Factors Affecting the Discrepancy Between Coagulation Times on Extracorporeal Circulation Using Unfractionated Heparin in Children and Young Adults.

In unfractionated heparin (UFH) monitoring during extracorporeal circulation, the traditional measures of activated clotting time (ACT) or activated partial thromboplastin time (APTT) may diverge, confounding anticoagulant adjustments. We aimed to explore the factors explaining this discrepancy in children and young adults. This retrospective observational study, conducted at an urban regional tertiary hospital, included consecutive pediatric patients who received UFH during extracorporeal circulation (continuous kidney replacement therapy or extracorporeal membrane oxygenation) between April 2017 and March 2021. After patients whose ACT and APTT were not measured simultaneously or who were also taking other anticoagulants were excluded, we analyzed 94 samples from 23 patients. To explain the discrepancy between ACT and APTT, regression equations were created using a generalized linear model (family = gamma, link = logarithmic) with ACT as the response variable. Other explanatory variables included age, platelet count, and antithrombin. Compared to APTT alone as an explanatory variable, the Akaike information criterion and pseudo-coefficient of determination improved from 855 to 625 and from 0.01 to 0.42, respectively, when these explanatory variables were used. In conclusion, we identified several factors that may explain some of the discrepancy between ACT and APTT in the routinely measured tests. Evaluation of these factors may aid in appropriate adjustments in anticoagulation therapy.

Factors associated with successful liberation from continuous renal replacement therapy in children and young adults: analysis of the worldwide exploration of renal replacement outcomes collaborative in Kidney Disease Registry.

PURPOSE: Continuous renal replacement therapy (CRRT) is used for supportive management of acute kidney injury (AKI) and disorders of fluid balance (FB). Little is known about the predictors of successful liberation in children and young adults. We aimed to identify the factors associated with successful CRRT liberation. METHODS: The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease study is an international multicenter retrospective study (32 centers, 7 nations) conducted from 2015 to 2021 in children and young adults (aged 0-25 years) treated with CRRT for AKI or FB disorders. Patients with previous dialysis dependence, tandem extracorporeal membrane oxygenation use, died within the first 72 h of CRRT initiation, and those who never had liberation attempted were excluded. Patients were categorized based on first liberation attempt: reinstituted (resumption of any dialysis within 72 h) vs. success (no receipt of dialysis for ≥ 72 h). Multivariable logistic regression was used to identify factors associated with successful CRRT liberation. RESULTS: A total of 622 patients were included: 287 (46%) had CRRT reinstituted and 335 (54%) were successfully liberated. After adjusting for sepsis at admission and illness severity parameters, several factors were associated with successful liberation, including higher VIS (vasoactive-inotropic score) at CRRT initiation (odds ratio [OR] 1.35 [1.12-1.63]), higher PELOD-2 (pediatric logistic organ dysfunction-2) score at CRRT initiation (OR 1.71 [1.24-2.35]), higher urine output prior to CRRT initiation (OR 1.15 [1.001-1.32]), and shorter CRRT duration (OR 0.19 [0.12-0.28]). CONCLUSIONS: Inability to liberate from CRRT was common in this multinational retrospective study. Modifiable and non-modifiable factors were associated with successful liberation. These results may inform the design of future clinical trials to optimize likelihood of CRRT liberation success.

Major Adverse Kidney Events in Pediatric Continuous Kidney Replacement Therapy.

Importance: Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death. Objective: To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults. Design, Setting, and Participants: This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023. Exposure: Patient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation. Main Outcomes and Measures: MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed. Results: Among 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04). Conclusions and Relevance: In this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.

A case of anti-NPX-2 antibody-positive dermatomyositis resulting in massive haemothorax with acquired factor XIII deficiency.

Autoimmune diseases, including dermatomyositis, can be complicated by an acquired autoimmune coagulation factor XIII deficiency, which sometimes results in fatal bleeding. Here, we report the case of a young woman with anti-NPX-2 antibody-positive dermatomyositis who developed massive haemothorax with acquired factor XIII deficiency during treatment, including plasma exchange therapy. Emergency transcatheter arterial embolisation was performed and coagulation factor XIII concentrates (Fibrogammin P® 240 U/day for 5 days) were supplemented. Subsequently, the patient was discharged and managed with oral prednisolone and tacrolimus. Coagulation system test results were followed up regularly and remained within normal limits and the patient progressed without recurrence of bleeding symptoms. Coagulation factor XIII deficiency cannot be assessed without measuring coagulation factor XIII activity because common coagulation-fibrinolytic system test results are not abnormal. The measurement of factor XIII activity should be performed when autoimmune diseases are complicated by unexplained bleeding.

Characteristics of pediatric continuous renal replacement therapies in hospitals with pediatric intensive care units in Japan.

INTRODUCTION: Information on the implementation of continuous renal replacement therapy (CRRT) in pediatric intensive care units (PICUs) is limited. We investigated the real-world practice of this therapy in Japan. METHODS: We conducted a cross-sectional survey of 26 hospitals with PICUs in Japan. One physician per hospital responded to the questionnaire. RESULTS: Fewer than half of the hospitals followed the CRRT practice guidelines; treatment options were often selected at a physician's discretion. PICUs varied widely in continuous renal replacement settings, circuit priming methods, frequency of circuit exchange, and policies for using CRRT in sepsis. Only two anticoagulants were used: nafamostat mesylate and unfractionated heparin. Most units did not change the nutritional dosage according to CRRT use. Many facilities were proactive concerning rehabilitation. CONCLUSION: Nafamostat-centered anticoagulation management was unique to Japan. Our results may help identify areas where additional clinical studies are needed to standardize CRRT practice.

The Japanese Pediatric Continuous Renal Replacement Therapy (jpCRRT) Registry: Study Protocol.

BACKGROUND: The use of continuous renal replacement therapy (CRRT) in critically ill children is rapidly increasing, but the standard of care has not yet been established and prognosis remains poor. To develop optimal CRRT strategies, we launched a research project generating the Japanese Pediatric CRRT registry, a multicenter registry of CRRT in Japanese pediatric intensive care units (PICUs), to investigate the actual status of CRRT in recent years in PICUs, where data are lacking. METHODS: This manuscript presents a protocol for planning a multicenter prospective registry. As of April 2023, 15 Japanese PICUs are voluntarily participating. Patients enrolled are those <16 years of age who enter the PICUs of the collaborating institutions, require CRRT, and have the guardians' consent. CRRT is defined as anticipated to be required for >24 hours, and CRRT connected to extracorporeal membrane oxygenation is also included. The registry is an online registry system managed by the University Hospital Medical Information Network. The primary outcomes are Pediatric Cerebral Performance Category Scale at PICU discharge and 6 months post-discharge (deaths included), persistent need for dialysis, and PICU readmission within 6 months. The secondary outcomes are adverse events during and immediately after CRRT initiation, and initial circuit life span. CONCLUSIONS: This project will examine the differences in outcomes of CRRT in PICUs in specific patient and treatment groups and will be used to design future interventional studies. We will also aim to establish a platform for a multicenter registry study in Japanese PICUs, considering the current lack of such a platform.

Effect of post-ICU follow-up by a rapid response team after congenital heart surgery.

Patients with congenital heart disease who have a variety of cardiac/extracardiac problems are at high risk for deterioration. This study aimed to determine the effectiveness of post-intensive care unit (ICU) follow-up by a rapid response team (RRT) after congenital heart surgery. This before-and-after study was conducted at an urban regional tertiary hospital. We enrolled 572 consecutive patients who underwent congenital heart surgery and were transferred alive from the paediatric ICU (PICU) between April 2015 and March 2020. Post-ICU follow-up for 48 h was started in April 2018. The primary and secondary endpoints were unplanned ICU readmission and clinical outcomes at ICU readmission, respectively. Overall, 346 and 226 patients were analysed pre- and post-intervention, respectively. Patient demographics were similar between groups, but in the post-intervention group, patients tended to have had more complicated surgery. Unplanned ICU readmission rates within 30 days were similar between groups. Regarding the demographics and outcomes at ICU readmission, patients in the post-intervention group had lower predicted mortality rates (1.7% vs 5.3%, P = 0.001), required less ventilator days (median, 0.5 days [interquartile range (IQR) 0-1] vs median, 3 days [IQR 0.5-4], P = 0.02), and had a shorter ICU stay (median, 3 days [IQR 2-4] vs median, 6 days [IQR 3-9], P = 0.03), but there was no significant between-group difference in ICU mortality. Post-ICU follow-up by a RRT after congenital heart surgery did not decrease unplanned ICU readmission but improved several outcomes at ICU readmission.

Liouvillian Skin Effect: Slowing Down of Relaxation Processes without Gap Closing.

It is highly nontrivial to what extent we can deduce the relaxation behavior of a quantum dissipative system from the spectral gap of the Liouvillian that governs the time evolution of the density matrix. We investigate the relaxation processes of a quantum dissipative system that exhibits the Liouvillian skin effect, which means that the eigenmodes of the Liouvillian are localized exponentially close to the boundary of the system, and find that the timescale for the system to reach a steady state depends not only on the Liouvillian gap Δ, but also on the localization length ξ of the eigenmodes. In particular, we show that the longest relaxation time τ that is maximized over initial states and local observables is given by τ∼Δ^{-1}(1+L/ξ) with L being the system size. This implies that the longest relaxation time can diverge for L→∞ without gap closing.

Heatstroke-like symptoms in a patient with coronavirus disease pneumonia.

While there are no clear indications for body temperature control during viral infections such as COVID-19, if heat stress caused by COVID-19 leads to organ failure, then proactive body temperature regulation may be an effective treatment option.

Characteristics of Patients With Congenital Heart Disease Requiring ICU Admission From Japanese Emergency Departments.

OBJECTIVES: To evaluate the characteristics of patients with congenital heart disease requiring ICU admission from emergency departments and determine the associations between the reasons for emergency department visits and specific congenital heart disease types or cardiac procedures. DESIGN: Retrospective observational study using data from a Japanese multicenter database. SETTING: Twelve PICUs and 11 general ICUs in Japan. PATIENTS: All patients requiring ICU admission from an emergency department during 2013-2018, divided into two groups: with congenital heart disease and without congenital heart disease groups. INTERVENTIONS: None for this analysis. MEASUREMENTS AND MAIN RESULTS: Of the 297 patients with congenital heart disease (9.2% of a total of 3,240 patients), more than half had moderate-to-high complexity congenital heart disease; most of them were pediatric patients who had visited specialized congenital heart disease centers. All the patients' clinical outcomes were similar. Regarding the reasons for emergency department admission, seizure was significantly associated with a single ventricle anatomy (odds ratio, 3.3; 95% CI, 1.1-10.0), post-Glenn shunt placement (odds ratio, 5.6; 95% CI, 1.1-29.4), and a Fontan-type operation status (odds ratio, 6.3; 95% CI, 1.5-25.5). Sepsis and gastrointestinal bleeding were associated with asplenia (odds ratio, 21.1; 95% CI, 4.3-104 and odds ratio, 21.0; 95% CI, 3.1-141, respectively); gastrointestinal bleeding was also associated with systemic-to-pulmonary artery shunt placement (odds ratio, 18.8; 95% CI, 2.8-125) and a Fontan-type operation status (odds ratio, 17.0; 95% CI, 2.6-112). Arrhythmia was associated with a single ventricle anatomy (odds ratio, 21.0; 95% CI, 3.1-141), systemic-to-pulmonary artery shunt placement (odds ratio, 18.8; 95% CI, 2.8-125), and a Fontan-type operation status (odds ratio, 17.0; 95% CI, 2.6-112). CONCLUSIONS: Classification of the reasons for emergency department admission by congenital heart disease type and surgical stage may guide clinicians in the selection of appropriate treatments in such settings.

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.

Association Between Post-procedure Intracardiac Pressures and the Use of Temporary Epicardial Pacing Wires After Pediatric Cardiac Surgery.

The indications for using temporary epicardial pacing wires after pediatric cardiac surgery remain unclear. Post-procedure intracardiac pressure is valuable for detecting circulatory disturbances and residual lesions. This study aimed to examine the association between post-procedure intracardiac pressures and the use of temporary epicardial pacing wires. We performed a retrospective, case-control study at the pediatric intensive care unit of an urban regional tertiary hospital that included patients who had undergone congenital heart surgery between January 2015 and December 2016. We measured post-procedure intracardiac pressures, and data regarding baseline characteristics, procedures performed, and intraoperative variables were collected as covariates. Of the 186 included patients, 34 (18.3%) were treated using temporary epicardial pacing wires. The optimal cutoff values used to predict the use of pacing wires for central venous pressure, left atrial pressure, pulmonary arterial pressure/systemic blood pressure ratio, and right ventricular pressure/left ventricular pressure ratio were 11 mmHg (55.6% sensitivity, 86.2% specificity), 13 mmHg (50% sensitivity, 84.6% specificity), 0.39 (69.6% sensitivity, 78.7% specificity), and 0.51 (74.1% sensitivity, 64.2% specificity), respectively. Multivariable logistic regression analyses showed that the use of temporary epicardial pacing wires was significantly associated with left atrial pressure ≥ 11 mmHg (odds ratio 4.4; 95% confidence interval 1.01-18.9), and a pulmonary arterial pressure/systemic blood pressure ratio ≥ 0.39 (odds ratio 6.3; 95% confidence interval 1.3-31.4). High post-procedure intracardiac pressures were associated with the use of temporary epicardial pacing wires. These data can aid in the decision-making for the proper use of temporary epicardial pacing wires.

Divergence of the Floquet-Magnus expansion in a periodically driven one-body system with energy localization.

The Floquet-Magnus expansion is a useful tool to calculate an effective Hamiltonian for periodically driven systems. In this study, we investigate the convergence of the expansion for a one-body nonlinear system in a continuous space, a driven anharmonic oscillator. In this model, all eigenstates of the time-evolution operator are found to be localized in energy space, and the expectation value of the energy is bounded from above. We first propose a general procedure to estimate the radius of convergence of the Floquet-Magnus expansion for periodically driven systems with an unbounded energy spectrum. By applying it to the driven anharmonic oscillator, we numerically show that the expansion diverges for all driving frequencies even if the anharmonicity is arbitrarily small. This conclusion contradicts the widely accepted belief that the divergence of the Floquet-Magnus expansion is a direct consequence of quantum ergodicity, which implies that each eigenstate of the time-evolution operator is a linear combination of all available eigenstates of the unperturbed Hamiltonian and the system heats up to infinite temperature after long intervals.

Nonequilibrium quasi-long-range order of a driven random-field O(N) model.

We investigate three-dimensional O(N) spin models driven with a uniform velocity over a random field. Within a spin-wave approximation, it is shown that in the strong driving regime the model with N=2 exhibits a quasi-long-range order in which the spatial correlation function decays in a power-law form. Furthermore, for the cases that N=2 and 3, we numerically demonstrate a nonequilibrium phase transition between the quasi-long-range order phase and the disordered phase, which turns out to resemble the Kosterlitz-Thouless transition in the two-dimensional pure XY model in equilibrium.