Seitaro Fujishima

Despite advances in treatment and the expansion of standard care, pneumonia remains a major cause of mortality. It frequently leads to complications such as septic shock and acute respiratory distress syndrome (ARDS), both of which carry high fatality rates. Although antimicrobial therapy is the cornerstone of treatment, additional supportive care and adjunctive therapies, such as corticosteroids, are often required, especially in severe community-acquired pneumonia (CAP). Recent updates to major guidelines on CAP, sepsis, ARDS, and critical illness-related corticosteroid insufficiency generally support corticosteroid use in severe CAP. However, the REMAP-CAP randomized controlled trial, published in 2025, failed to demonstrate significant benefit, potentially influencing future recommendations. Currently, corticosteroid therapy should be individualized based on CAP severity, particularly the degree of hypoxemia and respiratory failure. In eligible patients, early initiation and flexible duration of corticosteroid use based on clinical response may be appropriate. For nonbacterial pneumonia, strong evidence supporting corticosteroid use exists only for COVID-19 and Pneumocystis jirovecii pneumonia in HIV-infected individuals. Conversely, observational data do not support corticosteroid use for influenza or fungal infections. In CAP complicated by septic shock or ARDS, corticosteroid use is endorsed by recent guidelines; however, the recommended timing, dosage, and duration vary. Although combination therapy with hydrocortisone and fludrocortisone is a potential option, further direct evidence is needed. Biomarkers such as C-reactive protein and, in the near future, insights into corticosteroid-related immune repair mechanisms in COVID-19 may aid in identifying corticosteroid-responsive phenotypes.

Acute respiratory failure (ARF) is defined by acute and progressive hypoxemia caused by various cardiorespiratory or systemic diseases in previously healthy patients. Among ARF, acute respiratory distress syndrome (ARDS) is a serious condition with bilateral lung infiltration, which develops secondary to a variety of underlying conditions, diseases, or injuries. This review summarizes the current standard of care for ARF and ARDS based on current major guidelines in this field. When administering fluid in patients with ARF, particularly ARDS, restrictive strategies need to be considered in patients without shock or multiple organ dysfunction. Regarding oxygenation targets, avoiding excessive hyperoxemia and hypoxemia is probably a reasonable choice. As a result of the rapid spread and accumulation of evidence for high-flow nasal cannula oxygenation, it is now weakly recommended for the respiratory management of ARF in general and even for initial management of ARDS. Noninvasive positive pressure ventilation is also weakly recommended for the management of certain ARF conditions and as initial management of ARDS. Low tidal volume ventilation is now weakly recommended for all patients with ARF and strongly recommended for patients with ARDS. Limiting plateau pressure and high-level PEEP are weakly recommended for moderate-to-severe ARDS. Prone position ventilation with prolonged hours is weakly to strongly recommended for moderate-to-severe ARDS. In patients with COVID-19, ventilatory management is essentially the same as for ARF and ARDS, but awake prone positioning may be considered. In addition to standard care, treatment optimization and individualization, as well as the introduction of exploratory treatment, should be considered as appropriate. As a single pathogen, such as SARS-CoV-2, exhibits a wide variety of pathologies and lung dysfunction, ventilatory management for ARF and ARDS may be better tailored according to the respiratory physiologic status of individual patients rather than the causal or underlying diseases and conditions.

Aim: This study aimed to investigate the association of early vasopressor initiation with improved septic shock outcomes.Methods: This multicenter observational study was conducted in 17 intensive care units in Japan and included adult patients with sepsis admitted to the intensive care unit from July 2019 to August 2020 and treated with vasopressor therapy. Patients were divided into the early vasopressor group (≤1 h from sepsis recognition) and the delayed vasopressor group (>1 h). The impact of early vasopressor administration on risk‐adjusted in‐hospital mortality was estimated using logistic regression analyses adjusted by an inverse probability of treatment weighting analysis with propensity scoring.Results: Among the 97 patients, 67 received vasopressor therapy within 1 h from sepsis recognition and 30 received vasopressor after 1 h. In‐hospital mortality was 32.8% in the early vasopressor group and 26.7% in the delayed vasopressor group (p = 0.543). The adjusted odds ratio for in‐hospital mortality was 0.76 (95% confidence interval 0.17–3.29) when comparing patients in the early vasopressor with those in the delayed vasopressor group. The fit curve from the mixed‐effects model showed a relatively lower trend toward an infusion volume over time in the early vasopressor group than in the delayed vasopressor group.Conclusion: Our study did not reach a definitive conclusion for early vasopressor administration. However, early vasopressor administration may help avoid volume overload in the long course of sepsis care.

Purpose Data regarding harm from nasal intubation in trauma patients have been conflicting. This study aims to elucidate whether nasal intubation is associated with increased in-hospital mortality compared with oral intubation. Methods A retrospective cohort study on a nationwide trauma registry of 2004–2019 was conducted. Adult trauma patients who underwent nasal or oral intubation during initial resuscitation were selected. In-hospital mortality and lung complications were compared between nasal and oral intubations. A generalized estimating equation model accounting for within-institution clustering was adopted. Patient demographics, comorbidities, mechanism, injury severity, and vital signs on hospital arrival were adjusted. Subgroup analyses were conducted based on age, Abbreviated Injury Scale [AIS] for the head and face, and vital signs on arrival. Results Among 29,271 patients eligible for the study, 667 were intubated nasally. In-hospital mortality was higher in nasal intubation compared with oral intubation (OR, 1.28 [95% CI, 1.01–1.64]). There were more noninfectious pulmonary complications in nasal intubation (OR, 1.48 [1.14–1.94]). The harms of nasal intubation were observed only in the elderly (age ≥ 75), patients with severe head injury (AIS in the head ≥ 4), and normotensive patients (systolic blood pressure ≥ 90 mmHg). Conversely, mortality was comparable regardless of the route of intubation in patients with complicated facial injury (AIS in the face ≥ 3). Conclusion Nasal intubation was associated with increased in-hospital mortality, particularly in older patients and severe head injury, but not severe facial injury. The route of intubation should be judiciously decided during trauma resuscitation.

Background: The development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. This study aimed to characterize “severe” sepsis DIC patients and to identify the patient population benefiting from anticoagulant therapy. Methods: We conducted a retrospective sub-analysis of a prospective multicenter study, enrolling 1,178 adult patients with severe sepsis. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR). Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Findings: Organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of < 1∙5, and this trend was more pronounced with higher DIC scores. Three-way interaction analysis demonstrated that anticoagulant therapy was associated with better survival outcome in patients with high DIC scores and high PT-INR. Furthermore, we identified a DIC score of ≥ 5 and PT-INR of ≥ 1∙5 as clinical thresholds for the identification of optimal targets for anticoagulant therapy. Interpretations: The combination of the DIC score and PT-INR selected the optimal patient population for anticoagulant therapy in sepsis-induced DIC. Diagnosing DIC with a sensitive DIC scoring system, followed by the selection of the optimal patient population for anticoagulant therapy may be useful for controlling sepsis-induced DIC. Funding: This study was supported by the Japanese Association for Acute Medicine (2014-01). Declaration of Interests: None of the authors declare any conflicts of interests in connection with the submitted article. TW reported receiving personal fees from Asahi Kasei Pharma America Inc. and Asahi Kasei Pharma Japan Inc. outside the submitted work. AS reported receiving personal fees from CSL Behring outside the submitted work. The other authors have no conflict of interest to declare. Ethics Approval Statement: This study was approved by the JAAM and the Ethics Committee of all participating hospitals waiving written informed consent (JAAM, 2014-01, Hokkaido University Graduate School of Medicine, Head institute of the FORECAST group, 014-0307) after written informed consent was obtained from each patient or their next of kin and was performed in accordance with the tenets underlying the Declaration of Helsinki.

Background: Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes. Methods: A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016–2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO₂ of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models. Results: Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10–21) vs 23 (16–26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12–22) vs 23 (19–26), p = 0.004], but not among those intubated at the ED [18 (9–20) vs 15 (8–23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay. Conclusions: Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED. Trial registration: UMIN-CTR, UMIN000019588. Registered on November 15, 2015.