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.

A review of four cases of COVID-19 medically evacuated by ambulance jet from Asian countries to Japan: Importance of strict infection control measures against multidrug-resistant organisms.

International medical evacuation, which is an option to receive better medical care for travelers with emergencies staying in low- and middle-income countries, has been more challenging during the coronavirus disease 2019 (COVID-19) pandemic. We herein discuss our experience with four Japanese patients with COVID-19 who required medical evacuation from Asian countries during the pandemic. Of these, none of the patients had received a COVID-19 vaccine; three patients needed oxygen therapy on admission to our hospital; and one patient died due to respiratory failure on day 50 after hospitalization. It was observed that multidrug-resistant organisms were colonized in two patients after obtaining culture results based on active surveillance. Strict infection control measures against multidrug-resistant organisms should be implemented during the care of patients with COVID-19 who require medical evacuation from high-risk countries. Further, it is important to communicate timely updates regarding the patient's condition with travel assistance agencies as the patient's condition may rapidly change during the course of arranging the evacuation.

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.

Estimating body weight of pigs from posture analysis using a depth camera.

A noninvasive method for estimating the body weight (BW) of a pig considering its posture using a low-cost depth camera (Kinect v2) was proposed. A total of 150 pigs were used, and 738 depth images (point clouds) were obtained for them. The pig "volume" was calculated from the pig point cloud, and it was found to have a very high correlation to BW. To evaluate the posture of a pig quantitatively, seven posture angles were calculated based on the "spine" extracted from a pig point cloud. We found the posture angles representing the height of the head position correlated with the accuracy of BW estimation using the "volume." Based on this finding, we proposed an "adjusted volume," which was adjusted based on the relationship between the posture angles and the estimation error. The BW of pigs was estimated using the simple regression model with the "adjusted volume," and the MAPE and RMSPE were 4.87% and 6.13%, respectively. The accuracy of the suggested model was similar to that of the volume-based estimation models of other studies that used only data with an appropriate pig posture for BW estimation.

Early diagnosis of Cryptococcus neoformans var. grubii meningitis using multiplex PCR assay in an immunocompetent patient.

Cryptococcosis is an invasive fungal infection that mainly affects the lungs and central nervous system. While patients with cell-mediated immunodeficiency are at high risk of developing cryptococcosis, there have been increasing reports of cryptococcosis in immunocompetent individuals with no underlying conditions. Herein, we report a case of cryptococcal meningitis in a 55-year-old apparently immunocompetent man with a history of heavy alcohol consumption. Although the patient was initially treated for tuberculous meningitis and varicella-zoster virus induced vasculopathy due to a history of exposure to tuberculosis and a presence of stroke, a multiplex polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) identified Cryptococcus species unexpectedly, enabling swift treatment and a favorable clinical outcome. The multiplex PCR assay, which can identify multiple pathogens simultaneously and instantly, may lead to early diagnosis and treatment by detecting unanticipated pathogens. Furthermore, the strain was identified through multilocus sequence typing (MLST) analysis as Cryptococcus neoformans var. grubii, Sequence Type 5, molecular type: VNI. Although simplified microbial identification techniques such as mass spectrometry have recently been developed, molecular biological assays are still essential for the accurate identification of infectious strains.

The profile of patients hospitalized with COVID-19 under the Quarantine Act in a designated hospital near an international airport in Japan.

The Japanese Government has implemented quarantine measures in response to the COVID-19 pandemic. Individuals testing positive at the airport's quarantine office were lodged either in a designated hotel or hospital under the Quarantine Act. The aim of this study is to describe the management of patients with COVID-19 admitted under the Quarantine Act and to evaluate its impact on medical resources. Data were retrospectively collected, including demographics, comorbidities, status at admission, clinical condition, treatment, outcomes, status at discharge, duration of hospitalization, and the cost of hospitalization for all patients hospitalized with COVID-19 at this facility under the Quarantine Act between January 2020 and April 2021. A total of 48 patients (39 males, 9 females; median age: 38.5 years) with COVID-19, half (52.1%) of which were Japanese, were hospitalized under the Quarantine Act. The majority (87.5%) of the patients lived or planned to stay outside of Chiba Prefecture. The most frequent time of admission was 9 PM-1 AM. Hypoxia on admission was observed in 10 (20.8%) patients and oxygen therapy was provided to 8 (16.7%). One patient died due to respiratory failure. The median duration of hospitalization was 11 days. The total cost of hospitalization was 82,705,289 yen (approximately $760,000), which was covered by public funds. Patients hospitalized with COVID-19 under the Quarantine Act were younger and less severely ill than inpatients with COVID-19 from among the general population in Japan (according to a COVID-19 registry), but consumed a significant amount of medical resources at this hospital. An efficient system to manage patients with COVID-19 in designated hotels should be created and indications for hospitalization should be determined.

Septic shock with emphysematous cholecystitis and disseminated infection caused by hypervirulent Klebsiella pneumoniae capsular genotype K2-ST65 in a Japanese man with diabetes mellitus: A case report.

Hypervirulent Klebsiella pneumoniae capsular genotypes K1 and K2 are common pathogens responsible for community-acquired liver abscesses and invasive infections especially in East Asia. We report a Japanese man with diabetes mellitus who rapidly developed emphysematous cholecystitis and fulminant disseminated infection with life-threatening multiple organ-system failure due to K. pneumoniae K2 strains belonging to sequence type 65. In East Asia, clinicians should be aware of fulminant infections caused by hypervirulent K2 strains in patients with community-acquired K. pneumoniae infections. Further epidemiological studies are warranted to elucidate the clinical features associated with the virulence K. pneumoniae K2 strains.

Omics Studies of the Murine Intestinal Ecosystem Exposed to Subchronic and Mild Social Defeat Stress.

The microbiota-gut-brain axis plays an important role in the development of stress-induced mental disorders. We previously established the subchronic and mild social defeat stress (sCSDS) model, a murine experimental model of depression, and investigated the metabolomic profiles of plasma and liver. Here we used omics approaches to identify stress-induced changes in the gastrointestinal tract. Mice exposed to sCSDS for 10 days showed the following changes: (1) elevation of cholic acid and reduction of 5-aminovaleric acid among cecal metabolites; (2) downregulation of genes involved in the immune response in the terminal ileum; (3) a shift in the diversity of the microbiota in cecal contents and feces; and (4) fluctuations in the concentrations of cecal metabolites produced by gut microbiota reflected in plasma and hepatic metabolites. Operational taxonomic units within the family Lachnospiraceae showed an inverse correlation with certain metabolites. The social interaction score correlated with cecal metabolites, IgA, and cecal and fecal microbiota, suggesting that sCSDS suppressed the ileal immune response, altering the balance of microbiota, which together with host cells and host enzymes resulted in a pattern of accumulated metabolites in the intestinal ecosystem distinct from that of control mice.

Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress.

Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice.

Effects of diet quality on vulnerability to mild subchronic social defeat stress in mice.

OBJECTIVES: The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. METHODS: Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semi-purified diet + control (no sCSDS), and non-purified diet + control. RESULTS: Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P < 0.05). For comparison, the susceptible-like phenotype rates were estimated at 12.5 and 8.3% in healthy control mice fed semi-purified and non-purified diets, respectively. DISCUSSION: These results suggest that diet quality affects the vulnerability of mice to social defeat stress.

Plasma and liver metabolic profiles in mice subjected to subchronic and mild social defeat stress.

To improve the quality of life of animals, understanding of stress-induced changes is necessary. Previously, we established a subchronic and mild social defeat stress (sCSDS) model in mice, which showed significantly higher body weight gain, food intake, and water intake compared to control mice. In this study, we elucidated metabolic profiles of plasma, liver, and urine in sCSDS mice by using metabolome and biochemical analyses. There was no significant difference between defeated and control mice in the plasma metabolites. In the liver of sCSDS mice, levels of taurocyamine (GES), phosphorylcholine, D-alanyl-D-alanine (D-ala-D-ala), and 1-methylnicotinamide (MNA) were elevated compared to controls. Taurine plays a role in osmotic regulation, and GES is a potential inhibitor of the taurine transporter. The polydipsia and increased body water content in sCSDS mice may disrupt body fluid balance following GES elevation. Furthermore, sCSDS increased heart and spleen weight significantly. Because MNA and D-ala-D-ala have anti-inflammatory and hepatoprotective effects, they may reduce inflammation in the liver of sCSDS mice. Finally, suppressed excretion of urine sodium was observed in sCSDS mice. Therefore, sCSDS induces various changes in metabolite concentrations, especially related to osmoregulation and inflammation, that may be used as biomarkers for stress-induced changes in animals.

Subchronic and mild social defeat stress accelerates food intake and body weight gain with polydipsia-like features in mice.

Development and characterization of animal models of depression are essential for fully understanding the pathogenesis of depression in humans. We made and analyzed a mouse model exhibiting social deficit and hyperphagia-like behavior using a subchronic and mild social defeat stress (sCSDS) paradigm. The body weight, food and water intake of mice were monitored during a test period, and their behaviors and serum components were analyzed at two stages: immediately after the sCSDS period and 1 month after the sCSDS. The body weight and food intake of defeated mice were significantly higher than control mice at the sCSDS period, and these differences were sustained until 1 month after the sCSDS, whereas the water intake of defeated mice was significantly higher than control mice for the period of sCSDS only. Behavioral analyses revealed that the defeated mice exhibit significant social aversion to unfamiliar mice in a social interaction test and a trend of anxiety-like behavior in an elevated-plus maze test. Possibly due to polydipsia-like symptoms, defeated mice had significantly lower levels of albumin and blood urea nitrogen than control mice immediately after the sCSDS period but not at 1 month after sCSDS. The present study revealed that our sCSDS mice keep much more water in their body than control mice. This study reports the first step toward an understanding of the mechanisms of stress-induced overhydration, over-eating and resultant weight gain.