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.

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.

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.

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.

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.

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.

Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury.

Drug-induced liver injury (DILI) is one of the major causes for the discontinuation of drug development and withdrawal of drugs from the market. Since it is known that reactive metabolite formation and being substrates or inhibitors of cytochrome P450s (P450s) are associated with DILI, we systematically investigated the association between human P450 inhibition and DILI. The inhibitory activity of 266 DILI-positive drugs (DILI drugs) and 92 DILI-negative drugs (no-DILI drugs), which were selected from Liver Toxicity Knowledge Base (US Food and Drug Administration), against 8 human P450 forms was assessed using recombinant enzymes and luminescent substrates, and the threshold values showing the highest balanced accuracy for DILI discrimination were determined for each P450 enzyme using receiver operating characteristic analyses. The results showed that among the P450s tested, CYP1A1 and CYP1B1 were inhibited by DILI drugs more than no-DILI drugs with a statistical significance. We found that 91% of drugs that showed inhibitory activity greater than the threshold values against CYP1A1 or CYP1B1 were DILI drugs. The results of internal 5-fold cross-validation confirmed the usefulness of CYP1A1 and CYP1B1 inhibition data for the threshold-based discrimination of DILI drugs. Although the contribution of these P450s to drug metabolism in the liver is considered minimal, our present findings suggest that the assessment of CYP1A1 and CYP1B1 inhibition is useful for screening DILI risk of drug candidates at the early stage of drug development.

Long-Axis In-Plane Approach Versus Short-Axis Out-of-Plane Approach for Ultrasound-Guided Central Venous Catheterization in Pediatric Patients: A Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to compare the occurrence of posterior wall puncture between the long-axis in-plane and the short-axis out-of-plane approaches in a randomized controlled trial of pediatric patients who underwent cardiovascular surgery under general anesthesia. DESIGN: Prospective randomized controlled trial. SETTING: Operating room of Osaka Women's and Children's Hospital. PATIENTS: Pediatric patients less than 5 years old who underwent cardiovascular surgery. INTERVENTIONS: Ultrasound-guided central venous catheterization using the long-axis in-plane approach and short-axis out-of-plane approach. MEASUREMENTS AND MAIN RESULTS: The occurrence of posterior wall puncture was compared between the long-axis in-plane and short-axis out-of-plane approaches for ultrasound-guided central venous catheterization. Patients were randomly allocated to a long-axis group or a short-axis group and underwent ultrasound-guided central venous catheterization in the internal jugular vein using either the long-axis in-plane approach (long-axis group) or the short-axis out-of-plane approach (short-axis group). After exclusion, 97 patients were allocated to the long-axis (n = 49) or short-axis (n = 48) groups. Posterior wall puncture rates were 8.2% (4/49) and 39.6% (19/48) in the long-axis and short-axis groups, respectively (relative risk, 0.21; 95% CI, 0.076-0.56; p = 0.0003). First attempt success rates were 67.3% (33/49) and 64.6% (31/48) in the long-axis and short-axis groups, respectively (relative risk, 1.04; 95% CI, 0.78-1.39; p = 0.77). Overall success rates within 20 minutes were 93.9% (46/49) and 93.8% (45/48) in the long-axis and short-axis groups, respectively (relative risk, 0.99; 95% CI, 0.90-1.11; p = 0.98). CONCLUSIONS: The long-axis in-plane approach for ultrasound-guided central venous catheterization is a useful technique for avoiding posterior wall puncture in pediatric patients, compared with the short-axis out-of-plane approach.

Combined Approach Versus 2 Conventional Approaches in Ultrasound-Guided Central Venous Catheterization: A Randomized Controlled Trial.

OBJECTIVE: The authors compared the occurrence of posterior wall puncture using the short-axis out-of-plane and long-axis in-plane approaches with that using the combined short-axis-and-long-axis approach that the authors previously showed to be effective in observational and manikin studies. DESIGN: Randomized controlled study. SETTING: Single tertiary institution. PARTICIPANTS: One hundred twenty patients who underwent cardiac or vascular surgery under general anesthesia. INTERVENTIONS: The patients were divided randomly into combined short-axis-and-long-axis (n = 40), short-axis out-of-plane (SA-OOP) (n = 40), and long-axis in-plane (LA-IP) (n = 40) groups and received ultrasound-guided central venous catheterization at the right internal jugular vein. MEASUREMENTS AND MAIN RESULTS: Successful guidewire insertion without posterior wall puncture was performed in 40 patients (100%) in the combined short-axis-and-long-axis approach group, 28 (70%) in the short-axis out-of-plane approach group, and 38 (95%) in the LA-IP approach group (combined short-axis-and-long-axis v SA-OOP, p = 0.0002 [relative risk = 1.43; 95% CI: 1.17-1.75]; combined short-axis-and-long-axis v LA-IP, p = 0.49 [relative risk = 1.05; 95% CI: 0.98-1.13]). Procedure durations were 28.5 (24.1-36.4) seconds in the combined short-axis-and-long-axis group, 31.7 (24.4-40.6) seconds in the SA-OOP group, and 24.3 (20.8-32.1) seconds in the long-axis in-plane group (combined short-axis-and-long-axis v SA-OOP, p = 0.53; combined short-axis-and-long-axis v LA-IP, p = 0.044). CONCLUSION: The combined short-axis-and-long-axis approach for ultrasound-guided central venous catheterization had a lower posterior wall puncture rate than the SA-OOP approach, but there was no significant difference with the long-axis in-plane approach.

Transient severe distributive shock due to early dumping syndrome: a case report.

BACKGROUND: Early dumping syndrome characterized by palpitation, dizziness, cold sweat, feebleness, and abdominal symptoms, occurs within 30 minutes after meals in patients who have undergone gastrectomy. This case report describes the case of a patient who presented with severe distributive shock due to early dumping syndrome; he recovered within a few hours after massive fluid infusion and vasopressor administration. CASE PRESENTATION: Our patient was a 68-year-old Japanese man who underwent total gastrectomy for gastric cancer and was diagnosed as having late dumping syndrome. On admission, he developed severe shock and was treated with massive fluid administration. Based on the history of the present illness, past medical history, normal findings of blood chemistry test, transient course, and Sigtad score, which helps diagnose dumping syndrome, early dumping syndrome was considered the cause of severe distributive shock. CONCLUSIONS: Early dumping syndrome can cause severe shock requiring massive fluid infusion and vasopressor administration. It should be considered a cause of severe distributive shock in patients who have undergone gastrectomy.

[Rapidly deteriorated lobar intracerebral hemorrhages: possible association of varicella zoster virus-vasculopathy].

A 75-year-old man having dementia and lifestyle related diseases developed a lobar intracerebral hemorrhage (LICH) in the left parietal and a small cerebellar infarction in the left occipital lobe. Many micro bleeds (MB) due to cerebral amyloid angiopathy (CAA) in the subcortical areas and multiple vascular stenosis were also found by MRI and MRA. He developed herpes zoster in his buttocks on day 6 of hospitalization and complicated with varicella zoster virus (VZV) meningitis with positive for VZV-DNA in the cerebrospinal fluid. Subsequently, LICHs occurred in the left frontal lobe and in the right parietal lobe for a short period of time and died on the day 18. We speculated that the repeating hemorrhages was primarily caused by VZV vasculopathy and additionally the subcortical MBs increased the hemorrhagic risk. The relationship between VZV vasculopathy and CAA should be studied in the future.

Tracheal injury detected immediately after median sternotomy by inexperienced surgeons: two case reports.

BACKGROUND: Although median sternotomy is standard during cardiac surgery, the procedure is associated with a risk of injury to mediastinal organs. Here, we discuss two cases of tracheal injury following median sternotomy during cardiac surgery. CASE PRESENTATION: Ventilation failure occurred in a 78-year-old Japanese man and a 71-year-old Japanese man after median sternotomy, and tracheal injury was identified. The sites of injury were directly repaired and covered with mediastinal fat tissue, following which ventilation was successful. The burn-like deposits observed at the site of tracheal injury and on the removed endotracheal tube support the notion that the injuries in our patients were caused by electrocautery prior to median sternotomy. In one case, short sternotracheal distance may have contributed to tracheal injury during post-sternal manipulation. In both cases, the relative inexperience of both surgeons also supports the suspected cause of injury. CONCLUSIONS: Tracheal injury represents a potential complication following median sternotomy, especially when performed by inexperienced surgeons or in cases of short sternotracheal distance. Anesthesiologists should consider this rare yet potentially lethal complication.

Retraction:Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: A case presented brain calcification and corpus callosum atrophy from over 10 years before the onset of dementia.

This article was retracted by author's request.

Clinical, epidemiological and etiological studies of adult aseptic meningitis: Report of 11 cases with varicella zoster virus meningitis.

We treated 11 cases (52.7 ± 14.9 years, all male) with varicella zoster virus (VZV) meningitis and 437 cases with adult aseptic meningitis from 2004 to 2016. The incidence rate of adult VZV meningitis in the cases with aseptic meningitis was 2.5%. Herpes zoster infections are reported to have occurred frequently in summer and autumn. VZV meningitis also occurred frequently in the similar seasons, in our patients. The diagnoses were confirmed in 9 cases with positive VZV-DNA in the cerebrospinal fluid and in 2 cases with high VZV-IgG indexes (> 2.0). For diagnosis confirmation, the former test was useful for cases within a week of disease onset, and the latter index was useful for cases after a week of disease onset. Zoster preceded the meningitis in 8 cases, while the meningitis preceded zoster in 1 case, and 2 cases did not have zoster (zoster sine herpete). Two patients were carriers of the hepatitis B virus, 1 patient was administered an influenza vaccine 4 days before the onset of meningitis, and 1 patient was orally administered prednisolone for 2 years, for treatment. Their immunological activities might have been suppressed. The neurological complications included trigeminal neuralgia, facial palsy (Ramsay Hunt syndrome), glossopharyngeal neuralgia, and Elsberg syndrome. Because the diseases in some patients can become severe, they require careful treatment.

Repetitive postoperative extubation failure and cardiac arrest due to laryngomalacia after general anesthesia in an elderly patient: a case report.

The authors report a case involving an elderly patient who experienced repetitive perioperative cardiac arrest caused by laryngomalacia. The patient underwent surgery under general anesthesia; however, 2 h after initial extubation, he experienced cardiopulmonary arrest. Return of spontaneous circulation was achieved by immediate resuscitation. Four hours later, a second extubation was performed without any neurological complications. However, 2 h later, he experienced cardiopulmonary arrest again. Immediately after the third extubation, 12 h after the second cardiopulmonary arrest, fiberoptic laryngoscopy revealed laryngomalacia. His respiratory condition stabilized after emergent tracheostomy. Laryngomalacia should be considered even in adult cases when signs of upper airway obstruction manifest after extubation.

Adult-onset neuronal intranuclear inclusion disease presented transient global amnesia-a case report.

A 65-year-old man had a transient amnesia for about 3 hours. Similar symptoms appeared three years ago. He did not manifest dementia, cerebellar ataxia and involuntary movements. Peripheral neuropathy was observed by the neurophysiological examinations. Diffusion weighted image showed high intensity signal in the area of the corticomedullary junction of the frontal to parietal lobes and immunohistochemical studies of biopsied skin revealed many intranuclear inclusion bodies. Adult-onset neuronal intranuclear inclusion disease was diagnosed. As there was no similar member in his family, he was a sporadic case. Clinical characteristics of his amnesia was fulfilled with the criteria of transient global amnesia (TGA). The transient disturbance of limbic system was suspected.

[Survey of patients at the preoperative evaluation clinic (PAC)].

Anesthesia requires informed consent because it is an invasive procedure with high risks. We carried out a questionnaire study in 1,050 patients who were seen at the preoperative evaluation clinic (PAC). Patients who heard about PAC for the first time accounted for 77.9% in spite of having experienced anesthesia. Many patients were provided with the information about anesthesia the day before surgery and medication control and additional checking were difficult to carry out. Some patients (34.2%) were told about anesthesia with no attendant. In particular, about complications of anesthesia, many patients did not remember what the specific explanation had been offered in the past. We thought that it is necessary to explain the complications of anesthesia even if it is the second anesthesia for patients.