Complex of human neutrophil elastase with 1/2SLPI

The 1/2SLPI and HNE complex structure was solved at 1.7 Å resolution and compared with the interaction mechanism of elafin

Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study

Background: Reintubation is a common complication in critically ill patients requiring mechanical ventilation. Although reintubation has been demonstrated to be associated with patient outcomes, its time definition varies widely among guidelines and in the literature. This study aimed to determine the association between reintubation and patient outcomes as well as the consequences of the time elapsed between extubation and reintubation on patient outcomes. Methods: This was a multicenter retrospective cohort study of critically ill patients conducted between April 2015 and March 2021. Adult patients who underwent mechanical ventilation and extubation in intensive care units (ICUs) were investigated utilizing the Japanese Intensive Care PAtient Database. The primary and secondary outcomes were in-hospital and ICU mortality. The association between reintubation and clinical outcomes was studied using Cox proportional hazards analysis. Among the patients who underwent reintubation, a Cox proportional hazard analysis was conducted to evaluate patient outcomes according to the number of days from extubation to reintubation. Results: Overall, 184,705 patients in 75 ICUs were screened, and 1849 patients underwent reintubation among 48,082 extubated patients. After adjustment for potential confounders, multivariable analysis revealed a significant association between reintubation and increased in-hospital and ICU mortality (adjusted hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.359–1.700, and adjusted HR 1.325, 95% CI 1.076–1.633, respectively). Among the reintubated patients, 1037 (56.1%) were reintubated within 24 h after extubation, 418 (22.6%) at 24–48 h, 198 (10.7%) at 48–72 h, 111 (6.0%) at 72–96 h, and 85 (4.6%) at 96–120 h. Multivariable Cox proportional hazard analysis showed that in-hospital and ICU mortality was highest in patients reintubated at 72–96 h (adjusted HR 1.528, 95% CI 1.062–2.197, and adjusted HR 1.334, 95% CI 0.756–2.352, respectively; referenced to reintubation within 24 h). Conclusions: Reintubation was associated with a significant increase in in-hospital and ICU mortality. The highest mortality rates were observed in patients who were reintubated between 72 and 96 h after extubation. Further studies are warranted for the optimal observation of extubated patients in clinical practice and to strengthen the evidence for mechanical ventilation.Tanaka A., Shimomura Y., Uchiyama A., et al. Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study. Critical Care 27, 378 (2023); https://doi.org/10.1186/s13054-023-04668-3

Prediction Model of Extubation Outcomes in Critically Ill Patients: A Multicenter Prospective Cohort Study

Liberation from mechanical ventilation is of great importance owing to related complications from extended ventilation time. In this prospective multicenter study, we aimed to construct a versatile model for predicting extubation outcomes in critical care settings using obtainable physiological predictors. The study included patients who had been extubated after a successful 30 min spontaneous breathing trial (SBT). A multivariable logistic regression model was constructed to predict extubation outcomes (successful extubation without reintubation and uneventful extubation without reintubation or noninvasive respiratory support) using eight parameters: age, heart failure, respiratory disease, rapid shallow breathing index (RSBI), PaO2/FIO2, Glasgow Coma Scale score, fluid balance, and endotracheal suctioning episodes. Of 499 patients, 453 (90.8%) and 328 (65.7%) achieved successful and uneventful extubation, respectively. The areas under the curve for successful and uneventful extubation in the novel prediction model were 0.69 (95% confidence interval (CI), 0.62–0.77) and 0.70 (95% CI, 0.65–0.74), respectively, which were significantly higher than those in the conventional model solely using RSBI (0.58 (95% CI, 0.50–0.66) and 0.54 (95% CI, 0.49–0.60), p = 0.004 and <0.001, respectively). The model was validated using a bootstrap method, and an online application was developed for automatic calculation. Our model, which is based on a combination of generally obtainable parameters, established an accessible method for predicting extubation outcomes after a successful SBT

Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study

Abstract Background Reintubation is a common complication in critically ill patients requiring mechanical ventilation. Although reintubation has been demonstrated to be associated with patient outcomes, its time definition varies widely among guidelines and in the literature. This study aimed to determine the association between reintubation and patient outcomes as well as the consequences of the time elapsed between extubation and reintubation on patient outcomes. Methods This was a multicenter retrospective cohort study of critically ill patients conducted between April 2015 and March 2021. Adult patients who underwent mechanical ventilation and extubation in intensive care units (ICUs) were investigated utilizing the Japanese Intensive Care PAtient Database. The primary and secondary outcomes were in-hospital and ICU mortality. The association between reintubation and clinical outcomes was studied using Cox proportional hazards analysis. Among the patients who underwent reintubation, a Cox proportional hazard analysis was conducted to evaluate patient outcomes according to the number of days from extubation to reintubation. Results Overall, 184,705 patients in 75 ICUs were screened, and 1849 patients underwent reintubation among 48,082 extubated patients. After adjustment for potential confounders, multivariable analysis revealed a significant association between reintubation and increased in-hospital and ICU mortality (adjusted hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.359–1.700, and adjusted HR 1.325, 95% CI 1.076–1.633, respectively). Among the reintubated patients, 1037 (56.1%) were reintubated within 24 h after extubation, 418 (22.6%) at 24–48 h, 198 (10.7%) at 48–72 h, 111 (6.0%) at 72–96 h, and 85 (4.6%) at 96–120 h. Multivariable Cox proportional hazard analysis showed that in-hospital and ICU mortality was highest in patients reintubated at 72–96 h (adjusted HR 1.528, 95% CI 1.062–2.197, and adjusted HR 1.334, 95% CI 0.756–2.352, respectively; referenced to reintubation within 24 h). Conclusions Reintubation was associated with a significant increase in in-hospital and ICU mortality. The highest mortality rates were observed in patients who were reintubated between 72 and 96 h after extubation. Further studies are warranted for the optimal observation of extubated patients in clinical practice and to strengthen the evidence for mechanical ventilation

Analysis for Distinctive Activation Patterns of Pain and Itchy in the Human Brain Cortex Measured Using Near Infrared Spectroscopy (NIRS)

<div><p>Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area) were found to be clearly different between pain (<i>τ</i> = +18.7 sec) and itch (<i>τ</i> = +0.63 sec) stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing.</p></div

Cross correlation analysis of [HbO2] NIRS data from each channels at prefrontal area for pain stimulation.

<p>(A) Cross correlation function of [HbO2] traces from each channel against those from Ch7 for pain (left) was calculated. Average correlation coefficient was 0.62, with grey channels exhibiting a significant correlation (coefficient was over 0.7). (B) Representative data shown are from subject III. Note, the cross correlation analysis revealed that the correlation peak delay (<i>τ</i> = +19 sec for Ch1, +10.7 sec for Ch6, +3.4 sec for Ch2) was observed in pain stimulation. (C) Averages of the time-lag between well correlated channels (14 trials from 4 subjects) were calculated for pain stimulation. Data are shown as Mean ± SD. Difference in the lag time between Ch1 and Ch3 (none delay channel) was significant. ^**<i>P</i><0.01.</p

Dynamic NIR imaging after 7 random-intensity sequential pain stimulations.

<p>(A) The image collected during which the subject reported the most pain is shown for each of 3 subjects (I, II, and III). Among the three subjects according to the relationship between the stimulation and the NIRS response, subject M-1 (I) exhibited the smallest response, subject F-2 (II) exhibited a strong response, and subject M-2 (III) exhibited the clearest response in the frontal area. The rectangles indicate the location of the channels for which the dynamic pattern is shown in B: channels 10, 11, 12, and 13 in the frontal area, and channels 3 and 22 in the parietal area. (B) The dynamic pattern from channel 10 in the frontal area is shown in I-Frontal-10, II-Frontal-10, and III-Frontal-10. Channel 3 in the parietal area exhibited similar but smaller responses compared with those in the frontal area (I-Parietal-3, II-Parietal-3, and III-Parietal-3). Channel 22 recorded an unrelated pattern (I-Parietal-22, II-Parietal-22, and III-Parietal-22). Dynamic changes in other channels in the parietal area exhibited a similar response with intensities between those recorded in channel 3 and 22. The time interval between pain stimulations was 3 minutes. Arrows indicate the time points when the subjects reported the most pain, corresponded to the NIRS images shown in A. The different color bars represent pain stimulations of different intensities.</p

Cross correlation analysis of [HbO2] NIRS data from each channels at prefrontal area for itch stimulation.

<p>(A) Cross correlation function of [HbO2] traces from each channel against those from CH7 for pain (left) was calculated. Average correlation coefficient was 0.60, with grey channels exhibiting a significant correlation (coefficient was over 0.7). (B) Representative data shown are from subject III. No or small peak delay was observed in itch stimulation. (C) Averages of this lag time were calculated for itch stimulation (8 trials from 4 subjects). Data are shown as Mean ± SD.</p

Sequential responses of channel 10 in the frontal area to constant or increasing pain intensities.

<p>(A) Responses to sequential applications of constant pain stimulation. The yellow bar represents the pain stimulation intensity (2.1 N) and the blue bar represents the subjective pain score (VAS). Red, blue, and green traces of the dynamic response represent [HbO2], [HbR], and [HbT], respectively. The traces are from channel 10 in the frontal area of subject M-1. (B) Mean (n = 4 subjects) peak responses in [HbO2] in channel 10 in the frontal area. NIRS signals were significantly decreased when constant intensities of stimulation were given (**<i>p</i><0.05, vs the first response). Error bars represent SD. (C) Responses to applications of increased pain stimulation. The yellow bar represents the pain stimulation intensity (0.5 N, 1.0 N, 1.7 N, and 3.0 N) and the blue bar represents the subjective pain score (VAS). Red, blue, and green traces of the dynamic response represent [HbO2], [HbR], and [HbT], respectively. The traces are from channel 10 in the frontal area of subject M-1. (D) Mean (n = 4 subjects) peak responses in [HbO2] in channel10 in the frontal area when pain stimulation intensity was gradually increased (**<i>p</i><0.05, vs the response in the first stimulation (0.5 N)). Error bars represent SD.</p