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.

Personalized ventilatory strategy based on lung recruitablity in COVID-19-associated acute respiratory distress syndrome: a prospective clinical study.

BACKGROUND: Heterogeneity is an inherent nature of ARDS. Recruitment-to-inflation ratio has been developed to identify the patients who has lung recruitablity. This technique might be useful to identify the patients that match specific interventions, such as higher positive end-expiratory pressure (PEEP) or prone position or both. We aimed to evaluate the physiological effects of PEEP and body position on lung mechanics and regional lung inflation in COVID-19-associated ARDS and to propose the optimal ventilatory strategy based on recruitment-to-inflation ratio. METHODS: Patients with COVID-19-associated ARDS were consecutively enrolled. Lung recruitablity (recruitment-to-inflation ratio) and regional lung inflation (electrical impedance tomography [EIT]) were measured with a combination of body position (supine or prone) and PEEP (low 5 cmH2O or high 15 cmH2O). The utility of recruitment-to-inflation ratio to predict responses to PEEP were examined with EIT. RESULTS: Forty-three patients were included. Recruitment-to-inflation ratio was 0.68 (IQR 0.52-0.84), separating high recruiter versus low recruiter. Oxygenation was the same between two groups. In high recruiter, a combination of high PEEP with prone position achieved the highest oxygenation and less dependent silent spaces in EIT (vs. low PEEP in both positions) without increasing non-dependent silent spaces in EIT. In low recruiter, low PEEP in prone position resulted in better oxygenation (vs. both PEEPs in supine position), less dependent silent spaces (vs. low PEEP in supine position) and less non-dependent silent spaces (vs. high PEEP in both positions). Recruitment-to-inflation ratio was positively correlated with the improvement in oxygenation and respiratory system compliance, the decrease in dependent silent spaces, and was inversely correlated with the increase in non-dependent silent spaces, when applying high PEEP. CONCLUSIONS: Recruitment-to-inflation ratio may be useful to personalize PEEP in COVID-19-associated ARDS. Higher PEEP in prone position and lower PEEP in prone position decreased the amount of dependent silent spaces (suggesting lung collapse) without increasing the amount of non-dependent silent spaces (suggesting overinflation) in high recruiter and in low recruiter, respectively.

Control of blood glucose levels by an artificial pancreas in patients with severe coronavirus disease 2019 pneumonia.

BACKGROUND: Many patients with severe coronavirus disease 2019 (COVID-19) pneumonia experience hyperglycemia. It is often difficult to control blood glucose (BG) levels in such patients using standard intravenous insulin infusion therapy. Therefore, we used an artificial pancreas. This study aimed to compare the BG status of the artificial pancreas with that of standard therapy. METHODS: Fifteen patients were included in the study. BG values and the infusion speed of insulin and glucose by the artificial pancreas were collected. Arterial BG and administration rates of insulin, parenteral sugar, and enteral sugar were recorded during the artificial pancreas and standard therapy. The target BG level was 200 mg/dl. RESULTS: Arterial BG was highly correlated with BG data from the artificial pancreas. A higher BG slightly increased the difference between the BG data from the artificial pancreas and arterial BS. No significant difference in arterial BG was observed between the artificial pancreas and standard therapy. However, the standard deviation with the artificial pancreas was smaller than that under standard therapy (p < 0.0001). More points within the target BG range were achieved with the artificial pancreas (180-220 mg/dl) than under standard therapy. The hyperglycemic index of the artificial pancreas (8.7 ± 15.6 mg/dl) was lower than that of standard therapy (16.0 ± 21.5 mg/dl) (p = 0.0387). No incidence of hypoglycemia occurred under the artificial pancreas. CONCLUSIONS: The rate of achieving target BG was higher using artificial pancreas than with standard therapy. An artificial pancreas helps to control BG in critically ill patients.

Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: A propensity score analysis.

INTRODUCTION: COVID-19 patients have been reported to have digestive symptoms with poor outcome. Ivermectin, an antiparasitic drug, has been used in COVID-19 patients. The objective of this study was to evaluate whether ivermectin has effects on gastrointestinal complications and ventilator-free days in ventilated patients with COVID-19. METHODS: COVID-19 patients who were mechanically ventilated in the ICU were included in this study. The ventilated patients who received ivermectin within 3 days after admission were assigned to the Ivermectin group, and the others were assigned to the Control group. Patients in the Ivermectin group received ivermectin 200 µg/kg via nasal tube. The incidence of gastrointestinal complications and ventilator-free days within 4 weeks from admission were evaluated as clinical outcomes using a propensity score with the inverse probability weighting method. RESULTS: We included 88 patients in this study, of whom 39 patients were classified into the Ivermectin group, and 49 patients were classified into the Control group. The hazard ratio for gastrointestinal complications in the Ivermectin group as compared with the Control group was 0.221 (95% confidence interval [CI], 0.057 to 0.855; p = 0.029) in a Cox proportional-hazard regression model. The odds ratio for ventilator-free days as compared with the Control group was 1.920 (95% CI, 1.076 to 3.425; p = 0.027) in a proportional odds logistic regression model. CONCLUSIONS: Ivermectin improved gastrointestinal complications and the number of ventilator-free days in severe COVID-19 patients undergoing mechanical ventilation. Prevention of gastrointestinal symptoms by SARS-Cov-2 might be associated with COVID-19 outcome.

The prevalence and characteristics of rapid response systems in hospitals with pediatric intensive care units in Japan and barriers to their use.

OBJECTIVE: The use of pediatric rapid response systems (RRSs) to improve the safety of hospitalized children has spread in various western countries including the United States and the United Kingdom. We aimed to determine the prevalence and characteristics of pediatric RRSs and barriers to use in Japan, where epidemiological information is limited. DESIGN: A cross-sectional online survey. SETTING: All 34 hospitals in Japan with pediatric intensive care units (PICUs) in 2019. PARTICIPANTS: One PICU physician per hospital responded to the questionnaire as a delegate. MAIN OUTCOME MEASURES: Prevalence of pediatric RRSs in Japan and barriers to their use. RESULTS: The survey response rate was 100%. Pediatric RRSs had been introduced in 14 (41.2%) institutions, and response teams comprised a median of 6 core members. Most response teams employed no full-time members and largely comprised members from multiple disciplines and departments who served in addition to their main duties. Of 20 institutions without pediatric RRSs, 11 (55%) hoped to introduce them, 14 (70%) had insufficient knowledge concerning them and 11 (55%) considered that their introduction might be difficult. The main barrier to adopting RRSs was a perceived personnel and/or funding shortage. There was no significant difference in hospital beds (mean, 472 vs. 524, P = 0.86) and PICU beds (mean, 10 vs. 8, P = 0.34) between institutions with/without pediatric RRSs. CONCLUSIONS: Fewer than half of Japanese institutions with PICUs had pediatric RRSs. Operating methods for and obstructions to RRSs were diverse. Our findings may help to popularize pediatric RRSs.

Large Volume Fluid Resuscitation for Severe Acute Pancreatitis is Associated With Reduced Mortality: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP). METHODS: We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention. RESULTS: We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%; P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58; P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention. CONCLUSIONS: In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.

Potential contribution of erythrocyte microRNA to secondary erythrocytosis and thrombocytopenia in congenital heart disease.

BackgroundChildren with cyanotic heart disease develop secondary erythrocytosis and thrombocytopenia via unknown mechanisms. Mature erythrocyte microRNAs may reflect clinical pathologies and cell differentiation processes pre-enucleation. This study evaluated erythrocyte microRNAs in children with cyanotic heart disease.MethodsErythrocyte microRNAs from children with cyanotic and acyanotic heart disease and without cardiac disease were quantified with Ion PGM System (n=10 per group). Differential expression was confirmed by quantitative PCR (qPCR; n=20 per group).ResultsMir-486-3p, mir-486-5p, and mir-155-5p increased in patients with cyanotic heart disease compared with those without heart disease: fold differences (95% confidence interval): mir-486-3p: 1.92 (1.14-3.23), P=0.011; mir-486-5p: 2.27 (1.41-3.65), P<0.001; and mir-155-5p: 1.44 (1.03-2.03), P=0.028. Mir-486-5p was increased, and let-7e-5p and mir-1260a were decreased in patients with acyanotic heart disease compared with those without heart disease: mir-486-5p: 1.66 (1.03-2.66), P=0.035; let-7e-5p: 0.66 (0.44-0.99), P=0.049; and mir-1260a: 0.53 (0.29-0.99), P=0.045.ConclusionSeveral microRNA levels changed in children with cyanotic and acyanotic heart disease. Mir-486-3p and -5p are associated with hematopoietic differentiation. Mir-486-3p regulates the erythroid vs. megakaryocyte lineage fate decision. Mir-155 is a hypoxia-inducible microRNA, whose overexpression inhibits megakaryocyte differentiation. Erythrocyte microRNA expression changes may contribute to erythrocytosis and thrombocytopenia in children with cyanotic heart disease.

External Validation for Acute Kidney Injury Severity Scores: A Multicenter Retrospective Study in 14 Japanese ICUs.

BACKGROUND/AIMS: Acute kidney injury (AKI) is associated with high mortality. Multiple AKI severity scores have been derived to predict patient outcome. We externally validated new AKI severity scores using the Japanese Society for Physicians and Trainees in Intensive Care (JSEPTIC) database. METHODS: New AKI severity scores published in the 21st century (Mehta, Stuivenberg Hospital Acute Renal Failure (SHARF) II, Program to Improve Care in Acute Renal Disease (PICARD), Vellore and Demirjian), Liano, Simplified Acute Physiology Score (SAPS) II and lactate were compared using the JSEPTIC database that collected retrospectively 343 patients with AKI who required continuous renal replacement therapy (CRRT) in 14 intensive care units. Accuracy of the severity scores was assessed by the area under the receiver-operator characteristic curve (AUROC, discrimination) and Hosmer-Lemeshow test (H-L test, calibration). RESULTS: The median age was 69 years and 65.8% were male. The median SAPS II score was 53 and the hospital mortality was 58.6%. The AUROC curves revealed low discrimination ability of the new AKI severity scores (Mehta 0.65, SHARF II 0.64, PICARD 0.64, Vellore 0.64, Demirjian 0.69), similar to Liano 0.67, SAPS II 0.67 and lactate 0.64. The H-L test also demonstrated that all assessed scores except for Liano had significantly low calibration ability. CONCLUSIONS: Using a multicenter database of AKI patients requiring CRRT, this study externally validated new AKI severity scores. While the Demirjian's score and Liano's score showed a better performance, further research will be required to confirm these findings.

[Implantable Cardioverter Defibrillator and Perioperative Magnet Application: A Case Report].

An implantable cardioverter defibrillator (ICD) can falsely recognize noise by monopolar electrocautery as tachyarrhythmia and deliver inappropriate antitachycardia therapy. Application of a clinical magnet on an ICD suspends antitachycardia therapy, but it has not been widely used for this purpose. A 67-year-old male underwent laryngopharyngectomy, cervical esophagectomy, right neck dissection, tracheostomy and reconstruction with free jejunal transplant for recurrent hypopharyngeal cancer. He had an ICD (PARADYM DR8550, Sorin) implanted below the left clavicle for ventricular tachycardia and prolonged QT syndrome. During the operation, a clinical magnet was left on the ICD to disable antitachycardia therapy. The magnet mode of the ICD provided asynchronous AAI pacing at 96 beats x min(-1). The surgery proceeded uneventfully. No episode of ventricular tachyarrythmia or pacing inhibition by electromagnetic interference was observed on electrocardiogram. This case illustrated the potential role of a clinical magnet as an alternative to reprogramming of an ICD by a programmer in the perioperative management of a patient with an ICD when a technical expert to operate a programmer is not available.

The lower limit of intensity to control uremia during continuous renal replacement therapy.

INTRODUCTION: The recommended lower limit of intensity during continuous renal replacement therapy (CRRT) is 20 or 25 mL/kg/h. However, limited information is available to support this threshold. We aimed to evaluate the impact of different intensities of CRRT on the clearance of creatinine and urea in critically ill patients with severe acute kidney injury (AKI). METHODS: This is a multicenter retrospective study conducted in 14 Japanese ICUs in 12 centers. All patients older than 18 years and treated with CRRT due to AKI were eligible. We evaluated the effect of CRRT intensity by two different definitions: daily intensity (the mean intensity over each 24-h period) and average intensity (the mean of daily intensity during the period while CRRT was performed). To study the effect of different CRRT intensity on clearance of urea and creatinine, all patients/daily observations were arbitrarily allocated to one of 4 groups based on the average intensity and daily intensity: <10, 10-15, 15-20, and >20 mL/kg/h. RESULTS: Total 316 patients were included and divided into the four groups according to average CRRT intensity. The groups comprised 64 (20.3%), 138 (43.7%), 68 (21.5%), and 46 patients (14.6%), respectively. Decreases in creatinine and urea increased as the average intensity increased over the first 7 days of CRRT. The relative changes of serum creatinine and urea levels remained close to 1 over the 7 days in the "<10" group. Total 1,101 daily observations were included and divided into the four groups according to daily CRRT intensity. The groups comprised 254 (23.1%), 470 (42.7%), 239 (21.7%), and 138 observations (12.5%), respectively. Creatinine and urea increased (negative daily change) only in the "<10" group and decreased with the increasing daily intensity in the other groups. CONCLUSIONS: The lower limit of delivered intensity to control uremia during CRRT was approximately between 10 and 15 mL/kg/h in our cohort. A prescribed intensity of approximately 15 mL/kg/h might be adequate to control uremia for patients with severe AKI in the ICU. However, considering the limitations due to the retrospective nature of this study, prospective studies are required to confirm our findings.

Dysbiosis of gut microbiota in patients with severe COVID-19.

Aim: Altered gut microbiota has been proposed as one of the causes of exacerbation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) from the perspective of the gut-lung axis. We aimed to evaluate gut microbiota in mechanically ventilated patients with COVID-19 prior to using antibiotics. Methods: We retrospectively selected for enrollment COVID-19 patients who required mechanical ventilation on admission but who had not used antibiotics before admission to observe the influence of SARS-Cov-2 on gut microbiota. Fecal samples were collected serially on admission and were evaluated by 16S rRNA gene deep sequencing. Results: The phylum of Bacteroidetes decreased, and those of Firmicutes and Actinobacteria increased in COVID-19 patients compared with those in healthy controls (p < 0.001). The main commensals of Bacteroides, Faecalibacterium, and Blautia at the genus level were significantly decreased in the COVID-19 patients, and opportunistic bacteria including Corynebacterium, Anaerococcus, Finegoldia Peptoniphilus, Actinomyces, and Enterococcus were increased (p < 0.001). α-Diversity and ß-diversity in COVID-19 patients significantly changed compared with those in the healthy controls. Conclusion: The commensal gut microbiota were altered, and opportunistic bacteria increased in patients with severe COVID-19 who required mechanical ventilation on admission.

Validity of low-intensity continuous renal replacement therapy*.

OBJECTIVE: To study the hospital mortality of patients with severe acute kidney injury treated with low-intensity continuous renal replacement therapy. DESIGN: Multicenter retrospective observational study (Japanese Society for Physicians and Trainees in Intensive Care), combined with previously conducted multinational prospective observational study (Beginning and Ending Supportive Therapy). SETTING: Fourteen Japanese ICUs in 12 tertiary hospitals (Japanese Society for Physicians and Trainees in Intensive Care) and 54 ICUs in 23 countries (Beginning and Ending Supportive Therapy). PATIENTS: Consecutive adult patients with severe acute kidney injury requiring continuous renal replacement therapy admitted to the participating ICUs in 2010 (Japanese Society for Physicians and Trainees in Intensive Care, n = 343) and 2001 (Beginning and Ending Supportive Therapy Beginning and Ending Supportive Therapy, n = 1,006). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, variables at continuous renal replacement therapy initiation, continuous renal replacement therapy settings, and outcomes (ICU and hospital mortality and renal replacement therapy requirement at hospital discharge) were collected. Continuous renal replacement therapy intensity was arbitrarily classified into seven subclasses: less than 10, 10-15, 15-20, 20-25, 25-30, 30-35, and more than 35 mL/kg/hr. Multivariable logistic regression analysis was conducted to investigate risk factors for hospital mortality. The continuous renal replacement therapy dose in the Japanese Society for Physicians and Trainees in Intensive Care database was less than half of the Beginning and Ending Supportive Therapy database (800 mL/hr vs 2,000 mL/hr, p < 0.001). Even after adjusting for the body weight and dilution factor, continuous renal replacement therapy intensity was statistically different (14.3 mL/kg/hr vs 20.4 mL/kg/hr, p < 0.001). Patients in the Japanese Society for Physicians and Trainees in Intensive Care database had a lower ICU mortality (46.1% vs 55.3%, p = 0.003) and hospital mortality (58.6% vs 64.2%, p = 0.070) compared with patients in the Beginning and Ending Supportive Therapy database. In multivariable regression analysis after combining the two databases, no continuous renal replacement therapy intensity subclasses were found to be statistically different from the reference intensity (20-25 mL/kg/hr). Several sensitivity analyses (patients with sepsis, patients from Western countries in the Beginning and Ending Supportive Therapy database) confirmed no intensity-outcome relationship. CONCLUSIONS: Continuous renal replacement therapy at a mean intensity of 14.3 mL/kg/hr did not have worse outcome compared with 20-25 mL/kg/hr of continuous renal replacement therapy, currently considered the standard intensity. However, our study is insufficient to support the use of low-intensity continuous renal replacement therapy, and more studies are needed to confirm our findings.

Factors Associated With Prolonged Ventilation in Patients Receiving Prone Positioning Protocol With Muscle Relaxants for Severe COVID-19 Pneumonia.

BACKGROUND: Prone positioning and neuromuscular blocking agents (NMBAs) are frequently used to treat severe respiratory failure from COVID-19 pneumonia. Prone positioning has shown to improve mortality, whereas NMBAs are used to prevent ventilator asynchrony and reduce patient self-inflicted lung injury. However, despite the use of lung-protective strategies, high death rates in this patient population have been reported. METHODS: We retrospectively examined the factors affecting prolonged mechanical ventilation in subjects receiving prone positioning plus muscle relaxants. The medical records of 170 patients were reviewed. Subjects were divided into 2 groups according to ventilator-free days (VFDs) at day 28. Whereas subjects with VFDs < 18 d were defined as prolonged mechanical ventilation, subjects with VFDs ≥18 d were defined as short-term mechanical ventilation. Subjects' baseline status, status at ICU admission, therapy before ICU admission, and treatment in the ICU were studied. RESULTS: Under the proning protocol for COVID-19, the mortality rate in our facility was 11.2%. The prognosis may be improved by avoiding lung injury in the early stages of mechanical ventilation. According to multifactorial logistic regression analysis, persistent SARS-CoV-2 viral shedding in blood (P = .03), higher daily corticosteroid use before ICU admission (P = .007), delayed recovery of lymphocyte count (P < .001), and higher maximal fibrinogen degradation products (P = .039) were associated with prolonged mechanical ventilation. A significant relationship was found between daily corticosteroid use before admission and VFDs by squared regression analysis (y = -0.00008522x2 + 0.01338x + 12.8; x: daily corticosteroids dosage before admission [prednisolone mg/d]; y: VFDs/28 d, R2 = 0.047, P = .02). The peak point of the regression curve was 13.4 d at 78.5 mg/d of the equivalent prednisolone dose, which corresponded to the longest VFDs. CONCLUSIONS: Persistent SARS-CoV-2 viral shedding in blood, high corticosteroid dose from the onset of symptoms to ICU admission, slow recovery of lymphocyte counts, and high levels of fibrinogen degradation products after admission were associated with prolonged mechanical ventilation in subjects with severe COVID-19 pneumonia.

Mechanically ventilated children with 2009 pandemic influenza A/H1N1: results from the National Pediatric Intensive Care Registry in Japan.

OBJECTIVE: To outline the characteristics, clinical course, and outcome of pediatric patients requiring mechanical ventilation with influenza A/H1N1 infection in Japan. DESIGN: Prospective case registry analysis. SETTING: Eleven pediatric or general intensive care units in Japan. PATIENTS: Consecutive patients infected with A/H1N1, aged from 1 month to 16 yrs old admitted to the intensive care unit for mechanical ventilation between July 2009 and March 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-one children, aged 6.3 [0.8-13.6] (median [interquartile range]) years, were enrolled. Seventy-four (91%) had mechanical ventilation with tracheal intubation. Median duration of mechanical ventilation was 4 days (range 0.04-87) and 18 patients (23%) required mechanical ventilation >7 days. Two patients (2%) required extracorporeal membrane oxygenation. The in-hospital mortality was 1%. Forty-one patients (50%) had at least one underlying chronic condition, including 31 with asthma. Associated clinical symptoms and diagnosis were as follows: acute respiratory distress syndrome (9%), asthma or bronchitis (37%), pneumonia (68%) with 8 (14%) having bacterial pneumonia, neurological symptoms (32%), myocarditis (2%), and rhabdomyolysis (1%). Therapeutic interventions include inotropic support (21%), methylprednisolone therapy (33%), and antimicrobial therapy (88%). Multivariate analysis revealed that inotropic support was the only statistically significant factor associated with mechanical ventilation for more than a week (odds ratio 5.5, 95% confidence interval 1.5-20.5, p = .005). CONCLUSIONS: The clinical presentations of pediatric patients requiring mechanical ventilation for A/H1N1 in Japan were diverse. In-hospital mortality of this population was remarkably low. Rapid access to medical facilities in combination with early administration of antiviral agents may have contributed to the low mortality in this population.

Successful treatment of severe asthma-associated plastic bronchitis with extracorporeal membrane oxygenation.

We describe a case of near-fatal asthma requiring extracorporeal membrane oxygenation (ECMO). The patient presented with severe respiratory distress, which was not responsive to conventional pharmacological therapy. The patient also failed to respond to mechanical ventilation and thus was placed on venovenous ECMO for temporary pulmonary support. A fiberoptic bronchoscopy revealed that large amounts of thick bronchial secretions had occluded the main bronchus, which suggested plastic bronchitis secondary to asthma. Aggressive airway hygiene with frequent bronchoscopies and application of biphasic cuirass ventilation for facilitation of secretion clearance were performed to improve the patient's respiratory status. The patient achieved a full recovery and suffered no neurological sequelae. This case illustrates that aggressive pulmonary hygiene with ECMO is a useful therapy for patients with asthma-associated plastic bronchitis.

A case of massive refractory diarrhea in a patient with COVID-19.

Background: The new coronavirus disease (COVID-19) causes gastrointestinal symptoms as well as respiratory symptoms. Case Presentation: A 60-year-old man was transferred with respiratory difficulty. He was diagnosed as having COVID-19 and was intubated and placed on mechanical ventilation. He suffered from diarrhea from day 12 and produced a maximum of approximately 6,384 mL/day of watery diarrhea on day 21. He required massive transfusion. Adsorbents and pectin-containing oligomeric formulas were administered, which decreased the amount of diarrhea. Fecal metagenomic analysis showed the proportions of the genera Enterococcus and Staphylococcus were the most dominate at the genus level. The proportion of Bacteroidetes was <1%. Thereafter, his diarrhea decreased to several times, and he was transferred to another ward on day 104. Conclusion: Therapy for intestinal complications as well as that for pneumonia might be important in treating COVID-19.

Association between early tracheostomy and patient outcomes in critically ill patients on mechanical ventilation: a multicenter cohort study.

BACKGROUND: Tracheostomy is commonly performed in critically ill patients because of its clinical advantages over prolonged translaryngeal endotracheal intubation. Early tracheostomy has been demonstrated to reduce the duration of mechanical ventilation and length of stay. However, its association with mortality remains ambiguous. This study aimed to evaluate the association between the timing of tracheostomy and mortality in patients receiving mechanical ventilation. METHODS: We performed a retrospective cohort analysis of adult patients who underwent tracheostomy during their intensive care unit (ICU) admission between April 2015 and March 2019. Patients who underwent tracheostomy before or after 29 days of ICU admission were excluded. Data were collected from the nationwide Japanese Intensive Care Patient Database. The primary outcome was hospital mortality. The timing of tracheostomy was stratified by quartile, and the association between patient outcomes was evaluated using regression analysis. RESULTS: Among the 85558 patients admitted to 46 ICUs during the study period, 1538 patients were included in the analysis. The quartiles for tracheostomy were as follows: quartile 1, ≤ 6 days; quartile 2, 7-10 days; quartile 3, 11-14 days; and quartile 4, > 14 days. Hospital mortality was significantly higher in quartile 2 (adjusted odds ratio [aOR]: 1.52, 95% confidence interval [CI]: 1.08-2.13), quartile 3 (aOR: 1.82, 95% CI: 1.28-2.59), and quartile 4 (aOR: 2.26, 95% CI: 1.61-3.16) (p for trend < 0.001) than in quartile 1. A similar trend was observed in the subgroup analyses of patients with impaired consciousness (Glasgow Coma Scale score < 8) and respiratory failure (PaO2:FiO2 ≤ 300) at ICU admission (p for trend = 0.081 and 0.001, respectively). CONCLUSIONS: This multi-institutional observational study demonstrated that the timing of tracheostomy was significantly and independently associated with hospital mortality in a stepwise manner. Thus, early tracheostomy may be beneficial for patient outcomes, including mortality, and warrants further investigation.

Timing of tracheostomy and patient outcomes in critically ill patients requiring extracorporeal membrane oxygenation: a single-center retrospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an integral method of life support in critically ill patients with severe cardiopulmonary failure; however, such patients generally require prolonged mechanical ventilation and exhibit high mortality rates. Tracheostomy is commonly performed in patients on mechanical ventilation, and its early implementation has potential advantages for favorable patient outcomes. This study aimed to investigate the association between tracheostomy timing and patient outcomes, including mortality, in patients requiring ECMO. METHODS: We conducted a single-center retrospective observational study of consecutively admitted patients who were supported by ECMO and underwent tracheostomy during intensive care unit (ICU) admission at a tertiary care center from April 2014 until December 2021. The primary outcome was hospital mortality. Using the quartiles of tracheostomy timing, the patients were classified into four groups for comparison. The association between the quartiles of tracheostomy timing and mortality was explored using multivariable logistic regression models. RESULTS: Of the 293 patients treated with ECMO, 98 eligible patients were divided into quartiles 1 (≤ 15 days), quartile 2:16-19 days, quartile 3:20-26 days, and 4 (> 26 days). All patients underwent surgical tracheostomy and 35 patients underwent tracheostomy during ECMO. The complications of tracheostomy were comparable between the groups, whereas the duration of ECMO and ICU length of stay increased significantly as the quartiles of tracheostomy timing increased. Patients in quartile 1 had the lowest hospital mortality rate (19.2%), whereas those in quartile 4 had the highest mortality rate (50.0%). Multivariate logistic regression analysis showed a significant association between the increment of the quartiles of tracheostomy timing and hospital mortality (adjusted odds ratio for quartile increment:1.55, 95% confidence interval 1.03-2.35, p for trend = 0.037). CONCLUSIONS: The timing of tracheostomy in patients requiring ECMO was significantly associated with patient outcomes in a time-dependent manner. Further investigation is warranted to determine the optimal timing of tracheostomy in terms of mortality.

COVID-19 in a human T-cell lymphotropic virus type-1 carrier.

This is the first report of COVID-19 in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier. HTLV-1 infection can cause immune dysfunction even in asymptomatic carriers. This case highlights the need for guidance on management of COVID-19-HTLV-1 coinfection, specifically on the appropriate use of corticosteroid treatment while considering secondary infection.

The impact of relative hypotension on acute kidney injury progression after cardiac surgery: a multicenter retrospective cohort study.

BACKGROUND: Cardiac surgery is performed worldwide, and acute kidney injury (AKI) following cardiac surgery is a risk factor for mortality. However, the optimal blood pressure target to prevent AKI after cardiac surgery remains unclear. We aimed to investigate whether relative hypotension and other hemodynamic parameters after cardiac surgery are associated with subsequent AKI progression. METHODS: We retrospectively enrolled adult patients admitted to 14 intensive care units after elective cardiac surgery between January and December 2018. We defined mean perfusion pressure (MPP) as the difference between mean arterial pressure (MAP) and central venous pressure (CVP). The main exposure variables were time-weighted-average MPP-deficit (i.e., the percentage difference between preoperative and postoperative MPP) and time spent with MPP-deficit > 20% within the first 24 h. We defined other pressure-related hemodynamic parameters during the initial 24 h as exploratory exposure variables. The primary outcome was AKI progression, defined as one or more AKI stages using Kidney Disease: Improving Global Outcomes' creatinine and urine output criteria between 24 and 72 h. We used multivariable logistic regression analyses to assess the association between the exposure variables and AKI progression. RESULTS: Among the 746 patients enrolled, the median time-weighted-average MPP-deficit was 20% [interquartile range (IQR): 10-27%], and the median duration with MPP-deficit > 20% was 12 h (IQR: 3-20 h). One-hundred-and-twenty patients (16.1%) experienced AKI progression. In the multivariable analyses, time-weighted-average MPP-deficit or time spent with MPP-deficit > 20% was not associated with AKI progression [odds ratio (OR): 1.01, 95% confidence interval (95% CI): 0.99-1.03]. Likewise, time spent with MPP-deficit > 20% was not associated with AKI progression (OR: 1.01, 95% CI 0.99-1.04). Among exploratory exposure variables, time-weighted-average CVP, time-weighted-average MPP, and time spent with MPP < 60 mmHg were associated with AKI progression (OR: 1.12, 95% CI 1.05-1.20; OR: 0.97, 95% CI 0.94-0.99; OR: 1.03, 95% CI 1.00-1.06, respectively). CONCLUSIONS: Although higher CVP and lower MPP were associated with AKI progression, relative hypotension was not associated with AKI progression in patients after cardiac surgery. However, these findings were based on exploratory investigation, and further studies for validating them are required. Trial Registration UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm , UMIN000037074.