Adult-onset botulism in a Japanese woman with prolonged spore excretion.

We report a case of an 80-year-old woman with botulism from 2020 in Osaka, Japan. The patient complained of dysarthria and dizziness. On the same day, the patient developed respiratory failure, and was intubated and placed on mechanical ventilation. Subsequently, ophthalmoparesis and quadriparesis progressed rapidly. Ten days after onset, the patient failed to respond to any external stimulation. Blood tests showed anemia, and computed tomography revealed undiagnosed cervical cancer. Initially, diagnosis of neuromuscular junction disorder and acute motor neuropathy, including paraneoplastic syndrome, were considered. However, intravenous immunoglobulin therapy and plasma exchange were ineffective. A fecal sample on day 30 showed a large number of C. botulinum spores. On day 34, a mouse bioassay revealed botulinum toxin type A in the patient's serum; therefore, a botulinum antitoxin was administered. Later, the patient's muscle strength was gradually improved. However, severe muscle paralysis persisted, and the patient died of cachexia owing to cervical cancer on day 196. The etiology of this case was unknown because no contaminated food was identified during an inspection of the patient's home. Fecal 16S rRNA gene sequencing revealed dysbiosis of the intestinal microbiota with abundant Enterococcus species. Long-lasting excretion of substantial botulinum spores even on day 30 indicated colonization of C. botulinum in the intestinal tract. This case suggests that C. botulinum colonization with co-existing intestinal dysbiosis may be associated with severe and prolonged symptoms of botulism.

Clinical Phenotyping of Out-of-Hospital Cardiac Arrest Patients With Shockable Rhythm　- Machine Learning-Based Unsupervised Cluster Analysis.

BACKGROUND: The hypothesis of this study is that latent class analysis could identify the subphenotypes of out-of-hospital cardiac arrest (OHCA) patients associated with the outcomes and allow us to explore heterogeneity in the effects of extracorporeal cardiopulmonary resuscitation (ECPR).Methods and Results:This study was a retrospective analysis of a multicenter prospective observational study (CRITICAL study) of OHCA patients. It included adult OHCA patients with initial shockable rhythm. Patients from 2012 to 2016 (development dataset) were included in the latent class analysis, and those from 2017 (validation dataset) were included for evaluation. The association between subphenotypes and outcomes was investigated. Further, the heterogeneity of the association between ECPR implementation and outcomes was explored. In the study results, a total of 920 patients were included for latent class analysis. Three subphenotypes (Groups 1, 2, and 3) were identified, mainly characterized by the distribution of partial pressure of O2(PO2), partial pressure of CO2(PCO2) value of blood gas assessment, cardiac rhythm on hospital arrival, and estimated glomerular filtration rate. The 30-day survival outcomes were varied across the groups: 15.7% in Group 1; 30.7% in Group 2; and 85.9% in Group 3. Further, the association between ECPR and 30-day survival outcomes by subphenotype groups in the development dataset was as varied. These results were validated using the validation dataset. CONCLUSIONS: The latent class analysis identified 3 subphenotypes with different survival outcomes and potential heterogeneity in the effects of ECPR.

Gut Dysbiosis Associated with Antibiotics and Disease Severity and Its Relation to Mortality in Critically Ill Patients.

BACKGROUND: The gut microbiota are reported to be altered in critical illness. The pattern and impact of dysbiosis on prognosis has not been thoroughly investigated in the ICU setting. AIMS: We aimed to evaluate changes in the gut microbiota of ICU patients via 16S rRNA gene deep sequencing, assess the association of the changes with antibiotics use or disease severity, and explore the association of gut microbiota changes with ICU patient prognosis. METHODS: Seventy-one mechanically ventilated patients were included. Fecal samples were collected serially on days 1-2, 3-4, 5-7, 8-14, and thereafter when suitable. Microorganisms of the fecal samples were profiled by 16S rRNA gene deep sequencing. RESULTS: Proportions of the five major phyla in the feces were diverse in each patient at admission. Those of Bacteroidetes and Firmicutes especially converged and stabilized within the first week from admission with a reduction in α-diversity (p < 0.001). Significant differences occurred in the proportional change of Actinobacteria between the carbapenem and non-carbapenem groups (p = 0.030) and that of Actinobacteria according to initial SOFA score and changes in the SOFA score (p < 0.001). An imbalance in the ratio of Bacteroidetes to Firmicutes within seven days from admission was associated with higher mortality when the ratio was > 8 or < 1/8 (odds ratio: 5.54, 95% CI: 1.39-22.18, p = 0.015). CONCLUSIONS: Broad-spectrum antibiotics and disease severity may be associated with gut dysbiosis in the ICU. A progression of dysbiosis occurring in the gut of ICU patients might be associated with mortality.

The accuracy of contrast-enhanced computed tomography scans to detect postpartum haemorrhage: an observational study.

INTRODUCTION: Postpartum haemorrhage is a major cause of maternal mortality. Although contrast-enhanced computed tomography (CE-CT) is useful to reveal arterial bleeding, its accuracy in postpartum haemorrhage is unclear. The aim of this study was to evaluate the accuracy of CE-CT scanning in detecting postpartum haemorrhage. METHODS: This was a retrospective observational study. We included patients with postpartum haemorrhage treated by emergency physicians in collaboration with obstetricians. We calculated the sensitivity, specificity, and positive and negative predictive values for CE-CT scanning to detect arterial bleeding. RESULTS: CE-CT scanning was performed in 52 patients, and 31 patients had extravasation. The sensitivity of CE-CT scanning to detect arterial extravasation was 100% (15/15), specificity was 28.6% (2/7), positive predictive value was 75% (15/20), and negative predictive value was 100% (2/2). CONCLUSION: We showed the sensitivity of CE-CT scanning to detect arterial extravasation in patients with postpartum haemorrhage to be 100%.

Effectiveness of high-flow nasal cannula for tracheal intubation in the emergency department.

BACKGROUND: Tracheal intubation in the emergency department (ED) can cause serious complications. Available evidence on the use of a high-flow nasal cannula (HFNC) during intubation in the ED is limited. This study evaluated the effect of oxygen therapy by HFNC on oxygen desaturation during tracheal intubation in the ED. METHODS: This was a single-center before-and-after study designed to compare two groups that received oxygen therapy during intubation: one received conventional oxygen, and the other received oxygen therapy using HFNC. We included non-trauma patients who required tracheal intubation in the ED. Linear regression analysis was performed to evaluate the relationship between oxygen therapy using HFNC and the lowest peripheral oxygen saturation (SpO2) during intubation in the conventional and HFNC groups. RESULTS: The study population included 87 patients (conventional group, n = 67; HFNC group, n = 20). The median lowest SpO2 in the HFNC group was significantly higher than that in the conventional group (94% [84-99%] vs. 85% [76-91%], p = 0.006). The percentage of cases with oxygen desaturation to < 90% during the intubation procedure in the HFNC group was significantly lower than that in the conventional group (40% vs. 63.8%, p = 0.037). The use of HFNC was significantly associated with the lowest SpO2, and the use of HFNC increased the lowest SpO2 during intubation procedures by 3.658% (p = 0.048). CONCLUSION: We found that the use of HFNC during tracheal intubation was potentially associated with a higher lowest SpO2 during the procedure in comparison to conventional oxygen administration in non-trauma patients in the ED.

Nationwide improvements in geriatric mortality due to traumatic brain injury in Japan.

BACKGROUND: Traumatic brain injury (TBI), both isolated and in combination with extracranial lesions, is a global health problem associated with high mortality. Among various risk factors for poor clinical outcomes, age is the most important independent predictor of mortality in patients with TBI. TBI-related mortality is expected to increase as the society ages. However, in a super-aged society such as Japan, little is known about the trend of TBI-related mortality among older adults. Herein, we assessed the nationwide trend of the incidence and clinical outcomes of geriatric patients with TBI in Japan using the national Japanese Trauma Data Bank (JTDB) registry. METHODS: In this retrospective cohort study, cases of TBI (aged ≥65 years) in hospitals registered with the JTDB database between January 2004 and December 2018 were included. In-hospital mortality was the primary outcome, and mortality in the emergency department was the secondary outcome. The odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital deaths with respect to 3-year periods were assessed using multivariable analysis after adjusting for potential confounders. RESULTS: The main cause of TBI in older individuals was falls. The proportion of patients who died after hospitalization during the study period decreased markedly from 29.5% (194/657) during 2004-2006 to 14.2% (1309/9240) during 2016-2018 in the isolated TBI group (adjusted OR = 0.42, 95% CI: 0.33-0.53) and from 48.0% (119/248) during 2004-2006 to 21.7% (689/3172) during 2016-2018 in the multiple trauma group (adjusted OR = 0.32, 95% CI: 0.23-0.45). The adjusted ORs for the 3-year increment were 0.84 (95% CI: 0.81-0.88) and 0.78 (95% CI: 0.75-0.83) for the isolated TBI and multiple trauma groups, respectively. CONCLUSIONS: Using the national JTDB registry, we demonstrated a nationwide reduction in TBI-related mortality. Our findings in the super-aged society of Japan may provide insight for the treatment of geriatric patients with TBI worldwide.

Hydrogen Gas Therapy Attenuates Inflammatory Pathway Signaling in Septic Mice.

BACKGROUND: Molecular hydrogen (H2) has been used in clinical cases. However, there are few studies of H2 therapy to treat sepsis, and anti-inflammatory mechanisms of H2 are mostly unknown. We aimed to confirm effects of H2 therapy on sepsis and reveal its therapeutic mechanism via RNA sequencing in multiple organs in septic mice. METHODS: Nine-week-old C57BL/6 male mice underwent cecal ligation and puncture (CLP) or sham procedure. Subsequently, the CLP model received immediate ± continuous inhalation of 7% H2. Mice were observed for a week to assess survival rates. Serum inflammatory cytokines were evaluated at 24 h after CLP procedure. Liver, intestine, and lungs in CLP mice receiving 24-h ± H2 therapy were assessed by RNA sequencing. Data were analyzed with Ingenuity Pathways Analysis (QIAGEN Inc). RESULTS: Seven-day survival rate in septic mice was significantly improved in the H2 inhalation group compared with that in the control group (75% versus 40%, P < 0.05). H2 treatment attenuated serum interleukin-6 and tumor necrosis factor-α levels at 24 h after CLP, and blood glucose levels were maintained in the H2-treated group. In RNA sequencing, canonical pathway analysis revealed inactivity of various inflammatory signaling pathways, for example, acute phase response signaling and STAT3 pathways, in the liver and intestine in the CLP model after 24-h H2 inhalation. We detected significantly decreased expressions of upstream regulator genes such as the CD14 antigen gene in the liver and various cytokine receptor genes in the intestine and lungs in the H2-treated group. CONCLUSIONS: These findings may contribute to clarifying the mechanism of action of H2 therapy in sepsis.

Sex and age differences in isolated traumatic brain injury: a retrospective observational study.

BACKGROUND: Among the many factors that may influence traumatic brain injury (TBI) progression, sex is one of the most controversial. The objective of this study was to investigate sex differences in TBI-associated morbidity and mortality using data from the largest trauma registry in Japan. METHODS: This retrospective, population-based observational study included patients with isolated TBI, who were registered in a nationwide database between 2004 and 2018. We excluded patients with extracranial injury (Abbreviated Injury Scale score ≥ 3) and removed potential confounding factors, such as non-neurological causes of mortality. Patients were stratified by age and mortality and post-injury complications were compared between males and females. RESULTS: A total of 51,726 patients with isolated TBI were included (16,901 females and 34,825 males). Mortality across all ages was documented in 12.01% (2030/16901) and 12.76% (4445/34825) of males and females, respectively. The adjusted odds ratio (OR) of TBI mortality for males compared to females was 1.32 (95% confidence interval [CI], 1.22-1.42]. Males aged 10-19 years and ≥ 60 years had a significantly higher mortality than females in the same age groups (10-19 years: adjusted OR, 1.97 [95% CI, 1.08-3.61]; 60-69 years: adjusted OR, 1.24 [95% CI, 1.02-1.50]; 70-79 years: adjusted OR, 1.20 [95% CI, 1.03-1.40]; 80-89 years: adjusted OR, 1.50 [95% CI, 1.31-1.73], and 90-99 years: adjusted OR, 1.72 [95% CI, 1.28-2.32]). In terms of the incidence of post-TBI neurologic and non-neurologic complications, the crude ORs were 1.29 (95% CI, 1.19-1.39) and 1.14 (95% CI, 1.07-1.22), respectively, for males versus females. This difference was especially evident among elderly patients (neurologic complications: OR, 1.27 [95% CI, 1.14-1.41]; non-neurologic complications: OR, 1.29 [95% CI, 1.19-1.39]). CONCLUSIONS: In a nationwide sample of patients with TBI in Japan, males had a higher mortality than females. This disparity was particularly evident among younger and older generations. Furthermore, elderly males experienced more TBI complications than females of the same age.

Trends in In-Hospital Advanced Management and Survival of Out-of-Hospital Cardiac Arrest Among Adults From 2013 to 2017　- A Multicenter, Prospective Registry in Osaka, Japan.

BACKGROUND: The aim of our study was to investigate in detail the temporal trends in in-hospital characteristics, actual management, and survival, including neurological status, among adult out-of-hospital cardiac arrest (OHCA) patients in recent years.Methods and Results:From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all OHCA patients aged ≥18 years for whom resuscitation was attempted, and who were transported to participating hospitals between the years 2013 and 2017. The primary outcome measure was 1-month survival with favorable neurological outcome after OHCA. Temporal trends in in-hospital management and favorable neurological outcome among adult OHCA patients were assessed. Of the 11,924 patients in the database, we included a total of 10,228 adult patients from 16 hospitals. As for in-hospital advanced treatments, extracorporeal cardiopulmonary resuscitation (ECPR) use increased from 2.4% in 2013 to 4.3% in 2017 (P for trend <0.001). However, the proportion of adult OHCA patients with favorable neurological outcome did not change during the study period (from 5.7% in 2013 to 4.4% in 2017, adjusted odds ratio (OR) for 1-year increment: 0.98 (95% confidence interval: 0.94-1.23)). CONCLUSIONS: In this target population, in-hospital management such as ECPR increased slightly between 2013 and 2017, but 1-month survival with favorable neurological outcome after adult OHCA did not improve significantly.

Relationship between the number of pediatric patients with rotavirus and telephone triage for associated symptoms.

BACKGROUND: Earlier syndromic surveillance may be effective in preventing the spread of infectious disease. However, there has been no research on syndromic surveillance for rotavirus. The study aimed to assess the relationship between the incidence of rotavirus infections and the number of telephone triages for associated symptoms in pediatric patients under 4 years old in Osaka prefecture, Japan. METHODS: This was a retrospective observational study for which the study period was the 3 years between January 2015 and December 2017. We analyzed data on children under 4 years old who were triaged by telephone triage nurses using software. The primary endpoint was the number of rotavirus patients under 4 years triaged old per week. Using a linear regression model, we calculated the R square value of the regression model to assess the relationship between the number of patients with rotavirus and the number of telephone triages made for associated symptoms. Covariates in the linear regression model were the week number indicating seasonality and the weekly number of telephone triages related to rotavirus symptoms such as stomachache and vomiting. RESULTS: During the study period, there were 102,336 patients with rotavirus, and the number of people triaged by telephone was 123,720. The highest correlation coefficient was 0.921 in the regression model with the number of telephone triages for "stomachache + nausea/vomiting" and "stomachache + diarrhea + nausea/vomiting". CONCLUSION: The number of telephone triage symptoms was positively related to the incidence of pediatric patients with rotavirus in a large metropolitan area of Japan.

Original experimental rat model of blast-induced mild traumatic brain injury: a pilot study.

OBJECTIVE: Diagnosing blast-induced mild traumatic brain injury (mTBI) is difficult due to minimal imaging findings. This study aimed to establish a rat model of behavioral abnormality caused by blast-induced mTBI and detect new findings for therapeutic intervention. METHODS: We used a bench-top blast wave generator with the blast wave exiting through a 20-mm I.D. nozzle aimed at the focused target. The blast wave was directed at the head of male Wistar rats under general anesthesia positioned prone 2.5 cm below the nozzle. Peak shock wave pressure was 646.2 ± 70.3 kPa. RESULTS: After blast injury, mTBI rats did not show the findings of brain hemorrhage or contusion macroscopically and on hematoxylin-eosin-stained frozen sections but did show anorexia and weight loss in the early post-injury phase. Behavioral experiments revealed short-term memory impairment at 2 weeks and depression-like behavior at 2 and 6 weeks. Diffusion-weighted ex vivo MRI showed high-intensity areas in layers of the bilateral hippocampus. Immunohistochemical analysis revealed accumulation of reactive microglia and GFAP-positive astrocytes in the same region and loss of NeuN-positive neurons in the hippocampal pyramidal cell layer. CONCLUSIONS: This model can reflect the pathophysiology of blast-induced mTBI and could potentially be used to develop therapeutic interventions in the future.

Fecal Gram staining of phagocytosed bacteria to differentiate methicillin-resistant Staphylococcus aureus: A case report.

Antibiotic-associated diarrhea is a relatively common problem, and the main bacterial cause is Clostridioides difficile followed by Staphylococcus aureus and other pathogens. The diagnostic procedure for methicillin-resistant S. aureus enteritis is not well established. Phagocytosis is a key antimicrobial process involved in host defense. Phagocytosed bacteria identified by Gram staining are one marker to identify causative microorganisms and select subsequent treatment strategies. However, there are few reports on fecal Gram staining using phagocytosed bacteria as a target for diarrhea treatment. We report the successful use of fecal Gram staining to diagnose and treat methicillin-resistant S. aureus enteritis.

Poor Long-Term Survival of Out-of-Hospital Cardiac Arrest in Children.

The effect of post-cardiac arrest care in children with out-of-hospital cardiac arrest (OHCA) has not been adequately established, and the long-term outcome after pediatric OHCA has not been sufficiently investigated. We describe here detailed in-hospital characteristics, actual management, and survival, including neurological status, 90 days after OHCA occurrence in children with OHCA transported to critical care medical centers (CCMCs).We analyzed the database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study, which is a multicenter, prospective observational data registry designed to accumulate both pre- and in-hospital data on OHCA treatments. We enrolled all consecutive pediatric patients aged <18 years who had an OHCA and for whom resuscitation was attempted and who were transported to CCMCs between 2012 and 2016.A total of 263 pediatric patients with OHCA were enrolled. The average age of the patients was 6.3 years, 38.0% were aged < 1 year, and 60.8% were male. After hospital arrival, 4.9% of these pediatric patients received defibrillation; 1.9%, extracorporeal life support; 6.5%, target temperature management; and 88.2% adrenaline administration. The proportions of patients with 90-day survival and a pediatric cerebral performance category (PCPC) score of 1 or 2 were 6.1% and 1.9%, respectively. The proportion of patients with a PCPC score of 1 or 2 at 90 days after OHCA occurrence did not significantly improve during the study period.The proportion of pediatric patients with a 90-day PCPC score of 1 or 2 transported to CCMCs was extremely low, and no significant improvements were observed during the study period.

Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: a randomized controlled trial.

BACKGROUND: Commensal microbiota deteriorate in critically ill patients. The preventive effects of probiotic/synbiotic therapy on microbiota and septic complications have not been thoroughly clarified in patients with sepsis. The objective of this study was to evaluate whether synbiotics have effects on gut microbiota and reduce complications in mechanically ventilated patients with sepsis. METHODS: Sepsis patients who were mechanically ventilated in the intensive care unit (ICU) were included in this randomized controlled study. Patients receiving daily synbiotics (Bifidobacterium breve strain Yakult, Lactobacillus casei strain Shirota, and galactooligosaccharides) initiated within 3 days after admission (the Synbiotics group) were compared with patients who did not receive synbiotics (the No-Synbiotics group). The primary outcome was infectious complications including enteritis, ventilator-associated pneumonia (VAP), and bacteremia within 4 weeks from admission. The secondary outcomes included mortality within 4 weeks, fecal bacterial counts, and organic acid concentration. Enteritis was defined as the acute onset of continuous liquid stools for more than 12 h. RESULTS: Seventy-two patients completed this trial; 35 patients received synbiotics and 37 patients did not receive synbiotics. The incidence of enteritis was significantly lower in the Synbiotics than the No-Synbiotics group (6.3% vs. 27.0%; p < 0.05). The incidence of VAP was also significantly lower in the Synbiotics than the No-Synbiotics group (14.3% vs. 48.6%; p < 0.05). The incidence of bacteremia and mortality did not differ significantly between the two groups. In the analysis of fecal bacteria, the number of Bifidobacterium and Lactobacillus in the Synbiotics group was significantly higher than that in the No-Synbiotics group. In the analysis of fecal organic acids, total organic acid concentration, especially the amounts of acetate, were significantly greater in the Synbiotics group than in the No-Synbiotics group at the first week (p < 0.05). CONCLUSIONS: Prophylactic synbiotics could modulate the gut microbiota and environment and may have preventive effects on the incidence of enteritis and VAP in patients with sepsis. TRIAL REGISTRATION: UMIN, R000007633 . Registered on 29 September 2011.

Association of prophylactic synbiotics with reduction in diarrhea and pneumonia in mechanically ventilated critically ill patients: A propensity score analysis.

INTRODUCTION: The preventive association of synbiotics therapy has not been thoroughly clarified in mechanically ventilated patients. The purpose of this study was to evaluate whether synbiotics therapy has preventive association against septic complications in ventilated critically ill patients. METHODS: Critically ill patients who were mechanically ventilated were included in this retrospective observational study. Patients who received synbiotics (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) within 3 days after admission (denoted as synbiotics group) were compared with patients who did not receive synbiotics. The incidences of enteritis, pneumonia, and bacteremia were evaluated as clinical outcome. Enteritis was defined as an acute onset of diarrhea consisting of continuous liquid watery stools for more than 12 h. The confounding factors include APACHE II on admission, gender, the cause of admission and antibiotics. RESULTS: We included 179 patients in this study: 57 patients received synbiotics and 122 patients did not receive synbiotics. The incidences of enteritis were significantly lower in the synbiotics group compared with the control group (3.5% vs. 15.6%; p < 0.05). The odds ratios for diarrhea-free days during the first 28 days for the synbiotics group as compared with the controls were 4.354 (95% confidence interval (CI), 2.407 to 7.877; p < 0.001) in an ordinal logistic regression model with propensity scores. The odds ratios for pneumonia-free days during the first 28 days for the synbiotics group were 2.529 (95% CI, 1.715 to 3.731; p < 0.001). The incidences of bacteremia did not have significant differences. CONCLUSION: Prophylactic synbiotics appeared to have preventive association on enteritis and pneumonia in mechanically ventilated critically ill patients.

Relationship Between Infarct Volume and Prothrombin Time-International Normalized Ratio in Ischemic Stroke Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: In Japan, warfarin treatment at prothrombin time-international normalized ratio (PT-INR) of 1.60-2.60 is recommended for elderly patients with nonvalvular atrial fibrillation (NVAF). But it remains unknown whether PT-INR 1.60-1.99 has a similar effect on stroke severity as a value >2.0. The purpose of this study was to clarify the association between infarct volume and PT-INR levels.Methods and Results:The 180 patients (mean age, 76 years [SD, 10 years], 53% male) selected from 429 consecutive ischemic stroke patients admitted within 48 h of onset between 2004 and 2014 with NVAF were included. We classified them into 4 groups according to their PT-INR values on admission: no warfarin (NW), 129 patients; PT-INR <1.60 (poor control: PC), 29 patients; PT-INR 1.60-1.99 (low-intensity control: LC), 14 patients; and PT-INR ≥2.00 (high-intensity control: HC), 8 patients. Median (interquartile range: IQR) of infarct volume was 55 mL (IQR 14-175) in the NW, 42 mL (IQR 27-170) in the PC, 36 mL (IQR 6-130) in the LC, and 11 mL (IQR 0-39) in the HC groups. The infarct volume of the HC group was significantly smaller than in the other 3 groups, but no difference existed between the LC and PC groups or the LC and NW groups. CONCLUSIONS: Warfarin control at PT-INR of 1.60-1.99 is not effective for reducing the severity of ischemic stroke in NVAF patients.

Both high and low plasma glutamine levels predict mortality in critically ill patients.

PURPOSE: Plasma amino acids are important indicators for understanding human kinetics and amino acid dynamics. We aimed to investigate the association between the plasma glutamine levels and the mortality rates and determine whether plasma glutamine can predict the prognosis of critically ill patients. METHODS: The clinical records of adult patients who were admitted to an ICU were retrospectively evaluated to investigate the plasma levels of amino acids, including glutamine. RESULTS: Two hundred fourteen patients were included in this study (male, 62%; median age, 64 years; range 20-97 years). The patients' diagnoses included sepsis (45%), trauma (14%), cardiovascular disease (9%), fulminant hepatitis (9%), burns (4%), and others (19%). The mortality rates in patients with plasma glutamine <400 nmol/mL (group L; 39%, 28/71) or ≥700 nmol/mL (group H; 50%, 15/30) were significantly higher (p < 0.05 and p < 0.01, respectively) than those in patients with plasma glutamine levels of 400-700 nmol/mL (group M; 21%, 24/113). Among patients with sepsis, the mortality rates of group L (46%) and group H (67%) were significantly higher (p < 0.05 or p < 0.01, respectively) in comparison with group M (26%). CONCLUSION: Both lower and higher plasma glutamine levels were risk factors for mortality in critically ill patients.

Metagenomic Analysis Reveals Dynamic Changes of Whole Gut Microbiota in the Acute Phase of Intensive Care Unit Patients.

BACKGROUND: Metagenomic analysis targeting the 16S rRNA gene has made it possible to characterize the vast array of microorganisms contained in the gut. AIM: The purpose of this study was to evaluate how gut microbiota change in intensive care unit (ICU) patients in the acute phase after admission. METHODS: This prospective observational cohort study investigated 12 patients admitted to a single ICU of a large urban tertiary referral hospital. All patients were mechanically ventilated on admission. Fecal samples were collected from patients on days 1-2, 2-4, 5-8, and 7-10 after admission. DNA was extracted from fecal samples, and 16S rRNA deep sequencing was performed to monitor gut changes. RESULTS: Bacteria belonging to the phyla Firmicutes or Bacteroidetes were predominant in each sample. We observed serial dynamic changes in the percentages of Bacteroidetes and Firmicutes that were significantly altered during study period (p < 0.05). A ratio of Bacteroidetes to Firmicutes (B/F ratio) of >10 was seen in four of the six patients who died, whereas a B/F ratio of <0.10 was seen in only one of the six deaths. None of the survivors had a B/F ratio of >10 or <0.10. There was a statistical difference in the B/F ratio between the dead patients and survivors (p = 0.022). CONCLUSIONS: Dynamic changes in gut microbiota at the phylum level of ICU patients during the acute phase were identified by high-throughput DNA sequencing. An extreme imbalance in gut microbiota may be associated with prognosis in critically ill patients.

Temporal Trends in Outcomes after Out-of-Hospital Cardiac Arrests Witnessed by Emergency Medical Services in Japan: A Population-Based Study.

OBJECTIVE: Survival after out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical service (EMS) personnel has been insufficiently understood. The aim of this study was to evaluate temporal trends in survival after EMS-witnessed OHCAs in Japan. METHODS: A nationwide, population-based, observational cohort study of consecutive adult OHCA patients with emergency responder resuscitation attempts from January 2005 to December 2012 in Japan. We assessed the trends in annual incidence, characteristics, and outcomes of OHCA patients witnessed by EMS personnel. Multiple logistic regression analysis was used to assess factors that were potentially associated with neurologically favorable outcome defined as cerebral performance category scale 1or 2. RESULTS: During the study period, a total of 66,760 EMS-witnessed OHCAs were documented. The annual incidence rates per 100,000 persons of EMS-witnessed OHCA patients increased from 4.6 (n = 7219) in 2005 to 4.9 (n = 9256) in 2012 (p for trend = 0.035). The proportion of one-month survival with neurologically favorable outcome improved from 5.9% in 2005 to 8.6% in 2012 (p for trend < 0.001), and the proportion increased from 22.1% in 2005 to 30.2% in 2012 in cases with shockable rhythm (p for trend < 0.001). In a multivariate analysis, adults, male gender, shockable rhythm, presumed cardiac origin, and year were associated with a better neurological outcome. CONCLUSIONS: In this population, the proportion of one-month survival with neurologically favorable outcome among OHCA patients witnessed by EMS personnel significantly improved during the study period.