Intratracheal instillation of polyacrylic acid induced pulmonary fibrosis with elevated transforming growth factor-ß1 and connective tissue growth factor.

We investigated the intratracheal instillation of Polyacrylic acid (PAA) in rats to determine if it would cause pulmonary disorders, and to see what factors would be associated with the pathological changes. Male F344 rats were intratracheally instilled with low (0.2 mg/rat) and high (1.0 mg/rat) doses of PAA. They were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after PAA exposure to examine inflammatory and fibrotic changes in the lungs. There was a persistent increase in the neutrophil count, lactate dehydrogenase (LDH) levels, cytokine-induced neutrophil chemoattractant (CINC) values in bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in lung tissue. Transforming growth factor-beta 1 (TGF-ß1), a fibrotic factor, showed a sustained increase in the BALF until 6 months after intratracheal instillation, and connective tissue growth factor (CTGF) in lung tissue was elevated at 3 days after exposure. Histopathological findings in the lung tissue showed persistent (more than one month) inflammation, fibrotic changes, and epithelial-mesenchymal transition (EMT) changes. There was also a strong correlation between TGF-ß1 in the BALF and, especially, in the fibrosis score of histopathological specimens. Intratracheal instillation of PAA induced persistent neutrophilic inflammation, fibrosis, and EMT in the rats' lungs, and TGF-ß1 and CTGF appeared to be associated with the persistent fibrosis.

The Effects of Endoplasmic Reticulum Stress via Intratracheal Instillation of Water-Soluble Acrylic Acid Polymer on the Lungs of Rats.

Polyacrylic acid (PAA), an organic chemical, has been used as an intermediate in the manufacture of pharmaceuticals and cosmetics. It has been suggested recently that PAA has a high pulmonary inflammatory and fibrotic potential. Although endoplasmic reticulum stress is induced by various external and intracellular stimuli, there have been no reports examining the relationship between PAA-induced lung injury and endoplasmic reticulum stress. F344 rats were intratracheally instilled with dispersed PAA (molecular weight: 269,000) at low (0.5 mg/mL) and high (2.5 mg/mL) doses, and they were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure. PAA caused extensive inflammation and fibrotic changes in the lungs' histopathology over a month following instillation. Compared to the control group, the mRNA levels of endoplasmic reticulum stress markers Bip and Chop in BALF were significantly increased in the exposure group. In fluorescent immunostaining, both Bip and Chop exhibited co-localization with macrophages. Intratracheal instillation of PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA with molecular weight 269,000 may lead to pulmonary disorder. Furthermore, the presence of endoplasmic reticulum stress in macrophages was suggested to be involved in PAA-induced lung injury.

Utility of human cytochrome P450 inhibition data in the assessment of drug-induced liver injury.

1. Drug-induced liver injury (DILI) is a major cause of drug development discontinuation and drug withdrawal from the market, but there are no golden standard methods for DILI risk evaluation. Since we had found the association between DILI and CYP1A1 or CYP1B1 inhibition, we further evaluated the utility of cytochrome P450 (P450) inhibition assay data for DILI risk evaluation using decision tree analysis.2. The inhibitory activity of drugs with DILI concern (DILI drugs) and no DILI concern (no-DILI drugs) against 10 human P450s was assessed using recombinant enzymes and luminescent substrates. The drugs were also subjected to cytotoxicity assays and high-content analysis using HepG2 cells. Molecular descriptors were calculated by alvaDesc.3. Decision tree analysis was performed with the data obtained as variables with or without P450-inhibitory activity to discriminate between DILI drugs and no-DILI drugs. The accuracy was significantly higher when P450-inhibitory activity was included. After the decision tree discrimination, the drugs were further discriminated with the P450-inhibitory activity. The results demonstrated that many false-positive and false-negative drugs were correctly discriminated by using the P450 inhibition data.4. These results suggest that P450 inhibition assay data are useful for DILI risk evaluation.

DIRECTEUR: transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion.

MOTIVATION: Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR-inducing small molecules is challenging. RESULTS: Here we present a novel in silico method, DIRECTEUR, to predict small molecules that replace TFs for DR. We extracted DR-characteristic genes using transcriptome profiles of cells in which DR was induced by TFs, and performed a variant of simulated annealing to explore small molecule combinations with similar gene expression patterns with DR-inducing TFs. We applied DIRECTEUR to predicting combinations of small molecules that convert fibroblasts into neurons or cardiomyocytes, and were able to reproduce experimentally verified and functionally related molecules inducing the corresponding conversions. The proposed method is expected to be useful for practical applications in regenerative medicine. AVAILABILITY AND IMPLEMENTATION: The code and data are available at the following link: https://github.com/HamanoLaboratory/DIRECTEUR.git.

Comparison of radial, dorsalis pedis, and posterior tibial arteries for ultrasound-guided arterial catheterisation with dynamic needle tip positioning in paediatric patients: a randomised controlled trial.

BACKGROUND: Arterial catheterisation in children can be challenging and time-consuming. We aimed to compare the success rates of ultrasound-guided arterial catheterisation utilising the short-axis out-of-plane approach with dynamic needle tip positioning in the radial, dorsalis pedis, and posterior tibial arteries in paediatric patients. We also examined the factors influencing the catheterisation success using dynamic needle tip positioning. METHODS: Paediatric patients (aged <3 yr) undergoing cardiac surgery were randomly assigned to three groups based on puncture sites: radial artery (Group R), dorsalis pedis artery (Group D), and posterior tibial artery (Group P). The first-attempt and overall success rates of arterial catheterisation were compared, followed by multiple logistic regression analysis (dependent variable: first-attempt success; independent variables: body weight, diameter and depth of the artery, targeted artery, and trisomy 21). RESULTS: The study included 270 subjects (n=90 per group). There was no significant difference in the first-attempt (Group R: 82%, Group D: 76%, and Group P: 81%) and overall success rates (Group R: 94%, Group D: 93%, and Group P: 91%) among the three groups. The diameter of the artery (per 0.1 mm) (odds ratio: 1.32, 95% confidence interval: 1.09-1.60) and trisomy 21 (odds ratio: 0.43, 95% confidence interval: 0.20-0.92) were independent predictors of first-attempt success or failure. CONCLUSION: The first-attempt and overall success rates of arterial catheterisation of the dorsalis pedis and posterior tibial arteries were not inferior to those in the radial artery when using dynamic needle tip positioning. These two lower extremity peripheral arteries present viable alternative catheterisation sites in paediatric patients. CLINICAL TRIAL REGISTRATION: UMIN000042847.

Quantifying the effect of isolation and negative certification on COVID-19 transmission.

Isolation of close contact people and negative test certification are used to manage the spread of new coronavirus infections worldwide. These effectively prevent the spread of infection in advance, but they can lead to a decline in socio-economic activity. Thus, the present study quantified the extent to which isolation and negative test certification respectively reduce the risk of infection. To this end, a discrete-time SEIR model was used as the infectious disease model, and equations for calculating the conditional probability of non-infection status given negative test results on two different days were derived. Then the respective non-infection probabilities with two negative PCR test results, and with one negative PCR test result and one antigen test result, were quantified. By substituting initial parameters of the SEIR model into these probabilities, the present study revealed the following: (1) isolating close contact individuals can reduce by [Formula: see text] the risk of infection during the first 5 days, but five more days are needed to reduce the risk [Formula: see text] more, and seven more days to reduce the risk [Formula: see text] more; and (2) if an individual with a negative PCR test result has a negative antigen test result the next day, then his or her infection probability is between 0.6 and [Formula: see text]. Our results show that 5-day isolation has a proportionally greater effect on risk reduction, compared to longer isolation; and thus, if an isolation period of longer than 5 days is contemplated, both the risk reduction and the negative effects from such increased isolation should be considered. Regarding negative test certification, our results provide those in managerial positions, who must decide whether to accept the risk and hold mass-gathering events, with quantitative information that may be useful in their decision-making.

Efficacy of perioperative prophylactic administration of corticosteroids in pediatric cardiac surgeries using cardiopulmonary bypass: a systematic review with meta-analysis.

An updated systematic review with meta-analysis comparing perioperative prophylactic administration of corticosteroids with placebo in pediatric cardiac surgeries using cardiopulmonary bypass was conducted. The Cochrane Central Register of Controlled Trials and MEDLINE (via PubMed) were searched for relevant randomized controlled trials published between January 1, 2000, and February 14, 2023. The primary outcome was postoperative in-hospital mortality. Secondary outcomes were duration of mechanical ventilation, length of intensive care unit and hospital stay, postoperative low cardiac output syndrome, and adverse events. A total of 11 studies were included in the meta-analysis. Corticosteroid administration did not decrease postoperative in-hospital mortality compared with placebo (relative risk, 0.69; 95% confidence interval, 0.40-1.17). Subgroup analyses according to the type of corticosteroids and neonates revealed that corticosteroids did not decrease postoperative in-hospital mortality. In the trial sequential analysis, the last point in the z-curve was within the futility borders. Although the duration of mechanical ventilation (mean difference, -5.54 h; 95% confidence interval (CI), -9.75 - -1.34) and incidence of low cardiac output syndrome (relative risk, 0.75; 95% CI, 0.59 - 0.96) decreased with corticosteroid administration, it did not affect the length of intensive care unit (mean difference, -0.28 days; 95% CI, -0.74 - 0.17) and hospital stay (mean difference, -0.59 days; 95% CI, -1.31 - 0.14). In conclusion, perioperative prophylactic corticosteroid administration in pediatric cardiac surgeries using cardiopulmonary bypass did not decrease postoperative in-hospital mortality compared with placebo. According to the trial sequential analysis results, additional randomized controlled trials assessing mortality are not required. PROSPERO REGISTRY NUMBER: CRD 42023391789.

Ultrasound-Guided Short-Axis Out-of-Plane Approach With or Without Dynamic Needle-Tip Positioning for Peripheral Venous Catheterization in Pediatric Patients: A Systematic Review With Network Meta-Analysis.

OBJECTIVES: To compare the efficacy of the ultrasound-guided approach with and without dynamic needle-tip positioning and the palpation technique regarding success for peripheral venous catheterization in children. DESIGN: A systematic review with network meta-analysis. SETTING: Databases of MEDLINE (via PubMed) and Cochrane Central Register of Controlled Trials. PARTICIPANTS: Patients (<18 years) undergoing peripheral venous catheter insertion. INTERVENTIONS: Randomized clinical trials were included to compare the following techniques: the ultrasound-guided short-axis out-of-plane approach with dynamic needle-tip positioning, the approach without dynamic needle-tip positioning, and the palpation technique. MEASUREMENTS AND MAIN RESULTS: The outcomes were first-attempt and overall success rates. Eight studies were included in the qualitative analyses. According to the estimate of network comparison, dynamic needle-tip positioning was associated with higher first-attempt (risk ratio [RR] 1.67; 95% CI 1.33-2.09) and overall success rates (RR 1.25; 95% CI 1.08-1.44) than palpation. The approach without dynamic needle-tip positioning was not associated with higher first-attempt (RR 1.17; 95% CI 0.91-1.49) and overall success rates (RR 1.10; 95% CI 0.90-1.33) than palpation. Compared to the approach without dynamic needle-tip positioning, dynamic needle-tip positioning was associated with a higher first-attempt success rate (RR 1.43; 95% CI 1.07-1.92), but not a higher overall success rate (RR 1.14; 95% CI 0.92-1.41). CONCLUSIONS: Dynamic needle-tip positioning is efficacious for peripheral venous catheterization in children. It would be better to include dynamic needle-tip positioning for the ultrasound-guided short-axis out-of-plane approach.

New intra-conduit thrombus detected using transesophageal echocardiography immediately after weaning from cardiopulmonary bypass during the Fontan procedure: a case report.

This study reports a case wherein a new thrombus was detected by transesophageal echocardiography in the conduit during extracardiac conduit Fontan procedure. Immediately after weaning from the cardiopulmonary bypass and administration of protamine, a thrombus was noted in the conduit by transesophageal echocardiography. Since the patient was hemodynamically stable, anticoagulation therapy was initiated after admission to the intensive care unit. One week post-surgery, imaging results showed residual thrombus, but the patient was safely discharged. Even during Fontan procedure, careful observation with transesophageal echocardiography is important because of the possibility of thrombus formation in the conduit.

Ultrasound-guided short-axis out-of-plane approach with or without dynamic needle tip positioning for arterial line insertion in children: A systematic review with network meta-analysis.

The efficacy of the short-axis out-of-plane (SA-OOP) approach with and without dynamic needle tip positioning (DNTP) remains unclear. This systematic review with network meta-analysis aimed to compare the success rate of arterial line insertion in children using the SA-OOP approach with and without DNTP and the palpation technique. We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials. We included randomized controlled trials that compared two of the following techniques for arterial line insertion in children: (1) the ultrasound-guided SA-OOP approach with DNTP; (2) the ultrasound-guided SA-OOP approach without DNTP; and (3) the palpation technique. A network meta-analysis was performed. The outcomes were first-attempt and overall success rates. Eight studies were finally included in this network meta-analysis. The ultrasound-guided SA-OOP approach with DNTP was associated with increased first-attempt (relative risk RR = 3.45 [95% confidence interval (CI) 2.51-4.74]) and overall success rates (RR = 1.81 [1.41-2.32]) when compared with palpation. The same approach performed without DNTP was also associated with increased first-attempt (RR = 1.96 [1.59-2.42]) and overall success rates (RR = 1.25 [1.05-1.49]) when compared with palpation. The ultrasound-guided SA-OOP approach with DNTP was associated with increased first-attempt (RR = 1.76 [1.26-2.44]) and overall success rates (RR = 1.45 [1.10-1.91]) when compared with the same approach performed without DNTP. DNTP should be performed during the ultrasound-guided SA-OOP approach for arterial line insertion in children, as this can help increase first attempt and overall success rates.

Influence of maternal position during combined spinal-epidural anesthesia for labor analgesia on technical difficulties and complications.

PURPOSE: Generally, combined spinal-epidural anesthesia (CSEA) for labor analgesia is performed in the lateral or sitting position; however, only few studies have investigated the effect of maternal position on labor analgesia induction. We aimed to retrospectively assess the influence of maternal position on induction time and complications. METHODS: We retrospectively analyzed anesthetic and medical records regarding labor analgesia in 201 parturients treated between January 2019 and November 2019. Patients were classified into 2 groups based on their position (sitting or lateral) during induction. The primary outcome was the time required for CSEA induction. We compared 2 groups on the primary outcome and the occurrences of other complications during CSEA induction using hyperbaric bupivacaine. Moreover, we performed multiple linear regression analysis to identify independent factors associated with induction time. RESULTS: There was no significant between-group difference in the time required for induction. Multiple linear regression analysis revealed an independent association of the distance from the skin to the epidural space with the time required for induction. The lateral group had a significantly higher incidence of paresthesia than the sitting group (P = 0.028). The lateral group had a significantly higher ephedrine requirement (P < 0.001) than the sitting group. CONCLUSION: Maternal position was not associated with the time required for CSEA induction. However, the sitting group had a lower paresthesia occurrence and ephedrine requirement than the lateral group. Other technical complications were not associated with maternal position during CSEA induction.

Crosslinked Structure of Polyacrylic Acid Affects Pulmonary Fibrogenicity in Rats.

We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.

Incidence of catheter-related bloodstream infections following ultrasound-guided central venous catheterization: a systematic review and meta-analysis.

BACKGROUND: Ultrasonographic guidance is widely used for central venous catheterization. Several studies have revealed that ultrasound-guided central venous catheterization increases the rate of success during the first attempt and reduces the procedural duration when compared to the anatomical landmark-guided insertion technique, which could result in protection from infectious complications. However, the effect of ultrasound-guided central venous catheterization on catheter-related bloodstream infections remains unclear. We aimed to conduct a systematic review and meta-analysis to evaluate the value of ultrasound guidance in preventing catheter-related bloodstream infections and catheter colonization associated with central venous catheterization. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE (via PubMed) were searched up to May 9, 2022 for randomized controlled trials (RCTs) comparing ultrasound-guided and anatomical landmark-guided insertion techniques for central venous catheterization. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool for RCTs. A meta-analysis was performed for catheter-related bloodstream infections and catheter colonization, as primary and secondary outcomes, respectively. RESULTS: Four RCTs involving 1268 patients met the inclusion criteria and were analyzed. Ultrasound-guided central venous catheterization was associated with a slightly lower incidence of catheter-related bloodstream infections (risk ratio, 0.46; 95% confidence interval [CI], 0.16-1.32) and was not associated with a lower incidence of catheter colonization (risk ratio, 1.36; 95% CI, 0.57-3.26). CONCLUSION: Ultrasound-guided central venous catheterization might reduce the incidence of catheter-related bloodstream infections. Additional RCTs are necessary to further evaluate the value of ultrasound guidance in preventing catheter-related bloodstream infections with central venous catheterization.

Combined short-axis out-of-plane and long-axis in-plane approach versus long-axis in-plane approach for ultrasound-guided central venous catheterization in infants and small children: A randomized controlled trial.

The ultrasound-guided long-axis in-plane approach for central venous catheterization in infants and small children can prevent posterior wall penetration. The combined short-axis out-of-plane and long-axis in-plane approach reportedly prevents such penetration in adults. To test the hypothesis of non-inferiority of the combined approach to the long-axis in-plane approach, we compared the two approaches in infants and small children. Patients were randomized based on whether they underwent ultrasound-guided internal jugular vein catheterization using the combined or long-axis in-plane approach. Posterior wall penetration rates, first-attempt success rates, overall success rates within 20 min; scanning, puncture, and procedure durations; and number of attempts were compared between the groups. In the combined and long-axis in-plane groups (n = 55 per group), the posterior wall penetration rates were 5.5% (3/55) and 3.6% (2/55) (P = 0.65), the first-attempt success rates were 94.5% (52/55) and 92.7% (51/55) (P = 0.70), and the overall success rates within 20 min were 100% (55/55) and 98.2% (54/55) (P = 0.32), respectively. In the combined and long-axis in-plane groups, the median (interquartile range) scanning durations were 21 (16.5-34.8) s and 47 (29.3-65) s (P<0.0001), the puncture durations were 114 (83-170) s and 74 (52.3-117.3) s (P = 0.0002), and the procedure durations were 141 (99-97.8) s and 118 (88.5-195.5) s (P = 0.14), respectively. The median number of attempts was 1 (interquartile range: 1-1, range: 1-3) in both groups (P = 0.72). Similar to the long-axis in-plane approach, the combined approach for internal jugular vein catheterization prevented posterior wall penetration in infants and small children. Trial registration: This trial was registered before patient enrollment in the University Hospital Medical Information Network Clinical Trials Registry, registration number UMIN000039387 (https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000044907).

Small compound-based direct cell conversion with combinatorial optimization of pathway regulations.

MOTIVATION: Direct cell conversion, direct reprogramming (DR), is an innovative technology that directly converts source cells to target cells without bypassing induced pluripotent stem cells. The use of small compounds (e.g. drugs) for DR can help avoid carcinogenic risk induced by gene transfection; however, experimentally identifying small compounds remains challenging because of combinatorial explosion. RESULTS: In this article, we present a new computational method, COMPRENDRE (combinatorial optimization of pathway regulations for direct reprograming), to elucidate the mechanism of small compound-based DR and predict new combinations of small compounds for DR. We estimated the potential target proteins of DR-inducing small compounds and identified a set of target pathways involving DR. We identified multiple DR-related pathways that have not previously been reported to induce neurons or cardiomyocytes from fibroblasts. To overcome the problem of combinatorial explosion, we developed a variant of a simulated annealing algorithm to identify the best set of compounds that can regulate DR-related pathways. Consequently, the proposed method enabled to predict new DR-inducing candidate combinations with fewer compounds and to successfully reproduce experimentally verified compounds inducing the direct conversion from fibroblasts to neurons or cardiomyocytes. The proposed method is expected to be useful for practical applications in regenerative medicine. AVAILABILITY AND IMPLEMENTATION: The code supporting the current study is available at the http://labo.bio.kyutech.ac.jp/~yamani/comprendre. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation.

BACKGROUND: We conducted intratracheal instillations of different molecular weights of polyacrylic acid (PAA) into rats in order to examine what kinds of physicochemical characteristics of acrylic acid-based polymer affect responses in the lung. METHODS: F344 rats were intratracheally exposed to a high molecular weight (HMW) of 598 thousand g/mol or a low molecular weight (LMW) of 30.9 thousand g/mol PAA at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months post exposure. RESULTS: HMW PAA caused persistent increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 3 months and 6 months following instillation. On the other hand, LMW PAA caused only transient increases in neutrophil influx, CINC in BALF, and HO-1 in the lung tissue from 3 days to up to 1 week or 1 month following instillation. Histopathological findings of the lungs demonstrated that the extensive inflammation and fibrotic changes caused by the HMW PAA was greater than that in exposure to the LMW PAA during the observation period. CONCLUSION: HMW PAA induced persistence of lung disorder, suggesting that molecular weight is a physicochemical characteristic of PAA-induced lung disorder.

ARDS Clinical Practice Guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

ARDS clinical practice guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Diffusion-Weighted Imaging Hyperintensities in Acute and Subacute-Phase Intracerebral Hemorrhage.

OBJECTIVE: Diffusion-weighted imaging hyperintensities are observed in intracerebral hemorrhage patients at times and might be associated with unfavorable functional outcomes. However, the suitable time to evaluate diffusion-weighted imaging hyperintensities to influence stroke outcome remains unclear. This study investigated the associations between acute and sub-acute diffusion-weighted imaging hyperintensities and functional outcomes among patients with acute intracerebral hemorrhage. METHODS: Diffusion-weighted imaging hyperintensities were evaluated within 24 h (acute phase) and at 14 ± 5 days (sub-acute phase). An unfavorable functional outcome was a score of 5-6 on the modified Rankin Scale at 3 months. RESULTS: Among 268 intracerebral hemorrhage patients, diffusion-weighted imaging hyperintensities in the acute phase were observed in 32 (11.9%). Among 227 patients who underwent a second magnetic resonance imaging in the sub-acute phase, diffusion-weighted imaging hyperintensities were observed in 57 (25.1%). Multivariable analysis revealed that the baseline intracerebral hemorrhage volume, history of stroke, and severe white matter lesions were associated with sub-acute diffusion-weighted imaging hyperintensities. The patients with unfavorable outcomes (n = 37) had a higher frequency of sub-acute diffusion-weighted imaging hyperintensities than those without (n = 190) (51.4% vs. 20.0%, P < 0.001); the frequencies of acute diffusion-weighted imaging hyperintensities were not significantly different between the groups (13.5% vs. 10.0%, P = 0.559). Sub-acute diffusion-weighted imaging hyperintensities were independently associated with unfavorable outcomes after adjusting for confounding factors (Odds Ratio, 3.35, 95% CI 1.20-9.35, P = 0.021). CONCLUSION: The rate of sub-acute diffusion-weighted imaging hyperintensities was higher than acute diffusion-weighted imaging hyperintensities among acute intracerebral hemorrhage patients and likely to be associated with unfavorable outcomes.