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Studies have shown that elevated plasma levels of platelet-derived soluble TREM-like transcript-1 (sTLT-1) are associated with an unfavorable outcome in patients with septic shock. However, the underlying molecular mechanisms are not well defined. This research aimed to study the role of sTLT-1 in mediating immune dysfunction during the development of sepsis. Our study demonstrated that patients with septic shock have significantly higher plasma concentrations of sTLT-1, whereas sTLT-1 is not detectable in healthy subjects. Plasma concentrations of sTLT-1 were correlated with the degree of immunosuppressive parameters in monocytes from patients with septic shock. sTLT-1 can first activate monocytes by binding to the TLR4/MD2 complex but subsequently induce immunosuppressive phenotypes in monocytes. Blocking Abs against TLR4 and MD2 led to a significant decrease in sTLT-1–induced activation. Treatment with an anti–TLT-1 Ab also significantly reduces sTLT-1 binding to monocytes and proinflammatory cytokine secretion in a mouse model of endotoxemia. sTLT-1 acts as an endogenous damage-associated molecular pattern molecule, triggering the activation of monocytes through the TLR4/MD2 complex followed by sustained immune suppression. This process plays a crucial role in the development of sepsis-associated pathophysiology. Our findings outline, to our knowledge, a novel pathway whereby platelets counteract immune dynamics against infection through sTLT-1.

Background Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. Method This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH Results We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. Conclusions Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Proper clinical transfers of patient care (known as handovers) are important to patient safety. The aim of this study was to investigate the efficacy and satisfaction of an electronic system for clinical transfers of patients with complex surgical procedures. The design was a single-center observational study auditing the handover process. The electronic handover system combined with an electronic health record system was developed to help verbal handover. The system has a checklist to guide the structured handover process and provided information from the health record system. With the system, the elapsed time for surgical handover decreased from 10.5 to 5.4 minutes. The questionnaire analysis showed that clinician satisfaction with surgical handover increased from 69.4% to 79.3%, and the perception of communication completeness increased from 67.2% to 81.6%. The electronic handover system improved communication for the transfer of care for surgical patients.

Additional file 1. Supplementary materials include detailed methods and supplementary results as referenced inthe article.

Summary Background Patients with severe sepsis and acute respiratory failure often developed muscle weakness because of their critical illness and immobility. We hypothesized electric muscle stimulation (EMS) may prevent the weakness and shorten the duration of mechanical ventilation (MV). Methods Elderly patients with severe sepsis and acute respiratory failure were enrolled and randomized to EMS or control group on the third day of MV. The EMS was applied to both quadriceps 32 minutes in weekdays with minimal voltage to induce visible muscle contraction (device: HELEX 573 ® , programmed strength aggravating mode). Control group had passive exercise of extremities. Duration of MV support was compared. Results 545 patients were screened and 25 patients were randomized in 2:1 ratio. (18 patients into EMS and 7 into control group). 64% of the acute respiratory failures resulted from pneumonia. Both group had similar demographic data and median age of all participants was 78 years-old (interquartile range 72–82). The mean duration of ventilator dependence was 6 days (IQR 6–15) in control group and 6.5 days (IQR 5–10) in EMS group (P = 0.85). Conclusion EMS did not help critical-ill septic elderly to reduce the duration of mechanical ventilation in our pilot study. Further larger study is warranted with adequate study power and identical weaning strategy to test the EMS benefits.

Cytotoxic T-cells in patients with advanced tumors are often dysfunctional due to persistent cancer antigen exposure. These dysfunctional T-cells, known as exhausted T-cells, are characterized by an increased expression of inhibitory receptors and the gradual loss of effector functions, which contribute to immune evasion of cancer cells. Immune checkpoint blockade therapy works by removing the inhibitory signals, reversing the T-cell exhausted state, thereby leading to immune-mediated tumor regression. While immunotherapy has become a front-line treatment for many lung cancer patients for its promising clinical outcome, the durability of this reversal of T-cell exhaustion still remains unsatisfactory, which contributes to eventual treatment failure. Emerging evidence in animal models suggests that exhausted T-cells have a distinct epigenetic landscape that remains unaltered following immune checkpoint blockade therapy. Thus, we hypothesized that epigenetic therapy may reprogram tumor-reactive T-cells to enhance their effector functions. We isolated CD3+ T-cells from malignant pleural effusion or primary tumor tissues of 20 lung cancer patients and examined their immunophenotypes, including surface markers (CD4 and CD8), proliferative index (Ki67), as well as inhibitory receptors (PD-1, TIM3, and CTLA4). T-cells were subject to in vitro daily treatment of decitabine, a DNA methyltransferase inhibitor, for 72 hours. Polyfunctional T-cells that co-express effector functions (i.e., TNF-α, IFN-γ, IL-2 and CD107a) were analyzed by multichromatic flow cytometry. We discovered that T-cells in the malignant pleural effusion or primary lung cancer tissues have higher CD4/CD8 ratios as compared with peripheral blood mononuclear cells from healthy volunteers. The majority of T-cells from lung cancer patients exhibited the exhausted phenotype and expressed at least one inhibitory receptor at higher levels. This indicates that T-cells from malignant pleural effusion could potentially reflect dysfunctional immune states in lung cancer patients when tumor tissues are not available. Moreover, treatment of decitabine at clinically relevant concentrations significantly increased the polyfunctionality of PD-1 positive CD4+ and CD8+ T-cells from selected patients. Interestingly, the reinvigoration of polyfunctional T-cell responses did not associate with the downregulation of PD-1. On the other hand, the effects of decitabine on PD-1 negative CD4+ and CD8+ T-cells were only modest. This suggests that malignant pleural effusion T-cells, which are often PD-1 positive, may respond to epigenetic reprogramming via PD-1-independent mechanisms. Our data shed light on the potential uses of epigenetic therapy in lung cancer treatment by immunomodulation. Citation Format: Hsing-Chen Tsai, Yi-Chieh Wu, Shu-Yung Lin, I-Yu Chen, Jih-Hsiang Lee, Kuang-Hua Cheng, Ping-Huai Wang, Huan-Jang Ko, Wen-Chien Huang, Yi-Jhen Huang, Kai-Lin Wei, Chong-Jen Yu, Yen-Ling Chiu. Epigenetic therapy restores polyfunctionality of malignant pleural effusion T-cells in patients with non-small cell lung cancer without downregulation of PD-1 [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A221.

Background: The study investigated the effectiveness of dexamethasone injections for reducing the occurrence of postextubation airway obstruction (PEAO). Methods: One hundred and thirty-eight patients who were intubated for ≥ 48 hours with a cuff-leak volume (CLV) < 110 mL were treated with low-dose dexamethasone (5 mg; n = 41), high-dose dexamethasone (10 mg; n = 42), or placebo (normal saline; n = 43) injection every 6 hours for a total of four doses on the day preceding extubation. CLV was measured before the first injection, 1 hour after each injection, and 24 hours after the fourth injection. Extubation was performed 24 hours after the last injection. PEAO was recorded within 48 hours postextubation. Results: Administration of dexamethasone resulted in a significant increase in absolute CLV and change of CLV relative to baseline tidal volume occurred (p