Long-Term Outcomes of Brugada Substrate Ablation: A Report from BRAVO (Brugada Ablation of VF Substrate Ongoing Multicenter Registry).

BACKGROUND: Treatment options for high-risk Brugada syndrome (BrS) with recurrent ventricular fibrillation (VF) are limited. Catheter ablation is increasingly performed but a large study with long-term outcome data is lacking. We report the results of the multicenter, international BRAVO (Brugada Ablation of VF Substrate Ongoing Registry) for treatment of high-risk symptomatic BrS. METHODS: We enrolled 159 patients (median age 42 years; 156 male) with BrS and spontaneous VF in BRAVO; 43 (27%) of them had BrS and early repolarization pattern. All but 5 had an implantable cardioverter-defibrillator for cardiac arrest (n=125) or syncope (n=34). A total of 140 (88%) had experienced numerous implantable cardioverter-defibrillator shocks for spontaneous VF before ablation. All patients underwent a percutaneous epicardial substrate ablation with electroanatomical mapping except for 8 who underwent open-thoracotomy ablation. RESULTS: In all patients, VF/BrS substrates were recorded in the epicardial surface of the right ventricular outflow tract; 45 (29%) patients also had an arrhythmic substrate in the inferior right ventricular epicardium and 3 in the posterior left ventricular epicardium. After a single ablation procedure, 128 of 159 (81%) patients remained free of VF recurrence; this number increased to 153 (96%) after a repeated procedure (mean 1.2±0.5 procedures; median=1), with a mean follow-up period of 48±29 months from the last ablation. VF burden and frequency of shocks decreased significantly from 1.1±2.1 per month before ablation to 0.003±0.14 per month after the last ablation (P<0.0001). The Kaplan-Meier VF-free survival beyond 5 years after the last ablation was 95%. The only variable associated with a VF-free outcome in multivariable analysis was normalization of the type 1 Brugada ECG, both with and without sodium-channel blockade, after the ablation (hazard ratio, 0.078 [95% CI, 0.008 to 0.753]; P=0.0274). There were no arrhythmic or cardiac deaths. Complications included hemopericardium in 4 (2.5%) patients. CONCLUSIONS: Ablation treatment is safe and highly effective in preventing VF recurrence in high-risk BrS. Prospective studies are needed to determine whether it can be an alternative treatment to implantable cardioverter-defibrillator implantation for selected patients with BrS. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04420078.

Efficacy of left atrial posterior wall isolation guided by lesion size prediction module for non-paroxysmal atrial fibrillation.

AIMS: The efficacy of left atrial posterior wall isolation (PWI) is controversial. Lesion durability may be a major cause of arrhythmia recurrence. The use of the lesion size prediction module improves lesion durability. This study aimed to compare the clinical outcomes of pulmonary vein isolation (PVI) alone and PWI in addition to PVI (PVI + PWI) in patients with non-paroxysmal atrial fibrillation (AF) using a lesion size prediction module. METHODS AND RESULTS: This study is a sub-analysis of the recently published prospective multicentre observational study called ALCOHOL-AF (association of alcohol consumption with outcome of catheter ablation of AF). In this sub-analysis, patients with non-paroxysmal AF in whom PVI alone or PVI + PWI was performed using the lesion size prediction module were included. Freedom from atrial tachyarrhythmia was compared between PVI alone and PVI + PWI groups using propensity score analyses. Of the 3474 patients registered in the ALCOHOL-AF study, 572 patients (age 65.6 ± 10.1 years, male 77.4%, longstanding persistent AF 25.5%) were included in this sub-analysis. We selected 212 patients treated with PVI alone and 212 treated with PVI + PWI using one-to-one propensity score matching. During the follow-up period, atrial tachyarrhythmia recurrence was documented in 92 (43.4%) and 50 (23.6%) patients in the PVI alone and PVI + PWI groups, respectively. Freedom from atrial tachyarrhythmia recurrence without anti-arrhythmic drugs after a single procedure was significantly higher in PVI + PWI than in PVI alone groups (hazard ratio: 0.452, 95% confidence interval: 0.308-0.664, P < 0.001). CONCLUSION: In this hypothesis-generating study, lesion size prediction module-guided PVI + PWI was associated with better clinical outcomes than PVI alone in patients with persistent or longstanding persistent AF.

Investigation of differences in coagulation characteristics between hospitalized patients with SARS-CoV-2 Alpha, Delta, and Omicron variant infection using rotational thromboelastometry (ROTEM): A single-center, retrospective, observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 Omicron variant has a low rate of serious illness, is highly contagious, and has spread rapidly since January 2022. The number of severe cases and deaths remains problematic. Here, we aimed to elucidate the coagulation pathology of Omicron-infected patients using rotational thromboelastometry. METHODS: Patients with coronavirus disease 2019, hospitalized and treated from January 2021 to April 2022, were included. The Alpha-Delta and Omicron groups were defined during admission. Blood tests, clinical course, and rotational thromboelastometry measurements were compared using a propensity score-matched cohort. RESULTS: Both groups had 21 patients each. Lactate dehydrogenase (Alpha-Delta group [interquartile range] vs. Omicron group [interquartile range]; 449 [368-518] U/L vs. 241 [196-398] U/L, p = 0.01) and ferritin (1428 [1145-3061] ng/dl vs. 481 [188-881] ng/dl, p = 0.0002) levels were significantly lower in the Omicron group. In rotational thromboelastometry, the thrombus hardness indexes FIBTEM A5 (29 [23-34] mm vs. 23 [18-28] mm, p = 0.034) and maximum clot firmness (34 [27-40] mm vs. 26 [21-33] mm, p = 0.021) were significantly lower in the Omicron group, whereas the fibrinolysis index FIBTEM LI60 (98 [92-100] % vs. 100 [100-100] %, p = 0.0082) was higher. CONCLUSION: Severe coagulation abnormalities may be less likely in Omicron-infected patients than in those infected with the previous Alpha and Delta variants.

Incidence and Characteristics of Coronary Artery Spasms Related to Atrial Fibrillation Ablation Procedures　- Large-Scale Multicenter Analysis.

BACKGROUND: Coronary artery spasms (CASs), which can cause angina attacks and sudden death, have been recently reported during catheter ablation. The aim of the present study was to report the incidence, characteristics, and prognosis of CASs related to atrial fibrillation (AF) ablation procedures.Methods and Results:The AF ablation records of 22,232 patients treated in 15 Japanese hospitals were reviewed. CASs associated with AF ablation occurred in 42 of 22,232 patients (0.19%). CASs occurred during ablation energy applications in 21 patients (50%). CASs also occurred before ablation in 9 patients (21%) and after ablation in 12 patients (29%). The initial change in the electrocardiogram was ST-segment elevation in the inferior leads in 33 patients (79%). Emergency coronary angiography revealed coronary artery stenosis and occlusions, which were relieved by nitrate administration. No air bubbles were observed. A comparison of the incidence of CASs during pulmonary vein isolation between the different ablation energy sources revealed a significantly higher incidence with cryoballoon ablation (11/3,288; 0.34%) than with radiofrequency catheter, hot balloon, or laser balloon ablation (8/18,596 [0.04%], 0/237 [0%], and 0/111 [0%], respectively; P<0.001). CASs most often occurred during ablation of the left superior pulmonary vein. All patients recovered without sequelae. CONCLUSIONS: CASs related to AF ablation are rare, but should be considered as a dangerous complication that can occur anytime during the periprocedural period.

Prevention of long-lasting atrial fibrillation through antitachycardia pacing in DDDR pacemakers.

OBJECTIVE: The MINERVA trial showed that in pacemaker patients with atrial fibrillation (AF) history, DDDRP pacing combining three algorithms - (a) atrial antitachycardia pacing with Reactive ATP enabled, (b) atrial preventive pacing and (c) managed ventricular pacing (MVP)-may effectively delay progression to persistent/permanent AF compared with standard DDDR pacing. We performed a comparative non-randomised evaluation to evaluate if Reactive ATP can be the main driver of persistent/permanent AF reduction independently on preventive pacing. METHODS: Thirty-one centres included consecutive dual-chamber pacemaker patients with AF history. Reactive ATP was programmed in all patients while preventive atrial pacing was not enabled. These patients were compared with the three groups of MINERVA randomised trial (Control DDDR, MVP, and DDDRP). The main endpoint was the incidence of AF longer than 7 consecutive days. RESULTS: A total of 146 patients (73 years old, 54% male) were included and followed for a median observation period of 31 months. The 2-year incidence of AF > 7 days was 12% in the Reactive ATP group, very similar to that found in the DDDRP arm of the MINERVA trial (13.8%, P = .732) and significantly lower than AF incidence found in the MINERVA Control DDDR arm (25.8%, P = .012) and in the MINERVA MVP arm (25.9%, P = .025). CONCLUSIONS: In a real-world population of dual-chamber pacemaker patients with AF history, the use of Reactive ATP is associated with a low incidence of persistent AF, highlighting that the positive results of the MINERVA trial were related to the effectiveness of Reactive ATP rather than to preventive pacing.

Significance of body temperature in elderly patients with sepsis.

BACKGROUND: Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis. METHODS: This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome). RESULTS: In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07-2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29-3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03-1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05). CONCLUSIONS: In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients.

Characteristics and outcomes of frail patients with suspected infection in intensive care units: a descriptive analysis from a multicenter cohort study.

BACKGROUND: Frailty is associated with morbidity and mortality in patients admitted to intensive care units (ICUs). However, the characteristics of frail patients with suspected infection remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs. METHODS: This is a secondary analysis of a multicenter cohort study, including 22 ICUs in Japan. Adult patients (aged ≥16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes among three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score, 1-3), vulnerable (score, 4), and frail (score, 5-9). We conducted subgroup analysis of patients with sepsis defined as per Sepsis-3 criteria. We also produced Kaplan-Meier survival curves for 90-day survival. RESULTS: We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median CFS score of 3 (interquartile range [IQR] 3-5) were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 (31.4%) were frail. The median patient age was 72 years (IQR 60-81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (IQR 4-10), 8 (IQR 5-11), and 7 (IQR 5-10), respectively (p = 0.59). The median body temperatures of fit, vulnerable, and frail patients were 37.5 °C (IQR 36.5 °C-38.5 °C), 37.5 °C (IQR 36.4 °C-38.6 °C), and 37.0 °C (IQR 36.3 °C-38.1 °C), respectively (p < 0.01). The median C-reactive protein levels of fit, vulnerable, and frail patients were 13.6 (IQR 4.6-24.5), 12.1 (IQR 3.9-24.9), 10.5 (IQR 3.0-21.0) mg/dL, respectively (p < 0.01). In-hospital mortality did not statistically differ among the patients according to frailty (p = 0.19). Kaplan-Meier survival curves showed little difference in the mortality rate during short-term follow-up. However, more vulnerable and frail patients died after 30-day than fit patients; this difference was not statistically significant (p = 0.25). Compared with the fit and vulnerable groups, the rate of home discharge was lower in the frail group. CONCLUSION: Frail and vulnerable patients with suspected infection tend to have poor disease outcomes. However, they did not show a statistically significant increase in the 90-day mortality risk.

Influence of hyperbaric oxygen therapy on thrombus formation ability in humans.

Background: Hyperbaric oxygen (HBO2) therapy was introduced nearly 300 years ago. However, its effect on thrombus formation is unclear. This may be because platelet and coagulation functions are unstable, yielding variable results; hence, accurate measurement is difficult. Our study aimed to analyze changes in thrombus formation before and after HBO2 therapy by using a total thrombus formation analysis system (TTAS). Methods: Six patients were prescribed HBO2 therapy for skin and soft tissue ulcers, and necrotic fasciitis. Blood samples were collected immediately before and after treatment. Then samples were put into a reservoir that connected to AR-chip to assess changes in the thrombus formation ability of both platelets and coagulation factors. We examined the differences in the thrombus formation ability using T-TAS. Time until the onset of white thrombus formation (T10) and complete occlusion of the capillary (T80) were analyzed by a two-way repeated measure analysis of variance (ANOVA). Results: The duration to pressure increase of samples after HBO2 therapy was longer than the duration before HBO2 therapy (p<0.05). This suggests decreased clot adhesiveness to the inner surface of the simulated blood vessel and reduced clot formation ability. Conclusions: The results for T10 and T80 suggest that HBO2 therapy reduced thrombus formation ability in the enrolled patients. We believe that T-TAS is a promising method to predict the efficacy of HBO2 therapy.

Impact of Body Temperature Abnormalities on the Implementation of Sepsis Bundles and Outcomes in Patients With Severe Sepsis: A Retrospective Sub-Analysis of the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis and Trauma Study.

OBJECTIVES: To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients. DESIGN: Retrospective sub-analysis. SETTING: Fifty-nine ICUs in Japan, from January 2016 to March 2017. PATIENTS: Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature < 36°C, 36-38°C, > 38°C), using the core body temperature at ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compliance with the bundles proposed in the Surviving Sepsis Campaign Guidelines 2012, in-hospital mortality, disposition after discharge, and the number of ICU and ventilator-free days were evaluated. Of 1,143 enrolled patients, 127, 565, and 451 were categorized as having body temperature less than 36°C, 36-38°C, and greater than 38°C, respectively. Hypothermia-body temperature less than 36°C-was observed in 11.1% of patients. Patients with hypothermia were significantly older than those with a body temperature of 36-38°C or greater than 38°C and had a lower body mass index and higher prevalence of septic shock than those with body temperature greater than 38°C. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on the day of enrollment were also significantly higher in hypothermia patients. Implementation rates of the entire 3-hour bundle and administration of broad-spectrum antibiotics significantly differed across categories; implementation rates were significantly lower in patients with body temperature less than 36°C than in those with body temperature greater than 38°C. Implementation rate of the entire 3-hour resuscitation bundle + vasopressor use + remeasured lactate significantly differed across categories, as did the in-hospital and 28-day mortality. The odds ratio for in-hospital mortality relative to the reference range of body temperature greater than 38°C was 1.760 (95% CI, 1.134-2.732) in the group with hypothermia. The proportions of ICU-free and ventilator-free days also significantly differed between categories and were significantly smaller in patients with hypothermia. CONCLUSIONS: Hypothermia was associated with a significantly higher disease severity, mortality risk, and lower implementation of sepsis bundles.

Pulmonary vein-gap re-entrant atrial tachycardia following atrial fibrillation ablation: an electrophysiological insight with high-resolution mapping.

AIMS: The circuit of pulmonary vein-gap re-entrant atrial tachycardia (PV-gap RAT) after atrial fibrillation ablation is sometimes difficult to identify by conventional mapping. We analysed the detailed circuit and electrophysiological features of PV-gap RATs using a novel high-resolution mapping system. METHODS AND RESULTS: This multicentre study investigated 27 (7%) PV-gap RATs in 26 patients among 378 atrial tachycardias (ATs) mapped with Rhythmia™ system in 281 patients. The tachycardia cycle length (TCL) was 258 ± 52 ms with P-wave duration of 116 ± 28 ms. Three types of PV-gap RAT circuits were identified: (A) two gaps in one pulmonary vein (PV) (unilateral circuit) (n = 17); (B) two gaps in the ipsilateral superior and inferior PVs (unilateral circuit) (n = 6); and (C) two gaps in one PV with a large circuit around contralateral PVs (bilateral circuit) (n = 4). Rhythmia™ mapping demonstrated two distinctive entrance and exit gaps of 7.6 ± 2.5 and 7.9 ± 4.1 mm in width, respectively, the local signals of which showed slow conduction (0.14 ± 0.18 and 0.11 ± 0.10m/s) with fragmentation (duration 86 ± 27 and 78 ± 23 ms) and low-voltage (0.17 ± 0.13 and 0.17 ± 0.21 mV). Twenty-two ATs were terminated (mechanical bump in one) and five were changed by the first radiofrequency application at the entrance or exit gap. Moreover, the conduction time inside the PVs (entrance-to-exit) was 138 ± 60 ms (54 ± 22% of TCL); in all cases, this resulted in demonstrating P-wave with an isoelectric line in all leads. CONCLUSION: This is the first report to demonstrate the detailed mechanisms of PV-gap re-entry that showed evident entrance and exit gaps using a high-resolution mapping system. The circuits were variable and Rhythmia™-guided ablation targeting the PV-gap can be curative.

In-hospital mortality associated with the misdiagnosis or unidentified site of infection at admission.

BACKGROUND: Rapid detection, early resuscitation, and appropriate antibiotic use are crucial for sepsis care. Accurate identification of the site of infection may facilitate a timely provision of appropriate care. We aimed to investigate the relationship between misdiagnosis of the site of infection at initial examination and in-hospital mortality. METHODS: This was a secondary-multicenter prospective cohort study involving 37 emergency departments. Consecutive adult patients with infection from December 2017 to February 2018 were included. Misdiagnosis of the site of infection was defined as a discrepancy between the suspected site of infection at initial examination and that at final diagnosis, including those infections remaining unidentified during hospital admission, whereas correct diagnosis was defined as site concordance. In-hospital mortality was compared between those misdiagnosed and those correctly diagnosed. RESULTS: Of 974 patients included in the analysis, 11.6% were misdiagnosed. Patients diagnosed with lung, intra-abdominal, urinary, soft tissue, and CNS infection at the initial examination, 4.2%, 3.8%, 13.6%, 10.9%, and 58.3% respectively, turned out to have an infection at a different site. In-hospital mortality occurred in 15%. In both generalized estimating equation (GEE) and propensity score-matched models, misdiagnosed patients exhibited higher mortality despite adjustment for patient background, site infection, and severity. The adjusted odds ratios (misdiagnosis vs. correct diagnosis) for in-hospital mortality were 2.66 (95% CI, 1.45-4.89) in the GEE model and 3.03 (95% CI, 1.24-7.38) in the propensity score-matched model. The difference in the absolute risk in the GEE model was 0.11 (0.04-0.18). CONCLUSIONS: Among patients with infection, misdiagnosed site of infection is associated with a > 10% increase in in-hospital mortality.

Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study.

BACKGROUND: Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. METHODS: This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0-60, 61-120, 121-180, 181-240, 241-360, and 361-1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with "hospital" as the grouping variable. RESULTS: Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55-189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48-164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39-180 min)] and longest in patients transferred from wards [120 min (62-226)]. Overall crude mortality was 23.4%, where patients in the 0-60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3-34.1%)], whereas those in the 61-120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5-26.6%)]. Differences in mortality were noted only between the 0-60 min and 61-120 min groups. CONCLUSIONS: We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.

Prognostic Accuracy of Quick SOFA is different according to the severity of illness in infectious patients.

BACKGROUND: Sepsis-3 proposed the quick Sequential Organ Failure Assessment (qSOFA) to identify sepsis patients likely to have poor outcome. The clinical utility of qSOFA still remains controversial because its predictive accuracy for mortality is quite different across the validation studies. We hypothesized that one of the major causes for these controversial findings was the heterogeneity in severity across the studies, and evaluated the association between severity of illness and the prognostic accuracy of qSOFA. MATERIALS AND METHODS: This was a post hoc analysis of a prospective nationwide cohort of consecutive adult patients with sepsis in 59 intensive care units in Japan. Regression trees analysis for survival was used to classify patients according to severity of illness as determined by SOFA score on registration. We conducted receiver operating characteristic (ROC) analyses and evaluated the differences in the area under the ROC curve (AUROC). As a subgroup analysis, we conducted the above evaluations in emergency department (ED) and non-ED patients separately. RESULTS: We included 1114 patients fulfilling the criteria and classified them into three subsets according to severity. The AUROC for mortality was significantly different according to the severity of illness (p = 0.007), with the highest AUROC being in the low-severity subset (patients with SOFA score ≤ 7). Interestingly, our subgroup analysis revealed that a significant difference in the AUROC of qSOFA was observed only in ED patients. CONCLUSION: This study suggested that lower severity of illness was associated with the relatively higher prognostic accuracy of qSOFA, especially in ED patients.

Characteristics, management, and in-hospital mortality among patients with severe sepsis in intensive care units in Japan: the FORECAST study.

BACKGROUND: Sepsis is a leading cause of death and long-term disability in developed countries. A comprehensive report on the incidence, clinical characteristics, and evolving management of sepsis is important. Thus, this study aimed to evaluate the characteristics, management, and outcomes of patients with severe sepsis in Japan. METHODS: This is a cohort study of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) study, which was a multicenter, prospective cohort study conducted at 59 intensive care units (ICUs) from January 2016 to March 2017. We included adult patients with severe sepsis based on the sepsis-2 criteria. RESULTS: In total, 1184 patients (median age 73 years, interquartile range (IQR) 64-81) with severe sepsis were admitted to the ICU during the study period. The most common comorbidity was diabetes mellitus (23%). Moreover, approximately 63% of patients had septic shock. The median Sepsis-related Organ Failure Assessment (SOFA) score was 9 (IQR 6-11). The most common site of infection was the lung (31%). Approximately 54% of the participants had positive blood cultures. The compliance rates for the entire 3-h bundle, measurement of central venous pressure, and assessment of central venous oxygen saturation were 64%, 26%, and 7%, respectively. A multilevel logistic regression model showed that closed ICUs and non-university hospitals were more compliant with the entire 3-h bundle. The in-hospital mortality rate of patients with severe sepsis was 23% (21-26%). Older age, multiple comorbidities, suspected site of infection, and increasing SOFA scores correlated with in-hospital mortality, based on the generalized estimating equation model. The length of hospital stay was 24 (12-46) days. Approximately 37% of the patients were discharged home after recovery. CONCLUSION: Our prospective study showed that sepsis management in Japan was characterized by a high compliance rate for the 3-h bundle and low compliance rate for central venous catheter measurements. The in-hospital mortality rate in Japan was comparable to that of other developed countries. Only one third of the patients were discharged home, considering the aging population with multiple comorbidities in the ICUs in Japan. TRIAL REGISTRATION: UMIN-CTR, UMIN000019742 . Registered on 16 November 2015.

Effects of hyperbaric exposure on thrombus formation.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has a long history of use. However, its effect on thrombus formation is unclear. Many reports have indicated that it accelerates platelet aggregation, which suggests that it may increase thrombotic events. However, clinical trial results are inconsistent, and no previous reports have demonstrated that HBO2therapy does in fact increase thrombotic events. Here, we used a total thrombus formation analysis system (T-TAS) to analyze changes in thrombus formation in a specimen group exposed to constant hyperbaric pressure in vitro, and a control group. METHODS: Blood samples were collected from two sets of 10 healthy volunteers (mean age, 28.8 years) with no underlying disease. In the pressurized group, a constant pressure was applied to specimens in temperature-controlled test tubes; the non-pressurized group served as the control. Thrombus formation in samples from both the pressurized and control groups were measured using the T-TAS immediately, 20 minutes, and 40 minutes after pressurization. RESULTS: In the pressurized group, the onset of thrombus formation was significantly delayed, confirming a reduction in thrombus formation ability. However, the reduced ability for thrombus formation in the pressurized group recovered to the level of the control group. That is, the change in thrombus formation ability caused by pressure was proven to be reversible. CONCLUSIONS: We are the first to ascertain a decrease in the thrombus formation ability in specimens exposed to hyperbaric pressure using a T-TAS, which is capable of measuring thrombus formation in an environment similar to that in vivo.

[Anti DIC therapy].

A variety of disorders erratically activate coagulation cascades. The disseminated intravascular coagulation (DIC) is caused by unbalanced activation between coagulation and fibrinolysis. Some of auxiliary treatments for DIC on top of main therapy against causative disease are beneficial in terms of better outcome. The anticoagulation therapy is indicated when an activation of coagulation dominates in DIC caused by sepsis. Whereas in DIC associated with trauma, since balance between coagulation and fibrinolysis collapses drastically in a short period, both anticoagulantion therapy and antifibrinolytic therapy can be utilized depending on clinical conditions. There are quite a few of anti DIC agents in Japan. It is imperative to choose appropriate agents to treat DIC taking their pharmacological properties into account.

Risk factors for bowel necrosis in patients with hepatic portal venous gas.

PURPOSE: To evaluate the risk factors for bowel necrosis in adult patients with hepatic portal venous gas (HPVG). METHODS: This retrospective study comprised 33 adult patients treated for HPVG between August, 2008 and December, 2011. The patients were divided into a necrotic group (n = 14) and a non-necrotic group (n = 19). We analyzed the clinical demographics, laboratory data, multi-detector computed tomography findings, treatments, and outcomes in each group. RESULTS: Abdominal pain, peritoneal signs, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH), small intestinal dilatation, poor enhancement of the bowel wall, and intestinal pneumatosis were all significantly associated with bowel necrosis. Moreover, there were significantly more operative cases and deaths in the necrotic group. Multivariate analysis revealed that systolic BP (p = 0.048), LDH (p = 0.022), and intestinal pneumatosis (p = 0.038) were independent risk factors for bowel necrosis. Thus, we created new diagnostic criteria for bowel necrosis based on these three factors, the sensitivity, specificity, and accuracy of which were 100, 78.9, and 87.9 %, respectively. CONCLUSIONS: This study demonstrates new and important findings to evaluate the risk factors for bowel necrosis. Using our diagnostic criteria, the indications for emergency laparotomy can be established more accurately.

Metastasis of osteosarcoma to the trapezius muscle: a case report.

Metastasis of a primary osteosarcoma to the muscles is extremely rare. As there have been few reported cases, the necessity of surgical treatment for such metastatic lesions remains controversial. We present the case of a primary osteosarcoma with development of a solitary metastasis to the trapezius muscle during chemotherapy for pulmonary metastasis. The patient was a 51-year-old man diagnosed with osteosarcoma of the right tibia. After undergoing chemotherapy and femoral amputation, he developed pulmonary metastasis. Chemotherapy was reinitiated, however, after approximately 1 year a palpable tumor was identified in the patient's right shoulder. This tumor grew and was associated with pain in the right shoulder. It was surgically removed 3 years after the re-initiation of chemotherapy. The pathological diagnosis was osteosarcoma with metastasis to the trapezius muscle. Although the patient died of respiratory failure due to pulmonary metastasis 14 months after resection of the metastatic lesion in the trapezius muscle, no new extrapulmonary metastasis was observed after the resection.

The Relationship Between Acute-Phase Circuit Occlusion and Blood Calcium Concentration in an Ex Vivo Continuous Renal Replacement Therapy Model.

Background and objective Continuous renal replacement therapy (CRRT) is a blood purification therapy modality for the treatment of renal failure in critically ill hospitalized patients with multiorgan dysfunction, effectively preventing uremia and multiple organ failure while improving renal function. However, the perfusion of patient blood through extracorporeal circulation often results in unexpected early occlusion of the CRRT circuit or hemofilter, leading to frequent interruptions in CRRT and wastage of medical resources. Moreover, clinical research on such circuit occlusions is limited. In Japan, CRRT circuits require long-term perfusion, often lasting 24 hours or more, indicating the need for a model capable of inducing occlusion at any arbitrary time; this model can evaluate various aspects, including causes and underlying mechanisms, and contribute to the development of an occlusion prediction method. Hence, we hypothesized the need for a model for inducing occlusion at arbitrary time points. Consequently, we strove to develop an ex vivo circuit occlusion model involving the injection of calcium into circulating citrated animal blood to evaluate the relationship between the amount of calcium chloride injected, circuit occlusion time, and changes in circuit pressure over time. Methods We developed a circuit occlusion model using a commercially available CRRT circuit, polysulfone membrane hemofilter, heating extension tube, and thermostatic water bath, along with commercially available citrated bovine whole blood. The circuit was filled with blood over a 10-min duration using a roller pump and was occluded after a specific period by varying the flow rate of calcium injected into bovine whole blood. Additionally, continuous injection of 1 mEq/mL calcium chloride into the circuit was maintained while bovine whole blood circulated. Measurements were performed at each calcium injection flow rate (2, 3, and 4 mL/h), with each measurement performed five times. The group that did not receive calcium injection was used as the control (0 mL/h: Con), and the experiment was performed three times. Groups were defined as "0, 2, 3, and 4" for each calcium injection flow rate. The relationship among the amount of calcium chloride injected, circuit occlusion time, and changes in circuit pressure over time was evaluated. Furthermore, blood tests and blood viscoelastic tests were performed at arbitrary times. Results The circuit occlusion time varied with each calcium injection flow rate, and a significant difference was observed between each group (p<0.05). Circuit pressure gradually changed at four min before occlusion when calcium was injected at 2, 3, and 4 mL/h, with a more rapid change at one min before occlusion. We measured circuit pressure at four and one min before occlusion (-4 min, and -1 min, respectively), and at the time of circuit occlusion (0 min) in the Con and 4 mL/h groups. Significant differences were observed in AP between -4 min and 0 min and -1 min and 0 min at a calcium flow rate of 4 mL/h. Additionally, significant differences were seen in prefilter and return pressures between -4 min and 0 min, -4 min and -1 min, and -1 min and 0 min at a calcium flow rate of 4 mL/h (p<0.05). Conclusions Our proposed model accurately estimated the occlusion time based on changes in circuit pressure. This model can be used to create various experimental systems depending on the desired occlusion time.

Thromboelastometric Analysis of the Correlation Between Burn-Induced Coagulopathy and Severity of Burn Injury.

Background In this study, we aimed to analyze the association between the burn index (BI) and burn-induced coagulopathy. Methods Adult burn patients transported to our emergency department who underwent rotational thromboelastometry (ROTEM) between April 1, 2013, and December 31, 2021, were enrolled in this study. The patients were categorized into two groups based on burn severity. Severe burns were defined as BI scores of > 15. Patient demographics, clinical variables of burns, standard laboratory test data, ROTEM data, and clinical outcomes of both groups were evaluated. In addition, the correlation between severe burns and significant variables was evaluated using a univariate analysis. Results Seven patients were enrolled and categorized into the severe (n = 2) and control (n = 5) groups. The severe group had a significantly worse consciousness level and higher mortality rate and showed higher tendencies of burn severity and clinical severity scores. Disseminated intravascular coagulation was confirmed in one patient. All ROTEM variables in the severe group regarding clot firmness in the extrinsic coagulation cascade (EXTEM) and fibrinogen-specific coagulation cascade (FIBTEM) showed a decreasing tendency as compared to those in the control group. Moreover, correlation analyses revealed strong correlations between the BI and clot firmness (rho = -0.946 to -0.721). Conclusions Severe BI was strongly associated with decreased blood clot firmness in EXTEM, FIBTEM, and ROTEM. Future research using viscoelastic devices may provide new possibilities for the treatment of severe burns.