dose: 0.49 ± 0.56 mg) was significantly lower than that in the ASP-treated group (1.48 ± 1.35 mg, P-value = 0.037). After reaching a stable state by repeated systemic administration, clopidogrel sustained the analgesic efficacy for a certain period. In conclusion, microglial P2Y12 receptors may mediate signal transduction of postoperative nociceptive pain and enhance clinical opioid analgesia.

STAT3 serves as a key transcription factor in both immunity and inflammatory pathways. We examined whether in vivo introduction of STAT3 decoy oligodeoxynucleotides (ODNs) is beneficial in reducing septic end‐organ injury. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in mice. STAT3 was rapidly activated in major end‐organ tissues following CLP, which was accompanied by activation of the upstream kinase JAK2. Transfection of STAT3 decoy ODNs significantly improved histopathological changes in lung, liver, kidney, and heart tissues. STAT3 decoy ODN transfection downregulated pro‐inflammatory cytokine/chemokine overproduction and reduced the increases in tissue and serum levels of HMGB1 in CLP mice. These beneficial effects of STAT3 decoy ODNs led to s significant survival advantage in mice after CLP. Our results indicate a detrimental role of STAT3 in the sepsis pathophysiology and the potential usefulness of STAT3 decoy ODNs for sepsis therapy. Support or Funding Information: Grants‐in‐Aid for Scientific Research from Japan Society for Promotion of Science (17K08586, 19H03757)

Sepsis affects every major organ within the body, ultimately leading to their failure, and the development of one or more organs poses a major threat to the survival of septic patients. In sepsis, the respiratory system is the most frequently affected organ system, and lung dysfunction is the first step in the development of multiple organ failure. A major hurdle in the clinical management of septic patients suffering from acute lung injury and its most severe manifestation, the acute respiratory distress syndrome, is the lack of the effective treatment. The important goal in critical care medicine is to find significant therapeutic strategies that will impact favorably on patient outcome. Sepsis alters expression of many pathogenic factors that can potentially give rise to abnormalities in the respiratory system. A number of transcription factors, such as nuclear factor-kappaB and activator protein-1, can be linked to the altered gene activation during sepsis. Thus, several transcription factors may play a pivotal role in the pathophysiology of acute lung injury in sepsis. Given that sepsis can be regarded as a gene-related disorder, the potential usefulness of systemic delivery of decoy oligodeoxynucleotide against some transcription factors may be considered to be a promising novel therapeutic approach for treatment of acute lung injury in sepsis.

Clinical anesthesiologists, particularly residents, work in stressful environments. However, evidence-based physiological and psychological tests to evaluate stress are still lacking. In this single-center study of 33 residents, we investigated the relationship between heart rate variability (HRV), which had the potential to screen residents’ stress levels using Holter electrocardiography (ECG) and psychological mood as assessed by the Profile of Mood States (POMS) questionnaire. HRV analysis revealed 2 findings. Firstly, standard deviation of the average of 5-min normal-to-normal R–R intervals (SDANN) was significant lower than that of same-aged healthy volunteers (69.3 ± 27.9 vs. 137.0 ± 43.0 ms, P < 0.05), which indicated suppression of autonomic nervous system activity throughout their work. Secondly, at induction of anesthesia, significant higher low frequency/high frequency ratio (LF/HF ratio: 1.326 vs. 0.846; P < 0.05) and lower HF (3326 vs. 5967 ms²; P < 0.05) and lower standard deviation of normal-to-normal R–R intervals (SDNN: 50.5 vs. 79.4 ms; nervous system was suppressed at the induction of anesthesia: expected to be the most stressful period of their work. On the other hand, deviation scores of POMS questionnaire elucidated that all the residents were within normal range of psychological mood, and without any significant diurnal changes with respect to total mood disturbance deviation (TMD) scores (48 vs. 47; P = 0.368). HRV elucidated physiological stress among anesthesiology residents quantitatively by evaluating autonomic nervous activities, especially at induction of anesthesia. These changes in HRV could be observed regardless of psychological mood.

G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous member of the GRK family that restrains cellular activation by G protein-coupled receptor (GPCR) phosphorylation leading to receptor desensitization and internalization, but has been identified to regulate a variety of signaling molecules, among which may be associated with inflammation. In this study, we attempted to establish the regulatory role of GRK2 in the Toll-like receptor (TLR) signaling pathway for inducible nitric oxide synthase (iNOS) expression in microglial cells. When mouse MG6 cells were stimulated with the TLR4 ligands lipopolysaccharide (LPS) and paclitaxel, we found that interferon regulatory factor 1 (IRF1) protein expression and activation was upregulated, transcription of interferon-β (IFN-β) was accelerated, induction/activation of STAT1 and activation of STAT3 were promoted, and subsequently iNOS expression was upregulated. The ablation of GRK2 by small interfering RNAs (siRNAs) not only eliminated TLR4-mediated upregulation of IRF1 protein expression and nuclear translocation but also suppressed the activation of the STAT pathway, resulting in negating the iNOS upregulation. The TLR3-mediated changes in IRF1 and STAT1/3, leading to iNOS induction, were also abrogated by siRNA knockdown of GRK2. Furthermore, transfection of GRK2 siRNA blocked the exogenous IFN-β supplementation-induced increases in phosphorylation of STAT1 as well as STAT3 and abrogated the augmentation of iNOS expression in the presence of exogenous IFN-β. Taken together, our results show that GRK2 regulates the activation of IRF1 as well as the activation of the STAT pathway, leading to upregulated transcription of iNOS in activated microglial cells. Modulation of the TLR signaling pathway via GRK2 in microglia may be a novel therapeutic target for treatment of neuroinflammatory disorders.