Neutrophil extracellular trap (NET) formation, an innate immune system response, is associated with thrombogenesis and vascular endothelial injury. Circulatory disorders due to microvascular thrombogenesis are one of the principal causes of organ damage. NET formation in organs contributes to the exacerbation of sepsis, which is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. We have previously reported that recombinant human soluble thrombomodulin (rTM) reduces lipopolysaccharide (LPS)-induced NET formation in vitro. Here, we aimed to show that thrombomodulin (TM)-mediated suppression of NET formation protects against organ damage in sepsis. Mice were injected intraperitoneally (i.p.) with 10 mg/kg LPS. rTM (6 mg/kg/day) or saline was administered i.p. 1 h after LPS injection. In the LPS-induced murine septic shock model, extracellular histones, which are components of NETs, were observed in the liver and lungs. In addition, the serum cytokine (interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), macrophage chemotactic protein-1 (MCP-1), and interleukin-10 (IL-10)) levels were increased. The administration of rTM in this model prevented NET formation in the organs and suppressed the increase in the levels of all cytokines except IL-1β. Furthermore, the survival rate improved. We provide a novel role of TM in treating inflammation and NETs in organs during sepsis.

ABO blood groups have been implicated as potential risk factors for various diseases. However, no study has investigated the association between sepsis mortality and ABO blood types. We aimed to evaluate the impact of these blood types on mortality in patients with sepsis and septic shock. This retrospective observational study was conducted at two general hospitals in Japan. Patients diagnosed with sepsis or septic shock were included and divided into four groups based on blood type (O, A, B, and AB). The association between type O vs. other types and 28- and 90-day mortalities was evaluated using multivariate logistic regression analysis adjusted for age, sex, and Sequential (Sepsis-related) Organ Failure Assessment score. This study included 415 patients, of whom 131 (31.6%), 171 (41.2%), 81 (19.5%), and 32 (7.7%) had type O, A, B, and AB, respectively. Blood type O was not associated with 28-day (odds ratio: 1.7 p = 0.08) or 90-day mortality (odds ratio: 1.53, p = 0.091). However, type O was significantly associated with higher 90-day mortality (odds ratio: 3.26, p = 0.009) in patients with septic shock. The role of ABO blood type in risk stratification for septic shock and the mechanisms that potentially affect the prognosis of sepsis patients need further investigation.

We examined whether high lactate level in septic patients was associated with 90-day mortality based on the patients’ disseminated intravascular coagulation (DIC) status. We conducted a multicenter, retrospective, observational study of patients admitted to the intensive care unit (ICU) with a suspicion of severe infection and diagnosed with sepsis. Regression analyses were performed to estimate the interaction effect between DIC status and the lactate level. Then, the association between the lactate level and 90-day mortality was assessed in the DIC and non-DIC subgroups. The data of 415 patients were analyzed. We found a significant interaction between DIC status and the lactate level for predicting 90-day mortality (pinteraction = 0.04). Therefore, we performed a subgroup analysis and found that high lactate concentration was significantly associated with 90-day mortality in the DIC group (odds ratio = 2.31, p = 0.039) but not in the non-DIC group. In patients with DIC, a high lactate level significantly predicted 90-day mortality; no such association was found in the non-DIC group. Thus, DIC status may serve as a possible effect modifier of lactate level in predicting mortality in patients with sepsis.

Blood purification is performed to control cytokines in critically ill patients. The relationship between the clearance (CL) and the membrane area during adsorption is not clear. We hypothesized that the CL increases with the hydrophobic area when hydrophobic binding contributes to cytokine adsorption. We investigated the relationship between the hemofilter membrane area and the CL of the high mobility group box 1 protein (HMGB-1) and interleukin-6 (IL-6). We performed experimental hemofiltration in vitro using polymethyl methacrylate membranes CH-1.8W (1.8 m²) and CH-1.0N (1.0 m²), as well as polysulfone membrane NV-18X (1.8 m²). After adding 100 mg of HMGB1 or 10 μg of IL-6 into the test solution, experimental hemofiltration was conducted for 360 min in a closed-loop circulation system, and the same amount of HMGB1 and IL-6 was added after 180 min. With CH-1.8W and CH-1.0N, both HMGB-1 and IL-6 showed a rapid concentration decrease of more than 70% at 180 min and 360 min after the re-addition. At 15 min, the CL of HMGB-1 was CH-1.8W: 28.4 and CH-1.0N: 19.8, and that of IL-6 was CH-1.8W: 41.1 and CH-1.0N: 25.4. CH-1.8W and CH-1.0N removed HMGB1 and IL-6 by adsorption and CH-1.8W was superior in CL, which increased with a greater membrane area.

Background: Hemodynamic management during anesthesia in liver transplantation for patients with polycystic liver disease (PLD) can be more challenging because of the bleeding and hemodynamic alterations due to the markedly enlarged liver. We hereby report a case of PLD wherein transesophageal echocardiography (TEE) was employed for optimal hemodynamic monitoring during liver transplantation. Case presentation: A 61-year-old man was scheduled to undergo liver transplantation for massive PLD. Hemodynamic instability was associated with mechanical displacement of the giant cystic liver. TEE results revealed the collapse of the inferior vena cava due to liver displacement. TEE also detected intrathoracic hemorrhage triggered by detachment from the markedly enlarged liver. Conclusion: TEE is a valuable monitoring tool for sharing information with surgeons and diagnostic modality for finding the source of bleeding in liver transplantation for PLD and may contribute majorly to the quality of perioperative management.