Efficacy and safety of enteral supplementation with high-dose vitamin D in critically ill patients with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.

Soluble TREM-like Transcript-1 Acts as a Damage-Associated Molecular Pattern through the TLR4/MD2 Pathway Contributing to Immune Dysregulation during Sepsis.

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.

The Feasibility of a Machine Learning Approach in Predicting Successful Ventilator Mode Shifting for Adult Patients in the Medical Intensive Care Unit.

Background and Objectives: Traditional assessment of the readiness for the weaning from the mechanical ventilator (MV) needs respiratory parameters in a spontaneous breath. Exempted from the MV disconnecting and manual measurements of weaning parameters, a prediction model based on parameters from MV and electronic medical records (EMRs) may help the assessment before spontaneous breath trials. The study aimed to develop prediction models using machine learning techniques with parameters from the ventilator and EMRs for predicting successful ventilator mode shifting in the medical intensive care unit. Materials and Methods: A retrospective analysis of 1483 adult patients with mechanical ventilators for acute respiratory failure in three medical intensive care units between April 2015 and October 2017 was conducted by machine learning techniques to establish the predicting models. The input candidate parameters included ventilator setting and measurements, patients' demographics, arterial blood gas, laboratory results, and vital signs. Several classification algorithms were evaluated to fit the models, including Lasso Regression, Ridge Regression, Elastic Net, Random Forest, Extreme Gradient Boosting (XGBoost), Support Vector Machine, and Artificial Neural Network according to the area under the Receiver Operating Characteristic curves (AUROC). Results: Two models were built to predict the success shifting from full to partial support ventilation (WPMV model) or from partial support to the T-piece trial (sSBT model). In total, 3 MV and 13 nonpulmonary features were selected for the WPMV model with the XGBoost algorithm. The sSBT model was built with 8 MV and 4 nonpulmonary features with the Random Forest algorithm. The AUROC of the WPMV model and sSBT model were 0.76 and 0.79, respectively. Conclusions: The weaning predictions using machine learning and parameters from MV and EMRs have acceptable performance. Without manual measurements, a decision-making system would be feasible for the continuous prediction of mode shifting when the novel models process real-time data from MV and EMRs.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

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 < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. 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.

An Electronic Handover System to Improve Information Transfer for Surgical Patients.

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.